Keser, Zafer

BACKGROUND: Cervical artery dissection (CeAD) represents up to 15% to 25% of ischemic strokes in people under the age of 50 years. Noninvasive vessel imaging is increasingly used in clinical practice, but the impact on the frequency of detection of CeAD is unknown. In 2006, the yearly incidence rate of CeAD was estimated at 2.6 per 100 000 person-years, but the current incidence is unknown. METHODS: In this population-based retrospective observational cohort study, we utilized the resources of the Rochester Epidemiology Project to ascertain all adult residents of Olmsted County, MN, diagnosed with internal carotid artery dissection and common carotid artery dissection or vertebral artery dissection from 2002 to 2020. Patients with only intracranial involvement or CeAD following major trauma were excluded. Age-adjusted sex-specific and age- and sex-adjusted incidence rates were estimated using the US White 2010 decennial census, with rates expressed per 100 000 person-years. We assessed longitudinal trends by dividing the data into 5-year time intervals, with the last being a 4-year interval. RESULTS: We identified 123 patients with a diagnosis of CeAD. There were 63 patients with internal carotid artery dissection, 54 with vertebral artery dissection, 2 with concurrent internal carotid artery dissection and vertebral artery dissection, and 4 with common carotid artery dissection. There were 63 (51.2%) female patients and 60 (48.8%) male patients. The average age at diagnosis was 50.2 years (SD, 15.1 [95% CI, 20.1–90.5] years). The incidence rate of spontaneous CeAD encompassing all locations was 4.69 per 100 000 person-years (2.43 for internal carotid artery dissection and 2.01 for vertebral artery dissection). The incidence rate increased from 2.30 per 100 000 person-years from 2002 to 2006 to 8.93 per 100 000 person-years from 2017 to 2020 ( P <0.0001). The incidence rate for female patients rose from 0.81 per 100 000 person-years from 2002 to 2006 to 10.17 per 100 000 person-years from 2017 to 2020. CONCLUSIONS: The incidence rate of spontaneous CeAD increased nearly 4-fold over a 19-year period from 2002 to 2020. The incidence rate in women rose over 12-fold. The increase in incidence rates likely reflects the increased use of noninvasive vascular imaging.

Objective: Most cervical artery dissection (CeAD) cases are spontaneous or due to minor traumas, and preceding viral infections have been suggested to be a triggering event for CeAD in some. Herein, we analyze the prevalence of coronavirus disease 2019 (COVID-19) in hospitalized patients with CeAD using a national database. Methods: The National Inpatient Sample was queried from April 2020 to December 2020 for patients with a diagnosis of CeAD using International Classification of Diseases, 10th edition-Clinical Modification codes. Among these, patients with COVID-19 were identified. Multivariable logistic regression was conducted to assess the patient profile of those with COVID-19, in-patient mortality, and home discharge among patients with CeAD. Results: There were 360 (2.32%) hospitalizations involving COVID-19 among 15,500 with CeAD. Concomitant acute ischemic stroke constituted 43.06% of those with a COVID-19 diagnosis, whereas it was 43.73% among those without a COVID-19 diagnosis (P = 0.902). Home discharges were less common in patients with COVID-19 and CeAD compared to CeAD alone (34.85% vs. 48.63%; P = 0.03), but this was likely due to other factors as multivariate regression analysis did not show an association between COVID-19 and home discharges (odds ratio: 0.69; 95% CI: 0.39 to 1.25; P = 0.22). COVID-19 diagnosis had similar odds of inpatient mortality (odds ratio: 1.11; 95% CI: 0.43 to 2.84; P = 0.84). Conclusion: The prevalence of COVID-19 among hospitalized patients with CeAD is low with 2.32% of all CeAD cases. Concomitant COVID infection did not lead to an increased risk of stroke in CeAD. However, potentially worse functional outcomes (fewer home discharges) without an increase in mortality were seen in patients with COVID and CeAD.

Abstract BACKGROUND Hypercoagulability is a well-described paraneoplastic phenomenon associated with strokes in cancer patients, but whether driver mutations or antineoplastic treatments contribute in a significant way to recurrent stroke risk are not well understood. METHODS As part of a larger study focusing on lung cancer and stroke, we retrospectively identified 103 patients with tissue-confirmed adenocarcinoma and prior diagnosis of stroke treated at the Mayo Clinic between 2000-2022. We collected data regarding demographics, performance status, cerebrovascular risk factors, antithrombotic use, chemotherapy, radiation, and genetic testing data, which were assessed for impact on recurrent stroke risk. RESULTS 71.8% of patients had recurrent strokes (74/103). No class of chemotherapeutics was significantly associated with increased risk for recurrent strokes, including immune checkpoint inhibitors and thrombogenic chemotherapeutics (Gemcitabine, Cisplatin, Carboplatin, anti-VEGF therapies). 78 patients had genetic testing data available. Driver mutations in KRAS, EGFR, MET, and BRAF were not associated with increased risk for recurrent stroke. There was a signal towards increased risk for stroke recurrence in patients with ALK mutations (OR 2.647, p=0.4056). There was a trend towards increased risk for stroke recurrence in patients with advanced staging (Stage III/IV) at diagnosis (OR 2.125, p=0.09). Stroke recurrence risk was higher in patients treated with single antiplatelet agents compared to anticoagulation or dual antiplatelet therapy (OR 3.385, p=0.0061) though risk of hemorrhagic complications was similar (OR 1.559, p=0.3376). Patients with recurrent stroke had longer overall survival compared to those without (Median OS 43.2 months vs 26.3 months, Mantel-Haenszel HR 0.5202, p=0.0367). CONCLUSIONS In patients with lung adenocarcinoma who experienced ischemic stroke, prolonged survival and single antiplatelet therapy compared to dual antiplatelet therapy or anticoagulation were associated with increased recurrent stroke risk. ALK mutations and higher stage at initial diagnosis trended towards higher risk for stroke recurrence. Larger retrospective analyses are under way to confirm these findings.

Background Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. Objective To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). Methods In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. Results This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract ( d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [ rsp] = −0.56, p < 0.001), and forceps minor of corpus callosum ( rsp = -0.45, p < 0.01). Conclusion MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

Stroke is one of the leading causes of disability worldwide despite recent advances in hyperacute interventions to lessen the initial impact of stroke. Stroke recovery therapies are crucial in reducing the long-term disability burden after stroke. Stroke recovery treatment options have rapidly expanded within the last decade, and we are in the dawn of an exciting era of multimodal therapeutic approaches to improve post-stroke recovery. In this narrative review, we highlighted various promising advances in treatment and technologies targeting stroke rehabilitation, including activity-based therapies, non-invasive and minimally invasive brain stimulation techniques, robotics-assisted therapies, brain–computer interfaces, pharmacological treatments, and cognitive therapies. These new therapies are targeted to enhance neural plasticity as well as provide an adequate dose of rehabilitation and improve adherence and participation. Novel activity-based therapies and telerehabilitation are promising tools to improve accessibility and provide adequate dosing. Multidisciplinary treatment models are crucial for post-stroke neurorehabilitation, and further adjuvant treatments with brain stimulation techniques and pharmacological agents should be considered to maximize the recovery. Among many challenges in the field, the heterogeneity of patients included in the study and the mixed methodologies and results across small-scale studies are the cardinal ones. Biomarker-driven individualized approaches will move the field forward, and so will large-scale clinical trials with a well-targeted patient population.

ObjectiveEpidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent.Methods and ResultsIn the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non‐CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke‐free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke‐free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37–1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74–3.34), without aura (OR = 2.67, 95% CI = 2.15–3.32), and family history of vascular disease in first‐degree relatives (OR = 1.69, 95% CI = 1.39–2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47–0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62–0.91), and obese (OR = 0.41, 95% CI = 0.31–0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47–2.22) in comparison with patients with non‐CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti‐migraine preventive medications, especially beta‐blockers, compared with the other groups.InterpretationThe risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta‐blockers. ANN NEUROL 2023;94:585–595

Abstract Studies have shown that the integrity of white matter tracts connecting different regions in the left cerebral hemisphere is important for aphasia recovery after stroke. However, the impact of the underlying structural connection between the cortex and the cerebellum in post-stroke aphasia is poorly understood. We studied the microstructural integrity of the cerebellum and the corticocerebellar connections and their role in picture naming. Fifty-six patients with left cerebral infarcts (sparing the cerebellum) underwent diffusion tensor imaging (DTI) and Boston Naming Test. We compared the fractional anisotropy (FA) and mean diffusivity (MD) values of the right and the left cerebellum (lobular gray and white matter structures) and cerebellocortical connections. Recursive feature elimination and Spearman correlation analyses were performed to evaluate the relationship between naming performance and the corticocerebellar connections. We found that the right, relative to left, cerebellar structures and their connections with the left cerebrum showed lower FA and higher MD values, both reflecting lower microstructural integrity. This trend was not observed in the healthy controls. Higher MD values of the right major cerebellar outflow tract were associated with poorer picture naming performance. Our study provides the first DTI data demonstrating the critical importance of ascending and descending corticocerebellar connections for naming outcomes after stroke.

Background Traumatic posterior cerebral artery (tPCA) dissection and dissecting aneurysms are rare and constitute a challenging clinical entity. Objective We analyze existing literature on tPCA dissection and present our institutional experience. Methods We retrospectively queried our database for tPCA isolated dissection or dissecting aneurysms from 2008 until now and conducted a systematic literature review of published cases. We analyzed the clinical and radiographic characteristics and treatment outcomes of tPCA dissection. Results Including our case, a total of 11 cases with either isolated dissection ( n = 2) or dissecting aneurysms ( n = 9) were included. The median age was 27 years, and 45% were females. The median interval between trauma and tPCA dissection diagnosis was nine days. Mental status declined in four (36%) patients. Half of the patients demonstrated tentorial subdural hematoma on head CT. Ischemic stroke was detected in three (43%) patients. Four (36%) patients were conservatively managed, one (9.1%) patient was treated with surgical clipping of the proximal PCA, and six patients underwent endovascular treatments. The complication rate was 20%. Immediate total occlusion was demonstrated in five patients (100%), and the conservatively managed case showed immediate, spontaneous thrombosis of the aneurysm. Glasgow Coma Scale scores were 15 in eight (89%) and 14 in one (11%) patients at the last clinical follow-up with a median of six months. The mortality and retreatment rates were null. Conclusions tPCA dissection is diagnosed late and commonly affects the young population. The clinical outcome for this condition is typically favorable. Current endovascular techniques showed considerable efficacy and safety.

Introduction: Cervical artery dissection (CAD) is a well-recognized cause of acute ischemic stroke, especially in young adults, accounting for up to 20-25% of all cases. Several studies reported an incidence between 2.5-5 per 100,000 in the general population. However, the actual incidence may be higher as many patients remain asymptomatic. Even though CAD is one of the leading causes of ischemic stroke, there is a lack of consensus in management. Our study surveyed practicing clinicians involved in the management of CAD to characterize current practice trends and provide a foundation for future research. Methods: An online case-based questionnaire with 11 questions regarding the management of cervical artery dissection was developed and piloted internally with 12 Mayo Clinic cerebrovascular neurologist/neurosurgeons. The survey was finalized, and initially sent to the STOP-CAD study group. We then sent the survey to practicing vascular neurologists across different academic institutions. Surveys were sent to 126 unique individuals. Results: A total of 42 clinicians completed the questionnaires. The response rate was 33% (42/126). Aspirin antiplatelet monotherapy was seen as the most appropriate therapy for asymptomatic CAD (81% [34/42]). Anticoagulation was the treatment of choice for cases with CAD and concomitant intraluminal thrombus (74% [31/42]). Most (74% [31/42]) of the participants recommended repeat imaging at three months. However, no consistent response regarding the type of antithrombotic agent for symptomatic CAD without intramural thrombus or cases with pseudoaneurysm. There was marked variability regarding the duration of antithrombotic therapy, ranging from three months to life-long treatment. Conclusion: Marked variability was seen in the management of CAD, especially regarding the choice of antithrombotic agent in symptomatic and complicated (stenosis or pseudoaneurysm) cases and the duration of such therapy, which reflects the lack of definitive clinical trial data. Ongoing research is needed to better guide the optimal management of these patients.