Associations of carotid artery flow parameters with MRI markers of cerebral small vessel disease and patterns of brain atrophy

ObjectivesA growing body of evidence links age related brain pathologies to systemic vascular processes. We aimed to study the prevalence and interrelations between magnetic resonance imaging (MRI) markers of cerebral small vessel disease and patterns of brain atrophy, and their association to carotid duplex ultrasound flow parameters.Materials and methodsWe investigated a population based randomised cohort of older adults (n=391) aged 70-87, part of the Swedish Good Aging in Skåne Study. Peak systolic and end diastolic velocities of the carotid arteries were measured by ultrasound, and resistivity- and pulsatility indexes were calculated. Subjects with increased peak systolic velocity indicating carotid stenosis were excluded from analysis. Nine MRI findings were rated by visual scales: white matter changes, pontine white matter changes, microbleeds, lacunar infarctions, medial temporal lobe atrophy, global cortical atrophy, parietal atrophy, precuneus atrophy and central atrophy.ResultsMRI pathologies were found in 80% of subjects. Mean end diastolic velocity in common carotid arteries was inversely associated with white matter hyperintensities (OR=0.92; p=0.004), parietal lobe atrophy (OR=0.94; p=0.039), global cortical atrophy (OR=0.90; p=0.013), precuneus atrophy (OR=0.94; p=0.022), “number of CSV pathologies” (β=-0.07; p<0.001) and “MRI-burden score” (β=-0.11; p<0.001), after adjustment for age and sex. The latter three were also associated with pulsatility and resistivity indexes.ConclusionsLow carotid end diastolic velocity, as well as increased carotid resistivity and pulsatility, were associated with signs of cerebral small vessel disease and patterns of brain atrophy, indicating a vascular component in the process of brain aging.     

Median somatosensory evoked potential as a predictor of clinical outcome after urgent surgical extracranial internal carotid artery recanalization

ObjectiveChanges in the N20/P25 amplitude of somatosensory evoked potentials (SEP) of the median nerve have been found to correlate with those in cortical regional cerebral blood flow (rCBF). Our study presents the use of median nerve SEP amplitude in predicting the clinical outcome of urgent surgical internal carotid artery (ICA) recanalization.MethodsA total of 27 patients suffering an acute ischemic stroke (AIS) with extracranial ICA occlusion within 24 h were prospectively recruited. The primary preoperative endpoints included the SEP amplitude absolute value (SEP-amp) and the SEP amplitude side-to-side ratio (SEP-ratio).Clinical outcome at 3 months postoperatively was assessed using the modified Rankin scale (mRS-3M).ResultsThe positive predictive values (PPVs) for SEP-amp and SEP-ratio were 95.5% and 100%, respectively, with the negative predictive values (NPVs) being 60.0% and 100%, respectively. The SEP-ratio correlated fully with mRS-3M.ConclusionThe median SEP side-to-side N20/P25 amplitude ratio seems to be a very strong positive and negative predictor of the clinical outcome of urgent recanalization of an extracranial ICA occlusion.SignificanceThe results suggest that cortical evoked activity may help in selection patient for surgical recanalization and predict clinical recovery after an acute ischemic stroke.     

Predictors of CPAP adherence following stroke and transient ischemic attack

ObjectiveContinuous positive airway pressure (CPAP) has been shown to improve functional, motor and cognitive outcomes in post-stroke obstructive sleep apnea (OSA). However, rates of CPAP adherence are often low and factors impacting CPAP adherence remain under-explored. Our objective was to determine predictors of CPAP adherence in patients who had a stroke or transient ischemic attack (TIA).MethodsWe screened 313 stroke/TIA patients for OSA using in-hospital polysomnography or the ApneaLink home sleep apnea test. Potential predictors were recorded at baseline and adherence to CPAP was recorded during a six-month follow-up visit. Selected variables from our univariate analyses were included in multivariate regression models to determine predictors of CPAP adherence. For our logistic regression analyses, CPAP adherence (CPAP use of ≥4 h per night) was the dependent outcome variable. In our linear regression analyses, total CPAP use per week (recorded in hours) was the dependent outcome variable.ResultsEighty-eight patients (mean age 67.81 ± 13.09 years, 69.32% male, mean body mass index 27.93 ± 5.23 kg/m²) were diagnosed with OSA, prescribed CPAP, and assessed for adherence at a six-month follow-up visit. In these 88 patients, 46 (52.27%) were adherent with CPAP therapy. From our regression models, two significant predictors of CPAP adherence were identified: greater functional status (p = 0.04) and not endorsing daytime tiredness (p = 0.047) post-stroke/TIA.ConclusionPatients with greater functional capacity and those with less daytime fatigue demonstrated stronger adherence to CPAP therapy. Our findings may facilitate future treatment strategies for enhancing CPAP adherence in the vulnerable stroke/TIA population.     

Clinical features and prognostic factors in patients with cancer-associated multiple ischemic stroke: A retrospective observational study

ObjectivesTo investigate the patient demographics, survival after diagnosis, and prognostic factors among patients with multiple-territory cerebral infarctions due to cancer-associated ischemic stroke (multiple CAIS).Materials and methodsWe performed a retrospective review of the medical records from a 10-year period of consecutive patients with multiple CAIS, defined as (1) newly developed multiple cerebral infarctions involving two or more cerebrovascular territories, (2) association with active cancer diagnosed or treated <6 months before or after stroke, and (3) exclusion of obvious etiologies other than cancer-associated coagulopathy in routine screening. We extracted demographic features, stroke severity and characteristics, cancer characteristics, comorbidities, and laboratory data. Univariable Cox proportional hazards regression was used to idenify the prognostic factors.ResultsThe median age was 74 years (interquartile range, 68.3–80.5), and the median survival after diagnosis was 44.5 (27.3–76.8) days in 26 patients with complete follow-up. The median National Institutes of Health Stroke Scale was 5.5 (2.0–9.0). Twenty (76.9%) patients had received a cancer diagnosis prior to the diagnosis of multiple CAIS, and most patients (25 patients, 96.2%) had stage IV cancer. Univariate analysis showed that high serum albumin (hazard ratio, 0.31; 95% confidence interval, 0.11–0.88) was significantly associated with prolonged survival, whereas stroke severity and comorbidities were not associated with survival.ConclusionMultiple CAIS predominantly occurred in elderly patients with advanced cancer, and their survival was short. Serum albumin levels were significantly associated with prognosis, indicating the poor general condition associated with cancers may affect prognosis.     

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population.Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE.ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors.ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.     

PulseRider-assisted coil embolization for an unruptured internal carotid artery–persistent primitive trigeminal artery aneurysm

A persistent primitive trigeminal artery (PPTA) is a vessel remnant of carotid-vertebrobasilar anastomosis. The aneurysm at the bifurcation of the internal carotid artery (ICA) and PPTA tends to have a broad neck with the branch incorporated into the sac. Because PPTA supplies to the posterior circulation and branches off direct pontine perforators, PPTA preservation should always be considered when treating PPTA aneurysms to avoid ischemic complications.We report a case of the wide-neck ICA–PPTA aneurysm successfully treated with the PulseRider-assisted coil embolization, resulting in complete occlusion with PPTA patency. Relevant anatomy and endovascular strategy of the PPTA aneurysms are discussed.     

Difference in acute and chronic stage ischemic stroke metabolic markers with controls

BackgroundAcute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls.MethodsThrough the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations.ResultsThe sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls.ConclusionOur pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.     

Geriatric nutrition risk index predicts prolonged post-stroke dysphagia in acute ischemic stroke

BackgroundPost-stroke dysphagia (PSD) is a common complication after stroke. Malnutrition inhibits stroke recovery and is associated with stroke mortality. However, no studies have investigated the effects of nutritional state at admission on prolonged PSD.MethodsWe retrospectively analyzed ischemic stroke patients in our institute from January 2018 to December 2020. Swallowing function was assessed using the Food Oral Intake Scale; prolonged PSD was defined as levels 1–3 at 14 days after admission. The Geriatric Nutritional Risk Index (GNRI) was used to assess nutritional risks, which were classified as follows: >98, no nutritional risk; 92–98, mild nutritional risk; 82–92, moderate nutritional risk; and <82, severe nutritional risk. The association between GNRI and prolonged PSD was assessed.ResultsOf 580 patients (median age, 81 years; male, 53%), prolonged PSD was detected in 117 patients. Patients with severe dysphagia had older age, higher pre-stroke modified Rankin Scale score, lower GNRI, and higher National Institutes of Health Stroke Scale score. Logistic regression analysis revealed that lower GNRI was independently associated with prolonged PSD (continuous value; adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05). In addition, when "severe" and "moderate" nutritional risk was analyzed as a single class, moderate or severe nutritional risk (GNRI < 92) was independently associated with prolonged PSD (adjusted OR 2.50, 95% CI 1.29–4.87), compared with no nutritional risk patients (GNRI > 98).ConclusionsIn acute ischemic stroke, lower GNRI at admission was independently associated with prolonged PSD, suggesting that GNRI at admission might identify patients at risk of prolonged PSD.     

Comparison of clinical outcomes with left unilateral and sequential bilateral Transcranial Magnetic Stimulation (TMS) treatment of major depressive disorder in a large patient registry

BackgroundIt has been suggested that sequential bilateral (SBL) TMS, combining high frequency, left dorsolateral prefrontal cortex (DLPFC) stimulation and low frequency, right DLPFC stimulation, is more effective than unilateral TMS.ObjectiveTo contrast treatment outcomes of left unilateral (LUL) and SBL protocols.MethodsRegistry data were collected at 111 practice sites. Of 10,099 patients, 3,871 comprised a modified intent-to-treat (mITT) sample, defined as a primary MDD diagnosis, age ≥18, and PHQ-9 completion before TMS and at least one PHQ-9 assessment after baseline. The mITT sample received high frequency (10 Hz) LUL TMS exclusively (N = 3,327) or SBL TMS in at least 90% of sessions (N = 544). Completers (N = 3,049) were responders or had received ≥20 sessions and had an end of acute treatment PHQ-9 assessment. To control for site effects, a Matched sample (N = 653) included Completers at sites that used both protocols. To control for selection bias, the SBL group was also compared to a Restricted LUL group, drawn from sites where no patient switched to SBL after substantial exposure to LUL TMS. Secondary analyses were conducted on CGI-S ratings.ResultsThe LUL group had superior outcomes compared to the SBL group for multiple PHQ-9 and CGI-S continuous and categorical measures in the mITT, Completer and Matched samples, including in the specified primary analyses. However, outcome differences were not observed when comparing the Restricted LUL and SBL groups. Within SBL protocols, the LUL-RUL order had superior outcomes compared to the RUL-LUL order in all CGI-S, but not PHQ-9, measures.ConclusionsWhile limited by the naturalistic design, there was no evidence that SBL TMS was superior to LUL TMS. The sequential order of RUL TMS followed by LUL TMS may have reduced efficacy compared to LUL TMS followed by RUL TMS.     

Long-term mortality in ischemic stroke patients with concomitant chronic obstructive pulmonary disease

BackgroundLong-term mortality in ischemic stroke patients with concomitant COPD has been largely unexplored. This study aimed to compare long-term all-cause mortality in ischemic stroke patients with and without COPD.MethodsThis was a retrospective cohort study of ischemic stroke patients with and without COPD in the Geisinger Neuroscience Ischemic Stroke database to examine all-cause mortality up to 3 years using Kaplan-Meier estimator and Cox proportional hazards model.ResultsOf the 6,589 ischemic stroke patients included in this study, 5,525 (83.9%) did not have COPD (group A). Group B (n=1,006) consisted of patients with COPD diagnosis by ICD-9/10-CM codes. COPD patients in Group C (n=233) were diagnosed by spirometry, and in Group D (n=175) by both ICD-9/10-CM codes and spirometry confirmation. The survival probabilities at three years in Group B, C, and D were significantly lower than in Group A. Group B (HR=1.262, 95% CI 1.122–1.42, p<0.001) and group C (HR=1.251, 95% CI 1.01–1.55, p=0.041) had significantly lower hazard of mortality compared to group A. There was no significant difference in survival between COPD subtypes of chronic bronchitis and emphysema. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 stage had an increased mortality hazard compared to the GOLD 1 stage.ConclusionsWhile ischemic stroke patients with preexisting COPD have worse long-term survival than those without COPD, the results largely depended on the definition of COPD used. These results suggest that ischemic stroke patients with COPD need more personalized medical care to decrease long-term mortality.     

Another possible determinant for ischemic stroke with nonvalvular atrial fibrillation other than conventional oral anticoagulant treatment: The relationship between whole blood viscosity and stroke☆

ObjectivesPatients with nonvalvular atrial fibrillation (NVAF) still experience ischemic stroke despite recommended medications and this could be the consequence of increased whole blood viscosity (WBV). We evaluated the predictive value of WBV for stroke in patients with NVFA despite receiving oral anticoagulant (OAC) therapy.MethodsOne thousand and forty-three NVAF patients on OAC medication were followed up for median 36.13 ± 18.31 months. WBV was calculated according to the validated de Simone's formula.ResultsWBV was significantly higher in stroke group when compared to non-stroke group at both low shear rate (LSR) and high shear rate (HSR). Multiple regression analysis demonstrated an independent association between WBV and stroke when adjusted for other risk factors.ConclusionsWBV appears to be a profitable predictor of ischemic stroke in patients with NVAF receiving OAC.     

Risks and benefits of timely screw removal after thoracolumbar spine fractures treated with non-fusion technique

BackgroundPercutaneous-short segment screw fixation (SSSF) without bone fusion has proven to be a safe and effective modality for thoracolumbar spine fractures (TLSFs). When fracture consolidation is confirmed, pedicle screws are no longer essential, but clear indications for screw removal following fracture consolidation have not been established.MethodsIn total, we enrolled 31 patients with TLSFs who underwent screw removal following treatment using percutaneous-SSSF without fusion. Plain radiographs, taken at different intervals, measured local kyphosis using Cobb’ angle (CA), vertebra body height (VBH), and the segmental motion angle (SMA). A visual analogue scale (VAS) and the Oswestry disability index (ODI) were applied pre-screw removal and at the last follow-up.ResultsThe overall mean CA deteriorated by 1.58° (p < 0.05) and the overall mean VBH decreased by 0.52 mm (p = 0.001). SMA preservation was achieved in 18 patients (58.1%) and kyphotic recurrence occurred in 4 patients (12.9%). SMA preservation was statistically significant in patients who underwent screw removal within 12 months following the primary operation (p = 0.002). Kyphotic recurrence occurred in patients with a CA ≥ 20° at injury (p < 0.001) with a median interval of 16.5 months after screw removal. No patients reported worsening pain or an increased ODI score after screw removal.ConclusionScrew removal within 12 months can be recommended for restoration of SMA with improvement in clinical outcomes. Although, TLSFs with CA ≥ 20° at the time of injury can help to predict kyphotic recurrence after screw removal, the clinical outcomes are less relevant.     

Role of endovascular treatment for ruptured aneurysms involving the anterior spinal artery at the craniocervical junction

Ruptured aneurysms at the craniocervical junction (CCJ) involving the anterior spinal artery (ASA) are rare and consist of heterogenous lesions with variable clinical entities. However, the standard therapeutic strategy for the lesions has not been well-established. Moreover, despite advances in modern neurointervention, reports describing endovascular treatment for this specific lesion have been few. Here, we report three cases of ruptured aneurysms on the pial tributary of the ASA at the CCJ, which were subsequently treated by transarterial glue injection or coil embolization. Endovascular treatment can be a therapeutic option, particularly for these ruptured aneurysms. Either transarterial glue injection or coil embolization can be effective depending on the type of etiology and the surrounding vasculature anatomy.     

Vertebral Artery Tortuosity and Morphometric Characteristics of Patients with Recurrent Cervical Artery Dissection

BackgroundCervical Artery Dissection is an important cause of stroke in the young. Data on incidence and associations of recurrence in patients with cervical artery dissection are lacking. Increased Vertebral Artery Tortuosity Index has been reported in patients with cervical artery dissection and associated with earlier age of arterial dissection in patients with connective tissue disease.ObjectiveTo test the hypothesis that increased vertebral artery tortuosity is associated with recurrent cervical artery dissection.MethodsWe reviewed data from a single-center registry of cervical artery dissection patients enrolled between 2011-2021. CT angiography was reviewed for neck length, vertebral artery dominance, and vertebral artery tortuosity index. Incidence rate of recurrent dissection was calculated using Poisson regression. Differences between groups were analyzed using the Kruskal-Wallis rank sum test and Fisher's exact test.ResultsThe cohort included 155 patients: women (56%), mean (SD) age 42 (±10) years, and 116 single and 39 multiple artery dissections. Eleven (7.1%) had a recurrence with an incidence rate (95% CI) of 1.91 (1.06, 3.44) per 100 person-years. Vertebral artery tortuosity did not differ significantly between single and recurrent groups (median (IQR) 46.81 (40.85, 53.91) vs 44.97 (40.68, 50.62) p = 0.388). Morphometric characteristics of height, neck length, and BMI were not associated with recurrence. There was no difference in vertebral artery tortuosity by dissection location (carotid vs vertebral).ConclusionIn this single center cohort of patients with cervical artery dissection, there was no difference in VTI between single and recurrent groups.     

Real-time feedback on mobile application use for emergency management affects the door-to-needle time and functional outcomes in acute ischemic stroke

ObjectivesTime from onset to reperfusion affects mortality and favorable outcomes in patients with acute ischemic stroke (AIS). To evaluate effects of a real-time feedback mobile application on critical time intervals and functional outcomes in stroke emergency management.MethodsWe recruited patients with clinically suspected acute stroke from December 1st, 2020 until July 30st, 2022. All Patients had a non-contrast computed tomography (CT) and were included only if they had AIS. We divided the patients into two groups based on the date of availability on mobile application: pre-APP group and post-APP group. Onset to Door time (ODT), Door to Imaging Time (DIT), Door to Needle Time (DNT), Door to Puncture Time (DPT), Door to Recanalization Time (DRT), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were compared between two groups.ResultsWe retrospectively enrolled 312 AIS patients who were assigned into the pre-APP group (n = 159) and post-APP group (n = 153). The median ODT time and median admission NIHSS score were not significantly different between the two groups at baseline assessment. The median (IQR) DIT [44 (30-60) min vs 28 (20-36) min, P < 0.01] and DNT [44 (36.25-52) min vs 39 (29-45) min, P = 0.02] both decreased significantly in two groups. However, median DPT and DRT time showed no significant differences. The proportion of mRS score of 0 to 2 at day 90 was significantly higher in the post-App group than in the pre-App group, at 82.4% and 71.7%, respectively (dominance ratio OR=1.84, 95% CI: 1.07 to 3.16, P = 0.03).ConclusionThe present findings indicate that the real-time feedback of stroke emergency management used by a mobile application have potential for shortening the DIT and DNT time and improve the prognosis of stroke patients.     

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion

ObjectivesDiffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers.Materials and methodsRetrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed.ResultsWe included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038).ConclusionsIn this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.