Quiz case: a clinical reasoning challenge in the emergency stroke setting.

A right-handed woman in her 80s was admitted to the emergency department 1 h after sudden-onset global aphasia and right-sided hemiparesis. Medical history included arterial hypertension, dyslipidemia, hyperuricemia, aortic stenosis, osteoporosis, and recent pulmonary embolism. Medication consisted of apixaban, bisoprolol, hydrochlorothiazide, allopurinol, fenofibrate, and vitamin D. Vital parameters (blood pressure, heart rate, body temperature, oxygen saturation) and glycemia were all within normal range. Electrocardiogram showed a first-degree atrioventricular block. The patient was promptly transported to the emergency computed tomography (CT) scanner. Non-contrast brain CT revealed a unilateral hyperdensity in the left caudate and lentiform nuclei. No other intracranial lesion was visualized. Laboratory studies were not yet available at the time of imaging. What is your diagnosis?

Neutrophil-to-lymphocyte ratio predicts delirium after stroke.

BACKGROUND: Delirium is an underdiagnosed and possibly preventable complication in acute stroke and is linked to poor outcome. Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, is also associated with poor outcome after acute ischemic stroke. AIM: To determine whether NLR is a predictor of post-stroke delirium (PSD). METHODS: We reviewed the UZ Brussel stroke database and included 514 patients with acute ischemic stroke within 24 hours from stroke onset between February 2009 and December 2014. The presence of delirium was evaluated by two raters based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, using a retrospective chart review method. When no consensus was reached, a third evaluator was consulted. Patients were divided into two groups: those who developed delirium within the first week after stroke onset (n = 201; 39%) and those who did not (n = 313; 61%). Receiver operating characteristics (ROC) and multiple logistic regression analysis (MLRA) were used to identify predictors of PSD. RESULTS: MLRA showed that NLR (odds ratio (OR) 1.14; 95% confidence interval (CI) 1.04-1.26), age (OR 1.05; 95% CI 1.03-1.07), National Institutes of Health Stroke Scale (NIHSS; OR 1.14; 95% CI 1.10-1.18), premorbid modified Rankin Scale (mRS) (OR 1.35; 95% CI 1.05-1.74) and premorbid cognitive dysfunction (OR 3.16; 95% CI 1.26-7.92) predicted PSD. ROC curve of a prediction model including NLR, age, NIHSS and premorbid cognitive dysfunction showed an area under the curve of 0.84 (95% CI = 0.81-0.88). CONCLUSIONS: Besides age, stroke severity, premorbid mRS and cognitive impairment, NLR is a predictor of PSD, even independent of the development of pneumonia or urinary tract infection.

Unassisted assessment of stroke severity using telemedicine.

BACKGROUND AND PURPOSE: Quantification of stroke severity through telemedicine consultation is challenging and relies on professional support at the patient's bedside. We aimed to develop a novel scale for assessing stroke severity through telemedicine without assistance from a third party (Unassisted TeleStroke Scale [UTSS]). METHODS: Stroke severity was assessed in 45 patients with suspicion of acute stroke by bedside examination using the National Institutes of Health Stroke Scale (NIHSS) and by teleconsultation using the UTSS. Scale reliability was evaluated by intrarater and interrater variability, internal consistency, and rater agreement. Concurrent and predictive validity were tested by relating the UTSS with the NIHSS and long-term outcome (modified Rankin Scale and mortality at 6 months). Clinimetric analysis of the UTSS was obtained via the Rasch model. RESULTS: The mean examination time for the UTSS was 3.1 minutes (SD, 1.1) versus 8.5 minutes for the NIHSS (SD, 2.6; P<0.001). Both UTSS and NIHSS showed excellent intrarater variability (r=0.97 and 0.98; P<0.001) and interrater variability (r=0.96 and 0.98; P<0.001), as well as excellent internal consistency and rater agreement. The UTSS correlated strongly with the NIHSS and was identified as an independent predictor of stroke outcome in logistic regression analysis. Rasch analysis indicated that the UTSS represents a unidimensional scale of stroke severity. CONCLUSIONS: The UTSS is a rapid, reliable, and valid tool for unassisted assessment of stroke severity through telemedicine.

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION: There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.

Skeletal Muscle Changes in the First Three Months of Stroke Recovery: A Systematic Review.

BACKGROUND: Rehabilitation is important in the first months after a stroke for recovery of functional ability, but it is also challenging, since distinct recovery trajectories are seen. Therefore, studying the early changes in muscle characteristics over time (e.g. muscle strength, muscle mass and muscle volume), which are known to be associated with functional abilities, may deepen our understanding of underlying recovery mechanisms of stroke survivors. OBJECTIVE: This systematic review aims to describe the longitudinal changes in skeletal muscles, including muscle strength, muscle mass and muscle volume, during the first 3 months post-stroke. METHODS: Electronic searches were conducted in Medline, Scopus and CENTRAL. Longitudinal cohort studies or controlled interventional trials that report data about patients in the first 3 months after stroke were identified. Skeletal muscle characteristics should be measured at least twice within 3 months post-stroke by objective, quantitative assessment methods (e.g. dynamometry, ultrasound, computed tomography). Effect sizes were calculated as Hedges' g using standardized mean differences. RESULTS: A total of 38 studies (1,097 subjects) were found eligible. Results revealed an mean increase on the paretic side for upper and lower limb muscle strength (small to moderate effect sizes), whereas muscle thickness decreased (moderate to large effect sizes). Similar, but smaller, effects were found on the non-paretic side. There were insufficient data available to draw conclusions about lean muscle mass and muscle cross-sectional area. No studies aimed at investigating distinct trajectories of the muscle changes. CONCLUSION: Muscle strength and thickness changes during the first 3 months after stroke in both the paretic and non-paretic side. Future studies should aim to understand "how" the stroke-induced muscle strength changes are achieved. Exploring existing data from longitudinal studies, by using cluster analyses, such as pattern recognition, could add to the current knowledge-base.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.

BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Insulin-like growth factor I serum levels influence ischemic stroke outcome.

BACKGROUND AND PURPOSE: Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. METHODS: Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. RESULTS: After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group. CONCLUSIONS: Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.

Pre-stroke use of statins on stroke outcome: a meta-analysis of observational studies.

BACKGROUND: Animal pre-clinical studies suggest that statins may have neuroprotective effects in acute ischaemic stroke. Statins might also increase the risk of developing haemorrhagic transformation after thrombolytic treatment. METHODS: We performed a systematic review and included studies that compared good functional outcome, defined as a modified Rankin Scale (mRS) score < or = 2 at 3 months, in-hospital mortality and risk of symptomatic haemorrhagic transformation, between pre -stroke statin users and non users with acute ischaemic stroke. RESULTS: Eleven studies met our predefined inclusion criteria. Statin therapy before stroke-onset was associated with a lower risk of in-hospital mortality (OR 0.56; 95% CI: 0.40 to 0.78, P < 0.0006). There was no difference between the two groups for good functional outcome at 3 months (OR 1.01; 95% CI: 0.64 to 1.61, P = 0.96). Statin use was associated with an increased risk of developing symptomatic haemorrhagic transformation after thrombolytic therapy (OR 2.34; 95% CI 1.31 to 4.17, P = 0.004). CONCLUSIONS: Our meta-analysis suggests that pretreatment with statins does not improve 3 months functional outcome, defined as independence on mRS, but decreases in-hospital mortality and increases the risk of developing a symptomatic haemorrhagic transformation in patients treated with thrombolysis.

Usefulness of the Neutrophil-to-Lymphocyte Ratio as a Predictor of Pneumonia and Urinary Tract Infection Within the First Week After Acute Ischemic Stroke.

Background: A high Neutrophil-to-Lymphocyte ratio (NLR) in patients with acute ischemic stroke (AIS) has been associated with post-stroke infections, but it's role as an early predictive biomarker for post-stroke pneumonia (PSP) and urinary tract infection (UTI) is not clear. Aim: To investigate the usefulness of NLR obtained within 24 h after AIS for predicting PSP and UTI in the first week. Methods: Clinical and laboratory data were retrieved from the University Hospital Brussels stroke database/electronic record system. Patients were divided into those who developed PSP or UTI within the first week after stroke onset and those who didn't. Receiver operating characteristics (ROC) curves and logistic regression analysis were used to identify independent predictors. Results: Five hundred and fourteen patients were included, of which 15.4% (n = 79) developed PSP and 22% (n = 115) UTI. In univariate analysis, NLR was significantly higher in patients who developed PSP (4.1 vs. 2.8, p < 0.001) but not in those who developed UTI (3.3 vs. 2.9, p = 0.074). Multiple logistic regression analysis for PSP showed that NLR, male gender, dysphagia, and stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), were independent predictors of PSP. For NLR alone, the area under the curve (AUC) in the ROC curve was 0.66 (95% CI = 0.59-0.73). When combining NLR ≥ 4.7 with age >75 years, male gender, NIHSS > 7, and dysphagia, the AUC increased to 0.84 (95% CI = 0.79-0.89). Conclusion: The NLR within 24 h after AIS appears to have no predictive value for post-stroke UTI, and is only a weak predictor for identifying patients at high risk for PSP. Its predictive value for PSP appears to be much stronger when incorporated in a prediction model including age, gender, NIHSS score, and dysphagia.

Muscle changes after stroke and their impact on recovery: time for a paradigm shift? Review and commentary.

In stroke rehabilitation there is a growing body of evidence that not all patients have the same potential to recover. Understanding the processes that give rise to the heterogeneous treatment responses in stroke survivors will lay foundations for any conceivable advance in future rehabilitation interventions. This review was set out to shine new light on the debate of biomarkers in stroke rehabilitation by linking fundamental insights from biogerontological sciences to neurorehabilitation sciences. In particular, skeletal muscle changes and inflammation are addressed as two potential constructs from which biomarkers for stroke rehabilitation can be derived. Understanding the interplay between these constructs as well as their relation to recovery could enhance stroke rehabilitation in the future. The rationale for the selection of these constructs is three-fold: first, recent stroke literature emphasizes the importance of identifying muscle wasting (also called stroke-induced muscle wasting) in stroke patients, a concept that is widely investigated in geriatrics but less in the stroke population. Second, insights from transdisciplinary research domains such as gerontology have shown that inflammation has severe catabolic effects on muscles, which may impede rehabilitation outcomes such as gait recovery. Last, it has been proven that (high-intensity) muscle strengthening exercises have strong anti-inflammatory effects in a non-stroke population. Therefore, an evidence-based rationale is presented for developing research on individual changes of muscle and inflammation after a stroke.

The impact of COVID-19 on acute stroke care in Belgium.

A worldwide decline in stroke hospitalizations during the COVID-19 pandemic has been reported. Information on stroke care during the pandemic in Belgium is lacking. This study aims to analyze the impact of COVID-19 on acute stroke care in eight Belgian stroke centers. This Belgian study is part of an international observational and retrospective study in 70 countries and 457 stroke centers. We compared volumes of COVID-19 and stroke hospitalizations, intravenous thrombolysis and endovascular treatment rates, acute treatment time intervals and functional outcome at 90 days during the first wave of the pandemic to two control intervals (March-May 2019 and December-February 2020). From March 2020 to May 2020, 860 stroke patients were hospitalized. In the same time period, 2850 COVID-19 patients were admitted, of which 37 (1.3%) were diagnosed with a stroke. Compared to the months prior to the pandemic and the same time epoch one year earlier, stroke hospitalizations were reduced (relative difference 15.9% [p = 0.03] and 14.5% [p = 0.05], respectively). Despite a reduction in absolute volumes, there was no difference in the monthly proportion of thrombolysis or endovascular treatment provided to the overall stroke hospitalizations. Acute treatment time metrics did not change between COVID-19 pandemic and control time epochs. We found no difference in 90-day functional outcomes nor in mortality after stroke between patients admitted during the pandemic versus control periods. We found a decline in the volume of stroke hospitalizations during the first wave of the COVID-19 pandemic in Belgium. Stroke care quality parameters remained unchanged.

Post-stroke infections associated with spleen volume reduction: A pilot study.

BACKGROUND: Spleen volume reduction followed by re-expansion has been described in acute ischemic stroke in both animal and human studies. Splenic contraction might be partially due to sympathetic hyperactivity and might be accompanied by release of splenocytes in the peripheral circulation, leading to immunodepression. AIMS: To investigate whether spleen volume changes in the first week after stroke are associated with post-stroke infections, changes in lymphocytes count and autonomic dysfunction. METHODS: In patients with acute ischemic stroke, spleen sizes were calculated from abdominal CT images on day one and day seven. Spleen size reduction was defined as > 10% spleen size reduction between day one and day seven. Post stroke infections were diagnosed during the first seven days after stroke onset using the modified criteria of the US Center of Disease Control and Prevention. We assessed the time course of leukocyte subsets and analysed pulse rate variability (PRV) indices. RESULTS: Post-stroke infections occurred in six out of 11 patients (55%) with spleen size reduction versus in five out of 27 patients (19%) without spleen size reduction (p = 0,047). Spleen size reduction was associated with a drop in lymphocytes and several lymphocyte subsets from admission to day one, and a higher NIHSS at admission and at day three (p = 0,028 and p = 0,006 respectively). No correlations could be found between spleen volume change and PRV parameters. CONCLUSION: Post-stroke infections and a drop in lymphocytes and several lymphocyte subsets are associated with spleen volume reduction in acute ischemic stroke.

Progressive multifocal leukoencephalopathy as first manifestation of sarcoidosis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating neurologic disorder caused by a polyomavirus, called JC virus. PML affects mainly immunocompromised hosts. We report a case of PML as first manifestation of sarcoidosis in a previously healthy man. Treatment with cidofovir, resulted in a neurological and radiological stabilization. To our knowledge the association of PML and sarcoidosis without previous immunosuppressive treatment has only been described in a few cases, none of them were treated with cidofovir.

Role of infarct location and pre-existing depression on cardiac baroreceptor sensitivity in subacute ischemic stroke.

Reduced cardiac baroreceptor sensitivity (BRS) after acute stroke is associated with worse outcome. The underlying mechanisms of reduced BRS are unclear. We evaluated cross correlation BRS (xBRS) in 184 patients with suspected acute ischemic stroke within 72 h of symptom onset. Among these patients, 22 had a transient ischemic attack (TIA) and 27 had a stroke mimic. Sixty-four age- and sex-matched ambulant control subjects without stroke were included. Compared with controls, xBRS was significantly lower in patients with ischemic stroke, TIA, and stroke mimics (4.6, 4.7, and 4.4, respectively, vs 6.6, p < 0.01). There was no difference in xBRS between right and left hemispheric infarctions (4.3 vs 4.9, p = 0.144), right and left insular infarctions (4.5 vs 5.3, p = 0.286), and insular infarction vs non-insular infarctions (4.7 vs 4.5, p = 0.996). Stroke patients with pre-existing depression/use of antidepressant medication had lower xBRS values than stroke patients with normal mental health (2.9 vs 4.8, p < 0.05). Control patients with depression also had lower xBRS compared to controls without depression (3.4 vs 5.9, p < 0.01). Our results suggest that decreased xBRS in the subacute phase after stroke is not associated with infarct localization. We found preliminary evidence for an association between pre-existing depression and use of antidepressant medication, and decreased BRS.

Bilateral low frequency rTMS of the primary motor cortex may not be a suitable treatment for levodopa-induced dyskinesias in late stage Parkinson's disease.

BACKGROUND: In late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS), delivered at the primary motor cortex (MC) or the supplementary motor area (SMA), may reduce levodopa-induced dyskinesias (LID), either in a single or a multiple session stimulation protocol. In our current clinical research, we examined whether single or multiple (accelerated) sham-controlled bilateral LF rTMS session(s) applied to the primary motor cortices are able to reduce levodopa-induced dyskinesias in patients with advanced Parkinson's disease. METHODS: During a levodopa challenge test, we first investigated the effect of a single sham-controlled session of LF rTMS (1 Hz) to both left and right primary motor cortical areas on dyskinesias and motor function in nine late-stage Parkinson patients. In a second study, patients were assigned to a five day sham-controlled bilateral motor cortex cross-over accelerated LF rTMS protocol and effects on dyskinesias, motor and executive function and emotional status were assessed. RESULTS: We found no significant clinical change in levodopa-induced dyskinesias and motor function with either stimulation protocol. CONCLUSIONS: One or multiple bilateral LF rTMS session(s) applied to the primary motor cortex were unable to reduce levodopa-induced dyskinesias in late-stage Parkinson patients.

Autonomic dysfunction in acute ischemic stroke: an underexplored therapeutic area?

Impaired autonomic function, characterized by a predominance of sympathetic activity, is common in patients with acute ischemic stroke. This review describes methods to measure autonomic dysfunction in stroke patients. It summarizes a potential relationship between ischemic stroke-associated autonomic dysfunction and factors that have been associated with worse outcome, including cardiac complications, blood pressure variability changes, hyperglycemia, immune depression, sleep disordered breathing, thrombotic effects, and malignant edema. Involvement of the insular cortex has been suspected to play an important role in causing sympathovagal imbalance, but its exact role and that of other brain regions remain unclear. Although sympathetic overactivity in patients with ischemic stroke appears to be a negative prognostic factor, it remains to be seen whether therapeutic strategies that reduce sympathetic activity or increase parasympathetic activity might improve outcome.