A new autosomal dominant pure cerebellar ataxia.

A kindred is described with a dominantly inherited "pure" cerebellar ataxia in which the currently known spinocerebellar ataxias have been excluded. In the eight subjects studied, a notable clinical feature is slow progression, with the three least affected having only a mild degree of gait ataxia after three or more decades of disease duration. Pending an actual chromosomal locus discovery, the name spinocerebellar ataxia (SCA)15 is expectantly applied.

Chronic inflammatory demyelinating polyneuropathy associated with membranous glomerulonephritis: case report.

A case of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) with Membranous Glomerulonephritis (MGN) is reported. This is the second case recorded in the literature and the article compares this case with the other reported case, including immunological implications.

Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group.

OBJECTIVES: To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. DESIGN: Randomized, double-blind, placebo-controlled trial with 3-month follow-up. PARTICIPANTS: A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. INTERVENTION: Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. MAIN OUTCOME MEASURE: Combined death and disability score (Barthel index <60) 3 months after the stroke. RESULTS: Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2%[12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (P=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). CONCLUSION: The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.

Focal cerebral ischemia and antiphospholipid antibodies: a case for cardiac embolism.

We report clinical, neuroimaging and immunological findings in seven women with antiphospholipid antibodies (APLA) and cerebral ischemia. Two patients had systemic lupus erythematosus (SLE) and five had the antiphospholipid syndrome (APS). Autopsies were done in 3 women who died acutely with focal neurological deficits. Evidence for cerebral embolism was found in all patients: a) pathology demonstrated multiple cerebral infarctions and cerebral emboli from underlying non-bacterial thrombotic endocarditis (NBTE) in the patients who died. b) Three patients had thickened mitral valves and embolic cerebral occlusions were identified with cerebral angiography. c) In one patient, echocardiography detected a thrombus on the posterior leaflet of a prolapsing mitral valve at the time of ictus. Our data provide further evidence to implicate valvular endothelium in the genesis of cerebral ischemia in some patients with APLA.

Multiple sclerosis: report of a case in a Papua New Guinean.

Multiple sclerosis is rare in equatorial countries and has not been diagnosed in the indigenous population of Papua New Guinea. We describe the clinical features of a young Papua New Guinean with optic neuritis and a myelopathy which we believe to be due to multiple sclerosis.

Variability of repeated nerve conduction studies.

We have determined the variability of repeated measurements of sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) amplitude and motor and sensory conduction velocity (MCV and SCV) and examined the extent to which limb temperature is responsible for the variability. We made 10 serial measurements of SNAP, CMAP, MCV and SCV in each of 3 nerves in a single normal subject. The coefficients of variation for MCV and SCV ranged from 2.0% to 6.7% and the proportion of the variance due to temperature was 0.3-56%. The coefficients of variation were much greater for serial measurements of compound action potential amplitude. We used the standard deviations for serial measurements in each nerve to calculate the number of subjects required to detect a difference of 1/msec between the means of two sets of measurements with a power of 90%.

Social, neurological and cognitive disorders in alcoholics.

OBJECTIVES: To construct the social, neurological and neuropsychological profiles of patients with suspected alcohol related brain damage, and to test the hypothesis that cognitive dysfunction develops in alcoholics before signs of alcohol related neurological disease. DESIGN: The study design comprised: a retrospective analysis of patients' records; a comparison of patients' demographic and social variables with age-matched population data from the 1986 Census; and a comparison of neuropsychological test scores of male patients with suspected alcohol related brain damage and age-matched controls. SETTING: The Neuropsychology Unit of Royal Prince Alfred Hospital, a tertiary referral teaching hospital. PARTICIPANTS: All patients (n = 641) referred to the Neuropsychology Unit for assessment of suspected alcohol related brain damage from July 1, 1987 to June 30, 1989, and a control group (n = 93) consisting of healthy volunteers who drank no more than 40 g of alcohol per day. RESULTS: Of the patients, 515 (80%) were men and 410 (64%) were 55 years or younger; their median daily alcohol consumption was 180 g. Compared with the general population the patients were significantly more likely to be in receipt of social security payments, to be separated, divorced or widowed and living in rented or temporary accommodation. However, the proportion of professional and skilled individuals was the same as in the general population. Cerebellar degeneration (38%), peripheral neuropathy (34%) and seizures (14%) were the most frequent neurological disorders. Frontal lobe dysfunction (58%) and short-term memory loss (32%) were the most frequent cognitive abnormalities. Dementia was relatively uncommon (4%). The mean age of male patients with alcohol related brain damage but no neurological disorders (43 years) was significantly less than the mean age of those with neurological disease (54 years; P less than 0.001). In the former, neuropsychological tests of frontal lobe function showed significant impairment compared with control subjects (P less than 0.001), despite normal intelligence. CONCLUSIONS: Cognitive impairment in alcoholics frequently takes the form of frontal lobe dysfunction and may be relatively subtle, requiring a neuropsychological examination for diagnosis. Signs of cognitive impairment may precede those of alcohol related neurological disorders by more than ten years.

Effect of social drinking on neuropsychological performance.

The effects of social drinking on neuropsychological function have been assessed in a group of healthy male volunteers. Subjects were divided into three groups according to their daily alcohol consumption: (1) 40 g or less (n = 93), (2) 41-80 g (n = 22), (3) 81-130 g (n = 16). Group 1 had been drinking at the present level for a mean of 12.6 years, group 2 for 16.9 years and group 3 for 15.1 years; the differences are not significant. There are no significant differences on any neuropsychological tests variables between groups 1 and 2. However, subjects in group 3 were found to perform at a significantly lower level than groups 1 and 2 on the Rey Auditory Verbal Learning Test, the Austin Maze, and the Little Man and Spatial Memory Tests of the Bexley Maudsley Automated Psychological Screening Test. The pattern of deficits found in heavy social drinkers is less severe but otherwise similar to that found in alcoholics.

Disorders of the autonomic nervous system: Part 2. Investigation and treatment.

Autonomic function may be adequately tested with noninvasive tests of sympathetic and parasympathetic pathways, including: the response of blood pressure to change in posture and isometric contraction, heart rate response to standing, variation in heart rate with respiration, Valsalva ratio, sweat tests, and plasma noradrenaline measurements. Abnormal results in two or more of these tests indicate autonomic dysfunction. Intraarterial catheterization and tests of vasomotor function are usually required only in doubtful cases or for research purposes. Treatment of autonomic dysfunction is focused primarily on bladder control and control of orthostatic hypotension. Orthostatic hypotension is best treated with physical measures, pharmacologically with 9-alpha-fluorohydrocortisone and dihydroergotamine mesylate. A number of other agents may be tried but results have been less effective.

Disorders of the autonomic nervous system: Part 1. Pathophysiology and clinical features.

Autonomic dysfunction may result from diseases that affect primarily either the central nervous system or the peripheral autonomic nervous system. The most common pathogenesis of disturbed autonomic function in central nervous system diseases is degeneration of the intermediolateral cell columns (progressive autonomic failure) or disease or damage to descending pathways that synapse on the intermediolateral column cells (spinal cord lesions, cerebrovascular disease, brainstem tumors, multiple sclerosis). The peripheral autonomic nervous system may be damaged in isolation in the acute and subacute autonomic neuropathies or in association with a generalized peripheral neuropathy. The peripheral neuropathies most likely to cause severe autonomic disturbance are those in which small myelinated and unmyelinated fibers are damaged in the baroreflex afferents, the vagal efferents to the heart, and the sympathetic efferent pathways to the mesenteric vascular bed. Acute demyelination of the sympathetic and parasympathetic nerves in the Guillain-Barré syndrome may also cause acute autonomic dysfunction. Although autonomic disturbances may occur in other types of peripheral neuropathy, they are rarely clinically important.

Visual evoked responses in chronic alcoholics.

Visual evoked responses (VERs) were recorded on 52 chronic alcoholics patients without Wernicke-Korsakoff syndrome, 22 of whom had cerebellar ataxia, and eight chronic alcoholics with Wernicke-Korsakoff syndrome. Abnormal VERs were found in 23% of patients without and 37% of patients with Wernicke-Korsakoff syndrome. The main VER abnormalities of all the alcoholic groups were prolonged latency and reduced amplitude of the P100 component. Improvement followed a six month period of abstinence. VERs may be useful in the early detection of alcohol induced brain damage, and in following the progress of patients with the condition.

Brain stem auditory evoked responses in chronic alcoholics.

Brain stem auditory evoked responses (BAERs) were performed on 25 alcoholic patients with Wernicke-Korsakoff syndrome, 56 alcoholic patients without Wernicke-Korsakoff syndrome, 24 of whom had cerebellar ataxia, and 37 control subjects. Abnormal BAERs were found in 48% of patients with Wernicke-Korsakoff syndrome, in 25% of alcoholic patients without Wernicke-Korsakoff syndrome but with cerebellar ataxia, and in 13% of alcoholic patients without Wernicke-Korsakoff syndrome or ataxia. The mean value of the I-V interval was prolonged in all patient groups. There were more patients with prolonged I-V and I-III intervals in the Wernicke-Korsakoff syndrome group than in the group without the syndrome. The I-III interval was prolonged in 32% of those with Wernicke-Korsakoff syndrome but in only 6% of alcoholics without the syndrome. These abnormalities improved following thiamine treatment and abstinence from alcohol. The presence of prolonged I-III interval in an alcoholic should raise the possibility of Wernicke's encephalopathy.

Endoneurial oxygen tension and radial topography in nerve edema.

Endoneurial edema occurs in numerous human and experimental neuropathies. We tested the hypothesis that the resultant increase in intercapillary distance (ICD) may result in endoneurial hypoxia. Experimental galactose neuropathy (EGN) was chosen since in this model, edema is due to the accumulation of galactitol, which does not directly damage nerve fibers, so that it was possible to study the role of endoneurial edema alone. We measured endoneurial oxygen tensions (PnO2) using oxygen-sensitive microelectrodes and related PnO2 radial topography to ICD. We also determined local oxygen consumption (VLO2) and critical PnO2(PcritO2). EGN and age-matched controls were studied at 4 months. (1) Caudal nerve conduction velocity was reduced in EGN. (2) The PnO2 values were reduced in EGN and the PnO2 histogram was shifted into the hypoxic range. These changes were paralleled by a significant increase in ICD in EGN. (3) The radial topography of PnO2 in EGN differed from the relatively uniform distribution in control nerves. In EGN the subperineurial PnO2 was significantly lower than the PnO2 at the center of the fascicle. These changes were paralleled by a significantly greater increase in ICD in the periphery. (4) That the PnO2 reduction in EGN was significant is suggested by the marked reduction in VLO2 and the large percentage (greater than 75%) of intrafascicular regions that fell below PcritO2 in EGN.

Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy.

Endoneurial hypoxia has been suggested as a mechanism of human and experimental diabetic neuropathy (EDN). We found that rats rendered diabetic for 4 months had reduced nerve blood flow (NBF) and nerve oxygen tension (PnO2). The NBF was reduced by at least 33% in EDN and 60% of the oxygen tensions in the endoneurial O2 histogram were less than 25 mm Hg (3.3 kPa) in EDN compared with only 19% in the controls. To test the hypothesis that EDN may in part be due to hypoxia, we studied the effectiveness of oxygen supplementation in preventing some electrophysiologic and biochemical abnormalities. Rats with EDN had reduced caudal nerve conduction velocity and had a resistance to ischemic conduction block. When a matched groups of rats with EDN were O2 supplemented for 4 weeks, the time to 50% block of nerve conduction and nerve conduction velocity was no longer statistically different from controls. Endoneurial free sugars (glucose, fructose, sorbitol) were markedly increased in EDN. Oxygen supplementation resulted in no change in plasma glucose; by contrast, these increased endoneurial free sugars were significantly reduced (towards normal) by 60%, 33%, and 34%, respectively. myo-Inositol, however, was further decreased by oxygen supplementation. These findings of a partial prevention of electrophysiologic and biochemical abnormalities support a role of hypoxia in the pathogenesis of EDN.

Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy.

Endoneurial hypoxia has been postulated to be important in the pathogenesis of diabetic peripheral neuropathy and may be due to reduced nerve blood flow. Neither blood flow nor oxygen tension have previously been measured in peripheral nerve in diabetic neuropathy. We have therefore measured both nerve blood flow and endoneurial oxygen tension in the sciatic nerves of 8 rats with streptozotocin-induced diabetes for four months, and in 8 age-matched controls. In 7 of the diabetic animals mean nerve blood flow was 8.7 +/- 1.3 ml X min-1 X 100 g-1 which is significantly less than mean nerve blood flow in the controls (13.08 +/- 0.8 ml X min-1 X 100 g-1; P less than 0.01). In one diabetic animal, nerve blood flow was too low to be accurately measured. The reduction in nerve blood flow in diabetic neuropathy is due to an increase in resistance to flow which may be due to microangiopathy and to blood hyperviscosity. Endoneurial oxygen tension was also significantly reduced in experimental diabetic neuropathy in which 60 per cent of the oxygen measurements were less than 25 mmHg, compared with 19 per cent in the controls. Nerve blood flow was also measured in rats with experimental galactose neuropathy in which there is more marked sugar-alcohol accumulation, endoneurial oedema and elevation of endoneurial fluid pressure than in experimental diabetic neuropathy. The results obtained in this neuropathy suggest that the reduction in nerve blood flow which occurs in experimental diabetic neuropathy is due largely to factors other than sugar-alcohol accumulation in nerve. We postulate that endoneurial hypoxia may produce many of the observed morphological and biochemical changes in experimental diabetic neuropathy.