Objective Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”. Methods This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive (SARS‐CoV‐2+) and 50 laboratory‐negative (SARS‐CoV‐2‐) individuals) presenting to our Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient‐reported quality of life measures and standardized cognitive assessments. Results Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2+ than SARS‐CoV‐2‐ patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS‐CoV‐2+ patients performed worse in attention and working memory cognitive tasks compared to a demographic‐matched US population (T‐score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01). Interpretation Non‐hospitalized Covid‐19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.

Objective: Covid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19. Methods: We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression. Results: Neurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001). Interpretation: Neurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.

Status epilepticus (SE) is one of the most serious manifestations of epilepsy. Systemic inflammation and damage of blood-brain barrier (BBB) are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures. Whether an inflammatory-vascular-BBB mechanism could apply to the lithium–pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear cells. Serum IL-1β levels increased and BBB damage occurred concurrently to increased theta EEG activity. These events occurred prior to SE induced by cholinergic exposure. SE was elicited by lithium and pilocarpine irrespective of their sequence of administration supporting a common pathogenetic mechanism. Since IL-1β is an etiologic trigger for BBB breakdown and its serum elevation occurs before onset of SE early after LiCl and pilocarpine injections, we tested the hypothesis that intravenous administration of IL-1 receptor antagonists (IL-1ra) may prevent pilocarpine-induced seizures. Animals pre-treated with IL-1ra exhibited significant reduction of SE onset and of BBB damage. Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus.

Summary:Objectives: A common experimental model of status epilepticus (SE) utilizes intraperitoneal administration of the cholinergic agonist pilocarpine preceded by methylscopolamine treatment. Currently, activation of cholinergic neurons is recognized as the only factor triggering pilocarpine SE. However, cholinergic receptors are also widely distributed systemically and pretreatment with methyl-scopolamine may not be sufficient to counteract the effects of systemically injected pilocarpine. The extent of such peripheral events and the contribution to SE are unknown and the possibility that pilocarpine also induces SE by peripheral actions is yet untested.Methods: We measured in vivo at onset of SE: brain and blood pilocarpine levels, blood-brain barrier (BBB) permeability, Tlymphocyte activation and serum levels of IL-1β and TNF-α. The effects of pilocarpine on neuronal excitability was assessed in vitro on hippocampal slices or whole guinea pig brain preparations in presence of physiologic or elevated [K + ] out .Results: Pilocarpine blood and brain levels at SE were 1400 ± 200 µM and 200 ± 80 µM, respectively. In vivo, after pilocarpine injection, increased serum IL-1β, decreased CD4:CD8 T-lymphocyte ratios and focal BBB leakage were observed. In vitro, pilocarpine failed to exert significant synchronized epileptiform activity when applied at concentrations identical or higher to levels measured in vivo. Intense electrographic seizure-like events occurred only in the copresence of levels of K + (6 mM) mimicking BBB leakage.Conclusions: Early systemic events increasing BBB permeability may promote entry of cofactors (e. g. K + ) into the brain leading to pilocarpine-induced SE. Disturbance of brain homeostasis represents an etiological factor contributing to pilocarpine seizures.

Critical illness myopathy (CIM) and neuropathy are underdiagnosed conditions within the intensive care setting and contribute to prolonged mechanical ventilation and ventilator wean failure and ultimately lead to significant morbidity and mortality. These conditions are often further subdivided into CIM, critical illness polyneuropathy (CIP), or the combination-critical illness polyneuromyopathy (CIPNM). In this review, we discuss the epidemiology and pathophysiology of CIM, CIP, and CIPNM, along with diagnostic considerations such as detailed clinical examination, electrophysiological studies, and histopathological review of muscle biopsy specimens. We also review current available treatments and prognosis. Increased awareness and early recognition of CIM, CIP, and CIPNM in the intensive care unit setting may lead to earlier treatments and rehabilitation, improving patient outcomes.

Background and Purpose-The introduction of balloon remodeling has revolutionized the approach to coiling of wide-neck aneurysms. We studied the effects of balloon inflation during coil embolization on ischemic complications. Methods-A retrospective review was undertaken of the most recent 147 patients undergoing balloon remodeling for unruptured intracranial aneurysm coil embolization at a single institution (81 balloon, 66 unassisted). All underwent postprocedural MRI. Results-Among patients in the "balloon" group, the mean total inflation time was 18 minutes (range, 1-43), a mean number of inflations of 4 (range, 1-9), a mean maximum single inflation time of 7 minutes (range, 1-19), a mean reperfusion time of 2.2 minutes between inflations, and an average procedure time of 2 hours and 10 minutes. Asymptomatic diffusion-weighted imaging abnormalities were detected on postprocedural MRI in 21.5% of patients and symptomatic lesions were identified in 3.8%. Both silent and symptomatic ischemic rates were similar in the internal control group. Patients with ischemic findings were older and more likely have diabetes; no differences were found with respect to total balloon inflation time, number of inflations, maximum inflation time, or reperfusion times. Conclusions-We found no significant relationship between balloon inflation practices and ischemic events. Older and diabetic patients were more likely to have ischemic events develop.

Highlights COVID-19 disease is associated with stroke All strokes subtypes are seen in association with COVID-19, with ischemic stroke being most prevalent The most common etiology for ischemic stroke in SARS-CoV2 infection is cryptogenic Sex plays an important role in stroke outcomes in patients with COVID-19 disease Males have higher rates of ICU admission, in-hospital complications and more likely to have worse outcome at hospital discharge compare with females

Cerebrovascular complications of pregnancy, though uncommon, threaten women with severe morbidity or death, and they are the main causes of major long-term disability associated with pregnancy. In this review, we discuss the epidemiology, pathophysiology, presentation and diagnosis, and management and outcomes of ischemic and hemorrhagic stroke and cerebral venous thrombosis. We also discuss the posterior reversible encephalopathy syndrome, the reversible cerebral vasoconstriction syndrome including postpartum cerebral angiopathy, and their relationship as overlapping manifestations of pre-eclampsia-eclampsia.