Atypical forms of progressive multifocal leukoencephalopathy (PML) may simulate other disorders. A previously healthy 70-year-old female developed unsteadiness of gait, dysarthria, dementia and weakness leading to inanition and death from bronchopneumonia over a 43 month period. The diagnosis of PML was not suspected prior to death.

Neuropathologic examination of the brain disclosed characteristic findings of PML-deep bilateral cerebral demyelinative foci with enlarged gemistocytic astrocytes and swollen oligodendrocytes containing intranuclear inclusions. Electron microscopy identified papova virus particles within these inclusions. An underlying source of immunosuppression was not identified either premortem nor at the time of autopsy.

The prolonged clinical course, simulating that of a primary degenerative disease, and the lack of apparent immunocompromise are unusual features of PML and lend credence to the suggestions that variations in its expression and course are to be expected.

We describe a child with a cerebellar astrocytoma who presented with paroxysmal segmental rhythmic myoclonus. The movement disorder was characterized by focal onset in the left eyelid followed by a sequential march of clinical events. There were no clinical or laboratory findings to suggest brainstem infiltration or cerebral involvement. Marked clinical improvement followed tumour resection. We suggest that the cerebellar lesion was primarily responsible for the movement disorder.

In 1984 we made the first observation of a correlation between early age exposure to rural environment (and drinking well water) and development of idiopathic Parkinson's disease (IPD).13 These findings were subsequently confirmed elsewhere (Barbeau, 1985 ;25 Tanner, 198526). Analysis of all early age onset IPD (EPD) cases born and raised in Saskatchewan revealed that 20 of 22 had exclusively rural exposure during the first 15 years of life. This distribution was significantly different from the general population (p = 0.0141). Further study of the EPD group included sampling and metal analysis of childhood sources of drinking water in 18 cases and 36 age and sex-matched controls. Water collected from the two groups was analyzed for 23 metals (including 7 elements implicated in the etiology of IPD). There was no difference in the metal composition of the water between the two groups.17 Finally, a review of herbicide and pesticide use in Saskatchewan agriculture was undertaken to determine if there was an increased incidence of EPD following utilization of any particular chemical. No increase was found in the incidence of EPD with the introduction of any pesticide or herbicide, including Paraquat, for agricultural use. We conclude that there is a strong correlation between early age rural environmental exposure and development of IPD. We believe well water is a likely vehicle for the causal agent, but neither water metal concentration nor any of the herbicides and pesticides used in Saskatchewan agriculture are related to the cause.

A twenty-eight year old woman presenting with subarachnoid hemorrhage was found at angiography to have a left anterior cerebral-anterior communicating artery aneurysm. Also identified was a fenestration of the right supraclinoid internal carotid artery with an associated accessory middle cerebral artery. This appears to be the second reported case of fenestration of the intracranial internal carotid artery. Fenestrations of cerebral vessels and their possible embryologic origins are briefly reviewed.

A 35-year-old woman who died after a long history of an illness consistent with Shwachman-Diamond Syndrome, was found to have extensive calcified necrotizing lesions confined to the pontocerebellar fibers of the basis pontis. The possible relationship of this recently described lesion to the patient's immunosuppressed state and/or other systemic metabolic disturbances is discussed.

Three patients presented with hand wasting and weakness secondary to mid-cervical spinal cord compression. This was due to cervical spondylosis in two patients and a meningioma in one case. This phenomenon is probably similar to that seen with foramen magnum lesions and may be due to spinal cord ischemia distal to the compression, secondary to venous stasis.

Parkinson's disease (PD) has been proposed to result from the interaction of aging and environment in susceptible individuals. Defective metabolism of debrisoquine, inherited as an autosomal recessive, has been associated with this susceptibility. In 35 PD patients and 19 age-matched controls, no significant differences in debrisoquine metabolism were found, although a trend to impaired metabolism was noted in patients with disease onset ≤40. Foci of PD patients were associated with rural living and well water drinking, or rural living coupled with market gardening or wood pulp mills. In a questionnaire survey, patients with PD onset ≤age 47 were significantly more likely to have lived in rural areas and to have drunk well water than those with onset ≥age 54 (p≤0.01). Because of population mobility in North America, a case-control study designed to test environmental, occupational, dietary and other proposed risk factors for PD was conducted in China, where the population is more stationary and the environment more stable. No significant differences in incidences of head trauma, smoking or childhood measles were found between patients and controls.

A young man developed virologically proved hydrophobic rabies three months after being scratched on the cheek by a bat in Northern Alberta. He became comatose after 8 days and died 5 weeks after vigorous therapy with immune globulin, interferon and Vidarabine, and excellent maintenance of oxygenation. Electroencephalographic deterioration was gradual. At postmortem examination, the brain showed widespread loss of nerve cells, mild diffuse inflammatory changes and no Negri bodies. The lesions of massive laminar necrosis of the cerebral cortex, total loss of Purkinje cells with preservation of the granule cell layer, and severe softening of the amygdala are attributed to direct viral action rather than to anoxia or brain swelling with respirator brain.

Pineal tumours are commonly of germ cell origin. The endodermal sinus tumour is a rare histologic subtype that is highly malignant and radioresistant. A single case is described and compared to six reported intracranial cases in which chemotherapy was used in addition to surgery and/or radiation. Although a beneficial effect of chemotherapy cannot be proven, the probable benefit in non-CNS cases requires that it be strongly considered. A uniform approach to diagnosis, investigation and treatment for intracranial tumours of this type is suggested.

We report the experience at a large teaching hospital over a 10 year period with Miller Fisher Syndrome, facial diplegia, and multiple cranial nerve palsies. In these patients, absence of drowsiness on examination, normal cranial CT scans, albumino-cytological dissociation on CSF examination and slowing of nerve conduction, all suggest that a peripheral nerve dysfunction is the underlying mechanism. Pertinent literature is reviewed, in an attempt to separate these probable variants of Guillain-Barré Syndrome from brainstem encephalitis, with which they may be confused.

Herpes zoster ophthalmicus can be complicated by a delayed ipsilateral cerebral angiitis which may cause infarction and a smoldering meningoencephalitis. We describe such a case treated successfully with steroids and acyclovir. It is important to consider the diagnosis of this disorder early since therapeutic intervention may prevent an otherwise high morbidity and mortality. Steroids may have to be continued for some time after clinical resolution, using the ESR as a guideline for decreasing dosages.

Progressive degeneration of functionally related groups of neurons occurs in certain infective, toxic, nutritional and genetically determined neurological diseases. It also takes place in normal aging, and several of the regions that undergo selective decay with the passage of time seem to be the same target regions that are afflicted in degenerative disorders such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Infective etiology is relatively easy to exclude by a combination of immunological tests and transfer experiments. Genetic causation can be rendered unlikely when large kindreds are available for study. Nutritional deprivation and acute or subacute toxicity are accessible to explanation by examining the environment. The most difficult mechanism of pathogenesis to refute is chronic toxic damage, where the lesion may derive from long-term exposure to a relatively widespread noxious agent or agents. Variations in involvement of individuals within a population may stem from differing capacities to activate or inactivate a toxin. Inherent in this concept of etiology is recognition that compensatory potential within the central nervous system may contribute to prolonged existence of subclinical lesions so that a latent period may exist for several decades, between causal event and the onset of symptoms. Furthermore, progressive clinical deterioration may take place even though the cause may have been transient, many years before. The histological features associated with Parkinson's disease, Alzheimer's disease and ALS may be nonspecific indicators of neuronal “illness”, there being a predilection for certain morphological markers to appear more frequently in particular circumstances and particular regions associated with the pathology of particular diseases.

MPTP induces parkinsonism in monkeys by destruction of the substantia nigra, pars compacta. It can also damage ventral tegmental dopamine neurones and the noradrenergic locus coeruleus, both of which may be affected in Parkinson's disease. Motor symptoms in MPTP-treated monkeys respond readily to levodopa or dopamine agonist therapy. Administration of levodopa over 4-8 weeks leads to the emergence of “peak- dose” dyskinesia. Such abnormal movements are not seen following challenge doses of levodopa in animals not on long-term therapy. Radioligand studies reveal a 40-180% increase in D2 receptor binding in the striatum of parkinsonian monkeys. 2-deoxyglucose studies of regional brain metabolism indicate that MPTP-induced parkinsonism is characterised by abnormally increased activity of medial pallidal neurones which project to the thalamus and pedunculopontine nucleus and reduced activity of subthalamic nucleus neurones.

Although relatively uncommon, interhemispheric subdural hematoma (ISDH) occurs more frequently than was suspected before the advent of computerized tomographic (CT) scanning. When its mass is sufficiently large to compress the medial cerebral hemisphere, specific focal neurological abnormalities may occur. These include weakness of the contralateral leg, or contralateral hemiparesis with the leg being weaker than the arm. On the unenhanced CT scan ISDH is seen as a crescent shaped, midline hyperdensity. Treatment is dictated by the clinical course. Evacuation of the hematoma by parasagittal craniotomy is recommended if the symptoms are pronounced.

We report the seventh case of a self-limiting syndrome of brain, inner ear and retinal microangiopathy which affects adult women producing mild to moderate mental status and personality changes, mild pyramidal and cerebellar dysfunction, patchy and asymmetrical visual loss secondary to non-inflammatory retinal infarctions, and asymmetrical neurosensory hearing loss. There is no clinical or laboratory evidence of involvement beyond the brain, the eyes and the ears. Magnetic resonance imaging or brain biopsy in previously reported cases best outline the brain pathology: multiple microinfarcts. All cases have been treated with steroids or cyclophosphamide. The etiology is unknown but may be related to systemic lupus erythematosus.