Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)

Background CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary autosomal dominant non-atherosclerotic non-amyloid cerebral arteriopathy. It is a relatively novel disease, identified in 1993. To our knowledge its occurrence in South Africa has not been reported in the literature. Here we present the clinical and laboratory features of five patients with CADASIL. Methods Patients with the characteristic radiological white matter disease and typical features (family history, ischaemic events, migraine or dementia) were evaluated for possible CADASIL. The evaluation included a clinical examination, routine investigations for strokes, MRI, skin biopsy electron microscopy, evoked potentials and EEG. Results The clinical and laboratory features of our study correlate to a large extent with previously reported studies. However, all of the skin biopsies were positive, and the onset of migraine in our patients was considerably earlier. A new finding, to our knowledge, is the normality of visual, somatosensory and auditory evoked potentials. Conclusion This study clearly confirms the existence of CADASIL in South Africa. It also suggests that skin electron microscopy is useful, despite recent reports of its low sensitivity, and that evoked potentials in CADASIL are likely to be normal

Prevalence and correlates of non-medical stimulants and related drug use in a sample of South African undergraduate medical students

CITATION: Retief, M. & Verster, C. 2016. Prevalence and correlates of non-medical stimulants and related drug use in a sample of South African undergraduate medical students. South African Journal of Psychiatry, 22(1):1-6, doi:10.4102/sajpsychiatry.v22i1.795.The original publication is available at http://www.sajp.org.zaBackground: The non-medical use of prescription psychostimulants or cognitive-enhancing substances among healthy college students is a growing concern. This use appears to be particularly high among medical students. To our knowledge, no literature is available on the non-medical use of stimulants among South African medical students. Objective: To determine the prevalence and correlates of non-medical stimulant use as well as subjective opinion on peer numbers using stimulants and university attitude towards stimulant use among a sample of South African undergraduate medical students. Methods: A descriptive observational study was conducted by means of a self-report questionnaire. Second- and fourth-year medical students (n = 252) completed the questionnaire. Results: Of the sample, 44 (18%) reported a lifetime use of stimulants for non-medical purposes and 33 (85%) of this group reported use within the past year. A total of six (2%) students reported a diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD). In the group without a diagnosis of ADHD, non-medical stimulant use was associated with the year of study (p = 0.03) and illicit substance use (p = 0.01). Most of the students in this group (31, 32%) reported using stimulants to improve concentration. Conclusion: Non-medical use of stimulants to improve concentration and academic performance is prevalent among the South African medical students sampled in this study. Further research at other institutions and under non-medical students would be helpful to assess the scope of this phenomenon.https://www.sajp.org.za/index.php/sajp/article/view/795Publisher's versio

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leuco-encephalopathy (CADASIL) is a hereditary autosomal dominant non-atherosclerotic nonamyloid cerebral arteriopathy. The disease was identified in 1993. We are not aware of reports in the literature of its occurrence in South Africa, and we present the clinical and laboratory features of 5 patients with CADASIL. METHODS: Patients with the characteristic radiological white matter disease and typical features (family history, ischaemic events, migraine or dementia) were evaluated for possible CADASIL by means of clinical examination, routine investigations for strokes, magnetic resonance imaging, skin biopsy electron microscopy, evoked potentials and electroencephalography. RESULTS: The clinical and laboratory features of our study largely correlate with reported studies. However, all of the skin biopsies were positive, and the onset of migraine in our patients was considerably earlier. A new finding, to our knowledge, was the normality of visual, somatosensory and auditory evoked potentials. CONCLUSION: Our study confirms the existence of CADASIL in South Africa, and also suggests that skin electron microscopy is useful, despite recent reports of its low sensitivity, and that evoked potentials in CADASIL are likely to be normal

Attempted molecular detection of the thermally dimorphic human fungal pathogen Emergomyces africanus in terrestrial small mammals in South Africa

The ecological niche of Emergomyces africanus (formerly Emmonsia species), a dimorphic fungus that causes an AIDS-related mycosis in South Africa, is unknown. We hypothesized that natural infection with E. africanus occurs in wild small mammals. Using molecular detection with primers specific for E. africanus, we examined 1402 DNA samples from 26 species of mole-rats, rodents, and insectivores trapped in South Africa that included 1324 lung, 37 kidney, and 41 liver specimens. DNA of E. africanus was not detected in any animals. We conclude that natural infection of wild small mammals in South Africa with E. africanus has not been proven.The Finds Wetenschappelijk Onderzoek - Slanderer. ISS was supported by the R. Samuel McLaughlin - Manitoba Medical Services Foundation and University of Manitoba Dean's Fellowship Fund; and a Marie Curie International Research Staff Exchange Scheme award.https://academic.oup.com/mmy2019-06-01hj2018Mammal Research InstituteZoology and Entomolog

Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)