A review concerning the characteristics of the cerebellar serotoninergic system is presented. In rat, cat and oppossum, the perikarya of origin are located in the brain stem raphe nuclei and in other brainstem structures. The projections to the cerebellar layers and deep nuclei include synaptic connections, but also non synaptic terminals, espedaily in a diffuse cortical plexus. Serotoninergic receptors have been described: 5-HT1B in the molecular layer and 5-HT2 in the inferior olive. Serotonin exerts neurophysiological effects on several target cells, directly or indirectly, presynaptically or postsynaptically. A modulatory effect on Purkinje cells is well documented. In thiamine deprived animals, a specific serotoninergic cerebellar syndrome includes a selective degeneration of the serotoninergic cerebellar system, an increase of the 5-HIAA cerebellar values and an exaggerated serotoninergic turnover. In human here-doataxias (Friedreich’s ataxia and cerebellar cortical atrophy), serotoninergic disturbances have been observed in the CSF, including low 5-HIAA values and an increased serotoninergic turnover. Therapeutic results have been obtained with L-5-HTP, a precursor of serotonin, in several conditions presenting cerebellar ataxia. L-5-HTP resistance of olivo-pontocerebellar atrophies may be explained by the destruction of serotonin-sensitive target cells, especially Purkinje cells.

We report a 77-year-old woman who presented with partial seizures and was found to have an enhancing dural-based parietal convexity mass. The lesion enlarged on serial examination by computed tomography (CT) over a one year period. The clinical features and radiologic appearance were compatible with a pre-operative diagnosis of meningioma; however, pathologic findings were typical of a dural cavernous hemangioma. Accumulating evidence suggests that these lesions are an uncommon but distinct type of vascular malformation most often arising from the cavernous sinus, tentorium, or cerebello-pontine angle. With CT, magnetic resonance imaging and angiography, these lesions can closely resemble meningioma in terms of signal characteristics, enhancement pattern, and location. This is of importance both in the practical management of meningiomas where the diagnosis is often based on radiologic studies alone, and in clinical trials where incorrect entry diagnosis should be avoided.

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropatho-logical diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a cliniconeuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neu-rohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Excessive fragmentary myoclonus during sleep consists of high amounts of brief twitch-like movements occurring asynchronously and asymmetrically in different body areas and has been reported to occur in association with a number of sleep disorders. It was analyzed using a new technique of quantification, the fragmentary myoclonus index (FMI). The FMI exhibited high rates in all stages of sleep but with a somewhat lower frequency in slow wave sleep explaining, as well, a significantly lower rate in the first hour after sleep onset compared to later hours. There was no evidence for greater sleep fragmentation or lighter sleep compared to a matched patient group in whom it had not been noted.

We studied the activity of glutamate dehydrogenase (GDH) in leukocytes from 23 patients with domi-nantly inherited ataxia. All the patients were assessed with a rating scale for ataxias and met the clinical criteria for the diagnosis of Machado-Joseph disease. The mean age of onset of symptoms was 37.8, SD 13.4 years and the duration of the disease was 7.4, SD 4.9. Leukocyte GDH activity was significantly decreased (p < 0.001) when compared to 20 normal controls. These data extend previous reports indicating that a GDH deficiency is present in peripheral tissues from some patients with spinocerebellar degenerations. Furthermore, this study suggests that a genetic deficiency of GDH may underlie some forms of dominant ataxias; this deficiency may be marked in patients with Machado-Joseph disease and is not specific for any type of multiple system atrophy.

Dr. Bill Lougheed was able to navigate residents through even the most complex neurosurgical procedures with complete and often heroic patience, always ensuring for the patient his usual expert technical result but still leaving intact the resident’s sense of pride and achievement, the feeling that he, the resident, “had done it”. A gifted technical surgeon, a thoughtful and inventive neurosurgeon, Dr. Lougheed was above all else one of Canada’s great teachers of operative neurosurgery. Canada’s pioneer microneurosurgeon, Dr. Lougheed brought the Toronto General Hospital to the very forefront of the emerging field of vascular neurosurgery.

Paralysis induced by neuromuscular blocking agents facilitates ventilation of seriously ill patients but may preclude clinical recognition of seizures. We describe the occurrence of severe cognitive impairment in a 14-year-old girl in whom status epilepticus was recognized only when pancuronium was withdrawn after 14 hours of paralysis. This patient emphasizes a potential danger of paralysis from drugs in patients with acute cerebral dysfunction.

We performed a double-blind cross-over study with amantadine hydrochloride in 12 patients with Friedreich's disease and 2 with autosomal dominant cerebellar ataxia. Patients were randomly assigned to a placebo-amantadine or amantadine-placebo sequence. The interval between the treatments was two weeks. Patients were graded according to a functional ataxia scoring scale and videotaped in basal conditions and 90 min after a single oral dose of 100 mg amantadine or placebo. Three evaluators independently scored the videotapes. Statistical analysis showed no significant effect of amantadine in Friedreich's disease.

A feature of cerebellar ataxia is dysmetria, which is characterized by inaccurate movements. Studies of rapid movements at a single joint show prolonged acceleration phases and prolonged initial bursts of EMG activity in the agonist muscle. These two features correlate with each other, suggesting that the prolongation of the neural signal is responsible for the kinematic abnormality. This explains a tendency to hypermetria. Studies of multijoint movements show abnormalities in relative timing of the different joints. During locomotion, knee and ankle motions can be delayed differentially with respect to the gait cycle. Subjects attempting straight-line movements with the arm have systematic deviations that reflect incoordination of the shoulder and elbow with respect to each other. A possible explanation of dysmetria is a failure of sufficient force generation within the necessary time to accomplish a coordinated movement. Another possible explanation is that the cerebellum is responsible for timing of brain functions.

Denis Naldrett White was born in Bristol. He completed his premedical and medical education at Cambridge. This was followed by graduate training at the London Hospital with Russell Brain, Hospital for Sick Children, National Hospital for Nervous Diseases and the Institute of Psychiatry, University of London, where he completed a senior registrar post in 1948. That same year he was recruited by Dr. Ford Connell, Head of the Department of Medicine, to Queen’s University.

The anterior interosseous neuropathy is a rare focal neuropathy with typical clinical and electromyographic features. Most commonly reported etiologies include lesion of the median nerve following fracture of the radius and ulna, acute or repeated trauma or prolonged pressure on the forearm. In some cases, no predisposing factors can be elicited. Over a one-year period, two young women in their late twenties were evaluated for weakness of the flexor pollicis longus, flexor digitorum profundus of the 2nd and 3rd fingers, and pronator quadratus muscles that occurred within a month following parturition. Nerve conduction studies and concentric needle electrode examination of the upper extremities performed respectively 3 and 10 months after the onset of symptoms confirmed a severe anterior interosseous neuropathy and excluded more common conditions such as carpal tunnel syndrome, cervical radiculopathy or brachial plexopathy. The prognosis was unfavorable in both cases.

We describe a young man who, shortly after exposure to moldy silage, developed a neurological syndrome consisting of dementia and a remarkable tremor which was precipitated by movement. All symptoms resolved within one week. Despite investigation, no definitive diagnosis was reached. We propose that this patient's illness may have resulted from inhalation exposure to a tremorgenic mycotoxin.

A patient with an infarct in the distribution of the right superior cerebellar artery was studied with regard to his ability to make simple movements (visually triggered, self-terminated ballistic wrist movements), and compound movements (reaching to a visual target and precision pinch of a seen object). Movements on the right side of the body alone were affected. Control movements were made by the normal left upper extremity. Wrist movement on the right side was normal in reaction time, direction, peak velocity, and end-point position control ascompared to the left. By contrast, both reaching and pinching movements on the right were impaired. Reaching movements showed marked decomposition of the compound elbow-shoulder movement into seriatim simple movements madealternately at elbow and shoulder. Pinching movements were not made, and instead winkling movements (a movement of index alone) were substituted. These results are compared to similar results of controlled inactivation of the cerebellar dentate nucleus in monkeys. We conclude that one function of the cerebellum may be to combine elements in the movement repertoires of downstream movement generators. When that ability is lost, a strategy may be voluntarily adopted of using the preserved simple movements in place of the impaired compound movements.

The association of movement disorders with hypoglycemia has been rarely noted in the past. We recently observed 2 patients with documented hypoglycemia and paroxysmal dyskinesias. One patient had evidence of an insulin-secreting tumor. The other patient had insulin-dependent diabetes, and also experienced recurrent episodes of hypoglycemic hemiparesis. Classical adrenergic symptoms of hypoglycemia were absent in both patients. Our observations support the concept that the development of neuroglycopenic symptoms cannot be predicted from blood glucose measurements alone, but must depend on other factors controlling the availability or metabolism of glucose in the brain.

This report highlights the clinical features of two patients who presented with severe neuropathic chest wall pain caused by herniated C6-7 disc, and speculates on the pathophysiology of this syndrome. Worsening of symptoms with neck movement helped localize the process as cervical spine rather than plexus in origin. Both patients had herniated C6-7 disc material compressing the spinal cord and C7 nerve root, and neurological symptoms resolved promptly following surgery. Neuropathic chest wall pain should alert the clinician to consider the diagnosis of cervical disc herniation and prompt definitive imaging of the cervical spine by myelography or magnetic resonance imaging (MRI).

The Conference was held in Hamilton, Ontario, on May 18-21 1993, and was the successor to the meetings in New York, Monaco, Cyprus and Mainz. Normally the conferences are held every two years but in this instance the event had been deferred to as not to clash with the 1992 International Congress of EMG and Clinical Neurophysiology in Jerusalem. The Hamilton meeting had been immediately preceded by the International Course on Single Fiber EMG and Other Special Techniques and over 150 registrants and faculty attended the two events. A noted absentee was Dr. Erik Stalberg (Uppsala), the pioneer of single fiber EMG, who was unexpectedly taken ill shortly before the meetings began; by the unanimous decision of the participants, both the International Course and the International Conference were dedicated to Dr. Stalberg.

In recent years, substantial progress has been made in understanding the organization and function of the cerebellum at the neuronal, synaptic, and molecular level. More than any other region of the brain, the cerebellum utilizes amino acids as its main excitatory and inhibitory transmitters. Excitatory amino acids, such as glutamate and aspartate, in addition to serving as chemical messengers, may also mediate neurodegenerative processes in human ataxic disorders. Of the monoamines, serotonin has been proposed as a neuromodulator in the cerebellum and is thought to play a role in the pathophysiology of ataxia in animal models, and human cerebellar disorders. These considerations raise the possibility that pharmacologic modification of amino acid and serotonergic transmission may provide a means for therapeutic intervention in ataxia.

A 41-year-old woman with a history of birth injury to the brachial plexus suffered several delayed episodes of neurological deterioration. Magnetic resonance imaging studies revealed a syrinx extending from the conus medullaris into the brainstem and rostrally into both internal capsules. She died of an acute exacerbation of chronic respiratory failure. Autopsy demonstrated syringomyelia and syringobulbia with cavity extension bilaterally along the corticospinal tracts into the internal capsules. Islands of glial tissue in the subarachnoid space around the medulla caused obstruction of the subarachnoid space at the foramen magnum. These were probably the result of birth injury to the cerebellum. A detailed clinico-pathological correlation is provided to explain her neurological deficits. The pathogenesis of syrinx formation is discussed in terms of a late manifestation of birth trauma.

A 72-year-old man developed a very progressive neuropsychologic deficit 6 years ago, beginning with isolated visual topographic memory disturbances and visuo-constructive apraxia without additional manifestations of dementia. The syndrome worsened thereafter with the emergence of visual agnosia, simultagnosia, psychic paralysis of gaze, auditivo-verbal agnosia, and recently an amnestic syndrome with confabulation and confusion (at the end of 1989). CT scans, which remained unchanged over the years, showed mild, focal atrophic changes revealed by dilatation of the right occipital horn. His angiograms were normal. Two SPECT studies (with HMPAO measurements), performed 6 years from the onset, detected marked hypoperfusion in both parieto-occipital regions, mainly on the right side. Progressive focal degenerative disease without dementia is a relatively new syndrome, especially in cases with progressive aphasia.1 As noted in our patient, progressive disturbances initially localized in the right parieto-occipital region followed by posterior bilobar degeneration (pronounced on the right side) without dementia until late in the course may represent another exceptionally reported characteristic of this new syndrome. It is suggested that this variant of the Mesulam syndrome is more likely explained by progressive atrophy of the Alzheimer type.