Edward H. Lambert

Experimental autoimmune myasthenia gravis: a sequential and quantitative study of the neuromuscular junction ultrastructure and electrophysiologic correlations.

Neuromuscular junction ultrastructure in rat forelimb digit extensor muscle was sequentially and quantitatively investigated in experimental autoimmune myasthenia gravis (EAMG). Experimental animals were immunized with highly purified eel electroplax acetylcholine receptor protein plus complete Freunds adjuvant and B. pertussis vaccine; control animals received only adjuvant and vaccine. During the first 7 days (latent period) after immunization end-plate structure and neuromuscular transmission remained normal in the experimental group. Between day 7 and 11 (acute phase) mononuclear cells infiltrated those regions of muscle where the end-plates were located and there was intense degeneration of the postsynaptic regions with splitting away of abnormal junctional folds from the underlying muscle fibers. Macrophages entered the gaps thus formed and removed the degenerating folds by phagocytosis. The nerve terminals were displaced from their usual location but maintained their structural integrity. Neuromuscular transmission was blocked in many muscle fibers. Miniature end-plate potentials (MEPPs), detectable in only a few fibers, were of abnormally low amplitude. After day 11 (chronic phase) the nerve terminals returned to the highly simplified postsynaptic regions and the inflammatory reaction subsided. Subsequently the postsynaptic folds became reconstituted and again degenerated. Immature junctions with poorly differentiated postsynaptic regions and nerve sprouts near end-plates were also observed. In two animals relapsing

Clinical and electromyographic studies in a patient with primary hypokalemic periodic paralysis

Abstract A patient with severe primary hypokalemic periodic paralysis improved significantly on a regimen low in carbohydrate, restricted in sodium and high in potassium. Moderate weakness persisted in the proximal muscles and was associated with persistent vacuolation of muscle fibers. Enlargement of the motor end-plate zone is described in this case of primary hypokalemic periodic paralysis. Considerable weakness occurred even when serum potassium values were within the normal range. On an isocaloric nonreducing diet, the patient lost weight when the carbohydrate intake was reduced. Most of the weight loss could be accounted for by a loss of body water that was not associated with a negative sodium balance. Data obtained in the course of an acute attack are compatible with an increase in the total body water content and a shift of fluid from the extracellular into the intracellular compartment. Renal retention of potassium, sodium and chloride preceded changes in the patients strength and the decrease in serum potassium. Not more than 10 mEq. of potassium could have been lost from the patients erythrocytes during the attack despite the decreasing serum potassium levels. A fully paralyzed muscle and a muscle only somewhat weak were similar in their electrolyte and water content, except for the higher calcium and magnesium contents of the weaker muscle. Both muscles had chloride space and water levels which were higher than most normal values; sodium, chloride and magnesium levels higher than normal; and a potassium level which was lower than most normal values. The chloride space values were too high to be a measure of the extracellular space and could not be used for calculating intracellular electrolyte concentrations. Small doses of epinephrine, administered intra-arterially, had a direct adverse effect on the muscles of the perfused forearm. These effects were not mediated by systemic hypokalemia or hyperglycemia but may have been related to an acceleration of glycogenolysis and glycolysis in muscles. An increased uptake of sodium by the forearm tissues followed rather than preceded the decrease in action potential and twitch tension. Maximal voluntary exercise followed by rest caused a transient potentiation and then a depression of the action potential and of the twitch tension in the patient and in healthy subjects, but the patients response was at times quantitatively greater. The deviation from normal tended to be greatest when the patient was weakest. Excessive accumulation of lactic and pyruvic acids in the blood occurred after a standard work load. This may indicate a greater than normal release of these metabolites from muscle or an impaired metabolism by muscle, or both. There appears to be no impairment in glycogenolysis or glycolysis in muscle during exercise. A close relationship was again observed between carbohydrate metabolism and primary hypokalemic periodic paralysis. The present study points to a possible metabolic lesion, or a contributing mechanism, that can be activated by rapidly induced glycolysis.

EXPERIMENTAL AUTOIMMUNE MYASTHENIA: CLINICAL, NEUROPHYSIOLOGIC, AND PHARMACOLOGIC ASPECTS*

It has been suggested by several authors 1, that an autoimmune response against acetylcholine receptor ( AChR) could account for the symptoms of myasthenia gravis (MG) . Testing of this theory in vivo required the use of purified AChR and was therefore delayed until the techniques for the isolation of receptor could be perfected. In 1973 Patrick and Lindstrom3 reported the development of weakness in rabbits immunized with purified AChR from the electric eel (Electrophorus electricus). The character of the weakness and the improvement following anticholinesterase administration suggested a similarity to human MG. Our present work is an attempt to verify and extend these observations and to evaluate the usefulness of this disorder as an experimental model for MG. This paper reports the clinical and electrophysiological characteristics of the disorder in animals immunized with purified receptor and compares the disorder with human MG.

The Use of a Resistance Wire, Strain Gauge Manometer to Measure Intraarterial Pressure:

Summary The use of a resistance wire, strain gauge to convert pressure to electrical energy in making direct measurements of arterial blood pressure is described. The electrical circuits involved are simple. Recording is by means of a galvanometer without the use of electronic amplifiers. The calibration of the manometer is linear, stable and relatively insensitive to temperature changes. The natural frequencies of the manometer and galvanometer are 60 and 40 cycles per second, respectively.

Experimental Facial Nerve Paralysis: Influence of Decompression

An experimental model was employed to establish an endotemporal bone facial nerve paralysis in cats. Twelve facial nerves were initially surgically decompressed— Both bony decompression and sheath decompression—to determine if any harm was done to the nerves by these procedures. Transient harm was found in 3 of the 12 nerves. After the course of the facial paralysis without any decompression was determined, 39 cats underwent either bony or sheath nerve decompression, both immediately after injury and after a delay. The cats were followed clinically and electrophysiologically; the nerve excitability test and the amplitude and latency of muscle response evoked by nerve stimulation were used to evaluate nerve function. While immediate postinjury bony decompression resulted in slightly earlier recovery times, immediate sheath splitting significantly lengthened recovery times and worsened the electrophysiologic test results. Histologic studies confirmed the clinical and electrophysiologic results anatomically. Delayed nerve decompression, either bony or sheath, was not associated with faster recovery rates.