Biochemical, biomechanical and imaging biomarkers of ischemic stroke: Time for integrative thinking.

Stroke is one of the leading causes of adult disability affecting millions of people worldwide. Post-stroke cognitive and motor impairments diminish quality of life and functional independence. There is an increased risk of having a second stroke and developing secondary conditions with long-term social and economic impacts. With increasing number of stroke incidents, shortage of medical professionals and limited budgets, health services are struggling to provide a care that can break the vicious cycle of stroke. Effective post-stroke recovery hinges on holistic, integrative and personalized care starting from improved diagnosis and treatment in clinics to continuous rehabilitation and support in the community. To improve stroke care pathways, there have been growing efforts in discovering biomarkers that can provide valuable insights into the neural, physiological and biomechanical consequences of stroke and how patients respond to new interventions. In this review paper, we aim to summarize recent biomarker discovery research focusing on three modalities (brain imaging, blood sampling and gait assessments), look at some established and forthcoming biomarkers, and discuss their usefulness and complementarity within the context of comprehensive stroke care. We also emphasize the importance of biomarker guided personalized interventions to enhance stroke treatment and post-stroke recovery.

Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection.

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Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series.

Severe SARS-CoV-2 (COVID-19) infection has the potential for a high mortality rate. In this paper, we report the results of plasmapheresis treatment in a series of severely ill patients with COVID-19-related autoimmune meningoencephalitis in the Intensive Care Unit (ICU).

Behçet's disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study.

OBJECTIVE: This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçet's disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST). METHODS: VENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis. RESULTS: BD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%). CONCLUSIONS: BD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study.

AIM: Systemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics. MATERIAL AND METHOD: Among the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded. RESULTS: In total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up. CONCLUSIONS: SLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.

Comparison of conventional and modern methods in determining ischemic stroke etiology by general and stroke neurologists

Background/aim: This study aimed to investigate the consistency between stroke and general neurologists in subtype assignment using the Trial of ORG-10172 in Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Materials and methods: Fifty consecutive acute ischemic stroke patients admitted to the stroke unit were recruited. Patients were classified by two stroke and two general neurologists, each from different medical centers, according to TOAST followed by the CCS. Each neurologist was assessed for consistency and compliance in pairs. Concordance among all four neurologists was investigated and evaluated using the kappa (ĸ) value. Results: The kappa (ĸ) value of diagnostic compliance between stroke neurologists was 0.61 (95% CI: 0.45­0.77) for TOAST and 0.78 (95% CI: 0.62­0.94) for CSS-5. The kappa (ĸ) value was 0.64 (95% CI: 0.48­0.80) for TOAST and 0.75 (95% CI: 0.60­0.91) for CCS-5 for general neurologists. Compliance was moderate [ĸ: 0.59 (95% CI: 0.52­0.65)] for TOAST and was strong [ĸ: 0.75 (95% CI: 0.68­0.81)] for CCS-5 for all 4 neurologists. 'Cardioembolism' (91.04%) had the highest compliance in both systems. The frequency of the group with 'undetermined etiologies' was less in the CCS (26%) compared to TOAST. Conclusion: The CCS system improved compliance in both stroke and general neurologists compared with TOAST. This suggests that the automatic, evidence-based, easily reproducible CCS system was superior to the TOAST system.

Analyses of the Turkish National Intravenous Thrombolysis Registry.

BACKGROUND: The relatively late approval of use of recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke in Turkey has resulted in obvious underuse of this treatment. Here we present the analyses of the nationwide registry, which was created to prompt wider use of intravenous thrombolysis, as well as to monitor safe implementation of the treatment in our country. METHODS: Patients were registered prospectively in our database between 2006 and 2013. Admission and 24-hour National Institutes of Health Stroke Scale and 3-month modified Rankin Scale scores were recorded. A "high-volume center" was defined as a center treating 10 or more patients with rt-PA per year. RESULTS: A total of 1133 patients were enrolled into the registry by 38 centers in 18 cities. A nearly 4-fold increase in the study population and in the number of participating centers was observed over the 6 years of the study. The mean baseline NIHSS score was 14.5 ± 5.7, and the prevalence of symptomatic hemorrhage was 4.9%. Mortality at 3 months decreased from 22% to 11% in the 6 years of enrollment, and 65% of cases were functionally independent. Age older than 70 years, an NIHSS score higher than 14 upon hospital admission, and intracranial hemorrhage were independently associated with mortality, and being treated in a high-volume center was related to good outcome. CONCLUSIONS: We observed a decreasing trend in mortality and an acceptable prevalence of symptomatic hemorrhage over 6 years with continuous addition of new centers to the registry. The first results of this prospective study are encouraging and will stimulate our efforts at increasing the use of intravenous thrombolysis in Turkey.

Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey.

BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

A Case With New-Onset Neuromyelitis Optica Spectrum Disorder Following COVID-19 mRNA BNT162b2 Vaccination.

INTRODUCTION: In the midst of the coronavirus disease of 2019 pandemic, active immunization by effective vaccination gained utmost importance in terms of global health. The messenger RNA (mRNA) vaccines are novel strategies requiring clinical surveillance for adverse events. CASE REPORT: We report a 43-year-old previously healthy female with an optic neuritis attack 24 hours following immunization with the second dose of coronavirus disease of 2019 mRNA BNT162b2 vaccine. A second transverse myelitis attack together with an elevated anti-AQP-4 antibody titer confirmed the diagnosis of neuromyelitis optica spectrum disorder. CONCLUSION: Our case identifies the BNT162b2 vaccine as a possible trigger for neuromyelitis optica spectrum disorder. This rare and potentially coincidental event has no implications for vaccine administration practices. However, further research is needed to elucidate the effects of mRNA vaccines on humoral and cell-mediated immunity.

Headache as the sole presenting symptom of cerebral venous sinuses thrombosis: Subgroup analysis of data from the VENOST study.

OBJECTIVES: Headache is the most common complaint in cerebral venous sinus thrombosis (CVST) and it may sometimes be the only symptom in these patients. This retrospective and prospective study was an investigation of any differences in terms of clinical risk factors, radiological findings, or prognosis in patients with CVST who presented with isolated headache (IH) and cases with other concomitant findings (non-isolated headache [NIH]). METHODS: A total of 1144 patients from a multicenter study of cerebral venous sinus thrombosis (VENOST study) were enrolled in this research. The demographic, biochemical, clinical, and radiological aspects of 287 IH cases and 857 NIH cases were compared. RESULTS: There were twice as many women as men in the study group. In the IH group, when gender distribution was evaluated by age group, no statistically significant difference was found. The onset of headache was frequently subacute and chronic in the IH group, but an acute onset was more common in the NIH group. Other neurological findings were observed in 29% of the IH group during follow-up. A previous history of deep, cerebral, or other venous thromboembolism was less common in the IH group than in the NIH group. Transverse sinus involvement was greater in the IH group, whereas sagittal sinus involvement was greater in the NIH group. The presence of a plasminogen activator inhibitor (PAI) mutation was significantly greater in the IH group. CONCLUSION: IH and CVST should be kept in mind if a patient has subacute or chronic headache. PAI, which has an important role in thrombolytic events, may be a risk factor in CVST. Detailed hematological investigations should be considered. Additional studies are needed.

Cerebral Venous Sinus Thrombosis in Women: Subgroup Analysis of the VENOST Study.

BACKGROUND: Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelae; thus, the symptoms must be documented in detail for each group. METHODS: Out of 1144 patients with CVST, a total of 777 women were enrolled from a multicenter for the study of cerebral venous sinus thrombosis (VENOST). Demographic, biochemical, clinical, and radiological aspects were compared for 324 cases with RHRF and 453 cases without RHRF. RESULTS: The mean age of the RHRF (-) group (43.2 ± 13 years) was significantly higher than of the RHRF (+) group (34 ± 9 years). A previous history of deep venous thrombosis (3%), isolated cavernous sinus involvement (1%), cranial neuropathy (13%), comorbid malignancy (7%), and its disability scores after 12 months (9%) were significantly higher in the RHRF (-) group. The RHRF (+) group consisted of 44% cases of puerperium, 33% cases of OC users and 23% of pregnant women. The mean age was found to be higher in OC users (38 ± 9 years). A previous history of deep venous thrombosis was slightly higher in the pregnancy subgroup (4%). Epileptic seizures were more common in the puerperium group (44%). CONCLUSION: The results of our study indicate that the risk of CSVT increases parallel to age, OC use, and puerperium period. In addition, when considering the frequency of findings and symptoms, epileptic seizures in the puerperium subgroup of the RHRF (+) group and malignancies in the RHRF (-) group may accompany the CSVT. In daily practice, predicting these risks for the CSVT and early recognition of the symptoms will provide significant benefits to patients.

Epileptic seizures in cerebral venous sinus thrombosis: Subgroup analysis of VENOST study.

PURPOSE: The aim of this study is to evaluate the presence and prognostic impact of early seizures in cerebral venous sinus thrombosis patients (CVST). METHOD: VENOST is a retrospective and prospective national multicenter observational study. CVST patients with or without epileptic seizures (ES) were analyzed and compared in terms of demographic and imaging data, causative factors, clinical variables, and prognosis in a total of 1126 patients. RESULTS: The mean age of the patients in the ES group was 39.73 ± 12.64 and 40.17 ± 14.02 years in the non-ES group (p > 0.05). Epileptic seizures were more common (76.6 %) in females (p < 0.001). Early ES occurred in 269 of 1126 patients (23.9 %). Epileptic seizures mainly presented in the acute phase (71.4 %) of the disease (p < 0.001). Majority of these (60.5 %) were in the first 24 h of the CVST. The most common neurological signs were focal neurologic deficits (29.9 %) and altered consciousness (31.4 %) in the ES group. Superior sagittal sinus (SSS) and cortical veins (CV) involvement were the most common sites of thrombosis and the mostly related etiology were found puerperium in seizure group (30.3 % vs 13.9 %). Patients with seizures had worse outcome in the first month of the disease (p < 0.001) but these did not have any influence thereafter. CONCLUSIONS: In this largest CVST cohort (VENOST) reported female sex, presence of focal neurological deficits and altered consciousness, thrombosis of the SSS and CVs, hemorrhagic infarction were risk factors for ES occurrence in patients with CVST.

Predictors of refractoriness in a Turkish status epilepticus data bank.

Refractory status epilepticus (RSE) is known to constitute approximately 10-50% of all cases of status epilepticus (SE) and is associated with significant morbidity and mortality. In the present study, data from a prospectively collected SE database were analyzed. Patients with RSE (defined as a SE episode requiring a second line of intravenous treatment following intravenous phenytoin) were compared with patients with nonrefractory SE (NRSE); 290 episodes of SE were identified, of which 108 (38%) were defined as RSE. Univariate analysis revealed that age, female gender, SE type, SE duration, and acute etiology were associated with refractoriness, whereas electroencephalographic patterns were not. Nonconvulsive SE, which is probably associated with delays in treatment initiation, was a predictor of RSE, although it was not retained as a predictor in multivariate analysis. In the latter analysis, female gender (odds ratio: 1.815, 95% CI: 1.053-3.126) and acute etiology (odds ratio: 0.619, 95% CI: 0.429-0.894) were shown to be the only significant independent predictors of refractoriness.

Psychotic depression: a peculiar presentation for multiple sclerosis.

Multiple sclerosis (MS) is frequently associated with a number of different psychiatric syndromes. Solely psychiatric syndrome may be the first clinical presentation of multiple sclerosis. We report a patient whose first attack was psychotic depression. The present case emphasizes that psychiatric symptoms can occur at any time during the course of the disease and, moreover, may be the presenting feature.

Acute stroke increases QT dispersion in patients without known cardiac diseases.

BACKGROUND: Electrocardiographic changes are well known to appear with acute cerebrovascular events. OBJECTIVE: To investigate if QT dispersion (QTd) is increased in patients who have an acute stroke and if this increase could be related to lesion extent and/or localization. DESIGN: The study group consisted of 36 patients who had an acute stroke and no history or signs of cardiovascular disease. An age-matched control group (n = 19) free of cardiovascular disease was also included. Simultaneous 12-lead electrocardiograms (ECGs) were recorded within the first 24 hours (24h-ECG) and after 72 hours (72h-ECG) from stroke onset. QT dispersion was assessed both manually and automatically with assessors blinded to the clinical data. RESULTS: QT dispersion, corrected QTd, and automated QTd were significantly increased in the 24h-ECG compared with the 72h-ECG (60 [range, 20-80] milliseconds vs 40 [range, 0-80] milliseconds, P<.005; mean [SD], 56 [19] vs 36 [21] milliseconds, P<.001; and 50 [range, 14-94] vs 34 [range, 0-84] milliseconds, P<.005, respectively). However, QTd in the 72h-ECG was similar to QTd in the control group. While in the 24h-ECG corrected QTd was significantly greater in patients with large infarcts and large hemorrhages (mean [SD], 70 [20] vs 51 [20] milliseconds, P<.05), in the 72h-ECG corrected QTd was greater in patients with right vs left-sided lesions (mean [SD], 39 [18] vs 24 [18] milliseconds, P<.05). CONCLUSIONS: QT dispersion is increased in the first 24 hours in patients with acute stroke and no cardiovascular disease compared with the control group. Although this finding seems to be related to the size of the lesion rather than to the localization or type of stroke, after 72 hours specific lesion localization could also influence the QTd.

Pure superficial posterior cerebral artery territory infarction in The Lausanne Stroke Registry.

OBJECTIVE: To determine the patterns of clinical presentation, lesion topography, and etiology in patients with ischemic stroke limited to the superficial territory of the posterior cerebral artery (s-PCA). METHODS: In the Lausanne Stroke Registry (LSR, 1983-1998), we determined the patterns of clinical presentation, lesion topography and mechanisms of stroke, among 117 patients with s-PCA infarction (s-PCAI) on brain imaging. RESULTS: s-PCAIs accounted for 30.5 % of all PCA territory ischemic strokes. The presumed etiology was embolism in 64 (54.5 %) patients [cardiac in 51 (43.5 %) and arterial in 13 (11 %)], indeterminate in 38 (32 %), PCA atherothrombosis in 4 (3.4 %), migraine in 4 (3.4 %), other rare causes in 4 (3.4 %), and multiple potential sources of embolism in 3 (2.5 %). The clinical findings were hemianopsia in 78 (67 %), quadrantanopsia in 26 (22 %), and bilateral visual field defects in 8 (7 %). Motor, sensory, or sensorimotor deficits were detected in 14 (12 %), 8 (6.8 %), or 8 (6.8 %) patients, respectively. Neuropsychological dysfunction included memory impairment in 20 (17.5 %; with left [L], right [R], or bilateral [B] lesions in 15, 2, or 3 patients, respectively), dysphasia in 17 (14.5 %; L/B: 14/3), dyslexia with dysgraphia in 5 (4 %; L/B: 4/1), dyslexia without dysgraphia in 10 (8.5 %; L/B: 8/2), hallucinations in 12 (10 %; L/R/B: 5/5/2), visual neglect in 11 (9.5 %; L/R: 2/9), visual agnosia in 10 (8.5 %; L/B: 7/3), prosopagnosia in 7 (6 %; R/B: 4/3), and color dysnomia in 6 (5 %; L: 6). CONCLUSIONS: s-PCAIs are uncommon, representing less than a third of all PCA infarctions. Although embolism is the main cause in 60 % of patients, identification of the emboli source is often not possible. In 1/3 of cases, the stroke mechanism cannot be determined. Neuropsychological deficits are frequent if systematically searched for.

Spectrum of medial medullary infarction: clinical and magnetic resonance imaging findings.

Among 4200 consecutive patients admitted to three hospitals with acute ischemic stroke, we found only 11 patients in whom magnetic resonance imaging (MRI) had proved that they had medial medullary infarction (MMI). In our centers, patients with MMI were less than 1% of those with vertebrobasilar stroke. The infarcts documented by MRI were unilateral in 10 patients and bilateral in one. On clinico-topographical analysis there were four clinical patterns: (1) Classical Dejerine's syndrome was the most frequent, consisting of contralateral hemiparesis, lemniscal sensory loss and ipsilateral lingual palsy in 7 of the eleven patients. (2) Pure hemiparesis was present in 2 patients; (3) Sensorimotor stroke was present in 1 patient with contralateral hemiparesis, hypesthesia and mild decrease in pain sensation without lingual palsy; (4) Bilateral MMI syndrome in 1 patient, accompanied by tetraparesis, bilateral loss of deep sensation, dysphagia, dysphonia and anarthria. Presumed causes of MMI were intrinsic branch penetrator artery disease with concomitant vertebral artery stenosis in 6 of the 11 patients, vertebral artery occlusion in 2, dolichoectatic vertebrobasilar arteries in 2, a source of cardiac embolism in 1. Prognosis at 3 months was favorable in 8 patients, but the patient with bilateral MMI syndrome had persisting motor deficit causing limitation of daily activities, and 2 died from systemic causes. The classical triad of acute MMI facilitates the diagnosis, although the recognition of this syndrome in patients with incomplete manifestations can be difficult and occurs more frequently than commonly thought. Moreover, vertebral artery atherosclerosis and branch atheromatous disease of the penetrating arteries are the main causes of medullary infarction.

Asystole associated with cluster headache.

A 43-year-old man with asystole and syncope occurring during cluster headache attacks is reported. The asystole and syncope attacks disappeared completely following prophylactic therapy with methysergide maleate. To the authors' knowledge, the present case is unique in associating asystole with cluster headache attacks and may be due to hyperactivity of the parasympathetic system.

Stroke and status epilepticus: stroke type, type of status epilepticus, and prognosis.

Even though stroke is known to be a common cause of status epilepticus (SE), the types of stroke or SE that may be associated are not yet clearly defined. The aims of this study were to assess the timing and type of SE in stroke patients and to observe the effects of stroke and the type of SE on the response to treatment and mortality. From May 1998 to May 2001 a total of 121 patients were admitted with SE. Among these, 30 cases (24.8%) of poststroke SE were identified and evaluated. There were 20 early-onset, and 10 late-onset SE. All stroke types were evenly distributed within the early-onset group, whereas only ischaemic stroke was found in the late-onset group. Posterior cerebral artery (PCA) infarcts were significantly more common within the latter (P: 0.0017). Nonconvulsive SE (NCS) was more frequent than convulsive SE (CS) in the early-onset group (P: 0.0352). There was a delay in the time-to-treatment for NCS compared to CS (P: 0.0007). Without, however any effect on the rate of response to first step treatment (intravenous diazepam and phenytoin; P: 0.6334). Thirteen patients died (43.3%) during hospitalisation. Disability was significantly associated with higher mortality in the early-onset group (P: 0.0201). As a conclusion, NCS seems to be an important issue in stroke, thus requiring a high degree of suspicion in an acute stroke setting to avoid further neuronal injury and morbidity.