The contribution of the cerebellar cortex to coordination of a multi-joint throwing movement was studied by measuring various movement and EMG parameters while normal control subjects and patients with cerebellar cortical atrophy threw a ball at a target. Although patients did not throw as accurately as controls, several coordination measurements were normal in the patients. These included parameters used by us to assess elbow-wrist coordination and the coordination of hand opening with activation of more proximal arm muscles. Postural support for the movement at the shoulder was also normal in that the shoulder was not pushed backwards by the reaction forces resulting from the rapid forward acceleration of the forearm and hand. In contrast, however, patients were unable to coordinate the muscles so as to produce the same hand direction from trial to trial when throwing at the same target. In addition, EMG onset times were abnormal in the antagonist muscles relative to agonist EMG bursts and kinematic parameters of the movement. In conclusion, our patients with cerebellar cortical atrophy showed abnormalities in visual-motor coordination, in that they were unable to consistently produce the appropriate hand direction in response to a visual target. Agonist-antagonist relationships were also impaired. Other aspects of coordination, such as the relative timing of EMG onsets of agonist muscles, even when these were active at different joints, were normal.

Manual tracking performance was studied in five patients with cerebellar incoordination due to unilateral cerebellar hemisphere lesions. The subjects were required to track a target on an oscilloscope screen by moving a cursor controlled by flexion-extension movements of the wrist. In comparison to normal subjects, the cerebellar patients, using their clinically affected arm, demonstrated irregular tracking patterns with inappropriate accelerations and decelerations, numerous high velocity peaks of movement, and an increased time lag between the cursor and the target.

The addition of a viscous load provided by feeding back wrist velocity to a torque motor coupled to the apparatus resulted in significant improvement in tracking performance and suppression of the high velocity peaks. Increasing elastic stiffness by feeding back wrist position or inertial load by adding weights to the hand did not improve performance on this task. It is proposed that a hypotonic cerebellar limb behaves like an underdamped mechanical system. The addition of viscous loads helps restore more normal damping during voluntary movements of the arm.

We examined the role of the environment in the development of Parkinson's disease (PD). A group of 42 parkinsonians have been compared with a group of 84 matched controls. The epidemiological study (1987-1989) covered the territory of the Community Health Department of Valleyfield, in southern Quebec (Canada). Odds ratio adjusted for age and sex were calculated for seven environmental factors. A decreased risk for PD was associated with residence in rural areas (OR: 0.31; p ≤ 0.05) and residence near industry or mining (OR: 0.15; p ≤ 0.05). An increased risk for PD seems to be associated with occupational exposure to the three metals Mn, Fe and Al (OR: 2.28; p = 0.07) especially when the duration of exposure is longer than 30 years (OR: 13.64; p ≤ 0.05). Other environmental factors not found to be associated with PD were: pesticides manipulation, farm work, industrial work and well water consumption.

Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms.

Two patients with neuroacanthocytosis are described. One presented with parkinsonism and the other resembled diurnal dystonia of the Segawa type. Both patients responded well to dopaminomimetic therapy. A PET scan with fluorodopa revealed a nigrostriatal deficit in the first patient.

The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a Taql-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. Hindi detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

We investigated the possibility of an inherited tendency to faint by studying 30 consecutively referred well children with vasodepressor or vasovagal syncope. The family history of each patient was reviewed for syncope and for 24 cases was compared with the family history of the child's best friend. None of the best friends had syncope. 27/30 cases and 8/24 best friends had at least one first degree relative with syncope (p < 0.01). Of the 8 best friend controls with a parent or sibling with syncope, the mother was affected in 7; 4/7 of these mothers had first degree relative(s) with syncope. In 11/30 patients both a sibling and parent had syncope compared with 1/24 of control families (p < .01). We conclude that there is an inherited tendency to faint since most children who faint have a first degree relative who faints, a useful fact in differential diagnosis. This inherited tendency may be multifactorial but requires an environmental stimulus for expression.

We studied the value of CT scans for all children referred because of headache to one secondary and one tertiary pediatric centre during a 1 year period. Of 117 children who were seen by the Pediatric Neurology Service, at the I.W.K. Children's Hospital, 4 had CT scans and only 1 of these was abnormal. The consultant Pediatrician saw 40 children because of headache. CT scans were done on 3 of these patients and all were normal. None of the children who had a clinical assessment alone had unrecognized neurological disease during 20 months of follow-up. Therefore only 1 of 157 children had significant intracranial pathology. We conclude that CT scans have a limited role in the management of children with headache.

Clobazam, a novel benzodiazepine, was used as an add-on agent in 47 adult patients with intractable epilepsy and a variety of seizure types. A >75% reduction in seizure frequency was observed in 42% (18) of the patients and a >50% reduction in 65% (29) of the patients which was sustained over a mean follow-up period of 13.3 (±5.6) months. Nine patients had to discontinue the drug due to minor adverse effects or increased seizures. Possible tolerance developed in 6 patients. Plasma levels of the active metabolite N-desmethylclobazam were linearly related to dosage and appeared to correlate with both therapeutic and toxic responses. Clobazam appears to be a safe and effective add-on antiepileptic for a wide variety of seizure types in intractable epilepsy.

We report the results of a double-blind cross-over study comparing clobazam and placebo in the treatment of refractory childhood epilepsy. Fifty-two percent of patients had greater than 50% reduction in their seizure frequency when taking the clobazam. During the placebo phase no patient recorded a greater than 50% reduction in seizure frequency. Sex, age, seizure type, intellect did not appear to differentiate clobazam responsive from nonresponsive patients. Only 2/21 patients had behavioral changes on the drug sufficiently severe to require the patient to drop out of the study prematurely. Drug interactions between clobazam and the other anticonvulsant medicines did not occur.

There has been a recent renewal of interest in the extracranial repair of cerebrospinal fluid rhinorrhea because of the relatively high morbidity associated with the transcranial approach. The authors describe an extracranial approach that involves packing of the sphenoid and ethmoid sinuses on the side of the CSF leak. A case of successful treatment of CSF rhinorrhea by this method is presented. The extracranial approach may be advantageous for the repair of CSF rhinorrhea and the authors advocate an increase in its utilization by neurosurgeons and otolaryngologists working as a team.

A case of paraneoplastic encephalomyelitis and subacute pandysautonomia associated with an occult atypical carcinoid tumour of the lung is described. The main clinical features were lethargy, impaired memory, constipation, and orthostatic hypotension. Neurological investigation was unremarkable except for mononuclear pleocytosis and increased protein level in the cerebrospinal fluid (CSF). Tests of autonomic function revealed a low plasma norepinephrine level, a marked drop of blood pressure (BP) to vertical tilt and Valsalva maneuver, and a marked rise of BP to dilute norepinephrine infusion. A few days prior to death, the patient became hypothermic and had repeated episodes of respiratory arrest associated with transient atrioventricular block on the electrocardiogram (ECG). A polysomnography study confirmed a sleep apnea syndrome. Autopsy revealed an atypical carcinoid tumour in one tracheobronchial lymph node, widespread lymphocytic infiltrates and loss of neurones in the cerebral, cerebellar and brainstem gray matter, the spinal cord and roots, and the paravertebral sympathetic ganglia as well as microglial and astrocytic proliferation in the central nervous system.

Neurologic complications of the acquired immune deficiency syndrome (AIDS) most often present as brain dysfunction and/or a polyneuropathy. We describe a unique neurological problem of a woman with AIDS who presented with a Cauda equina mass due to primary CNS lymphoma. She subsequently developed a fulminant lymphomatous meningitis and died. Although previously rare, primary spinal cord lymphoma is expected to be encountered more often with the current AIDS epidemic and may be difficult to distinguish from infectious mass lesions.

We achieved a unique and timely recording of cerebral activity in a 70 year old woman immediately pre- and post-stroke, while studying the effect of acute cerebral infarction on sleep-electroencephalogram (EEG) patterns. Normal patterns, except for increased wakefulness, were recorded during two pre-infarct polysomnograms. Immediately following cerebral infarction increased delta activity was recorded from the infarcted hemisphere only. Initially, REM sleep could not be recorded from either side; however, on the third post infarct day REM sleep returned. Background EEG levels from both hemispheres became progressively slower, flatter and simpler. In addition, sleep spindles and the distinctive saw-tooth wave forms of sleep almost disappeared. At one year post-stroke sleep-EEG rhythm recordings from both hemispheres became more similar except for persisting delta activity from the left hemisphere. Unexpected deterioration of sleep-EEG pattern recordings from the undamaged hemisphere taken during the patient's clinical recovery remains unexplained. Serial sleep recording may facilitate the study of brain recovery, activity and reorganization following stroke.

A fatal intracerebral haemorrhage (ICH) associated with streptokinase (SK) treatment of an acute myocardial infarction is described. Autopsy examination showed a lobar ICH and severe cerebral amyloid angiopathy (CAA). The close temporal relationship between SK administration and intracranial haemorrhage, the absence of pretreatment risk factors for ICH, and the presence of CAA suggests that these are related phenomena. Accordingly: 1. There may be a synergistic relationship between CAA and intracranial haemorrhage induced by fibrinolytic agents; 2. Thrombolytic agents may induce more frequent than expected intracranial haemorrhage in conditions associated with a high incidence of CAA, notably old age and Alzheimer's disease; 3. A regional defect in haemostasis other than vessel fragility may contribute to the intracranial haemorrhagic predisposition of CAA; 4. Autopsy examination of cases of ICH is an essential part of the audit of clinical trials of fibrinolytic agents.