Richard H. Hewlett

Tuberculous cerebrovascular disease: A review

Cerebrovascular complications of tuberculous meningitis are common, and may represent its most serious legacy. They present in clinically diverse ways, and continue to develop during the initial stages of treatment. Magnetic resonance imaging is the imaging modality of choice in detecting brain infarcts, typically revealing multiple or bilateral lesions in the territories of the middle cerebral artery perforating vessels. Vessel pathology appears to be a consequence of its immersion in the local inflammatory exudate. Infiltrative, proliferative and necrotising vessel pathologies have been described, but the relative contributions of each and of luminal thrombosis to brain damage remain unclear. There is some evidence that vasospasm may mediate strokes early in the course of the disease and proliferative intimal disease later strokes. Anti-tuberculous chemotherapy appears to be relatively ineffective in preventing vascular complications, perhaps suggesting an immune mechanism. However, a preventive role for corticosteroids remains to be proven. Study of the molecular pathogenesis of TBM vasculopathy is in its infancy. This review focuses in particular on pathogenetic aspects of tuberculous cerebrovascular disease, with a view to its future targeted prevention.

DSM-III-R Classification of Psychiatric Symptoms in Systemic Lupus Erythematosus

DSM-III-R criteria applied in the evaluation of 88 systemic lupus erythematosus patients revealed a point prevalence rate of 18.2% for psychiatric disorders, the most common diagnosis being adjustment disorder (11.4%). No patients had disorders compatible with a functional psychosis. Psychiatric morbidity was not associated with increased disease activity, corticosteroid use, brain magnetic resonance imaging abnormalities, or electroencephalogram abnormalities. High scores on a life event scale were associated with psychiatric disorders, suggesting that psychosocial stress is etiologically important. Cognitive testing showed that poor performance on the Stroop Colour-Word Inference Test was associated with psychiatric disorders.

Resting brain perfusion in alcohol-induced psychotic disorder: A comparison in patients with alcohol dependence, schizophrenia and healthy controls

INTRODUCTION Alcohol-induced psychotic disorder (AIPD), also known as alcohol hallucinosis, is a rare complication of alcohol abuse. The underlying pathophysiology is poorly understood, and the disorder needs to be differentiated from alcohol withdrawal delirium and schizophrenia. No brain-imaging studies in AIPD have been reported to date. Case reports of brain imaging in AIPD suggest possible dysfunction in the thalamus, basal ganglia, frontal lobes and cerebellum. Our aim was to prospectively compare resting brain perfusion (rCBF) in patients with AIPD, uncomplicated alcohol dependence, schizophrenia and healthy volunteers. METHODS Single photon emission computed tomography (SPECT) was utilized to compare rCBF in patients with AIPD (n=19), schizophrenia (n=16), uncomplicated alcohol dependence (n=20) and healthy volunteers (n=19). RESULTS Increased rCBF was demonstrated in the right calcarine area in patients with AIPD compared to healthy volunteers, with a trend towards increased rCBF to the frontal and temporal lobes and the right pallidum. Decreased left sided rCBF to the putamen, parietal, mid-frontal and mid-temporal lobes and heterogenous flow to the cerebellum were demonstrated in patients with AIPD when compared to patients with uncomplicated alcohol dependence. The left posterior cingulate and right cerebellum showed higher and lower rCBF respectively in patients with AIPD compared to patients with schizophrenia. CONCLUSION Our findings implicate the right occipital lobe and possibly the cerebellum in the pathogenesis of AIPD and have similarities with those previously reported in alcohol withdrawal. Reduced rCBF to the frontal lobes, thalamus and basal ganglia in AIPD as suggested in previous case reports could not be confirmed.

Clinicoradiologic response of neurologic tuberculous mass lesions in children treated with thalidomide.

Neurologic tuberculous pseudoabscesses that clinically progress despite conventional antituberculosis therapy may be responsive to adjuvant thalidomide, a potent tumor necrosis factor-&agr; inhibitor. In this study, the addition of thalidomide provided substantial clinical benefit in the majority of patients, and magnetic resonance imaging evolution of lesions from early-stage “T2 bright” with edema to “T2 black” represented a marker of cure.

A study of meningiomas in South Africa: investigating a correlation between clinical presentation, histopathology and genetic markers.

Objective. To determine whether there are certain genetic markers which correlate with particular clinical characteristics of meningiomas including multiplicity, recurrence and calvarial erosion. Methods. Thirty-eight South African-born patients with meningiomas were recruited for this study. At surgery, blood and tumour specimens were obtained for histopathological, cytogenetic and molecular analysis. Loss of heterozygosity (LOH) on chromosomes 1p and 22q were investigated and the NF2 gene on 22q12.2 was screened for disease-causing mutations. Results. The commonest tumour locations were convexity (25%) and parasagittal (21%). The histology results showed that 86.8% of the patients had Grade I tumours and the remainder had Grade II tumours. A pathogenic nonsense mutation, R341X in the NF2 gene was found in only one patient. LOH on each of chromosomes 1p and 22q was observed in 44.7% of patients, but in different individuals. Significant associations were found between having specific tumour characteristics and both male gender (p-value = 0.0059) and 22q LOH (p-value = 0.0425). We estimated that having 22q LOH makes an individual approximately four times more likely to develop a tumour that exhibits multiplicity, recurrence or calvarial erosion (OR = 4.8; 95% CI: 1.2–23.4). Adjusting for gender strengthened this effect (OR = 6.1; 95% CI: 1.1–48.7). Conclusions. Our data indicate that male patients and patients with a meningioma that has 22q LOH are more likely to develop tumours exhibiting multiplicity, recurrence or calvarial erosion. We recommend that this subset of patients should be followed up more closely. Further study is needed to determine the benefit of adjuvant radiation therapy in this scenario.

Serotonin Receptors in the Medulla Oblongata of the Human Fetus and Infant: The Analytic Approach of the International Safe Passage Study

The Safe Passage Study is an international, prospective study of approximately 12 000 pregnancies to determine the effects of prenatal alcohol exposure (PAE) upon stillbirth and the sudden infant death syndrome (SIDS). A key objective of the study is to elucidate adverse effects of PAE upon binding to serotonin (5-HT) 1A receptors in brainstem homeostatic networks postulated to be abnormal in unexplained stillbirth and/or SIDS. We undertook a feasibility assessment of 5-HT1A receptor binding using autoradiography in the medulla oblongata (6 nuclei in 27 cases). 5-HT1A binding was compared to a reference dataset from the San Diego medical examiner’s system. There was no adverse effect of postmortem interval ⩽100 h. The distribution and quantitated values of 5-HT1A binding in Safe Passage Study cases were essentially identical to those in the reference dataset, and virtually identical between stillbirths and live born fetal cases in grossly non-macerated tissues. The pattern of binding was present at mid-gestation with dramatic changes in binding levels in the medullary 5-HT nuclei over the second half of gestation; there was a plateau at lower levels in the neonatal period and into infancy. This study demonstrates feasibility of 5-HT1A binding analysis in the medulla in the Safe Passage Study.