# Objectives Perinatal stroke (PS), a focal vascular brain injury near the beginning of life, can cause hemiparetic cerebral palsy (HCP) and lifelong disability for millions. Two PS subtypes, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI), differ in timing and mechanism of injury and can both lead to HCP. HCP results in asymmetric motor and sensory impairments, including disruptions in proprioception (limb-position sense) and visuomotor coordination (visual information integration and movement execution). Sensorimotor integration is essential for motor development in children, and its disruption contributes to motor deficits in HCP. This study investigated resting-state functional connectivity (FC) in sensorimotor networks of youth with two different PS subtypes and its association with proprioceptive and visuomotor performance. # Methods Resting-state fMRI was collected from children 6-19 years old with AIS or PVI and typically developing controls (TDC) (3.6 mm isotropic voxels, TR/TE=2000/30 ms, 150 volumes, 5 minutes). FC was assessed between primary motor cortex and other sensorimotor regions using the CONN toolbox. Proprioception and visuomotor coordination were evaluated using Kinarm robotic tasks. Mixed design analyses of covariance examined between-group and between-hemisphere FC differences, and between-group proprioception and visuomotor differences. Partial correlations assessed FC-behaviour associations, factoring out age. # Results There were 112 participants (33 AIS, 36 PVI, 43 TDC; mean age 12.4 ± 3.0 years; 43% female). Participants with PS exhibited lower interhemispheric FC, and lower FC within the lesioned hemisphere compared to TDC. Within the PS subgroups, AIS showed lower FC than PVI, particularly in interhemispheric cortical and subcortical (basal ganglia) regions, while thalamic connectivity was similarly lower than controls in both groups. Task performance was positively correlated with sensorimotor FC in all groups, with the largest number of correlations in AIS, The fewest correlations occurred in controls. In addition, FC was correlated with multiple visuomotor outcomes mainly in AIS, but not TDC. # Conclusion PS alters sensorimotor network organization. Subtype-specific differences in FC and FC-behaviour relationships suggest that lesion etiology influences developmental sensorimotor reorganization. Such imaging biomarkers may inform understanding of developmental sensorimotor connectivity and personalized rehabilitation strategies for youth with physical disabilities.

BACKGROUND AND OBJECTIVES:Immigration status is associated with stroke incidence and outcomes; however, its association with admission to and length of stay in the intensive care unit (ICU) in patients with stroke is unknown. We aimed to determine the association between immigration status and intensity of ICU care among patients with ischemic stroke. METHODS:We conducted a population-based retrospective cohort study of adults hospitalized for ischemic stroke in Ontario, Canada, between April 1, 2014, and March 30, 2023. People born outside Canada and who arrived after 1985 were defined as immigrants. We reported rates of thrombolysis, thrombectomy (reperfusion treatments), ventilatory support, and feeding tube insertion in immigrants and long-term residents. We calculated adjusted odds ratios (aOR) of ICU admission using logistic models and adjusted risk ratios (aRR) of longer ICU stays using negative binomial models, comparing immigrants with long-term residents, in the entire cohort and among those who did not receive reperfusion treatments. RESULTS:Of 85,507 patients included (45% female), 12.9% were immigrants. Immigrants were younger (median age 69 years vs 76 years, standardized difference = 0.38), had lower stroke severity and rates of reperfusion, and had higher rates of life-sustaining treatments compared with long-term residents. Immigrants had similar odds of ICU admission compared with long-term residents (18.2% vs 19.7%; aOR 0.97; 95% CI 0.91-1.04), but their ICU stays were longer (mean 5.6 ± 18.5 days vs 3.8 ± 7.7 days; aRR 1.30; 1.13-1.48) in the adjusted models, and this remained the case for those who did not receive reperfusion treatments (length of stay; aRR 1.27; 1.09-1.49). These associations did not vary by whether a hospital cared for a higher-than-median proportion of immigrants across all hospitals. Immigrants who came as refugees, and those who came from Africa, East Asia, and the Middle East, had longer ICU stays than long-term residents. DISCUSSION:Immigrant ischemic stroke patients have similar ICU admission rates, but longer ICU stays. The longer ICU stays among immigrant stroke patients may in part be driven by higher rates of life-saving treatments; however, the impact of these differences on the long-term functional outcomes remains to be studied.

With increased patient volumes and complexity, stroke occurrence in hospitalized patients has become relatively more common. The process of activating a code stroke in-hospital differs in many institutions. An emergency team-based response to inpatient acute code stroke is warranted, with many protocols modeled similarly to the cardiac arrest response. However, several studies have demonstrated delays in recognition and management of acute stroke in-hospital as compared to those arriving directly to the emergency department (ED). Furthermore, there are several shared challenges with code stroke resuscitation in the ED and the ward, which include the assembly of ad hoc teams and requirement of access to urgent imaging. Delays in activating in-hospital code stroke contributes to increased morbidity, mortality, prolonged hospitalization, and associated health care costs. In the following commentary, we discuss the current landscape of acute in-hospital code stroke protocols, review the differences in neurologic outcomes between inpatient vs ED/out-of-hospital code stroke patients, and propose future directions for in-hospital code stroke paradigms for improved patient outcomes and quality of care.

Background Different racial and ethnic groups have demonstrated heterogeneity in the clinical course of multiple sclerosis(MS). Objective We aimed to evaluate disease characteristics in African, Caribbean, and Black people with MS(ACB-MS) followed at a single centre in Toronto, Canada. Methods ACB-MS were compared with age- and sex-matched people with MS (pwMS) of European descent(EUR-MS) identified through the clinic registry. Results 344 PwMS were included(n = 172 ACB-MS, n = 172 EUR-MS; mean age 43 years, 68 % female). Baseline mean Expanded disability status scale (EDSS) scores (ACB-MS 2.3 ± 2.3 vs. EUR-MS 2.2 ± 2.0, p = 0.38) and subsequent clinical and radiological measures of disease activity were similar between groups, including annualized relapse rate (ARR)(ACB-MS 0.47 ± 0.47 vs. EUR-MS 0.41 ± 0.34, p = 0.2) and most recent EDSS (ACB-MS 2.7 ± 2.2 vs. EUR-MS 2.3 ± 2.1, p = 0.10). However, the proportion of MRI brain demonstrating new disease activity was higher(37% vs. 26 %, p < 0.05) and disability progression greater in ACB-MS vs. EUR-MS(43% vs. 33 %,p < 0.05) but measures of disease severity including MS Severity Score(3.17 vs. 2.58, p = 0.3) and Progression Index(PI) (0.27 vs. 0.30, p = 0.5) were comparable. Conclusion : Disability progression was seen more commonly in ACB-MS, though clinical disease activity and severity were generally comparable between ACB-MS and EUR-MS patients in Toronto, Canada. These findings partially differ from prior studies demonstrating more overtly aggressive MS disease courses in Black and African American PwMS, necessitating further studies to understand how structural determinants of health drive these disparities.

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ABSTRACT: Serum troponin is often elevated in patients with acute stroke and its mechanism is unknown. In a retrospective single-center cohort study, we evaluated the association between stroke severity and serum troponin in 187 patients with acute stroke using multivariable modified Poisson models. A one-point increase in the National Institutes of Health Stroke Scale (measure of stroke severity) was associated with a marginally higher serum troponin level in adjusted models (aIRR 1.03; 1.01–1.05, P = 0.001). The modest, yet potentially independent, association between stroke severity and serum troponins could suggest a neurogenic basis for a cardiac injury in patients with acute stroke.

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Stroke is one of the leading causes of mortality and morbidity worldwide, leaving approximately one in four stroke survivors with significant disability. In addition, stroke care is costly, with Canada alone spending approximately 3.6 billion dollars per year in stroke care. These costs include both direct costs (i.e., hospital beds, hospital personnel and time, diagnostic imaging, surgical interventions, prescription medications, and physician costs) and indirect costs (i.e., out-of-pocket expenses for rehabilitation, loss of productivity, and informal caregiving). Use of catheter-based endovascular thrombectomy (EVT) in eligible patients has been associated with a significant reduction in the disability and mortality associated with ischemic stroke. However, EVT is only available for patients with an ischemic stroke due to a large-vessel arterial occlusion, approximately 25–46% of all acute ischemic stroke patients, and of these, only few meet the inclusion criteria for EVT based on severity of symptoms and brain imaging. Further, it has additional costs associated with inter-hospital transfers; procedural and post-procedural care; and personnel costs, and so, it is only available at select few centers. Therefore, at a population level, investing in EVT programs that benefit only a selected few has been an area of considerable debate for policy makers and health economists. In this issue of the Journal, Thanh et al. evaluate if investments in provincial EVT programs can help save money from a provincial perspective. They examined the cost benefit of a provincial strategy, Endovascular Reperfusion Alberta (ERA) project, that aimed to improve access to EVT in Alberta. This provincially funded strategy included investments of $2.04 million and $3.73 million in the years 2018 and 2019, respectively, in the following areas: revision of emergency medical services triage and transport pathways, inter-hospital referrals, establishment of imaging in remote stroke centers, and improvement in processes to reduce treatment times. Subsequently, 172 and 218 more people received EVT in 2018 and 2019, respectively. To evaluate the savings that may have occurred from increasing access to EVT, the authors used health service utilization data and the associated direct costs, obtained from standardized provincial health care cost data, of 99 patients (52 of whom received EVT) with acute ischemic stroke who were enrolled in the ESCAPE randomized controlled trial in 2013–2014. The savings were calculated as a function of costs avoided by the reduced health care utilization among those who received EVT compared to those who did not. These were inflated to 2019 Canadian dollars. The net benefit was calculated as the sum of savings (from costavoidance) for all additional patients receiving EVT minus the provincial investment in the year. Overall, the greatest net cost saving was found at 1-year ($54,592 per patient) and 5-year ($47,070 per patient) time-points, but not at 90 days (-$7,313 per patient). At a population level, this translates to an estimated net savings of $9.4-$8.11 million in the long term, and a return on investment (ROI), calculated as the ratio of benefit and cost, of 5–5.6. The provincial strategy was cost beneficial across various sensitivity analyses. These findings mirror those of others that suggest EVT is cost-effective. It is impossible to directly attribute the increase in the number of people who received EVT to the provincial strategy, but such ecological fallacy plagues all public health interventions unless they are studied in natural experiment studies or cluster randomized trials. Unfortunately, cluster randomized trials are not possible for all new life-saving interventions due to the costs associated with such trials or the lack of clinical equipoise. Another important limitation acknowledged by the authors is the lack of data on indirect costs in their analysis. While some of these may not fall under the mandate of the provincial health ministry, a cross ministerial committee (including finance and health) could help make an economic argument for investment in EVT programs, especially because it could help reduce lost productivity in young stroke survivors. A review of ROIs from 23 public health interventions in the UK found the median ROI of any public health intervention to be 14.3, placing the ROI from the ERA project below the median. However, the ROI of local public health interventions is considerably lower (median ROI 4.1) compared to national public health interventions (median ROI 27.2), supporting the need to develop a national coordinated stroke strategy to improve EVT access and delivery. The study by Thanh et al. highlights the importance of longterm follow-up when evaluating public health interventions. For episodic conditions such as stroke, where the costs of stroke care are significant in the first few days following stroke, it is easy to conclude that an intervention has no benefit (or is harmful) if it is

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Introduction: Cardiac troponins are often elevated in patients with acute stroke and have been associated poor outcomes. Whether the elevation in cardiac troponins, a marker of acute myocardial injury, is due to neurogenic mechanisms or the underlying cardiac risk factors is unknown. We evaluated the association between stroke severity and serum cardiac troponin levels in people with acute stroke. Methods: We conducted a retrospective study of adults (≥ 40 years) with a discharge diagnosis of imaging confirmed stroke admitted to a quaternary stroke centre in Toronto, Canada between January 1, 2018 and December 31, 2018. We collected demographic and clinical information, including stroke severity using the National Institutes of Health Stroke Scale [NIHSS], modelled as a continuous variable. We recorded serum cardiac troponin levels on admission. We modelled serum troponin level both as a continuous and a categorical variable (normal vs. high, ≥ 15 ng/L). We evaluated the association between admission NIHSS and serum troponin level using multivariable negative binomial models and logistic regression models, adjusting for demographics (age and sex) and comorbidities [history of congestive heart failure or stroke, stroke type (ischemic vs. hemorrhagic), ST elevation on ECG, and creatinine levels]. Results: We included 218 patients with acute stroke (median age 76 years, 48.6% women), of whom 190 (87.2%) had an ischemic stroke. Median NIHSS was 6 (Q1-Q3, 2-14), and median cardiac troponin level was 17 ng/L (Q1-Q3, 9-30), with 108 (53.2%) patients having higher than normal levels. A one-point increase in NIHSS (stroke severity) was associated with a higher serum troponin level in age- and sex- (RR 1.03; 1.00-1.05) and multivariable- (RR 1.03; 1.01-1.05) adjusted models. However, stroke severity was not associated with the odds of having high troponin levels in adjusted models (OR 1.03; 0.98-1.08). Conclusions: The modest, yet independent, association between greater stroke severity and higher cardiac troponins in patients with acute stroke could suggest a neurogenic basis for mild cardiac injury in patients with acute stroke. Future work on the association between elevated troponin and poor stroke outcomes should account for stroke severity on admission.

Background and purpose Collateral assessment using CT angiography is a promising modality for selecting patients for endovascular thrombectomy (EVT) in the late window (6–24 hours). The outcome of these patients compared with those selected using perfusion imaging is not clear. Methods We pooled data from seven trials and registries of EVT-treated patients in the late-time window. Patients were classified according to the baseline imaging into collateral imaging alone (collateral cohort) and perfusion plus collateral imaging (perfusion cohort). The primary outcome was the proportion of patients achieving independent 90-day functional outcome (modified Rankin Scale ‘mRS’ 0–2). We used the propensity score–weighting method to balance important predictors between the cohorts. Results In 608 patients, the median onset/last-known-well to emergency arrival time was 8.8 hours and 53.2% had wake-up strokes. Both cohorts had collateral imaging and 379 (62.3%) had perfusion imaging. Independent functional outcome was achieved in 43.1% overall: 168/379 patients (45.5%) in the perfusion cohort versus 94/214 (43.9%) in the collateral cohort (p=0.71). A logistic regression model adjusting for inverse-probability-weighting showed no difference in 90-day mRS score of 0–2 among the perfusion versus collateral cohorts (adjusted OR 1.05, 95% CI 0.69 to 1.59, p=0.83) or in a favourable shift in 90-day mRS (common adjusted OR 1.01, 95% CI 0.69 to 1.47, p=0.97). Conclusion This pooled analysis of late window EVT showed comparable functional outcomes in patients selected for EVT using collateral imaging alone compared with patients selected using perfusion and collateral imaging. PROSPERO registration number CRD42020222003.

To evaluate the association between stroke severity and serum cardiac troponin levels in acute stroke.

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Perinatal ischemic stroke results in focal brain injury and life-long disability. Hemiplegic cerebral palsy and additional sequelae are common. With no prevention strategies, improving outcomes depends on understanding brain development. Reactive astrogliosis is a hallmark of brain injury that has been associated with outcomes but is unstudied in perinatal stroke. We hypothesized that gliosis was quantifiable and its extent would inversely correlate with clinical motor function. This is a population-based, retrospective, and cross-sectional study. Children with perinatal arterial ischemic stroke (AIS) or periventricular venous infarction (PVI) with magnetic resonance (MR) imaging were included. An image thresholding technique based on image intensity was utilized to quantify the degree of chronic gliosis on T2-weighted sequences. Gliosis scores were corrected for infarct volume and compared with the Assisting Hand and Melbourne Assessments (AHA and MA), neuropsychological profiles, and robotic measures. In total, 42 children were included: 25 with AIS and 17 with PVI (median=14.0 years, range: 6.3-19 years, 63% males). Gliosis was quantifiable in all scans and scores were highly reliable. Gliosis scores as percentage of brain volume ranged from 0.3 to 3.2% and were comparable between stroke types. Higher gliosis scores were associated with better motor function for all three outcomes in the AIS group, but no association was observed for PVI. Gliosis can be objectively quantified in children with perinatal stroke. Associations with motor outcome in arterial but not venous strokes suggest differing glial responses may play a role in tissue remodeling and developmental plasticity following early focal brain injury.

Background Collateral assessment using CT angiography (CTA) is promising to increase the eligibility for endovascular thrombectomy (EVT) in the late window (6–24 hours). The outcome of these patients compared to those selected using perfusion imaging is not clear. We aimed to describe the outcomes of EVT in patients selected using collateral vs perfusion imaging in the late time window. Methods We pooled individual patient-level data from seven trials and registries of EVT-treated patients in the late-time window. These studies were conducted in North America, Europe, and Korea. We collected clinical, imaging, and outcome data. We classified patients according to whether selection for EVT was done using collateral imaging alone (collateral cohort) vs perfusion plus collateral imaging (perfusion cohort). The primary outcome was the proportion of patients achieving independent 90-day functional outcome (modified Rankin scale 'mRS' 0–2). We also collected data on successful reperfusion (thrombolysis in cerebral infarction 2b-3), and symptomatic intracranial hemorrhage. We used the propensity score-weighting method to balance important predictors between the perfusion vs collateral cohorts. Results In 608 patients from seven studies, the mean (SD) age was 67.4 (14.6) years, and 50.5% were females. The median onset/last known well to emergency arrival time was 8.8 hours and 53.2% had wake-up strokes. Both cohorts had collateral imaging and 379 patients (62.3%) also had perfusion imaging. Independent functional outcome was achieved in 43.1% overall. In the perfusion cohort, 168/379 patients (45.5%) achieved functional independence vs 94/214 (43.9%) in the collateral cohort (P=0.71). A logistic regression model adjusting for inverse-probability-weighting showed no difference in 90-day mRS score of 0–2 (adjusted OR 1.05, 95%CI 0.69 to 1.59, P= 0.83) or in a favorable shift in 90-day mRS (common adjusted OR 1.01, 95%CI 0.69 to 1.47, P= 0.97) among patients in the perfusion vs collateral cohorts. Conclusion In this pooled individual patient-level analysis from multi-national studies and registries, late window patients who were selected for EVT using collateral imaging achieved comparable functional outcomes to patients who had perfusion imaging. Disclosures M. Almekhlafi: None. J. Thornton: None. I. Casetta: None. M. Goyal: None. N. Stefania: None. D. Herlihy: None. E. Fainardi: None. S. Power: None. V. Saia: None. A. Hegarty: None. G. Pracucci: None. A. Demchuk: None. S. Mangiafico: None. K. Boyle: None. P. Michel: None. F. Bala: None. R. Gill: None. A. Kuczynski: None. A. Ademola: None. M. Hill: None. D. Toni: None. S. Murphy: None. B. Kim: None. B. Menon: None.

Multiple sclerosis (MS) is an inflammatory disease that causes chronic neurological disability in young adults. Modulation of sphingosine 1-phosphate (S1P) receptors, a group of receptors that, among other things, regulate egression of lymphocytes from lymph nodes, has proven to be effective in treating relapsing MS. Fingolimod, the first oral S1P receptor modulator, has demonstrated potent efficacy and tolerability, but can cause undesirable side effects due to its interaction with a wide range of S1P receptor subtypes. This review will focus on ozanimod, a more selective S1P receptor modulator, which has recently received approval for relapsing MS. We summarize ozanimod's mechanism of action, and efficacy and safety from clinical trials that demonstrate its utility as another treatment option for relapsing MS.

Introduction: Numerous animal models have demonstrated the efficacy of mild to moderate therapeutic hypothermia (TH) in reducing cerebral edema and conferring protection after ischemic injury. We investigated whether TH had a beneficial effect in stroke patients after hemicraniectomy (HC). Methods: A MEDLINE systematic review was performed. Inclusion criteria included: ≥10 patients with acute malignant ischemic stroke having undergone HC, studies published in full in the English language, and studies reporting on clinical outcome and complications. Results: Thirty-four studies met our search criteria. Six studies with 302 patients with malignant ischemic stroke (TH: n=146, HC alone: n=156) were included. Age, and initial median NIHSS were comparable between the two groups. All studies used systemic TH; four utilized combined TH (venous endovascular and surface cooling), while one study used systemic surface and one used systemic venous endovascular TH. TH was initiated within 37.2 hours (range 24-42 hours) from onset for a median target temperature of TH was 33.6°C (range 33-35°C) and maintained for a median of 72 hours (range 48-96 hours). Target temperature was achieved within 4.5 hours (range 2-36 hours). All studies used rewarming (3 active rewarming). Clinical outcomes at follow-up were not different (follow-up modified Rankin’s 0-2; RR 1.04, 95% CI 0.60-1.80, p=0.9; Figure 1). Cardiac complications were greater in TH (RR 1.79, 95% CI 1.16-2.76, p<0.01). A suggestion of greater mortality was seen with TH (RR 1.43, 95% CI 0.97-2.10, p=0.07), and was significantly greater in studies that did not actively rewarm patients (RR 1.65, 95% CI 1.04-2.60, p<0.05). Conclusions: Clinical and functional outcomes were comparable between patients undergoing systemic TH vs. normothermia following HC despite higher complications associated with TH.

Background While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention. Methods Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures. Results The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional (“unaffected”) arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21–32% of the variance in number of balls hit with the unaffected hand. Conclusions Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills.

Reactivation of varicella zoster virus (VZV) in the cranial nerve, dorsal root, and autonomic ganglia can lead to unilateral radicular pain and cutaneous dermatomal involvement known as herpes zoster infection. Involvement of the ophthalmic branch (V1) of the trigeminal nerve, or herpes zoster ophthalmicus (HZO), may evolve to include complications such as meningoencephalitis, post-herpetic neuralgia, and contralateral hemiparesis (“crossed zoster syndrome”). Despite increasing reports of delayed contralateral hemiparesis secondary to HZO, the pathogenesis is not well understood. In this report, we review the clinical characteristics and investigations of a case of HZO presenting with posterior reversible encephalopathy syndrome (PRES) and subsequently developing crossed zoster syndrome. A 75-year-old right-hand dominant female presented to the emergency room in August 2018 with a one-week history of vesicular rash on the tip her nose (“Hutchinson’s sign”) and in the right V1 distribution including the forehead. Her medical history included monoclonal gammopathy of undetermined significance, idiopathic peripheral neuropathy, dyslipidemia, chronic obstructive pulmonary disease, osteopenia, depression, and a 40-pack-year smoking history. While the facial rash had evolved over the preceding week, she was taken to hospital when found by her daughter to be lethargic, in pain, and confused. Neurological examination revealed a right V1 distribution vesicular rash consistent with herpes zoster, mild encephalopathy, and a stable, length-dependent large and small fiber polyneuropathy. The patient received two doses of IV acyclovir 10mg/kg at 12hour intervals due to acute renal insufficiency (eGFR 58mL/min with Cr 85 μmol/L) but then received 10mg/kg every 8 hours (eGFR 85mL/min with Cr 62 μmol/L). Ophthalmological consultation revealed no abnormalities/complications. Initial investigations included (1) magnetic resonance imaging (MRI) demonstrating bilateral subcortical edema in the occipital and parietal lobes, with mild local mass effect and subtle leptomeningeal enhancement in keeping with PRES (Figure 1); (2) lumbar puncture with predominant lymphocytic pleocytosis (WBC 248, reference range 0–5× 10/L; 76% lymphocytes), elevated protein of 1.65 (reference range 0.15–0.45 g/L), negative bacterial and viral cultures, and positive VZV DNA amplification by polymerase chain reaction testing. After 2 days of acyclovir, the patient’s mental status improved to baseline, and she was discharged on oral valacyclovir 2 g three times a day to finish a 10-day course. The patient continued to improve at home over the next week. Just over 2 weeks after the patient’s initial presentation, she complained of feeling unwell and was emotionally labile, differing from her usual behavior. She had poor oral intake and lethargy and was subsequently brought to hospital. Repeat MRI brain demonstrated a right thalamic lesion (Figure 2), and 8 hours following this, she was found obtunded with left-sided hemiplegia and a right lateral gaze deviation. Emergent CT/CTA head demonstrated an acute right thalamic hematoma, intraventricular extension of the hemorrhage, and secondary hydrocephalus (Figure 2F,G). A diagnosis of VZV small vessel vasculitis with hemorrhagic evolution was made based on clinical and radiological findings. The patient received palliative care at the family’s request and passed away 6 days later. Following primary infection, VZV may become dormant in the nervous system and in some individuals may reactivate years after initial infection to cause shingles and neurological complications by spreading from the ganglia to cutaneous dermatomes and neural tissues. Delayed contralateral hemiparesis (“crossed zoster syndrome”) is the least common sequelae following HZO, having been described as acute onset of hemiparesis hours to months following resolution of the cutaneous rash. In the largest study of crossed zoster syndrome, the onset between HZO and hemiparesis was 7.3 weeks. In the current case report, we identify a previously independent 75-year-old female with contralateral hemiparesis 20 days following HZO. The pathogenesis of crossed zoster syndrome is not well understood. The anterior circulation intracranial arteries (middle and anterior cerebral arteries) receive sensory afferents from the ipsilateral trigeminal nerve and retrograde trans-axonal viral spread has been postulated. VZV vasculopathy may cause ischemic or hemorrhagic stroke, or the formation of intracerebral aneurysms which may or may not rupture. The patient in this report presented with Hutchinson’s sign. This nasal rash of vesicles on the tip or side of the nose, or involving the nasal mucosa, has been previously described, and is associated with an increased risk of complications such as pain, uveitis, and blindness. Hutchinson’s sign has been suggested to predict risk of HZO, but it remains unclear if it also increases risk of VZV-associated vasculitis. Antiviral treatment initiated within 72 hours of VZV cutaneous onset may have benefit and should be continued for 7 to 14 days. Improvement in hemiparesis has been noted in patients receiving concomitant steroids, but not all patients will benefit from these. Given the possible association with vasculitis, antiplatelet and/or anticoagulation therapy should be considered in patients with early thrombotic changes on imaging. There are several novel features to the presented case. Our patient initially presented with PRES, and this may be associated with her VZV infection. PRES is most commonly associated with hypertension, significant renal dysfunction, and immunosuppression – risk factors our patient did not have. To our knowledge, PRES has not been associated with VZV in an immunocompetent patient. Furthermore, we present serial imaging documenting the presence of an ipsilateral small vessel vasculitis that immediately preceded the onset of thalamic and ventricular hemorrhage reviewed by two independent neuroradiologists (CJW, RW). It is intriguing to speculate that LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES