Smads as muscle biomarkers in amyotrophic lateral sclerosis.

OBJECTIVE: To identify molecular signatures in muscle from patients with amyotrophic lateral sclerosis (ALS) that could provide insight into the disease process and serve as biomarkers. METHODS: RNA sequencing was performed on ALS and control muscle samples to identify Smad family members as potential markers of disease. Validation studies were performed in a cohort of 27 ALS patients and 33 controls. The markers were assessed in the G93A superoxide dismutase (SOD)1 mouse at different stages of disease and in a model of sciatic nerve injury. RESULTS: Smad8, and to a lesser extent Smad1 and 5, mRNAs were significantly elevated in human ALS muscle samples. The markers displayed a remarkably similar pattern in the G93A SOD1 mouse model of ALS with increases detected at preclinical stages. Expression at the RNA and protein levels as well as protein activation (phosphorylation) significantly increased with disease progression in the mouse. The markers were also elevated to a lesser degree in gastrocnemius muscle following sciatic nerve injury, but then reverted to baseline during the muscle reinnervation phase. INTERPRETATION: These data indicate that Smad1, 5, 8 mRNA and protein levels, as well as Smad phosphorylation, are elevated in ALS muscle and could potentially serve as markers of disease progression or regression.

Electromyography tests in patients with implanted cardiac devices are safe regardless of magnet placement.

METHODS: We compared the problems or complications associated with electrodiagnostic testing in 77 patients with implanted cardiac devices. Thirty tests were performed after magnet placement, and 47 were performed without magnet application. RESULTS: All electrodiagnostic tests were performed safely in all patients without any serious effect on the implanted cardiac devices with or without magnet placement. A significantly higher number of patient symptoms and procedure changes were reported in the magnet group (P < 0.013). No statistical difference was found in the testing difficulty or ECG changes. CONCLUSION: The magnet group patients had an approximately 11-fold greater risk of symptoms than those in the control group. Our data do not support a recommendation that magnet placement is necessary for routine electrodiagnostic testing in patients with implanted cardiac devices, as long as our general and specific guidelines are followed.

Clinical utility of sensory nerve conduction of medial femoral cutaneous nerve.

INTRODUCTION: In this investigation we report on the clinical utility of sensory nerve conduction studies of the medial femoral cutaneous (MFC) nerve. METHODS: Sensory nerve conduction of the MFC nerve was assessed in 22 patients for whom this test was considered clinically necessary. RESULTS: MFC nerve conduction was abnormal in 4 cases of MFC neuropathy. The most common cause was iatrogenic in 14 femoral neuropathy cases. MFC nerve conduction showed absent or low-amplitude sensory nerve action potential (SNAP) in 13 cases, with femoral motor nerve conduction abnormal in 5 cases. In 2 cases with acute lumbar plexopathy, the MFC SNAP was absent unilaterally. MFC nerve conduction was normal in 1 case with diabetic lumbar radiculopathy and in another case with postpolio syndrome. CONCLUSION: Assessment of MFC nerve conduction is extremely useful in the diagnosis of femoral neuropathy, medial femoral cutaneous neuropathy, and lumbar plexopathy.

Abnormal dip phenomenon: a characteristic electrophysiological marker in interdigital neuropathy of the foot.

OBJECTIVE: The nerve conduction findings in interdigital neuropathy of the foot (IDN; Morton's neuroma) have rarely been reported. We analyzed the nerve conduction data in 23 patients with suspected IDN studied between 1982 and 2002. METHOD: Diagnosis of IDN was made on the basis of clinical features. All patients underwent routine nerve conduction studies and a near-nerve needle sensory nerve conduction study of the interdigital nerves by Oh's method in the symptomatic foot. RESULTS: Of the 23 patients, the diagnosis of definite IDN was made in 13 cases and of possible NDN in the others cases. Nineteen were females. Twenty two patients had only one nerve affected. One patient had two nerves affected. The III-IV interdigital nerve was affected in 17 cases and the II-III interdigital nerve in 7 cases. The near-nerve needle nerve conduction showed abnormality in the affected interdigital nerves in all definite IDN cases and confirmed the diagnosis of IDN in 10 cases by the abnormal dip phenomenon (a selective decrease of 50% or more in the sensory CNAP amplitude of the affected nerve compared with that of the preceding interdigital nerve). In 11 possible IDN cases, IDN was identified by the abnormal dip phenomenon. CONCLUSION: The near-nerve needle sensory nerve conduction of the interdigital nerves is a highly sensitive diagnostic test, and abnormal dip phenomenon is the most characteristic electrophysiological marker for the diagnosis of IDN.

Abnormal dip phenomenon: a characteristic electrophysiological marker in interdigital neuropathy of the foot

OBJECTIVE: The nerve conduction findings in interdigital neuropathy of the foot (IDN; Morton's neuroma) have rarely been reported. We analyzed the nerve conduction data in 23 patients with suspected IDN studied between 1982 and 2002. METHOD: Diagnosis of IDN was made on the basis of clinical features. All patients underwent routine nerve conduction studies and a near-nerve needle sensory nerve conduction study of the interdigital nerves by Oh's method in the symptomatic foot. RESULTS:Of the 23 patients, the diagnosis of definite IDN was made in 13 cases and of possible NDN in the others cases. Nineteen were females. Twenty two patients had only one nerve affected. One patient had two nerves affected. The III-IV interdigital nerve was affected in 17 cases and the II-III interdigital nerve in 7 cases. The near-nerve needle nerve conduction showed abnormality in the affected interdigital nerves in all definite IDN cases and confirmed the diagnosis of IDN in 10 cases by the abnormal dip phenomenon (a selective decrease of 50 percent or more in the sensory CNAP amplitude of the affected nerve compared with that of the preceding interdigital nerve). In 11 possible IDN cases, IDN was identified by the abnormal dip phenomenon. CONCLUSION: The near-nerve needle sensory nerve conduction of the interdigital nerves is a highly sensitive diagnostic test, and abnormal dip phenomenon is the most characteristic electrophysiological marker for the diagnosis of IDN.

OBJETIVO: Os achados da condução nervosa na neuropatia interdigital do pé (NIP) têm sido raramente descritos. Nós analisamos os dados da condução nervosa de 23 pacientes com suspeita de NIP entre 1982 e 2002. MÉTODO: O diagnóstico de NIP foi clínico. Todos os pacientes foram submetidos a estudos de condução nervosa de rotina e ao estudo de condução sensitiva dos nervos interdigitais com agulha justa-neural pelo método de Oh. RESULTADOS: Dos 23 pacientes, o diagnóstico de NIP foi definitivo em 13 casos é possível nos demais. Dezenove pacientes eram mulheres e 22 tinham somente um nervo afetado. Apenas um paciente teve dois nervos comprometidos. O nervo interdigital III-IV foi afetado em 17 casos e o nervo interdigital II-III em 7 casos. A condução nervosa justa-neural foi anormal nos nervos interdigitais acometidos em todos os casos definitivos e confirmou o diagnóstico de neuropatia interdigital em 10 casos pelo fenômeno da diminuição de amplitude anormal (uma diminuição seletiva de 50 por cento ou mais da amplitude do PANS do nervo afetado quando comparado com o nervo anterior. Em 11 casos possíveis, a neuropatia interdigital foi identificada pelo fenômeno da diminuição de amplitude anormal. CONCLUSÃO: A condução nervosa sensitiva justa-neural dos nervos interdigitais do pé é um teste diagnóstico altamente sensível e o fenômeno da diminuição da amplitude anormal é o marcador eletrofisiológico mais característico para o diagnóstico de neuroma de Morton.

Electrophysiological differences in seropositive and seronegative Lambert-Eaton myasthenic syndrome.

In order to determine whether there is any difference between voltage-gated calcium-channel antibody (VGCC-Ab)-positive and -negative groups in Lambert-Eaton myasthenic syndrome (LEMS), we compared the clinical and electrophysiological features between 13 patients with VGCC-Ab and 6 VGCC-Ab-negative patients. No obvious difference was observed in the various clinical features or findings on single-fiber electromyography between seropositive and seronegative cases. In seropositive cases, the compound muscle action potential (CMAP) amplitude was lower but the increment on post-exercise facilitation (PEF) and high-rate stimulation (HRS) was significantly higher than in the seronegative group, indicating that the repetitive nerve stimulation (RNS) test in the seropositive group is more typical of LEMS and more severe. A 100% increment as the diagnostic criterion in the routine RNS test was satisfied in all seropositive cases but in only three seronegative cases, whereas a 60% increment as the diagnostic criterion was found in all seronegative cases. The classic triad (low CMAP amplitude, decrement at low rate of stimulation, and increment at PEF or HRS) of RNS is rare, adding to the difficulty in diagnosing LEMS in the seronegative group, and making a 60% increment criterion more critical for the diagnosis of this disorder.

Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis.

To better define electrophysiological abnormalities in myasthenia gravis (MG) patients with muscle-specific tyrosine kinase (MuSK) antibodies (Ab), we compared electrophysiological features of 14 MuSK Ab-positive, 73 acetylcholine receptor antibody (AChR Ab)-positive, and 22 MuSK and AChR Ab-negative (seronegative) patients with generalized disease. Repetitive nerve stimulation (RNS) abnormalities were observed in 86% of MuSK Ab-positive and 82% of AChR Ab-positive patients but in only 55% of seronegative patients. RNS decrements in the orbicularis oculi were more common and severe in the MuSK Ab-positive patients than the other two groups. Single-fiber electromyography (SFEMG) of the extensor digitorum communis was abnormal in 90% of MuSK Ab-positive patients. The high frequency of RNS abnormalities in facial muscles in the MuSK Ab-positive population reflects the propensity for facial muscle involvement in this form of MG and emphasizes the importance of including facial muscles in RNS protocols when evaluating these patients.

Electrophysiological diagnostic criteria of Lambert-Eaton myasthenic syndrome.

Various parameters of the repetitive nerve stimulation (RNS) test of the abductor digiti quinti muscle were analyzed statistically in 34 patients with Lambert-Eaton myasthenic syndrome (LEMS). The sensitivity and specificity of the increments after exercise and after 50-HZ stimulation for the diagnosis of LEMS were compared with reference values in 40 normal subjects and data from 538 tests in patients with myasthenia gravis (MG). When we used a 100% increment (the "gold standard") as the normal limit for the postexercise facilitation (PEF) or the high-rate stimulation (HRS) test, the diagnosis of LEMS was confirmed in 29 (85%) cases. When a 60% increment was used as the normal limit, the diagnosis of LEMS was made in 97% of cases. In MG, a 60% increment was observed in only 4 of 538 cases by HRS and in none by the exercise test. Thus, the use of a 60% increment showed a sensitivity of 97% for the diagnosis of LEMS and a specificity of 99% in excluding MG. A 60% increment in either the PEF or HRS test for the diagnosis of LEMS is a desirable alternative to the 100% increment previously considered to be the gold standard for this diagnosis.

Myokymia, neuromyotonia, dermatomyositis, and voltage-gated K+ channel antibodies.

A young woman presented with facial myokymia in association with dermatomyositis. There was no evidence of peripheral neuropathy. Needle electromyography showed prominent myokymic discharges and brief neuromyotonic discharges in addition to many small-amplitude, short-duration motor unit potentials. Myokymia and dermatomyositis both responded to immunosuppressive treatment. The presence of antibodies to voltage-gated potassium channels and the association with dermatomyositis indicated an autoimmune cause for myokymia, which may have been due to reversible peripheral nerve hyperexcitability.

Respiratory failure in lambert-eaton myasthenic syndrome precipitated by calcium-channel blockers: report of a case and literature review.

There have been a few reports in the literature documenting the effects of calcium-channel blockers in Lambert-Eaton myasthenic syndrome (LEMS). We report a case of a patient with LEMS who developed respiratory failure after administration of diltiazem and verapamil. A patient with LEMS, associated with small-cell carcinoma in remission, developed multifocal atrial tachycardia, necessitating the use of diltiazem and verapamil, which led to respiratory failure and intubation 5 days after admission. The patient was taken off all calcium-channel blockers and weaned off the respirator after 6 days. Oral time-release diltiazem was restarted without further exacerbation of LEMS. Most likely the combined use of two different calcium-channel blockers, verapamil and diltiazem, was responsible for this patient's respiratory failure. To date, 5 cases (2 patients with LEMS and 3 with myasthenia gravis) in which cardiac calcium-channel blockers had a definite detrimental effect have been reported.