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Background and Purpose: A large proportion of ischemic stroke patients lack a definitive stroke etiology despite extensive diagnostic testing. Varicella-Zoster Virus (VZV) can directly invade blood vessels causing vasculitis and may be associated with cryptogenic stroke (CS). Methods: We conducted a retrospective cross-sectional study of CS patients tested for VZV. The following were considered evidence of VZV reactivation (VZV+): positive CSF VZV PCR, anti-VZV IgM in CSF, or anti-VZV IgG CSF/serum ratio of 1:10 or higher. We describe the cohort, report VZV+ proportion with 95% confidence intervals (CI) determined with the Wald method, and compare patient groups using standard statistical tests. Results: A total of 72 CS patients met full study inclusion criteria. Most of the patients were Conclusion: We found a high proportion of CNS VZV reactivation in a cross-sectional cohort of CS patients selected for CSF testing. Testing for VZV might be reasonable in CS patients who are young, have multifocal infarcts, or had an ischemic stroke within the past year, but additional research is needed.

Background Altered mental status (AMS) is a common neurological manifestation of COVID-19 infection in hospitalized patients. The principal causes of AMS have yet to be determined. We aimed to identify the common causes of AMS in patients with COVID-19 presenting to the emergency department with AMS on arrival. Methods We conducted a retrospective observational study of patients presenting with AMS to three New York hospitals, from March 1 to April 16, 2020. Underlying causes of AMS on arrival to the emergency department (ED) were categorized as (1) neurological causes (stroke, seizure, encephalitis); (2) metabolic encephalopathy; (3) indeterminant. Multivariable analysis was used to assess independent predictors. Results Overall, 166 patients presented to the ED with AMS. Metabolic encephalopathy was diagnosed as the cause in 154 (92.8%), with 118 (71.1%) categorized as multifactorial ME and 36 (21.7%) with single-cause ME. Hypoxia 103 (62.0%) and renal failure 75 (45.2%) were the most common underlying mechanisms. Neurological causes of AMS occurred in a total 20 patients (12%) and as the sole factor in 5 (3.0%); 10 (6.0%) cases were seizure related and 10 (6.0%) were cerebrovascular events. Of the 7 patients with indeterminant causes, only 1 was suspicious for encephalitis (0.6%). Age, pre-existing dementia and cerebrovascular disease, and impaired renal function were independent predictors of AMS. Conclusion In patients with COVID-19, AMS on presentation to the ED is most frequently caused by metabolic encephalopathy (delirium). Seizures and cerebrovascular events contribute to a lesser degree; encephalitis appears rare. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10623-5.

After attempting to move a plegic limb, patients with anosognosia for hemiplegia (AHP) may claim that limb movement occurred, even though the limb remained motionless. The authors investigated the characteristics, natural history, and anatomical basis of AHP phenomenology.Twenty-nine right-hemisphere stroke patients with acute anosognosia for hemiplegia (AHP) were prospectively assessed for the presence and characteristics of movement claims and observable behavior during movement attempts.AHP was transient, with the condition resolving in 68% of patients by 1 week. Patients made movement claims during 31% of unilateral movement attempts and 50% of bilateral movement attempts. Movement claims were idiosyncratic, lacked internal consistency within individual patients, and even dissociated from explicit denial, as several patients made movement claims after they began to explicitly acknowledge hemiplegia. Observable behavior during movement attempts revealed allochiria (moving the right arm instead of the left) in 31% of patients, signs of implicit knowledge of weakness in 24%, and intact intention in 34%. Lesion analysis revealed that allochiria was associated with inferior right parietal lobe damage.These results highlight that heterogeneity, phenomenological complexity, and transience are hallmarks of AHP. This advances clinical AHP assessment by showing that assessment of performance, rather than just verbal response, uncovers multiple dimensions of AHP. Allochiria emerges as an anatomically distinct subcomponent of the disorder. These findings also have theoretical implications, because they do not lend support to unitary pathogenic models proposing that illusions of movement or impaired intention form the basis of AHP. Most patients rapidly improve, which should invigorate the search for typical compensatory mechanisms underlying spontaneous recovery.

Background Patients who present emergently with focal neurological deficits concerning for acute ischemic stroke can be extremely challenging to diagnose and treat. Unnecessary administration of thrombolytics to potential stroke patients whose symptoms are not caused by an acute ischemic stroke—stroke mimics—may result in patient harm, although the overall risk of hemorrhagic complications among stroke mimics is low. Case Report We present a case of a stroke mimic patient with underlying psychiatric disease who was treated with intravenous alteplase on four separate occasions in four different emergency departments in the same city. Although he did not suffer hemorrhagic complications, this case highlights the importance of rapid exchange of health information across institutions to improve diagnostic quality and safety. Why Should an Emergency Physician Be Aware of This? Increased awareness of stroke mimics by emergency physicians may improve diagnostic safety for a subset of high-risk patients. Establishing rapid cross-institutional communication pathways that are integrated into provider's workflows to convey essential patient health information has potential to improve stroke diagnostic decision-making and thus represents an important topic for health systems research in emergency medicine.

We present a radiology-pathology case series of 3 patients with coronavirus disease 2019 (COVID-19) with acute ischemic stroke due to fulminant carotid thrombosis overlying mild atherosclerotic plaque and propose a novel stroke mechanism: COVID-associated carotid atherothrombosis.

The role of Varicella zoster virus (VZV) in neurological illness, particularly cerebrovascular disease, has been increasingly recognized. Primary infection by VZV causes varicella (chickenpox), after which the virus remains latent in neuronal ganglia. Later, during aging or immunosuppression, the virus can reactivate causing zoster (shingles). Virus reactivation can also spread to cerebral arteries causing vasculitis and stroke. Zoster is a recognized risk factor for stroke, but stroke can occur without preceding zoster rash. The diagnosis of VZV cerebral vasculitis is established by abnormal brain imaging and confirmed by presence of viral DNA or anti-VZV antibodies in cerebrospinal fluid. Treatment with acyclovir with or without prednisone is usually recommended. VZV vasculitis is a unique and uncommon stroke mechanism that has been under recognized. Careful diagnostic investigation may be warranted in a subgroup of patients with ischemic stroke to detect VZV vasculitis and initiate appropriate therapy. In the following review, we detail the clinical presentation of VZV vasculitis, diagnostic challenges in VZV detection, and suggest the ways to enhance recognition and treatment of this uncommon disease.

Introduction: While coronavirus disease 2019 (COVID-19) has been associated with acute ischemic stroke (AIS), the causal relationship has yet to be elucidated. Factors that likely confer increased stroke risk are COVID-19-associated coagulopathy and hyperinflammatory response. Studying clinical features of patients with otherwise undetermined cause of AIS could help better define COVID-19-associated stroke. Methods: We performed a multicenter cross-sectional study of consecutive patients presenting with AIS and COVID-19 to one of two large healthcare systems in New York City during the local COVID-19 surge from March 1, 2020 to May 31, 2020. In-hospital stroke cases were excluded. We compared demographic and clinical features of patients with COVID-19 and a cryptogenic AIS subtype to patients with COVID-19 and a determined subtype. Baseline characteristics and clinical variables were compared using chi-squared and Fisher exact tests. Results: A total of 62 patients with AIS and COVID-19 at the time of hospital arrival were identified. Of these, 30 were classified as having a cryptogenic subtype (80% after complete diagnotics evaluation), and 32 had an identifiable stroke mechanism. Patients with cryptogenic AIS were significantly younger (p=0.011) and less likely to have co-morbid hypertension (p=0.019), coronary artery disease (p=0.024), heart failure (p=0.039), atrial fibrillation ( Conclusion: Patients with AIS in the setting of COVID-19 and no other determined stroke mechanism were younger, less likely to have classic risk factors, and had higher d-dimer levels when compared to those with a determined mechanism. Further study of COVID-19-associated hypercoagulability as a mechanism of stroke is warranted.

Introduction: Up to 15% of all strokes occur in patients who are already hospitalized for other conditions. A validated clinical tool to help rapidly discriminate between mimics and stroke among inpatients could greatly improve acute stroke care. Recently, the 2CAN score was developed and validated at a single Midwest academic medical center to identify inpatient strokes; a score of ≥2 was highly sensitive and specific for stroke. We sought to externally validate the 2CAN score at our institution. Methods: We conducted a retrospective cohort study of consecutive inpatient stroke codes at a single Northeast academic medical center from 7/1/2018 to 11/1/2019. Pre-specified variables, including patient demographics, vascular risk factors, and clinical features (neurological examination, vital signs, laboratory values, and final diagnoses), were abstracted from the electronic medical record. We determined the sensitivity, specificity, positive and negative predictive value of a 2CAN score ≥2 for stroke (ischemic stroke, hemorrhagic stroke, or TIA) in our cohort. The 2CAN score consists of clinical deficit score (0-3 points), recent cardiac procedure (1 point), atrial fibrillation (1 point), and code called within 24 hours of admission (1 point). We used multivariate logistic regression to identify additional determinants of stroke. Results: We identified 111 inpatient stroke codes on 110 patients, mean age 67 ± 1 year, 46.8% women, and 73.8% Black or Hispanic. Final diagnosis was stroke for 54 codes (48.6%) and mimic for 57 codes (51.3%), most commonly toxic-metabolic encephalopathy. 2CAN score ≥2 had 96.3% sensitivity, 45.6% specificity, 62.7% positive predictive value, and 92.3% negative predictive value for stroke. In a multivariable logistic regression model, only recent cardiac procedure (OR: 5.5; 95% CI: 1.1-27.5) and high clinical deficit score (OR: 3.9; 95% CI: 1.9-6.1) predicted stroke. Conclusion: The 2CAN score is externally valid and helps distinguish stroke from mimic in inpatients; having a score of

ObjectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality.MethodsA total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death.ResultsA total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04–1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65–5.92) had a higher risk of mortality than age- and severity-matched controls.ConclusionsThe incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Background: Headache is a common presenting symptom among patients with misdiagnosed cerebrovascular (CVD) disease. Recent studies report that the occurrence of a head CT (HCT) during emergency department (ED) visit for non-specific neurological symptoms, such as vertigo, is associated with increased risk of stroke after ED discharge. We sought to evaluate whether the occurrence of HCT at ED visit for headache is associated with increased CVD risk. Hypothesis: Patients with headache complaints who have a HCT performed in the ED (exposed) are more likely to have a CVD admission within 365 days of ED discharge than those who do not receive a HCT (unexposed). Methods: We conducted a retrospective study of consecutive adult patients with headache complaints discharged to home (treat-and-release visit) from all four of the EDs affiliated with a single academic institution. Patients with headache complaints were defined as those with primary ICD-9/10-CM discharge diagnosis of benign headache; patients were included in our study at their first ED treat-and-release visit from 2013 to 2018. Subsequent CVD hospitalizations were identified using ICD-9/10-CM inpatient discharge codes and confirmed via chart review. We matched exposed to unexposed patients in a one-to-one fashion using propensity score methods. Standard descriptive statistics and relative risk (RR) with 95% CIs are reported. Results: Among 28,121 patients with an ED treat-and-release visit for headache complaints, 45.6% (n=12,812) underwent HCT during ED visit. A total of 0.4% (n=112) patients had a subsequent CVD admission within 365 days of ED visit. Using propensity score matching, 80.3% (n=10,295) of patients with HCT (exposed) were able to be matched. In the matched sample, exposed patients had a nearly two-fold increased relative risk of CVD at 365 days (RR: 1.83; 95% CI: 1.12-3.01). In secondary analysis, CVD risk at 180 days was also higher in exposed (RR: 2.06; 95% CI: 1.13-3.74). Conclusion: Having a HCT performed at index ED treat-and-release visit among those with headache complaints establishes a clinically meaningful risk gradient for subsequent CVD hospitalization. Some ED patients given a headache diagnosis may have been misdiagnosed at index visit.

The presence of a phantom limb (PL) resulting from a cerebral lesion has been reported to be a rare event. No prior study, however, has systematically investigated the prevalence of this syndrome in a group of post-stroke individuals. Fifty post-stroke individuals were examined with structured interview/questionnaire to establish the presence and perceptual characteristics of PLs. We document the presence of phantom experiences in over half of these individuals (n=27). We provide details of these phantom experiences and further characterize these symptoms in terms of temporal qualities, posture, kinesthesia, and associated features. Twenty-two participants reported postural phantoms, which were perceived as illusions of limb position that commonly manifested while lying in bed at night - a time when visual input is removed from multi-sensory integration. Fourteen participants reported kinesthetic phantoms, with illusory movements ranging from simple single joint sensations to complex goal-directed phantom movements. A striking syndrome of near total volitional control of phantom movements was reported in four participants who had immobile plegic hands. Reduplicative phantom percepts were reported by only one participant. Similarly, phantom pain was present in only one individual - the sole participant with a pre-stroke limb amputation. The results suggest that stroke results in phantom experiences more commonly than previously described in the literature. We speculate that subtotal deafferance or defective motor efference after stroke may manifest intermittently as a PL.

Background and purpose: Recanalization reduces final infarct volume, an important predictor of clinical outcome. Lesion location is also a determinant of outcome, however, the extent to which recanalization affects lesion topography has yet to be explored. Are there brain regions more likely to be spared if recanalization occurs? We investigated this question by using voxel-based lesion mapping to examine the effect of recanalization on infarct topography in middle cerebral artery (MCA) occlusion. Methods: Consecutive patients with acute stroke from MCA occlusion were examined to identify brain regions characteristically spared with recanalization (R+) (TICI 2a to 3), but damaged in patients with persistent occlusions (R-). The lesions were drawn directly on the MRI or CT images and then transformed into stereotaxic space using MRIcroN software. Lesions were superimposed to create voxel-based lesion plots for each group. A leibemeister test was performed comparing the two groups at every brain voxel, with Bonferroni correction. Results: Twenty-one patients were included: 11 had endovascular recanalization (R+) and 10 received no or unsuccessful treatment (R-). The figure shows the lesion overlay plots and the statistical map resulting from the analysis. In total, 5,250,682 voxels were tested, yielding a Bonferroni corrected P 0.1). Conclusions: Our analysis did not reveal brain regions characteristically spared with recanalization. Prior studies have shown reduced infarct volume after recanalization; ours did not, and this may be the underlying reason why no salvage pattern was observed. The effect of recanalization on stroke topography remains an important, unexplored area. We have shown that voxel-based lesion mapping has potential as a biomarker in endovascular therapy.

A 57-year-old right-handed man complained of difficulty using his hands post–coronary artery bypass graft (figure). Neurologic examination revealed signs of callosal disconnection without hemiparesis. When asked to perform limb gestures such as “brush your teeth” or “wave goodbye,” the right hand performed flawlessly whereas the left hand was severely apraxic (video on the Neurology ® Web site at [www.neurology.org][1]). [1]: http://www.neurology.org

Background and Purpose— Most improvement from poststroke aphasia occurs within the first 3 months, but there remains unexplained variability in recovery. Recently, we reported a strong correlation between initial impairment and change scores in motor recovery at 90 days. We wanted to determine whether aphasia recovery (defined as a change from baseline to 90 days) shows a comparably strong correlation and whether the relation was similar to that in motor recovery. Methods— Twenty-one stroke patients had aphasia scores on the Western Aphasia Battery (WAB) obtained on stroke admission (WAB initial ) and at 90 days (WAB 3 mo ). The relation between actual change (Δ) scores (defined as WAB 3 mo − WAB initial ) and WAB initial was calculated in multiple-regression analysis. Results— Regression analysis demonstrated that WAB initial was highly correlated with ΔWAB ( R 2 =0.81, P initial and ΔWAB was proportional, such that patients recovered 0.73 of maximal potential recovery (WAB maximum −WAB initial ). Conclusions— We show that, like motor recovery, there is a highly predictable relation between aphasia recovery and initial impairment, which is also proportional in nature. The comparability of recovery from motor and language impairment suggests that common mechanisms may govern reduction of poststroke neurologic impairment across different functional domains and that they could be the focus of therapeutic intervention.

Clinicians have long recognized the enormous variability of recovery among patients with aphasia. Accordingly, the identification of specific factors most important in determining the extent of recovery has been the subject of many investigations. Yet, the reasons for two patients of the same age, nearly identical clinical presentations, and similar MRI findings having completely dissimilar recoveries are still unknown. It remains difficult for a clinician to make a valid prognosis of language recovery in an individual patient. This article provides a review of aphasia-recovery research and a framework for approaching the variability of recovery in clinical practice.

Background: Patients with Parkinson disease (PD) have deficits in the neurotransmitter systems important for the normal allocation of attention. We sought to examine how the presence of PD influences the spatial allocation of reactive (bottom-up) and volitional (top-down) attention. Methods: To assess the spatial allocation of attention, we used the line bisection task. When assessing "bottom-up" attention, lateral blinking lights were or were not present during the time the PD and normal subjects were attempting to perform line bisections. In the top-down condition, these subjects were asked to name the color of the laterally presented light before bisecting lines. Results: In the bottom-up condition, when compared with control subjects, the participants with PD were not abnormally distracted, but in the top-down condition, imperative stimuli on the right side of the line seemed to influence the PD subjects' allocation of attention. Conclusions: The results suggest that when voluntarily allocating attention rightward, PD patients have difficulty disengaging and/or reallocating their attention. This disengagement deficit might be related to the frontal-executive dysfunction associated with PD.

Objective: To study the prevalence of anosognosia for hemiplegia (AHP) in the hyperacute phase and track the natural history of the disorder, in order provide a more complete account of the phenomenon. Background Anosognosia for hemiplegia (AHP) after stroke contributes to clinical morbidity and poor outcome in several different ways, beginning at the time of acute injury (the hyperacute phase) and continuing through the course of the illness. AHP is the behavioral response to sudden hemiplegia in 33-58% of patients and has been found to be associated with longer rehabilitation and poorer functional outcomes following stroke. Despite the pragmatic implications, relatively little is known about the natural history and neuropsychological basis of AHP. Design/Methods: We assessed patients in the acute phase and subacute phase of stroke with serial neuro-cognitive exams. Enrolled patients underwent serial neurological and neuropsychological examinations while on our stoke unit. The neuropsychology battery included a detailed awareness interview (including the Bisiach and Feinberg Scales) and neglect batteries performed in the hours and days after stroke. Results: Of the 28 patients enrolled, AHP was frequent at 28% in the hyperacute phase ( Conclusions: Anosognosia for hemiplegia is a transient phenomenon that tends to dissipate with time, and thus it9s reported frequency and presentation may vary depending on when patients are evaluated. Although there is rapid improvement in explicit recognition of hemiplegia, the fact that AHP remains an independent predictor of poor functional recovery underscores the need to further understand the underlying mechanism of the disorder, and how it contributes to a poor global functional recovery. Disclosure: Dr. Antoniello has nothing to disclose. Dr. Gottesman has nothing to disclose.