Cross-Sectional Retrospective Study to Identify Clinical and Radiographic Features Associated With VZV Reactivation in Cryptogenic Stroke Patients With CSF Testing.

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 <65 years old, had few traditional vascular risk factors, and had multifocal infarcts. Mean age was 49 years (SD ±13) and 47% were women. A total of 14 patients (19.4%; CI: 11.4-30.8%) had evidence of CNS VZV reactivation. There was no difference in evaluated demographic or radiographic features between those with versus without evidence of VZV reactivation. History of ischemic stroke in the past year (11/14 vs 25/43, P<.05) and hypertension (13/14 vs 35/58 and P<.05) were associated with VZV+. 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.

Altered mental status in COVID-19.

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.

Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

OBJECTIVE: Severe 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: The 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.

The Phenomenology of Acute Anosognosia for Hemiplegia.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Multiple Administrations of Intravenous Thrombolytic Therapy to a Stroke Mimic.

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.

Varicella Zoster Virus Vasculitis and Adult Cerebrovascular Disease.

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.

Limb Misidentification: A Clinical-Anatomical Prospective Study.

The misidentification of one's own limb (LM) after right hemisphere stroke is a striking phenomenon that is incompletely understood. The authors prospectively studied the natural history and anatomy of LM in 36 patients with hyperacute right middle cerebral artery infarct. Unlike in previous studies, rapid clinical assessment was prioritized. The authors found LM to be common and transient, involving 61% at onset, evolving to 15% at 1 week. Voxel-based lesion-symptom mapping found supramarginal gyrus (SMG) damage associated with LM. This substantiates the SMG's importance in LM and has broader implications for lesion analysis: timing matters. Rapid assessment of transient disorders minimizes false negatives, which can improve lesion analysis.

Teaching video neuroimages: callosal apraxia: a straightforward model of ideomotor apraxia.

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 like "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).

Improvement in aphasia scores after stroke is well predicted by initial severity.

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 (Delta) 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 DeltaWAB (R(2)=0.81, P<0.001) and that, in addition, the relation between WAB(initial) and DeltaWAB 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.

Phantom limb after stroke: an underreported phenomenon.

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.

Variability in recovery from aphasia.

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.

Attentional grasp in Parkinson disease.

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.