Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group.

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.

Somatosensory evoked potentials and magnetic resonance imaging in syringomyelia.

Somatosensory evoked potentials (SEPs) to median and posterior tibial stimulation were obtained in 22 patients with syringomyelia. All patients had magnetic resonance imaging (MR) which defined the maximum transverse diameter of the syrinx as well as its longitudinal extension. SEP was abnormal in 16 (72%) patients. Median and posterior tibial SEPs were abnormal in 11 and 15 patients respectively. Both tests were abnormal in 10 patients. Ten patients showed absence of one or more central potentials (P/N13, N20, N22) and 7 patients demonstrated increased conduction times (N9-N20, P/N13-N20, N22-P40). The mean maximum transverse diameter of the syrinx was 7.5 mm in patients with normal SEPs and 16.2 mm in patients with abnormal SEPs. Abnormal SEP was observed in all 5 patients with loss of position sense, in 9 of 13 (69%) with loss of superficial pain and temperature, and 1 of 2 patients with motor deficit only. Central SEP abnormalities were observed in 3 of 5 patients with sensory deficits indistinguishable from a peripheral neuropathy and in 2 patients in the asymptomatic extremity. Three of 4 patients with syringomyelia and Chiari malformation had a normal SEP.

Somatosensory evoked potentials and magnetic resonance imaging in intraspinal neoplasms.

Median and posterior tibial somatosensory evoked potentials (SEPs) were studied on 25 patients with pathologically proven intraspinal neoplasms, and the results were compared and correlated with the details of clinical examination and the information derived from magnetic resonance imaging (MR). MR was abnormal in all cases and in 23 of 25 (92%) demonstrated an intraspinal expansile lesion. SEP was abnormal in 19 of 25 patients (76%). Abnormal SEPs were found in 18 of 19 patients (94%) with cervical or thoracic neoplasms but only in 1 of 6 patients (16%) with the tumor in the thoracolumbar or lumbar region. SEP-MR correlation was significant (P less than 0.05) for thoracic intraspinal neoplasms where all 9 had an abnormal SEP showing a similar pattern of normal median and abnormal posterior tibial study. Clinically, all 7 patients with posterior column sensory deficits had abnormal SEP (100%). Abnormal SEPs were seen in 7 of 11 (63%) patients with spinothalamic deficits and in 4 of 8 (50%) of those with normal sensory examinations. Four of 9 patients (44%) with a normal neurological examination or an examination disclosing ambiguous results indistinguishable from a peripheral pathology had an abnormal SEP strongly suggesting a central sensory disorder. Comparison of preoperative and postoperative SEPs did not disclose useful prognostic information pertaining to the functional recovery.

Unilateral syphilitic optic perineuritis presenting as the big blind spot syndrome.

Unilateral swelling of the optic nerve head in the absence of demonstrable optic nerve dysfunction (the big blind spot syndrome) has been described as an idiopathic self-limited phenomena. We report two patients who manifested this syndrome due to syphilitic optic perineuritis. Although unilateral syphilitic optic neuritis has been well described, optic perineuritis has been described previously only as a bilateral condition. The cases emphasize the need to consider syphilis in conditions affecting the optic nerve either unilaterally or bilaterally with or without an associated optic neuropathy.

Peripheral neuropathy in mitochondrial disease.

Clinical, electrophysiological, histological and biochemical studies of two patients with mitochondrial disease revealed a moderately advanced axonal neuropathy with mitochondrial paracrystalline inclusions in Schwann cells, fibroblasts and muscle fibers. In addition there was a myopathy, and the activity of muscle cytochrome c oxidase was diminished by more than 50%. There were electrophysiological signs of myopathy, neuropathy and failure of excitation-contraction coupling in both patients. The partial enzyme deficiency raises some questions as to its pathogenetic role in these neuromyopathies.

Effectiveness of trihexyphenidyl against pendular nystagmus and palatal myoclonus: evidence of cholinergic dysfunction.

Palatal myoclonus and acquired pendular nystagmus result from lesions in dentatorubroolivary pathways. We have investigated the effect of high doses of the anticholinergic drug trihexyphenidyl in four patients with palatal myoclonus and in four patients with acquired pendular nystagmus. The movements of each patient were videotaped three times: before administration of trihexyphenidyl, at the time of maximum or effective dosage, and after withdrawal from trihexyphenidyl. In five patients the movements were also electrographically recorded. A neurologist not familiar with the patients reviewed the tapes and rated the changes. In seven of eight patients, administration of trihexyphenidyl resulted in marked improvement of both movements and complaints by patients. This observation indicates that disturbance of cholinergic mechanisms plays an important role in the pathophysiology of these two movement disorders.

Improvement of ataxic hemiparesis with trihexyphenidyl.

In a patient with the syndrome of crural paresis and homolateral ataxia, administration of trihexyphenidyl resulted in improvement of disabling unilateral ataxia and gross intention tremor. Symptoms returned when drug therapy was interrupted. CT showed a radiolucent lesion deep in the parietal white matter close to the internal capsule.

Erythroid and granulocytic colony growth in cultures supplemented with human serum lipoproteins.

The ability of human serum to support erythroid and granulocytic colony formation has been investigated. It was found that normal human serum could replace fetal calf serum in the cultures and was able to support the growth of these hemopoietic colonies. Serum fractions enriched for low density lipoproteins, either by precipitation with Heparin-Mn++ or by ultracentrifugation, was found to contain this growth supporting activity of human serum.