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In rat skeletal muscle, trimetazidine (TMZ) caused a transmission defect without directly blocking binding of acetylcholine—ionophore impairment. In vivo, TMZ produced low-amplitude and cumulative depression of successive muscle responses, and immediate posttetanic exhaustion. These features differed from the effects of a-bungarotoxin (α-BuTx) or immunization with acetylcholine receptor (experimental autoimmune myasthenia gravis [EAMG]). In vitro, TMZ-induced block was similar to both α-BuTx-induced block and EAMG in many respects, but there were differences in endplate potentials evoked during and after rapid repetitive activations. These differences suggest that antibodies to the acetylcholine receptor do not affect the ionophore.

To gain a clue to the target of anti-AChR antibody, rats with acute and chronic experimental autoimmune myasthenia gravis (EAMG) that was induced by immunization with Narkeanti-acetylcholine receptor (AChR) were studied using agents acting on active Na-K transport. Postsynaptic response to epinephrine was defective in chronic EAMG with high titers of antibody, suggesting that active Na-K transport system modulated by cyclic adenosine monophosphate (AMP) may be affected primarily by antibody. Sensitivity to ouabain was less than normal in acute EAMG and became close to normal when treated with anticomplementary factor. Findings suggest that acute EAMG is a case of functional denervation. Normal response to insulin occurred in all phases of EAMG.

Motor endplate ultrastructure in the biceps brachii was quantitatively analyzed in five patients with ocular myasthenia gravis (56 endplates), six patients with generalized myasthenia gravis (83 endplates), and five controls (64 endplates). Ultrastructural changes of the motor endplates were observed in non weak limb muscles of patients with ocular myasthenia gravis as well as in generalized myasthenia; these changes were mostly restricted to the postsynaptic region. Decrease of the mean presynaptic and postsynaptic membrane length, and postsynaptic membrane density, were more remarkable in generalized myasthenia than in ocular myasthenia. Widening of the primary and secondary synaptic clefts was also observed more frequently in generalized myasthenia. There was no correlation between ultrastructural alterations and the duration of symptoms or treatment, severity of disease, or titers of antiacetylcholine receptor antibody.

Summary Twenty patients with schizophrenia and ten normal control subjects underwent magnetic resonance imaging of the brain. The volumes of several brain structures were measured using a computer image analysing system. The schizophrenic patients had significantly smaller left parahippocampal volume and larger left temporal horn volume than the control subjects. A larger body of the right lateral ventricle could be estimated in the schizophrenics, but this difference was not significant. In the patient group a non-significant negative corrlation was established between the presence of positive symptoms and the left temporal horn volume. There was no signieficant correlation between the temporal horn and temporal lobe or medial temporal structures. Our results indicate that the left medial temporal structure or left temporal lobe may be involved in schizophrenia and that temporal horn enlargement does not simply represent volume loss of the surrounding tissue.

The effects of prostaglandin E1(PGE1), a potent inhibitor of lymphocyte functions, were studied in rats immunized with acetylcholine receptor (AChR) to induce experimental autoimmune myasthenia gravis (EAMG). Daily injections of PGE1, 400 μg per day, prevented the development of acute EAMG, which is attributed to antibody-dependent, complement-mediated cytolysis. This was associated with suppression of delayed-type cutaneous hypersensitivity response to AChR. PGE, did not prevent the subsequent onset of chronic EAMG, which reflects accelerated degradation of AChR by antibody and complement-mediated cell lysis in the postsynaptic membrane.

Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in motor endplates. Brachial biceps muscle specimens were obtained from six patients with myasthenia gravis (MG) (two ocular and four generalized), five other patients with neuromuscular diseases (limb-girdle dystrophy, polymyositis, and amyotrophic lateral sclerosis) and two controls. In all patients with generalized MG, most of the endplates showed a marked decrease in P-BGT binding. In one of two patients with ocular MG, the amount and distribution of P-BGT binding appeared normal, whereas the other patient showed a slight decrease in P-BGT binding. There was a loose correlation between clinical severity of MG and acetylcholine receptor index or antiacetylcholine receptor antibodies. On the other hand, the amount and distribution of acetylcholine receptor in other neuromuscular diseases was well preserved, even at the endplates denuded of their nerve terminals in amyotrophic lateral sclerosis (ALS) cases.

Abstract: An autopsy case of pure akinesia (PA) is reported. The patient manifested l-dopa-unresponsive akinesia without accompanying rigidity, tremor, eye movement disorder or dementia from the age of 58 years. Brain magnetic resonance T2-weighted imaging at the age of 63 showed high intensity areas in the subthalamic regions, but brain atrophy was not observed. She received amantadine-HCl and l-threo-3,4-dihydroxyphenylserine (l-DOPS) for 5 years. At the age of 66, she died of the severe illness accompanied by consciousness disturbance, hyperthermia, muscle rigidity, abnormal blood pressure and elevated serum enzymes which were derived from the muscle. We considered her condition to be neuroleptic malignant syndrome (NMS). Pathologically the brain revealed degeneration in the subthalamic nucleus, globus pallidus and substantia nigra. Neurofibrillary tangles were detected in the temporal cortex, hippocampus, amygdaloid body and spinal cord, as well as in the basal ganglia, thalamus and brain stem. These findings were consistent with that of progressive supranuclear palsy (PSP); the change in the ventral pons was insignificant, suggesting that PA may have minimum involvement in the ventral pons. The skeletal muscle showed scattered necrosis that was compatible with NMS. As far as we know, this is the first report of NMS accompanied with PA.