Research Articles (Neurology)

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Parkinson’s disease : a systemic inflammatory disease accompanied by bacterial inflammagens
(Frontiers Media, 2019-08-27) Adams, Buin; Nunes, J. Massimo; Page, Martin J.; Roberts, Timothy; Carr, Jonathan; Nell, Theo A.; Kell, Douglas B.; Pretorius, Etheresia
Parkinson’s disease (PD) is a well-known neurodegenerative disease with a strong association established with systemic inflammation. Recently, the role of the gingipain protease group from Porphyromonas gingivalis was implicated in Alzheimer’s disease and here we present evidence, using a fluorescent antibody to detect gingipain R1 (RgpA), of its presence in a PD population. To further elucidate the action of this gingipain, as well as the action of the lipopolysaccharide (LPS) from P. gingivalis, low concentrations of recombinant RgpA and LPS were added to purified fluorescent fibrinogen. We also substantiate previous findings regarding PD by emphasizing the presence of systemic inflammation via multiplex cytokine analysis, and demonstrate hypercoagulation using thromboelastography (TEG), confocal and electron microscopy. Biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. In our PD and control blood analysis, our results show increased hypercoagulation, the presence of amyloid formation in plasma, and profound ultrastructural changes to platelets. Our laboratory analysis of purified fibrinogen with added RgpA, and/or LPS, showed preliminary data with regards to the actions of the protease and the bacterial membrane inflammagen on plasma proteins, to better understand the nature of established PD.
Emerging differences between Huntington's disease-like 2 and Huntington's disease : a comparison using MRI brain volumetry
(Elsevier, 2019) Anderson, David G.; Haagensen, Mark; Ferreira-Correia, Aline; Pierson, Ronald; Carr, Jonathan; Krause, Amanda; Margolis, Russell L.
ENGLISH ABSTRACT: Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.
EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy
(Elsevier, 2017-09) Staljanssens, Willeke; Strobbe, Gregor; Van Holen, Roel; Keereman, Vincent; Gadeyne, Stefanie; Carrette, Evelien; Meurs, Alfred; Pittau, Francesca; Momjian, Shahan; Seeck, Margitta; Boon, Paul; Vandenberghe, Stefaan; Vulliemoz, Serge; Vonck, Kristl; Van Mierlo, Pieter
ENGLISH ABSTRACT: the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LEpow and (ii) LEconn respectively). By comparing LEpow and LEconn, we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LEpow =0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LEpow ≤10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LEconn =0 mm and 94% for LEconn ≤10 mm. FC provided a significant added value to ESI alone (p < 0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy.
Clinical findings and genetic screening for copy number variation mutations in a cohort of South African patients with Parkinson’s disease
(Health & Medical Publishing Group, 2016) Mahne, Anna Cecelia; Carr, Jonathan; Bardien, Soraya; Schutte, Clara Maria
ENGLISH ABSTRACT: Background. Parkinson’s disease (PD), with a prevalence of up to 4% in Western countries, appears to be less common in Africa, possibly in part because of genetic factors. African studies investigating the genetic causation of PD are limited. Objective. To describe the clinical and genetic findings in a group of black South African patients with PD. Methods. All black African patients with PD from a tertiary hospital neurology clinic were examined. Symptoms were scored according to the Unified Parkinson’s Disease Rating Scale (UPDRS), and patients were classified according to motor features. Genomic DNA was extracted and multiplex ligation-dependent probe amplification was used for detection of copy number variation (CNV) mutations in the known PD-causing genes. Results. Sixteen patients were identified (ages 56 - 82 years). Three had a family history of PD. Classification into motor subtypes showed 44% mixed, 31% akinetic-rigid, and 25% tremor-dominant subtypes. UPDRS scores ranged from 7 to 88, with dementia in 20%. No patient had G2019S LRRK2 and A30P SNCA mutations, and all except one had no CNV mutations in the known PD-causing genes. A female patient (age of onset 50 years, no family history) had a parkin gene heterozygous deletion of exon 4. She had hyperreflexia, bilateral Hoffmann’s reflexes, normal plantar responses and no dystonia. Conclusion. This group of black African patients showed similar characteristics to patients in Western studies, possibly with a higher proportion having tremor-dominant disease. Genetic analysis showed one parkin gene mutation. The limited knowledge on PD-causing genes and mutations in black populations warrants further studies involving next-generation sequencing approaches.
Peritoneal dialysis technique survival at Tygerberg Hospital in Cape Town, South Africa
(African Association of Nephrology, 2017) Kapembwa, Kenneth C.; Bapoo, Nabeel A; Tannor, Elliot K.; Davids, M. Razeen
Background: The use of peritoneal dialysis (PD) as a treatment modality for patients with end-stage renal disease (ESRD) has been declining in many countries over the past few years. One of the reasons is technique failure, which occurs more frequently than is the case with chronic haemodialysis. Identifying and addressing the causes of technique failure is important in order to maintain more patients on PD, especially in settings where there are limited resources for chronic haemodialysis and a “PD first” approach is followed. Methods: In this retrospective study at Tygerberg Hospital in Cape Town, South Africa, we investigated 170 patients who were started on chronic ambulatory PD between January 2008 and July 2014, and determined rates of technique and patient survival. Demographic, clinical and laboratory data were assessed to identify risk factors for these outcomes. Results: The median age of the patients was 36 years and the most common cause of ESRD was glomerulonephritis. Only one patient had diabetes mellitus. Technique survival at 1, 3 and 5 years was 80%, 54% and 39%, respectively, while patient survival was 90%, 82% and 63%. Patients started on PD during the second half of the study period had improved rates of technique survival. Peritonitis was the most common cause of technique failure. Increasing age and Black ethnicity were associated with increased likelihood of technique failure. Other clinical and social factors were not significantly associated with the occurrence of technique failure. Conclusions: In our patients on PD, peritonitis, increased age and Black ethnicity were important factors associated with the development of technique failure. Concerted efforts are required to reduce peritonitis rates at our centre as this is the leading cause of technique failure.

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