This expert working group report proposes an updated approach to subtype definition of vascular parkinsonism (VaP) based on a review of the existing literature. The persistent lack of consensus on clear terminology and inconsistent conceptual definition of VaP formed the impetus for the current expert recommendation report. The updated diagnostic approach intends to provide a comprehensive tool for clinical practice. The preamble for this initiative is that VaP can be diagnosed in individual patients with possible prognostic and therapeutic consequences and therefore should be recognized as a clinical entity. The diagnosis of VaP is based on the presence of clinical parkinsonism, with variable motor and non-motor signs that are corroborated by clinical, anatomic or imaging findings of cerebrovascular disease. Three VaP subtypes are presented: (1) The acute or subacute post-stroke VaP subtype presents with acute or subacute onset of parkinsonism, which is typically asymmetric and responds to dopaminergic drugs; (2) The more frequent insidious onset VaP subtype presents with progressive parkinsonism with prominent postural instability, gait impairment, corticospinal, cerebellar, pseudobulbar, cognitive and urinary symptoms and poor responsiveness to dopaminergic drugs. A higher-level gait disorder occurs frequently as a dominant manifestation in the clinical spectrum of insidious onset VaP, and (3) With the emergence of molecular imaging biomarkers in clinical practice, our diagnostic approach also allows for the recognition of mixed or overlapping syndromes of VaP with Parkinson's disease or other neurodegenerative parkinsonisms. Directions for future research are also discussed.

Background and purpose Despite the increasing number of reports on the spectrum of neurological manifestations of COVID‐19 (neuro‐COVID), few studies have assessed short‐ and long‐term outcome of the disease. Methods This is a cohort study enrolling adult patients with neuro‐COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro‐covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as ‘stable/improved’ if the modified Rankin Scale score was equal to or lower than the pre‐morbid score, ‘worse’ if the score was higher than the pre‐morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. Results From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non‐hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow‐up. Conclusions Neuro‐COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.

Objective Inhibition of dihydroorotate dehydrogenase suppresses magnetic resonance imaging brain lesions and disease activity in multiple sclerosis but has limiting tolerability. We assessed the safety and efficacy of vidofludimus calcium, a novel, selective dihydroorotate dehydrogenase inhibitor, in patients with relapsing‐remitting multiple sclerosis. Methods This double‐blind, 24 weeks, placebo‐controlled, phase 2 trial (EMPhASIS) enrolled patients 18–55 years with relapsing‐remitting multiple sclerosis. Eligible patients were randomly assigned (1:1:1) to once‐daily vidofludimus calcium (30 mg or 45 mg) or placebo. The primary endpoint was the cumulative number of combined unique active lesions to week 24 between vidofludimus calcium 45 mg and placebo (http://clinicaltrials.gov number NCT03846219; EudraCT 2018–001896‐19). Results After 24 weeks, the mean cumulative number of combined unique active lesions was 6.4 (95% CI: 2.8–13.9) with placebo compared to 2.4 (95% CI: 1.1–4.9) with vidofludimus calcium 45 mg (rate ratio 0.38, 95% CI: 0.22–0.64; p = 0.0002); the rate ratio between vidofludimus calcium 30 mg and placebo was 0.30 (95% CI: 0.17–0.53; p < 0.0001). Treatment‐emergent adverse events occurred in 30 (44%) of patients assigned placebo and 60 (43%) of patients assigned vidofludimus calcium. Serious adverse events occurred in one (1%) assigned placebo and two (1%) assigned vidofludimus calcium. No increased incidence of infectious, hepatic, or renal treatment‐emergent adverse events or serious adverse events was observed. Interpretation Treatment with vidofludimus calcium led to a reduction in new magnetic resonance imaging lesions in patients with relapsing‐remitting multiple sclerosis and was well tolerated with a favorable safety profile. Assessment in longer, larger trials is justified.

The aim: Was to determine the relations between the the upper extremity function and cognition in post-stroke patients. Materials and methods: Totally there were 86 patients examined in the 1-year period after first-ever anterior circulation ischemic stroke. Examination of the upper extremity function was performed with the Fugl-Meyer assessment (FMA). Cognitive function was assessed with the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Trail-making Test A and B (TMT) and the Clock Drawing Test (CDT). Results: Motor dysfunction mostly manifested in low “Wrist” and “Hand” subtests scores (5 and 7 , respectively) and therefore resulted in decreased “Total motor function” score of 40 . The most significant relations were found out between the FMA “Hand”, “Total motor function” subtests and CI indices. MoCA score correlated with FMA “Wrist” (r=0.34; p=0.021), “Hand” (r=0.52; p=0.001) and “Total motor function” (r=0.48; p=0.003) scores. “Hand” score also correlated with the FAB (r=0.43; p=0.012), CDT (r=0.22; p=0.016), TMT-A (r=-0.31; p=0.023) and TMT-B (-0.48; p=0.009) scores. There was no significant correlation between the sensory FMA subtests. Conclusion: Our findings suggest that upper extremity motor impairment, especially hand and wrist dysfunction, are associated with cognitive impairment and executive functions disorder in particular.

Background and purpose: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. Methods: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in-and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/ subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. Results: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. Conclusions: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.