Atypical Presentations of Huntington Disease-like 2 in South African Individuals.

Background: Huntington disease-like 2 (HDL2) is a neurodegenerative disorder, affecting only individuals of African ancestry. Full penetrance occurs in individuals with 40 repeats or more.

Objective: To describe the phenotypic variability of HDL2 in a group of mixed ancestry individuals from South Africa.

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability.

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants.

Efficacy of deep brain stimulation of the anterior-medial globus pallidus internus in tic and non-tic related symptomatology in refractory Tourette syndrome.

Introduction: Although refractory Tourette Syndrome (TS) is rare, it poses great challenges in clinical practice. Co-morbid psychiatric symptoms often occur, negatively impacting quality of life. Deep brain stimulation (DBS) targeting different brain structures seems effective for tics, but specific literature regarding response of psychiatric symptoms is more limited.

Movement of prion-like α-synuclein along the gut-brain axis in Parkinson's disease: A potential target of curcumin treatment.

A pathological hallmark of the neurodegenerative disorder, Parkinson's disease (PD), is aggregation of toxic forms of the presynaptic protein, α-synuclein in structures known as Lewy bodies. α-Synuclein pathology is found in both the brain and gastrointestinal tracts of affected individuals, possibly due to the movement of this protein along the vagus nerve that connects the brain to the gut. In this review, we discuss current insights into the spread of α-synuclein pathology along the gut-brain axis, which could be targeted for therapeutic interventions.

Screening of the glucocerebrosidase (GBA) gene in South Africans of African ancestry with Parkinson's disease.

Sequence variants in glucocerebrosidase (GBA) are a major genetic risk factor for Parkinson's disease (PD), and display ethnic-dependent frequencies, for example, variants such as p.N370S and 84insGG are common in Ashkenazi Jewish patients. Notably, there are limited studies on black patients from the African continent; hence, we conducted a study on 30 South African black PD patients.

Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2.

Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7.

Frequency of the LRRK2 G2019S mutation in South African patients with Parkinson's disease.

G2019S in LRRK2 is the most common mutation associated with Parkinson's disease (PD). Highest frequencies are in North African Arabic (30-41%) and Ashkenazi Jewish (6-30%) populations, mostly due to founder effects. Here, we investigated the frequency of G2019S in 647 unrelated South African PD patients from different ancestral origins.

Longitudinal neuropsychological outcomes in treatment-resistant depression following bed nucleus of the stria terminalis-area deep brain stimulation: a case review.

Studies have demonstrated the effectiveness of deep brain stimulation (DBS) as a treatment modality for psychiatric conditions. We present a case reviewing the longitudinal neuropsychological performance outcomes following bed nucleus of the stria terminalis-area (BNST) DBS in a patient with treatment-resistant depression (TRD). The cognitive safety of DBS is well documented for various targets, however cognitive outcomes of BNST-area DBS have not been extensively reported for patients with TRD.

Familial cortical myoclonic tremor and epilepsy: Description of a new South African pedigree with 30 year follow up.

Aim: The aims of this study were to report the index case of a South African family with cortical myoclonic tremor and epilepsy, to describe the pedigree with the clinical findings and results of additional investigations, and to report the unique follow-up evaluation of affected and unaffected family members after 30 years.

Methods: The index case led to evaluation of the clinical files of patients from 1978/1979 and clinical assessment and investigation of patients from this cohort as well as newly identified family members. Patients were examined clinically; cortical myoclonic tremor severity was scored by using the Fahn-Tolosa- Marin-Tremor Rating Scale and the Myoclonus Rating Scale.

Severe porphyric neuropathy--importance of screening for porphyria in Guillain-Barré syndrome.

The hepatic porphyrias are a group of rare metabolic disorders, each of which is associated with a specific enzymatic alteration in the haem biosynthesis pathway. In South Africa (SA), a high incidence of variegate porphyria (VP) is seen as a result of a founder effect, but acute intermittent porphyria (AIP) is also encountered. The development of acute neurovisceral attacks is related to environmental factors, including medications, hormones and diet.

A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics.

Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele.

Successful treatment of disabling paroxysmal nonkinesigenic dyskinesia with deep brain stimulation of the globus pallidus internus.

Unlabelled: Paroxysmal nonkinesigenic dyskinesia (PNKD) causes episodes of treatment-resistant involuntary movements. Previous case reports showed effective treatment of PNKD with deep brain stimulation (DBS). We report 2 patients in whom DBS was highly successful when other treatment modalities had failed.