MRI findings of the brain in human African trypanosomiasis: a case series and review of the literature.

Human African Trypanosomiasis (HAT) is a neglected tropical disease that affected 3797 people worldwide in 2014. Without treatment mortality approaches 100%. Due to its low incidence and non-specific clinical features, diagnosis can be challenging and the role of MRI in diagnosis of HAT has not been evaluated outside of case reports. We carried out a retrospective, institutional review of three patients presenting with neurological stage (Stage 2) HAT presenting to the Hospital of Tropical Diseases, London between 2004 and 2016. MRI brain was performed in both the acute and follow-up stages of their infection. In addition to confirming that the most common MRI abnormality is T 2 weighted fluid-attenuated inversion recovery (T2W FLAIR) high signal intensity in the supratentorial white matter, this series has identified radiological findings not previously reported in the literature. In the acute stages, restricted diffusion can be seen in the internal capsules and splenium of the corpus callosum and microhaemorrhages not related to melarsoprol have been identified. Furthermore, the signal abnormality appears to be largely reversible upon treatment with regression associated with mild atrophy demonstrated on follow-up MRI post-treatment. We conclude that although direct microscopy remains the mainstay of diagnosis with serological and polymerase chain reaction (PCR) testing providing useful adjuncts, MRI brain can be helpful in assessing neurological involvement and may provide important prognostic information post-treatment.

The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons.

During the course of normal aging, certain populations of nerve growth factor (NGF)-responsive neurons become selectively vulnerable to cell death. Studies using dissociated neurons isolated from neonates have shown that c-Jun N-terminal kinases (JNKs) are important in regulating the survival and neurite outgrowth of NGF-responsive sympathetic neurons. Unlike neonatal neurons, adult sympathetic neurons are not dependent on NGF for their survival. Moreover, the NGF precursor, proNGF, is neurotoxic for aging but not young adult NGF-responsive neurons. Because of these age-related differences, the effects of JNK inhibition on the survival and growth of sympathetic neurons isolated from aged mice were studied. Aged neurons, as well as glia, were found to be dependent on JNK for their growth but not their survival. Conversely, proNGF neurotoxicity was JNK-dependent and mediated by the p75-interacting protein NRAGE, whereas neurite outgrowth was independent of NRAGE. These results have implications for the potential use of JNK inhibitors as therapies for ameliorating age-related neurodegenerative disease.