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.

ContributorsGIW wrote and revised the manuscript in response to co-author comments. He finalized all the figures and tables, performed the literature search, and assisted with data interpretation. HJK critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. IBA performed the data analysis, constructed the figures and tables, and made important suggestions to improve the manuscript. H-CK assisted with the data analysis and also reviewed the manuscript. GRC critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. All other authors were given the opportunity to review the manuscript and make suggestions which GIW received, either revising the paper or providing explanations. All who are not deceased were involved with approval of the manuscript.

A significant increase in hyperphosphorylated tau proteins (P-tau) in CSF has been shown in Alzheimer disease (AD), suggesting potential utility as biologic markers of AD. 1 Different subtypes of P-tau proteins perform differently in the discrimination of primary dementia disorders from AD. 2 Recently, we have shown that tau phosphorylated at threonine 231 (P-tau 231P ) correlates with cognitive decline in subjects with mild cognitive impairment (MCI), 3 a group at risk for AD. 4 Here, we examined in an exploratory study whether different P-tau epitopes differ in their accuracy to predict cognitive deterioration within subjects with MCI. Therefore, previously published results on P-tau 231P are again presented briefly for comparison. Moreover, we wished to know whether a combination of different P-tau epitopes is superior to a single P-tau marker for the prediction of cognitive decline.Three P-tau subtypes were measured at baseline in 59 patients with MCI. 4 Clinical follow-up was performed in all patients (mean interval 12.27 months, range 6 to 42 months). The mean (SD) age of the MCI patients (28 female) was 72.56 (7.6) years with a mean Mini-Mental State Examination (MMSE) score of 28.0 (1.9). There were 23 healthy control subjects (HC; 14 female; age 60.0 Ϯ 10.1 years; MMSE 29.2 Ϯ 0.7 points). Study subjects were recruited at two centers (Department of Psychiatry, Ludwig Maximilian University, Munich, Germany, and Department of Clinical Neuroscience, Göteborg, Sweden). P-Tau epitopes including P-tau 231P , tau protein phosphorylated at threonine 181 (P-tau 181P ), and serine 199 (P-tau 199P ) were measured using ELISAs. 2,3 Prediction of annual rate of cognitive decline (measured by MMSE change) was tested for each P-tau epitope in a separate multiple linear regression model. With use of a forward selection method, for each model, age, gender, MMSE at baseline, duration of interval, center, treatment with cognitive enhancers, and the baseline level of the respective P-tau epitope were entered as variables. A variable was entered into the model if the p value

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.

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.

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ObjectivesChronic inflammatory axonal polyneuropathy (CIAP) is defined on the basis of the clinical, electrophysiological and nerve biopsy findings and therapeutic responses of ‘immunotherapy responding chronic axonal polyneuropathy (IR-CAP)’.MethodsThe diagnosis of IR-CAP was made when all of three of the following mandatory criterion were met: (1) acquired, chronic progressive or relapsing symmetrical or asymmetrical polyneuropathy with duration of progression >2 months; (2) electrophysiological evidence of axonal neuropathy in at least two nerves without any evidence of ‘strict criteria of demyelination’; and (3) definite responsiveness to immunotherapy.ResultsThirty-three patients with IR-CAP showed similar clinical features of chronic inflammatory demyelinating polyneuropathy (CIDP) except ‘motor neuropathy subtype’. High spinal fluid protein was found in 27/32 (78%) cases. ‘Inflammatory axonal neuropathy’ was proven in 14 (45%) of 31 sural nerve biopsies.DiscussionsIR-CAP could well be ‘axonal CIDP’ in view of clinical similarity, but not proven as yet. Thus, IR-CAP is best described as CIAP, a distinct entity that deserves its recognition in view of responsiveness to immunotherapy.ConclusionDiagnosis of CIAP can be made by additional documentation of ‘inflammation’ by high spinal fluid protein or nerve biopsy in addition to the first two diagnostic criteria of IR-CAP.

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.