Clinical diagnosis of Parkinson's syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 year experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M- 50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinson's disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldt's disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration.

To determine whether a history of exposure to rural environmental factors leads to an increased likelihood of developing idiopathic Parkinson's disease, we conducted a case-control study of 130 cases and 260 randomly selected community controls (matched with the cases by sex and age ± 2.5 years at a ratio of 2 controls: 1 case) in the city of Calgary. The data were collected by personal interviews and were analyzed using conditional logistic regression for matched sets. The ages of the cases ranged from 36.5 to 90.7 years (mean = 68.5 ± 11.3 years). The mean age at diagnosis was 61.1 ± 12.4 years. The mean duration of disease was 7.8 ± 0.6 years. Eleven (9.1%) cases were diagnosed before age 40. In this sample from the Province of Alberta, Canada, no significant increase in risk for Parkinson's disease was associated with a history of rural living, farm living, or well water drinking in early childhood or at any time during the first 45 years of life.

Dendritic spheroid bodies (SBs) and Lewy bodies (LBs) were identified in comparable numbers in the substantia nigra pars compacta (SBC) of nine parkinsonian cases and one case of striatonigral degeneration but were not found irt cases of Huntington's disease or neurologically normal controls. The immunohistochemical profile of the SBs in dystrophic dendrites of nigrostriatal dopaminergic neurons was remarkably similar to that of the LBs found within dendrites or free of the SNC neuropil. Both types of inclusions stained positively with antibodies to tyrosine hydroxylase, ubiquitin and microtubule-associated protein-2 (MAP2), and negatively for Tau-2, although they had different ultrastructural appearances. A few intracellular LBs were stained by antibodies to neurofilament proteins (NFs) 68, 160, and 200 kD, but dendritic SBs and extracellular LBs were not so stained. These data indicate that dendritic SBs and extracellular LBs may have a common molecular pathogenetic origin in Parkinson's disease. On the other hand, the SBs seen in the pars reticulata (SNR) and in the distal nigrostriatal axons even in control cases were generally stained by antibodies to NFs and ubiquitin but not to MAP2. This latter staining pattern in similar to that shown by SBs in the anterior horn in ALS and in the cerebellum of neurologically normal brains and is believed typical of axonal as opposed to dendritic SBs.

Venous angiomas (developmental venous anomalies) are vascular malformations increasingly recognized in general neurosurgical or neurological practice. They are associated with intracranial hemorrhage, seizures, or progressive neurological deficits or found as incidental findings in patients who present with headaches or have neuroimaging studies for investigation of unrelated neurological disorders. Since venous angiomas drain normal cerebral tissue within a functionally normal arterial territory, resection can lead to venous infarction. This report studies 27 patients with venous angiomas, all of whom had conservative treatment. The venous angioma was considered to be responsible for the onset of neurological symptoms in 14 patients (7 with hemorrhage, 3 with hemorrhage and seizures, 2 with seizures, one with an extrapyramidal movement disorder, and one with motor deficit). Thirteen patients had incidental lesions (8 with headache, and 5 with unrelated neurological symptoms). Ten venous angiomas were in the posterior fossa; seven in the cerebellum. Location did not correlate with symptomatic presentation. No patient with hemorrhage required surgical evacuation of the hematoma. No patient died or had significant morbidity during the follow-up interval (mean of 3.7 years). Venous angiomas are low flow, low resistance vascular malformations, many of which are not associated with neurological sequelae. Our series supports the concept that surgical removal or radiosurgical obliteration should not be performed unless a patient has a second life threatening hemorrhage.

Patients with Myotonic Dystrophy (MyD) frequently suffer from a dysfunction of the primary sensory pathways, as documented by abnormalities of short-latency evoked potentials. Impairment of intellectual functions has been less extensively investigated. Short-latency brainstem auditory evoked potentials (BAEPs) as well as long-latency auditory event-related potentials (ERPs) were recorded from 5 female and 6 male patients affected by MyD. A simple discrimination (“oddball”) paradigm was used to record ERPs to tones from Fz, Cz, Pz. Both BAEPs and ERPs were significantly altered as compared to normals. BAEP abnormalities were detected in 9 patients and ERP components N2 and P3 were delayed or absent for all patients, who nonetheless correctly discriminated between tones. These data indicate that CNS dysfunction in MyD involves not only primary sensory systems but also neural mechanisms underlying cognitive events and ERP generation.

Amantadine hydrochloride (AH) was administered (200 mg/day) for more than three months to 17 patients with Friedreich's ataxia (FA) and to 12 patients with olivopontocerebellar atrophies (OPCA) in an open clinical trial. Reaction time (RT) and movement time (MT) with the right and left hand were measured before and after treatment. A striking improvement on both RT and MT was observed in the OPCA group (on seven out of eight measures), whereas in the FA patients improvement was seen only in two out of four MT measures with no improvement in RT. Both groups had low levels of homovanillic acid (HVA) in their cerebrospinal fluid before treatment, relative to their controls. However, improvement with AH was not related to HVA levels.

The clinical functions of the posterior columns of the spinal cord and the signs of disease of these structures have been debated for years. Todd in 1847 and Schiff in 1858 knew the functions of the posterior columns and 10 years later Brown-Sequard knew as well. Reynolds, Romberg, and Duchenne, each described a posterior column syndrome based on a disease in which the primary lesion was not in the posterior columns. In the last 150 years almost every white matter structure of the cord has been credited with serving the sensations that we now know are a function of the posterior columns. Vibration, joint position and movement as well as discriminatory touch each seem to be served by separate fibres of the posterior columns and medial lemniscus. There is evidence of this in cat and man. These sensations may be lost individually, totally, or in certain stereotyped combinations. Vibration or joint sense is commonly lost alone. When a discriminatory touch sensation is lost with one other sense, it is almost inevitably joint position sense. Absent discriminatory touch and vibration sense with normal joint position sense appears to be unknown. This functional separation continues into the thalamus. At the highest level there is no evidence that vibration sense has any conscious somatosensory cortical affiliation, while joint position and discriminatory touch senses definitely do.

This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antogonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.

A stereotyped 32 Hz rolandic rhythm maximal over the mesial cortex and occurring only with voluntary movement is described in a patient with tonic postural seizures. This abnormal but nonictal rhythm, which is probably generated subcortically, is expressed synchronously at the level of the cortex and peripherally in the EMG.

In a series of 23 patients, the commonest cause of accessory nerve palsy was surgical trauma at the time of lymph node biopsy. The less common causes were penetrating or blunt trauma and a few were of spontaneous onset. There was involvement of adjacent motor sensory nerves in about half of the patients. The prognosis was better following blunt trauma, stretch injuries and after a spontaneous onset. The anatomical relationships of the accessory nerve and aspects of the clinical picture and management are discussed.

A 29 year old man had an accessory branch of the superficial peroneal nerve which entered the foot by rostro-caudally traversing the lateral malleolus laterally. The nerve was entrapped by a fascial band, resulting in pain over the lateral malleolus and dorsum of foot. Symptoms resolved when the nerve was surgically released.

Neurologic manifestations, afflicting up to 70% of SLE patients, include psychosis, seizures, chorea, neuropathies, and stroke. MRI is useful in evaluation of lupus patients and several reports have documented cerebral atrophy or focal hyperintensities. We report an unusual MRI appearance in a 56-year-old woman with SLE, diagnosed on the basis of pleuritis, lymphopenia, anti-DNA antibodies, and neurologic involvement. She reported recent onset of Raynaud's phenomenon and generalized macular rash. She presented after two months of gradual deterioration with memory loss, flattened affect, dysphagia, dysarthria, anomia, and somnolence, without focal neurologic signs. Investigations included elevated ESR, reduced complement, normal CSF without oligoclonal bands, negative viral serology, normal hormone and vitamin levels, normal renal and hepatic function. Neuropsychologic testing showed widespread impairment (WAIS-R: FSIQ-63; WMS-69; DRS-98; RCPM-14; WAB AQ-78.8). CT was normal but MRI showed strikingly symmetric, confluent hyperintensities extensively involving cerebral and cerebellar white matter on Tl and T2 weighted scans. Basal ganglia and subependymal and subcortical white matter were spared. Treated with prednisone, the patient made a gradual, but incomplete, recovery. These MRI findings may reflect widespread vasculopathy or direct immunologic brain insult with or without imunologic blood-brain barrier disruption.

A Caucasian girl developed slowly progressive sensory neural deafness and bulbar and spinal muscle weakness typical of the Vialetto-Van Laere syndrome. As the condition progressed the major disabilities became dysphagia, respiratory muscle weakness and postural hypotension. Treatment with gastrostomy feedings, oxygen and fludrocortisone acetate produced worthwhile functional improvement.

We report the pathological and molecular biological findings of human T-cell lymphotropic virus type 1 (HTLV-1) infection of the spinal cord in a patient with a chronic progressive myelopathy. Light microscopy disclosed loss of myelin and axons, thickening of blood vessels and a lymphocytic cell infiltrate in the spinal cord especially at the cervical and thoracic levels. Electron microscopy confirmed the vascuolar appearance seen with light microscopy but virus particles were not observed. The HTLV-1 gag gene could be amplified (by polymerase chain reaction) from cervical spinal cord tissue while not from elsewhere in the neuroaxis. The presence of HTLV-1 geonomic material in spinal cord tissue has not been previously reported.

Most patients with brainstem hemorrhage have a poor prognosis. There are occasional reports of a favorable outcome with hematomas restricted to the mid-brain region. We report two patients with hematomas within the lower brainstem (pons and medulla) who made a good recovery. Diagnosis was unsuspected until the cranial CT scan was done. Angiography was normal in both cases. Recovery was excellent in one and fair in the second patient. Patients with medullary hemorrhage are at risk for aspiration and may suddenly develop respiratory arrest and therefore should be carefully observed. Our review of the literature suggests that with some small brain-stem hemorrhages recovery is good to excellent and recurrences are rare.

The course of a patient with an olfactory neuroblastoma treated with conventional doses of chemotherapeutic agents and radiotherapy is presented. The patient survived 34 months after tumour necrosis with resultant pneumocephalus requiring surgical intervention.

Little attention has been paid to an early Canadian experiment in neuronal regeneration and what may have been the world's first attempt to replace a damaged spinal cord with a transplant. In 1905, a paper entitled “Regeneration of the Axones of Spinal Neurones in Man” was published in the Montreal Medical Journal. It had been read at the Panamerican Congress in Panama. The author was David Alexander Shirres, a Scot who had trained in Aberdeen in neurology and neuropathology. He came to Canada in 1902 to assume the position of neurologist at the Montreal General Hospital, with the responsibility of establishing clinics and teaching undergraduates about the mysteries of the nervous system. To my knowledge, he was the first man in Canada to be appointed as a neurologist. (There were others, notably James Stewart, who devoted most of their time and writing to diseases of the nervous system but considered themselves to be internists. Stewart, for example, left the MGH to become the first chief of medicine at the Royal Victoria Hospital in Montreal.)