Neurology

NEW ORLEANS – Depression severity is correlated with seizure frequency and quality of life in adults with epilepsy, according to an analysis presented at the annual meeting of the American Epilepsy Society.

The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively

Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.

Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”

The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.

“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”

Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.

“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”

This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
 

egreb@mdedge.com

SOURCE: Kumar N et al. AES 2018, Abstract 1.371.

NEW ORLEANS – Depression severity is correlated with seizure frequency and quality of life in adults with epilepsy, according to an analysis presented at the annual meeting of the American Epilepsy Society.

The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively

Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.

Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”

The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.

“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”

Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.

“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”

This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
 

egreb@mdedge.com

SOURCE: Kumar N et al. AES 2018, Abstract 1.371.

NEW ORLEANS – Depression severity is correlated with seizure frequency and quality of life in adults with epilepsy, according to an analysis presented at the annual meeting of the American Epilepsy Society.

The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively

Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.

Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”

The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.

“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”

Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.

“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”

This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
 

egreb@mdedge.com

SOURCE: Kumar N et al. AES 2018, Abstract 1.371.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

jremaly@mdedge.com

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

jremaly@mdedge.com

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

jremaly@mdedge.com

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Clinicians should screen patients with pediatric epilepsy for depression regularly, according to research described at the annual meeting of the American Epilepsy Society. Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.

“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”

Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.

As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.

Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.

“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.

The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
 

egreb@mdedge.com

SOURCE: Thomas HM et al. Abstract 1.388.

NEW ORLEANS – Clinicians should screen patients with pediatric epilepsy for depression regularly, according to research described at the annual meeting of the American Epilepsy Society. Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.

“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”

Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.

As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.

Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.

“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.

The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
 

egreb@mdedge.com

SOURCE: Thomas HM et al. Abstract 1.388.

NEW ORLEANS – Clinicians should screen patients with pediatric epilepsy for depression regularly, according to research described at the annual meeting of the American Epilepsy Society. Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.

“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”

Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.

As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.

Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.

“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.

The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
 

egreb@mdedge.com

SOURCE: Thomas HM et al. Abstract 1.388.

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Three commonly used, brief cognitive tests erroneously identified dementia, resulting in more than a third of those screened being incorrectly classified, a retrospective analysis has concluded.

The likelihood of a false-positive or false-negative result declined sharply when all three tests were given, however; only about 2% of patients were misclassified in all three, David Llewellyn, PhD, and his colleagues reported in Neurology: Clinical Practice.

The Mini Mental State Examination (MMSE), Memory Impairment Screen (MIS), and animal naming (AN) were susceptible to different measurement biases, wrote Dr. Llewellyn of the University of Exeter (U.K.).

Just one variable – an informant’s perception of the patient’s memory as unimpaired – consistently predicted inaccuracy in all three tests. Most of the patients in this category carried the diagnosis of cognitively impaired but not demented (CIND), a finding that has important clinical implications.

“These participants may be in the very early stages of conversion to dementia. ... Therefore, of those with low or borderline cognitive assessment results, reassessment to detect further decline may be appropriate.”

The study comprised 824 patients included in the Aging, Demographics and Memory Study, which is a subsample of the Health and Retirement Study. They completed the tests from 2001-2004, during which time they were a mean of 82 years old. A panel of experts adjudicated diagnoses, which they then parsed into all-cause dementia, CIND, or cognitively normal. The testing included a self and informant assessment of memory decline. The investigators also looked at 22 predictors of cognition, including patient characteristics, apolipoprotein E carriage (ApoE e4), and sociodemographic factors.

The prevalence of dementia was 35.3%; of the nondemented patients, 43% met the criteria for CIND. The team found that 35.7% of cases were misclassified by at least one test, 13.4% by two, and 1.7% by all three.

The MMSE was the least accurate, with a 21% misclassification rate, reflected in an 18.6% false-positive rate for those without dementia and a 2.4% rate of false-negative for those with dementia.

The MIS had a 16% misclassification rate, with a 9.5% rate of false-positive for those with no dementia and a 6.3% rate of false-negative for those without.

The AN had a 14% misclassification rate, with a 6.8% false-positive rate for those without dementia and a 7.7% false-negative rate for those with dementia.

For the MMSE, MIS, and AN, the number of participants with false-positives that met the criteria for CIND were 74.5%, 82.1%, and 82.1%, respectively.

In the final multivariate model, seven variables predicted misclassification, including black ethnicity for the MMSE; age, visual impairment, ApoeE4 noncarrier, and depression for the MIS; and no hyperlipidemia and normal informant memory assessment for the AN. Lower years of education and heart problems predicted misclassification on both the MMSE and AN.

An absence of informant-related poor memory predicted misclassification on all three tests.

“Failing to detect dementia can delay access to treatment and support, whereas false alarms lead to unnecessary investigations, causing pressure on health care systems,” Dr. Llewellyn said in a press statement. “Identifying people with dementia in a timely fashion is important, particularly as new methods of treatment come onstream. Our findings show that we desperately need more accurate and less biased ways of detecting dementia swiftly in clinic.”

The study was supported by the Halpin Trust, the Mary Kinross Charitable Trust, the Engineering and Physical Sciences Research Council, and the U.K. National Institute for Health Research. None of the authors reported any financial conflicts relevant to the work.

msullivan@mdedge.com

SOURCE: Llewellyn D et al. Neuro Clin Pract. 2019;1:1-9.

Three commonly used, brief cognitive tests erroneously identified dementia, resulting in more than a third of those screened being incorrectly classified, a retrospective analysis has concluded.

The likelihood of a false-positive or false-negative result declined sharply when all three tests were given, however; only about 2% of patients were misclassified in all three, David Llewellyn, PhD, and his colleagues reported in Neurology: Clinical Practice.

The Mini Mental State Examination (MMSE), Memory Impairment Screen (MIS), and animal naming (AN) were susceptible to different measurement biases, wrote Dr. Llewellyn of the University of Exeter (U.K.).

Just one variable – an informant’s perception of the patient’s memory as unimpaired – consistently predicted inaccuracy in all three tests. Most of the patients in this category carried the diagnosis of cognitively impaired but not demented (CIND), a finding that has important clinical implications.

“These participants may be in the very early stages of conversion to dementia. ... Therefore, of those with low or borderline cognitive assessment results, reassessment to detect further decline may be appropriate.”

The study comprised 824 patients included in the Aging, Demographics and Memory Study, which is a subsample of the Health and Retirement Study. They completed the tests from 2001-2004, during which time they were a mean of 82 years old. A panel of experts adjudicated diagnoses, which they then parsed into all-cause dementia, CIND, or cognitively normal. The testing included a self and informant assessment of memory decline. The investigators also looked at 22 predictors of cognition, including patient characteristics, apolipoprotein E carriage (ApoE e4), and sociodemographic factors.

The prevalence of dementia was 35.3%; of the nondemented patients, 43% met the criteria for CIND. The team found that 35.7% of cases were misclassified by at least one test, 13.4% by two, and 1.7% by all three.

The MMSE was the least accurate, with a 21% misclassification rate, reflected in an 18.6% false-positive rate for those without dementia and a 2.4% rate of false-negative for those with dementia.

The MIS had a 16% misclassification rate, with a 9.5% rate of false-positive for those with no dementia and a 6.3% rate of false-negative for those without.

The AN had a 14% misclassification rate, with a 6.8% false-positive rate for those without dementia and a 7.7% false-negative rate for those with dementia.

For the MMSE, MIS, and AN, the number of participants with false-positives that met the criteria for CIND were 74.5%, 82.1%, and 82.1%, respectively.

In the final multivariate model, seven variables predicted misclassification, including black ethnicity for the MMSE; age, visual impairment, ApoeE4 noncarrier, and depression for the MIS; and no hyperlipidemia and normal informant memory assessment for the AN. Lower years of education and heart problems predicted misclassification on both the MMSE and AN.

An absence of informant-related poor memory predicted misclassification on all three tests.

“Failing to detect dementia can delay access to treatment and support, whereas false alarms lead to unnecessary investigations, causing pressure on health care systems,” Dr. Llewellyn said in a press statement. “Identifying people with dementia in a timely fashion is important, particularly as new methods of treatment come onstream. Our findings show that we desperately need more accurate and less biased ways of detecting dementia swiftly in clinic.”

The study was supported by the Halpin Trust, the Mary Kinross Charitable Trust, the Engineering and Physical Sciences Research Council, and the U.K. National Institute for Health Research. None of the authors reported any financial conflicts relevant to the work.

msullivan@mdedge.com

SOURCE: Llewellyn D et al. Neuro Clin Pract. 2019;1:1-9.

Three commonly used, brief cognitive tests erroneously identified dementia, resulting in more than a third of those screened being incorrectly classified, a retrospective analysis has concluded.

The likelihood of a false-positive or false-negative result declined sharply when all three tests were given, however; only about 2% of patients were misclassified in all three, David Llewellyn, PhD, and his colleagues reported in Neurology: Clinical Practice.

The Mini Mental State Examination (MMSE), Memory Impairment Screen (MIS), and animal naming (AN) were susceptible to different measurement biases, wrote Dr. Llewellyn of the University of Exeter (U.K.).

Just one variable – an informant’s perception of the patient’s memory as unimpaired – consistently predicted inaccuracy in all three tests. Most of the patients in this category carried the diagnosis of cognitively impaired but not demented (CIND), a finding that has important clinical implications.

“These participants may be in the very early stages of conversion to dementia. ... Therefore, of those with low or borderline cognitive assessment results, reassessment to detect further decline may be appropriate.”

The study comprised 824 patients included in the Aging, Demographics and Memory Study, which is a subsample of the Health and Retirement Study. They completed the tests from 2001-2004, during which time they were a mean of 82 years old. A panel of experts adjudicated diagnoses, which they then parsed into all-cause dementia, CIND, or cognitively normal. The testing included a self and informant assessment of memory decline. The investigators also looked at 22 predictors of cognition, including patient characteristics, apolipoprotein E carriage (ApoE e4), and sociodemographic factors.

The prevalence of dementia was 35.3%; of the nondemented patients, 43% met the criteria for CIND. The team found that 35.7% of cases were misclassified by at least one test, 13.4% by two, and 1.7% by all three.

The MMSE was the least accurate, with a 21% misclassification rate, reflected in an 18.6% false-positive rate for those without dementia and a 2.4% rate of false-negative for those with dementia.

The MIS had a 16% misclassification rate, with a 9.5% rate of false-positive for those with no dementia and a 6.3% rate of false-negative for those without.

The AN had a 14% misclassification rate, with a 6.8% false-positive rate for those without dementia and a 7.7% false-negative rate for those with dementia.

For the MMSE, MIS, and AN, the number of participants with false-positives that met the criteria for CIND were 74.5%, 82.1%, and 82.1%, respectively.

In the final multivariate model, seven variables predicted misclassification, including black ethnicity for the MMSE; age, visual impairment, ApoeE4 noncarrier, and depression for the MIS; and no hyperlipidemia and normal informant memory assessment for the AN. Lower years of education and heart problems predicted misclassification on both the MMSE and AN.

An absence of informant-related poor memory predicted misclassification on all three tests.

“Failing to detect dementia can delay access to treatment and support, whereas false alarms lead to unnecessary investigations, causing pressure on health care systems,” Dr. Llewellyn said in a press statement. “Identifying people with dementia in a timely fashion is important, particularly as new methods of treatment come onstream. Our findings show that we desperately need more accurate and less biased ways of detecting dementia swiftly in clinic.”

The study was supported by the Halpin Trust, the Mary Kinross Charitable Trust, the Engineering and Physical Sciences Research Council, and the U.K. National Institute for Health Research. None of the authors reported any financial conflicts relevant to the work.

msullivan@mdedge.com

SOURCE: Llewellyn D et al. Neuro Clin Pract. 2019;1:1-9.

A gene therapy for Parkinson’s disease, focusing on the subthalamic nucleus, appears to lead to the formation of unique brain circuitry that correlates with clinical improvement.

copyright graphicsdunia4you/Thinkstock

In a paper published online Nov. 28 in Science Translational Medicine, researchers describe the findings of a metabolic imaging study to explore the mechanism underlying benefits seen in a phase 2, blinded, sham-controlled clinical trial of the gene therapy.

The therapy in question used an adeno-associated viral vector to deliver the gene for glutamic acid decarboxylase into the subthalamic nucleus – a region of the brain known to be overactivated in Parkinson’s disease – which was intended to have an inhibitory effect on the neurons in that region.

Martin Niethammer, MD, PhD, of the Center for Neurosciences at The Feinstein Institute for Medical Research in New York, and his coauthors used ¹⁸F-fluorodeoxyglucose positron emission tomography at baseline, 6, and 12 months in 15 gene-therapy patients and 21 sham-treated patients, which revealed the development of new brain circuits in patients treated with the gene therapy.

The circuits, which researchers called the glutamic acid decarboxylase-related pattern, or GADRP, presented with increased metabolism in the premotor region – which also extended into the adjacent motor cortex – and in the supramarginal gyrus. There was also decreased metabolic activity in the caudate, anterior putamen, and adjacent globus pallidus; the ventral anterior and medial dorsal thalamic nuclei; and in the inferior frontal gyrus.

All 15 patients who received the gene therapy showed significant trends in GADRP expression after the treatment, compared with patients who underwent the sham procedure. Furthermore, these correlated significantly with improved clinical outcomes.

The imaging also revealed increased connectivity between regions in the GADRP space among patients who received the gene therapy, with researchers noting five new intrahemispheric node-to-node connections in these patients that were not seen in the sham procedure group.

These included connection linking the left caudate nucleus to the left superior frontal node, the right superior frontal node to the right supramarginal gyrus, and linking the left anterior putamen and globus pallidus with the ipsilateral thalamic node.

The authors also found that overall connectivity in the network rose to “abnormal” levels in the 12 months after gene therapy, while no similar increases were seen in the sham group.

Given that deep brain stimulation for Parkinson’s disease also targets the subthalamic nucleus, researchers looked at changes to the GADRP network in these patients, compared with those who received sham therapy and those who received gene therapy.

They saw that changes in GADRP expression were significantly different between the gene therapy-treated patients and those treated with deep brain stimulation and sham surgery. However, the differences between deep brain stimulation and sham surgery were not significant.

“The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials,” the authors wrote.

The study was supported by Neurologix. Two authors were consultants and stockholders of MeiraGTx.

SOURCE: Niethammer N et al. Sci Transl Med. 2018 Nov 28. doi: 10.1126/scitranslmed.aau0713.

A gene therapy for Parkinson’s disease, focusing on the subthalamic nucleus, appears to lead to the formation of unique brain circuitry that correlates with clinical improvement.

copyright graphicsdunia4you/Thinkstock

In a paper published online Nov. 28 in Science Translational Medicine, researchers describe the findings of a metabolic imaging study to explore the mechanism underlying benefits seen in a phase 2, blinded, sham-controlled clinical trial of the gene therapy.

The therapy in question used an adeno-associated viral vector to deliver the gene for glutamic acid decarboxylase into the subthalamic nucleus – a region of the brain known to be overactivated in Parkinson’s disease – which was intended to have an inhibitory effect on the neurons in that region.

Martin Niethammer, MD, PhD, of the Center for Neurosciences at The Feinstein Institute for Medical Research in New York, and his coauthors used ¹⁸F-fluorodeoxyglucose positron emission tomography at baseline, 6, and 12 months in 15 gene-therapy patients and 21 sham-treated patients, which revealed the development of new brain circuits in patients treated with the gene therapy.

The circuits, which researchers called the glutamic acid decarboxylase-related pattern, or GADRP, presented with increased metabolism in the premotor region – which also extended into the adjacent motor cortex – and in the supramarginal gyrus. There was also decreased metabolic activity in the caudate, anterior putamen, and adjacent globus pallidus; the ventral anterior and medial dorsal thalamic nuclei; and in the inferior frontal gyrus.

All 15 patients who received the gene therapy showed significant trends in GADRP expression after the treatment, compared with patients who underwent the sham procedure. Furthermore, these correlated significantly with improved clinical outcomes.

The imaging also revealed increased connectivity between regions in the GADRP space among patients who received the gene therapy, with researchers noting five new intrahemispheric node-to-node connections in these patients that were not seen in the sham procedure group.

These included connection linking the left caudate nucleus to the left superior frontal node, the right superior frontal node to the right supramarginal gyrus, and linking the left anterior putamen and globus pallidus with the ipsilateral thalamic node.

The authors also found that overall connectivity in the network rose to “abnormal” levels in the 12 months after gene therapy, while no similar increases were seen in the sham group.

Given that deep brain stimulation for Parkinson’s disease also targets the subthalamic nucleus, researchers looked at changes to the GADRP network in these patients, compared with those who received sham therapy and those who received gene therapy.

They saw that changes in GADRP expression were significantly different between the gene therapy-treated patients and those treated with deep brain stimulation and sham surgery. However, the differences between deep brain stimulation and sham surgery were not significant.

“The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials,” the authors wrote.

The study was supported by Neurologix. Two authors were consultants and stockholders of MeiraGTx.

SOURCE: Niethammer N et al. Sci Transl Med. 2018 Nov 28. doi: 10.1126/scitranslmed.aau0713.

A gene therapy for Parkinson’s disease, focusing on the subthalamic nucleus, appears to lead to the formation of unique brain circuitry that correlates with clinical improvement.

copyright graphicsdunia4you/Thinkstock

In a paper published online Nov. 28 in Science Translational Medicine, researchers describe the findings of a metabolic imaging study to explore the mechanism underlying benefits seen in a phase 2, blinded, sham-controlled clinical trial of the gene therapy.

The therapy in question used an adeno-associated viral vector to deliver the gene for glutamic acid decarboxylase into the subthalamic nucleus – a region of the brain known to be overactivated in Parkinson’s disease – which was intended to have an inhibitory effect on the neurons in that region.

Martin Niethammer, MD, PhD, of the Center for Neurosciences at The Feinstein Institute for Medical Research in New York, and his coauthors used ¹⁸F-fluorodeoxyglucose positron emission tomography at baseline, 6, and 12 months in 15 gene-therapy patients and 21 sham-treated patients, which revealed the development of new brain circuits in patients treated with the gene therapy.

The circuits, which researchers called the glutamic acid decarboxylase-related pattern, or GADRP, presented with increased metabolism in the premotor region – which also extended into the adjacent motor cortex – and in the supramarginal gyrus. There was also decreased metabolic activity in the caudate, anterior putamen, and adjacent globus pallidus; the ventral anterior and medial dorsal thalamic nuclei; and in the inferior frontal gyrus.

All 15 patients who received the gene therapy showed significant trends in GADRP expression after the treatment, compared with patients who underwent the sham procedure. Furthermore, these correlated significantly with improved clinical outcomes.

The imaging also revealed increased connectivity between regions in the GADRP space among patients who received the gene therapy, with researchers noting five new intrahemispheric node-to-node connections in these patients that were not seen in the sham procedure group.

These included connection linking the left caudate nucleus to the left superior frontal node, the right superior frontal node to the right supramarginal gyrus, and linking the left anterior putamen and globus pallidus with the ipsilateral thalamic node.

The authors also found that overall connectivity in the network rose to “abnormal” levels in the 12 months after gene therapy, while no similar increases were seen in the sham group.

Given that deep brain stimulation for Parkinson’s disease also targets the subthalamic nucleus, researchers looked at changes to the GADRP network in these patients, compared with those who received sham therapy and those who received gene therapy.

They saw that changes in GADRP expression were significantly different between the gene therapy-treated patients and those treated with deep brain stimulation and sham surgery. However, the differences between deep brain stimulation and sham surgery were not significant.

“The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials,” the authors wrote.

The study was supported by Neurologix. Two authors were consultants and stockholders of MeiraGTx.

SOURCE: Niethammer N et al. Sci Transl Med. 2018 Nov 28. doi: 10.1126/scitranslmed.aau0713.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

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Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

BERLIN – In addition to the pain, motor and sensory impairments, and cognitive dysfunction that can stalk multiple sclerosis (MS) patients, for many, there’s also the challenge of an invisible, tough-to-quantify entity: fatigue.

©RusN/Thinkstock.com

“Approximately 80% of patients suffer from fatigue, so it’s an immense problem in MS. There’s no real clear relationship with disease severity,” Vincent de Groot, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “Despite what a lot of people think, there’s no clear or strong relationship between fatigue and the amount of physical activity people undertake daily,” he noted.

“Patients all know what we are talking about when we ask about fatigue,” but there are a variety of definitions of fatigue used in research, a fact that has limited progress in the field, said Dr. de Groot.

Primary fatigue is related to the pathophysiology of MS itself, while secondary fatigue can result from MS symptoms, such as poor sleep from spasms. Secondary fatigue can also be a side effect of MS medications; baclofen, used for spasticity, is a good example, said Dr. de Groot. “We must not underestimate how many problems these drugs can give people.”

What’s the mechanism by which MS causes primary fatigue? “The simple answer is that we do not know,” said Dr. de Groot, a physiatrist and researcher at Vrije University, Amsterdam.

Though immune-mediated fatigue had been proposed as a factor for patients with MS, Dr. de Groot said that his own lab’s work has not found any connection between fatigue levels and any immune-related biomarkers. “So I don’t think the immune hypothesis has a lot of evidence.”

Similarly, though there might be mechanistic reasons to suspect the hypothalamic-pituitary-adrenal (HPA) axis as a culprit for MS fatigue, no consistent association has been found between any markers for HPA axis disruption and fatigue ratings, Dr. de Groot said.

Newer theories center on MS-related disruptions in brain connectivity, with imaging studies now able to detect some of these disruptions in functional connectivity that correlate with fatigue. “Right now, I think this is the hypothesis to bet money on,” Dr. de Groot said.

Many factors come into play, including environmental and psychological factors, he said.

“What can we do to treat MS-related fatigue?” Though several drugs have been used, “if you carefully look at the systematic reviews, the evidence is very, very disappointing,” Dr. de Groot said. For both amantadine and modafinil, “there is no evidence that these drugs are effective,” he said, citing a systematic review and meta-analysis that found a pooled effect size of 0.07 (95% confidence interval, –0.22 to 0.37) for medications (Mult Scler Int. 2014 May; doi: 10.1155/2014/798285).

Only two trials have looked at multidisciplinary rehabilitation for MS-related fatigue, Dr. de Groot said. Two studies that looked at multidisciplinary strategies that pulled in a variety of disciplines to help develop tailored fatigue management strategies saw no between-group effect when the multidisciplinary intervention was compared with nurse-provided information or with non–fatigue-related rehabilitation.

In an effort to determine whether MS-related fatigue is truly refractory to treatment, Dr. de Groot said that he and his colleagues decided to take “three steps back” to look at the individual interventions that make up a multidisciplinary approach to tackling fatigue. “So, we looked at exercise therapy, energy conservation management, and cognitive-behavioral therapy,” beginning with a literature review, he said.

Members of his research group found that effect sizes ranged from small to moderate for the three approaches, but there were methodologic problems with many of the studies; in the case of cognitive-behavioral therapy (CBT), the effect size waned over time, Dr. de Groot said. A newer randomized, controlled trial showed a relatively robust effect size of 0.52 for Internet-delivered CBT, which may provide a promising and practical approach (J Neurol Neurosurg Psychiatry. 2018 Sep;89[9]:970-6. doi: 10.1136/jnnp-2017-317463).

Looking at fatigue and societal participation, Dr. de Groot and his colleagues examined what effect aerobic training, energy conservation management, and CBT had on the two outcome measures. The three interventions were studied in three stand-alone trials, he said.

Patients were assessed at baseline, and at 8, 16, 26, and 52 weeks. The assessments were performed by a blinded researcher and were the same across trials: For fatigue, researchers used the Checklist Individual Strength–fatigue (CIS20R-fatigue), and for societal participation, they administered the Impact on Participation and Autonomy (IPA).

Each trial included 90 patients, randomized 1:1 to receive high- or low-intensity treatment. Patients had to have MS with no exacerbations within the prior 6 months and an Expanded Disability Status Scale score of 6 or less. However, the included patients had severe fatigue, with a CIS20R-fatigue subscore of 35 or higher, and the fatigue could not be attributable to such secondary causes as infection, depression, or thyroid or sleep problems. Finally, patients could not have been treated for fatigue in the 3 months prior to enrollment.

Those in the high-intensity treatment group received 12 sessions focused on the particular intervention over 4 months, provided by an expert therapist. Each type of intervention had a treatment protocol that was followed over the 4 months. Patients receiving low-intensity treatment saw an MS-specialized nurse three times over 4 months.

The aerobic training intervention had patients performing high-intensity exercise on a cycle ergometer for 30 minutes, three times weekly for 16 weeks. In addition to the 12 supervised sessions, patients also completed 36 home-based sessions. The level of intensity for each patient was personalized based on their baseline cardiopulmonary exercise test, Dr. de Groot said.

At the end of 1 year, patients in the high-intensity group and those in the low-intensity group reported virtually the same fatigue scores. Though there was an initial drop in fatigue for those in the high-intensity group, compared with baseline and with the low-intensity participants, values on the CIS20R never dropped below 35, the “severe fatigue” cutoff.

And, Dr. de Groot said, there was no effect on societal participation or in other fatigue scores. In sum, the effect size was barely significant at –0.54 (95% CI, –1.00 to –0.06), with a number needed to treat of 9.

Adherence to attempting the workouts was fairly good for participants in the high-intensity group; 74% completed the sessions, with 71% doing so at the prescribed workload. The median rate of perceived exertion on a 1-20 scale was 14.

However, the thrice-weekly exercise bouts didn’t improve aerobic fitness parameters: Neither V0₂peak, V0₂peak adjusted for body mass, nor anaerobic threshold changed for those in the high-intensity group. Peak power did increase by 11.7 watts (P = .048).

Energy conservation education, whether delivered in high- or low-intensity format, had almost no effect on fatigue scores, with a number needed to treat of 158 – a figure that is “neither significant nor clinically meaningful,” Dr. de Groot said. Other fatigue scores and societal participation levels also went unchanged.

However, CBT delivered in a series of 10 modules to address various beliefs and coping mechanisms about MS, fatigue, pain, and activity regulation did have a positive effect on fatigue. Here, the effect size was –0.79 (95% CI, –1.26 to –0.32). The number needed to treat was 3, and CIS20R values did dip below the “severe fatigue” threshold during treatment. A similar effect, Dr. de Groot said, was seen for other fatigue and quality of life measures, though societal participation scores didn’t change. No significant improvement was seen for the low-intensity CBT group.

“Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect in the long term,” Dr. de Groot said. Still, “it’s currently the best treatment option,” he said.

The fact that patients reverted to their preintervention fatigue levels regardless of the intervention shows that effective treatment for MS-related fatigue should probably be ongoing, viewed more as a process than an occurrence, Dr. de Groot said.

To that end, Dr. de Groot and his colleagues are conducting a randomized, controlled trial that includes 166 MS patients with fatigue. The study has two arms: The first is a noninferiority trial comparing face-to-face CBT with e-learning delivery of the content, and the second looks at the efficacy of ongoing booster sessions after initial CBT.

An online database of randomized, controlled trials of rehabilitation for MS patients can be found at www.appeco.net.

The study was funded by Fonds NutsOhra, a private Dutch foundation. Dr. de Groot reported no relevant conflicts of interest.

koakes@mdedge.com

SOURCE: de Groot V. Mult Scler. 2018;24(S2):83, Abstract 225.

BERLIN – In addition to the pain, motor and sensory impairments, and cognitive dysfunction that can stalk multiple sclerosis (MS) patients, for many, there’s also the challenge of an invisible, tough-to-quantify entity: fatigue.

©RusN/Thinkstock.com

“Approximately 80% of patients suffer from fatigue, so it’s an immense problem in MS. There’s no real clear relationship with disease severity,” Vincent de Groot, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “Despite what a lot of people think, there’s no clear or strong relationship between fatigue and the amount of physical activity people undertake daily,” he noted.

“Patients all know what we are talking about when we ask about fatigue,” but there are a variety of definitions of fatigue used in research, a fact that has limited progress in the field, said Dr. de Groot.

Primary fatigue is related to the pathophysiology of MS itself, while secondary fatigue can result from MS symptoms, such as poor sleep from spasms. Secondary fatigue can also be a side effect of MS medications; baclofen, used for spasticity, is a good example, said Dr. de Groot. “We must not underestimate how many problems these drugs can give people.”

What’s the mechanism by which MS causes primary fatigue? “The simple answer is that we do not know,” said Dr. de Groot, a physiatrist and researcher at Vrije University, Amsterdam.

Though immune-mediated fatigue had been proposed as a factor for patients with MS, Dr. de Groot said that his own lab’s work has not found any connection between fatigue levels and any immune-related biomarkers. “So I don’t think the immune hypothesis has a lot of evidence.”

Similarly, though there might be mechanistic reasons to suspect the hypothalamic-pituitary-adrenal (HPA) axis as a culprit for MS fatigue, no consistent association has been found between any markers for HPA axis disruption and fatigue ratings, Dr. de Groot said.

Newer theories center on MS-related disruptions in brain connectivity, with imaging studies now able to detect some of these disruptions in functional connectivity that correlate with fatigue. “Right now, I think this is the hypothesis to bet money on,” Dr. de Groot said.

Many factors come into play, including environmental and psychological factors, he said.

“What can we do to treat MS-related fatigue?” Though several drugs have been used, “if you carefully look at the systematic reviews, the evidence is very, very disappointing,” Dr. de Groot said. For both amantadine and modafinil, “there is no evidence that these drugs are effective,” he said, citing a systematic review and meta-analysis that found a pooled effect size of 0.07 (95% confidence interval, –0.22 to 0.37) for medications (Mult Scler Int. 2014 May; doi: 10.1155/2014/798285).

Only two trials have looked at multidisciplinary rehabilitation for MS-related fatigue, Dr. de Groot said. Two studies that looked at multidisciplinary strategies that pulled in a variety of disciplines to help develop tailored fatigue management strategies saw no between-group effect when the multidisciplinary intervention was compared with nurse-provided information or with non–fatigue-related rehabilitation.

In an effort to determine whether MS-related fatigue is truly refractory to treatment, Dr. de Groot said that he and his colleagues decided to take “three steps back” to look at the individual interventions that make up a multidisciplinary approach to tackling fatigue. “So, we looked at exercise therapy, energy conservation management, and cognitive-behavioral therapy,” beginning with a literature review, he said.

Members of his research group found that effect sizes ranged from small to moderate for the three approaches, but there were methodologic problems with many of the studies; in the case of cognitive-behavioral therapy (CBT), the effect size waned over time, Dr. de Groot said. A newer randomized, controlled trial showed a relatively robust effect size of 0.52 for Internet-delivered CBT, which may provide a promising and practical approach (J Neurol Neurosurg Psychiatry. 2018 Sep;89[9]:970-6. doi: 10.1136/jnnp-2017-317463).

Looking at fatigue and societal participation, Dr. de Groot and his colleagues examined what effect aerobic training, energy conservation management, and CBT had on the two outcome measures. The three interventions were studied in three stand-alone trials, he said.

Patients were assessed at baseline, and at 8, 16, 26, and 52 weeks. The assessments were performed by a blinded researcher and were the same across trials: For fatigue, researchers used the Checklist Individual Strength–fatigue (CIS20R-fatigue), and for societal participation, they administered the Impact on Participation and Autonomy (IPA).

Each trial included 90 patients, randomized 1:1 to receive high- or low-intensity treatment. Patients had to have MS with no exacerbations within the prior 6 months and an Expanded Disability Status Scale score of 6 or less. However, the included patients had severe fatigue, with a CIS20R-fatigue subscore of 35 or higher, and the fatigue could not be attributable to such secondary causes as infection, depression, or thyroid or sleep problems. Finally, patients could not have been treated for fatigue in the 3 months prior to enrollment.

Those in the high-intensity treatment group received 12 sessions focused on the particular intervention over 4 months, provided by an expert therapist. Each type of intervention had a treatment protocol that was followed over the 4 months. Patients receiving low-intensity treatment saw an MS-specialized nurse three times over 4 months.

The aerobic training intervention had patients performing high-intensity exercise on a cycle ergometer for 30 minutes, three times weekly for 16 weeks. In addition to the 12 supervised sessions, patients also completed 36 home-based sessions. The level of intensity for each patient was personalized based on their baseline cardiopulmonary exercise test, Dr. de Groot said.

At the end of 1 year, patients in the high-intensity group and those in the low-intensity group reported virtually the same fatigue scores. Though there was an initial drop in fatigue for those in the high-intensity group, compared with baseline and with the low-intensity participants, values on the CIS20R never dropped below 35, the “severe fatigue” cutoff.

And, Dr. de Groot said, there was no effect on societal participation or in other fatigue scores. In sum, the effect size was barely significant at –0.54 (95% CI, –1.00 to –0.06), with a number needed to treat of 9.

Adherence to attempting the workouts was fairly good for participants in the high-intensity group; 74% completed the sessions, with 71% doing so at the prescribed workload. The median rate of perceived exertion on a 1-20 scale was 14.

However, the thrice-weekly exercise bouts didn’t improve aerobic fitness parameters: Neither V0₂peak, V0₂peak adjusted for body mass, nor anaerobic threshold changed for those in the high-intensity group. Peak power did increase by 11.7 watts (P = .048).

Energy conservation education, whether delivered in high- or low-intensity format, had almost no effect on fatigue scores, with a number needed to treat of 158 – a figure that is “neither significant nor clinically meaningful,” Dr. de Groot said. Other fatigue scores and societal participation levels also went unchanged.

However, CBT delivered in a series of 10 modules to address various beliefs and coping mechanisms about MS, fatigue, pain, and activity regulation did have a positive effect on fatigue. Here, the effect size was –0.79 (95% CI, –1.26 to –0.32). The number needed to treat was 3, and CIS20R values did dip below the “severe fatigue” threshold during treatment. A similar effect, Dr. de Groot said, was seen for other fatigue and quality of life measures, though societal participation scores didn’t change. No significant improvement was seen for the low-intensity CBT group.

“Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect in the long term,” Dr. de Groot said. Still, “it’s currently the best treatment option,” he said.

The fact that patients reverted to their preintervention fatigue levels regardless of the intervention shows that effective treatment for MS-related fatigue should probably be ongoing, viewed more as a process than an occurrence, Dr. de Groot said.

To that end, Dr. de Groot and his colleagues are conducting a randomized, controlled trial that includes 166 MS patients with fatigue. The study has two arms: The first is a noninferiority trial comparing face-to-face CBT with e-learning delivery of the content, and the second looks at the efficacy of ongoing booster sessions after initial CBT.

An online database of randomized, controlled trials of rehabilitation for MS patients can be found at www.appeco.net.

The study was funded by Fonds NutsOhra, a private Dutch foundation. Dr. de Groot reported no relevant conflicts of interest.

koakes@mdedge.com

SOURCE: de Groot V. Mult Scler. 2018;24(S2):83, Abstract 225.

BERLIN – In addition to the pain, motor and sensory impairments, and cognitive dysfunction that can stalk multiple sclerosis (MS) patients, for many, there’s also the challenge of an invisible, tough-to-quantify entity: fatigue.

©RusN/Thinkstock.com

“Approximately 80% of patients suffer from fatigue, so it’s an immense problem in MS. There’s no real clear relationship with disease severity,” Vincent de Groot, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “Despite what a lot of people think, there’s no clear or strong relationship between fatigue and the amount of physical activity people undertake daily,” he noted.

“Patients all know what we are talking about when we ask about fatigue,” but there are a variety of definitions of fatigue used in research, a fact that has limited progress in the field, said Dr. de Groot.

Primary fatigue is related to the pathophysiology of MS itself, while secondary fatigue can result from MS symptoms, such as poor sleep from spasms. Secondary fatigue can also be a side effect of MS medications; baclofen, used for spasticity, is a good example, said Dr. de Groot. “We must not underestimate how many problems these drugs can give people.”

What’s the mechanism by which MS causes primary fatigue? “The simple answer is that we do not know,” said Dr. de Groot, a physiatrist and researcher at Vrije University, Amsterdam.

Though immune-mediated fatigue had been proposed as a factor for patients with MS, Dr. de Groot said that his own lab’s work has not found any connection between fatigue levels and any immune-related biomarkers. “So I don’t think the immune hypothesis has a lot of evidence.”

Similarly, though there might be mechanistic reasons to suspect the hypothalamic-pituitary-adrenal (HPA) axis as a culprit for MS fatigue, no consistent association has been found between any markers for HPA axis disruption and fatigue ratings, Dr. de Groot said.

Newer theories center on MS-related disruptions in brain connectivity, with imaging studies now able to detect some of these disruptions in functional connectivity that correlate with fatigue. “Right now, I think this is the hypothesis to bet money on,” Dr. de Groot said.

Many factors come into play, including environmental and psychological factors, he said.

“What can we do to treat MS-related fatigue?” Though several drugs have been used, “if you carefully look at the systematic reviews, the evidence is very, very disappointing,” Dr. de Groot said. For both amantadine and modafinil, “there is no evidence that these drugs are effective,” he said, citing a systematic review and meta-analysis that found a pooled effect size of 0.07 (95% confidence interval, –0.22 to 0.37) for medications (Mult Scler Int. 2014 May; doi: 10.1155/2014/798285).

Only two trials have looked at multidisciplinary rehabilitation for MS-related fatigue, Dr. de Groot said. Two studies that looked at multidisciplinary strategies that pulled in a variety of disciplines to help develop tailored fatigue management strategies saw no between-group effect when the multidisciplinary intervention was compared with nurse-provided information or with non–fatigue-related rehabilitation.

In an effort to determine whether MS-related fatigue is truly refractory to treatment, Dr. de Groot said that he and his colleagues decided to take “three steps back” to look at the individual interventions that make up a multidisciplinary approach to tackling fatigue. “So, we looked at exercise therapy, energy conservation management, and cognitive-behavioral therapy,” beginning with a literature review, he said.

Members of his research group found that effect sizes ranged from small to moderate for the three approaches, but there were methodologic problems with many of the studies; in the case of cognitive-behavioral therapy (CBT), the effect size waned over time, Dr. de Groot said. A newer randomized, controlled trial showed a relatively robust effect size of 0.52 for Internet-delivered CBT, which may provide a promising and practical approach (J Neurol Neurosurg Psychiatry. 2018 Sep;89[9]:970-6. doi: 10.1136/jnnp-2017-317463).

Looking at fatigue and societal participation, Dr. de Groot and his colleagues examined what effect aerobic training, energy conservation management, and CBT had on the two outcome measures. The three interventions were studied in three stand-alone trials, he said.

Patients were assessed at baseline, and at 8, 16, 26, and 52 weeks. The assessments were performed by a blinded researcher and were the same across trials: For fatigue, researchers used the Checklist Individual Strength–fatigue (CIS20R-fatigue), and for societal participation, they administered the Impact on Participation and Autonomy (IPA).

Each trial included 90 patients, randomized 1:1 to receive high- or low-intensity treatment. Patients had to have MS with no exacerbations within the prior 6 months and an Expanded Disability Status Scale score of 6 or less. However, the included patients had severe fatigue, with a CIS20R-fatigue subscore of 35 or higher, and the fatigue could not be attributable to such secondary causes as infection, depression, or thyroid or sleep problems. Finally, patients could not have been treated for fatigue in the 3 months prior to enrollment.

Those in the high-intensity treatment group received 12 sessions focused on the particular intervention over 4 months, provided by an expert therapist. Each type of intervention had a treatment protocol that was followed over the 4 months. Patients receiving low-intensity treatment saw an MS-specialized nurse three times over 4 months.

The aerobic training intervention had patients performing high-intensity exercise on a cycle ergometer for 30 minutes, three times weekly for 16 weeks. In addition to the 12 supervised sessions, patients also completed 36 home-based sessions. The level of intensity for each patient was personalized based on their baseline cardiopulmonary exercise test, Dr. de Groot said.

At the end of 1 year, patients in the high-intensity group and those in the low-intensity group reported virtually the same fatigue scores. Though there was an initial drop in fatigue for those in the high-intensity group, compared with baseline and with the low-intensity participants, values on the CIS20R never dropped below 35, the “severe fatigue” cutoff.

And, Dr. de Groot said, there was no effect on societal participation or in other fatigue scores. In sum, the effect size was barely significant at –0.54 (95% CI, –1.00 to –0.06), with a number needed to treat of 9.

Adherence to attempting the workouts was fairly good for participants in the high-intensity group; 74% completed the sessions, with 71% doing so at the prescribed workload. The median rate of perceived exertion on a 1-20 scale was 14.

However, the thrice-weekly exercise bouts didn’t improve aerobic fitness parameters: Neither V0₂peak, V0₂peak adjusted for body mass, nor anaerobic threshold changed for those in the high-intensity group. Peak power did increase by 11.7 watts (P = .048).

Energy conservation education, whether delivered in high- or low-intensity format, had almost no effect on fatigue scores, with a number needed to treat of 158 – a figure that is “neither significant nor clinically meaningful,” Dr. de Groot said. Other fatigue scores and societal participation levels also went unchanged.

However, CBT delivered in a series of 10 modules to address various beliefs and coping mechanisms about MS, fatigue, pain, and activity regulation did have a positive effect on fatigue. Here, the effect size was –0.79 (95% CI, –1.26 to –0.32). The number needed to treat was 3, and CIS20R values did dip below the “severe fatigue” threshold during treatment. A similar effect, Dr. de Groot said, was seen for other fatigue and quality of life measures, though societal participation scores didn’t change. No significant improvement was seen for the low-intensity CBT group.

“Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect in the long term,” Dr. de Groot said. Still, “it’s currently the best treatment option,” he said.

The fact that patients reverted to their preintervention fatigue levels regardless of the intervention shows that effective treatment for MS-related fatigue should probably be ongoing, viewed more as a process than an occurrence, Dr. de Groot said.

To that end, Dr. de Groot and his colleagues are conducting a randomized, controlled trial that includes 166 MS patients with fatigue. The study has two arms: The first is a noninferiority trial comparing face-to-face CBT with e-learning delivery of the content, and the second looks at the efficacy of ongoing booster sessions after initial CBT.

An online database of randomized, controlled trials of rehabilitation for MS patients can be found at www.appeco.net.

The study was funded by Fonds NutsOhra, a private Dutch foundation. Dr. de Groot reported no relevant conflicts of interest.

koakes@mdedge.com

SOURCE: de Groot V. Mult Scler. 2018;24(S2):83, Abstract 225.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.