Atypical presentation of scrub typhus encephalitis with cerebral hemorrhage

Scrub typhus, an arthropod borne infection caused by the rickettsial organism Orientia tsutsugamushi, is a fairly common disease in north-eastern sub-Himalayan India, particularly the forest areas, and is known to manifest with varied presentations ranging from non-specific fever to severe multi-organ complications. Hemorrhagic manifestations described in the literature are mostly gastrointestinal and genitourinary, secondary to vasculitis and/or thrombocytopenia, but reports of cerebral hemorrhage have been extremely rare. We report a case from sub-Himalayan eastern India where a 23 years old male tea plantation worker presented with recurrent convulsions with magnetic resonance imaging (MRI) brain showing multiple parenchymal hemorrhages with encephalitis involving both the cerebral hemispheres. Although patient developed fever and acute kidney injury later in the course, these were not the presenting complaints despite fever being the most consistent sign of a scrub typhus infection. We suggest consideration of scrub typhus as a differential diagnosis of a cerebral hemorrhage in endemic regions

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Atypical presentation of scrub typhus encephalitis with cerebral hemorrhage

International audienceScrub typhus, an arthropod borne infection caused by the rickettsial organism Orientia tsutsugamushi, is a fairly common disease in north-eastern sub-Himalayan India, particularly the forest areas, and is known to manifest with varied presentations ranging from non-specific fever to severe multi-organ complications. Hemorrhagic manifestations described in the literature are mostly gastrointestinal and genitourinary, secondary to vasculitis and/or thrombocytopenia, but reports of cerebral hemorrhage have been extremely rare. We report a case from sub-Himalayan eastern India where a 23 years old male tea plantation worker presented with recurrent convulsions with magnetic resonance imaging (MRI) brain showing multiple parenchymal hemorrhages with encephalitis involving both the cerebral hemispheres. Although patient developed fever and acute kidney injury later in the course, these were not the presenting complaints despite fever being the most consistent sign of a scrub typhus infection. We suggest consideration of scrub typhus as a differential diagnosis of a cerebral hemorrhage in endemic regions

The Binding of DNA Intercalating and Non-Intercalating Compounds to A-form and Protonated form of Poly(rC)Æpoly(rG): Spectroscopic and Viscometric Study

Abstract—Polymorphic RNA conformations may serve as potential targets for structure specific antiviral agents. As an initial step in the development of such drugs, the interaction of a wide variety of compounds which are characterized to bind to DNA through classical or partial intercalation or by mechanism of groove binding, with the A-form and the protonated form of poly(rC)Æpoly(rG), been evaluated by multifaceted spectroscopic and viscometric techniques. Results of this study suggest that (i) ethidium intercalates to the A-form of RNA, but does not intercalate to the protonated form, (ii) methylene blue intercalates to the protonated form of the RNA but does not intercalate to the A-form, (iii) actinomycin D does not bind to either conformations of the RNA, and (iv) berberine binds to the protonated form by partial intercalation process, while its binding to the A-form is very weak. The DNA groove binder distamycin A has much higher affinity to the protonated form of the RNA compared to the A-form and binds to both structures by non-intercalative mechanism. We conclude that the binding affinity characteristics of these DNA binding molecules to the RNA conformations are vastly different and may serve as data for the development of RNA based antiviral drugs