Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. In all major examples of these diseases there is strong evidence that mitochondrial dysfunction occurs early and acts causally in disease pathogenesis. Moreover, an impressive number of disease-specific proteins interact with mitochondria. Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise.

Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases

Parkinson's disease: Mechanisms and models

Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology

The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.

https://science.sciencemag.org/content/sci/299/5604/256.full.pdf

Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

Familial parkinsonism and dementia with cortical and subcortical Lewy bodies is uncommon, and no genetic defect has been reported in the previously described sibships We present a Spanish family with autosomal dominant parkinsonism, dementia, and visual hallucinations of variable severity The postmortem examination showed atrophy of the substantia nigra, lack of Alzheimer pathology, and numerous Lewy bodies which were immunoreactive to alpha-synuclein and ubiquitin in cortical and subcortical areas Sequencing of the alpha-synuclein gene showed a novel, nonconservative E46K mutation in heterozygosis The E46K mutation was present in all affected family members and in three young asymptomatic subjects, but it was absent in healthy and pathological controls The novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid such as lysine in a much conserved area of the protein, is likely to produce severe disturbance of protein function Our data show that, in addition to the previously described hereditary alpha-synucleinopathies, dementia with Lewy bodies is related to mutation of alpha-synuclein

The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.

/pdf/a-report-of-stiff-person-syndrome-in-tanzania-with-first-3stoq6y62t.pdf

A Report of Stiff Person Syndrome in Tanzania with First Epidemiological Figures for Sub-Saharan Africa

First familial Becker muscular dystrophy in Tanzania: Clinical and genetic features,

Chronic subdural hematomas (CSDH) initially present as focal neurological deficits with or without signs of increased intracranial pressure, for which admission to the general medical ward may occur if they present with poorly understood neurological deficits and no evident history of trauma. The symptoms may be long standing and mimic stroke upon presentation. Their distribution and specific clinical features in sub-Saharan Africa are largely unknown. We describe a series of subdural hematoma (SDH) inpatients from the medical ward of a tertiary referral center in Northern Tanzania, describing clinical and radiological characteristics and providing clinical outcome where possible. Our study population numbered 30, with a male majority (n = 19, 63.3%) and a mean age of 66.8 ± 14.5 years. Mean duration from symptom onset to admission in the medical ward was 20.0 ± 30.8 days. History of head injury was reported in only 43.3% of patients. Improvement in the neurological examination was noted in 68.1% of the 22 patients who underwent surgery. The mortality rate was 20.0%. A majority of the patients were elderly males and presented late to the hospital. Delayed presentation and diagnosis due to, amongst other reasons, postponed imaging resulted in a prolonged time to definitive treatment and a high mortality rate compared to other regions of the world.

/pdf/chronic-subdural-hematomas-a-case-series-from-the-medical-13cu0a8g4c.pdf

Chronic subdural hematomas: a case series from the medical ward of a north Tanzanian referral hospital

Study design Cross-sectional pilot study on spinal cord injury (SCI) among in- and outpatients. Objectives To evaluate the challenges faced by individuals with SCI during Clean Intermittent Catheterisation (CIC). Setting Kilimanjaro Christian Medical Center (KCMC), a tertiary referral hospital in Moshi, Tanzania. Methods A questionnaire was sent to individuals with SCI who were either admitted to the Orthopedic Rehabilitation Unit or attended the Outpatient clinic between January and April 2018. Inpatients were less than 1 year post-injury and outpatients were one to 3 years post-injury. Results In total, 48 individuals responded: 28 outpatients and 20 inpatients. Among the inpatient group, 80% were performing CIC as compared with 25% of outpatient group. Of the entire cohort, 35.4% reported doing well without catheter-based management. Failure to perform CIC was present in 16.7% of all individuals. CIC-equipment was unavailable in local villages for 58.3% of all patients. The most frequent complications of CIC were urinary tract infections (20.8%) and mild bleeding (14.6%). The majority of individuals (79.2%) reported satisfaction with their situation, regardless of the severity. Conclusions Some individuals performed CIC upon discharge, but the majority discontinued use, for which unavailability of CIC-equipment was a major determinant. While all individuals reported concerns prior to CIC, only a small minority actually experienced anxiety, pain or shame. Through targeted counselling and enhanced regular follow-up we will likely improve compliance to CIC. Sponsorship We are grateful to the International Network of SCI Nurses in collaboration with Wellspect Health Care for funding this study.

Intermittent catheterisation for individuals with disability related to spinal cord injury in Tanzania.

Objective HIV infection is a major cause of disease burden and disability across sub-Saharan Africa (SSA). HIV-associated neurocognitive impairment (HAND) is estimated to affect 8 million people with HIV infection across the continent and is associated with increased mortality and morbidity. As a result of demographic transition and increased coverage of combination antiretroviral therapy (cART) the proportion of people aged 50 and over living with HIV infection in SSA is predicted to triple (to over 9 million people by 2040). Despite this, few published data exist on the prevalence of, or risk factors for, HAND in older individuals in SSA. We aimed to estimate prevalence and risk factors for HAND in a stable population of HIV positive individuals under long term follow up at a government clinic in Northern Tanzania, one of the pioneer sites for cART in SSA. Method A systematic sample of individuals aged 50 and over attending a HIV care and treatment centre for routine follow up were assessed for HAND using a locally normed neuropsychological battery adapted to a low literacy setting. All participants subsequently underwent a clinical interview, neurological examination, informant history for functional impairment and standardised psychiatric screening questionnaire. HAND was defined according the American Academy of Neurology (AAN) 2007 criteria for Asymptomatic Neurocognitive Impairment, Minor Neurocognitive Disorder (MND) and HIV-associated Dementia (HAD). General and HIV-specific risk factors for symptomatic HAND were examined using univariable and multivariable logistic regression. Results Complete data were available for 227 participants (162 (71%) female, median age 57.9 years) of whom 35% had 4 years formal education or fewer. Median Cd4 count was 500/µl and 95.5% of participants were on cART. Preliminary data indicate that the overall prevalence of HAND was 61.2% (ANI 35.2%, MND 23.8%, HAD 2.2%) and of symptomatic HAND (MND and HAD) 25%. Presence of symptomatic HAND was not related to current or nadir Cd4 count, or time since HIV diagnosis, but was independently associated with older age, illiteracy, living alone and greater number of depression symptoms. Conclusion HAND was very prevalent in this stable outpatient cohort of older adults most of whom were on cART. Initial results suggest that in this cohort of older adults in SSA, risk factors for symptomatic neurocognitive impairment appeared to be less related to HIV infection and more similar to factors commonly associated with neurodegenerative dementias in both high income and low income country settings.

https://jnnp.bmj.com/content/jnnp/88/8/A19.1.full.pdf

16 Prevalence and risk factors for hiv-associated neurocognitive impairment (hand) amongst adults aged 50 and over attending a hiv clinic in northern tanzania

Marieke C. J. Dekker

Papers

A Report of Stiff Person Syndrome in Tanzania with First Epidemiological Figures for Sub-Saharan Africa

First familial Becker muscular dystrophy in Tanzania: Clinical and genetic features,

Chronic subdural hematomas: a case series from the medical ward of a north Tanzanian referral hospital

Intermittent catheterisation for individuals with disability related to spinal cord injury in Tanzania.

16 Prevalence and risk factors for hiv-associated neurocognitive impairment (hand) amongst adults aged 50 and over attending a hiv clinic in northern tanzania