Ahmed Bhigjee

Multidrug-Resistant Tuberculous Meningitis in KwaZulu-Natal, South Africa

Multidrug-resistant (MDR) pulmonary tuberculosis (TB) is well described in the literature. Reports of MDR TB meningitis (MDR-TBM), however, are limited to case reports and a single case series. During the period of 1999-2002, 350 patients with TBM were identified by cerebrospinal fluid culture for TB. Thirty patients (8.6%) had TB that was resistant to at least isoniazid and rifampicin. All 30 patients were included in this study. We reviewed hospital charts of the patients with MDR-TBM and describe our experience. Seventeen patients with MDR-TBM died, and, of those who were known to be alive, many experienced significant morbidity. Eighteen patients were HIV positive. Twenty-two patients had been treated for TB in the past, 3 patients had received no previous treatment for TB, and the history of TB treatment was unknown for 5 patients. The study highlights the prevalence of MDR-TBM and identifies new challenges in the management of affected patients.

Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting.

BackgroundIn Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings.MethodsWe evaluated the performance outcome of a novel standardized lipoarabinomannan (LAM) antigen-detection assay, using archived cerebrospinal fluid samples, in 50 African TBM suspects of whom 68% were HIV-positive.ResultsOf the 50 participants 14, 23 and 13 patients had definite, probable and non-TBM, respectively. In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with Mycobacterium tuberculosis could not be definitively excluded. The test sensitivities and specificities were as follows: LAM assay 64% and 69% (cut-point 0.22), smear microscopy 0% and 100% and PCR 93% and 77%, respectively.ConclusionIn this preliminary proof-of-concept study, a rapid diagnosis of TBM could be achieved using LAM antigen detection. Although specificity was sub-optimal, the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up. As PCR is largely unavailable, the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence settings. These preliminary results justify further enquiry and prospective studies are now required to definitively establish the place of this technology for the diagnosis of TBM.

Mild cognitive impairment and dementia in a heterogeneous elderly population: prevalence and risk profile

OBJECTIVE To describe the demographic, clinical and risk profile of Mild Cognitive Impairment and dementia in a sample of elderly South Africans within a residential setting. METHOD One hundred and forty participants residing in a group of residential homes for the elderly were assessed by psychiatrists and assigned diagnoses of dementia or Mild Cognitive Impairment (MCI). Participants diagnosed with dementia were also offered haematological investigations and a CT scan of the brain. RESULTS The sample consisted of 140 participants comprising 46.4% White, 29.3% Coloured, 20% Asian and 4.3% Black participants. There were 97 (69.3%) females and 106 (75.7%) participants had less than 12 years of education. Eleven (7.9%) dementia and 38 (27.1%) MCI cases were diagnosed. Increasing age was associated with cognitive impairment (MCI and dementia) (p=.020) but there was no association between gender and cognitive impairment (p=.165). MCI was significantly associated with a lower education level (p=.036) and no association was found between depression (current-p=.646; past-p=.719) and dementia or MCI. The presence of vascular risk factors (n=140) ranged from 66.4% (hypertension) to 14.3% (stroke). Subjective memory complaints were significantly associated with cognitive impairment (p=.001). Except for the use of the telephone (p=.225) and the television (p=.08), impairment in all domains of instrumental activities of daily living that were assessed were significantly associated with a dementia diagnosis. CONCLUSION The study showed that cognitive impairment was associated with increasing age and low education levels. The presence of vascular risk factors places this population at risk for future cognitive decline.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis

BACKGROUND HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Spectrum of myelopathies in HIV seropositive South African patients.

The authors determined the cause of myelopathies in 33 HIV seropositive individuals in KwaZulu/Natal, South Africa. The main associations were with human T-cell lymphotrophic virus–I, tuberculosis, herpes zoster, and syphilis. A novel association with probable bilharziasis was noted. Only one case of vacuolar myelopathy was identified. Opportunistic infections will probably persist until routine antiretroviral therapy becomes widely available in South Africa.

Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients--a prospective study.

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphreys visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM.

Screening a heterogeneous elderly South African population for cognitive impairment: the utility and performance of the Mini- Mental State Examination, Six Item Screener, Subjective Memory Rating Scale and Deterioration Cognitive Observee.

OBJECTIVE The aim of this study was to report on the prevalence of cognitive impairment, and to assess the performance and utility of subjective, objective and informant screening tools in a heterogeneous community sample. METHOD A sample of 302 elderly participants (>60 years) living in residential homes in a large city in South Africa were screened for the presence of cognitive impairment using objective (Mini-Mental State Examination [MMSE] and Six Item Screener-[SIS]), subjective (Subjective Memory Complaint [SMC]and Subjective Memory Rating Scale [SMRS]) and informant (Deterioration Cognitive Observee [DECO]) screening tools. All tools were compared to the MMSE and the influence of demographic variables on the performance on these tools was considered. RESULTS Significantly lower MMSE scores were found in participants aged 80-89 years (p=.023) and those who had 8-11 years of education (p=.002). For every one additional year of education, participants were 0.71 times less likely to screen positive on the MMSE. Differential item functioning on various components of the MMSE was demonstrated due to the effects of education, race and gender. There was significant differential performance between the recommended and alternate attention/concentration items (p<.001) with the alternate item favouring better performance. Based on the MMSE cutoff score of < 23, the prevalence of cognitive impairment was 16.9%; the prevalence yielded by the remaining tools ranged from 10.5% using the DECO to 46% as determined by the presence of a SMC. Using the MMSE as the reference standard for the presence of cognitive impairment, the SIS, SMC, SMRS and DECO had sensitivities of 82.3%, 54.6%, 17.0% and 37.5%, and specificities of 71.3%, 57.6%, 87.4% and 96.7% respectively. Age and race influenced performance on the MMSE, SIS and SMRS. CONCLUSION Different types of cognitive screening tools yielded varying sensitivities and specificities for identifying cognitive impairment when compared to the MMSE. The influence of race, age and education on test performance highlights the need for suitable, culture-fair screening tools. Locally, the alternate item for attention/concentration should be preferred.

New Insights into the Pathogenesis of Cryptococcal Induced Visual Loss Using Diffusion-Weighted Imaging of the Optic Nerve

Despite a successful antiretroviral drug rollout in South Africa, cryptococcal induced visual loss continues to be a major complication of cryptococcal meningitis. Preventive measures are lacking due to poor understanding of its pathogenesis. Optic nerve diffusion has shown some promise in investigating inflammatory and axonal changes of the optic nerve in vivo. The lack of post-contrast enhancement on T1 magnetic resonance imaging (MRI) and signal changes on T2 MRI with slightly increased apparent diffusion coefficient and reduced fractional anisotropy on diffusion imaging suggest that pressure-related effects are the dominant mechanism over inflammation and that there is early untested evidence of a compartment syndrome rather than papilloedema as the main contributor.

Visual loss in HIV-associated cryptococcal meningitis: A case series and review of the mechanisms involved

Permanent visual loss is a devastating yet preventable complication of cryptococcal meningitis. Early and aggressive management of cerebrospinal fluid pressure in conjunction with antifungal therapy is required. Historically, the mechanisms of visual loss in cryptococcal meningitis have included optic neuritis and papilloedema. Hence, the basis of visual loss therapy has been steroid therapy and intracranial pressure lowering without clear guidelines. With the use of high-resolution magnetic resonance imaging of the optic nerve, an additional mechanism has emerged, namely an optic nerve sheath compartment syndrome (ONSCS) caused by severely elevated intracranial pressure and fungal loading in the peri-optic space. An improved understanding of these mechanisms and recognition of the important role played by raised intracranial pressure allows for more targeted treatment measures and better outcomes. In the present case series of 90 HIV co-infected patients with cryptococcal meningitis, we present the clinical and electrophysiological manifestations of Cryptococcus-induced visual loss and review the mechanisms involved.