Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19.Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection.Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10 −12 ) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1,; p = 0.002) was a predictor of death. Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

Toxic leukoencephalopathy is a rare cause of encephalopathy. We describe two cases of toxic leukoencephalopathy associated with opiate abuse where they were misdiagnosed and admitted to the psychiatric ward. In our case series, both patients presented with behavioral changes, restlessness, pressured speech, and cognitive impairment for which they were initially labeled as psychiatric patients and were treated as such. However, after an extensive workup to elucidate the etiology of alteration in mental status, toxic leukoencephalopathy associated with heroin abuse was found to be the culprit in both cases. Toxic leukoencephalopathy is a rare condition that can be caused by inhalation of heroin. Clinically, it may present with confusion, behavioral changes, extrapyramidal symptoms, generalized motor deficit, unresponsiveness and even death. Our cases highlight the importance of recognizing the psychiatric presentation of toxic leukoencephalopathy.

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