Anand Moodley

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.

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.

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.

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.

The Optic Nerve Compartment Syndrome in Cryptococcus-Induced Visual Loss

Abstract Visual loss in cryptococcal meningitis has been postulated to be due to papilloedema and/or optic neuritis. A 28-year-old human immunodeficiency virus (HIV)-positive female presented with visual loss, swollen optic discs, and elevated intracranial pressure due to cryptococcal meningitis. Computerised tomographic cisternography and T2-weighted magnetic resonance imaging showed occlusion of the peri-optic subarachnoid space and its reopening after serial lumbar punctures. Presumably lowering of the intracranial pressure resulted in equalisation of pressure across the pressure gradient created by the fungal block. This case supports a third mechanism of visual loss in cryptococcal meningitis, namely, an optic nerve compartment syndrome, that seems more plausible as the principal mechanism.

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.

Intracanalicular Optic Nerve Swelling and Signal Change in Fulminant Untreated Idiopathic Intracranial Hypertension

ABSTRACT The role of the optic canal in the pathogenesis of papilloedema has been under scrutiny recently. Whether a larger canal precedes more severe papilloedema or is the result of bone remodelling from chronically raised pressure across a pressure gradient is not clear. The authors present the magnetic resonance imaging findings of a 29-year-old female with fulminant and untreated idiopathic intracranial hypertension. Imaging showed focal expansion and intrinsic signal changes of the intracanalicular optic nerve. The authors discuss the possibility of either fluid accumulation within the optic nerves from a water hammer effect across blocked optic canals resulting from the steep pressure gradient or opticomalacia (optic nerve softening) from chronic ischaemia.

Bilateral Tonic Pupils as the Initial Manifestation of Sjögren’s Syndrome

Abstract Adie’s pupil is characterised by pupil dilatation, segmental iris palsy, light-near dissociation, and slow re-dilatation. Most commonly, tonic pupils are unilateral and idiopathic, but can be caused by orbital disorders and autonomic neuropathies. There are only a few case reports of tonic pupils in patients with Sjögren’s syndrome, caused by an autoimmune ciliary ganglionitis. The authors report on two cases with bilateral tonic pupils as the initial manifestation of primary Sjögren’s syndrome. Both patients presented with blurred vision, bilateral tonic pupils, and sicca symptoms. The findings suggest that Sjögren’s syndrome should be considered in patients presenting with bilateral Adie’s tonic pupils.

Prevalence and outcomes of central venous catheter-related bacteraemia in HIV-infected versus non-HIV-infected patients undergoing haemodialysis treatment for end-stage kidney disease

Background Central venous catheter (CVC) haemodialysis (HD) to implement renal replacement therapy is the preferred choice in the urgent setting. Unfortunately, CVC placement is associated with multiple complications including nosocomial bloodstream infections. There is a paucity of data on the prevalence and pattern of pathogenic organisms in haemodialysed HIV-infected versus non-HIV-infected patients with end-stage kidney disease. Method and results We undertook a retrospective study of 228 patients who were dialysed using a CVC at a tertiary referral hospital in KwaZulu-Natal, South Africa. Seventy-eight patients (34.2%) complicated with bacteraemia and sepsis requiring antibiotics. Removal of the catheter was necessary in 58 patients (74.0%). The most common organisms isolated were Staphylococcus aureus (30.8%), Staphylococcus epidermidis (24.4%) and Klebsiella pneumoniae (15.4%). There was no statistically significant difference between HIV-infected and non-infected patients with regards to infection rate, time interval from insertion of CVC to infection and final outcome. However, HIV-infected patients took longer to recover; 54.3% of non-infected patients versus 10.3% HIV-infected patients had their sepsis controlled within one week. Acidosis, hypotension, line malfunction and line discharge were infrequent signs of sepsis. Fever, rigors and raised white cell count occurred in over 80.0% of patients. Conclusion The infection rate in CVC HD is not more frequent in HIV-infected patients, provided that CD4+ count is ≥ 200 cells/µL and the patient is virologically suppressed. Outcomes following intravenous antibiotic and removal of the CVC are similar in HIV-infected and non-infected patients but response to treatment is slower in HIV-infected patients. A high index of suspicion is needed in detecting CVC-related bacteraemia.

HIV-associated neurocognitive disorder in a KwaZulu-Natal HIV clinic: A prospective study

Introduction HIV-associated neurocognitive disorder (HAND) is a consequence of HIV infection of the central nervous system. The prevalence ranges between 15% and 60% in different settings. Objectives This prospective study determined the prevalence of HAND at a peri-urban HIV clinic in KwaZulu-Natal. Factors associated with HAND were examined, alternate neurocognitive tools were tested against the international HIV dementia scale (IHDS) score and an association between HAND and non-adherence to antiretroviral therapy (ART) was explored. Methods Between May 2014 and May 2015, 146 ART-naïve outpatients were assessed for HAND. IHDS score ≤ 10 established a diagnosis of HAND. Functional capacity was assessed using Eastern Cooperative Oncology Group (ECOG) score. Chi-squared test was used to identify risk factors for HAND. The get-up-and-go test (GUGT) and Center for Epidemiological Studies Depression scale – revised (CESD-r) were tested against the IHDS. HIV viral load done six months after initiating ART was used as a surrogate marker for adherence to ART. Results The prevalence of HAND was 53%. In total, 99.9% of patients with HAND had no functional impairment. Age > 50 years old was associated with HAND (p = 0.003). There was no correlation between the GUGT, CESD-r and the IHDS score. HAND was not associated with non-adherence (p = 0.06). Conclusions While the prevalence of HAND is high, it is not associated with functional impairment which suggests that asymptomatic neurocognitive impairment is prevalent. Age > 50 years old is a risk factor for HAND. The GUGT and CESD-r are not useful diagnostic tools for HAND. The relationship between HAND and non-adherence should be further explored.