ObjectiveTo report clinical and laboratory characteristics, as well as treatment and clinical outcomes of patients admitted for neurologic diseases with and without COVID-19.MethodsIn this retrospective, single center cohort study, we included all adult inpatients with confirmed COVID-19, admitted to a Neuro-COVID Unit from February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (FDR-corrected) to those of neurologic patients without COVID-19 admitted in the same period.ResultsOne hundred seventy-three patients were included in this study, of whom 56 were positive for COVID-19 while 117 were negative for COVID-19. Patients with COVID-19 were older (77.0, IQR 67.0–83.8 vs 70.1, IQR 52.9–78.6, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.5, IQR 0.4–0.6 vs 0.9, IQR 0.7–1.1, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. COVID-19 and non-COVID patients with stroke had similar baseline characteristics but patients with COVID-19 had higher modified Rankin scale scores at discharge (5.0, IQR 2.0–6.0 vs 2.0, IQR 1.0–3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (OR 4.47, 95% CI 1.21–16.5; p = 0.025), lower platelet count (0.98, 0.97–0.99; p = 0.005) and higher lactate dehydrogenase (1.01, 1.00–1.03; p = 0.009) on admission.ConclusionsCOVID-19 patients admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality, incident delirium and higher disability than patients without COVID-19.

Background Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes. Methods The ENCOVID multicentre study included patients with encephalitis with full infectious screening, CSF, EEG, MRI data and confirmed SARS-CoV-2 infection recruited from 13 centres in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. Results twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis. Conclusions SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment and outcomes.

Background Clinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity. Methods From a sample of 208 consecutive non-neurological patients hospitalised for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardised clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. Results At 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%) and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses. Conclusions Premorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations.

COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.

Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks, with a 14-week (T3), 24-week (T4), 36-week (T5) and 52-week follow-up (T6) (open-label phase). At each time point, a clinical, neuropsychological and neurophysiological evaluation was performed. Cerebellar-motor cortex connectivity was evaluated using transcranial magnetic stimulation (TMS). We observed a significant improvement in all motor scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale), in cognition (evaluated with the cerebellar cognitive affective syndrome scale), in quality-of-life scores, in motor cortex excitability and in cerebellar inhibition after real tDCS compared to sham stimulation and compared to baseline (T0), both at short and long-term. We observed an addon-effect after two repeated treatments with real tDCS compared to a single treatment with real tDCS. The improvement at motor and cognitive scores correlated with the restoration of cerebellar inhibition evaluated with TMS. Cerebello-spinal tDCS represents a promising therapeutic approach for both motor and cognitive symptoms in patients with neurodegenerative ataxia, a still orphan disorder of any pharmacological intervention.

COVID-19 impact on consecutive neurological patients admitted to the emergency department Letter copyright.

BackgroundPreclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection and for long term sequalae including neurological manifestationsMethodsa sample of 208 previously hospitalized COVID-19 patients, 165 patients were re-assessed at 6 months according to a structured standardized clinical protocol. Premorbid comorbidities and clinical status, severity of COVID-19 disease, complications during and after hospitalization were recorded.ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of neurological symptoms, being fatigue (34%), memory/attention (31%), and sleep disorders (30%) the most frequent. Subjects reporting neurological symptoms were affected by more severe respiratory SARS-CoV-2 infection parameters during hospitalisation. At neurological examination, 37.4% of patients exhibited neurological abnormalities, being cognitive deficits (17.5%), hyposmia (15.7%) and postural tremor (13.8%) the most common. Patients with cognitive deficits at follow-up were comparable for age, sex and pre-admission comorbidities but experienced worse respiratory SARS-CoV-2 infection disease and longer hospitalisation.Conclusionslong term neurological manifestations after hospitalization due to COVID-19 infection affects one third of survivors. Multiple neurological abnormalities including mild cognitive impairment are associated with severity of respiratory SARS-CoV-2 infection.

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.