Asymptomatic vasculitic neuropathy.

INTRODUCTION: We performed a retrospective analysis of the clinical, pathological, and electrophysiological features of 21 cases of Asymptomatic vasculitic neuropathy (AsVN). METHODS: Among 270 patients with biopsy-proven vasculitic neuropathy, we identified 21 (7.8%) who had asymptomatic neuropathy. RESULTS: Of the 21 patients with AsVN, 11 were women and 10 were men. Their mean age was 62.5 years. Referring physicians suspected systemic vasculitis on the basis of clinical and laboratory features, but none of the patients had neuropathy by examination. Screening nerve conduction studies identified neuropathy in all patients, leading us to perform a sural nerve biopsy, which confirmed the diagnosis of vasculitis. Twelve patients had active (type I), 6 had inactive (type II), and 3 had probable (type III) vasculitis. Vasculitis was primary in 10 patients and secondary in 11. CONCLUSIONS: Nerve conduction study is an important tool for identifying AsVN, a subtype of vasculitic neuropathy.

Epidemiological features of amyotrophic lateral sclerosis in a large clinic-based African American population.

Our objective was to identify the main clinical and epidemiological features of ALS in a large cohort of African American (AA) patients and compare them to Caucasian (CA) patients in a clinic-based population. We retrospectively identified 207 patients who were diagnosed with ALS based on the revised El Escorial criteria (60 AA and 147 CA subjects). Patients were seen in the Neuromuscular Division at the University Medical Center. We compared epidemiological and clinical features of these two groups, focusing on age of onset and diagnosis, clinical presentation and survival. Results showed that AA patients had a significantly younger age of disease onset (55 years vs. 61 years for CA, p = 0.011) and were diagnosed at an earlier age (56 years vs. 62 years, p = 0.012). In younger ALS patients (< 45 years of age), there was a significant difference in gender frequency, with females predominating in the AA population and males in the CA population (p = 0.025). In a multivariable Cox proportional hazard model, survival rates were not different between the groups. In both groups, survival significantly increased with younger age. In conclusion, AA patients presented at an earlier age, but there was no difference in survival compared to CA patients. A gender reversal occurred in younger ALS patients, with AA patients more likely to be female and CA patients more likely to be male.

Different characteristic phenotypes according to antibody in myasthenia gravis.

OBJECTIVES: To find the characteristic phenotypes of 3 different types of myasthenia gravis (MG). METHODS: The clinical and electrophysiological features among 15 cases of muscle-specific kinase antibody positive (MuSK Ab+) MG, 59 cases of double seronegative (DSN) MG, and 161 cases of acetylcholine receptor antibody (AChR Ab)+ MG in the University of Alabama at Birmingham were compared. RESULTS: AChR Ab was positive in 69% of cases and MuSK Ab in 6% of cases. MuSK Ab+ MG was more common (14%) in African Americans compared with whites (4%). AChR Ab+ MG is characterized by male predominance, later onset, a fewer cases of ocular MG, and a higher association with thymoma. DSN-MG is characterized by a greater prevalence of ocular MG, milder forms of MG with less number of crisis, and fewer abnormalities in the repetitive nerve stimulation test. MuSK Ab+ MG is characterized by younger age at onset, severe and bulbar forms of MG, predominant faciobulbar neck weakness, and a poor response to edrophonium, anticholinesterase, and intravenous immunoglobulin. Long-term outcome showed no difference among 3 types of MG. CONCLUSIONS: AChR Ab+ MG and DSN-MG are similar, with the exception of less severity in the latter. MuSK Ab+ MG has distinct clinical and electrophysiological features.

Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience.

We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.

3,4-Diaminopyridine is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS.

The purpose of this study was to investigate the clinical and electrophysiological efficacy of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS) in a randomized, double-blind, cross-over drug trial. The diagnosis of LEMS was made based on the combination of fluctuating muscle weakness, diminished or absent reflexes, and more than 60% increment of the compound muscle action potential (CMAP) amplitude after brief exercise or 50-HZ stimulation on a repetitive nerve stimulation (RNS) test. Evaluations were done at baseline, with placebo, and with 3,4-DAP (up to 75-80 mg/day). Assignment of placebo or 3,4-DAP was done in a double-blinded manner. Measurements included subjective symptoms score, objective clinical measurements [LEMS classification, muscle strength score, quantitative myasthenia gravis (QMG) score] and RNS test and single-fiber electromyography (SFEMG). The differences between placebo and baseline values (placebo change) were compared with the differences between 3,4-DAP and baseline or placebo values (DAP change). Seven patients with LEMS (QMG score >9) participated in the study. One patient had major side-effects with 3,4-DAP and withdrew from the study. Statistically significant efficacy was noted with DAP change (N = 13) compared with placebo change (N = 7) according to the subjective symptoms score (P = 0.01), LEMS classification (P < 0.001), muscle strength score (P < 0.006), QMG score (P = 0.02), and CMAP (P = 0.03). For long-term treatment, 2 patients preferred 3,4-DAP, 1 chose guanidine hydrochloride, 1 preferred pyridostigmine, and 2 chose no treatment. A randomized, double-blind, cross-over drug trial of 3,4-DAP showed significant efficacy over placebo in patients with LEMS. As a long-term treatment, however, not all patients preferred this drug.

Racial differences in myasthenia gravis in Alabama.

Demographic, clinical, and laboratory features were compared in 235 white and African-American (AA) patients with myasthenia gravis (MG) at the University of Alabama at Birmingham Neuromuscular Disease Clinic from May 2003 to January 2008. Seventy nine percent of patients were white. Acetylcholine receptor antibody was positive in 71% of white patients and in 59% of AA. In patients with seronegative generalized MG, the rate of positive muscle-specific tyrosine kinase antibody (MuSK-Ab) was significantly higher in AA than it was in whites (50% in AA vs. 17% in whites). Ocular MG was seronegative in 75% of AA patients. In AA, MG occurred earlier and more frequently in females, whereas, in whites, disease onset was later and more common in males. Another significant difference was a higher percentage of abnormality on repetitive nerve stimulation in AA. There was also a tendency for more severe forms of MG in AA. There are racial differences in MG between whites and AA in Alabama. These racial differences highlight the need to study biological factors in the pathogenesis of MG and to assess different approaches in diagnosis and treatment.

Statins may aggravate myasthenia gravis.

Statin-induced myopathy is well-known, but the effect of cholesterol-lowering agents on myasthenia gravis (MG) has not been studied in detail. We investigated statin use and its effects on MG among patients with this disease. Statin information was systemically obtained from 170 patients being treated at the Neuromuscular Disease Clinic at the University of Alabama at Birmingham. When a new myalgic syndrome or worsening of MG developed within 4 months after statin treatment, no other likely cause was found, and clinical improvement occurred either with or without discontinuation of the statin, we considered these symptoms to be statin-induced. Fifty-four patients (31%) were on statins. The statin group had proportionally more males, and older patients compared with the non-statin group. A myalgic syndrome was noted in 7 (13%) patients, but it resolved without any sequelae after withdrawal of the statin. MG worsening occurred in 6 (11%) patients without regard to type of MG or brand of statin. MG worsening occurred independently of myalgic syndrome and involved predominantly oculobulbar symptoms within 1-16 weeks of statin treatment. In 4 patients, additional treatment was needed to reverse MG worsening. Statins are safe in the majority of MG patients, but their use must be accompanied by close observation for possible MG worsening.

Anti-Hu antibody neuropathy: a clinical, electrophysiological, and pathological study.

OBJECTIVE: The objective is to report the clinical, electrophysiological, and histopathological features of 16 patients with anti-Hu antibody neuropathy. METHODS: Clinical and electrophysiological data in 16 patients (11 females and 5 males) with positive anti-Hu antibody and nerve biopsy data in 9 cases were analyzed. RESULTS: Cancer was detected in 11 patients, including 9 with small-cell lung cancer. Classical paraneoplastic subacute sensory neuronopathy (SSN) and/or encephalomyelitis (EM) was observed in 7 patients (44%), including 5 with SSN. The most common clinical feature was sensory-motor neuropathy (SMN), accounting for 50% of cases. Though sensory nerve conduction abnormality was the prominent feature in 14 (88%) cases, sensory and motor nerve conduction was abnormal in all cases. Motor nerve conduction findings were typical of axonal degeneration. The most common nerve conduction pattern was that of SMN, with a sensory neuronopathy pattern being observed in only 3 cases. Sural nerve biopsy in 9 patients showed axonal degeneration in all cases and inflammatory cells in 4 cases. CONCLUSIONS: Classical sensory neuronopathy is rarer than expected, both clinically and electrophysiologically. Motor involvement is not uncommon and motor nerve conduction abnormality is frequently seen. A diverse clinical and electrophysiological, and histopathological spectrum was observed in this neuropathy. SIGNIFICANCE: New guidelines for the selection of patients for anti-Hu antibody test are recommended.

Clinical nerve conduction and needle electromyography studies.

The electrodiagnostic study, consisting of nerve conduction studies and needle electromyography, is a useful adjunct to the clinical examination of the peripheral nervous system. The three types of nerve conduction study are motor, sensory, and mixed, of which motor is the least sensitive. Electromyography records the intrinsic electrical activity of muscle fibers, thus providing the physiologic status of muscle function. To interpret the electrodiagnostic study results, the clinician must understand the anatomic and physiologic basis of the studies. Peripheral nerve entrapment initially results in focal demyelination; thus, nerve conduction velocity slows across the site. However, with radiculopathy and nerve root compression, the nerve conduction study may be normal. Both nerve trauma and polyneuropathy show marked differences in their effect on the results of electrodiagnostic studies.

Control motor y nocicepción: parte II: hemiespasmo facial y toxina botulínica / Motor control and nociception: parte II: hemifacial spasm and botulinum toxin

Quince sujetos, 9 con hemiespasmo facial y 6 controlados, neurológica y neurofisiológicamente normales, fueron investigados en el laboratorio. Los 9 pacientes tenían una edad promedio de 57.4 años y una duración promedio de la enfermedad de 22.2 meses. En todos los pacientes se practicó el reflejo orbicular de los ojos de acuerdo con metodologías validadas en estudios previos, a nivel internacional. En 5 de los 9 pacientes y en los controles se pudo registrar el ROO de manera simultánea, tanto en el músculo orbicularis oculi (MOO) como en el músculo orbicularis oris (MOOr) bilateralmente. El ROO se practicó en los pacientes antes y después de la aplicación de toxina botulínica. Las latencias y las amplitudes de las respuestas obtenidas se midieron pre y post toxina botulínica en el MOO y en el MOOr. El detectar respuestas anormales en pacientes con HeFa, en músculos distantes al sitio de estimulación como aquellos observados a nivel contralateral del NeSo estimulado, sugiere que en esta patología estas respuestas aparecen no sólo por las sinkinesias neurales que se desarrollan en el curso de la enfermedad sino que además existe una hiperexcitabilidad neuronal alrededor de las interneuronas del tallo cerebral que median esta clase de respuestas. De otro lado, la modificación de la actividad anormal que produce la aplicación de la toxina botulínica se debe no sólo a la acción de la misma a nivel local en la unión neuromuscular, sino que existe además una modificación de la información aferente a nivel supraespinal con subsecuente reorganización del programa central del control motor en los humanos