Ataxia telangiectasia in Chinese children. A clinical and electrophysiological study.

The clinical manifestations, immunological, chromosomal, and multimodal electrophysiological studies of five Chinese patients with ataxia telangiectasia are described. One died of hepatocellular carcinoma not associated with Hepatitis B-antigenaemia. Another died of respiratory failure. Two siblings are free of sinopulmonary infections although they are wheelchair bound. Computed tomography of the brain showed cerebellar atrophy in four cases. Nerve conduction studies showed evidence of axonal neuropathy in all cases with the earliest detection at six years. Electromyography showed mild denervation changes in two cases. Two patients had abnormal somatosensory evoked potentials and one had abnormal visual and brain stem auditory evoked potentials. The level of alpha foetal protein was elevated whereas the serum carcino-embryonic antigen was normal in all patients.

Longitudinal evoked potential studies in hereditary ataxias.

We studied multimodal evoked potentials (EPs) longitudinally in a series of children with Friedreich's ataxia and ataxia telangiectasia to determine both their diagnostic utility and their correlation with clinical regression. The auditory brainstem responses (ABRs) were abnormal only in the children with Friedreich's ataxia. The abnormality seen in these patients was a rostral-caudal loss of the ABR waves. The visual EPs (VEPs) were abnormal in many of the patients; those with ataxia telangiectasia had unusually low amplitude or absent VEPs, occasionally with increased latencies, whereas those with Friedreich's ataxia had normal amplitude VEPs, often at increased latencies. The somatosensory EPs were usually of increased latency or absent in these patients. Unlike the ABR and VEPs, they did not serve to differentiate the groups. Changes in the EPs appeared to reflect clinical deterioration; patients with little change in their EPs over several years were regressing very slowly, whereas others had rapid deterioration in both EPs and clinical status. We suggest that the EPs are diagnostically of value in degenerative ataxias and may be of value in monitoring these patients and their response to therapy.

Infantile myasthenia.

A review of twelve Southern Chinese children whose myasthenic symptoms started within the first two years of life and followed up for one to sixteen years showed that, unlike some previous reports on non-Chinese children, the majority had only ocular myasthenia. Response to pyridostigmine was satisfactory and spontaneous remissions were frequent. Although more boys than girls were affected, familial myasthenia occurred in none. Serum acetylcholine receptor antibodies were not elevated in the majority. An association with HLA A11 and BW 46 needs further confirmation.

Pneumococcal meningitis in infants.

A review and follow-up study of 21 Chinese infants who had pneumococcal meningitis showed a mortality of 23.8% and high morbidity in survivors. Severe meningitis and delay in treatment as reflected by the presence of coma, pneumonia, disseminated intravascular coagulation, and lumbar CSF protein of over 368 mg% and glucose of lower than 10 mg% at the time of diagnosis were associated with fatality. Although the pneumococcus was sensitive to Penicillins which were given at usually recommended dosages and duration in these infants, the morbidity in survivors was high, and seemed to be associated with the presence of focal neurological abnormalities at the time of diagnosis, slow response in fever to treatment, short duration of afebrile period before discontinuation of antibiotics, and incompletely normal CSF parameters at the time of cessation of antibiotics. Serially sterile lumbar CSF did not guarantee against recrudescence of meningitis after cessation of antibiotics. The lack of uniformity in treating and monitoring these patients and suggested management are discussed.

Myasthenia gravis in Chinese children.

A clinical study of 50 Southern Chinese myasthenic children observed for periods of two to 18 years (six years on average) revealed manifestations different from those of caucasian patients. Onset was early, at an average of 4.8 years. 82 per cent had ocular myasthenia. Ophthalmoplegia followed ptosis between three months and 10 years later. Additional facial and isolated limb-muscle fatigability developed in only 6 per cent within three months to 3 1/2 years. Only 12 per cent developed generalized myasthenia. Although extension from ocular to the generalized form did not occur later than 20 months after onset, a deterioration in ocular symptoms, without extension into generalized myasthenia, occurred in nine of 18 children during adolescence. Ptosis and generalized myasthenia responded better to anticholinesterase and/or prednisone. Ophthalmoplegia was difficult to treat. The natural clinical course was benign. Spontaneous remission occurred in 62 per cent of cases, but 54.8 per cent of these relapsed, all confined to ocular muscles. Although there was no familial occurrence of myasthenia gravis, an association was found between myasthenia and thyroid disorders in some patients and their relatives. The association with HLA BW46 antigen was striking. Acetylcholine receptor antibodies were absent in the majority, but mildly elevated titres were found in three of five patients whose ocular symptoms deteriorated during adolescence, without extension into generalized myasthenia.

A patient with myasthenia gravis and progressive dystonia with marked diurnal fluctuation.

The authors describe a Chinese girl with myasthenia gravis and progressive dystonia with marked diurnal fluctuation. A combination of L-dopa and pyridostigmine therapy resulted in control of the myasthenic symptoms and disappearance of the dystonia.

Salmonella meningitis in infancy.

Despite adequate treatment, mortality and morbidity were high among the 13 cases of Salmonella meningitis in this series. Chloramphenicol, being a bacteriostatic agent against Salmonella species, is not a suitable antibiotic for the treatment of Salmonella meningitis. Treatment for 4-6 weeks is recommended with use of an antibiotic capable of achieving an adequate bactericidal concentration in the cerebrospinal fluid such as moxalactam. Intraventricular antibiotic treatment should be considered if there is a delay in the eradication of the Salmonella organisms from the cerebrospinal fluid after starting treatment.

Progressive dystonia with marked diurnal fluctuation in a Chinese family.

Two children in a Chinese family with progressive dystonia with marked diurnal variation in symptoms are described. Treatment with L-dopa resulted in complete disappearance of symptoms in one patient and marked improvement in the other patient.

Strong association of HLA BW46 with juvenile onset myasthenia gravis in Hong Kong Chinese.

The HLA antigen distribution and thyroid autoantibody status of 27 Chinese children in Hong Kong with juvenile onset myasthenia gravis have been compared with 110 healthy university students from the same population. Twenty-four of the patients had ocular myasthenia. There was a significantly increased prevalence of HLA BW46 in the patients compared with controls (67% vs 26.4%, p less than 0.005) indicating that BW46 confers a relative risk of 5.6 for juvenile onset myasthenia gravis in Chinese children. The increased prevalence of BW46 was not associated with thyroid autoimmunity in the patients although the antigen is known to be associated with thyrotoxicosis in Chinese. The possibility that BW46 confers protection against the development of acetyl-choline receptor antibodies in Chinese patients is discussed. One patient had the Caucasian antigen B8 and the question whether defective immune response genes were introduced into the Chinese through Caucasian admixture is raised.

Hemorrhagic tendency as a complication of Moxalactam therapy in bacterial meningitis.

Moxalactam penetrates cerebral spinal fluid (CSF) and subdural fluid well enough to be a promising antimicrobial for enteric bacterial meningitis in neonates and infants. Clinical trials in adults and children have found few adverse effects. Prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) with or without bleeding was reported in adults. This paper reports this complication in two infants occurring at a time of clinical improvement following addition of Moxalactam to other antibiotics to which the meningitis had failed to respond. It is not certain if this complication was related to the underlying meningitis, the use of Moxalactam together with other antibiotics, or a combination of many factors. Further observation, close hemostatic monitoring, and timely vitamin K administration during its use are warranted.