Search

In 30 patients with myasthenia gravis, serum assays were performed for antibodies to human nicotinic acetylcholine receptor. 19 of 20 generalized forms which were symptomatic and 6 of 9 patients in remission at the time of blood sample had detectable amounts of antibodies. The six highest levels were found in benign courses. 2 patients had a five- and twofold drop in antibody level during rapid deterioration. Patients in remission after thymectomy may still have low to moderate levels, while symptomatic patients occasionally have no detectable antibody.

Antisacer compositum, a commonly prescribed speciality which associated phenobarbitone and phenytoin in a dose ratio of 1:4, was withdrawn after demonstration of a negative interaction of this formula. A retrospective analysis is presented of phenytoin plasma levels during bitherapy and after passage to monotherapy, in 13 adult epileptics followed as outpatients. Phenytoin plasma levels increased over twofold in 12 cases, of whom 5 continued to take the same doses, while 7 received higher doses on, and in one case two weeks after, the withdrawal of phenobarbitone. Plasma level decreased slightly in the thirteenth in spite of increased doses. Five phenytoin intoxications occurred after this change of prescription: one amongst the 5 cases with identical doses, and 4 amongst the 7 cases with increased doses. The initially high levels of phenytoin tend to decrease after several months. Physicians required to change the prescription should be aware of the risk of initial intoxication and later underdosage.

Three cases of neuropathy with monoclonal gammopathy and amyloid deposits in peripheral nerves are described. They appeared to present a benign gammopathy because of the duration of the neuropathy in the absence of any clinical or biological sign of myeloma or macroglobulinaemia. The pathological abnormality found in the sural nerves of the three patients was characterised by a marked loss of myelinated and unmyelinated nerve fibres because of active axonal degeneration with Wallerian degeneration. The most striking feature in all three cases was the finding of deposits identified as an accumulation of microfibrils.

Thirteen cases of crural or, less often, lumbar plexus neuropathies are reported which were secondary to hematomas in patients under anticoagulant therapy. They are the most frequent peripheral neurological complications of anticoagulant therapy. The clinical symptoms, which often point directly to the diagnosis, are discussed and several additional investigations (conventional X-ray, transverse tomography, EMG, etc.) are presented. The criteria for prognosis and therapeutic problems, in particular the indication for surgical drainage of the hematoma or for neurolysis, are discussed. Finally, the pathogenic mechanisms of these neuropathies are outlined.

Plasma concentrations of diphenylhydantoin were determined by the method of Wallace (double extraction, spectrophotometry) in 150 samples taken from 121 epileptic patients. They correlated well with those determined by gas chromatography, were not dose-dependent and were often below 10 mul/ml. They were above 20 mul/ml in 6 patients with CNS intoxication. These determinations were also useful for detecting patients who did not take the drug as prescribed (14 suspected cases, 4 confirmed). However, blood levels did not seem to offer an accurate index of the effectiveness of diphenylhydantoin.

Electrophysiological, histological and ultrastructural studies on two patients (one family) with familial neuropathy and a liability to pressure palsies are reported. There was slowing of nerve conduction velocities and increase of distal latencies of clinically affected and clinically non-affected nerves. These alterations were confirmed by biopsy of the sural nerive which had the characterized signs of the disease. Pathogenetically there seems to be an endogeneous metabolic defect of the Schwann cell to synthetize a normal myelin sheath, which is responsible for the particular susceptibility to mechanical damage.

Clinical and electroencephalographic evolution, as well as the neuropathology, are described in a 25 year old man with a Hurst's acute haemorrhagic leucoencephalitis. Lesions, unusually symmetrical, coexists with those, without vascular necrosis nor haemorrhages, of the perivenous encephalomyelitis. The aspecific onset, course and results of complementary investigations appear on reviewing 44 clinical observations in the literature. Histologic examination of affected white matter is the only was to assess the diagnosis. Two features that may have been previously neglected are outlined: the predilection for 20 to 40 years old males, while the adolescent male, the most susceptible to perivenous encephalomyelitis after specific fevers, is not affected by Hurst's disease. Multiple sclerosis or a prodromal meningo-encephalitis, clinically undetected, could be not rare. Therapeutic results of surgical decompression, hyperosmolar substances and massive doses of corticosteroids (3 survivals out of 10 cases diagnosed on biopsy) cannto be evaluated at the present time. By analogy with the simple and the hyperacute forms of EAE, the myelinotoxicity may result from sensitized lymphocytes alone in the perivenous encephalomyelitis, from an association of circulating antibodies and lymphocytes in Hurst's disease. Whether the immunoglobulins enchance the cellular myelinotoxicity or induce an immune complex disease upon a perivenous encephalomyelitis is still to be determined.

In the diagnosis of epilepsy the prior approach will be to decide whether it is an epileptic attack or not. If so, is the epilepsy the primary disease or the symptom of an evolving cerebral affection or of a toxic or metabolic disorder? The causes of failure with phenytoin treatment are discussed. They may be exogenous, i.e. prescribing too low a dosage (the average dose in the adult is 5 mg/kg/day) or lack of cooperation by the patient who either takes the drug irregularly or fails to take it at all. The endogenous causes are harder to determine. Plasma phenytoin determination (therapeutic values from [5] to 10 to 20 mug/ml) makes it possible to adapt the dosage to the individual metabolism and sometimes to detect a drug interaction which lowers, and in rarer cases raises, plasma DPH levels. Toxic levels are rarely asymptomatic. In this condition repeated determinations may help to decide when the treatment is to be resumed and thus to avoid recurrence of attacks during or shortly after DPH withdrawal. Finally, plasma determination makes clear the extreme difficulty of adapting the dosage in the rare patients who react to a minimal of dose by a shift in blood level from insufficient to toxic values, or vice versa.