Shin J. Oh

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. Muscle Nerve, 2005

Sensory Guillain-Barré syndrome.

Objective: To report eight cases of sensory Guillain–Barré syndrome (GBS). Background: The concept of sensory equivalent to ascending paralysis of GBS was raised in 1958, and the diagnostic criteria for a sensory loss and areflexia variant of GBS were proposed in 1981. However, clinical cases meeting these criteria have been relatively scarce. Methods: During a 13-year period between 1986 and 1999, the authors collected eight cases of an acute sensory demyelinating neuropathy that met most of the proposed diagnostic criteria of a sensory variant of GBS. Results: In all patients, sensory neuropathy was sudden at onset and peaked to maximal deficit within 4 weeks. In five (63%) cases, there was an antecedent viral illness. All patients had objective sensory loss and diminished or absent reflexes. None showed any muscle weakness. In all four patients in whom the spinal fluid was examined during the first 4 weeks, there was albuminocytologic dissociation. All of the patients had electrophysiologic evidence of demyelination in at least two nerves. Demyelination was demonstrated in motor nerve conduction in seven patients and in sensory nerve conduction in one, indicating that motor nerve conduction studies were the key for the diagnosis of demyelinating neuropathy. All patients had sensory nerve conduction abnormalities in at least one nerve. Three patients responded to immunotherapies. All had a favorable outcome, with a monophasic course of disease and no sign of relapse. Conclusion: The current study confirms the existence of sensory GBS.

Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody-positive MG

Patients with seronegative myasthenia gravis (MG) often harbor antibodies for muscle-specific tyrosine kinase (MuSK).1 Nonresponsiveness or poor tolerability of anticholinesterase therapy has been mentioned in reports of this population2,3 but not comprehensively studied. We report anticholinesterase nonresponsiveness in 14 MuSK-antibody (Ab) positive patients seen at the University of Alabama at Birmingham (UAB) and University of Texas Southwestern Medical Center (UTSW), comparing them to MuSK-Ab-negative and acetylcholine receptor (AChR)-Ab seropositive patients from the UAB. Anticholinesterase hypersensitivity was defined when myasthenic symptoms worsened with medication; anticholinesterase intolerance when the patient developed severe cholinergic side effects with small doses of pyridostigmine or edrophonium, even with the administration of atropine or glycopyrrolate; and no improvement when there was no clinical benefit following administration of pyridostigmine. Hypersensitivity, intolerance, and no improvement were grouped together as anticholinesterase nonresponsiveness. At UAB, the AChR-Ab test was positive in 73 (72%) of 102 patients with generalized MG; the MuSK antibody test was positive in 7 (24%) of the …

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. Muscle Nerve, 2009

Anti-Hu-associated paraneoplastic sensory neuronopathy responding to early aggressive immunotherapy: Report of two cases and review of literature

Anti‐Hu‐associated paraneoplastic sensory neuropathy (PSN) has been reported to be nonresponsive to immunotherapy or cancer therapy. We report 2 patients with anti‐Hu‐associated PSN who achieved sustained clinical improvement with early and aggressive immunotherapy 10–15 months before the diagnosis of small‐cell lung carcinoma. Both had chronic “sensory neuronopathy plus”; in addition to sensory neuronopathy, case 1 had a motor‐autonomic dysfunction with encephalopathy, and case 2 had a motor‐autonomic dysfunction with swallowing difficulty. These two cases were unusual in that sustained clinical improvement was achieved with early aggressive immunotherapy before the detection of cancer and without any concomitant anticancer therapy or lowering of anti‐Hu antibody titer. We believe that early and aggressive immunotherapy should be tried in any patient with anti‐Hu‐associated PSN, as it may induce sustained clinical improvement.

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. Muscle Nerve, 2006

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.

Low‐dose guanidine and pyridostigmine: relatively safe and effective long‐term symptomatic therapy in Lambert‐Eaton myasthenic syndrome

Guanidine hydrochloride is known to be highly effective in the symptomatic treatment of the Lambert‐Eaton myasthenic syndrome (LEMS). However, because of its potentially dangerous side reactions of hematologic abnormalities and renal insufficiency, 3,4‐diaminopyridine, which is not readily available in the United States, is recommended as the preferred drug for LEMS. We used low‐dose guanidine and pyridostigmine combination therapy in 9 patients with LEMS and analyzed its long‐term safety and effectiveness. In all patients, a liberal amount of pyridostigmine was used, while daily guanidine dose was kept below 1000 mg a day, and guanidine was given between pyridostigmine dosings. This combination therapy was used for 3–102 months (mean: 34.1 months) and improved clinical status in all patients. Although guanidine had to be discontinued due to severe gastrointestinal symptoms in 3 cases, no serious side reactions such as bone marrow suppressions or signs of renal insufficiency developed in any case. Thus, we conclude that low‐dose guanidine therapy is relatively safe and effective for long‐term symptomatic treatment of LEMS when it is combined with pyridostigmine.

Large-fiber neuropathy in distal sensory neuropathy with normal routine nerve conduction

Near-nerve needle sensory nerve conduction of plantar nerves in 100 patients with distal sensory neuropathy with normal routine nerve conduction (DSN-NNC) found the definite neuropathy pattern (abnormality in more than three of six tested nerves) in 65%, axonal neuropathy in 35%, and the known cause in 37% of patients. Absent or diminished reflexes were a reliable indicator for large fiber neuropathy (LFN). This near-nerve needle plantar nerve study provides useful and unequivocal evidence of its value in identifying neuropathy in DSN-NNC by finding LFN in 65% of patients.

Carbohydrate metabolism in hypothyroid myopathy

The carbohydrate metabolism in hypothyroid patients was investigated. After an overnight fast, the blood glucose level was 24% lower and the blood lactate level was 35% lower in the untreated hypothyroid patients than that observed in the treated hypothyroid patients or in the normal subjects. There was no difference in the blood alanine or plasma free fatty acid values between the subject groups. Skeletal muscle biopsied from two hypothyroid patients with marked myopathy showed normal glycogen content, 0.83%-0.86% (normal 1.06%), but reduced activity of acid maltase, 32-50 nmoles/min/g (normal 97). Forearm ischemic stimulation applied to hypothyroid patients failed to elevate the level of lactate. The results are compatible with impaired glycogenolysis from the skeletal muscle, which may be a contributory factor in the myopathy in hypothyroidism.