We report the occurrence of cerebral aneurysms and subarachnoid hemorrhage (SAH) in a family with Graves' disease (GD). Nine affected individuals across three generations have GD alone; three in the same generation have SAH without GD; and three others in the same sibship have both conditions. The familial association of GD and SAH has not been previously described. The occurrence of these disorders in individuals of the same family and their coexistence in the same individuals suggests a possible genetic determination for some cerebral aneurysms and mayimply a genetic locus related to that of Graves' disease.

Levodopa is currently used at all stages of Parkinson's disease, particularly from Stage 3 onward. Most patients start levodopa within four years of the onset of disease, earlier in the akineto-rigid patients (average delay of 2.1 years) than in those where resting tremor predominates (average delay of 3.4 years). Advanced age (>80) is no deterrent to the use of levodopa if required. Wearing off is most noticeable in Stage 3 or after 10 years of therapy with levodopa. An inverse correlation was found between age and wearing off, suggesting a marked sensitivity of younger patients to levodopa. Future studies on the use of dopamine agonists should thus be stratified according to age.

We recorded cerebral evoked potentials, back and forward averaged from the EMG onset of the responding muscle, in three reaction time tasks, each requiring an identical motor response to an identical stimulus but differing in the nature of the sensory discrimination required. Two types of stimuli were presented: a rare one to which the subject responded with finger-extension, and a frequent one to which no response was required. We found a close but variable relationship between the cerebral events associated with performance of a task and the timing of the motor response. As completion of the discrimination process was delayed relative to stimulus occurrence, EMG activity began later relative to the cerebral potentials. Moreover, we were able to record these cerebral events only from the response to the rare (unexpected) stimulus and not when subjects were required to respond to the frequent stimulus, suggesting that the sensory discrimination, in these experiments, is an event that occurred only in the processing of the unexpected stimulus.

As the direct agonist with the widest clinical use, bromocriptine provides a unique window into the clinical spectrum of Parkinson's disease. The efficacy of bromocriptine for therapy of de novo Parkinson's disease has recently been confirmed using a double-blind design with L-Dopa (Sinemet). Over a period of 5.5 months, bromocriptine was found to be as effective as L-Dopa in reducing the functional and neurological disability of Parkinson's disease. This study complements others and demonstrates a role for bromocriptine as de novo therapy. A longitudinal study comparing bromocriptine with L-Dopa is underway, but previous observations with bromocriptine suggest modest, transient beneficial effects with significantly less fluctuation of disability and less dyskinesia when used alone or in combination with L-Dopa. The transient benefits of bromocriptine on progressive disability suggest that both pre-and post-synaptic defects are eventually involved in Parkinson's disease. While agonists with improved efficacy and minimal side effects are required for symptomatic treatment of Parkinson's disease, strategies to protect pre- and post-synaptic neuron populations against progressive dysfunction must be developed.

The ALS symposium in Vancouver was the first of its kind in Canada and was a contribution from both American and Canadian investigators. The main points presented were (1) a definition of what is truly ALS, in the clinical and pathological sense, based on what is called “classical” ALS; (2) how neurons may be cultured to provide a valuable experimental tool; (3) the significance of lipid abnormalities in ALS and the characterization of the ALS-like syndromes produced by hexosaminidase A deficiency; (4) the possible role of autoimmune disease as it may accompany classical ALS and nerve growth factor derived from skeletal muscle; (5) the western Pacific form of ALS as it has been intensely studied and has given rise to two hypotheses on pathogenesis: mineral toxicity caused by secondary hyperparathyroidism and poisoning through ingestion of the cycad seed, and (6) the possible abiotropic interaction of one or many environmental toxins over a lifetime with the aging nervous system, depleting it of its frail reserve of neurons.

This paper presents a review of the literature on the therapeutic action and the side effects of the two main dopaminergic agents: L-DOPA/decarboxylase inhibitor (L-DOPA/DI) and bromocriptine (Parlodel ®) used either as monotherapy or in combination in patients with Parkinson's disease. The combination of L-DOPA/DI and bromocriptine gives the best therapeutic efficacy (49% improvement) in the total score (bradykinesia, rigidity and tremor). However, treatment by monotherapy or combination gives the same pattern of activity: greatest improvement in tremor, followed by rigidity and bradykinesia. Improvement observed in the short term is not sustained over longer periods of time for monotherapy with either drug. The short-term side effects are similar for each treatment, whereas long-term complications (dyskinesia, end-of-dose deterioration and on-off phenomenon) appear only when levodopa is used, alone (high incidence) or in combination with bromocriptine (low incidence). The overall optimum treatment is obtained with a combination of L-DOPA/DI and bromocriptine.

We have evaluated 5 DA agonists-bromocriptine, lergotrile, lisuride, pergolide, and mesulergine in studies encompassing 278 patients with advanced PD. In most of our patients the DA agonist was added to levodopa. Most of our patients were no longer satisfactorily responding to levodopa. Previous attempts at managing these patients by changing the dose of levodopa (increasing or decreasing it), the treatment schedule, or the ratio of levodopa to carbidopa or by temporarily discontinuing levodopa [drug holiday] were unsuccessful. The majority of our patients had diurnal fluctuations in performance, either “wearing off” or “on-off” phenomena. The addition of a DA agonist resulted in a decrease in parkinsonian disability in most patients and a decrease in the severity of the diurnal fluctuations in performance. Improvement in many patients was maintained for at least 2 years. Adverse effects included mental changes, dyskinesias, orthostatic hypotension, and nausea. All of the adverse effects were reversible when the agonist was decreased or discontinued. As a group the agonists behaved similarly but individual patients often responded better to one agonist than another. The main role of agonists is in combination with levodopa in the treatment of patients with early PD who have not yet developed dyskinesias or diurnal fluctuations in performance.