A 53 year old man developed symptoms of motor neuron disease in childhood. There was a family history of a similar disorder and it was felt to represent a form of Kugelberg-Welander disease. In addition to the motor deficits, sensory abnormalities in his legs were documented during life. Autopsy revealed anterior horn cell loss throughout the length of the spinal cord, with preservation of the phrenic nucleus. The lumbar dorsal root ganglia showed active degeneration of sensory neurons, with nuclear changes exceeding cytoplasmic ones. The fasciculus gracilis showed Wallerian degeneration. The findings provide direct evidence that sensory neurons can degenerate in some forms of motor neuron disease, and that the “demyelination” or “degeneration” of posterior columns sometimes seen in the various forms of motor neuron disease may actually be secondary to cell body disease in the dorsal root ganglia.

The purpose of this study was to determine the effectiveness of the non-competitive N-methyl-D-aspartate receptor antagonist dizocilpine, or (+)-5-methyl-10,l l-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801) in mitigating ischemic neuronal necrosis in the rat. Ten minutes of transient forebrain ischemia was induced by a combination of bilateral carotid clamping and hypotension to 50 mm Hg. Control animals received intravenous saline, whereas treated animals received dizocilpine, either 1 mg/kg iv 20 min. pre ischemia, 1 mg/kg iv 20 min. post ischemia, 10 mg/kg iv 20 min. post ischemia, 10 mg/kg ip 2 hrs. post ischemia, 10 mg/kg ip 24 hrs. post ischemia. The groups receiving dizocilpine before or up to 20 min. after ischemia all showed a significant reduction in the number of dead neurons as assessed by quantitative histopathology in hippocampus, caudate nucleus and cerebral cortex after one week of recovery. However, dizocilpine administered either 2 or 24 hrs. after ischemia afforded no protection. These results suggest that the potent non-competitive NMDA antagonist dizocilpine may have some value in protecting the brain from hippocampal and cortical neuronal necrosis after a short insult consisting of dense transient cerebral ischemia. Noteworthy is the fact that pharmacologic intervention in the post-ischemic period was successful in preventing neuronal death, provided that drug administration occurred within dizocilpine's “therapeutic window”.

A 57 year old man developed bilateral hypoglossal nerve palsies 6 years after radiotherapy for carcinoma of the uvula. Follow-up over 2 years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement. Reactive fibrosis and vascular insufficiency secondary to radiation and may have lead to hypoglossal nerve compression and infarction.

We have attempted to verify the presence of increased aluminum (Al) levels in Alzheimer's disease (AD) brains by energy dispersive X-ray microanalysis (EDX) and flameless atomic absorption spectrophotometry (AAS). Tissue from seven AD brains, mounted on carbon polymerized coverslips, were stained with Congored or treated immunohistochemically to allow optical localization of AD-associated lesions during EDX. Despite a demonstrated sensitivity of 20-25 ppm, we were unable to detect Al in either plaque cores or neurons containing neurofibrillary tangles. For AAS, wet weight samples (ranging from 48-144 mg) from six of the seven AD brains and four controls were selected from regions similar to those studied under EDX, i.e., Brodmann areas 9, 11, 28, 46, 47, and the hippocampus. The tissue surrounding each sample site was sectioned and stained for thioflavin S. Both controls and AD samples revealed similar levels of Al ranging from undetectable to 1.80 ng/mg wet wt. (mean AD: 0.28 ± 0.39 (SD), control: 0.54 ± 0.58 (SD)), independent of degree of histopathology or age of the case. We conclude that the combined strengths of these two techniques on similar tissue specimens demonstrate that abnormal Al levels are not required to produce the histologic findings of AD and that this element may not accumulate in the aging brain. It is unlikely, therefore, that Al is essential in the etiology of pathogenesis of plaques and tangles in AD. Al's role as a primary or secondarily associated event, when present, needs further delineation.

Two cases of deep cerebral venous thrombosis are presented with specific reference to the CT and MR findings. The MR findings are discussed, with comparison to the findings of superficial cerebral sino-venous occlusion.

A review of biochemical findings is presented which support the idea that Alzheimer's disease represents a condition for which tetrahydroaminoacridine (tacrine) may have a beneficial effect. There is evidence that clinical and histopathologic hallmarks of the disease relate to cholinergic and serotonergic dysfunction, with less obvious abnormalities in other neurotransmitters (aspartate, dopamine, gamma-aminobutyrate, glutamate, noradrenaline and somatostatin). Clincially relevant concentrations of tacrine may ameliorate the above presynaptic deficits without producing harmful (neurotoxic) effects of aspartate and glutamate. The disease seems to be associated with an early and clinically relevant degeneration of some neurons with cortical perikarya that release these amino acid transmitters. Studies are now required on the effect of tacrine on postulated harmful peptide-bond hydrolase activity within and around such cells.

Central nervous system toxoplasmosis is a well known disease of immunocompromised patients. Neuropathologic examinations have only rarely demonstrated spinal cord involvement. This report describes a fatal case of toxoplasmosis that presented with a subacute myelopathy. Toxoplasmosis should be considered in immunocompromised patients, including patients with the acquired immune deficiency syndrome, that develop intramedullary lesions of the spinal cord.

Intra-cerebral hemorrhage is an unusual and often fatal complication of endarterectomy (CEA). Previous cerebral infarction, intra-operative or post operative hypertension, and the use of anti-coagulants are some of the defined major risk factors. Hemorrhage usually occurs early after CEA, and a second hemorrhage has only once been reported. We wish to report a patient who developed three separate hemorrhages following CEA. This patient had a long history of poorly controlled hypertension. We believe that poorly controlled hypertension, in addition to other reported factors, may be an important separate risk factor for post-CEA hemorrhage.

We examined platelet aggregability during nocturnal sleep and daytime wakefulness in patients with a history of sleep-related stroke onset (SOS) and compared it to that of matched awake-onset stroke (AOS) patients and controls without evidence of vascular disease. Aggregability was evaluated in-vitro at least seven weeks following stroke onset. Platelets were more aggregable to ADP, collagen and arachidonic acid (AA) during both sleep and wakefulness in patients with AOS (p<0.01). No significant difference in the mean aggregation thresholds during sleeping or waking periods were found between SOS and control groups. However, platelets were significantly more responsive to AA during sleep than during wakefulness in the SOS patients (p<0.01). This difference was confined to the subgroup of SOS patients who had experienced nocturnal as opposed to daytime sleep-related stroke onset, suggesting that the observed difference in platelet responsiveness to AA may be related to a circadian fluctuation in platelet aggregability rather than to a sleep-related fluctuation. Significant sleep-related changes in platelet aggregability were not identified in the other two groups.

An unusual case of Progressive Multifocal Leukoencephalopathy (PML) in a Haitian man with AIDS is reported. The lesions involving both white and gray matter are described radiologically and at post-mortem. The implications regarding neuroradiological differential diagnosis in AIDS as well as PML virulence in this type of patient are discussed.

A 39-year-old man presented with a pure motor stroke 9 days after cervical chiropractic manipulation. Computerised tomographic scanning showed a pontine infarct. Cerebral angiography showed changes consistent with the diagnosis of bilateral vertebral artery dissection. It is postulated that the infarct resulted from artery-to-artery embolism.

We report 12 patients with Sturge-Weber-Dimitri disease treated surgically between January 1975 and December 1987. Hemispherectomy was performed on ten, two others underwent occipital lobectomy for intractable seizures. All operations were performed between the ages of 3 months and 20 months, except in two at age 8 and 9 years. The onset of seizures in all was between 2 and 8 months of age, except for two at 15 months. There were no postoperative deaths. Postoperative shunt procedures were required in 3 out of 12 (25%). Postoperative seizure control for one year or more was achieved in 11 out of 12 patients. The remaining patient is on medication with no seizures, but follow-up is less than a year. Intellectual deterioration was not seen after surgery except in 2 patients who had late operations. We conclude that patients with Sturge-Weber-Dimitri syndrome who have intractable seizures in the first 6 months of life and unilateral hemispheric involvement should be considered for early resection of the involved hemisphere.

Anosognosia is a well-known manifestation of non-dominant parietal lobe lesions and typically lasts a few days. That anosognosia may last only a few minutes to a few hours, as observed in six patients, has not been reported. In five patients, transient anosognosia for equally brief left-sided hemiparesis was a manifestation of transient ischemic attacks (TIAs). In the sixth patient, anosognosia for both a left-sided motor seizure and a subsequent brief left hemiparesis could best be explained by an epileptic ictal and post-ictal transient dysfunction of the non-dominant parietotemporal cortex. Prompt recognition of transient anosognosia, whether ischemic or epileptic, is mandatory for proper diagnosis and for rapid initiation of specific therapy.

We report three siblings, offspring of normal consanguineous parents, with a progressive neurological illness that began in midlife and was characterized primarily by chorea and leading to death in the fourth decade. The proband had erythrocyte acanthocytosis with normal serum β-lipoprotein. Biopsy of left gastrocnemius muscle showed neurogenic muscular atrophy. There was a decrease in the numbers of large myelinated axons of the sural nerve. Postmortem examination of two cases showed marked atrophy, neuronal loss and gliosis of the caudate nucleus and putamen. Autosomal recessive inheritance is likely in this family.

Large pyramidal neurons of rat and human neocortex stain immunohistochemically for phosphate-activated glutaminase (PAG). In a limited number of postmortem brains, we find large reductions in cortical PAG activity in Alzheimer's disease (AD). This finding is consistent with histological evidence that pyramidal neurons are affected in AD. The reductions are greater than those found in the same samples in choline acetyltransferase (ChAT) but the possible deleterious effects of coma and similar premortem factors on human PAG activity have yet to be assessed. The activity of (β-glucuronidase, a lysosomal enzyme which occurs in reactive astrocytes, is elevated in the same samples. Positron emission tomography (PET) studies, using 18F-fluorodeoxyglucose (FDG), have demonstrated significant deficiencies in glucose metabolism in the cortex in AD, with the parietal, temporal and some frontal areas being particularly affected. We found in serial scans of 13 AD cases, including one relatively young (44-46 year old) familial case, an exacerbation of the defect over time in most cases. We have found a negative correlation between the regional metabolic rates for glucose (LCMR(s)) measured premortem and the (β-glucuronidase activities measured postmortem on a few AD cases that have come to autopsy. The correlations between LCMR(s) and PAG and ChAT activities tend to be positive. The results are consistent with previous suggestions that decreased LCMR(s) in AD reflect local neuronal loss and gliosis.

Hospital records of thirty patients with methanol poisoning were studied. Neurologic manifestations at presentation including coma, seizures and decreased visual acuity were seen in nineteen patients. The mean blood pH at presentation was significantly lower in the patients with these neurologic signs and symptoms than in the eleven patients without them (p < 0.05). Methanol levels at presentation tended to be higher in patients with neurologic manifestations at presentation and these patients tended to present later after methanol ingestion than those patients without neurologic manifestations. Fifteen patients with methanol poisoning developed serious neurologic sequelae or died. The mean blood pH was significantly lower in this patient group than in those who survived without neurologic sequelae (p < 0.05). Methanol levels at presentation were not different in the patients who developed neurologic sequelae or died as compared to those who did not. The time from ingestion of methanol to presentation at the hospital was however significantly longer in those patients who developed neurologic sequelae or died (p < 0.05). Initiation of treatment within eight hours of ingestion of methanol was associated with a better clinical outcome.

Involvement of the immune system in the pathogenesis of Alzheimer's disease was demonstrated in two ways: by the attachment of complement proteins to diseased tissue, and by the activation of cells associated with the immune system. Alzheimer brain tissue was stained immunohistochemically by antibodies to components of the classical, but not the alternative, complement pathway. Antibodies to Clq, C3d, and C4d stained senile plaques, dystrophic neurites, neuropil threads and some tangled neurons. Antibodies to a neoantigenic site on the C5b-9 membrane attack complex stained dystrophic neurites and many tangled neurons, but not senile plaques. Antibodies to Factor P and fraction Bb of Factor B, which are specific for the alternative complement pathway, did not stain Alzheimer brain tissue. The cellular immune response was evaluated by the presence of reactive microglia and by the infiltration of small numbers of T-cells into diseased brain tissue. Reactive microglia were identified by antibodies to HLA-DR, a class II major histocompatibility complex glycoprotein, and by enhanced staining with antibodies to leukocyte common antigen and the FC7RI and FcyRII receptors. T-cells were identified by antibodies to leukocyte common antigen, as well as the CD4 and CD8 surface proteins. Double immunostaining with antibodies to GFAP and MHC class I or class II antigens established that astrocytes, which are GFAP positive, do not express MHC antigens in Alzheimer's disease. Endothelial cells express MHC class I antigens while reactive microglia and some leukocytes express class II antigen.

A 77-year-old man developed progressive sensory and motor symptoms in the right lower leg. Examination showed neurological deficits in the distribution of the right tibial and common peroneal nerves. Swellings in both popliteal fossae were palpated. Investigation showed these to be large thrombosed aneurysms. On surgical examination on the right, the aneurysm was found to be compressing the distal sciatic nerve.

Most vascular injuries to the brain secondary to blunt head trauma involve the internal carotid circulation. A case of isolated basilar occlusion secondary to a clival fracture is described and compared to three other cases in the literature.

intraparenchymal solitary cyst of the medulla oblongata was diagnosed on MRI examination in a 66-year-old woman with a nine year history of progressive brainstem dysfunction and three negative CT scan examinations. Craniotomy and drainage of the cyst to the IVth ventricle led to remarkable clinical recovery. Biopsy of the wall of the cyst revealed an epithelial lining with tonofilaments, desmosomes and surface coating on ultrastructural examination. Immunohistochemistry demonstrated positive reactions of epithelium for keratins, cytokeratins, epithelial membrane antigen and Ulex Europeus lectin, indicating endodermal origin of the cyst.