Vagus Nerve Stimulation in Ischemic Stroke.

PURPOSE OF REVIEW: Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms. RECENT FINDINGS: Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery. The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.

Clinical pharmacist's contribution to treatment adherence and quality of life in patients with stroke.

PRIMARY OBJECTIVE: The optimal treatment adherence rate among patients with stroke is low. This study aims to determine the effect of clinical pharmacists' intervention on treatment adherence and quality of life (QOL) in patients with first-ever stroke. RESEARCH DESIGN: This open, controlled, prospective and interventional study was conducted sequentially at two different university hospitals for 3 months. Patients in the intervention group (IG) were provided with clinical pharmacist-led education whereas the control group (CG) only received routine care. METHODS AND PROCEDURES: Treatment adherence and QOL were assessed on discharge day, and in months 1 and 3 after discharge. Morisky Green Levine Adherence Scale and Stroke Specific Quality of Life Scale were employed to evaluate treatment adherence and QOL, respectively. MAIN OUTCOMES AND RESULTS: Changes in treatment adherence score were higher between discharge day, 1st and 3rd months after discharge in IG than CG (p < 0.001). Regarding 'energy' and 'work/productivity' domains, patients' scores in IG were higher than those from CG at months 1 and 3 after discharge (p < 0.05). CONCLUSION: Clinical pharmacist-led education improves treatment adherence in patients with first-ever stroke. The clinical pharmacist might be integrated into the multidisciplinary team to improve QOL and treatment adherence.

Alarms in a neurocritical care unit: a prospective study.

The contemporary practice of monitoring physiologic parameters in the critical care setting is based on alarm systems with high sensitivity but low specificity. A natural consequence of this approach is a massive amount of alarms, which potentially leads to fatigue in the personnel and negatively impacts the quality of care provided. The study objective is to determine the prevalence, types, and determinants of alarms in a neurological critical care unit (NCCU) prototype. During a one-month period corresponding to 272 days of monitoring in 34 patients, nursing staff recorded the type and number of sounding alarms in a university NCCU. Alarms were categorized into three types as type-A alarms that were merely handled by the nursing staff, type-B alarms that were primarily managed by nurses, but the physician was also notified, and type-C alarms that were principally handled by NCCU physicians. There were a total of 9439 alarms, with an average of daily 34.7 alarms per bed, corresponding to one alarm every 41.4 min. Most of the alarms were type-A (57.7%), followed by type-B (39.2%) and type-C (3.1%) alarms. Alarms originated from electrocardiogram (34.6%), pulse oximeter (33.7%), noninvasive blood pressure monitoring (9.8%), respiratory monitoring (9.7%), intravenous fluid pumps (4.5%), ventilator (3.9%), enteral pumps (2.1%) and invasive blood pressure systems (1.7%). A noticeable diurnal variation was observed for type-A pulse oximeter, type-A and -B ECG alarms (increase during morning shifts), and type-A ventilator alarms (decrease during morning shifts). Alarms are highly prevalent in NCCUs and can correspond to an important portion of the workload.

Incidental DWI Lesions in Patients with Recent Small Subcortical Infarctions.

OBJECTIVES: Incidental acute ischemic lesions distinct from the primary neurological insult are identified on diffusion-weighted imaging (DWI) in a number of conditions where cerebral microvascular pathology plays a central role. Another major manifestation of cerebral small vessel disease (CSVD) is ischemic stroke named as recent small subcortical infarction (RSSI). In this study, we sought to identify the prevalence and predictors of incidental DWI lesions in patients with RSSI. MATERIALS AND METHODS: We retrospectively analyzed a consecutive series of acute ischemic stroke patients with DWI evidence of acute lesions solely localized to perforator artery territories. Images were evaluated for the presence of additional acute or subacute subcortical DWI lesions, apart from the symptomatic lesion. Clinical features including vascular risk factor burden, together with imaging markers of chronic CSVD, were compared among patients with and without incidental acute or subacute lesions. RESULTS: Among 396 patients with no alternate stroke etiology additional incidental subcortical DWI bright lesions were identified in 74 (19%) cases. These lesions were primarily localized in the corona radiata, or centrum semiovale. Patients with incidental DWI lesions were more likely to have a history of hypertension, a higher white matter hyperintensities burden in the periventricular and subcortical region, higher perivascular spaces burden in the basal ganglia, multiple cerebral microbleeds, and multiple chronic lacunes. Presence of multiple chronic lacunes (OR 5.98, 95% CI 3.18-11.24) and ≥2 vascular risk factors (OR 2.03, 95% CI 1.05-3.91) stood out as features significantly associated with incidental DWI lesions in multivariate analysis. CONCLUSIONS: Our study shows that acute or subacute ischemic lesions can be incidentally detected in approximately one-fifth of patients with RSSI. This observation suggests that the course of CSVD might be more active, temporally and spatially, in a distinct subgroup of RSSI patients, specifically those with a higher chronic lacune and vascular risk factor burden.

Cortical Subarachnoid Hemorrhage in Behcet's Disease.

OBJECTIVE: Cortical subarachnoid hemorrhage (cSAH) can be resulted from by a wide variety of causes. A cSAH probably associated with Behcet's disease is herein reported for the first time. CASE REPORT: A 58-year-old male with stable Behcet's disease evaluated for sudden onset headache. Emergency computed tomography disclosed cSAH in the left frontal sulci. A ruptured middle cerebral artery cortical branch aneurysm was found. Surprisingly, this aneurysm obliterated completely after diagnostic catheter angiography. CONCLUSION: This case highlights three important points; First, non-mycotic (non-infectious) distal cerebral artery aneurysms may rarely cause cSAH. Second, distal dissecting aneurysms may rarely become obliterated after diagnostic cerebral angiography. Third, such aneurysms may be one of the long-term consequences of vascular inflammation in Behçet's disease.

Characteristic imaging features of neurovascular involvement in primary Sneddon's syndrome: an analysis of 12 cases.

OBJECTIVE: Sneddon's syndrome is a cerebrocutaneous non-inflammatory progressive distal arteriopathy, characterized by livedo racemosa, stroke, and neuropsychiatric symptoms. Our aim was to highlight the characteristic neuroimaging features of Sneddon's syndrome that might be helpful to clinicians in timely diagnosis of this entity. METHODS: Twelve patients (median age 49 years, 11 female) with primary Sneddon's syndrome, diagnosed in last 10 years, were analyzed from the perspective of magnetic resonance imaging (MRI) features. In addition, a novel pseudoangiomatosis score was defined for grading angiographic abnormalities (range: 0 to 6). RESULTS: Median interval from the onset of neurological symptoms to diagnosis was 6 years. Presentation was with acute stroke in 5, seizures in 3, dementia/speech problems in 2, seizures plus cognitive dysfunction in 1, and chronic progressive hemiparesis in 1. All patients had a typical lesion pattern on MRI. This included multiple (median 3) cortical-subcortical supratentorial and cerebellar non-territorial infarcts, accompanied by multifocal cerebral atrophy. Of note, large territorial infarcts due to cerebral parent artery occlusion, an embolic pattern with multi-territorial involvement on diffusion-weighted imaging, small vessel disease features like severe white matter involvement or lacunar infarcts, and cerebral hemorrhage in the absence of anticoagulation were not observed. MRI lesion severity was not correlated with angiographic arteriopathy severity, clinical stage, or presentation symptoms. CONCLUSION: Sneddon's syndrome is characterized by highly typical clinico-radiological features. Brain MRI has diagnostic value. By knowing the characteristics of the syndrome, misdiagnosis and potentially harmful treatment can be prevented in this entity that might pose a diagnostic challenge.

Stroke Mechanism in COVID-19 Infection: A Prospective Case-Control Study.

BACKGROUND: The characteristics and pathophysiological mechanisms involved in acute ischemic stroke in patients with COVID-19 infection have not been fully clarified. We prospectively studied the phenotypic and etiological features of acute stroke occurring in COVID-19 infection. PATIENTS & METHODS: Within nine months starting from April-2020, the presence of COVID-19 infection was determined by thoracic CT and SARS-CoV-2 PCR in all acute stroke cases managed in a single tertiary center. Consecutive and prospective data on vascular risk factors/comorbidities, in-hospital quality metrics, discharge outcomes, etiological subclassification and blood markers of thrombosis / inflammation were compared in 44 COVID-19 positive cases (37 acute ischemic stroke, 5 TIA, 2 intracerebral hematoma) and 509 COVID-19 negative patients (355 ischemic, 105 TIA, 44 hematoma and 5 stroke mimic). RESULTS: COVID-19 positive patients had more severe strokes, delayed hospital admission, longer hospital stay, higher mortality rates, but had similar vascular risk factors/comorbidities frequency, thrombolysis/thrombectomy utilization rates, metrics, and stroke etiological subtype. They had significantly higher CRP, fibrinogen, ferritin, leukocyte count and lower lymphocyte count. No difference was detected in aPTT, INR, D-dimer, platelet, hemoglobin, homocysteine levels and ANA, anti-dsDNA antibody and ENA panel positivity rates. Anti-phospholipid antibodies have been studied in 70% of COVID-19 positive and all cryptogenic patients, but were never found positive. Tests for coagulation factor levels and hereditary thrombophilia did not show major thrombophilia in any of the stroke patients with COVID-19. CONCLUSION: We documented that there is no significant difference in etiological spectrum in acute stroke patients with COVID-19 infection. In addition, cryptogenic stroke and antiphospholipid antibody positivity rates did not increase.

One Disease with two Faces: Semidominant Inheritance of a Novel HTRA1 Mutation in a Consanguineous Family.

OBJECTIVES: To identify the underlying genetic defect for a consanguineous family with an unusually high number of members affected by cerebral small vessel disease. MATERIALS AND METHODS: A total of 6 individuals, of whom 3 are severely affected, from the family were clinically and radiologically evaluated. SNP genotyping was performed in multiple members to demonstrate genome-wide runs-of-homozygosity. Coding variants in the most likely candidate gene, HTRA1 were explored by Sanger sequencing. Published HTRA1-related phenotypes were extensively reviewed to explore the effect of number of affected alleles on phenotypic expression. RESULTS: Genome-wide homozygosity mapping identified a 3.2 Mbp stretch on chromosome 10q26.3 where HTRA1 gene is located. HTRA1 sequencing revealed an evolutionarily conserved novel homozygous c.824C>T (p.Pro275Leu) mutation, affecting the serine protease domain of HtrA1. Early-onset of cognitive and motor deterioration in homozygotes are in consensus with CARASIL. However, there was a clear phenotypic variability between homozygotes which includes alopecia, a suggested hallmark of CARASIL. All heterozygotes, presenting as CADASIL type 2, had spinal disk degeneration and several neuroimaging findings, including leukoencephalopathy and microhemorrhage despite a lack of severe clinical presentation. CONCLUSION: Here, we clearly demonstrate that CARASIL and CADASIL type 2 are two clinical consequences of the same disorder with different severities thorough the evaluation of the largest collection of homozygotes and heterozygotes segregating in a family. Considering the semi-dominant inheritance of HTRA1-related phenotypes, genetic testing and clinical follow-up must be offered for all members of a family with HTRA1 mutations regardless of symptoms.

Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project.

IMPORTANCE: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. OBJECTIVE: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. PROCESS: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. EVIDENCE SYNTHESIS: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. RECOMMENDATIONS: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability. CONCLUSIONS AND RELEVANCE: This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

Isolated Sulcal Effacement and Response to Intravenous Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Isolated Sulcal Effacement (ISE) is focal cortical swelling without obscuration of cortical gray-white junction. The available information on its role in acute stroke patients treated with intravenous (IV) tissue plasminogen activator (tPA) is limited. METHODS: ISE along with ASPECT and rLMC collateral score were determined in pre-treatment CT/CT angiography of 195 consecutive acute stroke patients treated with IV tPA "only". In addition, ISE-ASPECT score was created. Role of ISE on responsiveness to IV tPA, thrombolysis-associated hemorrhage and functional outcome were studied in 102 patients with CT-angiography-confirmed anterior system proximal vessel occlusion. RESULTS: ISE was observed in 12 patients (6.2% of all and 11.4% of those with occlusion of the carotid terminus, M1, or proximal M2) corresponding to excellent specificity (100%) but fair sensitivity (12%) for diagnosis of anterior cerebral circulation proximal artery occlusion. ISE ASPECT score was significantly correlated with rLMC score (p=0.023). Presence of ISE was linked to younger age, female gender, lower NIHSS, along with higher ASPECT and rLMC scores. Albeit not persisted after adjustment for collateral status and NIHSS, dramatic response to IV tPA along with excellent (23% vs. 8%, p<0.05), good (21% vs. 6%, p<0.05) and acceptable (19% vs. 4%, p<0.05) functional outcome were significantly higher in patients with ISE. CONCLUSIONS: As a plain CT marker of sufficient collateral status and increased cerebral blood volume, ISE indicates a better response to IV tPA. However, it should be noted that this relatively rare CT finding is highly specific for cerebral large vessel occlusions amenable neurothrombectomy.

The Effect of Clot Volume and Permeability on Response to Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke.

BACKGROUND AND AIMS: The characteristics of clot causing acute ischemic stroke, such as size, content, and location, are among the main determinants of response to intravenous tissue plasminogen activator [IV tPA]. Clot heterogeneity and permeability are under-recognized features that might provide additional information in predicting the efficacy of IV tPA. METHODS AND PATIENTS: Patients with proximal middle cerebral artery occlusion treated with "IV tPA alone" were included. The mean Hounsfield's unit (HU) value, as objective measure of clot attenuation, and its standard deviation (SD), as proposed measure of clot heterogeneity, were obtained. The difference in HU values between CT Angiography and CT was defined as "clot permeability", or "perviousness'. The size (length and volume-mm3) of pre-clot pouch and occluding clot along with ASPECT score and Maas' silvian and leptomeningeal collateral score were measured. RESULTS: The study included 84 cases (44 women, age: 68 ± 14 years, pretPA NIHSS: 16 ± 5). Patients with excellent response to tPA (31%) had lower thrombus volume (37.54 ± 32.37 versus 63.49 ± 37.36, P = .009) and heterogeneity (4.05 ± 1.49 versus 5.35 ± 2.34, P = .011), along with higher clot permeability (48 ± 35.48 to 31.32 ± 18.62, P = .006). However, significance of permeability did not survived in the regression analysis with adjustment for NIHSS (ß:-.296, P = .003); clot volume (ß:-.240, P = .014) and collateral status (ß:.346, P < .001). In patients with good prognosis, clot volume was significantly lower (37.76 ± 30.08 versus 67.57 ± 37.83, P < .001), whereas permeability was significantly higher (43.97 ± 32.33 versus 31.13 ± 19.01, P = .026). However, this effect did not persist in the regression analysis after adjustment for NIHSS (ß:-.399, P < .001), collateral status (ß: .343, P < .001) and clot volume (ß:-.297, P = .001). Clot permeability was significantly higher (45.78 ± 36.34 versus 33 ± 20.2, P = .045) and heterogeneity was lower (4.1 ± 1.55 to 5.27 ± 2.32, P = .028) in patients with dramatic response to tPA (27%). In patients responding positively to IV tPA (48%), clot permeability was numerically higher (39.85 ± 31.79 to 33.47 ± 19.28, P = .268), while clot volume (48.15 ± 34.5 to 62.07 ± 39.62, P = .093) was lower. Clot volume, permeability and heterogeneity did not show a significant difference in any (38.1%) or symptomatic (8.3%) bleeders after IV tPA. The chance of IV tPA to be beneficial increased in patients with clot volume lower than 45 mm3, with an increased likelihood of this benefit to be observed within the first day after IV tPA. Our detailed explorative ROC analysis was not able to detect a volume threshold above which the positive effect of IV tPA disappeared. CONCLUSION: Clot volume is critical for the effectiveness of IV tPA in acute ischemic stroke. Clot permeability and heterogeneity may modify its effect. CT technologies, which are readily available when evaluating a stroke patient in an emergency setting, provide us with useful parameters regarding the size, permeability and heterogeneity of the clot.

Determinants of preventable stroke-Ankara ACROSS stroke preventability study.

BACKGROUND: Unhealthy lifestyle and inadequate control of vascular risk factors are the major contributors of stroke burden. Failure in achieving the target levels in control of these factors, not only designate missed opportunities contributing to the preventability of an incident stroke, but also set the post-stroke treatment goals in a case wise basis. In this study, we analyzed pre-event clinical features that play a role in stroke preventability, and determined the cumulative burden of risk factors that necessitate optimization following the ischemic insult. METHODS: Information about the pre-stroke optimal control of seven major modifiable risk factors (Life's Simple 7: hypertension, diabetes mellitus, hyperlipidemia, smoking, obesity, diet, and physical activity) was prospectively collected in ischemic stroke patients admitted to three tertiary academic centers in Ankara. Stroke preventability was evaluated by the overall number of factors requiring optimization with patients ≥4 risk factor conditions categorized as those suffering from a preventable stroke. Bivariate and multivariate analyzes were performed to uncover predictors of stroke preventability. RESULTS: Among 787 patients, 386 (49.0%) had ≥4 risk factor conditions requiring optimization. Preventable stroke was more common in younger patients, and patients with small artery occlusion. Multivariate analyses taking into account the pre-stroke antithrombotic treatment regimen, have highlighted age (OR: 0.99, 95%CI 0.98-1.00), female gender (1.59, 95%CI 1.17-2.16), coronary artery disease (1.54, 95%CI 1.10-2.14), small artery occlusion (1.90, 95%CI 1.13-3.18), and cardio-aortic embolism (0.53, 95%CI 0.35-0.82) as significant factors associated with preventability. CONCLUSIONS: Approximately half of the ischemic stroke patients have preventable stroke from the perspective of risk factor control. Extra care should be given to strategies directed to risk factor control and lifestyle interventions in certain high-risk groups for the prevention of future complications.

The Fragility Index in Randomized Controlled Trials for Patent Foramen Ovale Closure in Cryptogenic Stroke.

BACKGROUND AND PURPOSE: The routine use of percutaneous transcatheter patent foramen ovale closure (PPFOC) to prevent recurrent stroke in patients with cryptogenic stroke is still a matter of debate after completion major randomized controlled trials (RCTs). METHODS: The fragility index of RCTs evaluating effect of PPFOC against medial therapy alone in stroke prevention was calculated to assess the robustness of statistically significant findings. RESULTS: Literature search with PubMed identifies 6 RCTs on PPFOC. Median number of patients who underwent PPFOC and medical treatment were 340 and 229, respectively. Median number of the patients lost to follow-up was 20 in PPFOC and 18 in medical group. Fragility index was 0 for 4 studies. Median fragility index was also 0 for both "stroke" (interquartile range: 0-5.3) and "combined stroke and TIA" (interquartile range: 0-2) endpoints. In all studies except CLOSE, fragility index was smaller than or equal to the number of the subjects lost to follow-up. CONCLUSIONS: Recent positive results of PFO closure studies should be interpreted cautiously because of their fragile characteristics. Routine PFO closure should be reserved for prevention of recurrence when suspicion for paradoxical embolism is high. Detailed individualized decision-making is crucial before ordering PPFOC for stroke prevention in patients with cryptogenic embolism.

Floating Aortic Thrombus: A Rare Cause of Acute Ischemic Stroke Necessitating Modification of Access Route for Thrombectomy.

We report 2 patients with acute occlusion of middle cerebral artery successfully treated by mechanical thrombectomy performed via transbrachial access. Both patients had floating aortic arch thrombi precluding safe transfemoral access due to risk of further iatrogenic embolization. Moreover both patients were diagnosed with hypercoagulopathy secondary to lung malignancy (paraneoplastic etiology, Trousseau's syndrome) as the cause of both aortic thrombi and acute ischemic stroke. Mechanical thrombectomy in the setting of a floating aortic thrombus has been mentioned only once as part of general management of floating aortic thrombi in the whole body. To the best of our knowledge, it has never been described previously in the literature in the context of cerebral mechanical thrombectomy technique. However, the diagnosis of this entity bears clinical importance for it can modify the treatment approach. A modified transbrachial approach allowed us to treat both patients without neurologic complications and resulted in modified Rankin scores of 1 on follow-up. We advise that the cross-sectional imaging of acute stroke patients should include an evaluation of the aortic arch and should be scrutinized in detail especially in patients with possible hypercoagulable state. Flat panel computed tomography technology allowed us to obtain such an imaging study in the angiography suite.

Isolated Upper Limb Weakness From Ischemic Stroke: Mechanisms and Outcome.

OBJECTIVE: To characterize isolated upper extremity (UE) weakness from stroke. METHODS: In our Get with the Guidelines-Stroke dataset (n = 7643), 87 patients (1.14%) had isolated UE weakness and underwent thorough stroke evaluation with diffusion-weighted magnetic resonance imaging and good-quality arterial imaging. We analyzed clinical-imaging features, etiology, management, and outcome. Since isolated UE weakness is typically associated with contralateral hand-knob area infarcts, patients were classified into Group-A (motor strip infarct) or Group-B (non-motor strip infarct). RESULTS: The mean age was 68 years; 66% were male, 72% had hypertension, 22% diabetes, 53% hyperlipidemia, and 16% were smokers. In Group-A (n = 71), 18 patients had single and 53 had multiple infarcts involving the contralateral motor strip. In Group-B (n = 16), 6 patients had contralateral subcortical white matter infarcts, 9 had bihemispheric infarcts and 1 had a brainstem infarct. Compared to Group-B, patients in Group-A more often had carotid artery stenosis or irregular plaque (84.5% versus 50%, P = .006) and large-artery atherosclerosis mechanism (46% versus 19%, P = .05), and less often cardioembolic mechanism (13% versus 44%, P = .008). Among 36 patients with large-artery mechanism, 27 had less than 70% stenosis including 19 with plaque ulceration/thrombus. Recurrent strokes occurred in 10 patients (11.5%), including 5 with mild-moderate carotid stenosis and plaque ulceration/thrombosis, over 1515 days follow-up. CONCLUSION: Stroke mechanism in acute isolated UE weakness is variable. Contralateral motor-strip infarcts are associated with carotid stenosis, often with plaque ulceration ("vulnerable carotid plaque"), and infarcts in other locations with cardioembolism. Recurrent stroke risk is high especially with mild-moderate carotid artery stenosis and plaque ulceration/thrombus.

Cerebral vasomotor reactivity in reversible cerebral vasoconstriction syndrome.

Background Altered cerebrovascular tone is implicated in reversible cerebral vasoconstriction syndrome (RCVS). We evaluated vasomotor reactivity using bedside transcranial Doppler in RCVS patients. Methods In this retrospective case-control study, middle cerebral artery (MCA) blood flow velocities were compared at rest and in response to breath-hold in RCVS ( n = 8), Migraineurs ( n = 10), and non-headache Controls ( n = 10). Hyperventilation response was measured in RCVS. Results In RCVS, Breath Holding Index (BHI) was severely reduced in seven of eight patients and 14/16 MCAs; seven of 16 MCAs showed exhausted (BHI < 0.1) or inverted (BHI < 0) vasomotor reactivity. Mean BHI in RCVS (0.23 ± 0.5) was significantly lower than Migraine (1.52 ± 0.57) and Controls (1.51 ± 0.32), p < 0.001. Triphasic velocity responses were seen in all groups. The maximum Vmean decline during the middle negative phase was -15.5 ± 9.2% in RCVS, -15.4 ± 7% in Migraine, and -10.3 ± 5% in Controls ( p = 0.04). In the late positive phase, average Vmean increase was 6.2 ± 14% in RCVS, which was significantly lower ( p < 0.001) than Migraine (30.5 ± 11%) and Controls (30.2 ± 6%). With hyperventilation, RCVS patients showed 23% decrease in Vmean. Conclusion Cerebral arterial tone is abnormal in RCVS, with proximal vasoconstriction and abnormally reduced capacity for vasodilation. Further studies are needed to determine the utility of BHI to diagnose RCVS before angiographic reversibility is established, and to estimate prognosis.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with Cervicocephalic Dolichoarteriopathy.

BACKGROUND AND PURPOSE: Cervicocephalic dolichoarteriopathy is not rare in patients with acute stroke. Results of intravenous (IV) tissue plasminogen activator (tPA) treatment have not been documented in this specific population. METHODS: One hundred (58 females, age: 69 ± 13 years) consecutive patients treated with IV tPA for acute anterior circulation stroke were analyzed. Smoker's criteria were used to score basilar artery dolichoarteriopathy and combined criteria of Weibel-Fields and Metz for cervical carotid artery dolichoarteriopathy. RESULTS: Adjusted rates of effective response to tPA (defined as a decrease of the National Institutes of Health Stroke Scale [NIHSS] score to 1 or 0, or a total decrease ≥4 point by the end of the first 24 hours; in 51%); first-day dramatic response (≥8 NIHSS score decrease; seen in 27%); 3-month favorable (modified Rankin score ≤2; in 46%) and excellent (modified Rankin score ≤1; in 37%) functional prognosis, and hemorrhagic complications (any hemorrhage in 34%, significant Fiorelli's parenchymal hemorrhage type 2 in 8%) of IV tPA were not modified with presence and categories of the basilar and extracranial carotid artery dolichoarteriopathy. Univariate analysis documented that basilar artery dolichoarteriopathy was significantly more prevalent in patients with effective response to IV tPA (22% versus 6%, odds ratio: 4.22, P = .041). However, an exploratory multiple regression analysis disclosed that NIHSS (per 1 point, ß = -.256, P = .009) and time to needle (per 15-minutes, ß = -2.389, P = .019) were significant determiners of early favorable prognosis, whereas dolichoectasia was not (ß = .141, P = .159). CONCLUSION: IV tPA is safe and effective in acute anterior circulation stroke coexistent with intracranial posterior circulation dolichoarteriopathy and cervical carotid artery kinking, tortuosity, or coiling.

The Interplay between Stroke Severity, Antiplatelet Use, and Aspirin Resistance in Ischemic Stroke.

BACKGROUND: The issue of whether prior antiplatelet use favorably affects stroke severity is currently unresolved. In this study, we evaluated the effect of antiplatelet use on clinical stroke severity and ischemic lesion volume, and assessed the confounding effect of laboratory-defined aspirin resistance on this relationship. METHODS: Admission National Institutes of Health Stroke Scale (NIHSS) score, ischemic lesion volumes on diffusion-weighted imaging (DWI), and in vitro aspirin resistance, in addition to other pertinent stroke features, were determined in a series of ischemic stroke patients. Univariate and multivariate analyses were performed to compare clinical and imaging markers of stroke severity among patients with and without prior antiplatelet use, taking into consideration the presence or absence of aspirin resistance. RESULTS: Antiplatelet users experienced more severe strokes, per NIHSS score, in comparison to antiplatelet-naive patients (P = .007). No significant difference was observed with respect to admission DWI lesion volume. When analyses were repeated after adjustment for stroke subtype and other confounders, no association was observed between antiplatelet use and stroke severity. On the other hand, NIHSS scores were significantly higher in aspirin-unresponsive patients than in both aspirin responders (P = .049) and aspirin nonusers (P = .005). CONCLUSION: We were unable to demonstrate a substantial positive influence of prestroke antiplatelet usage on stroke severity. Although the presence of more severe strokes among patients with laboratory resistance suggests a protective influence of aspirin sensitivity on stroke severity, the hypothesis could not be validated as no difference was observed among aspirin-naive and aspirin-sensitive patients with respect to admission NIHSS score or DWI lesion volume.

Elevations in Tissue Fluid-Attenuated Inversion Recovery Signal Are Related to Good Functional Outcome after Thrombolytic Treatment.

BACKGROUND: Early elevations in the parenchymal signal intensity on T2-weighted images, including fluid-attenuated inversion recovery (FLAIR) sequences, within the ischemic territory are considered as a marker of successful recanalization following thrombolytic treatment. In this study, our aim was to assess whether quantitatively determined FLAIR hyperintensity increases could be predictive of improved functional outcome in patients with acute ischemic stroke. METHODS: Patients receiving intravenous thrombolysis for proximal anterior circulation strokes were included in the study. FLAIR hyperintensity ratio was determined on magnetic resonance imaging obtained within 72 hours of symptom onset. Univariate and multivariate analyses were performed to determine predictors of good functional outcome at 90 days. RESULTS: The study population was composed of 65 patients. The median (interquartile range) FLAIR hyperintensity ratio was significantly higher among patients with good functional outcome (modified Rankin Scale score ≤ 3 at day 90, 1.4 [1.2-1.7] versus 1.2 [1.1-1.4], P = .005). Patients with a FLAIR hyperintensity ratio of 1.3 or higher were 4.4 (95% confidence interval 1.6-12.7) times more likely to be independent functionally at the end of 3 months. Higher admission National Institutes of Health Stroke Scale score and age, together with lower FLAIR hyperintensity ratio (P = .006), were found to be significantly and independently related to unfavorable outcome at 90-day follow-up in multivariate analyses. CONCLUSIONS: Our findings suggest that a rise in FLAIR hyperintensity signal within the ischemic tissue is suggestive of favorable outcome in patients undergoing intravenous thrombolysis. This tissue marker of favorable outcome is irrespective of other parameters that are crucial in the prognosis of ischemic stroke, such as age and stroke severity.