Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

SAN DIEGO—The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it may mean that Corynebacterium triggers Parkinson’s disease in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for Parkinson’s disease identified to date, but it is not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there is a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, Professor of Neurology and Genomics at the University of Alabama, Birmingham.

Genotypes and Triggers

The finding, which was presented at the 142nd Annual Meeting of the American Neurological Association, may begin to clarify the link between the dozens of genetic risk factors for Parkinson’s disease and environmental triggers that lead to the disease. Different bacteria may be associated with different genetic risk factors. Eventually, the researchers aim to map out which genetic susceptibilities are associated with which elements of the microbiome and which genotypes are associated with other environmental factors, such as pesticides, Dr. Payami, leader of the multicenter neurogenetics research collaboration, said.

Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged patients with Parkinson’s disease and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their guts and then looked for interactions between rs356219 genotype, gut microbiome, and Parkinson’s disease risk.

The medical literature has been full of hints that Parkinson’s disease might be set off by something going wrong in the gastrointestinal (GI) tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in Parkinson’s disease are among the many clues. The goal of the work was to find the link between Parkinson’s disease and its GI aberrations.

Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.

Heightened Risk

As in past studies, the rs356219 AA genotype did not increase the odds of Parkinson’s disease, and there was no difference in microbiome abundance between patients with Parkinson’s disease and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9). If people had GG plus Corynebacterium, however, developing Parkinson’s disease was a certainty.

Corynebacterium was more abundant in GA subjects with Parkinson’s disease than in GA subjects without Parkinson’s disease, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had Parkinson’s disease.

Corynebacteria are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It is not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.

Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of Parkinson’s disease Lewy bodies that is known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that there is no turning back, and it is enough to cause Parkinson’s disease,” Dr. Payami said.

The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab. The study was supported by the NIH.

—M. Alexander Otto

SAN DIEGO—The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it may mean that Corynebacterium triggers Parkinson’s disease in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for Parkinson’s disease identified to date, but it is not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there is a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, Professor of Neurology and Genomics at the University of Alabama, Birmingham.

Genotypes and Triggers

The finding, which was presented at the 142nd Annual Meeting of the American Neurological Association, may begin to clarify the link between the dozens of genetic risk factors for Parkinson’s disease and environmental triggers that lead to the disease. Different bacteria may be associated with different genetic risk factors. Eventually, the researchers aim to map out which genetic susceptibilities are associated with which elements of the microbiome and which genotypes are associated with other environmental factors, such as pesticides, Dr. Payami, leader of the multicenter neurogenetics research collaboration, said.

Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged patients with Parkinson’s disease and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their guts and then looked for interactions between rs356219 genotype, gut microbiome, and Parkinson’s disease risk.

The medical literature has been full of hints that Parkinson’s disease might be set off by something going wrong in the gastrointestinal (GI) tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in Parkinson’s disease are among the many clues. The goal of the work was to find the link between Parkinson’s disease and its GI aberrations.

Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.

Heightened Risk

As in past studies, the rs356219 AA genotype did not increase the odds of Parkinson’s disease, and there was no difference in microbiome abundance between patients with Parkinson’s disease and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9). If people had GG plus Corynebacterium, however, developing Parkinson’s disease was a certainty.

Corynebacterium was more abundant in GA subjects with Parkinson’s disease than in GA subjects without Parkinson’s disease, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had Parkinson’s disease.

Corynebacteria are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It is not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.

Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of Parkinson’s disease Lewy bodies that is known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that there is no turning back, and it is enough to cause Parkinson’s disease,” Dr. Payami said.

The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab. The study was supported by the NIH.

—M. Alexander Otto

SAN DIEGO—The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it may mean that Corynebacterium triggers Parkinson’s disease in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for Parkinson’s disease identified to date, but it is not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there is a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, Professor of Neurology and Genomics at the University of Alabama, Birmingham.

Genotypes and Triggers

The finding, which was presented at the 142nd Annual Meeting of the American Neurological Association, may begin to clarify the link between the dozens of genetic risk factors for Parkinson’s disease and environmental triggers that lead to the disease. Different bacteria may be associated with different genetic risk factors. Eventually, the researchers aim to map out which genetic susceptibilities are associated with which elements of the microbiome and which genotypes are associated with other environmental factors, such as pesticides, Dr. Payami, leader of the multicenter neurogenetics research collaboration, said.

Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged patients with Parkinson’s disease and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their guts and then looked for interactions between rs356219 genotype, gut microbiome, and Parkinson’s disease risk.

The medical literature has been full of hints that Parkinson’s disease might be set off by something going wrong in the gastrointestinal (GI) tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in Parkinson’s disease are among the many clues. The goal of the work was to find the link between Parkinson’s disease and its GI aberrations.

Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.

Heightened Risk

As in past studies, the rs356219 AA genotype did not increase the odds of Parkinson’s disease, and there was no difference in microbiome abundance between patients with Parkinson’s disease and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9). If people had GG plus Corynebacterium, however, developing Parkinson’s disease was a certainty.

Corynebacterium was more abundant in GA subjects with Parkinson’s disease than in GA subjects without Parkinson’s disease, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had Parkinson’s disease.

Corynebacteria are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It is not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.

Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of Parkinson’s disease Lewy bodies that is known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that there is no turning back, and it is enough to cause Parkinson’s disease,” Dr. Payami said.

The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab. The study was supported by the NIH.

—M. Alexander Otto

ANAHEIM, CA—Thirty million Americans became hypertensive overnight with the introduction of a new high blood pressure guideline from the American College of Cardiology (ACC) and American Heart Association (AHA).

The guideline changes the definition of adult hypertension from the long-standing threshold of 140/90 mm Hg to 130/80 mm Hg. As a result, adult prevalence of hypertension in the United States increased from roughly 32% to 46%, bringing the national hypertensive population to 103 million. The guideline was presented at the AHA’s 2017 Scientific Sessions and published in the Journal of the American College of Cardiology and Hypertension.

In addition to those with hypertension, another 12% of American adults have what the new guideline calls elevated blood pressure—a systolic pressure of 120–129 mm Hg with a diastolic pressure of less than 80 mm Hg. This group warrants lifestyle interventions to arrest progression, according to the guideline. In selected subgroups, the prevalence of hypertension is even greater. Among African American men and women, for example, approximately 55% have hypertension under the new guideline. And among men and women ages 65 and older, more than three-quarters now have hypertension.

Goal Is to Transform Care

Beyond the guideline’s epidemiologic implications, it includes 106 recommendations for preventing, detecting, evaluating, and managing adult hypertension. The guideline addresses every aspect of blood pressure in American medical practice, from how it is measured to how medical systems can try to ensure that every person with a blood pressure outside the redefined limits gets a comprehensive package of interventions.

The guideline includes a risk-based approach to making treatment decisions, a reduced treatment target of less than 130/80 mm Hg, and strategies to improve treatment efficacy, said Paul K. Whelton, MD, chair of the guidelines task force and Professor of Global Health at Tulane University in New Orleans.

One Goal for All Adults

“The systolic blood pressure goal for older people has gone from 140 mm Hg to 150 mm Hg and now to 130 mm Hg” within a few years, commented Dr. Appel. In fact, the guideline simplifies the treatment goal to less than 130/80 mm Hg for all adults, including patients with diabetes, those with chronic kidney disease, and the elderly.

“It will be clearer and easier now that everyone should be less than 130/80 mm Hg. You will not need to remember a second target,” said Sandra J. Taler, MD, a nephrologist and Professor of Medicine at the Mayo Clinic in Rochester, Minnesota, and a member of the guidelines task force. “Some people may be upset that we changed the rules on them. They had normal blood pressure yesterday, and today it is high. But it is a good awakening, especially for using lifestyle interventions.”

Preferred Intervention: Lifestyle, Not Drugs

The guideline cites lifestyle optimization as the cornerstone of intervention for everyone and as the only endorsed intervention for patients with hypertension of 130–139 mm Hg but below a 10% risk for a cardiovascular disease event during the next 10 years, as assessed by the ACC’s online risk calculator. The guideline lists six lifestyle goals: weight loss, following a DASH (Dietary Approaches to Stop Hypertension) diet, reducing sodium intake, enhancing potassium intake, getting 90–150 minutes per week of physical activity, and moderating alcohol intake.

The guideline may encourage “a recommitment to lifestyle changes” for preventing and managing hypertension, said the task force’s vice chair, Robert M. Carey, MD, Professor of Medicine at the University of Virginia in Charlottesville.

Team-Based Care Is Essential

The guideline emphasizes a team-based management approach that includes nurses, nurse practitioners, pharmacists, dietitians, and other clinicians, allowing for more frequent and focused care. Dr. Whelton and others cited the VA Health System and Kaiser-Permanente as operating team-based and system-driven blood pressure management programs that have resulted in control rates for more than 90% of patients with hypertension. The team-based approach is a key component of Target:BP, a program founded by the AHA and American Medical Association to promote implementation of the new guideline, Dr. Carey said. Another systems recommendation in the guideline is that every patient with hypertension should have a “clear, detailed, and current evidence-based plan of care.”

“Using nurse practitioners, physician assistants, and pharmacists has been shown to improve blood pressure levels,” and health systems that take this approach have had “great success,” commented Donald M. Lloyd-Jones, MD, Professor and Chairman of Preventive Medicine at Northwestern University in Chicago, who was not part of the guidelines task force. Financial penalties and incentives from payers exist to push for higher levels of blood pressure control, and the alignment of financial and health incentives should result in big changes, Dr. Lloyd-Jones predicted.

—Mitchel L. Zoler

Suggested Reading

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection,evaluation, and management of high bood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017 Nov 7 [Epub ahead of print].

ANAHEIM, CA—Thirty million Americans became hypertensive overnight with the introduction of a new high blood pressure guideline from the American College of Cardiology (ACC) and American Heart Association (AHA).

The guideline changes the definition of adult hypertension from the long-standing threshold of 140/90 mm Hg to 130/80 mm Hg. As a result, adult prevalence of hypertension in the United States increased from roughly 32% to 46%, bringing the national hypertensive population to 103 million. The guideline was presented at the AHA’s 2017 Scientific Sessions and published in the Journal of the American College of Cardiology and Hypertension.

In addition to those with hypertension, another 12% of American adults have what the new guideline calls elevated blood pressure—a systolic pressure of 120–129 mm Hg with a diastolic pressure of less than 80 mm Hg. This group warrants lifestyle interventions to arrest progression, according to the guideline. In selected subgroups, the prevalence of hypertension is even greater. Among African American men and women, for example, approximately 55% have hypertension under the new guideline. And among men and women ages 65 and older, more than three-quarters now have hypertension.

Goal Is to Transform Care

Beyond the guideline’s epidemiologic implications, it includes 106 recommendations for preventing, detecting, evaluating, and managing adult hypertension. The guideline addresses every aspect of blood pressure in American medical practice, from how it is measured to how medical systems can try to ensure that every person with a blood pressure outside the redefined limits gets a comprehensive package of interventions.

The guideline includes a risk-based approach to making treatment decisions, a reduced treatment target of less than 130/80 mm Hg, and strategies to improve treatment efficacy, said Paul K. Whelton, MD, chair of the guidelines task force and Professor of Global Health at Tulane University in New Orleans.

One Goal for All Adults

“The systolic blood pressure goal for older people has gone from 140 mm Hg to 150 mm Hg and now to 130 mm Hg” within a few years, commented Dr. Appel. In fact, the guideline simplifies the treatment goal to less than 130/80 mm Hg for all adults, including patients with diabetes, those with chronic kidney disease, and the elderly.

“It will be clearer and easier now that everyone should be less than 130/80 mm Hg. You will not need to remember a second target,” said Sandra J. Taler, MD, a nephrologist and Professor of Medicine at the Mayo Clinic in Rochester, Minnesota, and a member of the guidelines task force. “Some people may be upset that we changed the rules on them. They had normal blood pressure yesterday, and today it is high. But it is a good awakening, especially for using lifestyle interventions.”

Preferred Intervention: Lifestyle, Not Drugs

The guideline cites lifestyle optimization as the cornerstone of intervention for everyone and as the only endorsed intervention for patients with hypertension of 130–139 mm Hg but below a 10% risk for a cardiovascular disease event during the next 10 years, as assessed by the ACC’s online risk calculator. The guideline lists six lifestyle goals: weight loss, following a DASH (Dietary Approaches to Stop Hypertension) diet, reducing sodium intake, enhancing potassium intake, getting 90–150 minutes per week of physical activity, and moderating alcohol intake.

The guideline may encourage “a recommitment to lifestyle changes” for preventing and managing hypertension, said the task force’s vice chair, Robert M. Carey, MD, Professor of Medicine at the University of Virginia in Charlottesville.

Team-Based Care Is Essential

The guideline emphasizes a team-based management approach that includes nurses, nurse practitioners, pharmacists, dietitians, and other clinicians, allowing for more frequent and focused care. Dr. Whelton and others cited the VA Health System and Kaiser-Permanente as operating team-based and system-driven blood pressure management programs that have resulted in control rates for more than 90% of patients with hypertension. The team-based approach is a key component of Target:BP, a program founded by the AHA and American Medical Association to promote implementation of the new guideline, Dr. Carey said. Another systems recommendation in the guideline is that every patient with hypertension should have a “clear, detailed, and current evidence-based plan of care.”

“Using nurse practitioners, physician assistants, and pharmacists has been shown to improve blood pressure levels,” and health systems that take this approach have had “great success,” commented Donald M. Lloyd-Jones, MD, Professor and Chairman of Preventive Medicine at Northwestern University in Chicago, who was not part of the guidelines task force. Financial penalties and incentives from payers exist to push for higher levels of blood pressure control, and the alignment of financial and health incentives should result in big changes, Dr. Lloyd-Jones predicted.

—Mitchel L. Zoler

Suggested Reading

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection,evaluation, and management of high bood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017 Nov 7 [Epub ahead of print].

ANAHEIM, CA—Thirty million Americans became hypertensive overnight with the introduction of a new high blood pressure guideline from the American College of Cardiology (ACC) and American Heart Association (AHA).

The guideline changes the definition of adult hypertension from the long-standing threshold of 140/90 mm Hg to 130/80 mm Hg. As a result, adult prevalence of hypertension in the United States increased from roughly 32% to 46%, bringing the national hypertensive population to 103 million. The guideline was presented at the AHA’s 2017 Scientific Sessions and published in the Journal of the American College of Cardiology and Hypertension.

In addition to those with hypertension, another 12% of American adults have what the new guideline calls elevated blood pressure—a systolic pressure of 120–129 mm Hg with a diastolic pressure of less than 80 mm Hg. This group warrants lifestyle interventions to arrest progression, according to the guideline. In selected subgroups, the prevalence of hypertension is even greater. Among African American men and women, for example, approximately 55% have hypertension under the new guideline. And among men and women ages 65 and older, more than three-quarters now have hypertension.

Goal Is to Transform Care

Beyond the guideline’s epidemiologic implications, it includes 106 recommendations for preventing, detecting, evaluating, and managing adult hypertension. The guideline addresses every aspect of blood pressure in American medical practice, from how it is measured to how medical systems can try to ensure that every person with a blood pressure outside the redefined limits gets a comprehensive package of interventions.

The guideline includes a risk-based approach to making treatment decisions, a reduced treatment target of less than 130/80 mm Hg, and strategies to improve treatment efficacy, said Paul K. Whelton, MD, chair of the guidelines task force and Professor of Global Health at Tulane University in New Orleans.

One Goal for All Adults

“The systolic blood pressure goal for older people has gone from 140 mm Hg to 150 mm Hg and now to 130 mm Hg” within a few years, commented Dr. Appel. In fact, the guideline simplifies the treatment goal to less than 130/80 mm Hg for all adults, including patients with diabetes, those with chronic kidney disease, and the elderly.

“It will be clearer and easier now that everyone should be less than 130/80 mm Hg. You will not need to remember a second target,” said Sandra J. Taler, MD, a nephrologist and Professor of Medicine at the Mayo Clinic in Rochester, Minnesota, and a member of the guidelines task force. “Some people may be upset that we changed the rules on them. They had normal blood pressure yesterday, and today it is high. But it is a good awakening, especially for using lifestyle interventions.”

Preferred Intervention: Lifestyle, Not Drugs

The guideline cites lifestyle optimization as the cornerstone of intervention for everyone and as the only endorsed intervention for patients with hypertension of 130–139 mm Hg but below a 10% risk for a cardiovascular disease event during the next 10 years, as assessed by the ACC’s online risk calculator. The guideline lists six lifestyle goals: weight loss, following a DASH (Dietary Approaches to Stop Hypertension) diet, reducing sodium intake, enhancing potassium intake, getting 90–150 minutes per week of physical activity, and moderating alcohol intake.

The guideline may encourage “a recommitment to lifestyle changes” for preventing and managing hypertension, said the task force’s vice chair, Robert M. Carey, MD, Professor of Medicine at the University of Virginia in Charlottesville.

Team-Based Care Is Essential

The guideline emphasizes a team-based management approach that includes nurses, nurse practitioners, pharmacists, dietitians, and other clinicians, allowing for more frequent and focused care. Dr. Whelton and others cited the VA Health System and Kaiser-Permanente as operating team-based and system-driven blood pressure management programs that have resulted in control rates for more than 90% of patients with hypertension. The team-based approach is a key component of Target:BP, a program founded by the AHA and American Medical Association to promote implementation of the new guideline, Dr. Carey said. Another systems recommendation in the guideline is that every patient with hypertension should have a “clear, detailed, and current evidence-based plan of care.”

“Using nurse practitioners, physician assistants, and pharmacists has been shown to improve blood pressure levels,” and health systems that take this approach have had “great success,” commented Donald M. Lloyd-Jones, MD, Professor and Chairman of Preventive Medicine at Northwestern University in Chicago, who was not part of the guidelines task force. Financial penalties and incentives from payers exist to push for higher levels of blood pressure control, and the alignment of financial and health incentives should result in big changes, Dr. Lloyd-Jones predicted.

—Mitchel L. Zoler

Suggested Reading

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection,evaluation, and management of high bood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017 Nov 7 [Epub ahead of print].

KANSAS CITY, MO—Mass psychogenic illness is a condition where signs and symptoms spread rapidly between members of a cohesive group. The illness may entail loss or alteration of function, and patients unconsciously manifest physical symptoms. “Our brains are wired to be empathetic and to pick up on the symptoms of others,” said Jonathan W. Mink, MD, PhD, at the 46th Annual Meeting of the Child Neurology Society. “In mass psychogenic illness, those symptoms persist, and there is that contagion from individual to individual.”

A recent occurrence of mass psychogenic illness in Le Roy, New York, suggests that news media attention and patients’ use of social media may play a role in the spread and perpetuation of symptoms. Few descriptions of mass psychogenic illness have been published in pediatric neurology journals, but prior cases may provide useful information about the condition, its risk factors, and treatment, Dr. Mink said.

Teens With Tic-Like Movements

Between August 2011 and January 2012, 19 teenage students at Le Roy Junior–Senior High School developed a sudden onset of tic-like movements. Two had a prior diagnosis of a tic disorder: one had Tourette syndrome, and one had chronic motor tic disorder. Eighteen of the 19 were girls. Six of the 19 had additional symptoms (eg, syncope and paroxysmal nonepileptic attacks), and 10 had clearly identified significant life stressors. All of the patients had otherwise normal neurologic exams. The movements “were not tics,” Dr. Mink said. “They had no premonitory urge. They were not suppressible. They were not stereotyped. But they were often referred to as tic-like.”

The cases drew national and local media attention. News reports portrayed the cases as mysterious and suggested that the symptoms could have autoimmune or environmental causes. Furthermore, social media may have contributed to the spread of symptoms. “It has often been said that mass psychogenic illness, or what was formerly called mass hysteria, was conveyed by line-of-sight transmission. It was seeing the symptoms of other people,” Dr. Mink said. “Many of these girls had posted videos or detailed descriptions of their symptoms.”

Most of the patients were seen at the Dent Neurologic Institute in Buffalo. To help confirm the diagnosis, a majority of the patients also were seen at Dr. Mink’s center in Rochester.

Insights From Prior Research

In 2004, Roach and Langley described an occurrence of mass psychogenic illness among a cohort of 10 teenage girls at a school in rural North Carolina. The patients developed paroxysmal episodes that resembled epilepsy or syncope. The episodes were relatively infrequent and typically occurred between classes. Four patients underwent video-EEG monitoring, which showed that the seizures were not epileptic. Symptoms mostly resolved after a two-week holiday break from school. “More than half of them had been treated with one or more antiepileptic medications,” Dr. Mink said.

A study of environmental chemical incidents in the United Kingdom found that a substantial minority of cases could involve mass psychogenic illness. Page et al examined incidents over a 15-month period between 2007 and 2008. Of 965 total incidents, 747 were eligible for inclusion in the study, and 280 were selected randomly for detailed evaluation.

The British researchers’ criteria for diagnosing mass psychogenic illness included the presence of somatic symptoms, a preexisting social connection between two or more of the affected people, the spread of symptoms from person to person, and the attribution of symptoms by affected individuals or by their parents or caregivers to a threatening external agent of a physical or spiritual nature. Finally, the symptoms and signs were not compatible with environmental exposures that reasonably could have been expected to be present at the time.

Nineteen of the 280 incidents were classified as probable or highly probable mass psychogenic illness (six highly probable and 13 probable), which represented 7% of the incidents and 16% of incidents in which people reported symptoms that were attributed to the chemical incident. Factors that were more common among cases of mass psychogenic illness included the presence of a nonsmoke odor and occurrence in a school or health care facility.

Experimental Induction of Mass Psychogenic Illness

Broderick et al in 2011 described a randomized controlled experimental induction of mass psychogenic illness. Their study included 39 healthy adults with a mean age of 42. A little more than half were women, half were college graduates, and almost 80% were Caucasian.

A control group sat in a room and engaged in quiet activity, while two psychogenic illness induction groups received a pill. One of the induction groups was shown a video (ie, the pill-plus-media group).

Researchers told participants in the pill groups that the study was designed to further evaluate the side effects of a new carrier compound for an antiviral medication. The participants were told that the compound contained only cellulose and did not produce serious side effects.

In the pill groups, confederates (one man and one woman) feigned illness (eg, nausea, dizziness, and headache) about 20 minutes after participants took the pills. Nurses attended to the confederates and to any participant who simulated or experienced symptoms, by taking their blood pressure and pulse, providing cool cloths for their foreheads, supplying bowls for potential vomiting, and sometimes putting participants with symptoms on gurneys outside the room within view of the other participants. An hour after taking the pills, the pill-plus-media group watched a public television documentary about the 1918 flu pandemic.

All three groups were assessed at baseline, at one hour, and at two hours. Participants rated their current symptoms by questionnaire, and nurses measured participants’ heart rate and blood pressure. Researchers debriefed all participants after the third assessment, and participants completed a psychosocial risk factor battery within a week of the initial experiment.

The primary outcome was symptom score. Participants in all three groups had some symptoms at baseline (eg, elevated heart rate and slight discomfort). At one hour, the control group had reduced symptoms, whereas the pill groups had increased symptom scores. At two hours, the control group still had few symptoms, but the psychogenic illness induction groups’ symptoms increased further. Symptoms did not differ between the pill-only and pill-plus-media groups, however.

An analysis of the psychosocial risk factor questionnaires found that participants’ total number of traumatic life events was positively associated with increased symptoms, but this relationship was not particularly strong. “It seems that the most important thing is … being exposed to people who are feigning symptoms or displaying symptoms in the setting of being told that there is a potential agent that might cause those symptoms,” Dr. Mink said.

Outcomes in Le Roy

Amid media coverage of the cases in Le Roy, Dr. Mink declined daily invitations to appear on television. “The last time I talked to the producer, I said, ‘You know, you would do these girls a big favor if you would just leave them alone,’” he said. “While the media attention persisted for another week, the improvement of their symptoms did coincide with reduced media attention, so one can speculate that that might have played a role.”

The patients in Le Roy received varying therapies, including cognitive behavioral therapy and supportive psychotherapy. They all received education about functional neurologic disorders. Some received pharmacotherapy for coexisting anxiety, and treatment of coexisting anxiety or depression coincided with patient improvement as well.

At last follow-up about two years ago, five of the 19 no longer had symptoms. Six of the 19 had experienced a greater than 85% improvement. A couple of patients continued to have symptoms, including the patients with a prior diagnosis of a chronic tic disorder. Two patients who had not improved sued the school district and alleged environmental toxins as the cause of their symptoms. The other patients were lost to follow up.

Treatment Principles

When treating patients with mass psychogenic illness, “First of all, you have to be an ally of your patient and not challenge the veracity,” Dr. Mink said. “For some of these girls, I think that there was some factitious component,” but this factor was not especially relevant to treatment recommendations.

“For mass psychogenic illness, reducing attention from social media groups and perhaps finding a way to disrupt the social cohesiveness of that group, at least until the symptoms can improve,” may be beneficial, he said. “Regular follow-up is helpful for all conversion disorders…. You do not want the patient to have to get worse to be able to see their doctor.”

Once neurologists have confirmed the diagnosis of mass psychogenic illness, they should “reinforce the certainty of the diagnosis” to occupational therapists, physical therapists, psychotherapists, and others on the health care team who treat these patients, Dr. Mink said. In addition,“It is important to prepare the therapist, particularly in an unusual situation like this where there has been a lot of media attention.”

—Jake Remaly

Suggested Reading

Bartholomew RE, Wessely S, Rubin GJ. Mass psychogenic illness and the social network: is it changing the pattern of outbreaks? J R Soc Med. 2012;105(12):509-512.

Broderick JE, Kaplan-Liss E, Bass E. Experimental induction of psychogenic illness in the context of a medical event and media exposure. Am J Disaster Med. 2011;6(3):163-172.

Page LA, Keshishian C, Leonardi G, et al. Frequency and predictors of mass psychogenic illness. Epidemiology. 2010;21(5):744-747.

Roach ES, Langley RL. Episodic neurological dysfunction due to mass hysteria. Arch Neurol. 2004;61(8):1269-1272.

KANSAS CITY, MO—Mass psychogenic illness is a condition where signs and symptoms spread rapidly between members of a cohesive group. The illness may entail loss or alteration of function, and patients unconsciously manifest physical symptoms. “Our brains are wired to be empathetic and to pick up on the symptoms of others,” said Jonathan W. Mink, MD, PhD, at the 46th Annual Meeting of the Child Neurology Society. “In mass psychogenic illness, those symptoms persist, and there is that contagion from individual to individual.”

A recent occurrence of mass psychogenic illness in Le Roy, New York, suggests that news media attention and patients’ use of social media may play a role in the spread and perpetuation of symptoms. Few descriptions of mass psychogenic illness have been published in pediatric neurology journals, but prior cases may provide useful information about the condition, its risk factors, and treatment, Dr. Mink said.

Teens With Tic-Like Movements

Between August 2011 and January 2012, 19 teenage students at Le Roy Junior–Senior High School developed a sudden onset of tic-like movements. Two had a prior diagnosis of a tic disorder: one had Tourette syndrome, and one had chronic motor tic disorder. Eighteen of the 19 were girls. Six of the 19 had additional symptoms (eg, syncope and paroxysmal nonepileptic attacks), and 10 had clearly identified significant life stressors. All of the patients had otherwise normal neurologic exams. The movements “were not tics,” Dr. Mink said. “They had no premonitory urge. They were not suppressible. They were not stereotyped. But they were often referred to as tic-like.”

The cases drew national and local media attention. News reports portrayed the cases as mysterious and suggested that the symptoms could have autoimmune or environmental causes. Furthermore, social media may have contributed to the spread of symptoms. “It has often been said that mass psychogenic illness, or what was formerly called mass hysteria, was conveyed by line-of-sight transmission. It was seeing the symptoms of other people,” Dr. Mink said. “Many of these girls had posted videos or detailed descriptions of their symptoms.”

Most of the patients were seen at the Dent Neurologic Institute in Buffalo. To help confirm the diagnosis, a majority of the patients also were seen at Dr. Mink’s center in Rochester.

Insights From Prior Research

In 2004, Roach and Langley described an occurrence of mass psychogenic illness among a cohort of 10 teenage girls at a school in rural North Carolina. The patients developed paroxysmal episodes that resembled epilepsy or syncope. The episodes were relatively infrequent and typically occurred between classes. Four patients underwent video-EEG monitoring, which showed that the seizures were not epileptic. Symptoms mostly resolved after a two-week holiday break from school. “More than half of them had been treated with one or more antiepileptic medications,” Dr. Mink said.

A study of environmental chemical incidents in the United Kingdom found that a substantial minority of cases could involve mass psychogenic illness. Page et al examined incidents over a 15-month period between 2007 and 2008. Of 965 total incidents, 747 were eligible for inclusion in the study, and 280 were selected randomly for detailed evaluation.

The British researchers’ criteria for diagnosing mass psychogenic illness included the presence of somatic symptoms, a preexisting social connection between two or more of the affected people, the spread of symptoms from person to person, and the attribution of symptoms by affected individuals or by their parents or caregivers to a threatening external agent of a physical or spiritual nature. Finally, the symptoms and signs were not compatible with environmental exposures that reasonably could have been expected to be present at the time.

Nineteen of the 280 incidents were classified as probable or highly probable mass psychogenic illness (six highly probable and 13 probable), which represented 7% of the incidents and 16% of incidents in which people reported symptoms that were attributed to the chemical incident. Factors that were more common among cases of mass psychogenic illness included the presence of a nonsmoke odor and occurrence in a school or health care facility.

Experimental Induction of Mass Psychogenic Illness

Broderick et al in 2011 described a randomized controlled experimental induction of mass psychogenic illness. Their study included 39 healthy adults with a mean age of 42. A little more than half were women, half were college graduates, and almost 80% were Caucasian.

A control group sat in a room and engaged in quiet activity, while two psychogenic illness induction groups received a pill. One of the induction groups was shown a video (ie, the pill-plus-media group).

Researchers told participants in the pill groups that the study was designed to further evaluate the side effects of a new carrier compound for an antiviral medication. The participants were told that the compound contained only cellulose and did not produce serious side effects.

In the pill groups, confederates (one man and one woman) feigned illness (eg, nausea, dizziness, and headache) about 20 minutes after participants took the pills. Nurses attended to the confederates and to any participant who simulated or experienced symptoms, by taking their blood pressure and pulse, providing cool cloths for their foreheads, supplying bowls for potential vomiting, and sometimes putting participants with symptoms on gurneys outside the room within view of the other participants. An hour after taking the pills, the pill-plus-media group watched a public television documentary about the 1918 flu pandemic.

All three groups were assessed at baseline, at one hour, and at two hours. Participants rated their current symptoms by questionnaire, and nurses measured participants’ heart rate and blood pressure. Researchers debriefed all participants after the third assessment, and participants completed a psychosocial risk factor battery within a week of the initial experiment.

The primary outcome was symptom score. Participants in all three groups had some symptoms at baseline (eg, elevated heart rate and slight discomfort). At one hour, the control group had reduced symptoms, whereas the pill groups had increased symptom scores. At two hours, the control group still had few symptoms, but the psychogenic illness induction groups’ symptoms increased further. Symptoms did not differ between the pill-only and pill-plus-media groups, however.

An analysis of the psychosocial risk factor questionnaires found that participants’ total number of traumatic life events was positively associated with increased symptoms, but this relationship was not particularly strong. “It seems that the most important thing is … being exposed to people who are feigning symptoms or displaying symptoms in the setting of being told that there is a potential agent that might cause those symptoms,” Dr. Mink said.

Outcomes in Le Roy

Amid media coverage of the cases in Le Roy, Dr. Mink declined daily invitations to appear on television. “The last time I talked to the producer, I said, ‘You know, you would do these girls a big favor if you would just leave them alone,’” he said. “While the media attention persisted for another week, the improvement of their symptoms did coincide with reduced media attention, so one can speculate that that might have played a role.”

The patients in Le Roy received varying therapies, including cognitive behavioral therapy and supportive psychotherapy. They all received education about functional neurologic disorders. Some received pharmacotherapy for coexisting anxiety, and treatment of coexisting anxiety or depression coincided with patient improvement as well.

At last follow-up about two years ago, five of the 19 no longer had symptoms. Six of the 19 had experienced a greater than 85% improvement. A couple of patients continued to have symptoms, including the patients with a prior diagnosis of a chronic tic disorder. Two patients who had not improved sued the school district and alleged environmental toxins as the cause of their symptoms. The other patients were lost to follow up.

Treatment Principles

When treating patients with mass psychogenic illness, “First of all, you have to be an ally of your patient and not challenge the veracity,” Dr. Mink said. “For some of these girls, I think that there was some factitious component,” but this factor was not especially relevant to treatment recommendations.

“For mass psychogenic illness, reducing attention from social media groups and perhaps finding a way to disrupt the social cohesiveness of that group, at least until the symptoms can improve,” may be beneficial, he said. “Regular follow-up is helpful for all conversion disorders…. You do not want the patient to have to get worse to be able to see their doctor.”

Once neurologists have confirmed the diagnosis of mass psychogenic illness, they should “reinforce the certainty of the diagnosis” to occupational therapists, physical therapists, psychotherapists, and others on the health care team who treat these patients, Dr. Mink said. In addition,“It is important to prepare the therapist, particularly in an unusual situation like this where there has been a lot of media attention.”

—Jake Remaly

Suggested Reading

Bartholomew RE, Wessely S, Rubin GJ. Mass psychogenic illness and the social network: is it changing the pattern of outbreaks? J R Soc Med. 2012;105(12):509-512.

Broderick JE, Kaplan-Liss E, Bass E. Experimental induction of psychogenic illness in the context of a medical event and media exposure. Am J Disaster Med. 2011;6(3):163-172.

Page LA, Keshishian C, Leonardi G, et al. Frequency and predictors of mass psychogenic illness. Epidemiology. 2010;21(5):744-747.

Roach ES, Langley RL. Episodic neurological dysfunction due to mass hysteria. Arch Neurol. 2004;61(8):1269-1272.

KANSAS CITY, MO—Mass psychogenic illness is a condition where signs and symptoms spread rapidly between members of a cohesive group. The illness may entail loss or alteration of function, and patients unconsciously manifest physical symptoms. “Our brains are wired to be empathetic and to pick up on the symptoms of others,” said Jonathan W. Mink, MD, PhD, at the 46th Annual Meeting of the Child Neurology Society. “In mass psychogenic illness, those symptoms persist, and there is that contagion from individual to individual.”

A recent occurrence of mass psychogenic illness in Le Roy, New York, suggests that news media attention and patients’ use of social media may play a role in the spread and perpetuation of symptoms. Few descriptions of mass psychogenic illness have been published in pediatric neurology journals, but prior cases may provide useful information about the condition, its risk factors, and treatment, Dr. Mink said.

Teens With Tic-Like Movements

Between August 2011 and January 2012, 19 teenage students at Le Roy Junior–Senior High School developed a sudden onset of tic-like movements. Two had a prior diagnosis of a tic disorder: one had Tourette syndrome, and one had chronic motor tic disorder. Eighteen of the 19 were girls. Six of the 19 had additional symptoms (eg, syncope and paroxysmal nonepileptic attacks), and 10 had clearly identified significant life stressors. All of the patients had otherwise normal neurologic exams. The movements “were not tics,” Dr. Mink said. “They had no premonitory urge. They were not suppressible. They were not stereotyped. But they were often referred to as tic-like.”

The cases drew national and local media attention. News reports portrayed the cases as mysterious and suggested that the symptoms could have autoimmune or environmental causes. Furthermore, social media may have contributed to the spread of symptoms. “It has often been said that mass psychogenic illness, or what was formerly called mass hysteria, was conveyed by line-of-sight transmission. It was seeing the symptoms of other people,” Dr. Mink said. “Many of these girls had posted videos or detailed descriptions of their symptoms.”

Most of the patients were seen at the Dent Neurologic Institute in Buffalo. To help confirm the diagnosis, a majority of the patients also were seen at Dr. Mink’s center in Rochester.

Insights From Prior Research

In 2004, Roach and Langley described an occurrence of mass psychogenic illness among a cohort of 10 teenage girls at a school in rural North Carolina. The patients developed paroxysmal episodes that resembled epilepsy or syncope. The episodes were relatively infrequent and typically occurred between classes. Four patients underwent video-EEG monitoring, which showed that the seizures were not epileptic. Symptoms mostly resolved after a two-week holiday break from school. “More than half of them had been treated with one or more antiepileptic medications,” Dr. Mink said.

A study of environmental chemical incidents in the United Kingdom found that a substantial minority of cases could involve mass psychogenic illness. Page et al examined incidents over a 15-month period between 2007 and 2008. Of 965 total incidents, 747 were eligible for inclusion in the study, and 280 were selected randomly for detailed evaluation.

The British researchers’ criteria for diagnosing mass psychogenic illness included the presence of somatic symptoms, a preexisting social connection between two or more of the affected people, the spread of symptoms from person to person, and the attribution of symptoms by affected individuals or by their parents or caregivers to a threatening external agent of a physical or spiritual nature. Finally, the symptoms and signs were not compatible with environmental exposures that reasonably could have been expected to be present at the time.

Nineteen of the 280 incidents were classified as probable or highly probable mass psychogenic illness (six highly probable and 13 probable), which represented 7% of the incidents and 16% of incidents in which people reported symptoms that were attributed to the chemical incident. Factors that were more common among cases of mass psychogenic illness included the presence of a nonsmoke odor and occurrence in a school or health care facility.

Experimental Induction of Mass Psychogenic Illness

Broderick et al in 2011 described a randomized controlled experimental induction of mass psychogenic illness. Their study included 39 healthy adults with a mean age of 42. A little more than half were women, half were college graduates, and almost 80% were Caucasian.

A control group sat in a room and engaged in quiet activity, while two psychogenic illness induction groups received a pill. One of the induction groups was shown a video (ie, the pill-plus-media group).

Researchers told participants in the pill groups that the study was designed to further evaluate the side effects of a new carrier compound for an antiviral medication. The participants were told that the compound contained only cellulose and did not produce serious side effects.

In the pill groups, confederates (one man and one woman) feigned illness (eg, nausea, dizziness, and headache) about 20 minutes after participants took the pills. Nurses attended to the confederates and to any participant who simulated or experienced symptoms, by taking their blood pressure and pulse, providing cool cloths for their foreheads, supplying bowls for potential vomiting, and sometimes putting participants with symptoms on gurneys outside the room within view of the other participants. An hour after taking the pills, the pill-plus-media group watched a public television documentary about the 1918 flu pandemic.

All three groups were assessed at baseline, at one hour, and at two hours. Participants rated their current symptoms by questionnaire, and nurses measured participants’ heart rate and blood pressure. Researchers debriefed all participants after the third assessment, and participants completed a psychosocial risk factor battery within a week of the initial experiment.

The primary outcome was symptom score. Participants in all three groups had some symptoms at baseline (eg, elevated heart rate and slight discomfort). At one hour, the control group had reduced symptoms, whereas the pill groups had increased symptom scores. At two hours, the control group still had few symptoms, but the psychogenic illness induction groups’ symptoms increased further. Symptoms did not differ between the pill-only and pill-plus-media groups, however.

An analysis of the psychosocial risk factor questionnaires found that participants’ total number of traumatic life events was positively associated with increased symptoms, but this relationship was not particularly strong. “It seems that the most important thing is … being exposed to people who are feigning symptoms or displaying symptoms in the setting of being told that there is a potential agent that might cause those symptoms,” Dr. Mink said.

Outcomes in Le Roy

Amid media coverage of the cases in Le Roy, Dr. Mink declined daily invitations to appear on television. “The last time I talked to the producer, I said, ‘You know, you would do these girls a big favor if you would just leave them alone,’” he said. “While the media attention persisted for another week, the improvement of their symptoms did coincide with reduced media attention, so one can speculate that that might have played a role.”

The patients in Le Roy received varying therapies, including cognitive behavioral therapy and supportive psychotherapy. They all received education about functional neurologic disorders. Some received pharmacotherapy for coexisting anxiety, and treatment of coexisting anxiety or depression coincided with patient improvement as well.

At last follow-up about two years ago, five of the 19 no longer had symptoms. Six of the 19 had experienced a greater than 85% improvement. A couple of patients continued to have symptoms, including the patients with a prior diagnosis of a chronic tic disorder. Two patients who had not improved sued the school district and alleged environmental toxins as the cause of their symptoms. The other patients were lost to follow up.

Treatment Principles

When treating patients with mass psychogenic illness, “First of all, you have to be an ally of your patient and not challenge the veracity,” Dr. Mink said. “For some of these girls, I think that there was some factitious component,” but this factor was not especially relevant to treatment recommendations.

“For mass psychogenic illness, reducing attention from social media groups and perhaps finding a way to disrupt the social cohesiveness of that group, at least until the symptoms can improve,” may be beneficial, he said. “Regular follow-up is helpful for all conversion disorders…. You do not want the patient to have to get worse to be able to see their doctor.”

Once neurologists have confirmed the diagnosis of mass psychogenic illness, they should “reinforce the certainty of the diagnosis” to occupational therapists, physical therapists, psychotherapists, and others on the health care team who treat these patients, Dr. Mink said. In addition,“It is important to prepare the therapist, particularly in an unusual situation like this where there has been a lot of media attention.”

—Jake Remaly

Suggested Reading

Bartholomew RE, Wessely S, Rubin GJ. Mass psychogenic illness and the social network: is it changing the pattern of outbreaks? J R Soc Med. 2012;105(12):509-512.

Broderick JE, Kaplan-Liss E, Bass E. Experimental induction of psychogenic illness in the context of a medical event and media exposure. Am J Disaster Med. 2011;6(3):163-172.

Page LA, Keshishian C, Leonardi G, et al. Frequency and predictors of mass psychogenic illness. Epidemiology. 2010;21(5):744-747.

Roach ES, Langley RL. Episodic neurological dysfunction due to mass hysteria. Arch Neurol. 2004;61(8):1269-1272.

Stuart D. Cook, MD, and Abdul Rahman Alchaki

Dr. Cook is the Ruth Dunietz Kushner and Michael Jay Serwitz Professor of Neurology/Neurosciences at Rutgers, the State University of New Jersey, Newark. Dr. Alchaki is a resident in the Deptartment of Neurology/Neurosciences at Rutgers, the State University of New Jersey, Newark.

Disclosure: Stuart Cook has received honoraria for lectures from Bayer HealthCare and Merck Serono. He has served as a consultant for Merck Serono, Bayer HealthCare, Teva, Novartis, Sanofi-Aventis, Biogen Idec, and Actinobac Biomed. He has served on steering committees for the BEYOND and CLARITY Studies and as a member of Advisory Boards for Merck Serono, Bayer HealthCare, Teva, Biogen Idec, Sanofi Aventis, and Actinobac Biomed.

The Initial Years (1838 to 1930s)

The earliest recognition of MS clinical features and pathology was attributed to Jean-Martin Charcot, Robert Carswell, and Jean Cruveilhier in Europe from 1838 to 1868. Beyond those early descriptions, relatively few MS breakthroughs occurred until the 1930s, when Thomas Rivers discovered experimental autoimmune encephalomyelitis (EAE), a demyelinating disease, in animals. His insightful concepts were widely cited and ultimately contributed to undestanding of the immune mechanisms of MS and acute disseminated encephalomyelitis (ADEM).

Advances in Diagnosis (1965 to 1992)

In 1965, Schumacher et al provided the essential clinical criteria for MS diagnosis. Poser et al refined these criteria in 1983. In 2001, McDonald et al added neuroimaging, CSF analysis, and evoked potentials to further complement MS clinical diagnosis. For the first time, the disease could generally be recognized.

Early Treatments

Various treatments for MS were tried over the years, without great success. However, in 1953, a small descriptive trial by Miller and Gibbons reported clinical benefits in patients using intramuscular (IM) adrenocorticotropic hormone (ACTH) for MS and disseminated encephalomyelitis. This was followed in 1970 by a Cooperative Study of IM ACTH versus placebo by Rose et al, which resulted in ACTH, and subsequently oral corticosteroids, being widely used to treat MS, particularly for acute exacerbations of the disease. However, robust evidence of long-term steroids remain limited, even to the present.

High-Dose Steroids

By 1980, the initial descriptive treatment of high-dose intravenous (IV) steroids for demyelinating diseases, including MS and transverse myelitis, by Dowling et al resulted in rapid clinical improvement in some patients. This result was ultimately confirmed by others. High-dose IV steroids became the gold standard for acute attacks, particularly those aggressive in nature. In the mid 1980s, work by Troiano et al, as well as others, showed that the rapid use of high-dose IV as well as oral steroids showed similar effects, with reduction or elimination of CT contrast-enhancing lesions within as few as eight hours, while lower doses or alternative-day treatments were less effective. In addition, descriptive studies of immune modulatory and immunosuppressive drugs, as well as small randomized studies, were published. These agents did not receive FDA approval.

The Golden Age of Therapy (1993 to 2018)

A remarkable era in MS prognosis and treatment began with immunomodulation injections of Betaseron (INFβ-1b), Avonex (INFβ-1a), and Copaxone (glatiramer acetate). This can be attributed, at least in part, to advances in molecular biology, genetics, and neuroimaging, and support by corporate, private, and public funding. Since the initial FDA approval of INFβ-1b, 15 MS therapies have become clinically available, including eight injectables, three orals, and four infusion treatments (see Table 1). In addition, two other drugs have been FDA approved for uses other than MS: rituximab (approved for lymphoma) and cladribine (for hairy cell leukemia), with the latter now approved by the European Medicines Agency for MS. Table 1 depicts characteristics of these therapies approved by US or European agencies (or for other disorders increasingly used off label for MS) in an attempt to compare annual relapse rates (ARR) and decreases in the percent of gadolinium-enhancing MS lesions versus placebo. This information was chosen because ARR has been uniformly selected and defined for such trials, while percent decrease of gadolinium-enhancing lesions on MRI has been the most sensitive barometer available for assessing acute clinical activity. As a result, risk-benefit considerations have been critical in evaluating these drug treatments, with efficacy improving greatly over time, whereas risks have been more variable.

Disease Categories

In 1996, Lublin and Reingold provided a new classification, not specifically for the diagnosis of MS, but rather for the clinical course of the disease. Initially, there were four categories—relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive-relapsing MS—that were universally identified. These were thought to be relatively distinct clinical categories, but over time it became clear that the classification did not fully distinguish MS disease activity within these categories. For that reason, it was subsequently recommended, by Lincoln et al in 2009 and Cook et al in 2012, to include MRI, a vastly more sensitive modality, as well as clinical data in assessing disease activity.

On another note, MS and neuromyelitis optica (NMO), although having similar features, were clearly identified as different diseases by Lennon et al in 2004. Differences in pathology, clinical characteristics, immunology, and therapy separate the two disorders.

MRI in MS

Work by Young et al in 1981 established the central role of MRI brain imaging in MS diagnosis and therapeutic considerations. Since then it has become ubiquitous.

An example of a sensitive and highly productive MRI protocol is the BECOME study of MS and clinically isolated syndrome by Cadavid et al from 2009 to 2017. In this study, IFNβ-1b was compared with glatiramer acetate treatment. Cadavid et al used a 3T scanner with triple-dose gadolinium, performed monthly for as long as 24 consecutive months. This unique study brought about a virtual gold mine of valuable research and clinical information. This included proof that gadolinium-enhancing lesions persisted for six months or more, evidence of a 30:1 ratio of new MRI brain lesions to clinical activity, and documentation that 96% of T2 lesions and black holes derive from prior gadolinium-enhancing lesions. It was further noted that 80% to 90% of acute black holes disappeared with treatment and 75% to 80% of patients taking IFNβ-1b or glatiramer acetate had new MRI lesions despite continuing treatment. Perhaps most interestingly, monthly MRIs could predict relapse and disability in a relatively small number of patients, depending upon the frequency and activity of MRI lesions. In 2017, Brown et al documented that magnetization transfer ratio recovery in MS brain lesions occurred more significantly with glatiramer acetate than with IFNβ-1b, whereas more chronic black hole lesions were found with glatiramer acetate. Also in 2017, Maranzano et al found evidence of acute inflammatory leukocortical lesions, which were not as well recognized previously.

In summary, it has become increasingly clear that MRI is the most sensitive available barometer for evaluating activity, pathology, and prognosis in most aspects of MS.

The Future of MS

While it is not yet a curable disease, there is growing evidence that MS prognosis has improved and will continue to improve. This is based on incremental decreases in acute MS exacerbations, progressive disability, and MRI lesion activity, as well as a combination of the three—no evidence of disease activity (NEDA).

Not only are drug therapies becoming more effective, but patients and physicians now have many more treatment options to carefully consider with regard to efficacy, side effect profiles, treatment frequency, route of administration, cost, and quality of life. Newer drugs with different mechanisms of action such as cladribine, now approved in Europe, fulfill most of these beneficial criteria (see Giovannoni et al, 2010). More promising MS treatments, including long-acting induction therapies, are still being evaluated. As with other complex diseases, multiple therapies are likely to be used as well.

In summary, compared with the time before 1993, MS will be much less likely to be a progressive disease, and quality of life will be much improved. In my opinion, patients will be less fearful about their prognosis than ever before, and with appropriate evaluations and treatments, we may realize that disabling MS will be far less common.

Suggested Reading

Brown JW, Pardini M, Brownlee WJ, et al. An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis. Brain. 2017;140(2):387-398.

Cadavid D, Wolansky LJ, Skurnick J, et al. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology. 2009;72(23):1976-1983.

Cook SD, Dhib-Jalbut S, Dowling P, et al. Use of magnetic resonance imaging as well as clinical disease activity in the clinical classification of multiple sclerosis and assessment of its course: a report from an international CMSC consensus conference, March 5-7, 2010. Int J MS Care. 2012;14(3):105-114.

Dowling PC, Bosch VV, Cook SD. Possible beneficial effect of high-dose intravenous steroid therapy in acute demyelinating disease and transverse myelitis. Neurology. 1980;30(7 Pt 2):33-36.

Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416-426.

Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106-2112.

Lincoln JA, Cadavid D, Pollard J, et al. We should use magnetic resonance imaging to classify and monitor the course of multiple sclerosis. Arch Neurol. 2009;66(3):412-414.

Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996;46(4):907-911.

Maranzano J, Rudko DA, Nakamura K, et al. MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis. Neurology. 2017;89(7):714-721.

McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127.

Miller HG, Gibbons JL. Acute disseminated encephalomyelitis and acute disseminated sclerosis; results of treatment with A.C.T.H. Br Med J. 1953;2(4850):1345-1348.

Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13(3):227-231.

Rose AS, Kuzma JW, Kurtzke JF, et al. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology. 1970;20(5):1-59.

Troiano R, Hafstein M, Ruderman M, et al. Effect of high-dose intravenous steroid administration on contrast-enhancing computed tomographic scan lesions in multiple sclerosis. Ann Neurol. 1984;15(3):257-263.

Troiano RA, Hafstein MP, Zito G, et al. The effect of oral corticosteroid dosage on CT enhancing multiple sclerosis plaques. J Neurol Sci. 1985;70(1):67-72.

Young IR, Hall AS, Pallis A, et al. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet. 1981;2(8255):1063-1066.

Stuart D. Cook, MD, and Abdul Rahman Alchaki

Dr. Cook is the Ruth Dunietz Kushner and Michael Jay Serwitz Professor of Neurology/Neurosciences at Rutgers, the State University of New Jersey, Newark. Dr. Alchaki is a resident in the Deptartment of Neurology/Neurosciences at Rutgers, the State University of New Jersey, Newark.

Disclosure: Stuart Cook has received honoraria for lectures from Bayer HealthCare and Merck Serono. He has served as a consultant for Merck Serono, Bayer HealthCare, Teva, Novartis, Sanofi-Aventis, Biogen Idec, and Actinobac Biomed. He has served on steering committees for the BEYOND and CLARITY Studies and as a member of Advisory Boards for Merck Serono, Bayer HealthCare, Teva, Biogen Idec, Sanofi Aventis, and Actinobac Biomed.

The Initial Years (1838 to 1930s)

The earliest recognition of MS clinical features and pathology was attributed to Jean-Martin Charcot, Robert Carswell, and Jean Cruveilhier in Europe from 1838 to 1868. Beyond those early descriptions, relatively few MS breakthroughs occurred until the 1930s, when Thomas Rivers discovered experimental autoimmune encephalomyelitis (EAE), a demyelinating disease, in animals. His insightful concepts were widely cited and ultimately contributed to undestanding of the immune mechanisms of MS and acute disseminated encephalomyelitis (ADEM).

Advances in Diagnosis (1965 to 1992)

In 1965, Schumacher et al provided the essential clinical criteria for MS diagnosis. Poser et al refined these criteria in 1983. In 2001, McDonald et al added neuroimaging, CSF analysis, and evoked potentials to further complement MS clinical diagnosis. For the first time, the disease could generally be recognized.

Early Treatments

Various treatments for MS were tried over the years, without great success. However, in 1953, a small descriptive trial by Miller and Gibbons reported clinical benefits in patients using intramuscular (IM) adrenocorticotropic hormone (ACTH) for MS and disseminated encephalomyelitis. This was followed in 1970 by a Cooperative Study of IM ACTH versus placebo by Rose et al, which resulted in ACTH, and subsequently oral corticosteroids, being widely used to treat MS, particularly for acute exacerbations of the disease. However, robust evidence of long-term steroids remain limited, even to the present.

High-Dose Steroids

By 1980, the initial descriptive treatment of high-dose intravenous (IV) steroids for demyelinating diseases, including MS and transverse myelitis, by Dowling et al resulted in rapid clinical improvement in some patients. This result was ultimately confirmed by others. High-dose IV steroids became the gold standard for acute attacks, particularly those aggressive in nature. In the mid 1980s, work by Troiano et al, as well as others, showed that the rapid use of high-dose IV as well as oral steroids showed similar effects, with reduction or elimination of CT contrast-enhancing lesions within as few as eight hours, while lower doses or alternative-day treatments were less effective. In addition, descriptive studies of immune modulatory and immunosuppressive drugs, as well as small randomized studies, were published. These agents did not receive FDA approval.

The Golden Age of Therapy (1993 to 2018)

A remarkable era in MS prognosis and treatment began with immunomodulation injections of Betaseron (INFβ-1b), Avonex (INFβ-1a), and Copaxone (glatiramer acetate). This can be attributed, at least in part, to advances in molecular biology, genetics, and neuroimaging, and support by corporate, private, and public funding. Since the initial FDA approval of INFβ-1b, 15 MS therapies have become clinically available, including eight injectables, three orals, and four infusion treatments (see Table 1). In addition, two other drugs have been FDA approved for uses other than MS: rituximab (approved for lymphoma) and cladribine (for hairy cell leukemia), with the latter now approved by the European Medicines Agency for MS. Table 1 depicts characteristics of these therapies approved by US or European agencies (or for other disorders increasingly used off label for MS) in an attempt to compare annual relapse rates (ARR) and decreases in the percent of gadolinium-enhancing MS lesions versus placebo. This information was chosen because ARR has been uniformly selected and defined for such trials, while percent decrease of gadolinium-enhancing lesions on MRI has been the most sensitive barometer available for assessing acute clinical activity. As a result, risk-benefit considerations have been critical in evaluating these drug treatments, with efficacy improving greatly over time, whereas risks have been more variable.

Disease Categories

In 1996, Lublin and Reingold provided a new classification, not specifically for the diagnosis of MS, but rather for the clinical course of the disease. Initially, there were four categories—relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive-relapsing MS—that were universally identified. These were thought to be relatively distinct clinical categories, but over time it became clear that the classification did not fully distinguish MS disease activity within these categories. For that reason, it was subsequently recommended, by Lincoln et al in 2009 and Cook et al in 2012, to include MRI, a vastly more sensitive modality, as well as clinical data in assessing disease activity.

On another note, MS and neuromyelitis optica (NMO), although having similar features, were clearly identified as different diseases by Lennon et al in 2004. Differences in pathology, clinical characteristics, immunology, and therapy separate the two disorders.

MRI in MS

Work by Young et al in 1981 established the central role of MRI brain imaging in MS diagnosis and therapeutic considerations. Since then it has become ubiquitous.

An example of a sensitive and highly productive MRI protocol is the BECOME study of MS and clinically isolated syndrome by Cadavid et al from 2009 to 2017. In this study, IFNβ-1b was compared with glatiramer acetate treatment. Cadavid et al used a 3T scanner with triple-dose gadolinium, performed monthly for as long as 24 consecutive months. This unique study brought about a virtual gold mine of valuable research and clinical information. This included proof that gadolinium-enhancing lesions persisted for six months or more, evidence of a 30:1 ratio of new MRI brain lesions to clinical activity, and documentation that 96% of T2 lesions and black holes derive from prior gadolinium-enhancing lesions. It was further noted that 80% to 90% of acute black holes disappeared with treatment and 75% to 80% of patients taking IFNβ-1b or glatiramer acetate had new MRI lesions despite continuing treatment. Perhaps most interestingly, monthly MRIs could predict relapse and disability in a relatively small number of patients, depending upon the frequency and activity of MRI lesions. In 2017, Brown et al documented that magnetization transfer ratio recovery in MS brain lesions occurred more significantly with glatiramer acetate than with IFNβ-1b, whereas more chronic black hole lesions were found with glatiramer acetate. Also in 2017, Maranzano et al found evidence of acute inflammatory leukocortical lesions, which were not as well recognized previously.

In summary, it has become increasingly clear that MRI is the most sensitive available barometer for evaluating activity, pathology, and prognosis in most aspects of MS.

The Future of MS

While it is not yet a curable disease, there is growing evidence that MS prognosis has improved and will continue to improve. This is based on incremental decreases in acute MS exacerbations, progressive disability, and MRI lesion activity, as well as a combination of the three—no evidence of disease activity (NEDA).

Not only are drug therapies becoming more effective, but patients and physicians now have many more treatment options to carefully consider with regard to efficacy, side effect profiles, treatment frequency, route of administration, cost, and quality of life. Newer drugs with different mechanisms of action such as cladribine, now approved in Europe, fulfill most of these beneficial criteria (see Giovannoni et al, 2010). More promising MS treatments, including long-acting induction therapies, are still being evaluated. As with other complex diseases, multiple therapies are likely to be used as well.

In summary, compared with the time before 1993, MS will be much less likely to be a progressive disease, and quality of life will be much improved. In my opinion, patients will be less fearful about their prognosis than ever before, and with appropriate evaluations and treatments, we may realize that disabling MS will be far less common.

Suggested Reading

Brown JW, Pardini M, Brownlee WJ, et al. An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis. Brain. 2017;140(2):387-398.

Cadavid D, Wolansky LJ, Skurnick J, et al. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology. 2009;72(23):1976-1983.

Cook SD, Dhib-Jalbut S, Dowling P, et al. Use of magnetic resonance imaging as well as clinical disease activity in the clinical classification of multiple sclerosis and assessment of its course: a report from an international CMSC consensus conference, March 5-7, 2010. Int J MS Care. 2012;14(3):105-114.

Dowling PC, Bosch VV, Cook SD. Possible beneficial effect of high-dose intravenous steroid therapy in acute demyelinating disease and transverse myelitis. Neurology. 1980;30(7 Pt 2):33-36.

Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416-426.

Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106-2112.

Lincoln JA, Cadavid D, Pollard J, et al. We should use magnetic resonance imaging to classify and monitor the course of multiple sclerosis. Arch Neurol. 2009;66(3):412-414.

Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996;46(4):907-911.

Maranzano J, Rudko DA, Nakamura K, et al. MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis. Neurology. 2017;89(7):714-721.

McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127.

Miller HG, Gibbons JL. Acute disseminated encephalomyelitis and acute disseminated sclerosis; results of treatment with A.C.T.H. Br Med J. 1953;2(4850):1345-1348.

Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13(3):227-231.

Rose AS, Kuzma JW, Kurtzke JF, et al. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology. 1970;20(5):1-59.

Troiano R, Hafstein M, Ruderman M, et al. Effect of high-dose intravenous steroid administration on contrast-enhancing computed tomographic scan lesions in multiple sclerosis. Ann Neurol. 1984;15(3):257-263.

Troiano RA, Hafstein MP, Zito G, et al. The effect of oral corticosteroid dosage on CT enhancing multiple sclerosis plaques. J Neurol Sci. 1985;70(1):67-72.

Young IR, Hall AS, Pallis A, et al. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet. 1981;2(8255):1063-1066.

Stuart D. Cook, MD, and Abdul Rahman Alchaki

Dr. Cook is the Ruth Dunietz Kushner and Michael Jay Serwitz Professor of Neurology/Neurosciences at Rutgers, the State University of New Jersey, Newark. Dr. Alchaki is a resident in the Deptartment of Neurology/Neurosciences at Rutgers, the State University of New Jersey, Newark.

Disclosure: Stuart Cook has received honoraria for lectures from Bayer HealthCare and Merck Serono. He has served as a consultant for Merck Serono, Bayer HealthCare, Teva, Novartis, Sanofi-Aventis, Biogen Idec, and Actinobac Biomed. He has served on steering committees for the BEYOND and CLARITY Studies and as a member of Advisory Boards for Merck Serono, Bayer HealthCare, Teva, Biogen Idec, Sanofi Aventis, and Actinobac Biomed.

The Initial Years (1838 to 1930s)

The earliest recognition of MS clinical features and pathology was attributed to Jean-Martin Charcot, Robert Carswell, and Jean Cruveilhier in Europe from 1838 to 1868. Beyond those early descriptions, relatively few MS breakthroughs occurred until the 1930s, when Thomas Rivers discovered experimental autoimmune encephalomyelitis (EAE), a demyelinating disease, in animals. His insightful concepts were widely cited and ultimately contributed to undestanding of the immune mechanisms of MS and acute disseminated encephalomyelitis (ADEM).

Advances in Diagnosis (1965 to 1992)

In 1965, Schumacher et al provided the essential clinical criteria for MS diagnosis. Poser et al refined these criteria in 1983. In 2001, McDonald et al added neuroimaging, CSF analysis, and evoked potentials to further complement MS clinical diagnosis. For the first time, the disease could generally be recognized.

Early Treatments

Various treatments for MS were tried over the years, without great success. However, in 1953, a small descriptive trial by Miller and Gibbons reported clinical benefits in patients using intramuscular (IM) adrenocorticotropic hormone (ACTH) for MS and disseminated encephalomyelitis. This was followed in 1970 by a Cooperative Study of IM ACTH versus placebo by Rose et al, which resulted in ACTH, and subsequently oral corticosteroids, being widely used to treat MS, particularly for acute exacerbations of the disease. However, robust evidence of long-term steroids remain limited, even to the present.

High-Dose Steroids

By 1980, the initial descriptive treatment of high-dose intravenous (IV) steroids for demyelinating diseases, including MS and transverse myelitis, by Dowling et al resulted in rapid clinical improvement in some patients. This result was ultimately confirmed by others. High-dose IV steroids became the gold standard for acute attacks, particularly those aggressive in nature. In the mid 1980s, work by Troiano et al, as well as others, showed that the rapid use of high-dose IV as well as oral steroids showed similar effects, with reduction or elimination of CT contrast-enhancing lesions within as few as eight hours, while lower doses or alternative-day treatments were less effective. In addition, descriptive studies of immune modulatory and immunosuppressive drugs, as well as small randomized studies, were published. These agents did not receive FDA approval.

The Golden Age of Therapy (1993 to 2018)

A remarkable era in MS prognosis and treatment began with immunomodulation injections of Betaseron (INFβ-1b), Avonex (INFβ-1a), and Copaxone (glatiramer acetate). This can be attributed, at least in part, to advances in molecular biology, genetics, and neuroimaging, and support by corporate, private, and public funding. Since the initial FDA approval of INFβ-1b, 15 MS therapies have become clinically available, including eight injectables, three orals, and four infusion treatments (see Table 1). In addition, two other drugs have been FDA approved for uses other than MS: rituximab (approved for lymphoma) and cladribine (for hairy cell leukemia), with the latter now approved by the European Medicines Agency for MS. Table 1 depicts characteristics of these therapies approved by US or European agencies (or for other disorders increasingly used off label for MS) in an attempt to compare annual relapse rates (ARR) and decreases in the percent of gadolinium-enhancing MS lesions versus placebo. This information was chosen because ARR has been uniformly selected and defined for such trials, while percent decrease of gadolinium-enhancing lesions on MRI has been the most sensitive barometer available for assessing acute clinical activity. As a result, risk-benefit considerations have been critical in evaluating these drug treatments, with efficacy improving greatly over time, whereas risks have been more variable.

Disease Categories

In 1996, Lublin and Reingold provided a new classification, not specifically for the diagnosis of MS, but rather for the clinical course of the disease. Initially, there were four categories—relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive-relapsing MS—that were universally identified. These were thought to be relatively distinct clinical categories, but over time it became clear that the classification did not fully distinguish MS disease activity within these categories. For that reason, it was subsequently recommended, by Lincoln et al in 2009 and Cook et al in 2012, to include MRI, a vastly more sensitive modality, as well as clinical data in assessing disease activity.

On another note, MS and neuromyelitis optica (NMO), although having similar features, were clearly identified as different diseases by Lennon et al in 2004. Differences in pathology, clinical characteristics, immunology, and therapy separate the two disorders.

MRI in MS

Work by Young et al in 1981 established the central role of MRI brain imaging in MS diagnosis and therapeutic considerations. Since then it has become ubiquitous.

An example of a sensitive and highly productive MRI protocol is the BECOME study of MS and clinically isolated syndrome by Cadavid et al from 2009 to 2017. In this study, IFNβ-1b was compared with glatiramer acetate treatment. Cadavid et al used a 3T scanner with triple-dose gadolinium, performed monthly for as long as 24 consecutive months. This unique study brought about a virtual gold mine of valuable research and clinical information. This included proof that gadolinium-enhancing lesions persisted for six months or more, evidence of a 30:1 ratio of new MRI brain lesions to clinical activity, and documentation that 96% of T2 lesions and black holes derive from prior gadolinium-enhancing lesions. It was further noted that 80% to 90% of acute black holes disappeared with treatment and 75% to 80% of patients taking IFNβ-1b or glatiramer acetate had new MRI lesions despite continuing treatment. Perhaps most interestingly, monthly MRIs could predict relapse and disability in a relatively small number of patients, depending upon the frequency and activity of MRI lesions. In 2017, Brown et al documented that magnetization transfer ratio recovery in MS brain lesions occurred more significantly with glatiramer acetate than with IFNβ-1b, whereas more chronic black hole lesions were found with glatiramer acetate. Also in 2017, Maranzano et al found evidence of acute inflammatory leukocortical lesions, which were not as well recognized previously.

In summary, it has become increasingly clear that MRI is the most sensitive available barometer for evaluating activity, pathology, and prognosis in most aspects of MS.

The Future of MS

While it is not yet a curable disease, there is growing evidence that MS prognosis has improved and will continue to improve. This is based on incremental decreases in acute MS exacerbations, progressive disability, and MRI lesion activity, as well as a combination of the three—no evidence of disease activity (NEDA).

Not only are drug therapies becoming more effective, but patients and physicians now have many more treatment options to carefully consider with regard to efficacy, side effect profiles, treatment frequency, route of administration, cost, and quality of life. Newer drugs with different mechanisms of action such as cladribine, now approved in Europe, fulfill most of these beneficial criteria (see Giovannoni et al, 2010). More promising MS treatments, including long-acting induction therapies, are still being evaluated. As with other complex diseases, multiple therapies are likely to be used as well.

In summary, compared with the time before 1993, MS will be much less likely to be a progressive disease, and quality of life will be much improved. In my opinion, patients will be less fearful about their prognosis than ever before, and with appropriate evaluations and treatments, we may realize that disabling MS will be far less common.

Suggested Reading

Brown JW, Pardini M, Brownlee WJ, et al. An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis. Brain. 2017;140(2):387-398.

Cadavid D, Wolansky LJ, Skurnick J, et al. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology. 2009;72(23):1976-1983.

Cook SD, Dhib-Jalbut S, Dowling P, et al. Use of magnetic resonance imaging as well as clinical disease activity in the clinical classification of multiple sclerosis and assessment of its course: a report from an international CMSC consensus conference, March 5-7, 2010. Int J MS Care. 2012;14(3):105-114.

Dowling PC, Bosch VV, Cook SD. Possible beneficial effect of high-dose intravenous steroid therapy in acute demyelinating disease and transverse myelitis. Neurology. 1980;30(7 Pt 2):33-36.

Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416-426.

Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106-2112.

Lincoln JA, Cadavid D, Pollard J, et al. We should use magnetic resonance imaging to classify and monitor the course of multiple sclerosis. Arch Neurol. 2009;66(3):412-414.

Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996;46(4):907-911.

Maranzano J, Rudko DA, Nakamura K, et al. MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis. Neurology. 2017;89(7):714-721.

McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127.

Miller HG, Gibbons JL. Acute disseminated encephalomyelitis and acute disseminated sclerosis; results of treatment with A.C.T.H. Br Med J. 1953;2(4850):1345-1348.

Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13(3):227-231.

Rose AS, Kuzma JW, Kurtzke JF, et al. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. Neurology. 1970;20(5):1-59.

Troiano R, Hafstein M, Ruderman M, et al. Effect of high-dose intravenous steroid administration on contrast-enhancing computed tomographic scan lesions in multiple sclerosis. Ann Neurol. 1984;15(3):257-263.

Troiano RA, Hafstein MP, Zito G, et al. The effect of oral corticosteroid dosage on CT enhancing multiple sclerosis plaques. J Neurol Sci. 1985;70(1):67-72.

Young IR, Hall AS, Pallis A, et al. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet. 1981;2(8255):1063-1066.

WASHINGTON, DC—Alcohol is a major seizure precipitant in the context of hazardous drinking and withdrawal, according to a study presented at the 71st Annual Meeting of the American Epilepsy Society. Occasional social drinking, however, is an uncommon cause of seizure breakthrough in predominantly focal epilepsy, said the researchers.

The seizure-inducing effect of alcohol withdrawal in chronic alcohol abuse is apparent, but the effect of binge drinking and modest social drinking among patients with epilepsy is less clear. Christian Samsonsen, MD, a neurologist at St. Olav’s University Hospital in Trondheim, Norway, and colleagues conducted a prospective, observational cross-over study to examine the relationship between alcohol and seizure disorders in acutely hospitalized patients. They also examined the clinical characteristics of patients with alcohol-related seizures and their drinking patterns.

Evaluating Drinking Patterns

The study included 134 consecutive patients with seizures. Ninety-two patients had epilepsy, and 42 patients had isolated seizures not diagnosed as epilepsy. At hospital admission, researchers conducted a semistructured interview and applied the Alcohol Use Disorders Identification Test (AUDIT).

Investigators defined withdrawal seizure as having an AUDIT score of 8 or greater and alcohol intake within the last two days. They defined binge drinking as drinking more than four units in one session for females and more than five units in one session for males. They defined social drinking as having an AUDIT score of less than 8 and not drinking more than 12 units in one day.

The researchers recorded daily alcohol consumption during the five days prior to the seizure, as well as sleep time during the prior three days. Researchers then performed a follow-up telephone interview on a seizure-free day at least four weeks later.

Seizures Were More Common on Sunday and Monday

In all, 28% of patients had an AUDIT score of 8 or greater (ie, hazardous drinking), including 22% of patients with epilepsy and 43% of patients with isolated seizures. Alcohol consumption and nonfocal seizures were increased in isolated seizures, suggesting withdrawal.

One in five patients with epilepsy had been binge drinking, and 59 (64%) patients with epilepsy had been socially drinking. Among the patients who had been socially drinking, alcohol intake was not different prior to seizure, compared with follow-up, downgrading the role of modest social drinking as a seizure precipitant, said the researchers. Among the 19 patients with idiopathic generalized epilepsy, however, “even social drinking two days prior to seizure was associated with seizures,” the researchers said. Patients with epilepsy were more likely to have had their seizures on a Sunday (21%) or Monday (23%)than on other days. Patients with single seizures were more likely to have had their seizures on a Monday (29%) than on other days. Seizures associated with binge drinking were more common on Sunday.

Overall, binge drinking was associated with loss of seizure control in people with epilepsy; however, “alcohol alone should not always be blamed,” said the researchers. “In people with epilepsy, alcohol intake is often combined with other seizure precipitants,” such as sleep loss, they concluded.

—Erica Tricarico

Suggested Reading

Samsonsen C, Sand T, Brathen G, et al. The impact of sleep loss on the facilitation of seizures: A prospective case-crossover study. Epilepsy Res. 2016;127:260-266.

WASHINGTON, DC—Alcohol is a major seizure precipitant in the context of hazardous drinking and withdrawal, according to a study presented at the 71st Annual Meeting of the American Epilepsy Society. Occasional social drinking, however, is an uncommon cause of seizure breakthrough in predominantly focal epilepsy, said the researchers.

The seizure-inducing effect of alcohol withdrawal in chronic alcohol abuse is apparent, but the effect of binge drinking and modest social drinking among patients with epilepsy is less clear. Christian Samsonsen, MD, a neurologist at St. Olav’s University Hospital in Trondheim, Norway, and colleagues conducted a prospective, observational cross-over study to examine the relationship between alcohol and seizure disorders in acutely hospitalized patients. They also examined the clinical characteristics of patients with alcohol-related seizures and their drinking patterns.

Evaluating Drinking Patterns

The study included 134 consecutive patients with seizures. Ninety-two patients had epilepsy, and 42 patients had isolated seizures not diagnosed as epilepsy. At hospital admission, researchers conducted a semistructured interview and applied the Alcohol Use Disorders Identification Test (AUDIT).

Investigators defined withdrawal seizure as having an AUDIT score of 8 or greater and alcohol intake within the last two days. They defined binge drinking as drinking more than four units in one session for females and more than five units in one session for males. They defined social drinking as having an AUDIT score of less than 8 and not drinking more than 12 units in one day.

The researchers recorded daily alcohol consumption during the five days prior to the seizure, as well as sleep time during the prior three days. Researchers then performed a follow-up telephone interview on a seizure-free day at least four weeks later.

Seizures Were More Common on Sunday and Monday

In all, 28% of patients had an AUDIT score of 8 or greater (ie, hazardous drinking), including 22% of patients with epilepsy and 43% of patients with isolated seizures. Alcohol consumption and nonfocal seizures were increased in isolated seizures, suggesting withdrawal.

One in five patients with epilepsy had been binge drinking, and 59 (64%) patients with epilepsy had been socially drinking. Among the patients who had been socially drinking, alcohol intake was not different prior to seizure, compared with follow-up, downgrading the role of modest social drinking as a seizure precipitant, said the researchers. Among the 19 patients with idiopathic generalized epilepsy, however, “even social drinking two days prior to seizure was associated with seizures,” the researchers said. Patients with epilepsy were more likely to have had their seizures on a Sunday (21%) or Monday (23%)than on other days. Patients with single seizures were more likely to have had their seizures on a Monday (29%) than on other days. Seizures associated with binge drinking were more common on Sunday.

Overall, binge drinking was associated with loss of seizure control in people with epilepsy; however, “alcohol alone should not always be blamed,” said the researchers. “In people with epilepsy, alcohol intake is often combined with other seizure precipitants,” such as sleep loss, they concluded.

—Erica Tricarico

Suggested Reading

Samsonsen C, Sand T, Brathen G, et al. The impact of sleep loss on the facilitation of seizures: A prospective case-crossover study. Epilepsy Res. 2016;127:260-266.

WASHINGTON, DC—Alcohol is a major seizure precipitant in the context of hazardous drinking and withdrawal, according to a study presented at the 71st Annual Meeting of the American Epilepsy Society. Occasional social drinking, however, is an uncommon cause of seizure breakthrough in predominantly focal epilepsy, said the researchers.

The seizure-inducing effect of alcohol withdrawal in chronic alcohol abuse is apparent, but the effect of binge drinking and modest social drinking among patients with epilepsy is less clear. Christian Samsonsen, MD, a neurologist at St. Olav’s University Hospital in Trondheim, Norway, and colleagues conducted a prospective, observational cross-over study to examine the relationship between alcohol and seizure disorders in acutely hospitalized patients. They also examined the clinical characteristics of patients with alcohol-related seizures and their drinking patterns.

Evaluating Drinking Patterns

The study included 134 consecutive patients with seizures. Ninety-two patients had epilepsy, and 42 patients had isolated seizures not diagnosed as epilepsy. At hospital admission, researchers conducted a semistructured interview and applied the Alcohol Use Disorders Identification Test (AUDIT).

Investigators defined withdrawal seizure as having an AUDIT score of 8 or greater and alcohol intake within the last two days. They defined binge drinking as drinking more than four units in one session for females and more than five units in one session for males. They defined social drinking as having an AUDIT score of less than 8 and not drinking more than 12 units in one day.

The researchers recorded daily alcohol consumption during the five days prior to the seizure, as well as sleep time during the prior three days. Researchers then performed a follow-up telephone interview on a seizure-free day at least four weeks later.

Seizures Were More Common on Sunday and Monday

In all, 28% of patients had an AUDIT score of 8 or greater (ie, hazardous drinking), including 22% of patients with epilepsy and 43% of patients with isolated seizures. Alcohol consumption and nonfocal seizures were increased in isolated seizures, suggesting withdrawal.

One in five patients with epilepsy had been binge drinking, and 59 (64%) patients with epilepsy had been socially drinking. Among the patients who had been socially drinking, alcohol intake was not different prior to seizure, compared with follow-up, downgrading the role of modest social drinking as a seizure precipitant, said the researchers. Among the 19 patients with idiopathic generalized epilepsy, however, “even social drinking two days prior to seizure was associated with seizures,” the researchers said. Patients with epilepsy were more likely to have had their seizures on a Sunday (21%) or Monday (23%)than on other days. Patients with single seizures were more likely to have had their seizures on a Monday (29%) than on other days. Seizures associated with binge drinking were more common on Sunday.

Overall, binge drinking was associated with loss of seizure control in people with epilepsy; however, “alcohol alone should not always be blamed,” said the researchers. “In people with epilepsy, alcohol intake is often combined with other seizure precipitants,” such as sleep loss, they concluded.

—Erica Tricarico

Suggested Reading

Samsonsen C, Sand T, Brathen G, et al. The impact of sleep loss on the facilitation of seizures: A prospective case-crossover study. Epilepsy Res. 2016;127:260-266.

“BLACK PATIENTS PRESENT WITH MORE SEVERE VASCULAR DISEASE AND A GREATER BURDEN OF RISK FACTORS THAN WHITE PATIENTS AT TIME OF MAJOR VASCULAR INTERVENTION.” Journal of Vascular Surgery, February 2018.

African Americans come into the vascular operating room with significant co-morbidities that may explain their more severe level of disease and higher risk factors, report researchers who reviewed 76,000 vascular cases for their report in the February edition of the Journal of Vascular Surgery.

This study drills deeper into the severity of vascular disease in African Americans, adding more fuel to the discussion of health disparities between racial and ethnic groups explored by the American Medical Association, which found that minorities are less likely to receive routine medical care and face higher rates of morbidity and mortality than non-minorities.

Invited commentator Dr. William R. Flinn found the study so profound he stated, “It should be read by every vascular surgeon, in fact, by every physician.”

Researchers have observed similar outcomes in vascular surgical procedures, but determining the cause of these disparities is difficult, since databases do not provide detail on disease severity.

For this report, a multi-institutional team of vascular surgeons led by vascular surgeon Dr. Marc Schermerhorn from Beth Israel Deaconess Medical Center took direct aim at this problem. Using de-identified data from the Vascular Quality Initiative gathered between 2009 and 2014, they found that compared to white patients, black patients were:

• Younger
• More likely to smoke
• More often diagnosed with insulin-dependent diabetes, hypertension, congestive heart failure and end-stage renal disease
• Less often medicated with statins
• Less often insured

Black patients also were sicker at the time of surgery. Compared with whites, black patients had more severe:

• Carotid disease (36% versus 31% symptomatic lesions)
• AAA (27% versus 16% symptoms/rupture, and more iliac aneurysm)
• PAD (73% versus 62% critical limb ischemia)

Furthermore, black patients were less likely to be discharged on aspirin and statin therapy after treatment for AAA and PAD than whites.

The authors note that their study is limited by factors common to all database studies including missing data, variability in definitions, and no way to adjust for socio-economic factors, compliance, family support, hospital type and timing of referral.

“Even in hospitals invested in quality improvement – as evidenced by participation in the VQI – black patients present with more advanced disease and more comorbidities compared with whites, despite presenting at a younger age,” states first author Dr. Peter Soden.  “And these disparities were uniform across the spectrum of vascular disease, including carotids, AAA and PAD.” 

The increase in presenting risk factors, along with disparity in medical management, offers clues as to the well-reported worse outcomes for black patients after major vascular procedures.

“The majority of the disparities highlighted in this manuscript are not from biologic differences, but instead from social, economic and health care delivery factors,” noted Dr. Flinn. “What this most clearly suggests is that there are untold numbers of black [patients] throughout the country with undiagnosed and untreated carotid disease, abdominal aortic aneurysm and PAD (and hypertension, and diabetes, and chronic kidney disease) because they do not have equitable access to health care in the United States in the 21^st century.

“The vascular community has a unique opportunity to contribute to the health care debate in this country,” he added. “I hope we have both the scientific rigor and the political courage to pursue it aggressively.”

To download the complete article (freely available Jan.  22 - March 31), click: vsweb.org/JVS-Severe.

“BLACK PATIENTS PRESENT WITH MORE SEVERE VASCULAR DISEASE AND A GREATER BURDEN OF RISK FACTORS THAN WHITE PATIENTS AT TIME OF MAJOR VASCULAR INTERVENTION.” Journal of Vascular Surgery, February 2018.

African Americans come into the vascular operating room with significant co-morbidities that may explain their more severe level of disease and higher risk factors, report researchers who reviewed 76,000 vascular cases for their report in the February edition of the Journal of Vascular Surgery.

This study drills deeper into the severity of vascular disease in African Americans, adding more fuel to the discussion of health disparities between racial and ethnic groups explored by the American Medical Association, which found that minorities are less likely to receive routine medical care and face higher rates of morbidity and mortality than non-minorities.

Invited commentator Dr. William R. Flinn found the study so profound he stated, “It should be read by every vascular surgeon, in fact, by every physician.”

Researchers have observed similar outcomes in vascular surgical procedures, but determining the cause of these disparities is difficult, since databases do not provide detail on disease severity.

For this report, a multi-institutional team of vascular surgeons led by vascular surgeon Dr. Marc Schermerhorn from Beth Israel Deaconess Medical Center took direct aim at this problem. Using de-identified data from the Vascular Quality Initiative gathered between 2009 and 2014, they found that compared to white patients, black patients were:

• Younger
• More likely to smoke
• More often diagnosed with insulin-dependent diabetes, hypertension, congestive heart failure and end-stage renal disease
• Less often medicated with statins
• Less often insured

Black patients also were sicker at the time of surgery. Compared with whites, black patients had more severe:

• Carotid disease (36% versus 31% symptomatic lesions)
• AAA (27% versus 16% symptoms/rupture, and more iliac aneurysm)
• PAD (73% versus 62% critical limb ischemia)

Furthermore, black patients were less likely to be discharged on aspirin and statin therapy after treatment for AAA and PAD than whites.

The authors note that their study is limited by factors common to all database studies including missing data, variability in definitions, and no way to adjust for socio-economic factors, compliance, family support, hospital type and timing of referral.

“Even in hospitals invested in quality improvement – as evidenced by participation in the VQI – black patients present with more advanced disease and more comorbidities compared with whites, despite presenting at a younger age,” states first author Dr. Peter Soden.  “And these disparities were uniform across the spectrum of vascular disease, including carotids, AAA and PAD.” 

The increase in presenting risk factors, along with disparity in medical management, offers clues as to the well-reported worse outcomes for black patients after major vascular procedures.

“The majority of the disparities highlighted in this manuscript are not from biologic differences, but instead from social, economic and health care delivery factors,” noted Dr. Flinn. “What this most clearly suggests is that there are untold numbers of black [patients] throughout the country with undiagnosed and untreated carotid disease, abdominal aortic aneurysm and PAD (and hypertension, and diabetes, and chronic kidney disease) because they do not have equitable access to health care in the United States in the 21^st century.

“The vascular community has a unique opportunity to contribute to the health care debate in this country,” he added. “I hope we have both the scientific rigor and the political courage to pursue it aggressively.”

To download the complete article (freely available Jan.  22 - March 31), click: vsweb.org/JVS-Severe.

“BLACK PATIENTS PRESENT WITH MORE SEVERE VASCULAR DISEASE AND A GREATER BURDEN OF RISK FACTORS THAN WHITE PATIENTS AT TIME OF MAJOR VASCULAR INTERVENTION.” Journal of Vascular Surgery, February 2018.

African Americans come into the vascular operating room with significant co-morbidities that may explain their more severe level of disease and higher risk factors, report researchers who reviewed 76,000 vascular cases for their report in the February edition of the Journal of Vascular Surgery.

This study drills deeper into the severity of vascular disease in African Americans, adding more fuel to the discussion of health disparities between racial and ethnic groups explored by the American Medical Association, which found that minorities are less likely to receive routine medical care and face higher rates of morbidity and mortality than non-minorities.

Invited commentator Dr. William R. Flinn found the study so profound he stated, “It should be read by every vascular surgeon, in fact, by every physician.”

Researchers have observed similar outcomes in vascular surgical procedures, but determining the cause of these disparities is difficult, since databases do not provide detail on disease severity.

For this report, a multi-institutional team of vascular surgeons led by vascular surgeon Dr. Marc Schermerhorn from Beth Israel Deaconess Medical Center took direct aim at this problem. Using de-identified data from the Vascular Quality Initiative gathered between 2009 and 2014, they found that compared to white patients, black patients were:

• Younger
• More likely to smoke
• More often diagnosed with insulin-dependent diabetes, hypertension, congestive heart failure and end-stage renal disease
• Less often medicated with statins
• Less often insured

Black patients also were sicker at the time of surgery. Compared with whites, black patients had more severe:

• Carotid disease (36% versus 31% symptomatic lesions)
• AAA (27% versus 16% symptoms/rupture, and more iliac aneurysm)
• PAD (73% versus 62% critical limb ischemia)

Furthermore, black patients were less likely to be discharged on aspirin and statin therapy after treatment for AAA and PAD than whites.

The authors note that their study is limited by factors common to all database studies including missing data, variability in definitions, and no way to adjust for socio-economic factors, compliance, family support, hospital type and timing of referral.

“Even in hospitals invested in quality improvement – as evidenced by participation in the VQI – black patients present with more advanced disease and more comorbidities compared with whites, despite presenting at a younger age,” states first author Dr. Peter Soden.  “And these disparities were uniform across the spectrum of vascular disease, including carotids, AAA and PAD.” 

The increase in presenting risk factors, along with disparity in medical management, offers clues as to the well-reported worse outcomes for black patients after major vascular procedures.

“The majority of the disparities highlighted in this manuscript are not from biologic differences, but instead from social, economic and health care delivery factors,” noted Dr. Flinn. “What this most clearly suggests is that there are untold numbers of black [patients] throughout the country with undiagnosed and untreated carotid disease, abdominal aortic aneurysm and PAD (and hypertension, and diabetes, and chronic kidney disease) because they do not have equitable access to health care in the United States in the 21^st century.

“The vascular community has a unique opportunity to contribute to the health care debate in this country,” he added. “I hope we have both the scientific rigor and the political courage to pursue it aggressively.”

To download the complete article (freely available Jan.  22 - March 31), click: vsweb.org/JVS-Severe.

Applications are due March 2 for the Wylie Scholar Award, co-sponsored by the SVS Foundation and Vascular Cures. The three-year, $150,000 grant is awarded to a promising vascular surgeon-scientist in North America and is designed to support outstanding surgeon-scientists conducting innovative academic research in the early stages of their careers.

Applications are due March 2 for the Wylie Scholar Award, co-sponsored by the SVS Foundation and Vascular Cures. The three-year, $150,000 grant is awarded to a promising vascular surgeon-scientist in North America and is designed to support outstanding surgeon-scientists conducting innovative academic research in the early stages of their careers.

Applications are due March 2 for the Wylie Scholar Award, co-sponsored by the SVS Foundation and Vascular Cures. The three-year, $150,000 grant is awarded to a promising vascular surgeon-scientist in North America and is designed to support outstanding surgeon-scientists conducting innovative academic research in the early stages of their careers.

SVS members, please remind any vascular PAs with whom you work to consider submitting an abstract for the inaugural PA programming or be a speaker during our 2018 Vascular Annual Meeting. More information is here -- please forward to your PAs!

SVS members, please remind any vascular PAs with whom you work to consider submitting an abstract for the inaugural PA programming or be a speaker during our 2018 Vascular Annual Meeting. More information is here -- please forward to your PAs!

SVS members, please remind any vascular PAs with whom you work to consider submitting an abstract for the inaugural PA programming or be a speaker during our 2018 Vascular Annual Meeting. More information is here -- please forward to your PAs!

Postpartum psychosis is a psychiatric emergency that can endanger the life of the mother and the newborn child if untreated. About 1 to 2 mothers in 1,000 experiences postpartum psychosis after delivery.¹ This rate is much higher among women with an established diagnosis of bipolar disorder before pregnancy.¹

Expedient recognition, diagnosis, and referral to a high-level psychiatric facility (usually a locked inpatient unit) are critical for ensuring the safety of mother and infant. A diligent medical workup followed by thorough education for the patient and family are important steps in caring for patients with postpartum psychosis. Close mental health follow-up, pharmacologic interventions, informed decision making regarding breastfeeding, and preserving the sleep-wake cycle are critical for stabilization.²

The authors present the case of a patient admitted to VA Central California Health Care System (VACCHCS) with postpartum psychosis and a discussion on existing research on the prevalence of postpartum psychosis, relevant risk factors, the association with bipolar disorder, and treatment strategies.

Case Presentation

A 31-year-old active-duty female with no history of mental illness was admitted to the psychiatric unit because new-onset disorganized behavior was preventing her from functioning at her workplace. Two weeks after giving birth to her second child, the patient began exhibiting an uncharacteristic, debilitating labile mood and disorganized behavior. Her supervisors required her to present for medical attention about 3 months after the birth of her child. She was transferred to VACCHCS for higher level medical care on military orders. The patient’s husband initially attributed these psychiatric symptoms to vocational stress and taking care of 2 young children. He observed the patient exhibiting tearfulness about her job, which quickly alternated with euphoric episodes of singing and dancing at inappropriate times, such as when the children had quieted down and were being prepared to go to bed.

At the initial psychiatric evaluation after transfer to VACCHCS, the patient appeared well-kept and slightly overweight. In general her appearance was unremarkable. Throughout the examination she sang both subtly and loudly and at times was confrontational and irritable.

She related oddly and often was guarded and difficult to engage; she sang and played with her blanket in a childlike way. She smiled and laughed inappropriately, mumbled incoherently to herself, scanned the room suspiciously, and often made intense eye contact. Her affect was labile, both tearful and euphoric at several points in the examination. Her thought process was tangential, illogical, grandiose, difficult to redirect, and with loose associations. Her thought content consisted of delusions (“I’ve got the devil on my back”) and grandiosity (“I am everyone, I am you…the president, the mayor”), and she often stated that she planned to become a singer or performer.

The patient claimed she was neither suicidal nor had thoughts of infanticide. She reported having no visual and auditory hallucinations but often seemed to be responding to internal stimuli: She mumbled to herself and looked intensely at parts of the room. Cognitively, the patient was fully intact to recent and remote events but displayed a poor attention span. She did not exhibit any motor abnormalities, such as tremor, rigidity, weakness, sensory loss, or abnormal gait.

The patient’s workup included full chemistry, complete blood count, thyroid-stimulating hormone, antithyroid antibodies, calcium, rapid plasma reagin to rule out syphilis, toxicology, folate, vitamin B₁₂, and vitamin D. All laboratory results were negative or within normal limits, although the urine drug screen was positive for cannabis. The patient’s husband noted that his wife never used cannabis except the weekend before her admission, when she impulsively went dancing, which was out of character for her. Her psychotic symptoms had been present weeks before the cannabis use; therefore, the her symptoms could not be attributed to a substance-induced psychotic disorder. A test for synthetic cannabis derivatives was negative. Newer synthetic compounds can cause more severe substance-induced psychotic symptoms than those of cannabis.³

The patient was diagnosed with postpartum psychosis and was started on the oral antipsychotic olanzapine 10 mg at bedtime. Additional doses were administered to control ongoing symptoms, which included a disorganized thought process; loose associations; euphoria; grandiosity; delusional content, such as “You are just a tool in place to help me;” reports of feeling as though she were in “outer space, outside in the galaxy;” decreased need for sleep; and irritability. The patient spent an entire interview with her eyes closed, stating that she could “hear” better because she was overstimulated if her eyes were open. She also described olfactory hallucinations of “strong perfume,” which the 2 providers present could not detect.

Olanzapine was not well tolerated because of sedation and was discontinued in favor of risperidone, 2 mg twice daily. Risperidone was more effective and better tolerated. Lithium was initiated the next day with target dosing at 300 mg in the morning and 600 mg at night. The patient became capable of linear, organized discussion and planning but remained euphoric with high energy; she exhibited grandiosity with frequent singing and dancing throughout her hospital stay. She often described her mood as “good, excellent, exuberant, exciting,” perseverating on the way words sounded and giggling in a childlike manner. She continued to have intrusive dreams of “hell and the devil” and that she was killed by gunshot.

The patient was continued on lithium and risperidone and transferred to a larger military hospital for further inpatient management, respecting military orders. Before discharge, a family conference was held with the patient and her husband to educate them on the importance of continued treatment, close follow-up, regular sleep patterns, and not breastfeeding while taking the prescribed medications. Although she was not back to her baseline at the time of transfer, the patient had stabilized significantly and gained sufficient insight into her condition.

Discussion

Postpartum psychosis can present with a prodromal phase consisting of fatigue, insomnia, restlessness, tearfulness, and emotional lability, making early identification difficult. Later, florid psychotic symptoms can include suspiciousness, confusion, incoherence, irrational statements, obsessive concern about the infant’s health, and delusions, including a belief that the baby is dead or defective. Some women might deny that the birth occurred or feel that they are unmarried, virginal, or persecuted.¹ More concerning symptoms include auditory hallucinations commanding the mother to harm or kill the infant and/or herself. Symptoms often begin within days to weeks of birth, usually 2 to 3 weeks after delivery but can occur as long as 8 weeks postpartum.¹ Several cases of infanticide and suicide have been documented.¹ The risk of experiencing another psychotic episode in subsequent pregnancies can be as high as 50%.^4-6 Regardless of symptom severity at onset, postpartum psychosis is a psychiatric emergency and must be treated as such.

Bipolar Disorder and Postpartum Psychosis

A close relationship exists between postpartum psychosis and development of bipolar disorder. A postpartum psychotic episode often is the harbinger of bipolar illness.⁷ About two-thirds of women who have an episode of postpartum psychosis will experience an underlying affective disorder within a year of childbirth.^1,8 It is unclear what triggers the psychotic episode, but it has been theorized that major systemic shifts in hormone levelsor trauma of delivery could instigate development of symptoms.^1,9

Risk factors include obstetric complications; perinatal infant mortality; previous episodes of bipolar disorder, psychosis, or postpartum psychosis; family history of bipolar disorder or postpartum psychosis; sleep deprivation; increased environmental stress; and lack of partner support.¹⁰ The strongest risk factor for developing postpartum psychosis is a personal or family history of bipolar disorder or a related psychotic disorder.¹¹ This risk factor is identified in about 40% to 50% cases of postpartum psychosis.¹¹

Treatment

Standard treatment for postpartum psychosis includes an antipsychotic and often lithium and benzodiazepines.^1,7,10,11 This treatment approach differs slightly from treating a patient with a nonpostpartum psychotic illness, who generally would not receive mood stabilizers, such as lithium. Including a mood stabilizer for postpartum psychosis is warranted because of the association between postpartum psychosis and bipolar disorder, which is treated with a mood stabilizer.

Prevalence

Postpartum psychosis is identified in 1 to 2 per 1,000 childbirths. In women who have had an earlier episode of postpartum psychosis or have a diagnosis of bipolar disorder, the rate is up to 100 times higher.¹ Kendell and colleagues found that psychiatric admissions occurred at a rate 7 times higher in the 30 days after birth than in the prepregnancy period, suggesting that metabolic factors might be involved in triggering postpartum psychotic symptoms.¹² An abrupt hormonal loss occurs at childbirth; hormones peak 200-fold during gestation and decline rapidly within a day after birth.⁹ Despite the severity of symptoms in postpartum psychosis, these patients tend to have a better prognosis than that of women with psychotic episodes not related to pregnancy.⁴

Patients with bipolar disorder have the highest risk of psychotic episodes during the postpartum period, with a study reporting 260 episodes of psychosis per deliveries among women with bipolar disorder.¹³ Studies such as this suggest that episodes of postpartum psychosis might be a variant or atypical presentation of an underlying bipolar disorder or a predisposition to developing the disorder.¹⁴ In a study that compared 58 patients with postpartum psychosis with to 52 individuals with nonchildbearing-related psychosis, manic symptoms were more common among the postpartum group.¹⁵ Family studies have shown that the risk of psychiatric illness among first-degree relatives of women with postpartum psychosis is 10% to 50%, which is higher than in the general population.¹⁴

Brockington and colleagues found that patients with postpartum psychosis had more mood lability, distractibility, and confusion than those with psychosis unrelated to pregnancy.¹⁵ Patients with postpartum psychosis were more likely to have impaired sensorium, bizarre quality of delusions, and memory loss. Psychosis with onset after childbirth included high levels of thought disorganization, delusions of reference, delusions of persecution, and greater levels of homicidal ideation and behavior.¹⁶ This study also reported symptoms such as visual, tactile, and olfactory hallucinations and a presentation similar to that of delirium.

Chandra and colleagues found that 53% of women with postpartum psychosis had delusions about the infant, including beliefs that someone would harm or kill the baby or that the baby would be harmed by their breast milk.¹⁷ Compared with women with bipolar disorder, Oostheuizen and colleagues found that women with postpartum psychosis had delusions of control, such as feeling under the influence of an overpowering force that controlled their actions.¹⁸ Infanticidal thoughts are common among patients with postpartum psychosis, and about 4% of women committed infanticide.¹

Rapid stabilization and treatment are important because postpartum psychosis is considered a psychiatric emergency.⁷ Potential consequences of delayed diagnosis and treatment include harm or death of the infant by infanticide and death of the mother by suicide. A thorough physical examination is important to rule out metabolic or neuroendocrine causes of psychosis other than postpartum hormonal shifts. These could include causes of altered mental status: stroke, pulmonary embolism, amniotic fluid emboli, Sheehan syndrome, thyroid disorders, electrolyte abnormalities, acute hemorrhage, sepsis, and substance toxicity or withdrawal.¹⁰ A complete blood count, full chemistry, thyroid function tests, antithyroid antibody tests, calcium, vitamin B₁₂, and folate should be measured.^7,10

Initial treatment should include antipsychotics and often mood stabilizers such as lithium. Managing insomnia aggressively is also necessary for initial stabilization and to prevent a repeat manic episode if the patient develops bipolar disorder.² Many experts argue that sleep loss in combination with other risk factors might be the final common pathway for development of postpartum psychosis in women predisposed to this disorder.^19,20

Treating insomnia in an outpatient setting includes teaching sleep hygiene practices and relaxation techniques. Although these methods to regulate sleep could be encouraged during the emergent inpatient stabilization of a patient with postpartum psychosis, pharmacologic approaches are necessary for acute mania and psychosis. Concern about possible dependence on benzodiazepines and other sedating sleep aids are valid; however, the benefit of acute stabilization of psychotic symptoms outweighs the potential risk of dependence.

Typically, first-line treatment is an antipsychotic, and second-generation antipsychotics generally are preferred over first-generation antipsychotics because of their more benign adverse effect profile.^21,22 There are no controlled trials that compare antipsychotics with placebo or other interventions for postpartum psychosis. Therefore, use of atypical antipsychotics is based on randomized trials demonstrating efficacy in reducing psychosis in bipolar disorder, depression with psychotic features, and schizoaffective disorder.^23,24 Once the patient is treated with an antipsychotic, further use of psychotropic medications, such as lithium or other mood stabilizers, should be based on the patient’s clinical presentation. For example, the patient in this case study primarily had manic symptoms consistent with bipolar disorder, making lithium or another mood stabilizer an appropriate choice.

Bergink and colleagues demonstrated positive outcomes with a treatment algorithm involving sequential use of benzodiazepines to improve sleep, an antipsychotic to decrease acute manic symptoms, lithium to stabilize mood based on symptoms, and electroconvulsive therapy if other treatments were not successful.²⁵ Case studies document that administering estrogen led to recovery from postpartum psychosis, although patients often relapsed when estrogen was stopped.²⁶ Electroconvulsive therapy has shown promising results, especially in patients who do not respond to antipsychotic medications or lithium.^27,28

Antipsychotic and Other Psychotropic Medications

Choice of an antipsychotic and other psychotropic medications to treat postpartum psychosis is based on the patient’s breastfeeding status. The benefits of treatment should be weighed against the risks of a breastfeeding infant’s exposure to the medication. Because postpartum psychosis is a psychiatric emergency, the benefits of the medication are considered to outweigh any potential adverse effect to the breastfeeding infant exposed to the medication. Risks of untreated postpartum psychosis to the infant include rejection of the infant, poor parental relationships, suicide, infanticide, long-term failure to bond with the child, delayed infant development, and failure to thrive.²⁹ Also, many mothers—including the patient in this presentation—decide that the benefits of treatment outweigh those of breastfeeding and choose to feed their infant with formula. Even if the patient chooses to bottle-feed her infant, consider administering medications that are considered safer for breastfeeding because the patient may need to continue the psychotropic during later pregnancies to prevent future psychotic episodes.³⁰ All psychotropic medications pass into breast milk.²⁹ Studies on the long-term effect of these medications on the infant are limited, but experts tend to recommend olanzapine, quetiapine, and risperidone over aripiprazole and ziprasidone.^21,31-33

Lithium often is used to treat postpartum psychosis. Studies examining risk to the infant after long-term exposure to lithium through breast milk have not been conducted, but the American Academy of Pediatrics discourages its use during breastfeeding because of concerns about toxicity in the infant.^34-36

Sleep regulation is important to treat bipolar disorder and to prevent future episodes.^2,20,21 To ensure safety of the infant and mother before discharge, family education is imperative to establish close follow-up, adequate sleep, and reduction of stressors.^7,10 Separation from the infant might be necessary after discharge, and someone should monitor the infant at all times until the outpatient mental health provider confirms that all psychotic symptoms have resolved.^7,10 Successful treatment of postpartum psychosis requires close communication among the mental health provider, the pediatrician, and the obstetrician or women’s health provider.¹⁰ Because a close-knit team approach after discharge from the acute psychiatric unit is necessary, the care of such a patient and her child provides an educational opportunity for individuals working in integrated care clinics.

Conclusion

Postpartum psychosis is a psychiatric emergency requiring immediate treatment to prevent dire outcomes such as suicide or infanticide. Treatment considerations include the cost-benefit analysis of breastfeeding and the toxicity of psychotropic medications when ingested by the infant via breast milk. A close relationship has been demonstrated between postpartum psychosis and bipolar disorder.

Preferred treatment regimens include lithium and an antipsychotic. Educate the family as a unit about the diagnosis and treatment, the importance of adequate sleep for treatment and prophylaxis, and the decision on whether to discontinue breastfeeding despite its well-known benefits for mother and infant. Stabilization is a multifaceted process and needs to be reinforced with a solid plan for support and follow-up appointments. Because of the higher risk of relapse, educate patients about prophylactic treatment during subsequent pregnancies and monitor for development of bipolar disorder in the future.

Postpartum psychosis is a psychiatric emergency that can endanger the life of the mother and the newborn child if untreated. About 1 to 2 mothers in 1,000 experiences postpartum psychosis after delivery.¹ This rate is much higher among women with an established diagnosis of bipolar disorder before pregnancy.¹

Expedient recognition, diagnosis, and referral to a high-level psychiatric facility (usually a locked inpatient unit) are critical for ensuring the safety of mother and infant. A diligent medical workup followed by thorough education for the patient and family are important steps in caring for patients with postpartum psychosis. Close mental health follow-up, pharmacologic interventions, informed decision making regarding breastfeeding, and preserving the sleep-wake cycle are critical for stabilization.²

The authors present the case of a patient admitted to VA Central California Health Care System (VACCHCS) with postpartum psychosis and a discussion on existing research on the prevalence of postpartum psychosis, relevant risk factors, the association with bipolar disorder, and treatment strategies.

Case Presentation

A 31-year-old active-duty female with no history of mental illness was admitted to the psychiatric unit because new-onset disorganized behavior was preventing her from functioning at her workplace. Two weeks after giving birth to her second child, the patient began exhibiting an uncharacteristic, debilitating labile mood and disorganized behavior. Her supervisors required her to present for medical attention about 3 months after the birth of her child. She was transferred to VACCHCS for higher level medical care on military orders. The patient’s husband initially attributed these psychiatric symptoms to vocational stress and taking care of 2 young children. He observed the patient exhibiting tearfulness about her job, which quickly alternated with euphoric episodes of singing and dancing at inappropriate times, such as when the children had quieted down and were being prepared to go to bed.

At the initial psychiatric evaluation after transfer to VACCHCS, the patient appeared well-kept and slightly overweight. In general her appearance was unremarkable. Throughout the examination she sang both subtly and loudly and at times was confrontational and irritable.

She related oddly and often was guarded and difficult to engage; she sang and played with her blanket in a childlike way. She smiled and laughed inappropriately, mumbled incoherently to herself, scanned the room suspiciously, and often made intense eye contact. Her affect was labile, both tearful and euphoric at several points in the examination. Her thought process was tangential, illogical, grandiose, difficult to redirect, and with loose associations. Her thought content consisted of delusions (“I’ve got the devil on my back”) and grandiosity (“I am everyone, I am you…the president, the mayor”), and she often stated that she planned to become a singer or performer.

The patient claimed she was neither suicidal nor had thoughts of infanticide. She reported having no visual and auditory hallucinations but often seemed to be responding to internal stimuli: She mumbled to herself and looked intensely at parts of the room. Cognitively, the patient was fully intact to recent and remote events but displayed a poor attention span. She did not exhibit any motor abnormalities, such as tremor, rigidity, weakness, sensory loss, or abnormal gait.

The patient’s workup included full chemistry, complete blood count, thyroid-stimulating hormone, antithyroid antibodies, calcium, rapid plasma reagin to rule out syphilis, toxicology, folate, vitamin B₁₂, and vitamin D. All laboratory results were negative or within normal limits, although the urine drug screen was positive for cannabis. The patient’s husband noted that his wife never used cannabis except the weekend before her admission, when she impulsively went dancing, which was out of character for her. Her psychotic symptoms had been present weeks before the cannabis use; therefore, the her symptoms could not be attributed to a substance-induced psychotic disorder. A test for synthetic cannabis derivatives was negative. Newer synthetic compounds can cause more severe substance-induced psychotic symptoms than those of cannabis.³

The patient was diagnosed with postpartum psychosis and was started on the oral antipsychotic olanzapine 10 mg at bedtime. Additional doses were administered to control ongoing symptoms, which included a disorganized thought process; loose associations; euphoria; grandiosity; delusional content, such as “You are just a tool in place to help me;” reports of feeling as though she were in “outer space, outside in the galaxy;” decreased need for sleep; and irritability. The patient spent an entire interview with her eyes closed, stating that she could “hear” better because she was overstimulated if her eyes were open. She also described olfactory hallucinations of “strong perfume,” which the 2 providers present could not detect.

Olanzapine was not well tolerated because of sedation and was discontinued in favor of risperidone, 2 mg twice daily. Risperidone was more effective and better tolerated. Lithium was initiated the next day with target dosing at 300 mg in the morning and 600 mg at night. The patient became capable of linear, organized discussion and planning but remained euphoric with high energy; she exhibited grandiosity with frequent singing and dancing throughout her hospital stay. She often described her mood as “good, excellent, exuberant, exciting,” perseverating on the way words sounded and giggling in a childlike manner. She continued to have intrusive dreams of “hell and the devil” and that she was killed by gunshot.

The patient was continued on lithium and risperidone and transferred to a larger military hospital for further inpatient management, respecting military orders. Before discharge, a family conference was held with the patient and her husband to educate them on the importance of continued treatment, close follow-up, regular sleep patterns, and not breastfeeding while taking the prescribed medications. Although she was not back to her baseline at the time of transfer, the patient had stabilized significantly and gained sufficient insight into her condition.

Discussion

Postpartum psychosis can present with a prodromal phase consisting of fatigue, insomnia, restlessness, tearfulness, and emotional lability, making early identification difficult. Later, florid psychotic symptoms can include suspiciousness, confusion, incoherence, irrational statements, obsessive concern about the infant’s health, and delusions, including a belief that the baby is dead or defective. Some women might deny that the birth occurred or feel that they are unmarried, virginal, or persecuted.¹ More concerning symptoms include auditory hallucinations commanding the mother to harm or kill the infant and/or herself. Symptoms often begin within days to weeks of birth, usually 2 to 3 weeks after delivery but can occur as long as 8 weeks postpartum.¹ Several cases of infanticide and suicide have been documented.¹ The risk of experiencing another psychotic episode in subsequent pregnancies can be as high as 50%.^4-6 Regardless of symptom severity at onset, postpartum psychosis is a psychiatric emergency and must be treated as such.

Bipolar Disorder and Postpartum Psychosis

A close relationship exists between postpartum psychosis and development of bipolar disorder. A postpartum psychotic episode often is the harbinger of bipolar illness.⁷ About two-thirds of women who have an episode of postpartum psychosis will experience an underlying affective disorder within a year of childbirth.^1,8 It is unclear what triggers the psychotic episode, but it has been theorized that major systemic shifts in hormone levelsor trauma of delivery could instigate development of symptoms.^1,9

Risk factors include obstetric complications; perinatal infant mortality; previous episodes of bipolar disorder, psychosis, or postpartum psychosis; family history of bipolar disorder or postpartum psychosis; sleep deprivation; increased environmental stress; and lack of partner support.¹⁰ The strongest risk factor for developing postpartum psychosis is a personal or family history of bipolar disorder or a related psychotic disorder.¹¹ This risk factor is identified in about 40% to 50% cases of postpartum psychosis.¹¹

Treatment

Standard treatment for postpartum psychosis includes an antipsychotic and often lithium and benzodiazepines.^1,7,10,11 This treatment approach differs slightly from treating a patient with a nonpostpartum psychotic illness, who generally would not receive mood stabilizers, such as lithium. Including a mood stabilizer for postpartum psychosis is warranted because of the association between postpartum psychosis and bipolar disorder, which is treated with a mood stabilizer.

Prevalence

Postpartum psychosis is identified in 1 to 2 per 1,000 childbirths. In women who have had an earlier episode of postpartum psychosis or have a diagnosis of bipolar disorder, the rate is up to 100 times higher.¹ Kendell and colleagues found that psychiatric admissions occurred at a rate 7 times higher in the 30 days after birth than in the prepregnancy period, suggesting that metabolic factors might be involved in triggering postpartum psychotic symptoms.¹² An abrupt hormonal loss occurs at childbirth; hormones peak 200-fold during gestation and decline rapidly within a day after birth.⁹ Despite the severity of symptoms in postpartum psychosis, these patients tend to have a better prognosis than that of women with psychotic episodes not related to pregnancy.⁴

Patients with bipolar disorder have the highest risk of psychotic episodes during the postpartum period, with a study reporting 260 episodes of psychosis per deliveries among women with bipolar disorder.¹³ Studies such as this suggest that episodes of postpartum psychosis might be a variant or atypical presentation of an underlying bipolar disorder or a predisposition to developing the disorder.¹⁴ In a study that compared 58 patients with postpartum psychosis with to 52 individuals with nonchildbearing-related psychosis, manic symptoms were more common among the postpartum group.¹⁵ Family studies have shown that the risk of psychiatric illness among first-degree relatives of women with postpartum psychosis is 10% to 50%, which is higher than in the general population.¹⁴

Brockington and colleagues found that patients with postpartum psychosis had more mood lability, distractibility, and confusion than those with psychosis unrelated to pregnancy.¹⁵ Patients with postpartum psychosis were more likely to have impaired sensorium, bizarre quality of delusions, and memory loss. Psychosis with onset after childbirth included high levels of thought disorganization, delusions of reference, delusions of persecution, and greater levels of homicidal ideation and behavior.¹⁶ This study also reported symptoms such as visual, tactile, and olfactory hallucinations and a presentation similar to that of delirium.

Chandra and colleagues found that 53% of women with postpartum psychosis had delusions about the infant, including beliefs that someone would harm or kill the baby or that the baby would be harmed by their breast milk.¹⁷ Compared with women with bipolar disorder, Oostheuizen and colleagues found that women with postpartum psychosis had delusions of control, such as feeling under the influence of an overpowering force that controlled their actions.¹⁸ Infanticidal thoughts are common among patients with postpartum psychosis, and about 4% of women committed infanticide.¹

Rapid stabilization and treatment are important because postpartum psychosis is considered a psychiatric emergency.⁷ Potential consequences of delayed diagnosis and treatment include harm or death of the infant by infanticide and death of the mother by suicide. A thorough physical examination is important to rule out metabolic or neuroendocrine causes of psychosis other than postpartum hormonal shifts. These could include causes of altered mental status: stroke, pulmonary embolism, amniotic fluid emboli, Sheehan syndrome, thyroid disorders, electrolyte abnormalities, acute hemorrhage, sepsis, and substance toxicity or withdrawal.¹⁰ A complete blood count, full chemistry, thyroid function tests, antithyroid antibody tests, calcium, vitamin B₁₂, and folate should be measured.^7,10

Initial treatment should include antipsychotics and often mood stabilizers such as lithium. Managing insomnia aggressively is also necessary for initial stabilization and to prevent a repeat manic episode if the patient develops bipolar disorder.² Many experts argue that sleep loss in combination with other risk factors might be the final common pathway for development of postpartum psychosis in women predisposed to this disorder.^19,20

Treating insomnia in an outpatient setting includes teaching sleep hygiene practices and relaxation techniques. Although these methods to regulate sleep could be encouraged during the emergent inpatient stabilization of a patient with postpartum psychosis, pharmacologic approaches are necessary for acute mania and psychosis. Concern about possible dependence on benzodiazepines and other sedating sleep aids are valid; however, the benefit of acute stabilization of psychotic symptoms outweighs the potential risk of dependence.

Typically, first-line treatment is an antipsychotic, and second-generation antipsychotics generally are preferred over first-generation antipsychotics because of their more benign adverse effect profile.^21,22 There are no controlled trials that compare antipsychotics with placebo or other interventions for postpartum psychosis. Therefore, use of atypical antipsychotics is based on randomized trials demonstrating efficacy in reducing psychosis in bipolar disorder, depression with psychotic features, and schizoaffective disorder.^23,24 Once the patient is treated with an antipsychotic, further use of psychotropic medications, such as lithium or other mood stabilizers, should be based on the patient’s clinical presentation. For example, the patient in this case study primarily had manic symptoms consistent with bipolar disorder, making lithium or another mood stabilizer an appropriate choice.

Bergink and colleagues demonstrated positive outcomes with a treatment algorithm involving sequential use of benzodiazepines to improve sleep, an antipsychotic to decrease acute manic symptoms, lithium to stabilize mood based on symptoms, and electroconvulsive therapy if other treatments were not successful.²⁵ Case studies document that administering estrogen led to recovery from postpartum psychosis, although patients often relapsed when estrogen was stopped.²⁶ Electroconvulsive therapy has shown promising results, especially in patients who do not respond to antipsychotic medications or lithium.^27,28

Antipsychotic and Other Psychotropic Medications

Choice of an antipsychotic and other psychotropic medications to treat postpartum psychosis is based on the patient’s breastfeeding status. The benefits of treatment should be weighed against the risks of a breastfeeding infant’s exposure to the medication. Because postpartum psychosis is a psychiatric emergency, the benefits of the medication are considered to outweigh any potential adverse effect to the breastfeeding infant exposed to the medication. Risks of untreated postpartum psychosis to the infant include rejection of the infant, poor parental relationships, suicide, infanticide, long-term failure to bond with the child, delayed infant development, and failure to thrive.²⁹ Also, many mothers—including the patient in this presentation—decide that the benefits of treatment outweigh those of breastfeeding and choose to feed their infant with formula. Even if the patient chooses to bottle-feed her infant, consider administering medications that are considered safer for breastfeeding because the patient may need to continue the psychotropic during later pregnancies to prevent future psychotic episodes.³⁰ All psychotropic medications pass into breast milk.²⁹ Studies on the long-term effect of these medications on the infant are limited, but experts tend to recommend olanzapine, quetiapine, and risperidone over aripiprazole and ziprasidone.^21,31-33

Lithium often is used to treat postpartum psychosis. Studies examining risk to the infant after long-term exposure to lithium through breast milk have not been conducted, but the American Academy of Pediatrics discourages its use during breastfeeding because of concerns about toxicity in the infant.^34-36

Sleep regulation is important to treat bipolar disorder and to prevent future episodes.^2,20,21 To ensure safety of the infant and mother before discharge, family education is imperative to establish close follow-up, adequate sleep, and reduction of stressors.^7,10 Separation from the infant might be necessary after discharge, and someone should monitor the infant at all times until the outpatient mental health provider confirms that all psychotic symptoms have resolved.^7,10 Successful treatment of postpartum psychosis requires close communication among the mental health provider, the pediatrician, and the obstetrician or women’s health provider.¹⁰ Because a close-knit team approach after discharge from the acute psychiatric unit is necessary, the care of such a patient and her child provides an educational opportunity for individuals working in integrated care clinics.

Conclusion

Postpartum psychosis is a psychiatric emergency requiring immediate treatment to prevent dire outcomes such as suicide or infanticide. Treatment considerations include the cost-benefit analysis of breastfeeding and the toxicity of psychotropic medications when ingested by the infant via breast milk. A close relationship has been demonstrated between postpartum psychosis and bipolar disorder.

Preferred treatment regimens include lithium and an antipsychotic. Educate the family as a unit about the diagnosis and treatment, the importance of adequate sleep for treatment and prophylaxis, and the decision on whether to discontinue breastfeeding despite its well-known benefits for mother and infant. Stabilization is a multifaceted process and needs to be reinforced with a solid plan for support and follow-up appointments. Because of the higher risk of relapse, educate patients about prophylactic treatment during subsequent pregnancies and monitor for development of bipolar disorder in the future.

Postpartum psychosis is a psychiatric emergency that can endanger the life of the mother and the newborn child if untreated. About 1 to 2 mothers in 1,000 experiences postpartum psychosis after delivery.¹ This rate is much higher among women with an established diagnosis of bipolar disorder before pregnancy.¹

Expedient recognition, diagnosis, and referral to a high-level psychiatric facility (usually a locked inpatient unit) are critical for ensuring the safety of mother and infant. A diligent medical workup followed by thorough education for the patient and family are important steps in caring for patients with postpartum psychosis. Close mental health follow-up, pharmacologic interventions, informed decision making regarding breastfeeding, and preserving the sleep-wake cycle are critical for stabilization.²

The authors present the case of a patient admitted to VA Central California Health Care System (VACCHCS) with postpartum psychosis and a discussion on existing research on the prevalence of postpartum psychosis, relevant risk factors, the association with bipolar disorder, and treatment strategies.

Case Presentation

A 31-year-old active-duty female with no history of mental illness was admitted to the psychiatric unit because new-onset disorganized behavior was preventing her from functioning at her workplace. Two weeks after giving birth to her second child, the patient began exhibiting an uncharacteristic, debilitating labile mood and disorganized behavior. Her supervisors required her to present for medical attention about 3 months after the birth of her child. She was transferred to VACCHCS for higher level medical care on military orders. The patient’s husband initially attributed these psychiatric symptoms to vocational stress and taking care of 2 young children. He observed the patient exhibiting tearfulness about her job, which quickly alternated with euphoric episodes of singing and dancing at inappropriate times, such as when the children had quieted down and were being prepared to go to bed.

At the initial psychiatric evaluation after transfer to VACCHCS, the patient appeared well-kept and slightly overweight. In general her appearance was unremarkable. Throughout the examination she sang both subtly and loudly and at times was confrontational and irritable.

She related oddly and often was guarded and difficult to engage; she sang and played with her blanket in a childlike way. She smiled and laughed inappropriately, mumbled incoherently to herself, scanned the room suspiciously, and often made intense eye contact. Her affect was labile, both tearful and euphoric at several points in the examination. Her thought process was tangential, illogical, grandiose, difficult to redirect, and with loose associations. Her thought content consisted of delusions (“I’ve got the devil on my back”) and grandiosity (“I am everyone, I am you…the president, the mayor”), and she often stated that she planned to become a singer or performer.

The patient claimed she was neither suicidal nor had thoughts of infanticide. She reported having no visual and auditory hallucinations but often seemed to be responding to internal stimuli: She mumbled to herself and looked intensely at parts of the room. Cognitively, the patient was fully intact to recent and remote events but displayed a poor attention span. She did not exhibit any motor abnormalities, such as tremor, rigidity, weakness, sensory loss, or abnormal gait.

The patient’s workup included full chemistry, complete blood count, thyroid-stimulating hormone, antithyroid antibodies, calcium, rapid plasma reagin to rule out syphilis, toxicology, folate, vitamin B₁₂, and vitamin D. All laboratory results were negative or within normal limits, although the urine drug screen was positive for cannabis. The patient’s husband noted that his wife never used cannabis except the weekend before her admission, when she impulsively went dancing, which was out of character for her. Her psychotic symptoms had been present weeks before the cannabis use; therefore, the her symptoms could not be attributed to a substance-induced psychotic disorder. A test for synthetic cannabis derivatives was negative. Newer synthetic compounds can cause more severe substance-induced psychotic symptoms than those of cannabis.³

The patient was diagnosed with postpartum psychosis and was started on the oral antipsychotic olanzapine 10 mg at bedtime. Additional doses were administered to control ongoing symptoms, which included a disorganized thought process; loose associations; euphoria; grandiosity; delusional content, such as “You are just a tool in place to help me;” reports of feeling as though she were in “outer space, outside in the galaxy;” decreased need for sleep; and irritability. The patient spent an entire interview with her eyes closed, stating that she could “hear” better because she was overstimulated if her eyes were open. She also described olfactory hallucinations of “strong perfume,” which the 2 providers present could not detect.

Olanzapine was not well tolerated because of sedation and was discontinued in favor of risperidone, 2 mg twice daily. Risperidone was more effective and better tolerated. Lithium was initiated the next day with target dosing at 300 mg in the morning and 600 mg at night. The patient became capable of linear, organized discussion and planning but remained euphoric with high energy; she exhibited grandiosity with frequent singing and dancing throughout her hospital stay. She often described her mood as “good, excellent, exuberant, exciting,” perseverating on the way words sounded and giggling in a childlike manner. She continued to have intrusive dreams of “hell and the devil” and that she was killed by gunshot.

The patient was continued on lithium and risperidone and transferred to a larger military hospital for further inpatient management, respecting military orders. Before discharge, a family conference was held with the patient and her husband to educate them on the importance of continued treatment, close follow-up, regular sleep patterns, and not breastfeeding while taking the prescribed medications. Although she was not back to her baseline at the time of transfer, the patient had stabilized significantly and gained sufficient insight into her condition.

Discussion

Postpartum psychosis can present with a prodromal phase consisting of fatigue, insomnia, restlessness, tearfulness, and emotional lability, making early identification difficult. Later, florid psychotic symptoms can include suspiciousness, confusion, incoherence, irrational statements, obsessive concern about the infant’s health, and delusions, including a belief that the baby is dead or defective. Some women might deny that the birth occurred or feel that they are unmarried, virginal, or persecuted.¹ More concerning symptoms include auditory hallucinations commanding the mother to harm or kill the infant and/or herself. Symptoms often begin within days to weeks of birth, usually 2 to 3 weeks after delivery but can occur as long as 8 weeks postpartum.¹ Several cases of infanticide and suicide have been documented.¹ The risk of experiencing another psychotic episode in subsequent pregnancies can be as high as 50%.^4-6 Regardless of symptom severity at onset, postpartum psychosis is a psychiatric emergency and must be treated as such.

Bipolar Disorder and Postpartum Psychosis

A close relationship exists between postpartum psychosis and development of bipolar disorder. A postpartum psychotic episode often is the harbinger of bipolar illness.⁷ About two-thirds of women who have an episode of postpartum psychosis will experience an underlying affective disorder within a year of childbirth.^1,8 It is unclear what triggers the psychotic episode, but it has been theorized that major systemic shifts in hormone levelsor trauma of delivery could instigate development of symptoms.^1,9

Risk factors include obstetric complications; perinatal infant mortality; previous episodes of bipolar disorder, psychosis, or postpartum psychosis; family history of bipolar disorder or postpartum psychosis; sleep deprivation; increased environmental stress; and lack of partner support.¹⁰ The strongest risk factor for developing postpartum psychosis is a personal or family history of bipolar disorder or a related psychotic disorder.¹¹ This risk factor is identified in about 40% to 50% cases of postpartum psychosis.¹¹

Treatment

Standard treatment for postpartum psychosis includes an antipsychotic and often lithium and benzodiazepines.^1,7,10,11 This treatment approach differs slightly from treating a patient with a nonpostpartum psychotic illness, who generally would not receive mood stabilizers, such as lithium. Including a mood stabilizer for postpartum psychosis is warranted because of the association between postpartum psychosis and bipolar disorder, which is treated with a mood stabilizer.

Prevalence

Postpartum psychosis is identified in 1 to 2 per 1,000 childbirths. In women who have had an earlier episode of postpartum psychosis or have a diagnosis of bipolar disorder, the rate is up to 100 times higher.¹ Kendell and colleagues found that psychiatric admissions occurred at a rate 7 times higher in the 30 days after birth than in the prepregnancy period, suggesting that metabolic factors might be involved in triggering postpartum psychotic symptoms.¹² An abrupt hormonal loss occurs at childbirth; hormones peak 200-fold during gestation and decline rapidly within a day after birth.⁹ Despite the severity of symptoms in postpartum psychosis, these patients tend to have a better prognosis than that of women with psychotic episodes not related to pregnancy.⁴

Patients with bipolar disorder have the highest risk of psychotic episodes during the postpartum period, with a study reporting 260 episodes of psychosis per deliveries among women with bipolar disorder.¹³ Studies such as this suggest that episodes of postpartum psychosis might be a variant or atypical presentation of an underlying bipolar disorder or a predisposition to developing the disorder.¹⁴ In a study that compared 58 patients with postpartum psychosis with to 52 individuals with nonchildbearing-related psychosis, manic symptoms were more common among the postpartum group.¹⁵ Family studies have shown that the risk of psychiatric illness among first-degree relatives of women with postpartum psychosis is 10% to 50%, which is higher than in the general population.¹⁴

Brockington and colleagues found that patients with postpartum psychosis had more mood lability, distractibility, and confusion than those with psychosis unrelated to pregnancy.¹⁵ Patients with postpartum psychosis were more likely to have impaired sensorium, bizarre quality of delusions, and memory loss. Psychosis with onset after childbirth included high levels of thought disorganization, delusions of reference, delusions of persecution, and greater levels of homicidal ideation and behavior.¹⁶ This study also reported symptoms such as visual, tactile, and olfactory hallucinations and a presentation similar to that of delirium.

Chandra and colleagues found that 53% of women with postpartum psychosis had delusions about the infant, including beliefs that someone would harm or kill the baby or that the baby would be harmed by their breast milk.¹⁷ Compared with women with bipolar disorder, Oostheuizen and colleagues found that women with postpartum psychosis had delusions of control, such as feeling under the influence of an overpowering force that controlled their actions.¹⁸ Infanticidal thoughts are common among patients with postpartum psychosis, and about 4% of women committed infanticide.¹

Rapid stabilization and treatment are important because postpartum psychosis is considered a psychiatric emergency.⁷ Potential consequences of delayed diagnosis and treatment include harm or death of the infant by infanticide and death of the mother by suicide. A thorough physical examination is important to rule out metabolic or neuroendocrine causes of psychosis other than postpartum hormonal shifts. These could include causes of altered mental status: stroke, pulmonary embolism, amniotic fluid emboli, Sheehan syndrome, thyroid disorders, electrolyte abnormalities, acute hemorrhage, sepsis, and substance toxicity or withdrawal.¹⁰ A complete blood count, full chemistry, thyroid function tests, antithyroid antibody tests, calcium, vitamin B₁₂, and folate should be measured.^7,10

Initial treatment should include antipsychotics and often mood stabilizers such as lithium. Managing insomnia aggressively is also necessary for initial stabilization and to prevent a repeat manic episode if the patient develops bipolar disorder.² Many experts argue that sleep loss in combination with other risk factors might be the final common pathway for development of postpartum psychosis in women predisposed to this disorder.^19,20

Treating insomnia in an outpatient setting includes teaching sleep hygiene practices and relaxation techniques. Although these methods to regulate sleep could be encouraged during the emergent inpatient stabilization of a patient with postpartum psychosis, pharmacologic approaches are necessary for acute mania and psychosis. Concern about possible dependence on benzodiazepines and other sedating sleep aids are valid; however, the benefit of acute stabilization of psychotic symptoms outweighs the potential risk of dependence.

Typically, first-line treatment is an antipsychotic, and second-generation antipsychotics generally are preferred over first-generation antipsychotics because of their more benign adverse effect profile.^21,22 There are no controlled trials that compare antipsychotics with placebo or other interventions for postpartum psychosis. Therefore, use of atypical antipsychotics is based on randomized trials demonstrating efficacy in reducing psychosis in bipolar disorder, depression with psychotic features, and schizoaffective disorder.^23,24 Once the patient is treated with an antipsychotic, further use of psychotropic medications, such as lithium or other mood stabilizers, should be based on the patient’s clinical presentation. For example, the patient in this case study primarily had manic symptoms consistent with bipolar disorder, making lithium or another mood stabilizer an appropriate choice.

Bergink and colleagues demonstrated positive outcomes with a treatment algorithm involving sequential use of benzodiazepines to improve sleep, an antipsychotic to decrease acute manic symptoms, lithium to stabilize mood based on symptoms, and electroconvulsive therapy if other treatments were not successful.²⁵ Case studies document that administering estrogen led to recovery from postpartum psychosis, although patients often relapsed when estrogen was stopped.²⁶ Electroconvulsive therapy has shown promising results, especially in patients who do not respond to antipsychotic medications or lithium.^27,28

Antipsychotic and Other Psychotropic Medications

Choice of an antipsychotic and other psychotropic medications to treat postpartum psychosis is based on the patient’s breastfeeding status. The benefits of treatment should be weighed against the risks of a breastfeeding infant’s exposure to the medication. Because postpartum psychosis is a psychiatric emergency, the benefits of the medication are considered to outweigh any potential adverse effect to the breastfeeding infant exposed to the medication. Risks of untreated postpartum psychosis to the infant include rejection of the infant, poor parental relationships, suicide, infanticide, long-term failure to bond with the child, delayed infant development, and failure to thrive.²⁹ Also, many mothers—including the patient in this presentation—decide that the benefits of treatment outweigh those of breastfeeding and choose to feed their infant with formula. Even if the patient chooses to bottle-feed her infant, consider administering medications that are considered safer for breastfeeding because the patient may need to continue the psychotropic during later pregnancies to prevent future psychotic episodes.³⁰ All psychotropic medications pass into breast milk.²⁹ Studies on the long-term effect of these medications on the infant are limited, but experts tend to recommend olanzapine, quetiapine, and risperidone over aripiprazole and ziprasidone.^21,31-33

Lithium often is used to treat postpartum psychosis. Studies examining risk to the infant after long-term exposure to lithium through breast milk have not been conducted, but the American Academy of Pediatrics discourages its use during breastfeeding because of concerns about toxicity in the infant.^34-36

Sleep regulation is important to treat bipolar disorder and to prevent future episodes.^2,20,21 To ensure safety of the infant and mother before discharge, family education is imperative to establish close follow-up, adequate sleep, and reduction of stressors.^7,10 Separation from the infant might be necessary after discharge, and someone should monitor the infant at all times until the outpatient mental health provider confirms that all psychotic symptoms have resolved.^7,10 Successful treatment of postpartum psychosis requires close communication among the mental health provider, the pediatrician, and the obstetrician or women’s health provider.¹⁰ Because a close-knit team approach after discharge from the acute psychiatric unit is necessary, the care of such a patient and her child provides an educational opportunity for individuals working in integrated care clinics.

Conclusion

Postpartum psychosis is a psychiatric emergency requiring immediate treatment to prevent dire outcomes such as suicide or infanticide. Treatment considerations include the cost-benefit analysis of breastfeeding and the toxicity of psychotropic medications when ingested by the infant via breast milk. A close relationship has been demonstrated between postpartum psychosis and bipolar disorder.

Preferred treatment regimens include lithium and an antipsychotic. Educate the family as a unit about the diagnosis and treatment, the importance of adequate sleep for treatment and prophylaxis, and the decision on whether to discontinue breastfeeding despite its well-known benefits for mother and infant. Stabilization is a multifaceted process and needs to be reinforced with a solid plan for support and follow-up appointments. Because of the higher risk of relapse, educate patients about prophylactic treatment during subsequent pregnancies and monitor for development of bipolar disorder in the future.