Clinical and Experimental Studies in Japanese Encephalitis: Lessons Learnt

Abstract

ABSTRACT Introduction: Managing encephalitis for last 3 decades and conducting experimental studies have provided a number of important findings some which are presented.. Method: Summary of important clinical, radiological, neurophysiological and biochemical studies are presented. The results of experimental studies in a rat model have been used to investigate the basis of behavioral changes, histology, and molecular alterations in Japanese encephalitis (JE) and finally an approach to acute encephalitis syndrome (AES) is presented. Result: The patients with encephalitis can be produced by a number of noninfectious, infectious. The local prevalence and time of the year are crucial for clinical decision making. The affinity of JEV for thalamus, corpus striatum, substantia nigra, cerebellum and anterior horn cell was documented by imaging studies, which was further confirmed on immune histopathological and real time PCR studies highlighting the tropism of JEV. The lower motor neuron involvement on EMG studies was attributed to anterior horn cell involvement. JE results in frequent and severe movement disorders. The basis of movement disorders was revealed in MRI and SPECT studies showing thalamic and cortical hyperperfusion suggesting the involvement of thalamo-cortical projections. Hyperkinetic or hypokinetic movement disorders were due to differential involvement of excitatory or inhibitory circuits in the brain. Reduction in catecholamine and its metabolites in CSF of patients was supported by reduction of catecholamine and dopamine receptors in the JE tropic areas in thalamus, corpus striatum and brainstem resulting in dopamine deficiency. The learning and memory deficits in JE were attributed to cholinergic dysfunction reveled by expression of CHAT, HQNB CHR M2 mscarinic receptors in the JE affected areas of brain.A syndromic approach to AES categorizing the patients into neurologic or systemic group and using rational investigations; imaging and Acyclovir therapy in pure neurologic group and avoiding these in systemic group is recommended. In systemic group, treatment with doxycycline for scrub typhus, artesunate for malaria, ceftriaxone for leptospira and fluid management for dengue are recommended. Conclusion: A combined clinical and experimental approach provides valuable information to understand the basis of clinical alterations in JE.