- Email: [email protected]
74. Idiopathic hyperhomocysteinemia and peripheral neuropathy
e110
Society Proceedings / Clinical Neurophysiology 120 (2009) e89–e126
Objectives: To maximize the diagnostic utility of electrodiagnostic studies for early DPN recognition. Methods: Subjects with diabetes without neuropathy or with <5 years of symptoms underwent nerve conduction studies (NCSs), vibration and cold detection thresholds using quantitative sensory threshold (QST), quantitative sudomotor axon reflex testing, and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Subjects are classified as having neuropathy based on symptoms and test abnormalities (0: no, 1–2: possible, 3: definite). The prevalence of abnormal tests was determined and receiver operating characteristic (ROC) analysis performed. Results: Among 221 subjects, 45% have possible neuropathy, 38% have definite neuropathy, and 17% have no neuropathy. Of those with definite DPN, 97% exhibited signs or symptoms. NCSs were abnormal in 43%. Even when all other neuropathy measures are abnormal, only 50% have abnormal NCSs. ROC analysis indicates a similar degree of diagnostic utility for NCSs, QST, and IENFD (area under the curve; 0.77). A sural sensory cutoff of 6 uV results in excellent specificity (87%) but poor sensitivity (54%). The sural amplitude demonstrating the best balance of sensitivity and specificity is 8.4 lV with a peroneal motor conducting velocity of 42.8ms (70% sensitivity and specificity for each). Conclusions: Commonly used population-derived normative NCS values have poor diagnostic sensitivity. ROC analysis suggests the optimal diagnostic threshold is lower in this high-risk population. A Bayesian approach to DPN diagnosis may be preferable. Study supported by grant R01-KD064814. doi:10.1016/j.clinph.2008.10.091
74. Idiopathic hyperhomocysteinemia and peripheral neuropathy—J.J. Luo, F. Bumanlag, A. Nouh, J. Song, X. Yang, H. Wang, N. Dun (Philadelphia, PA, USA) Introduction: Homocysteine is an intermittent metabolite of methionine. Hyperhomocysteinemia (HHcy) could be caused by a deficiency of vitamin B12 and/or folic acid. HHcy produces various neurovascular morbidities including stroke and dementia. HHcy also potentiates diabetic neuropathy. The authors previously reported that HHcy may act as an independent risk factor for the development of peripheral neuropathy (PN). The additional evidence of HHcy causing PN is presented. Objective: To report clinical, laboratory, and neuroelectrodiagnostic findings of PN that may be caused by idiopathic HHcy. Methods: Consecutive patients with PN seen in a neuromuscular clinic, from October 1, 2004, to February 28, 2008, were studied. Clinical history, physical examination, and laboratory data including plasma level of homocysteine, methylmalonic acid, B12, folic acid, mean corpuscular volume, glucose, creatinine, lipids, hepatitis profile, erythrocyte sedimentation rate, anti-nuclear antibodies, thyroid stimulating hormone, rapid plasma reagin, and Lyme titters, and neuroelectrodiagnostic findings, were collected. Patients with identifiable etiology for PN, such as metabolic, toxic, endocrinologic, infectious, inflammatory, renal or liver diseases, were excluded. Results: A total of 347 patients with PN were initially identified. Of these, 22 subjects (age: 64.9 ± 11.3 years old, mean ± SD, range: 36-81, M/F = 13/9) were found to have HHcy (18.2 ± 7.4 lmol/L; range: 12.1–44.1, normal: <11.4), but they exhibited other normal laboratory findings. All subjects complained of numbness and tingling. A neurological examination showed that all had a glove-stocking pattern of sensory deficits. Neurophysiology studies demonstrated large fiber neuropathy (8/15) and carpal tunnel syndrome (3/15). The incidence is estimated at 1.81% in patients with PN caused by idiopathic HHcy.
Conclusions: The data suggest that idiopathic HHcy may cause PN. Early identifying HHcy in those patients and promptly initiating treatment are warranted. doi:10.1016/j.clinph.2008.10.092
75. Lewis-sumner syndrome associated with infliximab therapy in rheumatoid arthritis—D.R. Hooper, S.K. Baker, M.A. Tarnopolsky (Hamilton, Ont., Canada) Introduction: The authors present two cases of Lewis-Sumner syndrome (LSS) associated with infliximab therapy for rheumatoid arthritis (RA). Case Report 1: A 60-year-old female with RA developed a gradual onset of predominantly left arm paresthesiae and weakness in multiple nerve territories 3 months after initiation of infliximab. Electrodiagnostic examination demonstrated definite conduction block in the forearm of the left median nerve. Investigations for vasculitis, human immunodeficiency virus, hepatitis, anti-GM1 antibodies, and protein electrophoresis were unremarkable. Sural nerve biopsy demonstrated mild large fiber axonopathy. Monthly treatment with intravenous immunoglobulin (IVIg) led to gradual improvement. Cyclophosphamide, later replaced by azathioprine, was added to intensify immunosuppression. Sensorimotor deficits resolved within 4 years. The patient continues to receive IVIg. Case Report 2: A 47-year-old male with RA experienced a gradual onset of sensory loss and weakness in a mononeuropathy multiplex pattern 7 months after starting infliximab. On consultation, the patient reported reduced facial sensation with stocking-glove loss in the limbs. Weakness affecting the arms was greater proximally than distally. The left leg was also affected. Electrodiagnostic examination revealed multiple definite and probable conduction blocks in the upper and lower extremities. Investigations for vasculitis, sarcoid, paraneoplastic, and anti-GM1 antibodies were unremarkable. Lumbar puncture indicated mildly increased albumin. Treatment with monthly infusions of IVIg led to moderate strength gains. IVIg interval was reduced and azathioprine was added. Quantitative strength measurements demonstrated progressive gains despite persistent conduction blocks. Conclusions: The two cases support the concept that infliximabinduced LSS is responsive to IVIg. This report adds to the phenotype variability of anti-TNFa-induced neuropathy. D.R. Hooper is a Junior Member Recognition Award Recipient. doi:10.1016/j.clinph.2008.10.093
76. Compressive mononeuropathies in diabetic subjects with or without neuropathy—J.C. Wagner, J.R. Singleton, B. Bixby, C. Dolan, C.J. Aresnault, A. Burch, A.G. Smith (Salt Lake City, UT, USA) Objectives: To determine the prevalence of carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in diabetic subjects with and without neuropathy and other potential risk factors. Methods: Symptoms and signs of CTS and UNE were sought, and nerve conduction data were gathered. Quantitative sensory testing, quantitative sudomotor axon reflex testing, clinical scales, body mass index (BMI), skin biopsies, lipid panel and 24-hour urine albumin were obtained. Subjects were categorized as having no neuropathy, possible neuropathy or definite neuropathy. Electrodiagnostic (EDX) CTS was defined as median minus ulnar sensory peak latency greater than 0.4 ms or motor latency difference greater than 1.4 ms. UNE was defined as 10 m/s or greater slowing of conduction velocity across the elbow.
Society Proceedings / Clinical Neurophysiology 120 (2009) e89–e126
Objectives: To maximize the diagnostic utility of electrodiagnostic studies for early DPN recognition. Methods: Subjects with diabetes without neuropathy or with <5 years of symptoms underwent nerve conduction studies (NCSs), vibration and cold detection thresholds using quantitative sensory threshold (QST), quantitative sudomotor axon reflex testing, and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Subjects are classified as having neuropathy based on symptoms and test abnormalities (0: no, 1–2: possible, 3: definite). The prevalence of abnormal tests was determined and receiver operating characteristic (ROC) analysis performed. Results: Among 221 subjects, 45% have possible neuropathy, 38% have definite neuropathy, and 17% have no neuropathy. Of those with definite DPN, 97% exhibited signs or symptoms. NCSs were abnormal in 43%. Even when all other neuropathy measures are abnormal, only 50% have abnormal NCSs. ROC analysis indicates a similar degree of diagnostic utility for NCSs, QST, and IENFD (area under the curve; 0.77). A sural sensory cutoff of 6 uV results in excellent specificity (87%) but poor sensitivity (54%). The sural amplitude demonstrating the best balance of sensitivity and specificity is 8.4 lV with a peroneal motor conducting velocity of 42.8ms (70% sensitivity and specificity for each). Conclusions: Commonly used population-derived normative NCS values have poor diagnostic sensitivity. ROC analysis suggests the optimal diagnostic threshold is lower in this high-risk population. A Bayesian approach to DPN diagnosis may be preferable. Study supported by grant R01-KD064814. doi:10.1016/j.clinph.2008.10.091
74. Idiopathic hyperhomocysteinemia and peripheral neuropathy—J.J. Luo, F. Bumanlag, A. Nouh, J. Song, X. Yang, H. Wang, N. Dun (Philadelphia, PA, USA) Introduction: Homocysteine is an intermittent metabolite of methionine. Hyperhomocysteinemia (HHcy) could be caused by a deficiency of vitamin B12 and/or folic acid. HHcy produces various neurovascular morbidities including stroke and dementia. HHcy also potentiates diabetic neuropathy. The authors previously reported that HHcy may act as an independent risk factor for the development of peripheral neuropathy (PN). The additional evidence of HHcy causing PN is presented. Objective: To report clinical, laboratory, and neuroelectrodiagnostic findings of PN that may be caused by idiopathic HHcy. Methods: Consecutive patients with PN seen in a neuromuscular clinic, from October 1, 2004, to February 28, 2008, were studied. Clinical history, physical examination, and laboratory data including plasma level of homocysteine, methylmalonic acid, B12, folic acid, mean corpuscular volume, glucose, creatinine, lipids, hepatitis profile, erythrocyte sedimentation rate, anti-nuclear antibodies, thyroid stimulating hormone, rapid plasma reagin, and Lyme titters, and neuroelectrodiagnostic findings, were collected. Patients with identifiable etiology for PN, such as metabolic, toxic, endocrinologic, infectious, inflammatory, renal or liver diseases, were excluded. Results: A total of 347 patients with PN were initially identified. Of these, 22 subjects (age: 64.9 ± 11.3 years old, mean ± SD, range: 36-81, M/F = 13/9) were found to have HHcy (18.2 ± 7.4 lmol/L; range: 12.1–44.1, normal: <11.4), but they exhibited other normal laboratory findings. All subjects complained of numbness and tingling. A neurological examination showed that all had a glove-stocking pattern of sensory deficits. Neurophysiology studies demonstrated large fiber neuropathy (8/15) and carpal tunnel syndrome (3/15). The incidence is estimated at 1.81% in patients with PN caused by idiopathic HHcy.
Conclusions: The data suggest that idiopathic HHcy may cause PN. Early identifying HHcy in those patients and promptly initiating treatment are warranted. doi:10.1016/j.clinph.2008.10.092
75. Lewis-sumner syndrome associated with infliximab therapy in rheumatoid arthritis—D.R. Hooper, S.K. Baker, M.A. Tarnopolsky (Hamilton, Ont., Canada) Introduction: The authors present two cases of Lewis-Sumner syndrome (LSS) associated with infliximab therapy for rheumatoid arthritis (RA). Case Report 1: A 60-year-old female with RA developed a gradual onset of predominantly left arm paresthesiae and weakness in multiple nerve territories 3 months after initiation of infliximab. Electrodiagnostic examination demonstrated definite conduction block in the forearm of the left median nerve. Investigations for vasculitis, human immunodeficiency virus, hepatitis, anti-GM1 antibodies, and protein electrophoresis were unremarkable. Sural nerve biopsy demonstrated mild large fiber axonopathy. Monthly treatment with intravenous immunoglobulin (IVIg) led to gradual improvement. Cyclophosphamide, later replaced by azathioprine, was added to intensify immunosuppression. Sensorimotor deficits resolved within 4 years. The patient continues to receive IVIg. Case Report 2: A 47-year-old male with RA experienced a gradual onset of sensory loss and weakness in a mononeuropathy multiplex pattern 7 months after starting infliximab. On consultation, the patient reported reduced facial sensation with stocking-glove loss in the limbs. Weakness affecting the arms was greater proximally than distally. The left leg was also affected. Electrodiagnostic examination revealed multiple definite and probable conduction blocks in the upper and lower extremities. Investigations for vasculitis, sarcoid, paraneoplastic, and anti-GM1 antibodies were unremarkable. Lumbar puncture indicated mildly increased albumin. Treatment with monthly infusions of IVIg led to moderate strength gains. IVIg interval was reduced and azathioprine was added. Quantitative strength measurements demonstrated progressive gains despite persistent conduction blocks. Conclusions: The two cases support the concept that infliximabinduced LSS is responsive to IVIg. This report adds to the phenotype variability of anti-TNFa-induced neuropathy. D.R. Hooper is a Junior Member Recognition Award Recipient. doi:10.1016/j.clinph.2008.10.093
76. Compressive mononeuropathies in diabetic subjects with or without neuropathy—J.C. Wagner, J.R. Singleton, B. Bixby, C. Dolan, C.J. Aresnault, A. Burch, A.G. Smith (Salt Lake City, UT, USA) Objectives: To determine the prevalence of carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in diabetic subjects with and without neuropathy and other potential risk factors. Methods: Symptoms and signs of CTS and UNE were sought, and nerve conduction data were gathered. Quantitative sensory testing, quantitative sudomotor axon reflex testing, clinical scales, body mass index (BMI), skin biopsies, lipid panel and 24-hour urine albumin were obtained. Subjects were categorized as having no neuropathy, possible neuropathy or definite neuropathy. Electrodiagnostic (EDX) CTS was defined as median minus ulnar sensory peak latency greater than 0.4 ms or motor latency difference greater than 1.4 ms. UNE was defined as 10 m/s or greater slowing of conduction velocity across the elbow.