Browsing by Author "Leepan, Edward"

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    Open Access
    An audit of the epidemiological, clinical features and outcomes of patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) attending a South African Tertiary referral Hospital
    (2023) Gule, Manqoba; Leepan, Edward; Tucker Lawrence
    NMOSD is a severe CNS inflammatory disorder classically characterised by recurrent bouts of optic neuritis and myelitis. The pathogenic anti-aquaporin-4 antibody is present in most cases and distinguishes it from other forms of inflammatory CNS demyelination. This biomarker has led to recognising a broader clinical spectrum of NMOSD. Another recently discovered antibody, the anti-myelin-oligodendrocyte-glycoprotein-antibody, further broadens the spectrum of pathophysiological mechanisms and clinical presentations of NMOSD. NMOSD may be associated with infections, autoimmune diseases, and malignancies. Observational data from South Africa suggests an association between NMOSD and tuberculosis. Ethnicity and geographic locality play an important role in the epidemiology of NMOSD. Worldwide, non-European, particularly Black-African and Asian ethnicity, is associated with the highest incidence, prevalence and severity of NMOSD. Despite this, sub-Saharan African studies are under-represented in the medical literature. NMOSD is typically associated with aggressive attacks, which may recur, often in temporal clusters. When left untreated, NMOSD may result in severe permanent disability and death. Immune-based therapies are used to manage acute attacks and prevent recurrences. These include steroids and plasmapheresis, steroid-sparing agents, and large-molecule biological agents. Novel and highly effective disease-modifying treatments are continually being developed and examined in clinical trials. These agents are expensive, restricting their use in low-and middle-income settings. The prevalence of NMOSD in the study population remains unknown, nor is there local data on the clinical spectrum or whether an infectious trigger such as TB or HIV plays a role. This audit evaluated the characteristics of a cohort diagnosed with NMOSD attending a South African tertiary hospital. These included demographic, clinical, serological, radiologic, and therapeutic interventions and patient outcomes. We highlight serious shortcomings in case recognition and referral pathways. In our setting, NMOSD is under-recognised at district care facilities where 67% (26/39) of early NMOSD attacks presented and were not recognised. A further 38% (15/39) had recurrent admissions with unrecognised attacks. Moreover, 51% of patients with AQP4-Ab-positive serology captured by the PGWC Data Centre did not attend the referral neurology service. The demographic profiles of our cohort were similar to others that have been reported. Most of our patients were young women of non-European ancestry: Mixed-race (Coloured) and Black-African ethnicity. HIV and antecedent or concurrent tuberculosis were the most common comorbidities. At the neurology service, the AQP4-Ab-positivity rate was lower than compared with international cohorts. This was compounded by 20% of cases diagnosed with NMOSD despite not meeting diagnostic criteria. This raises the possibility of misdiagnosis and inappropriate management. Plasmapheresis is a highly effective, albeit expensive, treatment for acute attacks. Only 30% of patients were treated with plasmapheresis. The most frequently cited reasons were limited access and cost. Although understandable in low-and-middle-income settings, advocating for effective, equitable treatments materially affects patient outcomes. Robust local evidence of the disease burden and overall cost implications of relapses and subsequent disability will support this objective. Data from this, and other similar audits, will inform the development of evidence-based and cost-effective practices to guide immunotherapy and management strategies for NMOSD in resource-limited settings. Word Count: 495
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    Anterior temporal lobectomy. A cross-sectional observational study of potential surgical candidates at a single institute
    (2024) Soni, Aayesha; Leepan, Edward
    Background: Epilepsy is a common neurological disorder, associated with serious cognitive and psychosocial burdens, especially when poorly controlled. Mesial temporal lobe epilepsy (mTLE) is the most common form of human focal epilepsy. It is often refractory to antiepileptic drugs, and the most amenable to surgical treatment which often renders patients seizure free. Furthermore, surgery for mTLE has low procedural risk, is cost-effective and best performed early in the disease course for maximal benefit. It is surprising, therefore, that mTLE surgery remains widely under-utilised, in both well and poorly resourced settings. Objectives: The aim of this study was to establish the frequency of occurrence of patients with electroencephalographic epileptiform discharges consistent with mTLE attending a neurophysiology laboratory at a tertiary hospital in South Africa, and determine whether these patients may be candidates for anterior temporal lobectomy, the most commonly performed surgery for mTLE. Methods: This was a quantitative audit of all scalp electroencephalograms (EEG) performed at the Groote Schuur Neurophysiology laboratory during the period January 1st 2017 to December 31st 2019. Where CT and MRI brain scans had been performed, these were assessed for corroborative evidence of mTLE. Results: Over the three-year period, 4 342 EEGs were assessed. A total of 411 (11%) showed epileptiform discharges consistent with all epilepsy types. Of these, 327 (69%) were of focal onset and 108 (2% of the total number of EEGs performed) were consistent with mTLE. Of the patients with electroencephalographic features of mTLE, only 27 (25%) had had MRI brain scans performed according to an epilepsy surgery protocol. Of these, 6 exhibited MRI findings confirming mTLE, identifying them as potential surgical candidates. Over three years, 75% of patients with electroencephalographic evidence suggesting mTLE did not receive appropriate work-up for epilepsy surgery. Conclusion: Surgery, especially anterior temporal lobectomy, is widely acknowledged to be an efficacious and cost-effective intervention in patients with medically refractory mTLE. The findings of our study suggest that patients with mTLE are under-investigated for potential surgical management, and that epilepsy surgery is under-utilised in South Africa. These findings are in line with similar studies in both well-resourced and resourceconstrained countries. We hope that our study will highlight the utility of EEG as a screening tool to identify patients with drug-resistant epilepsy due to mTLE, who may be candidates for anterior temporal lobectomy.
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    Utility of EEG in the diagnosis of Efavirenz neurotoxity in HIV positive patients at a South African tertiary hospital
    (2023) Ssemmanda, Salvatore; Leepan, Edward; Tucker Lawrence
    Background: Efavirenz (EFV) is a widely used antiretroviral medication in HIV treatment, primarily metabolized by cytochrome P450 CYP2B6, an enzyme whose loss of function polymorphisms have been associated with risk of EFV neurotoxicity. Patients with late onset efavirenz neurotoxicity syndrome (LENS) may present with encephalopathy, for which scalp EEG (sEEG) is indicated. Although a characteristic pattern of sEEGs waveforms in this deleterious condition has been suggested before, this has not been studied. Objective: The aim of this study was to investigate the utility of sEEG as a biomarker of LENS. Methods: We analysed a 5-year retrospective period of sEEGs performed at Groote Schuur Hospital (GSH) neuro-electrophysiology laboratory between June 1, 2016, and May 31, 2021. From these we selected 5319 sEEGs with a “Dysrhythmia grade II generalized” (Mayo Clinic, Lemieux et al) classification performed on patients whose referral indication for sEEG was either encephalopathy, efavirenz neurotoxicity, encephalitis, delirium, confusion, neurocognitive decline or subclinical seizures. Following several exclusions, the analysed cohort of 63 sEEGs comprised of 13 sEEGs from adult HIV positive patients with laboratory confirmed EFV neurotoxicity (plasma EFV levels of > 4 ug/mL) and 50 sEEGs as controls. These were presented to two qualified and experienced blinded sEEG interpreters instructed to record if a sEEG was typical for waveform features of EFV neurotoxicity or not, following a demonstration using representative sEEG samples from outside the study duration. All data were anonymized and secured on password protected computers for standard statistical analyses including measurement of inter rater agreement, reliability, and correlation. A p-value of less than 0.05 was considered for statistical significance. Results: Patients with EFV neurotoxicity had characteristic sEEG findings of diffuse, monomorphic, bisynchronous, high voltage, rhythmic 4 – 7 Hz theta frequency waveform runs. These were detectable by the blinded interpreters with significantly strong inter rater agreement (mean kappa statistic = 0.88, p < 0.001), strong positive correlation (Spearman correlation coefficient = 0.81, p < 0.001) and significantly strong inter rater reliability (intraclass correlation coefficient = 0.86, 95% CI 0.77 – 0.92, p < 0.001). Conclusion: Our observation adds knowledge to existing literature on EFV neurotoxicity, by describing a characteristic sEEG pattern in patients with LENS that is reliably detectable by qualified sEEG interpreters. This is in view of our observation that in a tertiary hospital with people referred with a clinical diagnosis of encephalopathy and other confusional states meeting clinical referral criteria described in this study, with a proven Dysrhythmia grade II generalized pattern on sEEG, certain sEEG criteria may distinguish HIV positive patients with LENS from other patients with the same grade of dysrhythmia on sEEG. This may support the timeous diagnosis of EFV neurotoxicity and facilitate the workup of encephalopathic patientson EFV. Our finding may be representative of an effect of EFV on the oscillatory and spike rhythms of the reticular thalamic nuclei. Further research using a larger number of patients, studying correlation between plasma EFV levels in patients with LENS and their sEEG characteristics is suggested as it may be an electrophysiological biomarker of disease severity.