Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

A rare case of pulmonary embolism in a Mt. Kilimanjaro recreational hiker: A case report with review of literature.

Pulmonary embolism is one of the rarest complications of high-altitude sickness that can coexist with high altitude pulmonary edema. The risk of developing this phenomenon increases significantly with prolonged stay in high altitudes especially above 5000 m. Given the fatality of the condition, early screening and management is crucial; however, there is no gold standard approach in diagnosis. A 44-year-old male, a Tanzanian tourist first time hiking Mt. Kilimanjaro developed difficulty in breathing on the 4th day of ascending on a route that takes 6 days to summit whereby he was saturating at 38% on room air at the height of 4775 m. He was admitted with the clinical diagnosis of high altitude pulmonary edema. However, in the course of treatment for 72 h with no improvement, further investigations including computed tomography scan were suggestive of pulmonary embolism whereby he was treated with full recovery. Pulmonary embolism case reports are increasingly rising with the difficult to notice among high altitude pulmonary edema patients given their presentation similarities. A high index of suspicion based on clinical examination and investigations should prompt a clinician to include or exclude it.

Spinal ganglioneuroma with extension to the brachial plexus. The challenges for total surgical excision, a case report.

INTRODUCTION: Ganglioneuromas are benign neurogenic tumors that arise from the sympathetic ganglia. They are less aggressive compared to the more immature neuroblastomas and ganglioneuroblastomas but can grow to exert mass effect on surrounding tissues. PRESENTATION OF CASE: A 7 years old girl who presented with progressive quadriplegia for 4 months. On examination, she had a right supra-clavicular mass with reduced power in the right hand than the left. Power in the lower limbs was also reduced with hyper-reflexia, clonus and Babinski positive. Laboratory investigations were unremarkable and Chest X-Ray showed a widened mediastinum. Magnetic Resonance Imaging (MRI) scan revealed an extra-medullary spinal tumor at C6/C7 extending laterally on the right through the C6/7 neuro-foramen to the para-spinal tissue and brachial plexus. A C6/7 laminectomy with Spinal cord decompression by partial resection of the tumor was done. Histology of the resected tissue showed ganglioneuroma. DISCUSSION: The presentation of Ganglioneuromas is usually asymptomatic until they are huge enough to exert mass effect on surrounding tissue. Most are located in the posterior mediastinum, retro-peritoneum and neck. Due to this, it may be very challenging to achieve total resection especially when they surround major vessels or nerves. A multi-disciplinary approach is needed for the best surgical outcomes but this is not always realized in our setting. CONCLUSION: In resource limited settings, more collaboration and training is needed to realize appropriate management of complex surgical conditions. Although complications are not uncommon, total surgical excision is necessary to prevent recurrence and progression of Ganglioneuromas.

Parkinson's Disease in Sub-Saharan Africa: Pesticides as a Double-Edged Sword.

Long-term exposure to pesticides used in agriculture is increasingly being identified as a risk factor for developing Parkinson's disease. How chronic pesticide exposure might contribute to the growth of Parkinson's disease in the mainly agricultural communities of Sub-Saharan Africa has thus far received limited attention. There are specific concerns in this area of the world: aging of the population, in combination with chronic exposure to widely used pesticides, including those that have been restricted elsewhere in the world because of neurotoxicity and other health risks. Of interest, the prevalence of Parkinson's disease among specific (semi)nomadic populations in Tanzania seems very low, possibly due to their lack of exposure to agricultural chemicals. But at the same time, pesticides have also brought important benefits to this part of the world. Specifically, in Sub-Saharan Africa, pesticides have been directly helpful in preventing and controlling famine and in containing major human infectious diseases. This creates a complex risk-benefit ratio to the use of pesticides within a global perspective, and urgently calls for the development and implementation of affordable alternatives for areas such as Sub-Saharan Africa, including non-neurotoxic compounds and non-chemical alternatives for the use of pesticides.

Delivery of Allied Health Therapies to People with Parkinson's Disease in Africa.

Allied health therapies refer to a range of healthcare professionals, including physiotherapists, occupational and speech-language therapists, who aim to optimize daily function and quality of life in conjunction with medical care. In this narrative review of literature on allied health therapies in people with Parkinson's disease (PD), we focused on the diversity in healthcare access, state of the art, current challenges in the African continent, and proposed solutions and future perspectives. Despite the increasing prevalence and awareness of PD in Africa, numerous challenges persist in its management. These include resource limitations, geographical barriers, sociocultural beliefs, and economic constraints. Nevertheless, innovative solutions, including telerehabilitation and community-based rehabilitation, offer hope. Collaborative efforts within the continent and internationally have shown potential in bridging training and resource gaps. Significant strides can be made with tailored interventions, technological advancements, and multifaceted collaborations. This review offers practical insights for healthcare professionals, policymakers, and caregivers to navigate and optimize PD care in the African context.

Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease.

The biological basis of the neurodegenerative movement disorder, Parkinson's disease (PD), is still unclear despite it being 'discovered' over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology. The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease. To achieve this aim, we posed this question to thirteen "PD experts" from six continents (for global representation) and collated their personal opinions into this article. The views were varied, ranging from toxin exposure as a PD trigger, to LRRK2 as a potential root cause, to toxic alpha-synuclein being the most important etiological contributor. Notably, there was also growing recognition that the definition of PD as a single disease should be reconsidered, perhaps each with its own unique pathobiology and treatment regimen.

Preliminary evaluation of a smartphone application (DelApp) for identification of delirium in sub-Saharan Africa.

OBJECTIVE: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania. METHOD: Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus. RESULTS: Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant. CONCLUSION: In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent 'rule out' value in this setting.

The prevalence and outcomes of depression in older HIV-positive adults in Northern Tanzania: a longitudinal study.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.

Long COVID? Fatal case report of ischemic stroke and pulmonary embolism post COVID-19 infection.

Coronavirus disease 19 (COVID-19) may lead to post-COVID syndrome a few weeks to months after the infection with various symptoms. Post-COVID thromboembolic syndrome may be a result of coagulopathy that occurs in both the arterial and venous circulation. Apart from direct cellular infection, post-COVID syndrome may occur due to immune system dysregulation, endothelial injury, and hypercoagulability, leading to thrombosis. We present a 32-year-old man who was diagnosed with mild symptoms of COVID-19 infection 4 months before an acute ischemic stroke and an asymptomatic pulmonary embolism. A COVID-19 antigen test was negative. An analysis of prothrombotic factors was negative. He could not receive any therapeutic intervention before his demise. The extent of COVID-19 infection after the onset of symptoms is a mystery and poses a fatal concern due to the increasing number of complications. The long-term complications after COVID-19 infection are still not understood. Clinicians need to be aware of any signs and symptoms that may arise months after COVID-19 infection and its possible causal relationship.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

An Unusual Cause of Cerebral Infarction in a Tanzanian School Child.

Pediatric stroke is uncommon. A traumatic cause of pediatric ischemic stroke is even rarer. Ischemic stroke due to intraluminal thrombus can be acutely treated with thrombolysis but various factors in sub-Saharan Africa make this unfeasible. We present a case of an eight-year-old Tanzanian boy who sustained penetrating trauma to his palate developing an ischemic stroke of his right middle cerebral artery territory.

Neurological disorders in Northern Tanzania: A 6-year prospective hospital-based case series.

Background: The burden of neurological disorders is large and altered by the HIV epidemic. Objectives: We describe the pattern of neurological disorders and their association with HIV infection in adult patients attending a consultant hospital in Northern Tanzania. Methods: In this prospective cross-sectional study, we collected data on adult neurological referrals over a 6-year period between 2007-13. The odds of HIV infection, across neurological categories adjusted for age and sex, was calculated. Results: Of 2037 participants, 54.8% were male and 45.2% were female. The median age of participants was 43 years. The results for HIV screening were available for 992/2037 (48.7%) patients, of whom 306 (30.8%) were seropositive. The most frequent neurological disorders were cerebrovascular disease (19.9%), paraplegia (13.6%), and peripheral neuropathies (8%). Taken together CNS infection accounted for 278/2037 (13.6%). The adjusted odds (aOR) of HIV infection was highest amongst infections; brain abscesses (aOR 107, 95% CI 35.1-470.4) and meningitis/encephalitis (aOR 40.1, 95% CI 13.6-172.9), but also raised in cerebrovascular disease, paraplegia, peripheral neuropathies, cranial nerve palsies, seizures, cerebllar disorders, movement disorders, motor neuron disease and headache. Conclusion: The main pattern of neurological disorders in Northern Tanzania is presented. The odds of HIV infection was highest in CNS infections and in a wide range of non-communicable neurological disorders.

HIV-Associated Neurocognitive Disorders: The First Longitudinal Follow-Up of a cART-Treated Cohort of Older People in Sub-Saharan Africa.

BACKGROUND: HIV-associated neurocognitive disorders (HAND) are a highly prevalent chronic complication in older people living with HIV (PLWH) in high-income countries. Although sub-Saharan Africa has a newly emergent population of older combination antiretroviral therapy (cART)-treated PLWH, HAND have not been studied longitudinally. We assessed longitudinal prevalence of HAND and have identified possible modifiable factors in a population of PLWH aged 50 years or older, over 3 years of follow-up. METHODS: Detailed neuropsychological and clinical assessment was completed annually in the period 2016-2019 in a systematic sample of cART-treated PLWH in Kilimanjaro, Tanzania. A consensus panel defined HAND using American Academy of Neurology criteria for asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. HIV disease severity and other factors associated with HAND progression, improvement, and stability were evaluated in individuals fully assessed at baseline and in 2019. RESULTS: At baseline, 47% of the cohort (n = 253, 72.3% female individuals) met HAND criteria despite good HIV disease control [Y1 59.5% (n = 185), Y2 61.7% (n = 162), and Y3 57.9% (n = 121)]. Of participants fully assessed at baseline and year 3 (n = 121), HAND remained stable in 54% (n = 57), improved in 15% (n = 16), and declined in 31% (n = 33). Older age and lower education level significantly predicted HAND progression, whereas HIV-specific factors did not. Male sex and shorter cART duration were associated with improvement. CONCLUSIONS: In this first longitudinal study characterizing clinical course of HAND in older cART-treated PLWH in sub-Saharan Africa, HAND was highly prevalent with variable progression and reversibility. Progression may be more related to cognitive reserve than HIV disease in cART-treated PLWH.

Idiopathic Arachnoiditis of the Cauda Equina: A Case Report from Tanzania.

Arachnoiditis is a rare clinical entity that usually presents with severe debilitating radiating pain that can pose a challenge in diagnosis especially in areas without appropriate imaging modalities. We present a 26-year-old male with progressive lower back pain with radiation to the lower extremities, aggravated by movement and touch. We diagnosed idiopathic arachnoiditis based on cerebrospinal fluid analysis and magnetic resonance imaging. He was managed with a 5-day course of methylprednisolone and analgesics with a good outcome. Severe back pain without a specific cause in a young patient should be investigated with proper imaging modalities and lumbar puncture if warranted to evaluate the cause.

The Use of Remote Monitoring Technologies: A Review of Recent Regulatory Scientific Advices, Qualification Opinions, and Qualification Advices Issued by the European Medicines Agency.

Aims: Recently, the use of novel remote monitoring technologies (RMTs) in trials has gained much interest. To facilitate regulatory learning, we evaluated qualification opinions (QOs) and advices (QAs) and scientific advices (SAs) of the Committee for Medicinal Products for Human Use (CHMP) to gain insight in the types of devices that are intended to be used in clinical trials for supporting/submitting application for obtaining marketing authorization (registration trials) and the main recommendations of the CHMP. Methods: QOs, QAs, and SAs of the CHMP that assessed RMTs between 2013 and 2019 were eligible for our study. The following information was extracted from the documents: year of advice/opinion, device and endpoints used, type of endpoint (primary, secondary, exploratory, or safety), and main recommendations of the CHMP. Results: In total two QOs, four QAs, and 59 SAs were included in our study (total of SAs between 2013 and 2019 = 4,054). In the SAs, accelerometers to measure activity and/or sleep parameters (n = 31) were the most frequently used devices, followed by mobile applications (n = 6) and glucose monitoring devices (n = 6). Usually, these measures were proposed as secondary or exploratory endpoints (n = 32). The main recommendations of the CHMP were related to relevance of the (novel) outcome measure; validation; precision, accuracy, sensitivity, and specificity; compliance; sampling interval; and data handling and privacy. Conclusions: Although there was a trend toward an increased use over time, the use of RMTs in registration trials is still relatively rare. In the absence of formal European regulatory guidance on mHealth technologies, insight in the main recommendations of the CHMP may stimulate the use of novel RMTs in a regulatory context.

Fatal cerebral venous sinus thrombosis as a manifestation of uncontrolled systemic lupus erythematosus in a young African female.

In a young patient with systemic lupus erythematosus presenting with status epilepticus and neurological deficits, early brain imaging, risk factor identification and prompt treatment of underlying lupus flare-up and cerebral venous sinus thrombosis could significantly improve the management and prognosis.

Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency.

This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91-1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates.

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania.

There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the ageing in this population, and thus increase the prevalence of premature frailty. There is a paucity of data on the prevalence of frailty in an older HIV + population in SSA and screening and diagnostic tools to identify frailty in SSA. Patients aged ≥ 50 were recruited from a free Government HIV clinic in Tanzania. Frailty assessments were completed, using 3 diagnostic and screening tools: the Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and Brief Frailty Instrument for Tanzania (B-FIT 2). The 145 patients recruited had a mean CD4 + of 494.84 cells/µL, 99.3% were receiving cART and 72.6% were virally suppressed. The prevalence of frailty by FFP was 2.758%. FFP frailty was significantly associated with female gender (p = 0.006), marital status (p = 0.007) and age (p = 0.038). Weight loss was the most common FFP domain failure. The prevalence of frailty using the B-FIT 2 and the CFS was 0.68%. The B-FIT 2 correlated with BMI (r = - 0.467, p = 0.0001) and CD4 count in females (r = - 0.244, p = 0.02). There is an absence of frailty in this population, as compared to other clinical studies. This may be due to the high standard of HIV care at this Government clinic. Undernutrition may be an important contributor to frailty. It is unclear which tool is most accurate for detecting the prevalence of frailty in this setting as levels of correlation are low.

Altitude-Related Disorders on Mount Kilimanjaro, Tanzania: Two-Year Survey in a Local Referral Center.

INTRODUCTION: A significant number of climbers on Mount Kilimanjaro are affected by altitude-related disorders. The aim of this study was to determine the main causes of morbidity and mortality in a representative cohort of climbers based on local hospital records. METHODS: We conducted a 2-y retrospective chart review of all patients presenting to the main referral hospital in the region after a climb on Mount Kilimanjaro, including all relevant records and referrals for postmortem studies. RESULTS: We identified 62 climbers who presented to the hospital: 47 inpatients and 15 outpatients. Fifty-six presented with high altitude illness, which included acute mountain sickness (n=8; 14%), high altitude pulmonary edema (HAPE) (n=30; 54%), high altitude cerebral edema (HACE) (n=7; 12%), and combined HAPE/HACE (n=11; 20%). The mean altitude of symptom onset ranged from 4600±750 m for HAPE to 5000±430 m for HAPE/HACE. The vast majority of inpatients (n=41; 87%) were improved on discharge. Twenty-one deceased climbers, most having died while climbing (n=17; 81%), underwent postmortem evaluation. Causes of death were HAPE (n=16; 76%), HAPE/HACE (n=3; 14%), trauma (1), and cardiopulmonary (1). CONCLUSIONS: HAPE was the main cause of death during climbing as well as for hospital admissions. The vast majority of climbers who presented to hospital made a full recovery.