3,4‐diaminopyridine base effectively treats the weakness of Lambert‐Eaton myasthenia

Introduction: 3,4‐diaminopyridine has been used to treat Lambert‐Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double‐blind placebo‐controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4‐diaminopyridine base (3,4‐DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up‐and‐go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self‐assessment of LEM–related weakness (W‐SAS). Results: Thirty‐two participants were randomized to continuous 3,4‐DAP or placebo groups. None of the 14 participants who received continuous 3,4‐DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P < 0.0001). W‐SAS similarly demonstrated an advantage for continuous treatment over placebo (P < 0.0001). Requirement for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4‐DAP in the maintenance of strength in LEM. Muscle Nerve 57 : 561–568, 2018     

“Dropped head syndrome” caused by Lambert–Eaton myasthenic syndrome

A 67‐year‐old man was admitted with a 2‐year history of dropped head. Neurological examination revealed ptosis, dysarthria, neck weakness, hyporeflexia of all limbs, and autonomic failure. Electrophysiologic study showed a 400% increment response to high‐rate repetitive nerve stimulation. Serum anti‐P/Q‐voltage‐gated calcium channel antibody was positive, confirming the diagnosis of Lambert–Eaton myasthenic syndrome (LEMS). His symptoms and electrophysiological abnormalities improved with oral prednisolone following plasmapheresis. This is the first report of LEMS as a cause of dropped head syndrome. Muscle Nerve 40: 134–136, 2009     

Peroneal nerve repetitive nerve stimulation test: Its value in diagnosis of myasthenia gravis and Lambert–Eaton myasthenic syndrome

We have developed a repetitive nerve stimulation (RNS) technique for the peroneal nerve. Normal limits for the decremental responses for the anterior tibialis and extensor digitorum brevis muscles are 6–21% at the low rate of stimulation and 44–70% at the high rate of stimulation. These values exceed the normal limits for other commonly tested muscles. This may be due to the lower safety factor for neuromuscular transmission for the anterior tibialis and extensor digitorum brevis muscles. We present 4 cases in which the peroneal nerve RNS test was crucial for the diagnosis of the limb-girdle form of MG or LEMS. Thus, we conclude that, in a small number of patients with neuromuscular transmission disorders, the peroneal nerve RNS test is needed for confirmation of disease. © 1995 John Wiley & Sons, Inc.     

Myasthenia gravis and Lambert-Eaton myasthenic syndrome in the same patient

An 18-year-old-woman developed symptoms of generalized myasthenia gravis (MG). Antibodies to the acetylcholine receptor were found in her serum, but electrodiagnostic testing showed abnormalities typical of the Lambert-Eaton myasthenic syndrome (LEMS). Following thymectomy, the thymus gland showed thymic hyperplasia typical of MG, and the patient responded to treatment with 3,4-diaminopyridine and pyridostigmine. There have been few reports in the literature of MG and LEMS coexisting in the same patient. In this case, electrodiagnostic tests, antibody studies, thymus pathology, and response to treatment suggest that both disorders contributed to the patient's symptoms. Thymic hyperplasia, so far only known to be associated with MG, provides strong evidence that both diseases were symptomatic.     

Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or without therapy

To examine the quantitative relationship between indirectly evoked twitch and decreases in the number of either postsynaptic receptors or acetylcholine molecules released by a single stimulus, we studied these variables in a computer-simulated model of neuromuscular transmission. Twitch strength decreased if the number of receptors decreased to below 30% of normal or the number of acetylcholine molecules released by a stimulus decreased to below 80%. Inhibition of acetylcholine hydrolysis to 50% restored twitch strength in the presence of a decreased number of receptors. However, twitch strength was more easily restored to normalcy by augmenting the release of acetylcholine, if the release was diminished by disease. The simulations mimic the clinically known therapeutic outcomes in certain disorders of neuromuscular transmission. These results provide useful quantitative insights into the relationship between acetylcholine receptors or the stimulus-induced release of acetylcholine and muscle function in myasthenia gravis or Lambert-Eaton myasthenic syndrome.     

Anti‐Hu paraneoplastic syndrome presenting with brainstem‐cerebellar symptoms and Lambert–Eaton myasthenic syndrome

Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50‐year‐old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X‐ray findings, class IIIb sputum cytology, and positive anti‐Hu antibody established the diagnosis of PNS associated with small‐cell lung cancer (SCLC). Two cycles of combined chemotherapy resulted in shrinkage of the lung tumor together with complete recovery of neurological symptoms and disappearance of anti‐Hu antibody. Relapse of SCLC 4 months later with re‐appearance of anti‐Hu antibody required additional chemotherapy and irradiation. Eight months later, when multiple liver metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon compatible with Lambert–Eaton myasthenic syndrome (LEMS) developed. Postmortem examinations revealed residual SCLC in the primary lung, and massive liver metastasis with generalized lymph node involvement, but no tumors in the CNS. In the cerebellum, there was a slight loss of Purkinje cells with torpedo formation but without apparent lymphocytic infiltration. The present PNS was unique in that the relapse of SCLC was accompanied by the appearance of anti‐Hu antibody, and that initial signs of brainstem‐cerebellar symptoms, encephalopathy and autonomic failure were replaced by LEMS coinciding with the tumor recurrence.     

Repetitive nerve stimulation studies in the Lambert–Eaton myasthenic syndrome

We compared changes in amplitude and area of surface recorded compound motor action potentials (CMAPs) during 20-Hz repetitive nerve stimulation and after maximum voluntary contraction in patients with the Lambert–Eaton myasthenic syndrome (LEMS), myasthenia gravis (MG), and normal controls. There was greater potentiation of CMAP amplitude after voluntary contraction than during 20-Hz stimulation in 10 of 14 LEMS patients; CMAP area increased more after exercise than during 20-Hz stimulation in all LEMS patients. Although abnormal potentiation of CMAP area and amplitude was seen in equal numbers of LEMS patients, more LEMS patients demonstrated a greater than 100% potentiation of CMAP area than of CMAP amplitude. We conclude that maximum voluntary contraction is preferable to brief 20-Hz RNS to demonstrate potentiation in LEMS because it is at least as sensitive and is less painful. Measurement of CMAP area in LEMS patients is not better than measuring the change in CMAP amplitude in demonstrating abnormal potentiation. Testing of a single hand muscle for potentiation in LEMS does not demonstrate abnormal potentiation in all LEMS patients. © 1994 John Wiley & Sons, Inc.     

Lambert–Eaton syndrome antibodies target multiple subunits of voltage‐gated Ca2+ channels

Introduction: Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic neuromuscular disorder. Autoantibodies against subunits of voltage‐gated calcium channels (VGCCs) associated with acetylcholine release are thought to cause LEMS. Methods: HEK293 cells expressing specific individual recombinant subunits of α_1A, α_1B, α_1C, and α_1E; β₃; and α₂δ of human neuronal VGCCs were exposed to antibodies from 3 LEMS patients, 1 patient with small‐cell lung carcinoma, and 1 with myasthenia gravis. Results: All LEMS patient antibodies bound to cells containing any of the α₁ or β₃ subunits alone or combined with α₂δ subunits, but not α₂δ alone. Autoantibodies from the patient with small‐cell lung carcinoma but not the myasthenia gravis patient targeted the same VGCC subunits. Conclusions: Autoantibodies from LEMS patients bind directly to multiple VGCC α₁ subunits as well as the β₃ subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS. Muscle Nerve 51 : 176–184, 2015     

Myasthenia gravis,castleman disease,pemphigus, and anti‐phospholipid syndrome

Introduction: Myasthenia gravis is an autoimmune disease marked by neuromuscular transmission failure at the neuromuscular junction. Castleman disease is a rare lymphoproliferative disease characterized by non‐cancerous angiofolicular hyperplasia of lymphatic tissue. Methods and results: We describe a young man with rapid, successive manifestations of myasthenia gravis, a solitary form of Castleman disease, pemphigus vulgaris, and anti‐phospholipid syndrome, which resulted in 2 ischemic cerebrovascular events that caused a severe central neurological deficit. Discussion: We were unable to find a similar case in the literature, but we hypothesize that the temporal concidence of these clinical entities may be related to a common immunological pathway, such as B‐cell activation. Therefore, we treated the patient with an immunosuppressant and anticoagulant treatment, as well as rituximab, a monoclonal antibody therapy against CD20+. Muscle Nerve 47:447‐451, 2013     

A Patient with Coexisting Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome

Background

The coexistence of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) is very rare and remains controversial.

Case Report

A 48-year-old woman initially presented with noticeable right ptosis and intermittent diplopia. She then developed fluctuating proximal limb weakness and difficulty in swallowing. The serum titer of anti-acetylcholine-receptor antibody was elevated and the edrophonium (Tensilon) test was positive. However, repetitive nerve stimulation revealed abnormalities typical of LEMS. The patient exhibited a good response to treatment with anticholinesterase inhibitors and steroids, and long-term evaluation disclosed that she presented with the clinical, electrophysiological, and immunological characteristics of both diseases.

Conclusions

The reported clinical and electrophysiological features suggest that this patient was a very rare case of combined MG and LEMS.     

Myasthenia gravis treated with ciclosporin

Six patients (4 females, 2 males) with generalized myasthenia gravis (MG) have been treated in an open study with ciclosporin (5-10 mg/kg/day), originally for 28 weeks. The age of the patients ranged from 16-61 years and the duration of symptoms from 5-30 years. Four of the patients had been thymectomized. Ciclosporin was added to prednisolone in 5 of the patients. Three of these had in addition previously used azathioprine without satisfactory improvement. The efficacy was measured by scoring the degree of muscle weakness on clinical examination and by scoring of the patients' personal assessment of their fatigability and muscle strength. In 5 patients there was a moderate to marked improvement in muscle strength and fatigueability on ciclosporin therapy. In one patient the effect was slight to moderate. The degree of improvement was similar in the one patient who received ciclosporin alone and in those also using prednisolone. The levels of anti ACh-r antibodies decreased in 3 patients, increased in 2, and were unchanged in one patient. Side effects known to occur on ciclosporin therapy were noticed, but they were tolerable in all patients. An increase in serum creatinine (mean 10%) and decrease in creatinine clearance (mean 21%) were seen in all patients. The treatment with ciclosporin has been continued in all 6 patients, but the dosage has been reduced to 5 mg/kg/day. Deterioration 3-4 weeks after discontinuation of ciclosporin was seen in one case, but resumption of therapy resulted in improvement as before. The total treatment period is now 24-34 months (March, 1987).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Primary respiratory failure as the presenting symptom in Lambert–Eaton myasthenic syndrome

Myasthenia gravis can present with rapid respiratory failure as the first manifestation of disease. In the Lambert–Eaton myasthenic syndrome (LEMS), such a manifestation has rarely been reported. We are reporting a patient who developed respiratory failure as the first manifestation of LEMS without associated carcinoma.     

Lambert–Eaton myasthenic syndrome with prominent postexercise exhaustion

A 66-year-old man with Lambert–Eaton myasthenic syndrome, polyneuropathy, and small cell lung cancer, developed profound muscle weakness with a prolonged period of ventilatory dependency. Electrophysiological studies demonstrated very small compound muscle action potentials in response to supramaximal nerve stimulation, limited tetanic and postexercise facilitation, and prolonged prominent postexercise exhaustion (40–60% of baseline value) persisting up to 20 minutes. It is hypothesized that these changes may reflect both a severe defect in acetylcholine release and decreased availability of releasible acetylcholine from the terminal axon.     

The stretch reflex in the Eaton Lambert syndrome, myasthenia gravis and myotonic dystrophy

The stretch reflex at rest and after muscle work was studied in three cases of Eaton Lambert syndrome. After muscle work a potentiation of the stretch reflex was demonstrated clinically and electrophysiologically. The presence of muscle stretch reflexes and their potentiation after muscle work was correlated with the clinical stage of the disease. The enhancement of the stretch reflex after voluntary effort was absent in normal subjects, myastehenia gravis and myotonic dystrophy.