Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

OBJECTIVE: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19). METHODS: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning 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 (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period. RESULTS: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, 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 (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, 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. Patients with COVID-19 and without COVID 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 (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, p = 0.009) on admission. CONCLUSIONS: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features.

The role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. Several in vitro and in vivo studies performed in the last decade have dramatically improved our understanding of the molecular and functional effects induced by both NMDAR and AMPAR autoantibodies at the excitatory glutamatergic synapse and, consequently, their possible role in the onset of clinical symptoms. In particular, the method by which autoantibodies can modulate the localization at synapses of specific target subunits leading to functional impairments and behavioral alterations has been well addressed in animal studies. Overall, these preclinical studies have opened new avenues for the development of novel pharmacological treatments specifically targeting the synaptic activation of ionotropic glutamate receptors.

Diaphragmatic myoclonus due to SARS-CoV-2 infection.

A wide range of neurological signs and symptoms have been associated with SARS-CoV-2 infection. In the present report, we described two Italian patients diagnosed with diaphragmatic myoclonus after COVID-19. In both cases, mild lymphocytosis at cerebrospinal fluid analysis and no structural brain changes were reported. The pathophysiological origin of the myoclonus in the two cases was different. In case 1, electroencephalogram did not reveal any cortical correlates and brain imaging of the spine was unremarkable, while in case 2, cortical origin of myoclonus was demonstrated. With the present two cases, we confirm and extend the neurological manifestations of SARS-CoV-2 infection.

Effortful speech with distortion of prosody following SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a 48-year-old Caucasian woman with SARS-CoV-2 infection followed by the onset of word finding difficulties, effortful speech along with prosody distortion, in the context of spared semantic and syntactic abilities. The clinical picture, perceived as foreign accent syndrome (FAS), was not associated with structural and functional imaging changes or neurophysiological assessment abnormalities. We suggest that FAS, herein perceived as a regional accent syndrome, should be considered a possible additional neurological manifestation of SARS-CoV-2.