C. van der Meyden

X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27

To date over 150 X linked mental retardation (XLMR) conditions have been documented. We describe a five generation South African family with XLMR, comprising 16 affected males and 10 carrier females. The clinical features common to the 16 males included profound mental retardation (100%), mutism despite apparently normal hearing (100%), grand mal epilepsy (87.5%), and limited life expectancy (68.8%). Of the four affected males examined, all had mild craniofacial dysmorphology and three were noted to have bilateral ophthalmoplegia and truncal ataxia. Three of 10 obligate female carriers had mild mental retardation. Cerebellar and brain stem atrophy was shown by cranial imaging and postmortem examination. Linkage analysis shows the gene to be located between markers DXS424 (Xq24) and DXS548 (Xq27.3), with a maximum two point lod score of 3.10.

The Impact of HIV on Meningitis as Seen at a South African Academic Hospital (1994 to 1998)

SummaryBackground:The increase in HIV infections in South Africa is alarming. The aim of this prospective 4-year study was to evaluate the rising incidence of HIV-related admissions due to meningitis at the Pretoria Academic Hospital (PAH) adult neurology ward and to investigate the spectrum of meningitis during this time. Patients and Methods: Adults with meningitis presenting at the PAH neurology ward from March 1994 through February 1998 were included. HIV antibody status was determined and patients were assigned to five categories: bacterial, tuberculous, viral and cryptococcal meningitis, as well as an uncertain category. Results: Over the 4-year study period 141 patients with meningitis were seen. Of these, 44 were HIV-positive (31%), with TB meningitis occurring in 16 (36%), cryptococcal meningitis in 22 (50%) and acute bacterial meningitis in three (7%). In the first 2 years of the study, 14% of patients were HIV positive; this figure rose to 44% in the 3rd year, and 57% in the final year. The spectrum of meningitis also changed: bacterial meningitis remained relatively stable at about 25% of the total; TB meningitis almost doubled from 16% in the 1st year to 31% in the last year of the study; viral meningitis initially occurred in 8% of patients and later in 3% of cases, while cryptococcal meningitis showed the most significant increase from 6% of cases in 1994/5 to 31 and 26% respectively in the last 2 years of the study. Conclusion: Over a 4-year period the HIV epidemic was responsible for a marked shift in the spectrum of meningitis towards chronic infections such as TB and cryptococcal meningitis at the PAH.

Effects of clobazam and clonazepam on saccadic eye movements and other parameters of psychomotor performance.

SummaryThe effects of two benzodiazepine anti-convulsants clobazam (20 mg) and clonazepam (2 mg) in a variety of psychomotor performance tests were compared in a placebo controlled double-blind acute oral dose study in ten healthy volunteers. Assessments included critical flicker fusion (CFF) threshold, the Sternberg memory scanning and choice reaction time (CRT), peak saccadic velocity (PSV) and visual analogue scales, all previously shown to be sensitive to the effects of benzodiazepines.Clobazam did not significantly impair saccadic eye movements, CFF threshold, Sternberg memory scanning and CRT compared to placebo. Clonazepam significantly lowered PSV, reduced the CFF threshold, slowed the Sternberg CRT and decreased an alertness factor in the visual analogue scales compared to placebo. Clonazepam significantly increased memory scanning time compared to clobazam. Clobazam was remarkably free of cognitive and psychomotor side-effects.

A prospective study of Glasgow Coma Scale (GCS), age, CSF-neutrophil count, and CSF-protein and glucose levels as prognostic indicators in 100 adult patients with meningitis.

BACKGROUND The Glasgow coma scale (GCS) is an objective measurement of a patients level of consciousness and has prognostic implications in traumatic head injuries. Morbidity and mortality of patients with meningitis have been related amongst others to level of consciousness, hypoglycorrhachia, extremes of age, and high CSF protein values. In this prospective study of 100 patients the correlation between the GCS, age, CSF-neutrophil count and CSF-glucose and protein levels and the eventual outcome of the patients was assessed. METHODS In 100 consecutive patients with meningitis (bacterial, viral, tuberculous, cryptococcal and other) the GCS, age, CSF-neutrophil count and CSF-protein and glucose levels were determined at admission. After treatment the outcome of the patient was assigned to one of four categories: healthy, minor and severe neurological deficits and death. RESULTS From a non-parametric one-way analysis of variance it was found that with respect to mean GCS-values significant differences were present among the outcome categories (P < 0.0001). The outcome categories did not differ significantly with respect to age, CSF-neutrophil count or CSF-glucose level, but did differ significantly with respect to the CSF-protein level (P < 0.0025). Additionally, 88% of patients with a GCS value of > 12 had a good neurological outcome, while 88% of those with a GCS value of < or = 8 had a poor outcome. CONCLUSION A good correlation between both the GCS and CSF-protein level at admission and the outcome of patients with meningitis was found, with the GCS value being a better prognostic indicator than high CSF protein levels.

Effects of single doses of diazepam, chlorpromazine, imipramine and trihexyphenidyl on visual-evoked potentials.

There is increasing evidence that the P 100 peak of the pattern-reversal visual-evoked potential (VEP-PR) is delayed by drug-induced dopamine antagonism and in Parkinsons disease. Recent studies have reported that components of the flash-VEP (VEP-F) are delayed by an anticholinergic which does not affect the VEP-PR. The present study found that a single dose of chlorpromazine increased the latencies of the VEP-PR and of the VEP-F and increased the VEP-F P2 amplitude. Trihexyphenidyl increased the VEP-PR amplitude but had only minor effects on the VEP-F. There was a tendency for imipramine to increase VEP-F latencies, especially the N3 peak, but had no effect on the VEP-PR. Both VEPs were unaffected by diazepam. These VEP findings add further support to the role of dopamine in the human visual system. Possible reasons are advanced for the failure of trihexyphenidyl to cause previously reported VEP changes associated with hyoscine hydrobromide. Several important issues need to be addressed by future research.

Lymph node biopsy as an aid in the diagnosis of intracranial tuberculosis

This report describes five patients with intracranial tuberculosis (TB): four with tuberculous meningitis and one with intracranial tuberculomas. In all cases the diagnosis was confirmed by excision biopsy of an enlarged cervical or axillary lymph node. The biopsies showed caseating granulomas and acid fast bacilli, confirming the diagnosis of TB within 48 h of admission. Lymphnode biopsies may be an effective and practical aid in diagnosing intracranial TB.

The comparison of the effects of multi and single doses of buspirone, chlordiazepoxide and hydroxyzine on psychomotor function and EEG

Summary— This study compares the effects of buspirone (5 mg), chlordiazepoxide (5 mg), hydroxyzine (10 mg) and placebo on psychomotor function and EEG, when taken thrice daily for a period of two weeks, with those after a single dose administration. Nine healthy volunteers participated in the study. The battery of psychomotor tests included peak velocity of saccadic eye movements (SEM), a Sternberg memory scanning and choice reaction time test (SMS‐CRT) and critical flicker fusion frequency (CFFF). The peak velocity of saccadic eye movements was significantly impaired by the single dose of hydroxyzine (P = 0.03) in comparison to the multidose results. A similar comparison regarding buspirone only approached significance (P = 0.07). The SMS‐CRT and CFFF did not reveal any difference between the multi and single dose regimens. Spectral analysis of the EEG did not distinguish between the multi and single dosage schedules regarding the respective drugs in the low doses administered.

IgA in epileptics receiving anticonvulsant therapy

SummaryEpilepsy is a common disorder and requires long-term drug treatment. Epileptics on anticonvulsant therapy have often been reported to have a depressed immune system, especially an IgA deficiency. An association with clinical manifestations has not yet been clearly explored. So far investigations have been performed in Whites only. The objectives of this study were to assess if there is a racial difference in the immune response to anticonvulsants between Blacks and Whites and to establish the clinical significance of the IgA deficiency. Our results showed normal IgA values in Black and White epileptics on anticonvulsant therapy. This implies, at least at the present stage, that patients do not require immunological monitoring or protective measurements. Further studies including the determination of secretory IgA might help to explain the discrepancy between our findings and the literature and should provide deeper insight into the correlation between potential immune disturbances and clinical implications.

Effects of Two Anticholinergic Drugs on Electroretinograms and Visual Evoked Potentials in Healthy Human Subjects

A battery of electroretinograms (ERGs) and visual evoked potentials (VEPs) were recorded from 12 normal, male volunteers after the intravenous administration of either biperiden 2.5 mg, atropine 1.5 mg or placebo, at weekly intervals. Self-reports indicated that both drugs caused significantly reduced levels of alertness compared to placebo, but more so with biperiden than atropine. Biperiden was not, however, associated with significant changes to ERGs, while atropine caused a few isolated, significant increases to implicit times. There were no significant treatment effects on pattern ERGs or VEPs. The flash VEP latencies and amplitudes recorded after the anticholinergics did not differ from placebo. These preliminary findings suggest that these anticholinergics do not have marked effects on either ERGs or VEPs.

Discrimination between Viral and Nonviral Meningitis by Visually Analyzed and Quantitative Electroencephalography

A prospective study was conducted to assess the ability of the visually analyzed electroencephalogram (VEEG), the quantitative EEG (QEEG) and the Glasgow Coma Scale (GCS) to discriminate between patients with viral and nonviral meningitis. The 55 subjects, aged 14-75 years, fell into one of the following categories: viral (n = 12), bacterial (n = 19), tuberculous (n = 16) or cryptococcal (n = 8) meningitis. EEG recordings and Glasgow Coma Scale (GCS) scores were obtained within 48 hours of admission to hospital. The sensitivity of the VEEG and QEEG for the prediction of patients with nonviral meningitis (true positives in this context) attained reasonably high values of 70% and 80%, respectively. In contrast, the sensitivity of the GCS was only 38%. Each of the three tests achieved high degrees of consistency in this regard with positive predictive values of 94% or better. The specificity for each of the three tests was high, 100% for the VEEG and the GCS and 82% for the QEEG indicating a high probability for the correct prediction of viral meningitis (true negatives). The consistency of this prediction was, however, poor due to negative predictive values of only 53% for the QEEG, 48% for the VEEG and 32% for the GCS. The QEEG results did not reveal any obvious advantages over the VEEG. Rather the assessment of the occurrence of particular VEEG abnormalities showed that patients with delta abnormalities had a very high probability of nonviral meningitis. At the other end of the spectrum, all normal VEEGs occurred in viral meningitis. In important respects the predictive ability of the EEG was superior to that of the GCS. While there was statistically significant agreement between the VEEG and GCS, the degree of agreement was poor. This study indicates that the EEG is a valuable and probably underestimated test in the acute phase of meningitis and provides complementary information to the GCS.