AAEM case report #5: Amyotrophic lateral sclerosis.

A 40-year-old man presented with a gradual onset of gait unsteadiness and weakness in the arms. The stretch reflexes were normal in the upper extremities but hyperactive in the lower extremities with bilateral Babinski signs. A myelogram revealed a partial obstruction at C-5-6. Two prior electromyograms, 7 and 5 months prior to admission, reportedly showed positive waves only in two peroneal supplied muscles. Repeat electromyographic testing demonstrated normal nerve conduction velocities and needle electrode abnormalities in upper and lower extremities as well as thoracic paraspinal muscles allowing a diagnosis of amyotrophic lateral sclerosis (ALS). The importance of electromyographic testing in clinically nonaffected areas is stressed as well as its role in patients presenting with upper motor neuron signs. It is the task of the clinical electromyographer to consider other entities in the differential diagnosis, such as a multifocal motor neuropathy with conduction blocks and design the tests accordingly. The role of electromyography in the prediction of the course of ALS by assessing the degree of reinnervation is discussed. This will become increasingly important in the design of treatment trials.

AAEM minimonograph #14: The influence of temperature in clinical neurophysiology.

AAEM MINIMONOGRAPH # 14 Temperature affects biologic and neurophysiologic processes and is, therefore, always well controlled in in vitro experiments. Its role is equally important in the clinical laboratory but has often been neglected. Lower temperature cause slower nerve conduction velocities (NCVs), and increased amplitudes of muscle and nerve potentials. Fibrillations may disappear, and muscle contraction will be slower and weaker. Neuromuscular transmission improves. Somatosensory evoked potentials (SEPs) are similarly vulnerable in the peripheral segments, or with changes in central temperature. As a result, abnormalities are artificially created or existing defects are not detected, resulting in false or missed diagnoses. Control of temperature, albeit somewhat time consuming, will result in greater diagnostic accuracy.

M wave changes with temperature in amyotrophic lateral sclerosis and disorders of neuromuscular transmission.

Local cooling of the muscle resulted in significant increases in M wave surface areas in patients with ALS, myasthenia gravis, the Lambert-Eaton myasthenic syndrome, and also in controls. The most striking increases were seen in patients with early ALS who had minimal lower motor neuron involvement and/or little defect on neuromuscular transmission and patients with the myasthenic syndrome. Patients with myasthenia gravis had intermediate increases between these groups and the controls; there was a larger increase in M wave surface area in myasthenia gravis compared with controls but this could be accounted for by improvement in neuromuscular transmission. The large increase in M wave surface area in early ALS could be the result of temporal summation of individual muscle fibers in motor units with increased fiber densities. The increase in both ALS and the myasthenic syndrome could result also from the loss of a trophic factor causing changes at the muscle membrane.

Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies.

We studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high-titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme-linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high-titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84%) high titers of anti-GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti-GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo-GM1 that do not cross-react with GM1 ganglioside.

Trial of octacosanol in amyotrophic lateral sclerosis.

Octacosanol was tried in amyotrophic lateral sclerosis in a double-blind, placebo-controlled, crossover design. Neurologic and pulmonary function evaluations showed no benefit.

The treatment of subacute sclerosing panencephalitis with interferon: a case report.

A child with subacute sclerosing panencephalitis (SSPE) received intraventricular alpha interferon (IFN) as experimental treatment. The course was monitored by colleagues in pediatric neurology, neuro-opthalmology and clinical psychology, also by monthly EEGS and brain CT scans. Two courses of IFN were administered. During the first course, improvement occurred nearly to the premorbid level of function. About 1 month after this trial was stopped, a severe recrudescence rapidly produced a thalamic state. A second trial of IFN resulted in less improvement. When the brain CT showed severe degeneration, the second trial was stopped. Intraventricular administration of alpha IFN was well tolerated in both courses of therapy. Alpha IFN has promise in the treatment of SSPE but the optimal dosage and duration of treatment are undetermined.

Motor neurone disease: towards better care.

Even in the most severe forms of motor neurone disease--progressive bulbar palsy and amyotrophic lateral sclerosis--the symptoms and disabilities from progressive paralysis may be relieved in many patients by various symptomatic treatments. Quality of life may be improved even in the terminal stage, when narcotic administration should be considered. The physician's proper role is to offer and carefully supervise these treatments, not withhold them. Home care is recommended even for the most severely paralysed, though hospice care may be a good alternative. The underlying principle--to alleviate symptoms--applies to the management of all progressive incurable diseases.

Passive transfer experiments in amyotrophic lateral sclerosis.

To test the hypothesis that a serum factor might play a role in the pathogenesis of amyotrophic lateral sclerosis, whole plasma obtained by plasmapheresis from patients with the disease was injected daily intraperitoneally into mice for periods of up to three months. Similar experiments were carried out with an isolated immunoglobulin fraction. Control experiments were carried out simultaneously. The animals were tested electrophysiologically, and histologic examinations of the brain, spinal cord, and peripheral nerves were performed. No ill effects were noted in the animals, and no neurophysiologic or microscopic abnormalities were detected.

Clinical and subclinical oculomotor findings in the Eaton-Lambert syndrome.

Five patients with the Eaton-Lambert syndrome were examined neuro-ophthalmologically. Three were studied using electro-oculographic saccadic velocity recordings. Four complained of blurred vision and all complained of ptosis during the course of their disease. Clinical examination revealed mild ptosis in three of the five patients. Saccadic velocities before exercise were normal. After saccadic exercise, an increase in velocity of up to 40% was noted in two of the three patients studied.

Plasmapheresis and immunosuppressive drug therapy in the Eaton-Lambert syndrome.

Five patients with Eaton-Lambert syndrome (ELS) without associated malignancy were first treated by plasmapheresis alone, and subsequently by plasmapheresis combined with prednisone and azathioprine therapy. Three of the five were also treated by the immunosuppressive drugs alone. Although all three therapeutic regimens resulted in some clinical and electromyographic (EMG) improvement, the greatest improvement was seen during plasmapheresis combined with prednisone and azathioprine. The initial evoked compound muscle action potential (CMAP) increased during treatment in all patients, while facilitation of the initial CMAP by tetanic stimulation decreased. Overall, the EMG decrement elicited at 2 Hz lessened in four of the five patients. Serious complications probably attributable to guanidine toxicity developed in three patients: two had renal failure and one had gastrointestinal and urinary tract bleeding. Our results suggest that immunosuppressive therapy may have a place in the management of ELS and that circulating factors such as autoantibody may participate in its pathogenesis.

Amyotrophic lateral sclerosis. Impairment of neuromuscular transmission.

Neuromuscular transmission was studied in the ulnar-hypothenar group in 55 patients with amyotrophic lateral sclerosis. A decremental response was found in 67.0%. The decrement was larger and present more often in muscles showing atrophy. In addition, muscles with frequent fasciculations showed a larger decrement than the ones with rare fasciculation. A temperature effect similar to that in myasthenia gravis was observed, with a reduction of the decrement following local cooling of the muscles. Administration of edrophonium chloride improved the synaptic defect. Posttetanic exhaustion was observed as well. It is thought that the defect of neuromuscular transmission is due to a decreased trophic function of the neuron followed by morphological changes at the endplate.