White matter hyperintensities in dementia of Alzheimer's type and in healthy subjects without cerebrovascular risk factors. A magnetic resonance imaging study.

T2-weighted (0.5 T) magnetic resonance images were used to study the prevalence of subcortical white matter hyperintensities (WMHIs) in 22 patients with dementia of Alzheimer's type (DAT), 20 age-matched older healthy control subjects, and 10 younger healthy control subjects. Exclusionary criteria for all groups included cerebrovascular risk factors. All subjects had Hachinski Ischemic Index scores of less than 2 and computed tomographic scans showing no infarct. The WMHIs were classified as periventricular WMHIs or deep WMHIs and graded 0 through 3 (0 indicated absent, and 3, severe). For the group with DAT and older control subjects, periventricular WMHIs and deep WMHIs were graded 2 or 3 in fewer than 17% and 27% of subjects, respectively, whereas in the younger control subjects, all ratings were grade 1 or less. Serum cholesterol and systolic blood pressure values, although within the normal range, were elevated significantly in older control subjects when compared with those in younger control subjects. No significant differences in WMHI ratings, blood pressure, cholesterol, or triglyceride levels were found between patients with DAT and age-matched control subjects. Systolic blood pressure levels correlated with the severity of periventricular WMHIs only in older control subjects. Age correlated with periventricular WMHIs and deep WMHIs within both the older control subjects and the patients with DAT. There was no significant correlation between WMHIs and the severity of dementia in the group with DAT. These results suggest that, in subjects screened for cerebrovascular risk factors, WMHIs are rare and occur with identical frequency in patients with DAT as in age-matched healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenelzine toxicity responsive to dantrolene.

We describe a 44-year-old man with signs of phenelzine sulfate (a monoamine oxidase inhibitor) toxicity, including coma, hyperpyrexia, hypotension, tachycardia, generalized muscular rigidity, and hyperreflexia. He recovered after IV treatment with dantrolene. Dantrolene appears to be an effective treatment for phenelzine toxicity manifested by a hypermetabolic state.

Anti-Ro(SS-A) autoantibodies in central nervous system disease associated with Sjögren's syndrome (CNS-SS): clinical, neuroimaging, and angiographic correlates.

OBJECTIVE: To examine in Sjögren's syndrome (SS) the interrelationship between the presence of the anti-Ro(SS-A) antibody response and (1) concomitant presence and type (ie, focal or nonfocal) of CNS disease (CNS-SS), (2) cross-sectional brain MRI or CT, and (3) abnormal cerebral angiography. METHODS: Neurologic, neuroimaging, and angiographic features of CNS-SS patients were correlated with the presence of precipitating anti-Ro(SS-A) autoantibodies detected by gel double-immunodiffusion or quantitative ELISA, which detects antibodies directed against the 60-kd peptide. Statistical analyses were performed using Fisher's exact test (two-tailed) with Haldane's adjustment and odds ratio with Cornfield 95% confidence intervals. RESULTS: Precipitating antibodies against the Ro(SS-A) antigen, determined by gel double-immunodiffusion, were present in an increased frequency in CNS-SS patients with (1) documented clinical CNS disease, (2) focal clinical CNS manifestations and serious complications, (3) large regions of increased signal intensity, consistent with ischemia/infarcts on brain MRI scans or regions of decreased attenuation consistent with infarcts on CT, and (4) abnormal cerebral angiograms consistent with small-vessel angiitis. Finally, the anti-Ro(SS-A) antibody response in CNS was directed against the 60-kd peptide specificity, determined by ELISA. CONCLUSIONS: Clinical, neuroimaging (cerebral CT), and angiographic observation suggest that a subset of anti-Ro(SS-A) antibody-positive, in contrast with -negative, CNS-SS patients have more serious and extensive CNS disease, some with frank cerebral angiopathy. Anti-Ro(SS-A) antibodies are postulated to play a role in mediating or potentiating vascular injury in CNS-SS.

Blood buffy coat from Alzheimer's disease patients and their relatives does not transmit spongiform encephalopathy to hamsters.

There was a report of spongiform encephalopathy transmitted to Syrian hamsters by intracerebral inoculation with the blood buffy coat of patients with Alzheimer's disease (AD) and their unaffected first-degree relatives. We attempted to verify that report, taking measures to reduce the risk of contaminating samples with agents causing spongiform encephalopathies. We obtained blood from 50 subjects, including six patients with familial AD, 21 unaffected first-degree relatives (siblings and offspring) of patients with familial AD, and 20 control subjects. We inoculated the buffy coats intracerebrally into Syrian LVG hamsters, observed them for signs of neurologic disease, examined their brains for neuropathologic changes at time of death, and performed serial (blind) passages by inoculating suspensions of all recovered brains into fresh LVG hamsters. We discerned no clinical illness or histopathologic changes resembling experimental spongiform encephalopathy in any hamster inoculated with human buffy coat nor in blind-passage hamsters, nor were the life spans of those hamsters shortened. We conclude that AD is not caused by an agent that transmits spongiform encephalopathy to hamsters.

Thyrotropin-releasing hormone (TRH) in murine motor neuron disease (the wobbler mouse).

Clinical benefits of thyrotropin-releasing hormone (TRH) were tested in wobbler mice, an animal model of motor neuron disease. After the disease was clinically recognized at 3-4 weeks, the animals were divided into two groups, each group consisting of 5 pairs of wobbler mice and normal littermates. TRH (50 mg/kg) and normal saline (NS) were injected intraperitoneally daily, 6 times per week for 9 weeks, in a double-blind study. Weekly assessments consisted of front paw grip strength, push walking, body weight, and semiquantitative grading. At the end of the trial, the brain and spinal cord were sampled to measure TRH and cyclo (His-Pro) concentrations. Progression of motor neuron disease was evident in wobbler mice, regardless of treatment. Descriptive semiquantitative gradings showed the tendency of improvement in TRH-treated wobbler mice. In saline-injected controls, TRH levels in the cervical spinal cord were significantly increased (P less than 0.01) in wobbler mice compared to littermates. However, with TRH treatment, there was no significant difference in TRH and cyclo (His-Pro) levels in any neural tissue between wobbler and controls. The lack of clinical benefits with TRH in wobbler mice may be due to increased TRH levels found in diseased spinal cord in murine motor neuron disease.

Effect of gender on glucose utilization rates in healthy humans: a positron emission tomography study.

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women.