Utility of 18F FDG-PET in Parkinsonism in an African population.

Parkinson's Disease remains a diagnostic challenge. Misdiagnosis during life is approximately 25%. Diseases that resemble PD clinically, such as the Parkinsonianplus disorders usually have a poorer prognosis. A diagnostic biomarker is needed to differentiate PD from PPS. Geographical differences in PD prevalence, genetics and environmental factors may suggest a different pathogenesis of PD in Africa which may affect metabolic changes seen on 18F-FDG-PET. We investigated the utility of 18FFDG-PET in differentiating PD from PPS in a real-life clinical setting. The study was conducted at the Movement Disorder Clinic, South Africa. 81 patients with Parkinsonism had fluorine-18-labelled-fluorodeoxyglucose-PET; 53 PD and 28 PPS. Six persons living with HIV and Parkinsonism were included. Of the 22 Black African patients, 21 had PD and only one had a PPS. Image-based diagnosis was made by visual interpretation aided by statistical parametric mapping (SPM) analysis by a Nuclear Medicine Physician blinded to the clinical diagnosis. This was compared to the final clinical diagnosis made by two Movement disorder Neurologists blinded to the 18F-FDG-PET diagnosis. Patients were followed up for a median of 4 years. 18F-FDGPET diagnosis was in agreement with final clinical diagnosis in 91% of all subjects (90% PD, 93% all PPS). Our paper reports the clinically realistic sample of patients seen with Parkinsonism in Africa. The present data shows that 18F-FDG-PET can distinguish PD from PPS with good accuracy. Few Black Africans present with an Atypical Parkinsonian syndrome. The pattern of metabolism in PLH-PD is similar to PD patients without HIV.

Does antiretroviral therapy alter the course of Parkinson's disease in people living with HIV?

South Africa has the world's largest antiretroviral programme which has resulted in an increase in life expectancy in persons living with HIV. Parkinson's disease (PD) is an age-related neurodegenerative disorder. No data has been published in this setting with regards to the interaction between PD and people infected with HIV. This was a retrospective study which matched two HIV non-infected PD patients to one HIV-infected patient with PD. Patients with secondary causes of Parkinsonism were excluded. Demographic, clinical and laboratory data were extracted from the charts. Hoehn and Yahr scale was used to assess PD severity. Twenty PD patients were recruited from 1 January 2008 to 31 October 2020 and were diagnosed with HIV for a median of 72 months. The median age at onset of PD was 52 years. All patients were on antiretroviral therapy. There were no statistically significant differences in the levodopa equivalent daily dose, clinical phenotype, impulse control disorders (ICDs) and frequency of a positive family history between the two groups. HIV-infected patients had a higher frequency of dopamine dysregulation syndrome. At the end of follow-up, 3 (15%) PLH-PD had moderate to severe PD compared to 16 (40%) of PD controls. The OR of having moderate to severe PD in HIV non-infected PD patients was 4. Persons living with HIV and Parkinson's disease present with PD symptoms at a younger age, progress slower to a severe stage and respond well to dopaminergic replacement therapy.

Review of the neurological aspects of HIV infection.

There are almost 40 million people in the world who live with the human immunodeficiency virus (HIV). The neurological manifestations associated with HIV contribute to significant morbidity and mortality despite the advances made with anti-retroviral therapy (ART). This review presents an approach to classification of neurological disorders in HIV, differentiating diseases due to the virus itself and those due to opportunistic infection. The effects of antiretroviral therapy are also discussed. The emphasis is on the developing world where advanced complications of HIV itself and infections such as tuberculosis (TB), toxoplasmosis and cryptococcal meningitis remain prevalent.

Clinical series of Parkinson's disease in KwaZulu-Natal, South Africa: Retrospective chart review.

BACKGROUND: There is limited data on Parkinson's disease (PD) in South Africa. METHODS: Demographic and clinical information was extracted from the hospital records of patients who were coded as PD (International Classification of Diseases, 10th revision, G20) from 2002 to 2016.PD was diagnosed using the United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria (UKBBC). RESULTS: 414 patients met the criteria, 194 Indian, 130 Black, 16 Mixed Ancestry and 74 White patients. Median age at onset was 60 years, 53% were male and 20% had early onset PD (EOPD). There were no differences between the ethnic groups for the male: female ratio, age at onset, frequency of EOPD, family history, clinical phenotype and disease severity. Dyskinesia and neuropsychiatric symptoms were more frequent in Indian and White patients (p < 0.001). PD referral centre prevalence was 23/1000 neurological cases for the period 2002-2016. Referral centre prevalence of PD was 2.8 times higher in White compared to Black patients. Our study demonstrates an increase in referral centre prevalence of PD since the last clinical series in 1988 and an age related increase in prevalence. CONCLUSIONS: PD prevalence is increasing. The clinical profile of PD in Black patients is similar to the other ethnic groups. This study highlights the need for health care resource allocation to neurodegenerative disorders in an ageing African continent.

Sodium valproate and highly active antiretroviral therapy in HIV positive patients who develop new onset seizures.

Recurrent seizures may occur in up to 11% of HIV positive patients. The aetiology of the seizures includes opportunistic infections, neoplasia, HIV itself, metabolic derangements and drugs. Apart from treating the cause of the seizures, the challenge is to use the appropriate anticonvulsant drug (AED) to avoid potentially adverse drug-drug interactions in patients who are on concurrent highly active antiretroviral therapy (HAART). Initial recommendations were that the newer AEDs should preferably be used because of their simpler pharmacokinetics. We report on our experience with the use sodium valproate (SV) in eight patients who were on concurrent HAART. There were two males and six females with a mean age of 34.1 years. The mean dose of SV was 1075 mg per day. Seizure control was excellent, the CD4 count improved and there was successful viral suppression in all patients. This small study showed that SV was safe and effective. It is also relatively inexpensive compared to the newer AEDs - an important consideration in resource poor settings.

Diagnosis of tuberculous meningitis: clinical and laboratory parameters.

BACKGROUND: Confirming the clinical suspicion of tuberculous meningitis (TBM) has always been problematic. Whilst smear and culture positivity are diagnostic, these tests have low sensitivity. The polymerase chain reaction (PCR) assay has given variable results. AIM: This study attempted to improve the diagnostic yield by: (a) increasing the cerebrospinal fluid (CSF) volumes; (b) testing the yield from three specimens of CSF assumed to represent lumbar, cervico-thoracic cord, and base of brain CSF samples; (c) undertaking PCR assays using multiple primer sets; and (d) using real-time PCR. METHOD: Patients suspected of having cranial or spinal meningeal tuberculosis were entered into the study. Three aliquots of CSF were subjected to smear, culture, and conventional and real-time PCR. Three sets of primers - IS6110, MPB64, and PT8/9 - were used. Patients were retrospectively classified into four categories: 'definite TB' (culture positive), 'probable TB' (clinical and other tests suggestive of TB), 'not TB', and 'uncertain diagnosis'. RESULTS: A total of 68 patients were studied. There were 20 patients classified as definite TB, 24 probable TB, 17 not TB, and seven uncertain diagnosis. Forty-eight of 57 (84.2%) patients tested were HIV seropositive. The IS6110 PCR was positive in 27 patients which included 18/20 culture positive cases, six in the probable TB group, and three in the not TB group. The MPB64 and PT8/9 primers did not increase the yield. Real-time PCR was positive in seven additional patients. Combining the definite and probable TB, the sensitivity of all PCR assays was 70.5% (31/44) and specificity 87.5% (21/24). CONCLUSION: Targeting multiple sites of the TB genome using conventional PCR did not increase the number of positive cases. Real-time PCR was more sensitive. However, all the current techniques are still too insensitive to confidently exclude the diagnosis on laboratory grounds.

Neurological manifestations of HIV infection in Kwazulu-Natal South Africa.

South Africa has one of the fastest growing HIV epidemics in the world and KwaZulu-Natal, one of its nine provinces, is the epicentre of the epidemic. Of the estimated 5.3 million people infected with HIV in South Africa, 1.2 million reside in KwaZulu-Natal. Transmission of HIV is almost exclusively heterosexual, intravenous drug misuse does not occur and the patients attending state hospitals are antiretroviral drug naive. The neurological complications of HIV infection include bacterial and fungal meningitis, intracranial mass lesions, acute disseminated encephalomyelitis, a variety of spinal cord disorders, and peripheral nerve dysfunction. Tuberculous meningitis, especially that due to multidrug resistant organisms has a high mortality rate. Toxoplasmosis is the most frequent cause of intracranial mass lesions. These cases are successfully treated with cotrimoxazole alone. Multiple bacterial abscesses and tuberculomata are other important causes whilst primary central nervous system lymphoma is rare. The spinal cord disorders include co-infection with HTLV-I, tuberculosis and syphilis. Intramedullary tuberculomata, often multiple, and spinal epidural tuberculous abscess without bony disease are seen more commonly than in the pre HIV era. Peripheral nerve dysfunction include Gillian Barre Syndrome, chronic inflammatory demyelinating polyneuropathy and mononeuritis multiplex. Until the antiretroviral therapy roll out programme is well established the above HIV related neurological complications will continue to be seen for several years.