Andermann et al. described in 1972 an autosomal recessive inherited syndrome which associates agenesis of the corpus callosum, mental deficiency, and a peripheral motor deficit. We had the opportunity to study in detail 15 patients affected by this syndrome. As in the cases previously reported, the families of these children all originated from Charlevoix County and the Saguenay-Lac St-Jean area in the Province of Quebec.

Clinically, these patients have a characteristic facies and moderate mental retardation associated with a progressive motor neuropathy leading to loss of ambulation by adolescence and progressive scoliosis. In 13 of these 15 patients, neuroradiological investigation has shown either total or partial agenesis of the corpus callosum. In every patient in whom these tests were done, sensory nerve action potentials were absent and motor nerve conduction velocities reduced. We also found neurogenic abnormalities both on EMG and neuromuscular biopsies. These abnormalities are similar to those described in Friedreich’s ataxia and in hereditary motor and sensory neuropathy type II, although in our patients the motor deficit is much more severe than in these diseases.

The pathogenesis of the peripheral nervous system involvement is still unknown since there have so far been no autopsy studies of this syndrome.

The physician exposed to a large number of patients with a recessive form of ataxia, will occasionally observe slower progression forms which lack many of the severe features or cardinal symptoms of Friedreich's disease. We have studied 31 such cases in Acadians of the Maritime Provinces of Canada, and in their separated “cousins” from Louisiana, now called “Cajuns”. These patients are compared to a consecutive series of 22 Friedreich's disease cases in French Canada.

It is shown that the age of onset is slightly later, but the progression much slower and the age at death older in the Acadian patients. These cases develop signs of pyramidal and posterior column involvement gradually and later than the classical Friedreich. As a result, pes cavus and scoliosis are less marked, as well as muscle weakness and cardiomyopathy. On the other hand, the rate of progression of areflexic ataxia, the “core disease”, is identical in both groups. The main difference in progression rates of the disorders occurs after 10-12 years of evolution, thus after the period of hormono-ponderal growth.

These differences, coupled to the diverging genetic and genealogical backgrounds, are sufficiently large for the presumption of distinct disorders. Whether they are due to allelic mutations, linked but different genes, genes affecting the same metabolic pathway, but elsewhere or to completely distinct entities, will have to be left to further studies, but their existence in completely different populations and milieux is worthy of report.

A few human diseases may be viewed from a phylogenetic perspective. Some metabolic or degenerative diseases selectively affect recently evolved or exclusively mammalian structures of the brain and spare the older structures. Examples include Krabbe’s leukodystrophy, olivopontocerebellar atrophy, Friedreich’s ataxia, Pick’s disease, and Leber’s optic atrophy. Some pathologic conditions in man are similar to normal anatomy in other species, although the mechanisms may differ. Congenital muscle fiber-type disproportion in rodents, Dandy-Walker cyst in birds, and agenesis of the corpus callosum in marsupials are representative of this category. Loss of basal dendritic spines from pyramidal cells in Pick’s disease is reminiscent of certain large neurons normally found in the cortex of reptiles. Changes in metabolism in the evolution of mammals in general and of man in particular may explain some aspects of’phylogenetic diseases’. Some potential examples are the shift from predominantly phospholipids to galactolipids in myelin composition as mammals evolved, and the greater toxicity of cyanide and other poisons of oxidative metabolism in mammals than in other vertebrates because of less reliance on anaerobic metabolism as an alternative energy source.

The neuroleptic/dopamine receptor, with its picomolar affinity for potent neuroleptics, is the functional dopamine receptor of the brain. This receptor has been termed the D2 dopamine receptor, and it inhibits or interferes with dopamine-stimulated adenylate cyclase. This D2 receptor has two states, each having different affinity for dopamine. The high-affinity state, termed D2high, has a 10 nM affinity for dopamine and is the functional correlate for dopamine autoreceptors and for the dopamine receptor in the pituitary gland. The low-affinity state, termed D2low, has a 2000 nM affinity for dopamine, and may possibly represent the desensitized state of the dopamine receptor or the functional post-synaptic receptor.

52 recently abstinent chronic alcoholics were given repeated psychological tests and 20 of these had repeated CT scans. The first scan was done within 5 weeks of the last drink. The degree of measurably reversible cerebral atrophy on CT scan correlated negatively with the interval between the last drink and the first CT scan. Significantly more reversibility of cerebral atrophy was noted in those subjects claiming interscan abstinence. There were positive correlations between functional improvement scores on neurological exam and reversible cerebral atrophy measurements. Significant improvement on psychological test performance was restricted to patients tested initially within 3 weeks of the last drink. Both the CT results and the psychological test results suggest that reversible changes occur soon after the cessation of drinking.

Stenosis of the internal carotid artery reduces the flow velocity in the ophthalmic artery. Lowered velocity permits increased red cell aggregation and decreased red cell deformability which increases viscosity.

Contrary to the theory of remotely originating emboli, this is an alternate hypothesis regarding transient attacks of ocular and cerebral ischemia.

The ophthalmic artery circulation time was measured in two groups of patients. The circulation time was defined as the interval between the appearance of contrast media in the siphon of the internal carotid artery and in the ocular choroid. The measurement was made on 151 angiograms of 108 subjects. These vessels were normal. An additional 76 patients had 108 angiograms which showed various amounts of internal carotid artery stenosis. These 76 patients had transient ischemic attacks; retinal, cerebral, or both.

There is a significant difference in the ophthalmic artery circulation time in the two groups. The slowing in the ophthalmic artery is related to the degree of internal carotid artery narrowing.

The circulation time in a cerebral branch of the internal carotid was not measured. It is presumed that stenosis of the internal carotid artery would have the same effect on a cerebral artery as on the ophthalmic artery.

Intermittent oral or rectal administration of diazepam for the prophylactic treatment of febriie convulsions has given results comparable to the continuous use of phenobarbital while limiting side effects and risks of toxicity. Since we believe that nitrazepam is a better anticonvulsant than diazepam, we performed a study to evaluate the effectiveness of this medication in the prophylactic treatment of febrile convulsions. Nitrazepam was given only when the children had fever and almost exclusively in children with a high risk of recurrence (less than 12 months of age at first convulsion; atypical convulsion; one or several previous convulsions). Thirty one children with a high risk of recurrence received nitrazepam. The rate of recurrence in this group was 19.3% after a follow-up of 16 months, compared to 45.8% in 24 children who also had a high risk of recurrence but in whom the parents refused the medication or gave it inadequately (p<0.05). Fifty one children with a low risk of recurrence also were evaluated and followed for at least 12 months (mean 15.4 months). Six were treated with nitrazepam, mostly because of parental anxiety, and none had a recurrence; of the 45 untreated children in this group, 6 (13.6%) had another convulsion. These results show the efficiency of nitrazepam in the prophylactic treatment of febrile convulsions.

Although many types of sports and recreational activities have been identified as common causes of acute spinal cord injury, hockey has been a rare cause of acute cord injury in Canada or elsewhere. For example, from 1948 to 1973 there were no patients with cord injuries due to hockey in a series of 55 patients with acute cord injuries due to sports or other recreational activities admitted to two Toronto hospitals. In contrast, between 1974 and 1981, the Acute Spinal Cord Injury Unit, Sunnybrook Medical Centre treated six patients with cervical spinal injury due to hockey, five of whom were seen during a 13 month period from September, 1980 to October, 1981. Five of the six sustained a severe acute cervical spinal cord injury, and one a cervical root injury. The cord injury was complete in two cases, while three had complete motor loss but incomplete sensory loss below the level of the lesion. All were males aged 15 to 26 years. Of the players with cord injury, four struck the boards with the neck flexed, and one struck another player with the neck flexed. The one player without cord injury struck the boards with his neck extended. The commonest bony injury was a burst fracture of C5 or C6. One of the patients with a complete cord injury died three months later of a pulmonary embolus, and the other patients with cord injury showed some recovery of root function, but little or no cord recovery. The reasons for the increase in spinal injuries in hockey are unknown.

We report data on 3 members of a family affected by a dominantly inherited disorder closely resembling Roussy-Levy syndrome (RLS). Electrophysiological findings showed a marked decrease of motor and sensory conduction velocities and EMG signs of mild neurogenic damage. Light and electron microscopy of sural nerve biopsy showed a hypertrophic neuropathy with diffuse onion-bulb formations and marked decrease of large size fibers. Teased fiber preparations evidenced reduced internodal lengths and segmental demyelination. Other data from the literature on RLS are reviewed and discussed. The hypothesis that RLS is not a disease entity but a hypertrophic-type of Charcot-Marie-Tooth disease with essential tremor (HMSN type 1) is strongly supported.

Evidence supporting the validity of the ‘two dopamine receptor’ hypothesis is presented. The availability of the ‘first generation’ of selective agonists and antagonists of the D-1 and the D-2 dopamine receptors provides pharmacological support for the hypothesis. The demonstration that stimulation of the D-2 receptor either inhibits or has no effect upon adenylate cyclase activity while stimulation of the D-1 receptor enhances cAMP formation provides biochemical support for the hypothesis. Finally, binding assays demonstrating two affinity states for the D-1 and the D-2 receptors are briefly discussed.

The effect of desipramine, imidazole, thioridazine and trifluoperazine on blood-brain barrier(BBB) permeability after a 24 hour cold lesion was studied in rats. Changes in BBB permeability were determined using a quantitative horseradish peroxidase (HRP) assay. The four drugs tested did not alter the quantity of HRP in the cortex of control animals, or in the contralateral cortex of test animals. However, imidazole, desipramine and trifluoperazine significantly reduced the HRP extravasation in and around the cold lesion. Several mechanisms for this effect are suggested; one possible mechanism common to all these drugs is the reduction of increased vesicular transport in cortical vessels adjacent to the cold lesions.

Acute vasospasm of the transclivally exposed basilar artery of anesthetised cats was produced by the subarachnoid injection of platelet-rich plasma (PRP) treated with enough adenosine diphosphate (ADP) to induce platelet aggregation and secretion. Vasorelaxation was produced by the topical application of the calcium antagonist verapamil. Changes in the internal diameter of the basilar artery were determined by measuring the blood column diameter from photomicrographs taken sequentially, at 5 minute intervals, through the operating microscope. Changes in blood vessel diameter are expressed as a plus or minus percentage of the pretreatment diameter. Arterial blood pressure and blood gas values were kept in the physiological range for the cat.

The subarachnoid injection of PRP-ADP produced severe constriction of the basilar artery (mean constriction at 5 minutes after injection: -40.7% ± 2.8 SEM). Platelet-free plasma, ADP alone and Elliott’s A solution had no spasmogenic effect when injected into the subarachnoid space. The topical application of the calcium channel blocker verapamil (0.1 mg per kg) 30 minutes after the injection of PRP-ADP, with the basilar artery still in spasm (mean constriction: -23% ± 3.5 SEM), produced prompt and dramatic vasodilation (mean dilation at 5 minutes after application: + 52.7% ±18.1 SEM). This spasmolytic effect persisted in a decremental fashion for the 60 minute period of observation, by which time the previously constricted vessel had returned to its normal size. These observations indicate that the platelet fraction of whole blood may be involved in the genesis of acute vasospasm following subarachnoid hemmorhage and that this phenomenon can be readily reversed by calcium antagonism.

The recognition of the dopaminergic properties of some ergot derivatives has initiated new therapeutical approaches in endocrinology as well as in neurology. The pharmacological characterization of the different ergot derivatives during the last decade has largely improved our understanding of central dopaminergic systems. Their development has yielded valuable information on the pharmacology of dopamine receptors involved in the regulatory mechanisms of prolactin secretion and in striatal functions.

The clinical application of such new neurobiological concepts has underlined the therapeutical interest of such compounds either in the control of prolactin-dependent endocrine disorders or in the treatment of parkinsonism. Owing to their pharmacological profiles, dopaminergic agonists represent a valuable clinical option especially in the management of Parkinson’s disease in view of the problems arising from chronic L-Dopa treatment.

In an attempt to find the best electrophysiological indicator of improvement for the neuropathy present in patients with chronic renal failure undergoing hemodialysis, several types of nerve conduction were studied at the beginning of dialysis and six months later. Sural nerve conduction and late response latencies were recorded in addition to conventional motor and sensory nerve conductions. After six months of hemodialysis, sensory nerve conduction velocities in the median, ulnar and sural nerves were improved. These values appear to be the most sensitive indices of the beneficial effect of hemodialysis on the neuropathy.

A new method for continuous monitoring of the concentration of 131I-labelled iodoantipy rine during an autoradiographic local cerebral blood flow (LCBF) experiment is described. During infusion of iodoantipy rine, radioactivity in an external femoral arteriovenous loop is monitored by a scintillation detector. Data is collected with a variable time base, and the arterial activity curve displayed visually in its entirety. The main advantage of this method is that there is no blood loss. It will therefore be of particular importance in dual-label autoradiography. This method can also be used for other gamma-emitting blood flow tracers, e.g. 123I-iodoantipyrine.

Four members of a family with consanguineous relationships, the proband and his three children (2 sons and 1 daughter) are affected with Familial Spastic Ataxia and with Ehlers-Danlos' Syndrome with platelet aggregation dysfunction. In the four cases, this exceptional association appears remarkably homogeneous both in clinical and laboratory studies. The two syndromes are of dominant-autosomic transmission and probably originated in a new mutation which presumably maintained a genetic linkage. Spastic ataxia is characterized by a precocious onset and a slow evolution. The first-born son shows a dominant pyramidal syndrome with mild ataxia suggesting that it is a transitional form of familial spastic paraplegia. The Ehlers-Danlos syndrome pertains to form II or “mitis” with moderate skin hyperelasticity and joint hypermobility. The abnormal platelet aggregation curves have the same profile in all the patients. The first-born son also presents a mitral valve prolapsus as we may find either in Ehlers-Danlos syndrome or in spastic ataxia.

The major anatomical connections of the basal ganglia are reviewed, emphasizing the inputs to the striatum and efferent projections from the major output nuclei, the internal segment of globus pallidus and the pars reticulata of substantia nigra. The results from lesioning experiments, electrical stimulation, and chronic recording of single neuron activity have provided a wealth of data concerning the physiology of the basal ganglia. Although the deficits resulting from disease of the basal ganglia are well recognized, the specific role which these structures play in the control of normal movements remains speculative.

Thirty-three patients with advanced Parkinson’s disease complicated by end of dose deterioration were treated with bromocriptine. The drug was slowly increased so that by treatment week 24 the mean daily dose of bromocriptine was 22mg and levodopa had been decreased by an average of 15 percent. The majority of improvement in daily fluctuations and Parkinsonian disability score was documented by 8 weeks, at which time the mean daily bromocriptine dose was only 12mg.

End of dose deterioration was reduced in 78 percent of the patients (mean 43% improvement). Total Parkinsonian disability score was decreased by 33 percent. Adverse effects were minimal; the most common was mild transient early treatment nausea which occurred in 15 percent of the patients.

The slow introduction of small doses of bromocriptine, combined with minimal levodopa reduction, can give Parkinsonian patients significant improvement in end of dose deterioration.

The relationship between the segmented EMG activity in flexor carpi radialis evoked by imposed angular wrist displacement was studied with respect to the level of pre-existing background activity in 30 normal human subjects. Input-output response planes demonstrate that the magnitude of the Ml & M2-3 segments is dependent on both the displacement parameters and the level of pre-existing EMG activity in the stretched muscle. If the level of background activity exceeded 4-5% of the maximum voluntary contraction, the onset latency of the M1 segment and duration of the Ml and the M2-3 segments remained constant (within ± 2 msec) for different magnitudes of step load displacements, despite marked variation in the range of the displacement’s amplitude, duration, velocity, and acceleration. We propose that the dependency of the relationship between reflex magnitude and imposed movement parameters on tonic motoneuron activity, as represented by pre-existing EMG levels, may reflect an automatic adjustment mechanism that could be utilized in servo compensation of movements requiring markedly different force levels.

A 21-year-old woman receiving prolonged high dosage glucocorticoids developed spinal cord compression due to excessive accumulation of epidural fat. Computerized tomographic scanning confirmed the diagnosis and revealed a peculiar pattern of spinal cord displacement which we believe to be unique to compression by fat. Laminectomy did not afford relief, possibly because of prolonged neural compression or because of compression at a higher spinal level. Although an unusual complication of Cushing’s syndrome, epidural lipomatosis should be considered when such a patient develops symptoms of spinal cord or cauda equina compression.