Brain plasticity and adolescent HIV: A randomised controlled trial protocol investigating behavioural and hemodynamic responses in attention cognitive rehabilitation therapy.

Despite advances in antiretroviral pharmacology, neuroHIV in the central nervous system (CNS), causes neuronal dysregulation, which is associated with compromised neurocognition. Non-pharmaceutical interventions such as HIV cognitive rehabilitation training (HIV-CRT), have shown potential to partially reverse cognitive deficits, sequent HIV neuroinvasion. Nonetheless, no studies exist pairing cognitive outcomes with objective neuroimaging biomarkers in adolescent HIV-CRT. This longitudinal pre-post-quasi-experimental protocol examined cognitive outcomes, paired with optimal neuroimaging outcomes following customised attention training in adolescent HIV. Twenty-six adolescents living with HIV were randomly assigned to either the treatment group, which received attention CRT using ACTIVATE™, (n = 13), or to the treatment as usual group (n = 13). Cognitive outcomes were examined using the NEPSY-II, and BRIEF; whilst neuroimaging outcomes were determined by changes in oxygenated haemoglobin (HbO), as determined by functional near-infrared spectrometry (fNIRS). Functional connectivity fNIRS measures were evaluated using seed-based correlation analysis, located in the central executive network (CEN). This study serves to guide the development and identification of objective biomarkers for adolescent neuroHIV, sequent CRT amongst children living with HIV in Sub-Saharan Africa.

Huntington disease-like 2: insight into neurodegeneration from an African disease.

Huntington disease (HD)-like 2 (HDL2) is a rare genetic disease caused by an expanded trinucleotide repeat in the JPH3 gene (encoding junctophilin 3) that shows remarkable clinical similarity to HD. To date, HDL2 has been reported only in patients with definite or probable African ancestry. A single haplotype background is shared by patients with HDL2 from different populations, supporting a common African origin for the expansion mutation. Nevertheless, outside South Africa, reports of patients with HDL2 in Africa are scarce, probably owing to limited clinical services across the continent. Systematic comparisons of HDL2 and HD have revealed closely overlapping motor, cognitive and psychiatric features and similar patterns of cerebral and striatal atrophy. The pathogenesis of HDL2 remains unclear but it is proposed to occur through several mechanisms, including loss of protein function and RNA and/or protein toxicity. This Review summarizes our current knowledge of this African-specific HD phenocopy and highlights key areas of overlap between HDL2 and HD. Given the aforementioned similarities in clinical phenotype and pathology, an improved understanding of HDL2 could provide novel insights into HD and other neurodegenerative and/or trinucleotide repeat expansion disorders.

Hooper visual organization test: Psychometric properties and regression-based norms for the Venezuelan population.

The Hooper Visual Organization Test (HVOT) is used to assess visual organization and visual synthesis. Psychometric studies reveal cultural biases and associations between demographic variables and test performance capable of compromising the test's clinical utility. The present study aimed to adapt the HVOT, explore the psychometric properties of this test, and develop regression-based norms for the Venezuelan population. Using a cross-sectional design, the HVOT was administered to a stratified sample of 351 healthy adults (20-85 years of age and 0-23 years of education) from the Metropolitan Area of Caracas. The results revealed good levels of internal consistency and reliability. Confirmatory Factor Analysis suggests that the HVOT is unidimensional. Item difficulty, types and rate of errors and inappropriateness of some items indicated a potential cultural bias in our Venezuelan sample. Spearman's Correlation and Wilcoxon Rank test analysis (p<.001) showed a significant association between HVOT total score and age, education, and gender, but not with socioeconomic status. We present regression-norms stratified by age, years of education, and gender. Cultural biases were noted, which highlights the need for a revision of items in terms of inclusion, scoring, and order of presentation. Future studies of concurrent and predictive validity are needed.

A comparison between the neurocognitive profile of Huntington Disease-Like 2 and Huntington Disease: Exploring the presence of double dissociations.

Huntington Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. HDL2 is the Huntington Disease (HD) phenocopy that has the greatest clinical resemblance to HD. Both are characterized by movement, psychiatric and cognitive dysfunction, which progress to dementia. The present study compared the neuropsychological profile of HDL2 with that of HD. Using a Single Case-Control Methodology in Neuropsychology, three HDL2 and seven matched HD patients were assessed with a comprehensive neuropsychological battery and compared to matched control samples, considering age, years of education, type of school (public/government) and language (all bi/multilingual). Potential double dissociations were explored by using Crawford, Garthwaite, and Wood's Inferential Methods for Comparing the Scores of Two Single-Cases in Case-Control Designs. Double dissociation between HDL2 and HD were identified in three tests, namely Letter Number Sequencing, Rey Auditory Learning Test Delayed and Recognition Trials. These dissociations possible are due to methodological limitations.

The Neuropsychiatry of Huntington Disease-Like 2: A Comparison with Huntington's Disease.

BACKGROUND: Huntington Disease-Like 2 (HDL2) is a rare autosomal dominant disorder caused by an abnormal CAG/CTG triplet repeat expansion on chromosome 16q24. The symptoms of progressive decline in motor, cognitive and psychiatric functioning are similar to those of Huntington's disease (HD). The psychiatric features of the HDL2 have been poorly characterized. OBJECTIVE: To describe the neuropsychiatric features of HDL2 and compare them with those of HD. METHODS: A blinded cross-sectional design was used to compare the behavioural component of the Unified Huntington's Disease Rating Scale (UHDRS) in participants with HDL2 (n = 15) and HD (n = 13) with African ancestry. RESULTS: HDL2 patients presented with psychiatric symptoms involving mood disturbances and behavioural changes that were not significantly different from those in the HD group. Duration of disease and motor performance correlated (p < 0.001) with the Functional Capacity score and the Independence score of the UHDRS. HD patients reported movement dysfunction as the first symptom more frequently than HDL2 Patients (p < 0.001). CONCLUSION: The psychiatric phenotype of HDL2 is similar to that of HD and linked to motor decline and disease duration. Psychiatric symptoms seem more severe for HDL2 patients in the early stages of the disease.

Single case-control design for the study of the neuropsychological deficits and dissociations in Huntington's disease-like 2.

The Single-Case Methodology in Neuropsychology (Crawford & Howell, 1998) is a research design and robust inferential statistical method that facilitates the neuropsychological description of one case in terms of the differences between its profile and the performance of a carefully matched sample (Crawford & Garthwaite, 2012). The comparison is made by means of a t-test statistic that treats the normative sample as a sample and not as a population, with a particular effect-size associated with the size (n) of the sample. It is an ideal method for the neuropsychological investigation of rare diseases, such as Huntington's Disease Like-2 (HDL2), especially when the cases are embedded in contexts of great diversity. This paper presents a step by step guide to the implementation of this method in a series of demographically and clinically diverse group of patients. •The application of a Single-Case Methodology in Neuropsychology enables the characterisation of rare diseases while controlling for demographic and context-related variables.•The implementation Single-Case Methodology in Neuropsychology provides test norms for homogenous groups that can be used by practitioners in their clinical work.•The method was customised for the South African population by controlling variables of specific relevance, such as linguistic diversity and quality of education.

The neuropsychological deficits and dissociations in Huntington Disease-Like 2: A series of case-control studies.

OBJECTIVES: Huntington's Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. The Huntington's Disease (HD) phenocopy has the greatest clinical resemblance to HD, but its neurocognitive characterisation is poorly researched. This study reports on the neurocognitive profile of seven HDL2 patients including preserved functions, deficits and dissociations (classical and strong) and provides a general characterisation of the cognitive dysfunction of HDL2 in relation to the progression of the disease. METHODS: The neuropsychological performance of seven HDL2 patients were compared to one of four control groups, matched by age and level of education using a Single Case-Control design. All patients were polyglots and with public education (primary and secondary). Deficits, as well as classical and strong dissociations within each case profile, were identified by implementing Crawford and Howell's (1998) t-test and the Revised Standardized Difference Test (Crawford and Garthwaite, 2005), respectively. RESULTS: The HDL2 neurocognitive syndrome is heterogeneous with a variable rate of progression, with the psychomotor and dexterity domain consistently and severely impaired. CONCLUSION: HDL2 has a heterogeneous impact on cognitive functions from early stages in the disease, which evolve to dementia in a non-uniform manner, in keeping with preferential damage in the cerebrocortical-basal ganglia-thalamus-cerebrocortical circuit.

Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry.

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.

Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes.

BACKGROUND: Huntington's disease like 2 (HDL2) is the most common Huntington's disease (HD) phenocopy in many countries and described as the phenocopy with the greatest resemblance to HD. The current clinical description of HDL2 is based on retrospective data. It is unknown whether HDL2 has clinical features that distinguish it from HD. OBJECTIVE: To describe the HDL2 phenotype and compare it to HD systematically. METHODS: A blinded cross-sectional design was used to compare the HDL2 (n = 15) and HD (n = 13) phenotypes. African ancestry participants underwent assessments, including the Unified Huntington's Disease Rating Scale (UHDRS). The UHDRS motor component was video recorded and evaluated by blinded experts and the inter-rater reliability calculated. RESULTS: Both groups were homogeneous in terms of demographics and disease characteristics. However, HDL2 patients presented three years earlier with more prominent dysarthria and dystonia. Raters could not distinguish between the two diseases with a high level of agreement. No significant differences in the TMS between HDL2 and HD were found. In both disorders, disease duration correlated with motor scores, with the exception of chorea. Psychiatric and cognitive scores were not significantly different between the groups. CONCLUSIONS: The HDL2 phenotype is similar to HD and is initially characterized by dementia, chorea, and oculomotor abnormalities, progressing to a rigid and bradykinetic state, suggesting the UHDRS is useful to monitor disease progression in HDL2. Although HDL2 patients scored higher on some UHDRS domains, this did not differentiate between the two diseases; it may however be emerging evidence of HDL2 having a more severe clinical phenotype.

Barriers to the implementation of a computer-based rehabilitation programme in two public psychiatric settings.

BACKGROUND: Working memory (WM) deficits have a negative impact on treatment adherence and quality of life. Efficient and effective interventions are needed in order to improve the cognitive functioning of those affected, especially in low-resource communities. Computer-based rehabilitation programmes (CBRP) are low-cost therapeutic approaches for WM deficits. Perceptions and experiences of target users may influence whether CBRP constitute an effective therapeutic option for adults with cognitive impairment in under-resourced environments. AIM: The goal of the study was to explore the experiences of a group of volunteers with WM deficits (associated with diagnoses of HIV and schizophrenia), in terms of the perceived barriers they encountered during their participation in a CBRP. METHODS: A qualitative, descriptive research design was implemented. Short interviews and field notes were used in order to investigate the experiences of nine participants in relation to the CBRP. The sample included four participants living with HIV and five with schizophrenia, all with WM deficits. RESULTS: Using a thematic analysis, eight barriers were identified: unawareness of the cognitive deficit, anticipation of negative results, stigma, difficulties accessing a computer and/or Internet connection, ill health, negative emotional experiences, daily routine challenges and non-conducive or sabotaging environments. A representational model of these barriers is proposed. CONCLUSION: The implementation of a cognitive rehabilitation strategy should not only take into consideration issues of access to particular strategies and materials but should also be preceded by an exploration of how individual and contextual barriers are experienced by the potential users, as these contribute to the risk of dropout.

The Rey Auditory Verbal Learning Test: normative data developed for the Venezuelan population.

The Rey Auditory Verbal Learning Test (RAVLT) is a neuropsychological tool widely used to assess functions such as attention, memory, and learning ability in the auditory-verbal domain. Norms for the test have been developed in many different languages and they show different relationships with demographic variables. The main objective of this research was to develop specific norms for the Venezuelan population, with particular focus on the influences of age, education, gender, and socioeconomic status. A Spanish version of the test was administered to a quota sample of 629 healthy adults. Pearson's correlation analysis (p < .001) showed a significant association between RAVLT performance and age (r = -.401), education (r = .386), and socioeconomic status (r = -.196), but not between RAVLT performance and gender (r = -.054). Due to the strength of the correlations, only age and education were considered in the development of final norms.