What’s Hot: Immune-mediated neurologic disorders

Immune-mediated neurologic disorders has been a hot and rapidly evolving topic in high income setting such as the US for the past few years. Now there is a burgeoning body of evidence suggesting that immune mediated phenomena deserve more attention in tropical setting as well.  In 2017, Johnson et al. discovered a leiomodin-1 autoantibody in the sera and CSF of patients with nodding syndrome that may be a result of Onchocercal volvulus (OV) infection. OV is the cause of River Blindness and has long been associated with Nodding Syndrome though direct infectious links have been ruled out.1 Also in 2017, Neurology published a report of Post Malaria Neurologic Syndrome (PMNS) in a patient found to have NEUREXIN-3a2 antibodies and another case report of PMNS associated with anti-voltage-gated potassium channel antibodies.3 PMNS has been previously described primarily in adults and involves neuropsychiatric manifestations, confusion or coma, and seizures, but pediatric cases have also been reported.4 In malaria endemic regions, acute febrile pediatric illnesses with seizure and coma for which no underlying etiology can be identified is a not uncommon clinical conundrum. One has to wonder what the full spectrum of PMNS might entail.

  1.  Johnson TP, Tyagi R, Lee PR, et al. Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus. Sci Transl Med 2017; 9(377).
  2. Costa A, Silva-Pinto A, Alves J, et al. Postmalaria neurologic syndrome associated with neurexin-3alpha antibodies. Neurol Neuroimmunol Neuroinflamm 2017; 4(5): e392.
  3. Sahuguet J, Poulet A, Bou Ali H, Parola P, Kaphan E. Postmalaria Neurologic Syndrome-Autoimmune Encephalitis With Anti-Voltage-Gated Potassium-Channel Antibodies. Ann Intern Med 2017; 167(1): 70-1.
  4. Kernan RJ, Gavin PJ, Butler KM, Leahy TR, Lynch B, Leonard J. Expanding the Spectrum of Post-malaria Neurologic Syndrome in the Pediatric Population. Pediatr Infect Dis J 2018; 37(5): 499-500.

 

The Best Treatment for Cryptococcal Meningitis in Africa: Looks like Goldilocks got it right

Caring for cryptococcal meningitis in a resource limited setting can be a Scylla and Charybdis experience. Besides starting antiretrovirals and offering repeated lumbar punctures (if family will agree), the only treatment on offer to most patients is high dose oral fluconazole—cheap and available with limited toxicity, but not that great at clearing the infection. That is rock number one. Rock number 2 is the occasional patient who can afford amphotericin B. Not a fun drug to try and manage in the absence of the capacity to check and/or replenish electrolytes or evaluate renal function in a rapid and reliable fashion. So the recent clinical trial report in the NEJM provides incredibly valuable insights into optimal treatment for cryptococcal meningitis in the African setting.1 In their multi-country study, Molloy et al. found that 1 week of amphotericin plus flucytosine OR 2 weeks of high dose fluconazole plus flucytosine were both superior to 2 weeks of amphotericin B. Somewhere between the first and second week of ampho B is the tipping point for safety vs. efficacy in this fragile population. Two weeks of ampho B resulted in 8.8% of patients developing grade 3 or 4 elevated creatinines. Given that within the context of the study patients received preemptive electrolyte replacement (something not routinely available), the study may have under estimated the toxicity of ampho B in the ‘real work’ African setting. Thus my own preference for the fluconazole/ flucytosine option.

Key now is to see if the calls for generic, readily available flucytosine are successful.

  1. Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa. N Engl J Med 2018; 378(11): 1004-17.

 

How can/will low income countries copes with the emerging burden of dementia?

Amidst the global, explosive increase in the burden of non-communicable diseases (NCDs) in the past decade, the social and economic impact of the deluge of persons living with dementia really can’t be overstated. Dementia can effect persons who would still be working and productive. But even when the oldest old are effected, in lower income settings, the care for these individuals is largely provided by the family with minimal social supports from the public sector.

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Heads Up! Lots of Interesting Neurology in the American Journal of Tropical Medicine & Hygiene Feb 2018 Issue

It is unusual for a journal focused on tropical medicine to feature a predominance of articles addressing neurologic conditions. In general, one must review numerous tables of content in tropical medicine publications to accumulate enough ‘neurologic literature’ to fill an afternoon’s reading. So it was a real treat to open the February issue of AJTMH.

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The Neurological Burden Buried in the Neglected Tropical Diseases (NTDs)

Neglected Tropical Diseases (NDTs) are comprised of a discrete list of infectious diseases mainly occurring in tropical or subtropical regions which affect over a billion people and occur largely as a result of extreme poverty. Although rarely acknowledged, a third of the NTDs are primarily disorders of the neurologic system (rabies, neurocysticercosis, African sleeping sickness, leprosy) OR have neurologic system involvement as part of their most extreme and/or end stage manifestations (Chagas, schistosomiasis).

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The Burden of Cerebral Palsy in Africa-new insight reveal more epidemiological complexity

Epidemiological studies of cerebral palsy (CP) in sub-Saharan Africa are challenging to conduct leaving us with limited insights into the most basic aspects of CP in Africa including prevalence and risk factors. If saving baby brains is a priority, understanding what injures infant nervous systems, when and how would seem a critical first step in any public health intervention aimed at improving child health. Two recent publications—a rural, population-based study in Uganda1 and a well-designed case-control study in Botswana2 offer important new findings on CP in the African setting.

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Present and Future: Dementia in Latin America

In this week’s Neurology, Parra et al. present a compelling appeal and thoughtful plan for addressing the devastating and growing burden of dementia in Latin America. This report, which has its early roots in a meeting of experts in Santiago during the World Congress of Neurology in 2015, identifies the key challenges and maps a way forward with a public health approach that emphasizes optimizing affordable diagnostics and care over biomarker research given the opportunity cost of such activities. Challenges are identified in the limited epidemiological insights available for Latin America and the dearth of clinical experts in dementia. They identify a need to focus new training programs on front line healthcare workers and to mobilize existing experts to leverage political will to address the rapidly growing burden of dementia in the region. Lessons learned and successful actions taken in Latin American could be important for informing the growing global burden of dementia countries across the economic spectrum.

Looking at the Changing Landscape of Pediatric Neuro-HIV

It is a relatively rare occurrence for a physician, even over the course of a career, to witness the evolution of a disease from a universally fatal condition to a chronic but potentially manageable one. Dr. David Bearden, Assistant Professor in Neurology and Pediatrics at the University of Rochester, has done just that. From his earliest work with HIV in the US as the acute epidemic was waning to subsequent research and clinical care conducted in Botswana and now Zambia, Dr. Bearden’s perspective offers unique insights into the HIV epidemic across time and geography. Check it out as part of our “Global Stuff You Should Know” series.

Transitions in Perspective: The “Global Burden of Disease” project and Neurology

Perspective is everything.

If you were around and interested in “Global Neurology” prior to 1994, then you felt mightily alone. The metric for assessing the burden or impact of a disease or health condition was essentially a body count. This rather primitive approach failed to capture at all the burden of diseases that devastate without necessarily causing rapid death. Think severe cerebral palsy. Untreated, primary progressive multiple sclerosis. Dementia. Treatment resistant epilepsy. You get the idea. So the development of the Disability Adjusted Life Year (DALY) and efforts to quantify this through the Global Burden of Disease work were transformative for global neurology.1, 2 Neuropsychiatric disorders rose out of oblivion to become recognized as one of the top causes of the global burden.3 Let’s call this “Transition in Perspective: Phase 1”

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