Potential effects of a mobile stroke unit on time to treatment and outcome in patients treated with thrombectomy or thrombolysis: A Danish-German cross-border analysis.

BACKGROUND AND PURPOSE: A mobile stroke unit (MSU) reduces delays in stroke treatment by allowing thrombolysis on board and avoiding secondary transports. Due to the beneficial effect in comparison to conventional emergency medical services, current guidelines recommend regional evaluation of MSU implementation. METHODS: In a descriptive study, current pathways of patients requiring a secondary transport for mechanical thrombectomy were reconstructed from individual patient records within a Danish (n = 122) and an adjacent German region (n = 80). Relevant timestamps included arrival times (on site, primary hospital, thrombectomy centre) as well as the initiation of acute therapy. An optimal MSU location for each region was determined. The resulting time saving was translated into averted disability-adjusted life years (DALYs). RESULTS: For each region, the optimal MSU location required a median driving time of 35 min to a stroke patient. Time savings in the German region (median [Q1; Q3]) were 7 min (-15; 31) for thrombolysis and 35 min (15; 61) for thrombectomy. In the Danish region, the corresponding time savings were 20 min (8; 30) and 43 min (25; 66). Assuming 28 thrombectomy cases and 52 thrombolysis cases this would translate to 9.4 averted DALYs per year justifying an annual net MSU budget of $0.8M purchasing power parity dollars (PPP-$) in the German region. In the Danish region, the MSU would avert 17.7 DALYs, justifying an annual net budget of PPP-$1.7M. CONCLUSION: The effects of an MSU can be calculated from individual patient pathways and reflect differences in the hospital infrastructure between Denmark and Germany.

Aß38 and Aß43 do not differentiate between Alzheimer's disease and cerebral amyloid angiopathy.

Differential diagnosis between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) using cerebrospinal fluid (CSF) biomarkers is challenging. A recent study suggested that the addition of Aß38 and Aß43 to a standard AD biomarker panel (Aß40, Aß42, t-tau, p-tau) to improve the differential diagnosis. We tested this hypothesis in an independent German cohort of CAA and AD patients and controls using the same analytical techniques. We found excellent discrimination between AD and controls and between CAA and controls, but not between AD and CAA. Adding Aß38 and Aß43 to the panel did not improve the discrimination between AD and CAA.

[Improvement of the treatment of patients with spastic movement disorder after stroke]. / Verbesserung der Versorgung von Patientinnen und Patienten mit spastischer Bewegungsstörung nach Schlaganfall.

BACKGROUND: Spastic movement disorder (SMD) develops in up to 43% of cases as a sequela of stroke. In the event of a functionally relevant or daily life impairing SMD or to avoid an impending complication, the medicinal treatment of a focal, multifocal and segmental increase in muscle tone with botulinum neurotoxin A (BoNT-A) is recommended; however, treatment data reveal a lack of guideline-conform treatment with BoNT­A in Germany. OBJECTIVE: The aim of the reported expert meeting was to discuss solutions to the incorrect treatment and undertreatment of patients with SMD and to formulate consensus recommendations to improve the care situation. METHODS: At a consensus meeting held in April 2022, eight experts from the fields of neurology, physical medicine and rehabilitation discussed the causes for the incorrect treatment and undertreatment and formulated consensus solution approaches. RESULTS: Possible reasons for the current incorrect treatment and undertreatment in SMD management in Germany include insufficient awareness of SMD among physicians, a lack of treatment capacities, a lack of information transfer in discharge management as well as staff shortages in the specialized inpatient and outpatient SMD treatment centers. The committee therefore recommended a patient pathway in which affected patients with SMD are provided with correctly implemented BoNT­A treatment in combination with physical measures. CONCLUSION: The recommended treatment pathway for use in stroke patients is intended to close gaps in care and thus ensure guideline-conform treatment of post-stroke SMD.

Preserved Corticospinal Tract Revealed by Acute Perfusion Imaging Relates to Better Outcome After Thrombectomy in Stroke.

BACKGROUND: The indication for mechanical thrombectomy (MT) in stroke patients with large vessel occlusion has been constantly expanded over the past years. Despite remarkable treatment effects at the group level in clinical trials, many patients remain severely disabled even after successful recanalization. A better understanding of this outcome variability will help to improve clinical decision-making on MT in the acute stage. Here, we test whether current outcome models can be refined by integrating information on the preservation of the corticospinal tract as a functionally crucial white matter tract derived from acute perfusion imaging. METHODS: We retrospectively analyzed 162 patients with stroke and large vessel occlusion of the anterior circulation who were admitted to the University Medical Center Lübeck between 2014 and 2020 and underwent MT. The ischemic core was defined as fully automatized based on the acute computed tomography perfusion with cerebral blood volume data using outlier detection and clustering algorithms. Normative whole-brain structural connectivity data were used to infer whether the corticospinal tract was affected by the ischemic core or preserved. Ordinal logistic regression models were used to correlate this information with the modified Rankin Scale after 90 days. RESULTS: The preservation of the corticospinal tract was associated with a reduced risk of a worse functional outcome in large vessel occlusion-stroke patients undergoing MT, with an odds ratio of 0.28 (95% CI, 0.15-0.53). This association was still significant after adjusting for multiple confounding covariables, such as age, lesion load, initial symptom severity, sex, stroke side, and recanalization status. CONCLUSIONS: A preinterventional computed tomography perfusion-based surrogate of corticospinal tract preservation or disconnectivity is strongly associated with functional outcomes after MT. If validated in independent samples this concept could serve as a novel tool to improve current outcome models to better understand intersubject variability after MT in large vessel occlusion stroke.

Glyoxal in hyperglycaemic ischemic stroke - a cohort study.

BACKGROUND: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke. METHODS: In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested. RESULTS: Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid Nδ-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids Nε-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal. CONCLUSIONS: The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke.

Early or late initiation of dabigatran versus vitamin-K-antagonists in acute ischemic stroke or TIA: The PRODAST study.

BACKGROUND: The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications. AIMS: In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA. METHODS: PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early (⩽ 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. RESULTS: Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10-2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00-13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints. CONCLUSIONS: The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate.

Characterizing mixed location hemorrhages/microbleeds with CSF markers.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. PATIENTS AND METHODS: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. RESULTS: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. CONCLUSION: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

Acute Stroke and Atrial Fibrillation: Risk of Incorrect NOAC Dosage When Estimating Renal Function From Plasma Creatinine Only.

Background: Cardioembolic stroke (CS) due to atrial fibrillation (AF) bears a high risk of unfavorable outcome. Treatment with a non-vitamin K antagonist oral anticoagulant (NOAC) reduces this risk. NOAC dosage occurs on a thin line during the acute phase of the stroke unit when the patient is threatened by both recurrent CS and a hemorrhagic stroke. It is often adapted to renal function-usually glomerular filtration rate (GFR)-to prevent both under- and overdosing. This study investigates the hypothetical risk of incorrect NOAC dosage after acute stroke when relying on plasma creatinine alone in comparison to a more exact renal function assessment including urine collection. Methods: In a cohort study on consecutive 481 patients treated in a stroke unit with acute stroke and AF, the GFR estimated from plasma creatinine (eGFR) was compared to concurrent creatinine clearance measurement (CrCl) from urine collection regarding the hypothetically derived NOAC dosage. Results: The risk of incorrect dosage (mean, 95% confidence interval) was 6.9% (4.8-9.5), 26% (23-31), 38% (33-42), and 20% (16-23) for apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The overall risk for incorrect dosage of any NOAC was 23% (21-25). Thresholds for age and admission eGFR were optimized to achieve an overall risk below 5% by additional CrCl measurements in selected patients (apixaban <36 ml/min and any age, dabigatran <75 ml/min and >70 y, edoxaban >36 ml/min and >58 y, rivaroxaban <76 ml/min and >75 y, any NOAC <81 ml/min and >54 y). The resulting portion of patients requiring an additional CrCl measurement was 10, 60, 80, 55, and 65% for apixaban, dabigatran, edoxaban, rivaroxaban, and any NOAC, respectively. Conclusions: There is a considerable risk of incorrect NOAC dosage in patients with acute CS treated in a stroke unit that can be lowered by targeted CrCl measurements in selected patients.

On the quest for hidden ovarian teratomas in therapy-refractory anti-NMDA receptor encephalitis: a case report.

BACKGROUND: Anti-NMDA-receptor (anti-NMDAR) encephalitis is often associated with ovarian teratoma (OT). The best management of anti-NMDAR encephalitis patients with normal imaging studies (pelvic ultrasound/MRI) but clinically high risk of OT (e.g., female, adult, black) is unclear. We report on the surprising diagnostic quest in a young black woman with anti-NMDAR encephalitis, in whom invasive procedures could finally disclose two OTs that were hidden from the initial non-invasive diagnostics. CASE REPORT: The patient presented with a one-week history of psychotic symptoms, developing oro-facial dyskinesia, seizures and coma, eventually requiring mechanical ventilation. NMDA-receptor antibodies were positive in serum and cerebrospinal fluid. Pelvic MRI and transabdominal ultrasound were normal. Exploratory laparoscopy was also unremarkable at first, but due to a suspicious echogenic mass (15 mm) in the right ovary on perioperative transvaginal ultrasound, an ovarian incision was performed which led to the detection of a first OT and its removal via ovarian-preserving cystectomy. Following a severe therapy-refractory clinical course despite aggressive immunotherapy and tumor removal, 6 months later bilateral oophorectomy was performed as ultima ratio, disclosing a second micro-OT (6 mm) in the left ovary. Unfortunately, the patient has not improved clinically yet. CONCLUSIONS: In therapy-refractory anti-NMDAR encephalitis with high risk of OT, small and bilateral OTs hidden from primary non-invasive diagnostics should be considered, which may trigger further invasive diagnostic procedures.

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis.

BACKGROUND: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. METHODS: Beta-amyloid 1-40 (Aß40), beta-amyloid 1-42 (Aß42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. RESULTS: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. CONCLUSION: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.

Paraneoplastic encephalomyeloradiculits with multiple autoantibodies against ITPR-1, GFAP and MOG: case report and literature review.

BACKGROUND: Recently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies. CASE PRESENTATION AND LITERATURE REVIEW: A 44-year old caucasian woman with a flu-like prodrome presented with meningism, progressive cerebellar signs and autonomic symptoms, areflexia, quadriplegia and respiratory insufficiency. MRI showed diffuse bilateral T2w-hyperintense brain lesions in the cortex, white matter, the corpus callosum as well as a longitudinal lesion of the medulla oblongata and the entire spinal cord. Anti-ITPR1, anti-GFAP and anti-MOG antibodies were detected in cerebrospinal fluid along with lymphocytic pleocytosis. Borderline tumor of the ovary was diagnosed. Thus, the disease of the patient was deemed to be paraneoplastic. The patient was treated by surgical removal of tumor, steroids, immunoglobulins, plasma exchange and rituximab. Four months after presentation, the patient was still tetraplegic, reacted with mimic expressions to pain or touch and could phonate solitary vowels. An extensive literature research was performed. CONCLUSION: Our case and the literature review illustrate that multiple glial and neuronal autoantibodies can co-occur, that points to a paraneoplastic etiology, above all ovarian teratoma or thymoma. Clinical manifestation can be a mixture of typically associated syndromes, e.g. ataxia associated with anti-ITPR1 antibodies, encephalomyelitis with anti-GFAPα antibodies and longitudinal extensive myelitis with anti-MOG antibodies.

CT Hypoperfusion-Hypodensity Mismatch to Identify Patients With Acute Ischemic Stroke Within 4.5 Hours of Symptom Onset.

BACKGROUND AND OBJECTIVES: To test the hypothesis that CT hypoperfusion-hypodensity mismatch identifies patients with ischemic stroke within 4.5 hours of symptom onset. METHODS: We therefore performed the Retrospective Multicenter Hypoperfusion-Hypodensity Mismatch for The identification of Patients With Stroke Within 4.5 Hours study of patients with acute ischemic stroke and known time of symptom onset. The predictive values of hypoperfusion-hypodensity mismatch for the identification of patients with symptom onset within 4.5 hours were the main outcome measure. RESULTS: Of 666 patients, 548 (82.3%) had multimodal CT within 4.5 hours and 118 (17.7%) beyond 4.5 hours. Hypoperfusion-hypodensity mismatch was visible in 516 (94.2%) patients with symptom onset within and in 30 (25.4%) patients beyond 4.5 hours. CT hypoperfusion-hypodensity mismatch identified patients within 4.5 hours of stroke onset with 94.2% (95% confidence interval [CI] 91.9%-95.8%) sensitivity, 74.6% (95% CI 66.0%-81.6%) specificity, 94.5% (95% CI 92.3%-96.1%) positive predictive value, and 73.3% (95% CI 64.8%-80.4%) negative predictive value. Interobserver agreement for hypoperfusion-hypodensity mismatch was substantial (κ = 0.61, 95% CI 0.53-0.69). DISCUSSION: Patients with acute ischemic stroke with absence of a hypodensity on native CT (NCCT) within the hypoperfused core lesion on perfusion CT (hypoperfusion-hypodensity mismatch) are likely to be within the time window of thrombolysis. Applying this method may guide the decision to use thrombolysis in patients with unknown time of stroke onset. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04277728. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CT hypoperfusion-hypodensity mismatch identifies patients with stroke within 4.5 hours of onset.

Development and reliability of the histological THROMBEX-classification rule for thrombotic emboli of acute ischemic stroke patients.

BACKGROUND: Thrombus histology has become a potential diagnostic tool for the etiology assessment of patients with ischemic stroke caused by embolic proximal vessel occlusion. We validated a classification rule that differentiates between cardiac and arteriosclerotic emboli in individual stroke patients. We aim to describe in detail the development of this classification rule and disclose its reliability. METHODS: The classification rule is based on the hypothesis that cardiac emboli arise out of separation thrombi and arteriosclerotic emboli result from agglutinative thrombi. 125 emboli recovered by thrombectomy from stroke patients and 11 thrombi serving as references for cardiac (n = 5) and arteriosclerotic emboli (n = 6) were Hematoxylin and eosin, Elastica-van Gieson and CD61 stained and rated independently by two histopathologists blinded to the presumed etiology by several pre-defined criteria. Intra- and interobserver reliabilities of all criteria were determined. Out of the different criteria, three criteria with the most satisfactory reliability values were selected to compose the classification rule that was finally adjusted to the reference thrombi. Reliabilities of the classification rule were calculated by using the emboli of stroke patients. RESULTS: The classification rule reached intraobserver reliabilities for the two raters of 92.9% and 68.2%, respectively. Interobserver reliability was 69.9%. CONCLUSIONS: A new classification rule for emboli obtained from thrombectomy was established. Within the limitations of histological investigations, it is reliable and able to distinguish between cardioembolic and arteriosclerotic emboli.

First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule.

Endovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included. The corresponding emboli were histologically evaluated by two raters blinded to the etiology of stroke by means of a novel classification rule. Presumed etiology and classification results were compared. Agreement concerning cardiac emboli was 72.2% (95% CI: 58.4-83.5) for rater I and 78.2% (95% CI: 65.0-88.2) for rater II. Agreement concerning arteriosclerotic emboli was 70.4% (95% CI: 49.8-86.3) for rater I and 74.1% (95% CI: 53.7-88.9) for rater II. Overall agreement reached 71.6% (95% CI: 60.5-81.1) for rater I and 76.8% (95% CI: 66.2-85.4) for rater II. Within the limits of generally restricted accuracy of histological evaluations, the classification rule differentiates between cardiac and arteriosclerotic emboli of acute ischemic stroke patients. Further improvement is needed to provide valuable complementary data for stroke etiology workup.

Explicit Diagnostic Criteria for Transient Ischemic Attacks Used in the Emergency Department Are Highly Sensitive and Specific.

BACKGROUND: Making a correct diagnosis of a transient ischemic attack (TIA) is prone to errors because numerous TIA mimics exist and there is a shortage of evidence-based diagnostic criteria for TIAs. In this study, we applied for the first time the recently proposed explicit diagnostic criteria for transient ischemic attacks (EDCT) to a group of patients presenting to the emergency department of a large German tertiary care hospital with a suspected TIA. The aim was to determine the sensitivity and specificity of the EDCT in its clinical application. METHODS: A total of 128 patients consecutively presenting to the emergency department of the University Hospital of Lübeck, Germany, under the suspicion of a TIA were prospectively interviewed about their clinical symptoms at the time of presentation. The diagnosis resulting from applying the EDCT was compared to the diagnosis made independently by the senior physicians performing the usual diagnostic work-up ("gold standard"), allowing calculation of sensitivity and specificity of the EDCT. RESULTS: EDCT achieved a sensitivity of 96% and a specificity of 88%. When adding the additional criterion F ("the symptoms may not be better explained by another medical or mental disorder"), specificity significantly increased to 98%. CONCLUSIONS: The data show that the EDCT in its modified version as proposed by us are a highly useful tool for clinicians. They display a high sensitivity and specificity to accurately diagnose TIAs in patients referred to the emergency department with a suspected TIA.

Elevation of intracranial pressure affects the relationship between hemoglobin concentration and neuronal activation in human somatosensory cortex.

During neuronal activation, a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) occurs which is the basis of functional brain imaging with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Elevated intracranial pressure (eICP) has been shown to impair functional deoxy-Hb changes. This study investigated this effect and its relation to the underlying neuronal activity in the human primary somatosensory cortex (SI). Functional near-infrared spectroscopy (fNIRS) during somatosensory evoked potentials (SEP) monitoring was performed on 75 subjects during conditions of median nerve stimulation (MNS) and resting state, combined with normal breathing (NB) and eICP by escalating breathing maneuvers (breath holding [BH], Valsalva maneuver with 15 mmHg [V15] and 35 mmHg expiratory pressure [V35]). During NB, fNIRS revealed a typical oxygenated hemoglobin concentration (oxy-Hb) increase with deoxy-Hb decrease during MNS enabling SI brain mapping. Breathing maneuvers associated eICP produced a known global change of oxy-Hb and deoxy-Hb with and without MNS. When subtracting measurements during resting state from measurements during MNS, neither functional oxy-Hb nor deoxy-Hb changes could be recovered while SEPs remained unchanged. In conclusion, Valsalva-induced eICP prevents oxy-Hb and deoxy-Hb changes during neuronal activation in SI. This finding raises questions on the validity of oxy-Hb- and deoxy-Hb-based brain imaging (e.g., BOLD-fMRI) during eICP.

ICHD-3 is significantly more specific than ICHD-3 beta for diagnosis of migraine with aura and with typical aura.

BACKGROUND: In the emergency room, distinguishing between a migraine with aura and a transient ischemic attack (TIA) is often not straightforward and mistakes can be harmful to both the patient and to society. To account for this difficulty, the third edition of the International Classification of Headache disorders (ICHD-3) changed the diagnostic criteria of migraine with aura. METHODS: One hundred twenty-eight patients referred to the emergency room at the University Hospital of Lübeck, Germany with a suspected TIA were prospectively interviewed about their symptoms leading to admission shortly after initial presentation. The diagnosis that resulted from applying the ICHD-3 and ICHD-3 beta diagnostic criteria was compared to the diagnosis made independently by the treating physicians performing the usual diagnostic work-up. RESULTS: The new ICHD-3 diagnostic criteria for migraine with aura and migraine with typical aura display an excellent specificity (96 and 98% respectively), and are significantly more specific than the previous ICHD-3 beta classification system when it comes to diagnosing a first single attack (probable migraine with aura and probable migraine with typical aura). CONCLUSIONS: The ICHD-3 is a highly useful tool for the clinical neurologist in order to distinguish between a migraine with aura and a TIA, already at the first point of patient contact, such as in the emergency department or a TIA clinic.

Patients with low Alberta Stroke Program Early CT Score (ASPECTS) but good collaterals benefit from endovascular recanalization.

BACKGROUND: Benefit of thrombectomy in patients with a low initial Alberta Stroke Program Early CT Score (ASPECTS) is still uncertain. We hypothesized that, despite low ASPECTS, patients may benefit from endovascular recanalization if good collaterals are present. METHODS: Ischemic stroke patients with large vessel occlusion in the anterior circulation and an ASPECTS of ≤5 were analyzed. Collateral status (CS) was assessed using a 5-point-scoring system in CT angiography with poor CS defined as CS=0-1. Clinical outcome was determined using the modified Rankin Scale (mRS) score after 90 days. Edema formation was measured in admission and follow-up CT by net water uptake. RESULTS: 27/100 (27%) patients exhibited a CS of 2-4. 50 patients underwent successful vessel recanalization and 50 patients had a persistent vessel occlusion. In multivariable logistic regression analysis, collateral status (OR 3.0; p=0.003) and vessel recanalization (OR 12.2; p=0.009) significantly increased the likelihood of a good outcome (mRS 0-3). A 1-point increase in CS was associated with 1.9% (95% CI 0.2% to 3.7%) lowered lesion water uptake in follow-up CT . CONCLUSION: Endovascular recanalization in patients with ASPECTS of ≤5 but good collaterals was linked to improved clinical outcome and attenuated edema formation. Collateral status may serve as selection criterion for thrombectomy in low ASPECTS patients.

Antibodies against neural antigens in patients with acute stroke: joint results of three independent cohort studies.

BACKGROUND AND PURPOSE: Ischemic stroke (IS) and hemorrhagic stroke (HemS) typically lead to a breakdown of the blood-brain barrier with neural antigen presentation. This presentation could potentially generate destructive auto-immune responses. Pre-existing antineuronal and antiglial antibodies (AA), predominantly NMDA receptor antibodies, have been reported in patients with stroke. This article summarizes three independent prospective studies, the Lübeck cohort (LC), Barcelona cohort (BC), and Heidelberg cohort (HC), exploring the frequency and clinical relevance of AA in patients with acute stroke (AS). METHODS: In all cohorts together, 344 consecutive patients admitted with AS (322 × IS, 22 × HemS) were screened for AA in serum at admission. Clinical outcome parameters as well as a second AA screening were available at 30 days in the LC or at 90 days in the BC. A control group was included in the BC (20 subjects free from neurological disease) and the HC (78 neurological and ophthalmological patients without evidence for stroke). RESULTS: The rate of positivity for AA was similar in control subjects and AS patients (13%, 95% CI [7%, 22%] vs. 13%, 95% CI [10%, 17%]; p = 0.46) with no significant difference between cohorts (LC 25/171, BC 12/75, HC 9/98). No patient had developed new AA after 30 days, whereas 2 out of 60 patients had developed new AA after 90 days. AA positive patients did not exhibit significant differences to AA negative patients in stroke subtype (LC, BC), initial stroke severity (BC, LC, HC), infarct volume (BC), and functional status at admission (BC, LC, HC) and follow-up (BC, LC). CONCLUSIONS: AS does not induce AA to a relevant degree. Pre-existing AA can be found in the serum of stroke patients, but they do not have a significant association with clinical features and outcomes.

Transient Generalized Chorea in Influenza A Encephalopathy.

Background: Influenza A infections are a rare cause of movement disorders. Previously described patients have suffered from acute-onset myoclonus and/or dystonia or post-viral parkinsonism. Case Report: We present the case of a 74-year-old female patient with transient generalized chorea due to influenza A-mediated encephalopathy. Discussion: We discuss whether the clinical presentation and the magnetic resonance imaging changes may be attributable to cytokine-mediated encephalopathy or to direct cytotoxic effects of the virus. Additionally, we would like to make clinicians aware of this clinical sign in the context of viral encephalopathy.