Treatment of tuberculous meningitis in adults: Is the duration of intensive-phase therapy adequate?

Tuberculous meningitis (TBM) results in considerable morbidity and mortality, especially in developing countries such as South Africa. Treatment regimens have been extrapolated from treatment for pulmonary tuberculosis, and the intensive-phase duration of 2 months may be inadequate for treatment of patients with TBM. We highlight this situation with a case report of a patient with TBM whose illness progressed after institution of the maintenance phase of treatment. We propose that the intensive-phase treatment of TBM be revisited with regard to duration of treatment, choice of drugs during continuation-phase therapy, or both.

Presentation and outcome of patients with intracranial tuberculoma in a high HIV prevalence setting.

SETTING: A referral hospital in South Africa.OBJECTIVE: To describe the clinical presentation, serial brain imaging findings during treatment and outcome of patients with intracranial tuberculoma in a high human immunodeficiency virus (HIV) prevalence setting.DESIGN: This was a retrospective observational study conducted over a 12.5-year period. Records of adults (age ≥18 years) who presented with neurological TB were screened. We included patients with tuberculoma in whom sequential brain imaging was performed.RESULTS: Of 66 patients enrolled, HIV status was known in 61; 47 (71%) were HIV-infected and 14 (21%) were non-HIV-infected. Clinical and imaging findings and outcomes were similar between these groups. Persistent tuberculoma was present at 18 months follow-up in 20/41 (49%) patients who underwent repeat imaging at that timepoint; those with persistent tuberculoma were more likely to have persisting neurological abnormalities (85% vs. 52%; P = 0.043). Larger tuberculoma size at presentation (≥3 cm) was the only factor significantly associated with tuberculoma persistence (multivariable logistic regression, OR 19.9, 95%CI 1.27-309.68; P = 0.033).CONCLUSION: Tuberculoma is a severely disabling TB manifestation regardless of HIV coinfection, with half of patients showing radiologically persistent lesions at 18 months follow-up. Large size of tuberculoma at presentation heralds lower chance of its resolution within 18 months.

Clinical, neuroimaging and immunological phenotype of South African neuropsychiatric systemic lupus erythematosus patients.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an important cause of morbidity and mortality. We undertook this observational retrospective study of patients with NPSLE who had brain magnetic resonance imaging (MRI) to determine the indications for MRI and the correlation of clinical and laboratory findings with MRI. We identified 83 NPSLE patients (84.3% women) seen at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, between June 2003 and May 2017. The mean age at SLE diagnosis was 26.24 ± 12.81 years and the median interval to NPSLE was 11.0 (interquartile range, 4.0-39.0) months. The most common indications for MRI were seizures (45.8%), psychosis (18.1%) and cerebrovascular disease (18.1%). The MRI was abnormal in 68 (81.9%) with small-vessel disease in 65 (78.3%) and large-vessel disease in eight (9.6%). The small-vessel abnormalities were white-matter hyperintensities (WMH) (59.0%), atrophy (55.4%) and lacunae (4.6%). Our patients had high disease activity at NPSLE. Cerebrovascular disease was associated with an abnormal MRI ( p = 0.018) and large-vessel disease ( p = 0.014) on MRI. Our NPSLE patients were younger and had high disease activity, and seizures were more common compared with other studies. The most common MRI abnormalities were WMH and cortical atrophy, in agreement with other studies.

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.

The sensitivity and specificity of subjective memory complaints and the subjective memory rating scale, deterioration cognitive observee, mini-mental state examination, six-item screener and clock drawing test in dementia screening.

BACKGROUND: The effectiveness of dementia screening depends on the availability of suitable screening tools with good sensitivity and specificity to confidently distinguish normal age-related cognitive decline from dementia. The aim of this study was to evaluate the discriminant validity of 7 screening measures for dementia. METHODS: A sample of 140 participants aged ≥60 years living in a residential facility for the aged were assessed clinically and assigned caseness for dementia using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised diagnostic criteria. Sensitivity and specificity of a selection of the following screening measures were tested using receiver operating characteristic (ROC) analysis for individual and combined tests: the Mini-Mental State Examination (MMSE), Six-Item Screener (SIS), Subjective Memory Complaint, Subjective Memory Complaint Clinical (SMCC), Subjective Memory Rating Scale (SMRS), Deterioration Cognitive Observee (DECO) and the Clock Drawing Test (CDT). RESULTS: Using ROC analyses, the SMCC, MMSE and CDT were found to be 'moderately accurate' in screening for dementia with an area under the curve (AUC) >0.70. The AUCs for the SIS (0.526), SMRS (0.661) and DECO (0.687) classified these measures as being 'less accurate'. At recommended cutoff scores, the SMCC had a sensitivity of 90.9% and specificity of 45.7%; the MMSE had a sensitivity of 63.6% and a specificity of 76.0%, and the CDT had a sensitivity of 44.4% and a specificity of 88.9%. Combining the SMCC and MMSE did not improve their predictive power except for a modest increase when using the sequential rule. CONCLUSION: The SMCC is composed of valid screening questions that have high sensitivity, are simple to administer and ideal for administration at the community or primary health care level as a first level of 'rule-out' screening. The MMSE can be included at a second stage of screening at the general hospital level and the CDT in specialist clinical settings. Sequential use of the SMCC and MMSE will improve the specificity of the former and the sensitivity of the latter.

Clinical practice guidelines for management of neuropathic pain: expert panel recommendations for South Africa.

Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for diagnosis and management of NeuP in South Africa. Following accurate diagnosis of NeuP, pregabalin, gabapentin, low-dose tricyclic antidepressants (e.g. amitriptyline) and serotonin norepinephrine reuptake inhibitors (duloxetine and venlafaxine) are all recommended as first-line options for the treatment of peripheral NeuP. If the response is insufficient after 2 - 4 weeks, the recommended next step is to switch to a different class, or combine different classes of agent. Opioids should be reserved for use later in the treatment pathway, if switching drugs and combination therapy fails. For central NeuP, pregabalin or amitriptyline are recommended as first-line agents. Companion treatments (cognitive behavioural therapy and physical therapy) should be administered as part of a multidisciplinary approach. Dorsal root entry zone rhizotomy (DREZ) is not recommended to treat NeuP. Given the large population of HIV/AIDS patients in South Africa, and the paucity of positive efficacy data for its management, research in the form of randomised controlled trials in painful HIV-associated sensory neuropathy (HIV-SN) must be prioritised in this country.

Multiple sclerosis in KwaZulu Natal, South Africa: an epidemiological and clinical study.

BACKGROUND: Since the study by Dean, almost 40 years ago, there has been no systematic South African study on the prevalence of multiple sclerosis (MS) using the modern diagnostic criteria. KwaZulu-Natal (KZN), one of the nine provinces in South Africa, is home to 9.9 million people belonging to all racial groups. AIM: To determine the period prevalence of MS in KZN in the different racial groups, using the revised McDonald's criteria. METHODS: The charts of all KZN patients given the diagnosis of MS were reviewed to confirm the diagnosis. All patients were contacted telephonically over a period of one month (July 2005) to determine whether they were still alive and still resident in KZN. Clinical, laboratory and treatment data were also extracted from the charts. RESULTS: The crude period prevalence per 100 000 for whites was 25.63, for Indians 7.59, people of mixed ancestry 1.94 and for blacks 0.22. The corresponding age standardized prevalence per 100 000 were 25.64, 7.15, 1.72 and 0.23, respectively. The clinical features were similar to that seen in the Western world. Up to half of the 167 patients had significant motor disability and optic neuritis was seen in 43/167 (25.7%) of patients. Whilst all traceable MRI brain scans showed some abnormality, 96/139 (69.1%) met three of the four McDonald's MRI criteria. CSF oligoclonal bands were present in 102 of 124 (82.3%) samples tested. CONCLUSION: MS in KZN is more frequent than previously believed and occurs in all racial groups being most frequent in whites followed by Indians. MS, although rare, does occur in blacks. The increased prevalence figures may reflect better case ascertainment and use of modern diagnostic techniques. However, an absolute increase in numbers cannot be excluded.

Optimizing therapy of seizures in patients with HIV and cysticercosis.

Worldwide, about 40 million people are living with HIV and 50 million people have neurocysticercosis (NCC). About 5% of patients with HIV and the majority of patients with NCC develop recurrent seizures. Mechanisms of seizure production in HIV include mass lesions, meningitis, encephalitis, and ischemia. Seizures in NCC may occur at all stages of cyst development, from the vesicular and colloidal to the calcified stages. Seizures in HIV present special problems with regard to choice of antiepileptic drug (AED) and the potential for drug-drug interactions with antiretroviral (ARV) treatments. Newer AEDs with simpler pharmacokinetic profiles may be the preferred agents, particularly when protease inhibitors form part of ARV regimens. Seizures in NCC are easily controlled with the older AEDs. Although there has been some debate about the value of antiparasitic drugs in NCC, accumulating data suggest that the use of these agents in active disease decreases the risk for development of chronic epilepsy.

Seizures in HIV/AIDS: a southern African perspective.

South Africa, with a population of 44.8 million, has over 5 million human immunodeficiency virus (HIV)-infected individuals. Over 70% of HIV-infected patients will present with clinically relevant neurologic disease at some stage during the course of their disease. New onset seizures occur in 3-11% of these patients. The mechanism of seizure production in HIV-positive patients includes incidental association, HIV itself, opportunistic infections (OIs), neoplasia, cerebrovascular disease, drug toxicity, and metabolic derangements. In developing countries, OIs constitute the largest group presenting with seizures. Seizure management in HIV-positive patients presents special problems, especially with respect to drug-disease and drug-drug interactions. The older antiepileptic drugs (AEDs) are protein-bound and largely depend on the cytochrome p450 system for their metabolism. The newer AEDs may be safer in patients on antiretroviral drugs. However, they are expensive, an important consideration in developing countries.

Ischemic stroke in young HIV-positive patients in Kwazulu-Natal, South Africa.

Cerebrovascular disease occurs in HIV-positive individuals, but no relationship between the two has been established. The authors reviewed a cohort of patients aged 15 to 44 years to evaluate stroke in HIV-positive and negative subjects. Patients who were HIV-positive with no other identifiable etiology were compared to age- and race-matched HIV-negative patients. HIV-positive and HIV-negative groups did not differ in angiographic, cardiac, or serologic tests. A positive HIV test does not provide causal information or diagnosis.

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.

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.

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.

Role of cerebrospinal fluid shunting for human immunodeficiency virus-positive patients with tuberculous meningitis and hydrocephalus.

OBJECTIVE: Tuberculous meningitis (TBM) and its complications continue to have devastating neurological consequences for patients. Budgetary constraints, especially in developing countries, have made it necessary to select patients for shunting who are likely to experience good recoveries. To date, the value of cerebrospinal fluid shunting for human immunodeficiency virus (HIV)-positive patients with TBM has not been clearly established. METHODS: Thirty patients with TBM and hydrocephalus were prospectively evaluated. Coincidentally, one-half of the patients were HIV-positive. All patients underwent uniform treatment, including ventriculoperitoneal shunt placement and antituberculosis treatment. CD4 counts were measured for all patients. Outcomes were assessed at 1 month. RESULTS: No complications related to shunt insertion were noted. The HIV-positive group fared poorly (death, 66.7%; poor outcome, 64.7%), compared with the HIV-negative group (death, 26.7%; poor outcome, 30.8%). Despite cerebrospinal fluid shunting, no patient in the HIV-positive group experienced a good recovery (Glasgow Outcome Scale score of 5). This is in contrast to the six patients (40%) in the HIV-negative group who, with the same treatment, experienced good recoveries (Glasgow Outcome Scale scores of 5) at discharge (P<0.14). No patient (either HIV-positive or HIV-negative) who presented in TBM Grade 4 survived, whereas no HIV-positive patient who presented in TBM Grade 3 survived. A significant relationship was noted between CD4 counts and patient outcomes (P<0.031). CONCLUSION: In the absence of obvious clinical benefit, HIV-positive patients with TBM should undergo a trial of ventricular or lumbar cerebrospinal fluid drainage, and only those who exhibit significant neurological improvement should proceed to shunt surgery.

Sequence of the env gene of some KwaZulu-Natal, South African strains of HTLV type I.

Phylogenetic analysis of HTLV-I suggests three main subtypes, namely, cosmopolitan, Central African, and Australo-Melanesian. HTLV-I is endemic in KwaZulu-Natal, South Africa. However, sequence data on the local strains are limited to the LTR region. The env gene of the local strain was amplified and sequenced from the peripheral blood of five seropositive individuals. Four had HTLV-I-associated myelopathy and one had infective eczema. The sequence analysis of the env gene showed a greater then 99% homology of the local strains. They were closely related to the North American strains (99.3%), followed by the Japanese strains (98.3-98.9%). Phylogenetic studies linked the local strains to the cosmopolitan subtype. This study provides new sequence data on the env gene of the local HTLV-I strain.