Neurological Complications of Dengue Fever.

PURPOSE OF REVIEW: To discuss the neurological complications of dengue virus (DENV) infection and their pathogenesis. RECENT FINDINGS: Include recognition of the four different serotypes of DENV and their epidemiology as well as recognition of the expanded dengue syndrome encompassing multisystem involvement in the severe form of the disease including involvement of the central nervous system (CNS). DENV is a neurotropic virus with the ability to infect the supporting cells of the CNS. Neural injury during the acute stage of the infection results from direct neuro-invasion and/or the phenomenon of antibody-dependent enhancement, resulting in plasma leakage and coagulopathy. Immune mechanisms have been implicated in the development of the delayed neurological sequelae through molecular mimicry. A myriad of neurological syndromes has been described as a result of the involvement of the CNS, the peripheral nervous system (PNS), or both. Neurological manifestations in DENV infection are increasingly being recognized, some of which are potentially fatal if not treated promptly. DENV encephalopathy and encephalitis should be considered in the differential diagnosis of other acute febrile encephalopathies, autoimmune encephalitides, and in cases of encephalopathy/encephalitis related to SARS-CoV2 infection, especially in dengue-endemic areas. Acute disseminated encephalomyelitis (ADEM) may be occasionally encountered. Clinicians should be knowledgeable of the expanded dengue syndrome characterized by the concurrent compromise of cardiac, neurological, gastrointestinal, renal, and hematopopoietic systems. Isolated cranial nerve palsies occur rather uncommonly and are often steroid responsive. These neuropathies may result from the direct involvement of cranial nerve nuclei or nerve involvement or may be immune-mediated. Even if the diagnosis of dengue is confirmed, it is absolutely imperative to exclude other well-known causes of isolated cranial nerve palsies. Ischemic and hemorrhagic strokes may occur following dengue fever. The pathogenesis may be beyond the commonly observed thrombocytopenia and include cerebral vasculitis. Involvement of ocular blood vessels may cause maculopathy or retinal hemorrhages. Posterior reversible encephalopathy syndrome (PRES) is uncommon and possibly related to dysregulated cytokine release phenomena. Lastly, any patient developing acute neuromuscular weakness during the course or within a fortnight of remission from dengue fever must be screened for acute inflammatory demyelinating polyneuropathy (AIDP), hypokalemic paralysis, or acute myositis. Rarely, a Miller-Fisher-like syndrome with negative anti-GQ1b antibody may develop.

Neurological Complications of Malaria.

PURPOSE OF REVIEW: To discuss the neurological complications and pathophysiology of organ damage following malaria infection. RECENT FINDINGS: The principal advancement made in malaria research has been a better understanding of the pathogenesis of cerebral malaria (CM), the most dreaded neurological complication generally caused by Plasmodium falciparum infection. However, no definitive treatment has yet been evolved other than the use of antimalarial drugs and supportive care. The development of severe cerebral edema in CM results from two distinct pathophysiologic mechanisms. First, the development of "sticky" red blood cells (RBCs) leads to cytoadherence, where red blood cells (RBCs) get stuck to the endothelial walls and between themselves, resulting in clogging of the brain microvasculature with resultant hypoxemia and cerebral edema. In addition, the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP1) molecules protrude from the raised knob structures on the RBCs walls and are in themselves made of a combination of human and parasite proteins in a tight complex. Antibodies to surfins, rifins, and stevors from the parasite are also located in the RBC membrane. On the human microvascular side, a range of molecules involved in host-parasite interactions, including CD36 and intracellular adhesion molecule 1, is activated during interaction with other molecules such as endothelial protein C receptor and thrombospondin. As a result, an inflammatory response occurs with the dysregulated release of cytokines (TNF, interleukins 1 and 10) which damage the blood-brain barrier (BBB), causing plasma leakage and brain edema. This second mechanism of CNS injury often involves multiple organs in adult patients in endemic areas but remains localized only to the central nervous system (CNS) among African children. Neurological sequelae may follow both P. falciparum and P. vivax infections. The major brain pathology of CM is brain edema with diffuse brain swelling resulting from the combined effects of reduced perfusion and hypoxemia of cerebral neurons due to blockage of the microvasculature by parasitized RBCs as well as the neurotoxic effect of released cytokines from a hyper-acute immune host reaction. A plethora of additional neurological manifestations have been associated with malaria, including posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), malarial retinopathy, post-malarial neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), and cerebellar ataxia. Lastly, the impact of the COVID-19 pandemic on worldwide malaria control programs and the possible threat from co-infections is briefly discussed.

Bruns Syndrome - An Unusual Presentation.

Bruns syndrome is characterized by attacks of sudden severe headache, vomiting, and vertigo precipitated due to abrupt movements of the head due to presence of mobile deformable intraventricular lesion causing episodic obstructive hydrocephalus. Proposed underlying mechanism is intermittent or positional CSF obstruction resulting from ball-valve mechanism. Most common etiologies are NCC and intraventricular tumors. Here we present an unusual case of Bruns syndrome that was initially MRI negative.

Epidemiology of Peripheral Neuropathy: An Indian Perspective.

Peripheral neuropathy (PN) is a common disorder and presents as diagnostic and therapeutic challenge to physicians and neurologists. In epidemiological studies from India from various regions the overall prevalence of PN varied from 5 to 2400 per 10,000 population in various community studies. India is composed of a multiethnic, multicultural population who are exposed to different adverse environmental factors such as arsenic and lead. Use of different chemotherapeutic agents with propensity to affect peripheral nerves, increasing methods of diagnosis of connective tissue disorders and use of immunomodulating drugs, growing aging population is expected to change the spectrum and burden of peripheral neuropathy in the community. The other important aspect of peripheral neuropathies is in terms of the geographical and occupational distribution especially of toxic neuropathies like arsenic which is common in eastern belt; lead, mercury and organo-phosphorous compounds where occupational exposures are major sources. Inflammatory neuropathies either due to vasculitis or G B Syndrome, chronic inflammatory polyradiculopathies are another major group of neuropathies which is increasing due to increase longevity of Indian subjects and immunological impairment, also adds to morbidity of the patients and are potentially treatable. Leprous neuropathy is common in India and although its frequency is significantly decreasing because of national control program yet pure neuritic form still remains a cause of concern and similar is the case with another infective cause like diptheric neurpathy. Thus this article is an attempt to cover major categories and also highlight the areas where further studies are needed.