Case Reports

THE CASE

A 21-year-old college student was referred to us by the counseling center at our university for a psychiatric evaluation after 11 psychotherapy sessions over 3 months had failed to reduce her feelings of anxiety and panic.

During our evaluation, the patient described feeling “not quite right” for many months. She had been experiencing mental fogginess, fatigue, and worsening concentration/ memory. Her anxiety, which had been gradually increasing, was the result of being unsure about her gait. She first noticed this while walking down some bleachers; she felt dizzy, was afraid of falling, and couldn’t walk down without assistance. All episodes of “panic” occurred in situations where she experienced disequilibrium, unsteady gait, and fear of falling. She grew fearful of driving or going anywhere without assistance.

The patient had celiac disease that was well controlled with a gluten-free diet. She had no personal or family psychiatric history and no history of substance abuse.

THE DIAGNOSIS

Physical exam and lab studies, including a complete blood count, comprehensive metabolic panel, and thyrotropin and folate levels, were normal. Her homocysteine level was 11.8 μmol/L (reference range, 5.4-11.9 μmol/L) and vitamin B₁₂ level was 292 pg/mL (reference range, 200-1100 pg/mL). Her lab report included a note that read, “Although the reference range for vitamin B₁₂ is 200 to 1100 pg/mL, it has been reported that between 5% and 10% of patients with values between 200 and 400 pg/mL may experience neuropsychiatric and hematologic abnormalities due to occult B₁₂ deficiency; <1% of patients with values >400 pg/mL will have symptoms.”

Based on this vitamin B₁₂ level, the patient’s symptoms, and her borderline high homocysteine level, we diagnosed vitamin B₁₂ deficiency.

DISCUSSION

There are no recommendations by the US Preventive Services Task Force or any other major US medical society for routine vitamin B₁₂ screening.¹ In Canada, the Medical Services Commission of the British Columbia Ministry of Health recommends B₁₂ screening for patients who present with macrocytic anemia or unexplained neurologic symptoms (eg, paresthesia, numbness, poor motor coordination, memory lapses, or cognitive or personality changes).²

Vitamin B₁₂ deficiency can be caused by numerous conditions, including those that cause malabsorption (such as gastric bypass). It can also be caused by diseases such as human immunodeficiency virus infection or Crohn’s disease, long-term adherence to a vegetarian or vegan diet, or by any other lack of dietary intake.¹ The condition can cause hematologic-related signs and symptoms such as megaloblastic anemia, fatigue, and syncope. It also can have neurologic manifestations, including paresthesia, weakness, motor disturbances (including gait abnormalities), vision loss, and a wide range of cognitive and behavioral changes.¹ Anemia is uncommon because since 1998, the US Food and Drug Administration has required fortification of all enriched grain and cereal products with folic acid; thus, vitamin B₁₂ deficiency may proceed without anemia revealing its presence.¹

A controversial topic. Vitamin B₁₂ deficiency is a complicated and controversial subject. Specifically, there is uncertainty about the clinical importance of lower serum levels of vitamin B₁₂ (200-400 pg/mL), their impact on well-being, and the need for treatment. In addition to measuring a patient’s serum B₁₂ level, testing a second biomarker (such as homocysteine or methylmalonic acid) can be helpful in establishing a diagnosis of B₁₂ deficiency.¹ Levels of each of these are elevated in patients with B₁₂ deficiency.¹

Some evidence suggests B₁₂ supplementation may improve symptoms of depression and anxiety.

Although vitamin B₁₂ deficiency has been well studied in older patients,³ little has been published about the condition in young adults. National Health and Nutrition Examination Survey (NHANES) data from 2000 to 2004 shows that almost 40% of people ages 19 to 30 years have a B₁₂ level <400 pg/mL.¹ How many of these individuals are at risk of complications of B₁₂ deficiency is unknown.

B₁₂ supplementation might improve depression, anxiety

B₁₂ supplementation is inexpensive and has no significant adverse effects.¹ It can be administered orally, parenterally (intramuscularly or subcutaneously), or intranasally.¹ A common oral regimen is 1 mg/d; parental regimens vary widely, but might include a 1-mg injection once a week for 8 weeks, then once a month for life.¹

Some evidence suggests B₁₂ supplementation may improve symptoms of depression and anxiety. A Pakistani study randomized 73 patients with depression and “low normal” B₁₂ levels (190-300 pg/mL) to an antidepressant only (equivalent to imipramine 100-250 mg/d or fluoxetine 20-40 mg/d) or an antidepressant plus parenteral B₁₂ (1000 mcg once a week).⁴ At 3 months follow-up, 100% of the treatment group showed at least a 20% reduction in their Hamilton Depression Rating Scale (HAM-D) score, compared to 69% in the control arm (P<.001).⁴

A Swedish study analyzed the effects of several B vitamins, including 0.5 mg/d of B₁₂ vs placebo on mood in 65 celiac patients on a gluten-free diet who had borderline/low normal B₁₂ levels (>191 pg/mL).⁵ Patients who scored low on a measure of psychological well-being at the beginning of the study and who received B₁₂ experienced significant improvements in anxiety and depressed mood compared to those who received placebo.

Our patient

Because neurologic and psychiatric symptoms require assured compliance and urgent treatment, our patient received vitamin B₁₂ parenterally as cyanocobalamin 1 mg/mL. She was given this dosage intramuscularly once a day for 5 days, then once a week for 4 weeks. She will continue to receive it once a month indefinitely.

The patient was advised that if she wished to switch to oral therapy, she could do so after several months of parenteral treatment, as long as she had close follow-up with frequent B₁₂ measurements to assure that she was absorbing oral therapy. Her anxiety and mood symptoms resolved within one month, and her disequilibrium was almost entirely resolved within 3 months of treatment.

THE TAKEAWAY

Although more common in older patients, vitamin B₁₂ deficiency can also affect younger patients. “Low normal” B₁₂ levels (200-400 pg/mL) may affect psychological well-being.

Consider testing serum B₁₂ and a second biomarker—such as homocysteine or methylmalonic acid, if indicated—in patients who present with depressed mood, anxiety, cognitive symptoms, and/or fatigue. Vitamin B₁₂ supplementation can be administered orally and has no major adverse effects.

THE CASE

A 21-year-old college student was referred to us by the counseling center at our university for a psychiatric evaluation after 11 psychotherapy sessions over 3 months had failed to reduce her feelings of anxiety and panic.

During our evaluation, the patient described feeling “not quite right” for many months. She had been experiencing mental fogginess, fatigue, and worsening concentration/ memory. Her anxiety, which had been gradually increasing, was the result of being unsure about her gait. She first noticed this while walking down some bleachers; she felt dizzy, was afraid of falling, and couldn’t walk down without assistance. All episodes of “panic” occurred in situations where she experienced disequilibrium, unsteady gait, and fear of falling. She grew fearful of driving or going anywhere without assistance.

The patient had celiac disease that was well controlled with a gluten-free diet. She had no personal or family psychiatric history and no history of substance abuse.

THE DIAGNOSIS

Physical exam and lab studies, including a complete blood count, comprehensive metabolic panel, and thyrotropin and folate levels, were normal. Her homocysteine level was 11.8 μmol/L (reference range, 5.4-11.9 μmol/L) and vitamin B₁₂ level was 292 pg/mL (reference range, 200-1100 pg/mL). Her lab report included a note that read, “Although the reference range for vitamin B₁₂ is 200 to 1100 pg/mL, it has been reported that between 5% and 10% of patients with values between 200 and 400 pg/mL may experience neuropsychiatric and hematologic abnormalities due to occult B₁₂ deficiency; <1% of patients with values >400 pg/mL will have symptoms.”

Based on this vitamin B₁₂ level, the patient’s symptoms, and her borderline high homocysteine level, we diagnosed vitamin B₁₂ deficiency.

DISCUSSION

There are no recommendations by the US Preventive Services Task Force or any other major US medical society for routine vitamin B₁₂ screening.¹ In Canada, the Medical Services Commission of the British Columbia Ministry of Health recommends B₁₂ screening for patients who present with macrocytic anemia or unexplained neurologic symptoms (eg, paresthesia, numbness, poor motor coordination, memory lapses, or cognitive or personality changes).²

Vitamin B₁₂ deficiency can be caused by numerous conditions, including those that cause malabsorption (such as gastric bypass). It can also be caused by diseases such as human immunodeficiency virus infection or Crohn’s disease, long-term adherence to a vegetarian or vegan diet, or by any other lack of dietary intake.¹ The condition can cause hematologic-related signs and symptoms such as megaloblastic anemia, fatigue, and syncope. It also can have neurologic manifestations, including paresthesia, weakness, motor disturbances (including gait abnormalities), vision loss, and a wide range of cognitive and behavioral changes.¹ Anemia is uncommon because since 1998, the US Food and Drug Administration has required fortification of all enriched grain and cereal products with folic acid; thus, vitamin B₁₂ deficiency may proceed without anemia revealing its presence.¹

A controversial topic. Vitamin B₁₂ deficiency is a complicated and controversial subject. Specifically, there is uncertainty about the clinical importance of lower serum levels of vitamin B₁₂ (200-400 pg/mL), their impact on well-being, and the need for treatment. In addition to measuring a patient’s serum B₁₂ level, testing a second biomarker (such as homocysteine or methylmalonic acid) can be helpful in establishing a diagnosis of B₁₂ deficiency.¹ Levels of each of these are elevated in patients with B₁₂ deficiency.¹

Some evidence suggests B₁₂ supplementation may improve symptoms of depression and anxiety.

Although vitamin B₁₂ deficiency has been well studied in older patients,³ little has been published about the condition in young adults. National Health and Nutrition Examination Survey (NHANES) data from 2000 to 2004 shows that almost 40% of people ages 19 to 30 years have a B₁₂ level <400 pg/mL.¹ How many of these individuals are at risk of complications of B₁₂ deficiency is unknown.

B₁₂ supplementation might improve depression, anxiety

B₁₂ supplementation is inexpensive and has no significant adverse effects.¹ It can be administered orally, parenterally (intramuscularly or subcutaneously), or intranasally.¹ A common oral regimen is 1 mg/d; parental regimens vary widely, but might include a 1-mg injection once a week for 8 weeks, then once a month for life.¹

Some evidence suggests B₁₂ supplementation may improve symptoms of depression and anxiety. A Pakistani study randomized 73 patients with depression and “low normal” B₁₂ levels (190-300 pg/mL) to an antidepressant only (equivalent to imipramine 100-250 mg/d or fluoxetine 20-40 mg/d) or an antidepressant plus parenteral B₁₂ (1000 mcg once a week).⁴ At 3 months follow-up, 100% of the treatment group showed at least a 20% reduction in their Hamilton Depression Rating Scale (HAM-D) score, compared to 69% in the control arm (P<.001).⁴

A Swedish study analyzed the effects of several B vitamins, including 0.5 mg/d of B₁₂ vs placebo on mood in 65 celiac patients on a gluten-free diet who had borderline/low normal B₁₂ levels (>191 pg/mL).⁵ Patients who scored low on a measure of psychological well-being at the beginning of the study and who received B₁₂ experienced significant improvements in anxiety and depressed mood compared to those who received placebo.

Our patient

Because neurologic and psychiatric symptoms require assured compliance and urgent treatment, our patient received vitamin B₁₂ parenterally as cyanocobalamin 1 mg/mL. She was given this dosage intramuscularly once a day for 5 days, then once a week for 4 weeks. She will continue to receive it once a month indefinitely.

The patient was advised that if she wished to switch to oral therapy, she could do so after several months of parenteral treatment, as long as she had close follow-up with frequent B₁₂ measurements to assure that she was absorbing oral therapy. Her anxiety and mood symptoms resolved within one month, and her disequilibrium was almost entirely resolved within 3 months of treatment.

THE TAKEAWAY

Although more common in older patients, vitamin B₁₂ deficiency can also affect younger patients. “Low normal” B₁₂ levels (200-400 pg/mL) may affect psychological well-being.

Consider testing serum B₁₂ and a second biomarker—such as homocysteine or methylmalonic acid, if indicated—in patients who present with depressed mood, anxiety, cognitive symptoms, and/or fatigue. Vitamin B₁₂ supplementation can be administered orally and has no major adverse effects.

THE CASE

A 21-year-old college student was referred to us by the counseling center at our university for a psychiatric evaluation after 11 psychotherapy sessions over 3 months had failed to reduce her feelings of anxiety and panic.

During our evaluation, the patient described feeling “not quite right” for many months. She had been experiencing mental fogginess, fatigue, and worsening concentration/ memory. Her anxiety, which had been gradually increasing, was the result of being unsure about her gait. She first noticed this while walking down some bleachers; she felt dizzy, was afraid of falling, and couldn’t walk down without assistance. All episodes of “panic” occurred in situations where she experienced disequilibrium, unsteady gait, and fear of falling. She grew fearful of driving or going anywhere without assistance.

The patient had celiac disease that was well controlled with a gluten-free diet. She had no personal or family psychiatric history and no history of substance abuse.

THE DIAGNOSIS

Physical exam and lab studies, including a complete blood count, comprehensive metabolic panel, and thyrotropin and folate levels, were normal. Her homocysteine level was 11.8 μmol/L (reference range, 5.4-11.9 μmol/L) and vitamin B₁₂ level was 292 pg/mL (reference range, 200-1100 pg/mL). Her lab report included a note that read, “Although the reference range for vitamin B₁₂ is 200 to 1100 pg/mL, it has been reported that between 5% and 10% of patients with values between 200 and 400 pg/mL may experience neuropsychiatric and hematologic abnormalities due to occult B₁₂ deficiency; <1% of patients with values >400 pg/mL will have symptoms.”

Based on this vitamin B₁₂ level, the patient’s symptoms, and her borderline high homocysteine level, we diagnosed vitamin B₁₂ deficiency.

DISCUSSION

There are no recommendations by the US Preventive Services Task Force or any other major US medical society for routine vitamin B₁₂ screening.¹ In Canada, the Medical Services Commission of the British Columbia Ministry of Health recommends B₁₂ screening for patients who present with macrocytic anemia or unexplained neurologic symptoms (eg, paresthesia, numbness, poor motor coordination, memory lapses, or cognitive or personality changes).²

Vitamin B₁₂ deficiency can be caused by numerous conditions, including those that cause malabsorption (such as gastric bypass). It can also be caused by diseases such as human immunodeficiency virus infection or Crohn’s disease, long-term adherence to a vegetarian or vegan diet, or by any other lack of dietary intake.¹ The condition can cause hematologic-related signs and symptoms such as megaloblastic anemia, fatigue, and syncope. It also can have neurologic manifestations, including paresthesia, weakness, motor disturbances (including gait abnormalities), vision loss, and a wide range of cognitive and behavioral changes.¹ Anemia is uncommon because since 1998, the US Food and Drug Administration has required fortification of all enriched grain and cereal products with folic acid; thus, vitamin B₁₂ deficiency may proceed without anemia revealing its presence.¹

A controversial topic. Vitamin B₁₂ deficiency is a complicated and controversial subject. Specifically, there is uncertainty about the clinical importance of lower serum levels of vitamin B₁₂ (200-400 pg/mL), their impact on well-being, and the need for treatment. In addition to measuring a patient’s serum B₁₂ level, testing a second biomarker (such as homocysteine or methylmalonic acid) can be helpful in establishing a diagnosis of B₁₂ deficiency.¹ Levels of each of these are elevated in patients with B₁₂ deficiency.¹

Some evidence suggests B₁₂ supplementation may improve symptoms of depression and anxiety.

Although vitamin B₁₂ deficiency has been well studied in older patients,³ little has been published about the condition in young adults. National Health and Nutrition Examination Survey (NHANES) data from 2000 to 2004 shows that almost 40% of people ages 19 to 30 years have a B₁₂ level <400 pg/mL.¹ How many of these individuals are at risk of complications of B₁₂ deficiency is unknown.

B₁₂ supplementation might improve depression, anxiety

B₁₂ supplementation is inexpensive and has no significant adverse effects.¹ It can be administered orally, parenterally (intramuscularly or subcutaneously), or intranasally.¹ A common oral regimen is 1 mg/d; parental regimens vary widely, but might include a 1-mg injection once a week for 8 weeks, then once a month for life.¹

Some evidence suggests B₁₂ supplementation may improve symptoms of depression and anxiety. A Pakistani study randomized 73 patients with depression and “low normal” B₁₂ levels (190-300 pg/mL) to an antidepressant only (equivalent to imipramine 100-250 mg/d or fluoxetine 20-40 mg/d) or an antidepressant plus parenteral B₁₂ (1000 mcg once a week).⁴ At 3 months follow-up, 100% of the treatment group showed at least a 20% reduction in their Hamilton Depression Rating Scale (HAM-D) score, compared to 69% in the control arm (P<.001).⁴

A Swedish study analyzed the effects of several B vitamins, including 0.5 mg/d of B₁₂ vs placebo on mood in 65 celiac patients on a gluten-free diet who had borderline/low normal B₁₂ levels (>191 pg/mL).⁵ Patients who scored low on a measure of psychological well-being at the beginning of the study and who received B₁₂ experienced significant improvements in anxiety and depressed mood compared to those who received placebo.

Our patient

Because neurologic and psychiatric symptoms require assured compliance and urgent treatment, our patient received vitamin B₁₂ parenterally as cyanocobalamin 1 mg/mL. She was given this dosage intramuscularly once a day for 5 days, then once a week for 4 weeks. She will continue to receive it once a month indefinitely.

The patient was advised that if she wished to switch to oral therapy, she could do so after several months of parenteral treatment, as long as she had close follow-up with frequent B₁₂ measurements to assure that she was absorbing oral therapy. Her anxiety and mood symptoms resolved within one month, and her disequilibrium was almost entirely resolved within 3 months of treatment.

THE TAKEAWAY

Although more common in older patients, vitamin B₁₂ deficiency can also affect younger patients. “Low normal” B₁₂ levels (200-400 pg/mL) may affect psychological well-being.

Consider testing serum B₁₂ and a second biomarker—such as homocysteine or methylmalonic acid, if indicated—in patients who present with depressed mood, anxiety, cognitive symptoms, and/or fatigue. Vitamin B₁₂ supplementation can be administered orally and has no major adverse effects.

THE CASE

One month after moving into her mother’s apartment, a 27-year-old woman sought care at our clinic for fatigue, headache, blurred vision, nausea, and morning vomiting. She had weakness and difficulty sleeping, but denied any fever, rashes, neck stiffness, recent travel, trauma, or tobacco or illicit drug use. She did, however, have a 6-year history of migraines. Her physical exam was normal. She was sent home with a prescription for tramadol 50 mg bid for her headaches.

The patient subsequently went to the emergency department 3 times for the same complaints; none of the treatments she received there (mostly acetaminophen with codeine) relieved her symptoms. Three weeks later she returned to our clinic. She was distressed that the symptoms hadn’t gone away, and noted that her family was now experiencing similar symptoms.

Her temperature was 98.1°F (36.7°C), blood pressure was 131/88 mm Hg, pulse  was 85 beats/min, and respiratory rate was 18 breaths/min. Physical and neurologic exams were normal.

THE DIAGNOSIS

Although most of the patient’s lab test results were within normal ranges, her carboxyhemoglobin (COHb) level was 4.2%. COHb levels of >2% to 3% in nonsmokers or >9% to 10% in smokers suggest carbon monoxide (CO) poisoning.^1,2 Based on this finding and our patient’s symptoms, we diagnosed unintentional CO poisoning. We recommended that she and her mother vacate the apartment and have it inspected.

DISCUSSION

CO is the leading cause of poisoning mortality in the United States, and causes half of all fatal poisonings worldwide.^1,3,4 It is a colorless, odorless, and tasteless gas that is produced by the incomplete combustion of carbon-based products, such as coal or gas.^5,6 Exposure can occur from car exhaust fumes, faulty room heaters, and other sources (TABLE 1).⁶ The incidence of CO poisoning is higher during the winter months and after natural disasters. Individuals who have a lowered oxygen capacity, such as older adults, pregnant women (and their fetuses), infants, and patients with anemia, cardiovascular disease, or cerebrovascular disease, are more susceptible to CO poisoning.^5,6

COHb, a stable complex of CO that forms in red blood cells when CO is inhaled, impairs oxygen delivery and peripheral utilization, resulting in cellular hypoxia.¹ Signs and symptoms of CO poisoning are nonspecific and require a high degree of clinical suspicion for early diagnosis and treatment. Although cherry-red lips, peripheral cyanosis, and retinal hemorrhages are often described as “classic” symptoms of CO poisoning, these are rarely seen.⁶ The most common symptoms are actually headache (90%), dizziness (82%), and weakness (53%).⁷ Other symptoms include nausea, vomiting, confusion, visual disturbances, loss of consciousness, angina, seizure, and fatigue.^6,7 Symptoms of chronic CO poisoning may differ from those of acute poisoning and can include chronic fatigue, neuropathy, and memory deficit.⁸

The differential diagnosis for CO poisoning includes flu-like syndrome/influenza/other viral illnesses, migraine or tension headaches, depression, transient ischemic attack, encephalitis, coronary artery disease, gastroenteritis or food poisoning, seizures, and dysrhythmias.^1,4 Lab testing for COHb can help narrow the diagnosis. CO poisoning can be classified as mild, moderate, or severe based on COHb levels and the patient’s signs and symptoms (TABLE 2).⁶ However, COHb level is a poor predictor of clinical presentation and should not be used to dictate management.^2,7

Oxygen therapy is the recommended treatment

Early treatment with supplemental oxygen is recommended to reduce the length of time red blood cells are exposed to CO.¹ A COHb level >25% is the criterion for hyperbaric oxygen therapy.^1,3 Patients should receive treatment until their symptoms become less intense.

The 3 most common symptoms of CO poisoning are headache, dizziness, and weakness.

Delayed neuropsychiatric sequelae (DNS) can occur in up to one-third of patients with acute CO poisoning more than a month after apparent recovery.^1,6,9 DNS symptoms include cognitive changes, emotional lability, visual disturbances, disorientation, depression, dementia, psychotic behavior, parkinsonism, amnesia, and incontinence.^1,6,9 Approximately 50% to 75% of patients with DNS recover spontaneously within a year with symptomatic treatment.^1,6,9

Our patient

After recommending that our patient (and her mother) leave the apartment and have it inspected, we later learned that the fire department was unable to determine the source of the CO. A CO detector was installed and our patient was advised to keep the windows in the apartment open to allow for adequate oxygen flow. One month later she returned to our clinic and reported that her symptoms resolved; serum COHb was negative upon repeat lab tests.

THE TAKEAWAY

Patients who present with headaches, dizziness and/or fatigue should be evaluated for CO poisoning. The patient’s environmental history should be reviewed carefully, especially because CO poisoning is more common during the winter months. Oxygen therapy is the mainstay of treatment. Up to one-third of patients with acute poisoning may develop delayed neuropsychiatric sequelae, including cognitive changes, emotional lability, visual disturbances, disorientation, and depression, that may resolve within one year.

THE CASE

One month after moving into her mother’s apartment, a 27-year-old woman sought care at our clinic for fatigue, headache, blurred vision, nausea, and morning vomiting. She had weakness and difficulty sleeping, but denied any fever, rashes, neck stiffness, recent travel, trauma, or tobacco or illicit drug use. She did, however, have a 6-year history of migraines. Her physical exam was normal. She was sent home with a prescription for tramadol 50 mg bid for her headaches.

The patient subsequently went to the emergency department 3 times for the same complaints; none of the treatments she received there (mostly acetaminophen with codeine) relieved her symptoms. Three weeks later she returned to our clinic. She was distressed that the symptoms hadn’t gone away, and noted that her family was now experiencing similar symptoms.

Her temperature was 98.1°F (36.7°C), blood pressure was 131/88 mm Hg, pulse  was 85 beats/min, and respiratory rate was 18 breaths/min. Physical and neurologic exams were normal.

THE DIAGNOSIS

Although most of the patient’s lab test results were within normal ranges, her carboxyhemoglobin (COHb) level was 4.2%. COHb levels of >2% to 3% in nonsmokers or >9% to 10% in smokers suggest carbon monoxide (CO) poisoning.^1,2 Based on this finding and our patient’s symptoms, we diagnosed unintentional CO poisoning. We recommended that she and her mother vacate the apartment and have it inspected.

DISCUSSION

CO is the leading cause of poisoning mortality in the United States, and causes half of all fatal poisonings worldwide.^1,3,4 It is a colorless, odorless, and tasteless gas that is produced by the incomplete combustion of carbon-based products, such as coal or gas.^5,6 Exposure can occur from car exhaust fumes, faulty room heaters, and other sources (TABLE 1).⁶ The incidence of CO poisoning is higher during the winter months and after natural disasters. Individuals who have a lowered oxygen capacity, such as older adults, pregnant women (and their fetuses), infants, and patients with anemia, cardiovascular disease, or cerebrovascular disease, are more susceptible to CO poisoning.^5,6

COHb, a stable complex of CO that forms in red blood cells when CO is inhaled, impairs oxygen delivery and peripheral utilization, resulting in cellular hypoxia.¹ Signs and symptoms of CO poisoning are nonspecific and require a high degree of clinical suspicion for early diagnosis and treatment. Although cherry-red lips, peripheral cyanosis, and retinal hemorrhages are often described as “classic” symptoms of CO poisoning, these are rarely seen.⁶ The most common symptoms are actually headache (90%), dizziness (82%), and weakness (53%).⁷ Other symptoms include nausea, vomiting, confusion, visual disturbances, loss of consciousness, angina, seizure, and fatigue.^6,7 Symptoms of chronic CO poisoning may differ from those of acute poisoning and can include chronic fatigue, neuropathy, and memory deficit.⁸

The differential diagnosis for CO poisoning includes flu-like syndrome/influenza/other viral illnesses, migraine or tension headaches, depression, transient ischemic attack, encephalitis, coronary artery disease, gastroenteritis or food poisoning, seizures, and dysrhythmias.^1,4 Lab testing for COHb can help narrow the diagnosis. CO poisoning can be classified as mild, moderate, or severe based on COHb levels and the patient’s signs and symptoms (TABLE 2).⁶ However, COHb level is a poor predictor of clinical presentation and should not be used to dictate management.^2,7

Oxygen therapy is the recommended treatment

Early treatment with supplemental oxygen is recommended to reduce the length of time red blood cells are exposed to CO.¹ A COHb level >25% is the criterion for hyperbaric oxygen therapy.^1,3 Patients should receive treatment until their symptoms become less intense.

The 3 most common symptoms of CO poisoning are headache, dizziness, and weakness.

Delayed neuropsychiatric sequelae (DNS) can occur in up to one-third of patients with acute CO poisoning more than a month after apparent recovery.^1,6,9 DNS symptoms include cognitive changes, emotional lability, visual disturbances, disorientation, depression, dementia, psychotic behavior, parkinsonism, amnesia, and incontinence.^1,6,9 Approximately 50% to 75% of patients with DNS recover spontaneously within a year with symptomatic treatment.^1,6,9

Our patient

After recommending that our patient (and her mother) leave the apartment and have it inspected, we later learned that the fire department was unable to determine the source of the CO. A CO detector was installed and our patient was advised to keep the windows in the apartment open to allow for adequate oxygen flow. One month later she returned to our clinic and reported that her symptoms resolved; serum COHb was negative upon repeat lab tests.

THE TAKEAWAY

Patients who present with headaches, dizziness and/or fatigue should be evaluated for CO poisoning. The patient’s environmental history should be reviewed carefully, especially because CO poisoning is more common during the winter months. Oxygen therapy is the mainstay of treatment. Up to one-third of patients with acute poisoning may develop delayed neuropsychiatric sequelae, including cognitive changes, emotional lability, visual disturbances, disorientation, and depression, that may resolve within one year.

THE CASE

One month after moving into her mother’s apartment, a 27-year-old woman sought care at our clinic for fatigue, headache, blurred vision, nausea, and morning vomiting. She had weakness and difficulty sleeping, but denied any fever, rashes, neck stiffness, recent travel, trauma, or tobacco or illicit drug use. She did, however, have a 6-year history of migraines. Her physical exam was normal. She was sent home with a prescription for tramadol 50 mg bid for her headaches.

The patient subsequently went to the emergency department 3 times for the same complaints; none of the treatments she received there (mostly acetaminophen with codeine) relieved her symptoms. Three weeks later she returned to our clinic. She was distressed that the symptoms hadn’t gone away, and noted that her family was now experiencing similar symptoms.

Her temperature was 98.1°F (36.7°C), blood pressure was 131/88 mm Hg, pulse  was 85 beats/min, and respiratory rate was 18 breaths/min. Physical and neurologic exams were normal.

THE DIAGNOSIS

Although most of the patient’s lab test results were within normal ranges, her carboxyhemoglobin (COHb) level was 4.2%. COHb levels of >2% to 3% in nonsmokers or >9% to 10% in smokers suggest carbon monoxide (CO) poisoning.^1,2 Based on this finding and our patient’s symptoms, we diagnosed unintentional CO poisoning. We recommended that she and her mother vacate the apartment and have it inspected.

DISCUSSION

CO is the leading cause of poisoning mortality in the United States, and causes half of all fatal poisonings worldwide.^1,3,4 It is a colorless, odorless, and tasteless gas that is produced by the incomplete combustion of carbon-based products, such as coal or gas.^5,6 Exposure can occur from car exhaust fumes, faulty room heaters, and other sources (TABLE 1).⁶ The incidence of CO poisoning is higher during the winter months and after natural disasters. Individuals who have a lowered oxygen capacity, such as older adults, pregnant women (and their fetuses), infants, and patients with anemia, cardiovascular disease, or cerebrovascular disease, are more susceptible to CO poisoning.^5,6

COHb, a stable complex of CO that forms in red blood cells when CO is inhaled, impairs oxygen delivery and peripheral utilization, resulting in cellular hypoxia.¹ Signs and symptoms of CO poisoning are nonspecific and require a high degree of clinical suspicion for early diagnosis and treatment. Although cherry-red lips, peripheral cyanosis, and retinal hemorrhages are often described as “classic” symptoms of CO poisoning, these are rarely seen.⁶ The most common symptoms are actually headache (90%), dizziness (82%), and weakness (53%).⁷ Other symptoms include nausea, vomiting, confusion, visual disturbances, loss of consciousness, angina, seizure, and fatigue.^6,7 Symptoms of chronic CO poisoning may differ from those of acute poisoning and can include chronic fatigue, neuropathy, and memory deficit.⁸

The differential diagnosis for CO poisoning includes flu-like syndrome/influenza/other viral illnesses, migraine or tension headaches, depression, transient ischemic attack, encephalitis, coronary artery disease, gastroenteritis or food poisoning, seizures, and dysrhythmias.^1,4 Lab testing for COHb can help narrow the diagnosis. CO poisoning can be classified as mild, moderate, or severe based on COHb levels and the patient’s signs and symptoms (TABLE 2).⁶ However, COHb level is a poor predictor of clinical presentation and should not be used to dictate management.^2,7

Oxygen therapy is the recommended treatment

Early treatment with supplemental oxygen is recommended to reduce the length of time red blood cells are exposed to CO.¹ A COHb level >25% is the criterion for hyperbaric oxygen therapy.^1,3 Patients should receive treatment until their symptoms become less intense.

The 3 most common symptoms of CO poisoning are headache, dizziness, and weakness.

Delayed neuropsychiatric sequelae (DNS) can occur in up to one-third of patients with acute CO poisoning more than a month after apparent recovery.^1,6,9 DNS symptoms include cognitive changes, emotional lability, visual disturbances, disorientation, depression, dementia, psychotic behavior, parkinsonism, amnesia, and incontinence.^1,6,9 Approximately 50% to 75% of patients with DNS recover spontaneously within a year with symptomatic treatment.^1,6,9

Our patient

After recommending that our patient (and her mother) leave the apartment and have it inspected, we later learned that the fire department was unable to determine the source of the CO. A CO detector was installed and our patient was advised to keep the windows in the apartment open to allow for adequate oxygen flow. One month later she returned to our clinic and reported that her symptoms resolved; serum COHb was negative upon repeat lab tests.

THE TAKEAWAY

Patients who present with headaches, dizziness and/or fatigue should be evaluated for CO poisoning. The patient’s environmental history should be reviewed carefully, especially because CO poisoning is more common during the winter months. Oxygen therapy is the mainstay of treatment. Up to one-third of patients with acute poisoning may develop delayed neuropsychiatric sequelae, including cognitive changes, emotional lability, visual disturbances, disorientation, and depression, that may resolve within one year.

Intraneural ganglion cysts of peripheral nerves occurring within the epineural sheath are rare.^1-7 Case reports exist primarily within the neurosurgical literature, but very little in the orthopedic literature describes this condition. The peripheral nerve most commonly affected by an intraneural ganglion is the common peroneal nerve (CPN).^2,8,9 Such ganglia most often afflict middle-aged men with a history of micro- or macro-trauma and present with typical clinical manifestations of calf pain and progressive symptoms of ipsilateral foot drop and lower leg paresthesia.^2-5,10-12 The mechanism by which these ganglia form is not well understood and, as a result, treatment options are debated.⁶ Recent development of a “unified articular theory,” suggests that such intraneural ganglia of the CPN are fed by a small, recurrent articular branch of the CPN.^6,12,13 Cadaveric studies indicate that this branch originates from the deep peroneal nerve, just millimeters distal to the bifurcation of the CPN, and extends to the superior tibiofibular joint, providing direct access for cyst fluid to enter the CPN following the path of least resistance.^7,8,12,14 Therefore, according to the unified articular theory, the recommended treatment involves division of the articular branch, allowing the ganglion to be decompressed.⁶

We present a case of a 41-year-old man with an intraneural ganglion cyst of the CPN who was successfully treated, according to the recommendations of the unified articular theory. It is important for orthopedic surgeons to read about and recognize this condition, because knowledge of the operative technique outlined in our report allows it to be treated quite effectively. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 41-year-old man presented with a 2-month history of traumatic left lateral knee pain with numbness and weakness to the left foot and ankle. Initial examination showed a mild restriction of lumbosacral range of motion, with no complaints of lower back pain. Sciatic root stretch signs were negative. Strength testing of the lower extremities revealed 3+/5 strength of ankle dorsiflexion and great toe extension on the left side. There was a mild alteration in sensation to light touch on the lateral side of the left foot. Tenderness, without swelling, was present around the left fibular head. There was a positive Tinel sign over the peroneal nerve at the level of the fibular neck.

The patient was initially treated with anti-inflammatories and activity modification. An electromyogram (EMG)/nerve conduction study of the lower extremity showed a left peroneal nerve neurapraxia at the level of the fibular head. Noncontrast magnetic resonance imaging (MRI) of the left knee showed a “slightly prominent vein coursing posterior to the fibular head near the expected location of the common peroneal nerve,” according to the radiologist’s notes (Figure 1). The patient exhibited improvement with use of anti-inflammatories over several months. There was an increase in his ankle dorsiflexion strength to 4/5 and improvement in his pain and numbness.

Approximately 7 months after his initial presentation, the patient developed a marked worsening—increased numbness and weakness to ankle dorsiflexion—of his original symptoms. A repeat EMG/nerve conduction study of the lower extremity showed a persistent peroneal nerve neuropathy with a persistent denervation of the extensor hallucis longus, tibialis anterior, and extensor digitorum brevis muscles.

Because of continuing symptoms and increasing pain, the patient had surgery 8 months after his initial presentation. At that time, a markedly thickened peroneal nerve was identified. An incision in the epineural sheath released a clear gelatinous fluid consistent with a ganglion cyst. Through the epineural incision, the nerve was decompressed by manually “milking” the fluid from within the sheath. Approximately  30 mL of mucinous fluid was obtained and sent to pathology. No cells were identified.

Postoperatively, the patient noted a marked improvement in his pain. By 2 weeks postoperatively, the numbness in his foot had resolved. At 6 weeks after surgery, the strength of his tibialis anterior and extensor hallucis longus muscles had improved from 3+ to 4-, and he was free of pain.

At 2 months postoperatively, the patient redeveloped pain and numbness, and noted progressive weakness of his left foot and ankle. A repeat MRI of the left knee showed a dilated tubular structure corresponding to the course of the CPN. Comparison of this MRI with the initial MRI showed that the “prominent vein” was actually the dilated CPN.

He was taken to the operating room again 5 months after his first operation. At this time, the CPN was again noted to be markedly dilated (Figure 2). The nerve was explored and a recurrent branch to the proximal tibiofibular joint was identified and divided (Figures 3, 4). Through the divided branch, the CPN could be decompressed by manually “milking” the nerve in a proximal-to-distal direction, expressing clear gelatinous fluid consistent with a ganglion cyst (Figure 5). Pathology of the excised portion of the recurrent nerve was consistent with an intraneural ganglion cyst.

By 2 weeks postoperatively, the numbness of the patient’s left foot had completely resolved, as did his pain. By 3 months after surgery, his extensor hallucis longus strength was 5/5, and ankle dorsiflexion was 4-/5. At 6 months, his ankle dorsiflexion strength was 5/5, and he was completely asymptomatic. At 2 years postoperatively, he remained completely asymptomatic. A follow-up MRI of the left knee showed a ganglion cyst present at the proximal tibiofibular joint with resolution of the intraneural ganglion cyst within the CPN (Figure 6).

Discussion

Intraneural ganglia of peripheral nerves are relatively rare, most commonly occurring in the CPN.^6,8,9 A literature search reveals that this condition is only sparsely reported in orthopedic journals. This report, therefore, describes this rare, yet curable, condition. As noted, without appropriate intervention, the condition has a high likelihood of recurrence with only a brief interruption of symptoms.^6,8,9,12

The operative technique delineated in this report relies heavily on research demonstrating that peroneal intraneural ganglia develop from the superior tibiofibular joint and gain access to the CPN via the recurrent articular branch.^8,13 Research indicates that such ganglia preferentially proceed proximally along the deep portion of the CPN, within the epineurium.⁶ This hypothesis was corroborated in our case by the swollen appearance of the CPN proximal to its bifurcation.

Currently, there is no consensus on treatment of intraneural ganglion cysts of the CPN. However, evidence suggests that disconnection of the recurrent branch of the CPN may be important in successfully treating the condition.^6,9,14 This unified articular theory was initially proposed by Spinner and colleagues¹² in 2003 and recommends that surgical treatment focus on the articular branch as the source of cyst fluid.^6,9,12,14 This theory by Spinner and coauthors^12,14 was substantiated in our case: Once the articular branch was disconnected, cyst fluid was easily expressed via antegrade massage through the disconnected end. Pathologic analysis of a portion of the detached articular branch is also recommended to rule out other cystic lesions, such as cystic shwannomas.¹⁴

The history of the unified articular theory began in the mid-1990s, when Dr. Robert Spinner, board certified in both orthopedic and neurologic surgery, began researching causes of intraneural ganglion cysts. At the time, such ganglia were often treated by radical resection of the nerve and the cyst. Based on his review of literature, and his own cases, Spinner¹⁵ developed the theory that, just as with extraneural ganglia, these cysts are fed by fluid from the joint. According to Spinner,⁹ the sources of such connections were very small articular nerve branches that connect the nerve to the joint. His research led him to the original citation of such an intraneural ganglion of the ulnar nerve, first described by Dr. M. Beauchene, a French physician, in 1810.¹⁶ Spinner also discovered that Beauchene’s original dissection specimen had been preserved and was displayed in a medical museum in Paris. When Spinner went to France to view the specimen, he indeed found an intraneural ganglion of the ulnar nerve. On closer inspection, Spinner also discovered a small articular nerve branch containing a “hollow lumen” that would have been capable of allowing the passage of fluid into the nerve and leading to the development of a cyst.¹⁶

In our case, in the first operation, a simple incisional decompression of the CPN was performed. Unfortunately, the ganglion cyst quickly recurred, as did the patient’s symptoms. In the second surgical procedure, the articular branch connecting the peroneal nerve to the proximal tibiofibular joint was incised and disconnected from the nerve. This allowed the nerve to be decompressed and prevented a recurrence of the ganglion cyst within the nerve with complete resolution of the patient’s symptoms. This difference alone most likely accounts for the rapid recurrence of symptoms after the initial operation, since the fluid was simply drained, but the source was not detached, allowing the ganglion to recur.^6,12,14 This is similar in theory to excising the attachment of a ganglion cyst at the wrist from the underlying joint capsule rather than performing a needle aspiration or puncturing of the cyst.¹²

Regarding the imaging techniques used to identify intraneural ganglia, it is essential that the surgeon be aware of the unified articular theory and the likely presence of an articular branch. Such branches are extremely small and may be easily missed on imaging and intraoperatively.^17,18 MRI is the best method to image these cysts because of its superior ability to visualize soft-tissue lesions.^18,19 Intraneural ganglion cysts typically appear as homogenous, lobulated, well-circumscribed masses that are hyperintense on T2-weighted MRI.^3,19 Gadolinium may also offer diagnostic utility, because these masses do not enhance with its use on T1-weighted MRI.^3,17,19 By employing these techniques, one may easily view most of the ganglion cyst. To image the small articular branch, Spinner and colleagues¹⁷ recommend thin-section images with high–spatial resolution T2-imaging. They also advocate obtaining multiple image views and planes to increase the likelihood of successful imaging.¹⁷ 

The applications of the unified articular theory also extend beyond intraneural ganglia of the CPN. While the CPN is the most common location for intraneural ganglion occurrence,^6,17,20 cases have also been described of intraneural ganglion cysts of the tibial nerve at the proximal tibiofibular joint, as well as via the posterior tibial and medial plantar nerves at the subtalar joint within the tarsal tunnel.^11,18-23 Most cases involving the posterior tibial and medial plantar nerves were found in patients presenting with signs of tarsal tunnel syndrome.^22,23 Intraneural ganglia have also been found within the superficial peroneal nerve arising from the inferior tibiofibular joint.²⁰ In certain cases, these ganglia have also been noted to connect to the joint via a small articular branch.^19,22 In 1 case of an intraneural ganglion of the tibial nerve at the superior tibiofibular joint, initial conservative surgery led to early recurrence of symptoms.¹⁹ Just as in our case, the patient returned to the operating room and, after isolation and ligation of an articular branch, the patient experienced long-term resolution of both the symptoms and the cyst.¹⁹

Given the overwhelming evidence in support of the unified articular theory, we agree with the recommendation by Spinner and colleagues¹⁹ to search for an articular branch both via preoperative imaging and during the operation itself in all cases of intraneural ganglia. Assuming the mechanism of cyst formation is the same in most cases of intraneural ganglia, one could reasonably apply the same surgical techniques used in our case to the management of all intraneural ganglia, drastically reducing recurrence rates.

Conclusion

Based on research and corroborated by this case, the key to successful operative treatment of a common peroneal intraneural ganglion is division of the recurrent articular branch, which connects the proximal tibiofibular joint to the CPN.^6,9,11,12,14 Evidence has shown that disconnecting the articular branch and disrupting the source of the intraneural ganglion can resolve the condition and dramatically diminish the chance of recurrence.^6,8,12,14 This has become known as the unified articular theory.^6,12,14 Reports also suggest that, without disconnecting this articular branch, intraneural ganglion recurrence rates may be higher than 30%.^6,12,14,19 This case, therefore, supports the findings of previous authors^9-11,14 and provides an example of successful utilization of the treatment protocol delineated by Spinner and colleagues.^10,11

Intraneural ganglion cysts of peripheral nerves occurring within the epineural sheath are rare.^1-7 Case reports exist primarily within the neurosurgical literature, but very little in the orthopedic literature describes this condition. The peripheral nerve most commonly affected by an intraneural ganglion is the common peroneal nerve (CPN).^2,8,9 Such ganglia most often afflict middle-aged men with a history of micro- or macro-trauma and present with typical clinical manifestations of calf pain and progressive symptoms of ipsilateral foot drop and lower leg paresthesia.^2-5,10-12 The mechanism by which these ganglia form is not well understood and, as a result, treatment options are debated.⁶ Recent development of a “unified articular theory,” suggests that such intraneural ganglia of the CPN are fed by a small, recurrent articular branch of the CPN.^6,12,13 Cadaveric studies indicate that this branch originates from the deep peroneal nerve, just millimeters distal to the bifurcation of the CPN, and extends to the superior tibiofibular joint, providing direct access for cyst fluid to enter the CPN following the path of least resistance.^7,8,12,14 Therefore, according to the unified articular theory, the recommended treatment involves division of the articular branch, allowing the ganglion to be decompressed.⁶

We present a case of a 41-year-old man with an intraneural ganglion cyst of the CPN who was successfully treated, according to the recommendations of the unified articular theory. It is important for orthopedic surgeons to read about and recognize this condition, because knowledge of the operative technique outlined in our report allows it to be treated quite effectively. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 41-year-old man presented with a 2-month history of traumatic left lateral knee pain with numbness and weakness to the left foot and ankle. Initial examination showed a mild restriction of lumbosacral range of motion, with no complaints of lower back pain. Sciatic root stretch signs were negative. Strength testing of the lower extremities revealed 3+/5 strength of ankle dorsiflexion and great toe extension on the left side. There was a mild alteration in sensation to light touch on the lateral side of the left foot. Tenderness, without swelling, was present around the left fibular head. There was a positive Tinel sign over the peroneal nerve at the level of the fibular neck.

The patient was initially treated with anti-inflammatories and activity modification. An electromyogram (EMG)/nerve conduction study of the lower extremity showed a left peroneal nerve neurapraxia at the level of the fibular head. Noncontrast magnetic resonance imaging (MRI) of the left knee showed a “slightly prominent vein coursing posterior to the fibular head near the expected location of the common peroneal nerve,” according to the radiologist’s notes (Figure 1). The patient exhibited improvement with use of anti-inflammatories over several months. There was an increase in his ankle dorsiflexion strength to 4/5 and improvement in his pain and numbness.

Approximately 7 months after his initial presentation, the patient developed a marked worsening—increased numbness and weakness to ankle dorsiflexion—of his original symptoms. A repeat EMG/nerve conduction study of the lower extremity showed a persistent peroneal nerve neuropathy with a persistent denervation of the extensor hallucis longus, tibialis anterior, and extensor digitorum brevis muscles.

Because of continuing symptoms and increasing pain, the patient had surgery 8 months after his initial presentation. At that time, a markedly thickened peroneal nerve was identified. An incision in the epineural sheath released a clear gelatinous fluid consistent with a ganglion cyst. Through the epineural incision, the nerve was decompressed by manually “milking” the fluid from within the sheath. Approximately  30 mL of mucinous fluid was obtained and sent to pathology. No cells were identified.

Postoperatively, the patient noted a marked improvement in his pain. By 2 weeks postoperatively, the numbness in his foot had resolved. At 6 weeks after surgery, the strength of his tibialis anterior and extensor hallucis longus muscles had improved from 3+ to 4-, and he was free of pain.

At 2 months postoperatively, the patient redeveloped pain and numbness, and noted progressive weakness of his left foot and ankle. A repeat MRI of the left knee showed a dilated tubular structure corresponding to the course of the CPN. Comparison of this MRI with the initial MRI showed that the “prominent vein” was actually the dilated CPN.

He was taken to the operating room again 5 months after his first operation. At this time, the CPN was again noted to be markedly dilated (Figure 2). The nerve was explored and a recurrent branch to the proximal tibiofibular joint was identified and divided (Figures 3, 4). Through the divided branch, the CPN could be decompressed by manually “milking” the nerve in a proximal-to-distal direction, expressing clear gelatinous fluid consistent with a ganglion cyst (Figure 5). Pathology of the excised portion of the recurrent nerve was consistent with an intraneural ganglion cyst.

By 2 weeks postoperatively, the numbness of the patient’s left foot had completely resolved, as did his pain. By 3 months after surgery, his extensor hallucis longus strength was 5/5, and ankle dorsiflexion was 4-/5. At 6 months, his ankle dorsiflexion strength was 5/5, and he was completely asymptomatic. At 2 years postoperatively, he remained completely asymptomatic. A follow-up MRI of the left knee showed a ganglion cyst present at the proximal tibiofibular joint with resolution of the intraneural ganglion cyst within the CPN (Figure 6).

Discussion

Intraneural ganglia of peripheral nerves are relatively rare, most commonly occurring in the CPN.^6,8,9 A literature search reveals that this condition is only sparsely reported in orthopedic journals. This report, therefore, describes this rare, yet curable, condition. As noted, without appropriate intervention, the condition has a high likelihood of recurrence with only a brief interruption of symptoms.^6,8,9,12

The operative technique delineated in this report relies heavily on research demonstrating that peroneal intraneural ganglia develop from the superior tibiofibular joint and gain access to the CPN via the recurrent articular branch.^8,13 Research indicates that such ganglia preferentially proceed proximally along the deep portion of the CPN, within the epineurium.⁶ This hypothesis was corroborated in our case by the swollen appearance of the CPN proximal to its bifurcation.

Currently, there is no consensus on treatment of intraneural ganglion cysts of the CPN. However, evidence suggests that disconnection of the recurrent branch of the CPN may be important in successfully treating the condition.^6,9,14 This unified articular theory was initially proposed by Spinner and colleagues¹² in 2003 and recommends that surgical treatment focus on the articular branch as the source of cyst fluid.^6,9,12,14 This theory by Spinner and coauthors^12,14 was substantiated in our case: Once the articular branch was disconnected, cyst fluid was easily expressed via antegrade massage through the disconnected end. Pathologic analysis of a portion of the detached articular branch is also recommended to rule out other cystic lesions, such as cystic shwannomas.¹⁴

The history of the unified articular theory began in the mid-1990s, when Dr. Robert Spinner, board certified in both orthopedic and neurologic surgery, began researching causes of intraneural ganglion cysts. At the time, such ganglia were often treated by radical resection of the nerve and the cyst. Based on his review of literature, and his own cases, Spinner¹⁵ developed the theory that, just as with extraneural ganglia, these cysts are fed by fluid from the joint. According to Spinner,⁹ the sources of such connections were very small articular nerve branches that connect the nerve to the joint. His research led him to the original citation of such an intraneural ganglion of the ulnar nerve, first described by Dr. M. Beauchene, a French physician, in 1810.¹⁶ Spinner also discovered that Beauchene’s original dissection specimen had been preserved and was displayed in a medical museum in Paris. When Spinner went to France to view the specimen, he indeed found an intraneural ganglion of the ulnar nerve. On closer inspection, Spinner also discovered a small articular nerve branch containing a “hollow lumen” that would have been capable of allowing the passage of fluid into the nerve and leading to the development of a cyst.¹⁶

In our case, in the first operation, a simple incisional decompression of the CPN was performed. Unfortunately, the ganglion cyst quickly recurred, as did the patient’s symptoms. In the second surgical procedure, the articular branch connecting the peroneal nerve to the proximal tibiofibular joint was incised and disconnected from the nerve. This allowed the nerve to be decompressed and prevented a recurrence of the ganglion cyst within the nerve with complete resolution of the patient’s symptoms. This difference alone most likely accounts for the rapid recurrence of symptoms after the initial operation, since the fluid was simply drained, but the source was not detached, allowing the ganglion to recur.^6,12,14 This is similar in theory to excising the attachment of a ganglion cyst at the wrist from the underlying joint capsule rather than performing a needle aspiration or puncturing of the cyst.¹²

Regarding the imaging techniques used to identify intraneural ganglia, it is essential that the surgeon be aware of the unified articular theory and the likely presence of an articular branch. Such branches are extremely small and may be easily missed on imaging and intraoperatively.^17,18 MRI is the best method to image these cysts because of its superior ability to visualize soft-tissue lesions.^18,19 Intraneural ganglion cysts typically appear as homogenous, lobulated, well-circumscribed masses that are hyperintense on T2-weighted MRI.^3,19 Gadolinium may also offer diagnostic utility, because these masses do not enhance with its use on T1-weighted MRI.^3,17,19 By employing these techniques, one may easily view most of the ganglion cyst. To image the small articular branch, Spinner and colleagues¹⁷ recommend thin-section images with high–spatial resolution T2-imaging. They also advocate obtaining multiple image views and planes to increase the likelihood of successful imaging.¹⁷ 

The applications of the unified articular theory also extend beyond intraneural ganglia of the CPN. While the CPN is the most common location for intraneural ganglion occurrence,^6,17,20 cases have also been described of intraneural ganglion cysts of the tibial nerve at the proximal tibiofibular joint, as well as via the posterior tibial and medial plantar nerves at the subtalar joint within the tarsal tunnel.^11,18-23 Most cases involving the posterior tibial and medial plantar nerves were found in patients presenting with signs of tarsal tunnel syndrome.^22,23 Intraneural ganglia have also been found within the superficial peroneal nerve arising from the inferior tibiofibular joint.²⁰ In certain cases, these ganglia have also been noted to connect to the joint via a small articular branch.^19,22 In 1 case of an intraneural ganglion of the tibial nerve at the superior tibiofibular joint, initial conservative surgery led to early recurrence of symptoms.¹⁹ Just as in our case, the patient returned to the operating room and, after isolation and ligation of an articular branch, the patient experienced long-term resolution of both the symptoms and the cyst.¹⁹

Given the overwhelming evidence in support of the unified articular theory, we agree with the recommendation by Spinner and colleagues¹⁹ to search for an articular branch both via preoperative imaging and during the operation itself in all cases of intraneural ganglia. Assuming the mechanism of cyst formation is the same in most cases of intraneural ganglia, one could reasonably apply the same surgical techniques used in our case to the management of all intraneural ganglia, drastically reducing recurrence rates.

Conclusion

Based on research and corroborated by this case, the key to successful operative treatment of a common peroneal intraneural ganglion is division of the recurrent articular branch, which connects the proximal tibiofibular joint to the CPN.^6,9,11,12,14 Evidence has shown that disconnecting the articular branch and disrupting the source of the intraneural ganglion can resolve the condition and dramatically diminish the chance of recurrence.^6,8,12,14 This has become known as the unified articular theory.^6,12,14 Reports also suggest that, without disconnecting this articular branch, intraneural ganglion recurrence rates may be higher than 30%.^6,12,14,19 This case, therefore, supports the findings of previous authors^9-11,14 and provides an example of successful utilization of the treatment protocol delineated by Spinner and colleagues.^10,11

Intraneural ganglion cysts of peripheral nerves occurring within the epineural sheath are rare.^1-7 Case reports exist primarily within the neurosurgical literature, but very little in the orthopedic literature describes this condition. The peripheral nerve most commonly affected by an intraneural ganglion is the common peroneal nerve (CPN).^2,8,9 Such ganglia most often afflict middle-aged men with a history of micro- or macro-trauma and present with typical clinical manifestations of calf pain and progressive symptoms of ipsilateral foot drop and lower leg paresthesia.^2-5,10-12 The mechanism by which these ganglia form is not well understood and, as a result, treatment options are debated.⁶ Recent development of a “unified articular theory,” suggests that such intraneural ganglia of the CPN are fed by a small, recurrent articular branch of the CPN.^6,12,13 Cadaveric studies indicate that this branch originates from the deep peroneal nerve, just millimeters distal to the bifurcation of the CPN, and extends to the superior tibiofibular joint, providing direct access for cyst fluid to enter the CPN following the path of least resistance.^7,8,12,14 Therefore, according to the unified articular theory, the recommended treatment involves division of the articular branch, allowing the ganglion to be decompressed.⁶

We present a case of a 41-year-old man with an intraneural ganglion cyst of the CPN who was successfully treated, according to the recommendations of the unified articular theory. It is important for orthopedic surgeons to read about and recognize this condition, because knowledge of the operative technique outlined in our report allows it to be treated quite effectively. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 41-year-old man presented with a 2-month history of traumatic left lateral knee pain with numbness and weakness to the left foot and ankle. Initial examination showed a mild restriction of lumbosacral range of motion, with no complaints of lower back pain. Sciatic root stretch signs were negative. Strength testing of the lower extremities revealed 3+/5 strength of ankle dorsiflexion and great toe extension on the left side. There was a mild alteration in sensation to light touch on the lateral side of the left foot. Tenderness, without swelling, was present around the left fibular head. There was a positive Tinel sign over the peroneal nerve at the level of the fibular neck.

The patient was initially treated with anti-inflammatories and activity modification. An electromyogram (EMG)/nerve conduction study of the lower extremity showed a left peroneal nerve neurapraxia at the level of the fibular head. Noncontrast magnetic resonance imaging (MRI) of the left knee showed a “slightly prominent vein coursing posterior to the fibular head near the expected location of the common peroneal nerve,” according to the radiologist’s notes (Figure 1). The patient exhibited improvement with use of anti-inflammatories over several months. There was an increase in his ankle dorsiflexion strength to 4/5 and improvement in his pain and numbness.

Approximately 7 months after his initial presentation, the patient developed a marked worsening—increased numbness and weakness to ankle dorsiflexion—of his original symptoms. A repeat EMG/nerve conduction study of the lower extremity showed a persistent peroneal nerve neuropathy with a persistent denervation of the extensor hallucis longus, tibialis anterior, and extensor digitorum brevis muscles.

Because of continuing symptoms and increasing pain, the patient had surgery 8 months after his initial presentation. At that time, a markedly thickened peroneal nerve was identified. An incision in the epineural sheath released a clear gelatinous fluid consistent with a ganglion cyst. Through the epineural incision, the nerve was decompressed by manually “milking” the fluid from within the sheath. Approximately  30 mL of mucinous fluid was obtained and sent to pathology. No cells were identified.

Postoperatively, the patient noted a marked improvement in his pain. By 2 weeks postoperatively, the numbness in his foot had resolved. At 6 weeks after surgery, the strength of his tibialis anterior and extensor hallucis longus muscles had improved from 3+ to 4-, and he was free of pain.

At 2 months postoperatively, the patient redeveloped pain and numbness, and noted progressive weakness of his left foot and ankle. A repeat MRI of the left knee showed a dilated tubular structure corresponding to the course of the CPN. Comparison of this MRI with the initial MRI showed that the “prominent vein” was actually the dilated CPN.

He was taken to the operating room again 5 months after his first operation. At this time, the CPN was again noted to be markedly dilated (Figure 2). The nerve was explored and a recurrent branch to the proximal tibiofibular joint was identified and divided (Figures 3, 4). Through the divided branch, the CPN could be decompressed by manually “milking” the nerve in a proximal-to-distal direction, expressing clear gelatinous fluid consistent with a ganglion cyst (Figure 5). Pathology of the excised portion of the recurrent nerve was consistent with an intraneural ganglion cyst.

By 2 weeks postoperatively, the numbness of the patient’s left foot had completely resolved, as did his pain. By 3 months after surgery, his extensor hallucis longus strength was 5/5, and ankle dorsiflexion was 4-/5. At 6 months, his ankle dorsiflexion strength was 5/5, and he was completely asymptomatic. At 2 years postoperatively, he remained completely asymptomatic. A follow-up MRI of the left knee showed a ganglion cyst present at the proximal tibiofibular joint with resolution of the intraneural ganglion cyst within the CPN (Figure 6).

Discussion

Intraneural ganglia of peripheral nerves are relatively rare, most commonly occurring in the CPN.^6,8,9 A literature search reveals that this condition is only sparsely reported in orthopedic journals. This report, therefore, describes this rare, yet curable, condition. As noted, without appropriate intervention, the condition has a high likelihood of recurrence with only a brief interruption of symptoms.^6,8,9,12

The operative technique delineated in this report relies heavily on research demonstrating that peroneal intraneural ganglia develop from the superior tibiofibular joint and gain access to the CPN via the recurrent articular branch.^8,13 Research indicates that such ganglia preferentially proceed proximally along the deep portion of the CPN, within the epineurium.⁶ This hypothesis was corroborated in our case by the swollen appearance of the CPN proximal to its bifurcation.

Currently, there is no consensus on treatment of intraneural ganglion cysts of the CPN. However, evidence suggests that disconnection of the recurrent branch of the CPN may be important in successfully treating the condition.^6,9,14 This unified articular theory was initially proposed by Spinner and colleagues¹² in 2003 and recommends that surgical treatment focus on the articular branch as the source of cyst fluid.^6,9,12,14 This theory by Spinner and coauthors^12,14 was substantiated in our case: Once the articular branch was disconnected, cyst fluid was easily expressed via antegrade massage through the disconnected end. Pathologic analysis of a portion of the detached articular branch is also recommended to rule out other cystic lesions, such as cystic shwannomas.¹⁴

The history of the unified articular theory began in the mid-1990s, when Dr. Robert Spinner, board certified in both orthopedic and neurologic surgery, began researching causes of intraneural ganglion cysts. At the time, such ganglia were often treated by radical resection of the nerve and the cyst. Based on his review of literature, and his own cases, Spinner¹⁵ developed the theory that, just as with extraneural ganglia, these cysts are fed by fluid from the joint. According to Spinner,⁹ the sources of such connections were very small articular nerve branches that connect the nerve to the joint. His research led him to the original citation of such an intraneural ganglion of the ulnar nerve, first described by Dr. M. Beauchene, a French physician, in 1810.¹⁶ Spinner also discovered that Beauchene’s original dissection specimen had been preserved and was displayed in a medical museum in Paris. When Spinner went to France to view the specimen, he indeed found an intraneural ganglion of the ulnar nerve. On closer inspection, Spinner also discovered a small articular nerve branch containing a “hollow lumen” that would have been capable of allowing the passage of fluid into the nerve and leading to the development of a cyst.¹⁶

In our case, in the first operation, a simple incisional decompression of the CPN was performed. Unfortunately, the ganglion cyst quickly recurred, as did the patient’s symptoms. In the second surgical procedure, the articular branch connecting the peroneal nerve to the proximal tibiofibular joint was incised and disconnected from the nerve. This allowed the nerve to be decompressed and prevented a recurrence of the ganglion cyst within the nerve with complete resolution of the patient’s symptoms. This difference alone most likely accounts for the rapid recurrence of symptoms after the initial operation, since the fluid was simply drained, but the source was not detached, allowing the ganglion to recur.^6,12,14 This is similar in theory to excising the attachment of a ganglion cyst at the wrist from the underlying joint capsule rather than performing a needle aspiration or puncturing of the cyst.¹²

Regarding the imaging techniques used to identify intraneural ganglia, it is essential that the surgeon be aware of the unified articular theory and the likely presence of an articular branch. Such branches are extremely small and may be easily missed on imaging and intraoperatively.^17,18 MRI is the best method to image these cysts because of its superior ability to visualize soft-tissue lesions.^18,19 Intraneural ganglion cysts typically appear as homogenous, lobulated, well-circumscribed masses that are hyperintense on T2-weighted MRI.^3,19 Gadolinium may also offer diagnostic utility, because these masses do not enhance with its use on T1-weighted MRI.^3,17,19 By employing these techniques, one may easily view most of the ganglion cyst. To image the small articular branch, Spinner and colleagues¹⁷ recommend thin-section images with high–spatial resolution T2-imaging. They also advocate obtaining multiple image views and planes to increase the likelihood of successful imaging.¹⁷ 

The applications of the unified articular theory also extend beyond intraneural ganglia of the CPN. While the CPN is the most common location for intraneural ganglion occurrence,^6,17,20 cases have also been described of intraneural ganglion cysts of the tibial nerve at the proximal tibiofibular joint, as well as via the posterior tibial and medial plantar nerves at the subtalar joint within the tarsal tunnel.^11,18-23 Most cases involving the posterior tibial and medial plantar nerves were found in patients presenting with signs of tarsal tunnel syndrome.^22,23 Intraneural ganglia have also been found within the superficial peroneal nerve arising from the inferior tibiofibular joint.²⁰ In certain cases, these ganglia have also been noted to connect to the joint via a small articular branch.^19,22 In 1 case of an intraneural ganglion of the tibial nerve at the superior tibiofibular joint, initial conservative surgery led to early recurrence of symptoms.¹⁹ Just as in our case, the patient returned to the operating room and, after isolation and ligation of an articular branch, the patient experienced long-term resolution of both the symptoms and the cyst.¹⁹

Given the overwhelming evidence in support of the unified articular theory, we agree with the recommendation by Spinner and colleagues¹⁹ to search for an articular branch both via preoperative imaging and during the operation itself in all cases of intraneural ganglia. Assuming the mechanism of cyst formation is the same in most cases of intraneural ganglia, one could reasonably apply the same surgical techniques used in our case to the management of all intraneural ganglia, drastically reducing recurrence rates.

Conclusion

Based on research and corroborated by this case, the key to successful operative treatment of a common peroneal intraneural ganglion is division of the recurrent articular branch, which connects the proximal tibiofibular joint to the CPN.^6,9,11,12,14 Evidence has shown that disconnecting the articular branch and disrupting the source of the intraneural ganglion can resolve the condition and dramatically diminish the chance of recurrence.^6,8,12,14 This has become known as the unified articular theory.^6,12,14 Reports also suggest that, without disconnecting this articular branch, intraneural ganglion recurrence rates may be higher than 30%.^6,12,14,19 This case, therefore, supports the findings of previous authors^9-11,14 and provides an example of successful utilization of the treatment protocol delineated by Spinner and colleagues.^10,11

Osteoarthritis (OA) of the first carpometacarpal (CMC) joint is a common disabling condition that mostly affects women over 45 years of age.¹ Surgical intervention is usually indicated in advanced stage OA of the first CMC joint that has failed conservative treatment. Several surgical techniques have been described, including partial or total trapeziectomy, interposition arthroplasty with or without ligament reconstruction,^2,3 metacarpal osteotomy,⁴ hematoma and distraction arthroplasty,⁵ total joint arthroplasty, arthrodesis, and suspensionplasty.⁶ However, no single surgical procedure has proved to be superior.⁷

The Artelon implant (Artelon, Nashville, Tennessee) is a T-shaped spacer composed of a biocompatible and biodegradable polycaprolactone-based polyurethane urea polymer. The developers of the implant first presented its use in CMC OA in 2005.⁸ The device, an endoprosthetic replacement for the CMC joint, was designed to work through 2 modes of action: stabilization of the CMC joint by augmentation of the joint capsule and by formation of a new articular surface at the trapeziometacarpal interface. The interposed biomaterial has been described as preventing bony impingement and allowing time for replacement with a newly formed articular surface as it undergoes slow and controlled degradation.⁸

We present a patient with recurrent CMC pain and disability 4 years after arthroscopic hemitrapeziectomy and Artelon interposition and discuss the associated histologic findings. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 53-year-old man presented with painful disability of right thumb of several months’ duration. Clinical and radiographic evaluation supported the diagnosis of right thumb CMC joint Eaton stage III arthritis (Figures 1A, 1B). Surgical intervention was indicated after a failed course of conservative treatment, including splinting, nonsteroidal anti-inflammatory medications, activity modification, and corticosteroid injection. Preoperatively, the patient reported a visual analog scale (VAS) score of 8 with activity and 5 at rest, and a Disabilities of the Arm, Shoulder, and Hand (DASH) score of 72.5.

Arthroscopic débridement, hemitrapeziectomy, and interposition arthroplasty with the Artelon spacer were performed. Using standard thumb arthroscopy, 3 mm of the distal trapezium was excised and shaped parallel to scaphotrapezial joint. The wings of the standard-sized Artelon spacer were removed, and the central (articulating) portion was rolled into a tube and inserted through the 1R portal (directly radial to the abductor pollicis longus tendon) into the trapezial space. The Artelon spacer was unrolled within the joint to cover the remaining trapezium and was stabilized with the placement of a 0.045-inch Kirschner wire through the metacarpal, the spacer, and the remaining trapezium. The patient used a thumb spica splint for 4 weeks.

The postoperative radiographs showed a smooth and adequate hemitrapeziectomy with good alignment and implant position (Figures 2A, 2B). Four weeks after surgery, the Kirschner wire and cast were removed and physical therapy was initiated. The patient’s CMC pain gradually subsided. At the 3-month postoperative visit, the patient’s VAS score was 3 with activity and 1 at rest, with a DASH score of 28. His key pinch strength was 12 lb, compared with 20 lb on the contralateral side. At 6 months, the patient’s VAS score was 1 with activity and 0 at rest, with a DASH score of 12. His key pinch strength was 18 lb, compared with 22 lb on the contralateral side. At his 2-year postoperative visit, the patient was doing well with the exception of some mild residual pain when he opened tight jars. His VAS score was 1 with activity and 0 at rest, with a DASH score of 3. His key pinch strength was 20 lb, compared with 23 lb on the contralateral side. Radiographs showed good maintenance of the CMC space.

Four years postoperatively, the patient presented with worsening right CMC pain with decrease in pinch strength that interfered with his activities of daily living. His VAS score was 9 with activity and 6 at rest, with a DASH score of 70. On examination, pinch strength was 16 lb, compared with 22 lb on the contralateral side. Radiographs showed advancing arthritis with new osteophyte formation and irregular contour of distal trapezium (Figures 3A, 3B). The symptoms were refractory to conservative measures and continued to interfere with his activities of daily living. Revision surgical intervention was indicated and pursued in the form of an open CMC arthroplasty.

The intraoperative findings revealed degradation and disorganization of the Artelon implant within the central portion of the remaining distal trapezium. Rim osteophytes, especially along the ulnar aspect, were noted. Total trapeziectomy and débridement within the CMC space and suture-button suspensionplasty were performed.⁸ Slight degenerative changes of the distal scaphoid were also noted. The incision was irrigated, closed, and stabilized in a thumb spica splint (Figures 4A, 4B).

The harvested trapezium was immediately immersed in buffered formalin. The bone tissue was decalcified, dehydrated, embedded in paraffin, and sectioned in the coronal plane. The sections were stained with safranin O and trichrome, and light microscopic analysis was performed. Central erosion of distal trapezium without smooth resurfacing soft-tissue formation was noted grossly (Figure 5A) and microscopically (Figures 5B, 5C). The histologic morphology of the soft tissue over the distal trapezium was significantly different when compared with the smooth hyaline cartilage at the preserved trapezio-trapezoidal joint (Figures 6A-6F). Microscopic analysis also showed multinucleated giant cells within the soft tissue surrounding the degraded Artelon B (Figure 7).

Immunohistochemical analysis was performed to identify type I and type II collagen using the Histostain-Plus,3rd Gen IHC Detection Kit (Invitrogen Corporation, Camarillo, California) (Figures 8A-8F).⁹ The immunohistochemical stain was used to identify new hyaline cartilage formation that may have been induced by the Artelon as the resurfacing articulation. Hyaline cartilage contains mainly type II collagen, and collagen types VI, IX, X, XI, XII, and XIV all contribute to the mature matrix.¹⁰ Little type I collagen is found in hyaline cartilage. The results showed that the soft tissue over the distal trapezium with embedded Artelon fiber contained both type I and type II collagen. There was no visible hyaline cartilage formation induced by the Artelon. Both morphologic analysis and immunohistochemical staining revealed that the soft-tissue growth into the Artelon spacer on the distal trapezium consisted primarily of fibrocartilaginous tissue, which is composed mainly of type I collagen with some type II collagen.

Two weeks after total surgical excision of the Artelon implant, total trapeziectomy and suture-button suspensionplasty, the sutures were removed and physical therapy was initiated. Radiographs showed good alignment and position of thumb metacarpal with good maintenance of the implant and CMC space. Four months postoperatively, the patient reported that he was doing well without pain and without interference in his activities of daily living. On examination, the patient exhibited no pain with the CMC grind maneuver. Radial abduction of the right thumb was 85° and palmar abduction was 90° (compared with 100° and 90° of the left thumb), obtained by measuring the angle between thumb and index finger, respectively. Opposition was to the small finger metacarpophalangeal joint. Grip strength was 72 lb and pinch strength was 20 lb (compared with 70 lb and 24 lb, respectively, on the contralateral side). 

Discussion

The use of Artelon as an endoprosthetic spacer to treat osteoarthritis in the CMC joint of the thumb appears to stabilize and resurface the joint while avoiding total trapeziectomy.⁸ Nilsson and colleagues⁸ presented a prospective study concluding that the Artelon CMC spacer provided better pinch strength when compared with a traditional abductor pollicis longus suspensionplasty procedure. This study also suggested incorporation of the device in the surface of the adjacent bone with no signs of foreign-body reaction. The synthetic material was shown to be safe and biocompatible in vitro and in animal studies.^11-13

This case report describes the gross and histologic findings after continued pain led to explantation 4 years after arthroscopic partial trapeziectomy and insertion of the spacer. Intraoperative findings at this stage showed lack of incorporation of the Artelon material, central destruction of distal trapezium, and no evidence of smooth articular surface formation. Our histologic analysis showed only poorly organized fibrocartilage within the CMC space rather than a smooth articular surface. These histologic findings may correlate more with Jörheim and colleagues’¹⁴ matched cohort study, which showed that short-term outcomes after treatment with the Artelon implant were not clinically superior to those of tendon suspension-interposition arthroplasties. Multinucleated giant cells were also seen in our specimens. Choung and Tan¹⁵ presented a case report of foreign-body reaction to the Artelon spacer with histologic findings. The foreign body–type reactions associated with Artelon resulted in multinucleated giant cells in their specimens. Recently, several case reports have described similar foreign-body reactions.¹⁶ Nilsson and coauthors¹⁷ presented a randomized, controlled, multicenter study of 109 patients. They reported the Artelon CMC spacer did not result in superior results compared with tendon interposition arthroplasty. In a study by Gretzer and colleagues,¹⁸ the authors suggested that chronic inflammation may result from unstable Artelon fixation instead of the foreign-body reaction.

It is possible that the central erosion of the distal trapezium seen in our case may have resulted from chronic inflammation caused by foreign-body reaction and/or an unstably fixed spacer. The spacer was transfixed to the remaining trapezium in the CMC joint with a Kirschner wire followed by immobilization for 4 weeks. Poor soft-tissue integration of the Artelon spacer may have led to unintended motion and chronic inflammation, which may have also resulted in erosion between the Artelon spacer and the trapezium, leading to central destruction of the distal trapezium. Lastly, the byproducts formed by the degradation of the spacer may have resulted in erosion of the remaining trapezium.

Conclusion

The Artelon CMC spacer used in this patient provided comparable, but not superior, clinical results to other procedures. Histologically, the new articular surface in our patient was formed with rugged fibrocartilage instead of the expected smooth cartilaginous surface. The chronic inflammatory reaction may have resulted from foreign-body reaction, unstable implant fixation, or poor soft-tissue integration. This inflammatory reaction may have contributed to the patient’s recurrence of symptoms. These findings support recent clinical data that suggest the use of the Artelon spacer may not provide superior results to other surgical options for the treatment of CMC joint arthritis.

Osteoarthritis (OA) of the first carpometacarpal (CMC) joint is a common disabling condition that mostly affects women over 45 years of age.¹ Surgical intervention is usually indicated in advanced stage OA of the first CMC joint that has failed conservative treatment. Several surgical techniques have been described, including partial or total trapeziectomy, interposition arthroplasty with or without ligament reconstruction,^2,3 metacarpal osteotomy,⁴ hematoma and distraction arthroplasty,⁵ total joint arthroplasty, arthrodesis, and suspensionplasty.⁶ However, no single surgical procedure has proved to be superior.⁷

The Artelon implant (Artelon, Nashville, Tennessee) is a T-shaped spacer composed of a biocompatible and biodegradable polycaprolactone-based polyurethane urea polymer. The developers of the implant first presented its use in CMC OA in 2005.⁸ The device, an endoprosthetic replacement for the CMC joint, was designed to work through 2 modes of action: stabilization of the CMC joint by augmentation of the joint capsule and by formation of a new articular surface at the trapeziometacarpal interface. The interposed biomaterial has been described as preventing bony impingement and allowing time for replacement with a newly formed articular surface as it undergoes slow and controlled degradation.⁸

We present a patient with recurrent CMC pain and disability 4 years after arthroscopic hemitrapeziectomy and Artelon interposition and discuss the associated histologic findings. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 53-year-old man presented with painful disability of right thumb of several months’ duration. Clinical and radiographic evaluation supported the diagnosis of right thumb CMC joint Eaton stage III arthritis (Figures 1A, 1B). Surgical intervention was indicated after a failed course of conservative treatment, including splinting, nonsteroidal anti-inflammatory medications, activity modification, and corticosteroid injection. Preoperatively, the patient reported a visual analog scale (VAS) score of 8 with activity and 5 at rest, and a Disabilities of the Arm, Shoulder, and Hand (DASH) score of 72.5.

Arthroscopic débridement, hemitrapeziectomy, and interposition arthroplasty with the Artelon spacer were performed. Using standard thumb arthroscopy, 3 mm of the distal trapezium was excised and shaped parallel to scaphotrapezial joint. The wings of the standard-sized Artelon spacer were removed, and the central (articulating) portion was rolled into a tube and inserted through the 1R portal (directly radial to the abductor pollicis longus tendon) into the trapezial space. The Artelon spacer was unrolled within the joint to cover the remaining trapezium and was stabilized with the placement of a 0.045-inch Kirschner wire through the metacarpal, the spacer, and the remaining trapezium. The patient used a thumb spica splint for 4 weeks.

The postoperative radiographs showed a smooth and adequate hemitrapeziectomy with good alignment and implant position (Figures 2A, 2B). Four weeks after surgery, the Kirschner wire and cast were removed and physical therapy was initiated. The patient’s CMC pain gradually subsided. At the 3-month postoperative visit, the patient’s VAS score was 3 with activity and 1 at rest, with a DASH score of 28. His key pinch strength was 12 lb, compared with 20 lb on the contralateral side. At 6 months, the patient’s VAS score was 1 with activity and 0 at rest, with a DASH score of 12. His key pinch strength was 18 lb, compared with 22 lb on the contralateral side. At his 2-year postoperative visit, the patient was doing well with the exception of some mild residual pain when he opened tight jars. His VAS score was 1 with activity and 0 at rest, with a DASH score of 3. His key pinch strength was 20 lb, compared with 23 lb on the contralateral side. Radiographs showed good maintenance of the CMC space.

Four years postoperatively, the patient presented with worsening right CMC pain with decrease in pinch strength that interfered with his activities of daily living. His VAS score was 9 with activity and 6 at rest, with a DASH score of 70. On examination, pinch strength was 16 lb, compared with 22 lb on the contralateral side. Radiographs showed advancing arthritis with new osteophyte formation and irregular contour of distal trapezium (Figures 3A, 3B). The symptoms were refractory to conservative measures and continued to interfere with his activities of daily living. Revision surgical intervention was indicated and pursued in the form of an open CMC arthroplasty.

The intraoperative findings revealed degradation and disorganization of the Artelon implant within the central portion of the remaining distal trapezium. Rim osteophytes, especially along the ulnar aspect, were noted. Total trapeziectomy and débridement within the CMC space and suture-button suspensionplasty were performed.⁸ Slight degenerative changes of the distal scaphoid were also noted. The incision was irrigated, closed, and stabilized in a thumb spica splint (Figures 4A, 4B).

The harvested trapezium was immediately immersed in buffered formalin. The bone tissue was decalcified, dehydrated, embedded in paraffin, and sectioned in the coronal plane. The sections were stained with safranin O and trichrome, and light microscopic analysis was performed. Central erosion of distal trapezium without smooth resurfacing soft-tissue formation was noted grossly (Figure 5A) and microscopically (Figures 5B, 5C). The histologic morphology of the soft tissue over the distal trapezium was significantly different when compared with the smooth hyaline cartilage at the preserved trapezio-trapezoidal joint (Figures 6A-6F). Microscopic analysis also showed multinucleated giant cells within the soft tissue surrounding the degraded Artelon B (Figure 7).

Immunohistochemical analysis was performed to identify type I and type II collagen using the Histostain-Plus,3rd Gen IHC Detection Kit (Invitrogen Corporation, Camarillo, California) (Figures 8A-8F).⁹ The immunohistochemical stain was used to identify new hyaline cartilage formation that may have been induced by the Artelon as the resurfacing articulation. Hyaline cartilage contains mainly type II collagen, and collagen types VI, IX, X, XI, XII, and XIV all contribute to the mature matrix.¹⁰ Little type I collagen is found in hyaline cartilage. The results showed that the soft tissue over the distal trapezium with embedded Artelon fiber contained both type I and type II collagen. There was no visible hyaline cartilage formation induced by the Artelon. Both morphologic analysis and immunohistochemical staining revealed that the soft-tissue growth into the Artelon spacer on the distal trapezium consisted primarily of fibrocartilaginous tissue, which is composed mainly of type I collagen with some type II collagen.

Two weeks after total surgical excision of the Artelon implant, total trapeziectomy and suture-button suspensionplasty, the sutures were removed and physical therapy was initiated. Radiographs showed good alignment and position of thumb metacarpal with good maintenance of the implant and CMC space. Four months postoperatively, the patient reported that he was doing well without pain and without interference in his activities of daily living. On examination, the patient exhibited no pain with the CMC grind maneuver. Radial abduction of the right thumb was 85° and palmar abduction was 90° (compared with 100° and 90° of the left thumb), obtained by measuring the angle between thumb and index finger, respectively. Opposition was to the small finger metacarpophalangeal joint. Grip strength was 72 lb and pinch strength was 20 lb (compared with 70 lb and 24 lb, respectively, on the contralateral side). 

Discussion

The use of Artelon as an endoprosthetic spacer to treat osteoarthritis in the CMC joint of the thumb appears to stabilize and resurface the joint while avoiding total trapeziectomy.⁸ Nilsson and colleagues⁸ presented a prospective study concluding that the Artelon CMC spacer provided better pinch strength when compared with a traditional abductor pollicis longus suspensionplasty procedure. This study also suggested incorporation of the device in the surface of the adjacent bone with no signs of foreign-body reaction. The synthetic material was shown to be safe and biocompatible in vitro and in animal studies.^11-13

This case report describes the gross and histologic findings after continued pain led to explantation 4 years after arthroscopic partial trapeziectomy and insertion of the spacer. Intraoperative findings at this stage showed lack of incorporation of the Artelon material, central destruction of distal trapezium, and no evidence of smooth articular surface formation. Our histologic analysis showed only poorly organized fibrocartilage within the CMC space rather than a smooth articular surface. These histologic findings may correlate more with Jörheim and colleagues’¹⁴ matched cohort study, which showed that short-term outcomes after treatment with the Artelon implant were not clinically superior to those of tendon suspension-interposition arthroplasties. Multinucleated giant cells were also seen in our specimens. Choung and Tan¹⁵ presented a case report of foreign-body reaction to the Artelon spacer with histologic findings. The foreign body–type reactions associated with Artelon resulted in multinucleated giant cells in their specimens. Recently, several case reports have described similar foreign-body reactions.¹⁶ Nilsson and coauthors¹⁷ presented a randomized, controlled, multicenter study of 109 patients. They reported the Artelon CMC spacer did not result in superior results compared with tendon interposition arthroplasty. In a study by Gretzer and colleagues,¹⁸ the authors suggested that chronic inflammation may result from unstable Artelon fixation instead of the foreign-body reaction.

It is possible that the central erosion of the distal trapezium seen in our case may have resulted from chronic inflammation caused by foreign-body reaction and/or an unstably fixed spacer. The spacer was transfixed to the remaining trapezium in the CMC joint with a Kirschner wire followed by immobilization for 4 weeks. Poor soft-tissue integration of the Artelon spacer may have led to unintended motion and chronic inflammation, which may have also resulted in erosion between the Artelon spacer and the trapezium, leading to central destruction of the distal trapezium. Lastly, the byproducts formed by the degradation of the spacer may have resulted in erosion of the remaining trapezium.

Conclusion

The Artelon CMC spacer used in this patient provided comparable, but not superior, clinical results to other procedures. Histologically, the new articular surface in our patient was formed with rugged fibrocartilage instead of the expected smooth cartilaginous surface. The chronic inflammatory reaction may have resulted from foreign-body reaction, unstable implant fixation, or poor soft-tissue integration. This inflammatory reaction may have contributed to the patient’s recurrence of symptoms. These findings support recent clinical data that suggest the use of the Artelon spacer may not provide superior results to other surgical options for the treatment of CMC joint arthritis.

Osteoarthritis (OA) of the first carpometacarpal (CMC) joint is a common disabling condition that mostly affects women over 45 years of age.¹ Surgical intervention is usually indicated in advanced stage OA of the first CMC joint that has failed conservative treatment. Several surgical techniques have been described, including partial or total trapeziectomy, interposition arthroplasty with or without ligament reconstruction,^2,3 metacarpal osteotomy,⁴ hematoma and distraction arthroplasty,⁵ total joint arthroplasty, arthrodesis, and suspensionplasty.⁶ However, no single surgical procedure has proved to be superior.⁷

The Artelon implant (Artelon, Nashville, Tennessee) is a T-shaped spacer composed of a biocompatible and biodegradable polycaprolactone-based polyurethane urea polymer. The developers of the implant first presented its use in CMC OA in 2005.⁸ The device, an endoprosthetic replacement for the CMC joint, was designed to work through 2 modes of action: stabilization of the CMC joint by augmentation of the joint capsule and by formation of a new articular surface at the trapeziometacarpal interface. The interposed biomaterial has been described as preventing bony impingement and allowing time for replacement with a newly formed articular surface as it undergoes slow and controlled degradation.⁸

We present a patient with recurrent CMC pain and disability 4 years after arthroscopic hemitrapeziectomy and Artelon interposition and discuss the associated histologic findings. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 53-year-old man presented with painful disability of right thumb of several months’ duration. Clinical and radiographic evaluation supported the diagnosis of right thumb CMC joint Eaton stage III arthritis (Figures 1A, 1B). Surgical intervention was indicated after a failed course of conservative treatment, including splinting, nonsteroidal anti-inflammatory medications, activity modification, and corticosteroid injection. Preoperatively, the patient reported a visual analog scale (VAS) score of 8 with activity and 5 at rest, and a Disabilities of the Arm, Shoulder, and Hand (DASH) score of 72.5.

Arthroscopic débridement, hemitrapeziectomy, and interposition arthroplasty with the Artelon spacer were performed. Using standard thumb arthroscopy, 3 mm of the distal trapezium was excised and shaped parallel to scaphotrapezial joint. The wings of the standard-sized Artelon spacer were removed, and the central (articulating) portion was rolled into a tube and inserted through the 1R portal (directly radial to the abductor pollicis longus tendon) into the trapezial space. The Artelon spacer was unrolled within the joint to cover the remaining trapezium and was stabilized with the placement of a 0.045-inch Kirschner wire through the metacarpal, the spacer, and the remaining trapezium. The patient used a thumb spica splint for 4 weeks.

The postoperative radiographs showed a smooth and adequate hemitrapeziectomy with good alignment and implant position (Figures 2A, 2B). Four weeks after surgery, the Kirschner wire and cast were removed and physical therapy was initiated. The patient’s CMC pain gradually subsided. At the 3-month postoperative visit, the patient’s VAS score was 3 with activity and 1 at rest, with a DASH score of 28. His key pinch strength was 12 lb, compared with 20 lb on the contralateral side. At 6 months, the patient’s VAS score was 1 with activity and 0 at rest, with a DASH score of 12. His key pinch strength was 18 lb, compared with 22 lb on the contralateral side. At his 2-year postoperative visit, the patient was doing well with the exception of some mild residual pain when he opened tight jars. His VAS score was 1 with activity and 0 at rest, with a DASH score of 3. His key pinch strength was 20 lb, compared with 23 lb on the contralateral side. Radiographs showed good maintenance of the CMC space.

Four years postoperatively, the patient presented with worsening right CMC pain with decrease in pinch strength that interfered with his activities of daily living. His VAS score was 9 with activity and 6 at rest, with a DASH score of 70. On examination, pinch strength was 16 lb, compared with 22 lb on the contralateral side. Radiographs showed advancing arthritis with new osteophyte formation and irregular contour of distal trapezium (Figures 3A, 3B). The symptoms were refractory to conservative measures and continued to interfere with his activities of daily living. Revision surgical intervention was indicated and pursued in the form of an open CMC arthroplasty.

The intraoperative findings revealed degradation and disorganization of the Artelon implant within the central portion of the remaining distal trapezium. Rim osteophytes, especially along the ulnar aspect, were noted. Total trapeziectomy and débridement within the CMC space and suture-button suspensionplasty were performed.⁸ Slight degenerative changes of the distal scaphoid were also noted. The incision was irrigated, closed, and stabilized in a thumb spica splint (Figures 4A, 4B).

The harvested trapezium was immediately immersed in buffered formalin. The bone tissue was decalcified, dehydrated, embedded in paraffin, and sectioned in the coronal plane. The sections were stained with safranin O and trichrome, and light microscopic analysis was performed. Central erosion of distal trapezium without smooth resurfacing soft-tissue formation was noted grossly (Figure 5A) and microscopically (Figures 5B, 5C). The histologic morphology of the soft tissue over the distal trapezium was significantly different when compared with the smooth hyaline cartilage at the preserved trapezio-trapezoidal joint (Figures 6A-6F). Microscopic analysis also showed multinucleated giant cells within the soft tissue surrounding the degraded Artelon B (Figure 7).

Immunohistochemical analysis was performed to identify type I and type II collagen using the Histostain-Plus,3rd Gen IHC Detection Kit (Invitrogen Corporation, Camarillo, California) (Figures 8A-8F).⁹ The immunohistochemical stain was used to identify new hyaline cartilage formation that may have been induced by the Artelon as the resurfacing articulation. Hyaline cartilage contains mainly type II collagen, and collagen types VI, IX, X, XI, XII, and XIV all contribute to the mature matrix.¹⁰ Little type I collagen is found in hyaline cartilage. The results showed that the soft tissue over the distal trapezium with embedded Artelon fiber contained both type I and type II collagen. There was no visible hyaline cartilage formation induced by the Artelon. Both morphologic analysis and immunohistochemical staining revealed that the soft-tissue growth into the Artelon spacer on the distal trapezium consisted primarily of fibrocartilaginous tissue, which is composed mainly of type I collagen with some type II collagen.

Two weeks after total surgical excision of the Artelon implant, total trapeziectomy and suture-button suspensionplasty, the sutures were removed and physical therapy was initiated. Radiographs showed good alignment and position of thumb metacarpal with good maintenance of the implant and CMC space. Four months postoperatively, the patient reported that he was doing well without pain and without interference in his activities of daily living. On examination, the patient exhibited no pain with the CMC grind maneuver. Radial abduction of the right thumb was 85° and palmar abduction was 90° (compared with 100° and 90° of the left thumb), obtained by measuring the angle between thumb and index finger, respectively. Opposition was to the small finger metacarpophalangeal joint. Grip strength was 72 lb and pinch strength was 20 lb (compared with 70 lb and 24 lb, respectively, on the contralateral side). 

Discussion

The use of Artelon as an endoprosthetic spacer to treat osteoarthritis in the CMC joint of the thumb appears to stabilize and resurface the joint while avoiding total trapeziectomy.⁸ Nilsson and colleagues⁸ presented a prospective study concluding that the Artelon CMC spacer provided better pinch strength when compared with a traditional abductor pollicis longus suspensionplasty procedure. This study also suggested incorporation of the device in the surface of the adjacent bone with no signs of foreign-body reaction. The synthetic material was shown to be safe and biocompatible in vitro and in animal studies.^11-13

This case report describes the gross and histologic findings after continued pain led to explantation 4 years after arthroscopic partial trapeziectomy and insertion of the spacer. Intraoperative findings at this stage showed lack of incorporation of the Artelon material, central destruction of distal trapezium, and no evidence of smooth articular surface formation. Our histologic analysis showed only poorly organized fibrocartilage within the CMC space rather than a smooth articular surface. These histologic findings may correlate more with Jörheim and colleagues’¹⁴ matched cohort study, which showed that short-term outcomes after treatment with the Artelon implant were not clinically superior to those of tendon suspension-interposition arthroplasties. Multinucleated giant cells were also seen in our specimens. Choung and Tan¹⁵ presented a case report of foreign-body reaction to the Artelon spacer with histologic findings. The foreign body–type reactions associated with Artelon resulted in multinucleated giant cells in their specimens. Recently, several case reports have described similar foreign-body reactions.¹⁶ Nilsson and coauthors¹⁷ presented a randomized, controlled, multicenter study of 109 patients. They reported the Artelon CMC spacer did not result in superior results compared with tendon interposition arthroplasty. In a study by Gretzer and colleagues,¹⁸ the authors suggested that chronic inflammation may result from unstable Artelon fixation instead of the foreign-body reaction.

It is possible that the central erosion of the distal trapezium seen in our case may have resulted from chronic inflammation caused by foreign-body reaction and/or an unstably fixed spacer. The spacer was transfixed to the remaining trapezium in the CMC joint with a Kirschner wire followed by immobilization for 4 weeks. Poor soft-tissue integration of the Artelon spacer may have led to unintended motion and chronic inflammation, which may have also resulted in erosion between the Artelon spacer and the trapezium, leading to central destruction of the distal trapezium. Lastly, the byproducts formed by the degradation of the spacer may have resulted in erosion of the remaining trapezium.

Conclusion

The Artelon CMC spacer used in this patient provided comparable, but not superior, clinical results to other procedures. Histologically, the new articular surface in our patient was formed with rugged fibrocartilage instead of the expected smooth cartilaginous surface. The chronic inflammatory reaction may have resulted from foreign-body reaction, unstable implant fixation, or poor soft-tissue integration. This inflammatory reaction may have contributed to the patient’s recurrence of symptoms. These findings support recent clinical data that suggest the use of the Artelon spacer may not provide superior results to other surgical options for the treatment of CMC joint arthritis.

Symptomatic synovial cyst formation is a rare, late occurrence after total knee arthroplasty (TKA); these cysts are generally discovered by chance. If they enlarge, they can result in significant pain and disability. A few case reports have described the development of very large cysts that required revision knee surgery. In this patient, polyethylene wear disease after TKA resulted in a massive synovial cyst that extended into the posterior compartment of the leg, as well as a progressive peripheral neuropathy. Revision of a loose patella component and worn polyethylene liner with complete synovectomy, plus decompression of the cyst via needle aspiration, resulted in an excellent short-term outcome.

To the author’s knowledge, this is the first case report of peripheral neuropathy of the tibial nerve secondary to a massive Baker cyst after total knee replacement. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

The patient was a 65-year-old woman with a complex medical history and multiple left knee surgeries, including a high tibial osteotomy and subsequent cemented TKA performed in the mid-1990s. She presented to the orthopedic department at a university hospital with complaints of knee pain 13 years after TKA. Observation was recommended; however, she was lost to follow-up.

The patient presented to her primary care physician (PCP) 16 years after TKA with a very large, painful mass in the back of her left leg. An ultrasound showed a large Baker cyst, and the patient was sent to interventional radiology. A few months later, she had an ultrasound-guided aspiration into the left calf, which produced 300 mL of thick synovial fluid. A cell count was not performed, but bacterial cultures were negative. Immediately after the aspiration, the pain was relieved.

Approximately 3 months after the aspiration, she presented again to her PCP with re-accumulation of fluid in the back of her left leg and severe leg pain. She was referred to a different orthopedic surgeon who determined that the risk of surgery was too great given her complex medical history.

The woman’s PCP referred the woman to our office 6 months after the aspiration. On presentation, her pain was localized to the posterior left leg. She reported the pain level as a constant 9 out of 10 on the visual analog scale, despite ingesting high doses of narcotics, including oxycontin and morphine. Her physical examination was remarkable for an ill-defined large calf mass. The posterior compartment of her left leg was firm and severely tender, similar to the characteristic findings seen in acute compartment syndrome.

Radiographs showed evidence of asymmetric polyethylene wear on the medial side of the knee (Figures 1A, 1B). Serum labs were ordered to evaluate for infection. C-reactive protein was mildly elevated at 5.5 mg/L (normal range, 0-5 mg/L); however, the erythrocyte sedimentation rate was normal at 12 mm/h (normal range, 0-20 mm/h). Magnetic resonance imaging of the left lower extremity with intravenous contrast showed the presence of a very large Baker cyst contained within the posterior compartment of the knee and a smaller surrounding cyst adjacent to the popliteal neurovascular bundle (Figure 2).

The Baker cyst was re-aspirated in the office. The automated synovial fluid cell count could not be performed because of high fluid viscosity. However, a manual review of the fluid specimen under light microscopy revealed proteinaceous, viscous tan-colored fluid containing no neutrophils and a few macrophages. Fluid cytology was also sent for review under polarizing light microscopy as described by Peterson and colleagues.¹ Scattered fragments of polarizable foreign material were consistent with polyethylene debris (Figure 3). 

The patient was counseled about the risks and benefits of surgery and was offered revision TKA with polyethylene liner exchange and synovectomy, only after complete cessation of smoking. She underwent serum nicotine monitoring to ensure tobacco cessation; however, she also reported the onset of a progressive sensory deficit over her left foot during this period. Although her medical history was remarkable for spinal stenosis, she noted a progressive decline in sensory function and new-onset paresthesia of her left foot.

An urgent consult to neurology was requested for nerve conduction studies. According to the electrodiagnostic study, the patient had a moderately severe left tibial neuropathy, likely at the popliteal fossa or distal to it. The nerve conduction study showed a chronic tibial nerve peripheral compressive mononeuropathy, and she was immediately scheduled for revision knee surgery with decompression of her Baker cyst to prevent further neurologic deficit.

During surgery, the knee joint exhibited hypertrophic synovitis with a characteristic pale-yellowish discoloration secondary to significant polyethylene wear disease (Figure 4). The polyethylene liner was severely worn with pitting, cracking, and delamination (Figure 5). While the patellar component was grossly loose, the tibial and femoral components were stable. After a complete synovectomy, the loose patellar component and tibial polyethylene liner were replaced. Osteolytic areas within the tibia underwent curettage and allograft impaction grafting. Lastly, decompression of the ruptured Baker cyst was performed via a 16-gauge needle placed in the posterior compartment of the left leg. The calf was gently squeezed with a “milking” maneuver, which yielded approximately 200 mL of thick, mucoid yellowish-brown synovial fluid resembling tapioca pudding (Figure 6).

Postoperatively, all intraoperative cultures were negative, and the patient was followed closely at 1 week, 2 weeks, 6 weeks, and 3 months after the surgery. At her latest follow-up, the posterior leg compartment remained decompressed and her progressive sensory deficit had nearly resolved. Moreover, the left leg and posterior knee pain completely resolved.

Discussion

A leading cause of TKA failure is attributed to aseptic loosening from polyethylene wear disease.² Implanted high-molecular-weight polyethylene (HMWPE) liners are known to undergo a variety of mechanical wear patterns within the knee. Observed patterns include pitting, scratching, burnishing, scratching, and delamination, which can all liberate numerous fine polyethylene particles.³ This wear debris induces macrophage phagocytosis that triggers an inflammatory reaction within the knee joint and can lead to synovitis, repeat effusions and, ultimately, to aseptic loosening.

Prior to 1996, polyethylene used in total knee replacement underwent a sterilization process in air. This oxygen-rich environment led to the development of free radical formation within the HMWPE. Ultimately, this had a detrimental effect on the polyethylene, leading to the formation of increased wear debris.⁴

Subsequently, orthopedic companies have changed their sterilization and manufacturing methods. Polyethylene components now undergo a variety of processes to eliminate or reduce oxidation, free-radical formation, and mechanical wear debris. Now, sterilization typically takes place in an inert atmospheric environment. Modern HMWPE implants often undergo higher irradiation to induce mechanical cross-linking, followed by either a re-annealing or remelting step. In other cases, manufacturers “dope” their polyethylene with vitamin E to quench free radicals within the material. While these steps have reduced the number of in vitro wear particles, the problem of wear debris, subsequent osteolysis, and aseptic loosening has not been eliminated.^1-5 

Polyethylene wear debris within the synovial fluid or tissue of failed TKAs can be identified with scanning electron microscopy or by light microscopy utilizing polarized light.¹ In this particular case, wear debris was confirmed within the synovial tissue and in the fluid of the Baker cyst by microscopic analysis.

Formation of a popliteal or Baker cyst as a result of polyethylene wear disease is an infrequent but known complication of TKA. Reports have demonstrated variable success in cyst eradication when revision surgery is performed on knees with synovial cysts. Most of these reports indicate that cyst formation tends to occur as a late complication (7 or more years) after TKA.^6-12

Treatment options may include skillful observation with close follow-up or revision surgery. Polyethylene exchange with synovectomy when feasible, as well as component revision with or without excision of the synovial cyst, are surgical options.

Niki and colleagues¹³ described a gigantic popliteal synovial cyst caused by wear particles after TKA. In this report, the surgeon performed a synovectomy and polyethylene liner exchange with retention of prosthetic components. At 12-month follow-up, the patient was reported to be doing well.

Mavrogenis and coauthors¹⁴ reported a wear debris–induced pseudotumor in the popliteal fossa and calf after TKA. In this case, in addition to the synovectomy, the surgeon removed all prosthetic components and used a semi-constrained implant to revise the knee. At 30-month follow-up, the patient reported having a painless knee.

While case reports have indicated that revision TKA for large, painful synovial cysts is a reasonable treatment option in carefully selected patients, there is a paucity of literature on this subject. Moreover, the present case appears to be the first literature report of a tibial nerve compressive neuropathy secondary to a synovial cyst after TKA.

Conclusion

In this report, polyethylene wear disease after TKA resulted in a massive synovial cyst extending into the posterior compartment of the leg. A progressive peripheral neuropathy confirmed by electromyography was also discovered. The patient underwent revision of a loose patellar component and worn polyethylene liner with complete synovectomy plus decompression of the cyst via needle aspiration. This resulted in an excellent short-term outcome with resolution of pain and significant improvement of the peripheral neuropathy 3 months after surgery.

Symptomatic synovial cyst formation is a rare, late occurrence after total knee arthroplasty (TKA); these cysts are generally discovered by chance. If they enlarge, they can result in significant pain and disability. A few case reports have described the development of very large cysts that required revision knee surgery. In this patient, polyethylene wear disease after TKA resulted in a massive synovial cyst that extended into the posterior compartment of the leg, as well as a progressive peripheral neuropathy. Revision of a loose patella component and worn polyethylene liner with complete synovectomy, plus decompression of the cyst via needle aspiration, resulted in an excellent short-term outcome.

To the author’s knowledge, this is the first case report of peripheral neuropathy of the tibial nerve secondary to a massive Baker cyst after total knee replacement. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

The patient was a 65-year-old woman with a complex medical history and multiple left knee surgeries, including a high tibial osteotomy and subsequent cemented TKA performed in the mid-1990s. She presented to the orthopedic department at a university hospital with complaints of knee pain 13 years after TKA. Observation was recommended; however, she was lost to follow-up.

The patient presented to her primary care physician (PCP) 16 years after TKA with a very large, painful mass in the back of her left leg. An ultrasound showed a large Baker cyst, and the patient was sent to interventional radiology. A few months later, she had an ultrasound-guided aspiration into the left calf, which produced 300 mL of thick synovial fluid. A cell count was not performed, but bacterial cultures were negative. Immediately after the aspiration, the pain was relieved.

Approximately 3 months after the aspiration, she presented again to her PCP with re-accumulation of fluid in the back of her left leg and severe leg pain. She was referred to a different orthopedic surgeon who determined that the risk of surgery was too great given her complex medical history.

The woman’s PCP referred the woman to our office 6 months after the aspiration. On presentation, her pain was localized to the posterior left leg. She reported the pain level as a constant 9 out of 10 on the visual analog scale, despite ingesting high doses of narcotics, including oxycontin and morphine. Her physical examination was remarkable for an ill-defined large calf mass. The posterior compartment of her left leg was firm and severely tender, similar to the characteristic findings seen in acute compartment syndrome.

Radiographs showed evidence of asymmetric polyethylene wear on the medial side of the knee (Figures 1A, 1B). Serum labs were ordered to evaluate for infection. C-reactive protein was mildly elevated at 5.5 mg/L (normal range, 0-5 mg/L); however, the erythrocyte sedimentation rate was normal at 12 mm/h (normal range, 0-20 mm/h). Magnetic resonance imaging of the left lower extremity with intravenous contrast showed the presence of a very large Baker cyst contained within the posterior compartment of the knee and a smaller surrounding cyst adjacent to the popliteal neurovascular bundle (Figure 2).

The Baker cyst was re-aspirated in the office. The automated synovial fluid cell count could not be performed because of high fluid viscosity. However, a manual review of the fluid specimen under light microscopy revealed proteinaceous, viscous tan-colored fluid containing no neutrophils and a few macrophages. Fluid cytology was also sent for review under polarizing light microscopy as described by Peterson and colleagues.¹ Scattered fragments of polarizable foreign material were consistent with polyethylene debris (Figure 3). 

The patient was counseled about the risks and benefits of surgery and was offered revision TKA with polyethylene liner exchange and synovectomy, only after complete cessation of smoking. She underwent serum nicotine monitoring to ensure tobacco cessation; however, she also reported the onset of a progressive sensory deficit over her left foot during this period. Although her medical history was remarkable for spinal stenosis, she noted a progressive decline in sensory function and new-onset paresthesia of her left foot.

An urgent consult to neurology was requested for nerve conduction studies. According to the electrodiagnostic study, the patient had a moderately severe left tibial neuropathy, likely at the popliteal fossa or distal to it. The nerve conduction study showed a chronic tibial nerve peripheral compressive mononeuropathy, and she was immediately scheduled for revision knee surgery with decompression of her Baker cyst to prevent further neurologic deficit.

During surgery, the knee joint exhibited hypertrophic synovitis with a characteristic pale-yellowish discoloration secondary to significant polyethylene wear disease (Figure 4). The polyethylene liner was severely worn with pitting, cracking, and delamination (Figure 5). While the patellar component was grossly loose, the tibial and femoral components were stable. After a complete synovectomy, the loose patellar component and tibial polyethylene liner were replaced. Osteolytic areas within the tibia underwent curettage and allograft impaction grafting. Lastly, decompression of the ruptured Baker cyst was performed via a 16-gauge needle placed in the posterior compartment of the left leg. The calf was gently squeezed with a “milking” maneuver, which yielded approximately 200 mL of thick, mucoid yellowish-brown synovial fluid resembling tapioca pudding (Figure 6).

Postoperatively, all intraoperative cultures were negative, and the patient was followed closely at 1 week, 2 weeks, 6 weeks, and 3 months after the surgery. At her latest follow-up, the posterior leg compartment remained decompressed and her progressive sensory deficit had nearly resolved. Moreover, the left leg and posterior knee pain completely resolved.

Discussion

A leading cause of TKA failure is attributed to aseptic loosening from polyethylene wear disease.² Implanted high-molecular-weight polyethylene (HMWPE) liners are known to undergo a variety of mechanical wear patterns within the knee. Observed patterns include pitting, scratching, burnishing, scratching, and delamination, which can all liberate numerous fine polyethylene particles.³ This wear debris induces macrophage phagocytosis that triggers an inflammatory reaction within the knee joint and can lead to synovitis, repeat effusions and, ultimately, to aseptic loosening.

Prior to 1996, polyethylene used in total knee replacement underwent a sterilization process in air. This oxygen-rich environment led to the development of free radical formation within the HMWPE. Ultimately, this had a detrimental effect on the polyethylene, leading to the formation of increased wear debris.⁴

Subsequently, orthopedic companies have changed their sterilization and manufacturing methods. Polyethylene components now undergo a variety of processes to eliminate or reduce oxidation, free-radical formation, and mechanical wear debris. Now, sterilization typically takes place in an inert atmospheric environment. Modern HMWPE implants often undergo higher irradiation to induce mechanical cross-linking, followed by either a re-annealing or remelting step. In other cases, manufacturers “dope” their polyethylene with vitamin E to quench free radicals within the material. While these steps have reduced the number of in vitro wear particles, the problem of wear debris, subsequent osteolysis, and aseptic loosening has not been eliminated.^1-5 

Polyethylene wear debris within the synovial fluid or tissue of failed TKAs can be identified with scanning electron microscopy or by light microscopy utilizing polarized light.¹ In this particular case, wear debris was confirmed within the synovial tissue and in the fluid of the Baker cyst by microscopic analysis.

Formation of a popliteal or Baker cyst as a result of polyethylene wear disease is an infrequent but known complication of TKA. Reports have demonstrated variable success in cyst eradication when revision surgery is performed on knees with synovial cysts. Most of these reports indicate that cyst formation tends to occur as a late complication (7 or more years) after TKA.^6-12

Treatment options may include skillful observation with close follow-up or revision surgery. Polyethylene exchange with synovectomy when feasible, as well as component revision with or without excision of the synovial cyst, are surgical options.

Niki and colleagues¹³ described a gigantic popliteal synovial cyst caused by wear particles after TKA. In this report, the surgeon performed a synovectomy and polyethylene liner exchange with retention of prosthetic components. At 12-month follow-up, the patient was reported to be doing well.

Mavrogenis and coauthors¹⁴ reported a wear debris–induced pseudotumor in the popliteal fossa and calf after TKA. In this case, in addition to the synovectomy, the surgeon removed all prosthetic components and used a semi-constrained implant to revise the knee. At 30-month follow-up, the patient reported having a painless knee.

While case reports have indicated that revision TKA for large, painful synovial cysts is a reasonable treatment option in carefully selected patients, there is a paucity of literature on this subject. Moreover, the present case appears to be the first literature report of a tibial nerve compressive neuropathy secondary to a synovial cyst after TKA.

Conclusion

In this report, polyethylene wear disease after TKA resulted in a massive synovial cyst extending into the posterior compartment of the leg. A progressive peripheral neuropathy confirmed by electromyography was also discovered. The patient underwent revision of a loose patellar component and worn polyethylene liner with complete synovectomy plus decompression of the cyst via needle aspiration. This resulted in an excellent short-term outcome with resolution of pain and significant improvement of the peripheral neuropathy 3 months after surgery.

Symptomatic synovial cyst formation is a rare, late occurrence after total knee arthroplasty (TKA); these cysts are generally discovered by chance. If they enlarge, they can result in significant pain and disability. A few case reports have described the development of very large cysts that required revision knee surgery. In this patient, polyethylene wear disease after TKA resulted in a massive synovial cyst that extended into the posterior compartment of the leg, as well as a progressive peripheral neuropathy. Revision of a loose patella component and worn polyethylene liner with complete synovectomy, plus decompression of the cyst via needle aspiration, resulted in an excellent short-term outcome.

To the author’s knowledge, this is the first case report of peripheral neuropathy of the tibial nerve secondary to a massive Baker cyst after total knee replacement. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

The patient was a 65-year-old woman with a complex medical history and multiple left knee surgeries, including a high tibial osteotomy and subsequent cemented TKA performed in the mid-1990s. She presented to the orthopedic department at a university hospital with complaints of knee pain 13 years after TKA. Observation was recommended; however, she was lost to follow-up.

The patient presented to her primary care physician (PCP) 16 years after TKA with a very large, painful mass in the back of her left leg. An ultrasound showed a large Baker cyst, and the patient was sent to interventional radiology. A few months later, she had an ultrasound-guided aspiration into the left calf, which produced 300 mL of thick synovial fluid. A cell count was not performed, but bacterial cultures were negative. Immediately after the aspiration, the pain was relieved.

Approximately 3 months after the aspiration, she presented again to her PCP with re-accumulation of fluid in the back of her left leg and severe leg pain. She was referred to a different orthopedic surgeon who determined that the risk of surgery was too great given her complex medical history.

The woman’s PCP referred the woman to our office 6 months after the aspiration. On presentation, her pain was localized to the posterior left leg. She reported the pain level as a constant 9 out of 10 on the visual analog scale, despite ingesting high doses of narcotics, including oxycontin and morphine. Her physical examination was remarkable for an ill-defined large calf mass. The posterior compartment of her left leg was firm and severely tender, similar to the characteristic findings seen in acute compartment syndrome.

Radiographs showed evidence of asymmetric polyethylene wear on the medial side of the knee (Figures 1A, 1B). Serum labs were ordered to evaluate for infection. C-reactive protein was mildly elevated at 5.5 mg/L (normal range, 0-5 mg/L); however, the erythrocyte sedimentation rate was normal at 12 mm/h (normal range, 0-20 mm/h). Magnetic resonance imaging of the left lower extremity with intravenous contrast showed the presence of a very large Baker cyst contained within the posterior compartment of the knee and a smaller surrounding cyst adjacent to the popliteal neurovascular bundle (Figure 2).

The Baker cyst was re-aspirated in the office. The automated synovial fluid cell count could not be performed because of high fluid viscosity. However, a manual review of the fluid specimen under light microscopy revealed proteinaceous, viscous tan-colored fluid containing no neutrophils and a few macrophages. Fluid cytology was also sent for review under polarizing light microscopy as described by Peterson and colleagues.¹ Scattered fragments of polarizable foreign material were consistent with polyethylene debris (Figure 3). 

The patient was counseled about the risks and benefits of surgery and was offered revision TKA with polyethylene liner exchange and synovectomy, only after complete cessation of smoking. She underwent serum nicotine monitoring to ensure tobacco cessation; however, she also reported the onset of a progressive sensory deficit over her left foot during this period. Although her medical history was remarkable for spinal stenosis, she noted a progressive decline in sensory function and new-onset paresthesia of her left foot.

An urgent consult to neurology was requested for nerve conduction studies. According to the electrodiagnostic study, the patient had a moderately severe left tibial neuropathy, likely at the popliteal fossa or distal to it. The nerve conduction study showed a chronic tibial nerve peripheral compressive mononeuropathy, and she was immediately scheduled for revision knee surgery with decompression of her Baker cyst to prevent further neurologic deficit.

During surgery, the knee joint exhibited hypertrophic synovitis with a characteristic pale-yellowish discoloration secondary to significant polyethylene wear disease (Figure 4). The polyethylene liner was severely worn with pitting, cracking, and delamination (Figure 5). While the patellar component was grossly loose, the tibial and femoral components were stable. After a complete synovectomy, the loose patellar component and tibial polyethylene liner were replaced. Osteolytic areas within the tibia underwent curettage and allograft impaction grafting. Lastly, decompression of the ruptured Baker cyst was performed via a 16-gauge needle placed in the posterior compartment of the left leg. The calf was gently squeezed with a “milking” maneuver, which yielded approximately 200 mL of thick, mucoid yellowish-brown synovial fluid resembling tapioca pudding (Figure 6).

Postoperatively, all intraoperative cultures were negative, and the patient was followed closely at 1 week, 2 weeks, 6 weeks, and 3 months after the surgery. At her latest follow-up, the posterior leg compartment remained decompressed and her progressive sensory deficit had nearly resolved. Moreover, the left leg and posterior knee pain completely resolved.

Discussion

A leading cause of TKA failure is attributed to aseptic loosening from polyethylene wear disease.² Implanted high-molecular-weight polyethylene (HMWPE) liners are known to undergo a variety of mechanical wear patterns within the knee. Observed patterns include pitting, scratching, burnishing, scratching, and delamination, which can all liberate numerous fine polyethylene particles.³ This wear debris induces macrophage phagocytosis that triggers an inflammatory reaction within the knee joint and can lead to synovitis, repeat effusions and, ultimately, to aseptic loosening.

Prior to 1996, polyethylene used in total knee replacement underwent a sterilization process in air. This oxygen-rich environment led to the development of free radical formation within the HMWPE. Ultimately, this had a detrimental effect on the polyethylene, leading to the formation of increased wear debris.⁴

Subsequently, orthopedic companies have changed their sterilization and manufacturing methods. Polyethylene components now undergo a variety of processes to eliminate or reduce oxidation, free-radical formation, and mechanical wear debris. Now, sterilization typically takes place in an inert atmospheric environment. Modern HMWPE implants often undergo higher irradiation to induce mechanical cross-linking, followed by either a re-annealing or remelting step. In other cases, manufacturers “dope” their polyethylene with vitamin E to quench free radicals within the material. While these steps have reduced the number of in vitro wear particles, the problem of wear debris, subsequent osteolysis, and aseptic loosening has not been eliminated.^1-5 

Polyethylene wear debris within the synovial fluid or tissue of failed TKAs can be identified with scanning electron microscopy or by light microscopy utilizing polarized light.¹ In this particular case, wear debris was confirmed within the synovial tissue and in the fluid of the Baker cyst by microscopic analysis.

Formation of a popliteal or Baker cyst as a result of polyethylene wear disease is an infrequent but known complication of TKA. Reports have demonstrated variable success in cyst eradication when revision surgery is performed on knees with synovial cysts. Most of these reports indicate that cyst formation tends to occur as a late complication (7 or more years) after TKA.^6-12

Treatment options may include skillful observation with close follow-up or revision surgery. Polyethylene exchange with synovectomy when feasible, as well as component revision with or without excision of the synovial cyst, are surgical options.

Niki and colleagues¹³ described a gigantic popliteal synovial cyst caused by wear particles after TKA. In this report, the surgeon performed a synovectomy and polyethylene liner exchange with retention of prosthetic components. At 12-month follow-up, the patient was reported to be doing well.

Mavrogenis and coauthors¹⁴ reported a wear debris–induced pseudotumor in the popliteal fossa and calf after TKA. In this case, in addition to the synovectomy, the surgeon removed all prosthetic components and used a semi-constrained implant to revise the knee. At 30-month follow-up, the patient reported having a painless knee.

While case reports have indicated that revision TKA for large, painful synovial cysts is a reasonable treatment option in carefully selected patients, there is a paucity of literature on this subject. Moreover, the present case appears to be the first literature report of a tibial nerve compressive neuropathy secondary to a synovial cyst after TKA.

Conclusion

In this report, polyethylene wear disease after TKA resulted in a massive synovial cyst extending into the posterior compartment of the leg. A progressive peripheral neuropathy confirmed by electromyography was also discovered. The patient underwent revision of a loose patellar component and worn polyethylene liner with complete synovectomy plus decompression of the cyst via needle aspiration. This resulted in an excellent short-term outcome with resolution of pain and significant improvement of the peripheral neuropathy 3 months after surgery.