Clinical Course and Recurrence in Transient Global Amnesia: A Study From the TEMPiS Telestroke Network.

BACKGROUND AND PURPOSE: While the clinical hallmarks of transient global amnesia (TGA) are well defined, its pathophysiological causes are poorly understood. Specifically, risk factors for recurrences are yet to be determined. METHODS: This retrospective study analyzed TGA cases diagnosed and treated within the TEMPiS telestroke network and a university stroke center in Germany. Demographic and clinical data were assessed and characteristics of TGA episodes were recorded, such as season of occurrence, trigger factors, duration, and concomitant symptoms. Follow-up of the potential recurrence of TGA was performed using a standardized questionnaire. RESULTS: Overall 109 patients were included (age 64±8 years [mean±SD], 59.6% female). The most common vascular risk factor was arterial hypertension (60.6%), and other concomitant conditions included migraine (11.9%), hypothyroidism (22.9%), and atrial fibrillation (4.6%). The most frequent concomitant clinical feature accompanying the TGA episode at admission was elevated blood pressure (48.6%). Nineteen patients experienced at least one recurrent TGA episode. Migraine and hypothyroidism were only observed in subjects with a single TGA episode without recurrence (migraine: 14.4% without recurrence vs. none in the recurrence group, p=0.02; hypothyroidism: 27.8% without recurrence vs. none in the recurrence group, p=0.009). In contrast, atrial fibrillation was more common in subjects with TGA recurrence (p<0.001). CONCLUSIONS: Arterial hypertension is prevalent in TGA patients, with elevated blood pressure being the most-frequent concomitant condition. In our cohort, recurrence of TGA occurred in approximately one-fifth of patients. Concomitant conditions such as migraine, hypothyroidism, and atrial fibrillation occurred at different frequencies in the two groups.

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. METHODS: We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). RESULTS: We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). CONCLUSIONS: Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

OBJECTIVE: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: ß -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice.

PURPOSE: The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. METHODS: We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. RESULTS: Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3-14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. CONCLUSION: PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.

Interdisciplinary Decision Making in Hemorrhagic Stroke Based on CT Imaging-Differences Between Neurologists and Neurosurgeons Regarding Estimation of Patients' Symptoms, Glasgow Coma Scale, and National Institutes of Health Stroke Scale.

Background and Purpose: Acute intracerebral hemorrhage (ICH) requires rapid decision making toward neurosurgery or conservative neurological stroke unit treatment. In a previous study, we found overestimation of clinical symptoms when clinicians rely mainly on cerebral computed tomography (cCT) analysis. The current study investigates differences between neurologists and neurosurgeons estimating specific scores and clinical symptoms. Methods: Overall, 14 neurologists and 15 neurosurgeons provided clinical estimates and National Institutes of Health Stroke Scale (NIHSS) as well as Glasgow Coma Scale (GCS) based on cCT images and basic information of 50 patients with hypertensive and lobar ICH. Subgroup analyses were performed for the different professions (neurologists vs. neurosurgeons) and bleeding subtypes (typical location vs. atypical). The differences between the actual GCS and NIHSS scores and the cCT-imaging-based estimated scores were depicted as Bland-Altman plots and negative and positive predictive value (NPV and PPV) for prediction of clinical relevant items. ΔNIHSS points (ΔGCS points) were calculated as the difference between actual and rated NIHSS (GCS) including 95% confidence interval (CI). Results: Mean ΔGCS points for neurosurgeons was 1.16 (95% CI: -2.67-4.98); for neurologists, 0.99 (95% CI: -2.58-4.55), p = 0.308; mean ΔNIHSS points for neurosurgeons was -2.95 (95% CI: -12.71-6.82); for neurologists, -0.33 (95% CI: -9.60-8.94), p < 0.001. NPV and PPV for stroke symptoms were low, with large differences between different symptoms, bleeding subtypes, and professions. Both professions had more problems in proper rating of specific clinic-neurological symptoms than rating scores. Conclusion: Our results stress the need for joint decision making based on detailed neurological examination and neuroimaging findings also in telemedicine.

Primary cCT Imaging Based Clinico-Neurological Assessment-Calling for Addition of Telestroke Video Consultation in Patients With Intracerebral Hemorrhage.

Background and Purpose: Intracerebral hemorrhage (ICH) requires rapid decision making to decrease morbidity and mortality although time frame and optimal therapy are still ill defined. Ideally, specialized neurologists, neurosurgeons, and (neuro-) radiologists who know the patient's clinical status and their cerebral computed tomography imaging (cCT) make a joint decision on the clinical management. However, in telestroke networks, a shift toward cCT imaging criteria used for decision making can be observed for practical reasons. Here we investigated the "reverse correlation" from cCT imaging to the actual clinical presentation as evaluated by the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). Methods: CCT images and basic information (age, sex, and time of onset) of 50 patients with hypertensive and lobar ICH were presented to 14 experienced neurologists and 15 neurosurgeons. Based on this information, the NIHSS and GCS scores were estimated for each patient. The differences between the actual GCS and NIHSS scores and the cCT-imaging-based estimated scores were plotted in a bland-Altman plot. Results: The average estimated GCS score mainly based on cCT imaging was 12. 4 ± 2.8 (actual value: 13.0 ± 2.5; p = 0.100), the estimated NIHSS score was 13.9 ± 9.1 (actual value: 10.8 ± 7.3; p < 0.001). Thus, in cCT-imaging-based evaluation, the neurological status of patients especially employing the NIHSS was estimated poorer, particularly in patients with lobar ICH. "Reverse clinical" evaluation based on cCT-imaging alone may increase the rate of intubation and secondary transferal and neurosurgical treatment. Telestroke networks should consider both, videoassessment of the actual clinical picture and cCT-imaging findings to make appropriate acute treatment decisions.

Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks.

BACKGROUND AND PURPOSE: Up to 30% of acute stroke evaluations are deemed stroke mimics, and these are common in telestroke as well. We recently published a risk prediction score for use during telestroke encounters to differentiate stroke mimics from ischemic cerebrovascular disease derived and validated in the Partners TeleStroke Network. Using data from 3 distinct US and European telestroke networks, we sought to externally validate the TeleStroke Mimic (TM) score in a broader population. METHODS: We evaluated the TM score in 1930 telestroke consults from the University of Utah, Georgia Regents University, and the German TeleMedical Project for Integrative Stroke Care Network. We report the area under the curve in receiver-operating characteristic curve analysis with 95% confidence interval for our previously derived TM score in which lower TM scores correspond with a higher likelihood of being a stroke mimic. RESULTS: Based on final diagnosis at the end of the telestroke consultation, there were 630 of 1930 (32.6%) stroke mimics in the external validation cohort. All 6 variables included in the score were significantly different between patients with ischemic cerebrovascular disease versus stroke mimics. The TM score performed well (area under curve, 0.72; 95% confidence interval, 0.70-0.73; P<0.001), similar to our prior external validation in the Partners National Telestroke Network. CONCLUSIONS: The TM score's ability to predict the presence of a stroke mimic during telestroke consultation in these diverse cohorts was similar to its performance in our original cohort. Predictive decision-support tools like the TM score may help highlight key clinical differences between mimics and patients with stroke during complex, time-critical telestroke evaluations.

Thrombolysis in Postoperative Stroke.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) is beneficial in reducing disability in selected patients with acute ischemic stroke. There are numerous contraindications to IVT. One is recent surgery. The aim of this study was to analyze the safety of IVT in patients with postoperative stroke. METHODS: Data of consecutive IVT patients from the Telemedical Project for Integrative Stroke Care thrombolysis registry (February 2003 to October 2014; n=4848) were retrospectively searched for keywords indicating preceding surgery. Patients were included if surgery was performed within the last 90 days before stroke. The primary outcome was defined as surgical site hemorrhage. Subgroups with major/minor surgery and recent/nonrecent surgery (within 10 days before IVT) were analyzed separately. RESULTS: One hundred thirty-four patients underwent surgical intervention before IVT. Surgery had been performed recently (days 1-10) in 49 (37%) and nonrecently (days 11-90) in 85 patients (63%). In 86 patients (64%), surgery was classified as major, and in 48 (36%) as minor. Nine patients (7%) developed surgical site hemorrhage after IVT, of whom 4 (3%) were serious, but none was fatal. One fatal bleeding occurred remotely from surgical area. Rate of surgical site hemorrhage was significantly higher in recent than in nonrecent surgery (14.3% versus 2.4%, respectively, odds ratioadjusted 10.73; 95% confidence interval, 1.88-61.27). Difference between patients with major and minor surgeries was less distinct (8.1% and 4.2%, respectively; odds ratioadjusted 4.03; 95% confidence interval, 0.65-25.04). Overall in-hospital mortality was 8.2%. Intracranial hemorrhage occurred in 9.7% and was asymptomatic in all cases. CONCLUSIONS: IVT may be administered safely in postoperative patients as off-label use after appropriate risk-benefit assessment. However, bleeding risk in surgical area should be taken into account particularly in patients who have undergone surgery shortly before stroke onset.

Myopathy in Childhood Muscle-Specific Kinase Myasthenia Gravis.

BACKGROUND: Adult and pediatric patients suffering from MuSK (muscle-specific kinase) -antibody positive myasthenia gravis exhibit similar features to individuals with acetylcholine receptor (AChR) antibodies, but they differ in several characteristics such as a predominant bulbar, respiratory and neck weakness, a generally worse disease severity and a tendency to develop muscle atrophy. Muscle atrophy is a rare phenomenon that is usually restricted to the facial muscles. RESULTS: We describe a girl with MuSK-antibody positive myasthenia gravis who developed a myopathy with severe generalized muscular weakness, muscle atrophy, and myopathic changes on electromyography. CONCLUSION: This is the first published example of a generalized myopathic syndrome in myasthenia gravis. We review the relevant literature and discuss the hypothesis of a mitochondrial myopathy as a pathogenic mechanism in MuSK-antibody positive myasthenia gravis.

Inventory of a Neurological Intensive Care Unit: Who Is Treated and How Long?

Purpose. To characterize indications, treatment, and length of stay in a stand-alone neurological intensive care unit with focus on comparison between ventilated and nonventilated patient. Methods. We performed a single-center retrospective cohort study of all treated patients in our neurological intensive care unit between October 2006 and December 2008. Results. Overall, 512 patients were treated in the surveyed period, of which 493 could be included in the analysis. Of these, 40.8% had invasive mechanical ventilation and 59.2% had not. Indications in both groups were predominantly cerebrovascular diseases. Length of stay was 16.5 days in mean for ventilated and 3.6 days for nonventilated patient. Conclusion. Most patients, ventilated or not, suffer from vascular diseases with further impairment of other organ systems or systemic complications. Data reflects close relationship and overlap of treatment on nICU with a standardized stroke unit treatment and suggests, regarding increasing therapeutic options, the high impact of acute high-level treatment to reduce consequential complications.

Intracranial hemorrhage: frequency, location, and risk factors identified in a TeleStroke network.

Intracranial hemorrhages are associated with high rates of disability and mortality. Telemedicine in general provides clinical healthcare at a distance by using videotelephony and teleradiology and is used particularly in acute stroke care medicine (TeleStroke). TeleStroke considerably improves quality of stroke care (for instance, by increasing thrombolysis) and may be valuable for the management of intracranial hemorrhages in rural hospitals and hospitals lacking neurosurgical departments, given that surgical/interventional therapy is only recommended for a subgroup of patients. The aim of this study was to analyze the frequency, anatomical locations of intracranial hemorrhage, risk factors, and the proportion of patients transferred to specialized hospitals. We evaluated teleconsultations conducted between 2008 and 2010 in a large cohort of patients consecutively enrolled in the Telemedical Project for Integrated Stroke Care (TEMPiS) network. In cases in which intracranial hemorrhage was detected, all images were re-examined and analyzed with a focus on frequency, location, risk factors, and further management. Overall, 6187 patients presented with stroke-like symptoms. Intracranial hemorrhages were identified in 631 patients (10.2%). Of these, intracerebral hemorrhages were found in 423 cases (67.0%), including 174 (41.1%) in atypical locations and 227 (53.7%) in typical sites among other locations. After 14 days of hospitalization in community facilities, the mortality rate in patients with intracranial hemorrhages was 15.1% (95/631). Two hundred and twenty-three patients (35.3%) were transferred to neurological/neurosurgical hospitals for diagnostic workup or additional treatment. Community hospitals are confronted with patients with intracranial hemorrhage, whose management requires specific neurosurgical and hematological expertise with respect to hemorrhage subtype and clinical presentation. TeleStroke networks help select patients who need advanced neurological and/or neurosurgical care. The relatively low proportion of interhospital transfers shown in this study reflects a differentiated decision process on the basis of both guidelines and standard operating procedures.

Hyperperfusion syndrome after MCA embolectomy - a rare complication?

PATIENT: Female, 78 FINAL DIAGNOSIS: Cerebral hyperperfusion syndrome Symptoms: - MEDICATION: - Clinical Procedure: Endovascular embolectomy Specialty: Neurology. OBJECTIVE: Unknown ethiology. BACKGROUND: Cerebral hyperperfusion syndrome (cHS) is a well known but rare complication after carotid endarterectomy, carotid angioplasty with stenting, and stenting of intracranial arterial stenosis. The clinical presentation may vary from acute onset of focal oedema (stroke-like presentation) and intracerbral hemorrhage to delayed (>24h hours after the procedure) presentation with seizures, focal motor weakness, or late intracerebral hemorrhage. The incidence of cHS after carotid endarterectomy ranges from 0-3% and defined as an increase of the ipsilateral cerebral blood flow up to 40% over baseline in ultrasound. CASE REPORT: We present a case of a 78-year-old woman with an acute ischemic stroke due to left side middle cerebral artery territory with right sided hemiparesis and aphasia (NIHSS 16). After systemic thrombolysis embolectomy using a retractable stent (Solitaire(®) device) was performed and resulted in complete and successful recanalization of MCA including its branches about 210 minutes after symptom onset but, partial dislocation of thrombotic material into the anterior cerebral artery (ACA). CONCLUSIONS: Cerebral hyperperfusion syndrome should be considered in patients with clinical deterioration after successful recanalisation and the early diagnosis and treatment may be important for neurological outcome after endovascular embolectomy.

Amyloid-ß contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-ß (Aß) deposition in the blood-brain barrier (BBB). CAA contributes to injuries of the neurovasculature including lobar hemorrhages, cortical microbleeds, ischemia, and superficial hemosiderosis. We postulate that CAA pathology is partially due to Aß compromising the BBB. METHODS: We characterized 19 patients with acute stroke with "probable CAA" for neurovascular pathology based on MRI and clinical findings. Also, we studied the effect of Aß on the expression of tight junction proteins and matrix metalloproteases (MMPs) in isolated rat brain microvessels. RESULTS: Two of 19 patients with CAA had asymptomatic BBB leakage and posterior reversible encephalopathic syndrome indicating increased BBB permeability. In addition to white matter changes, diffusion abnormality suggesting lacunar ischemia was found in 4 of 19 patients with CAA; superficial hemosiderosis was observed in 7 of 9 patients. Aß(40) decreased expression of the tight junction proteins claudin-1 and claudin-5 and increased expression of MMP-2 and MMP-9. Analysis of brain microvessels from transgenic mice overexpressing human amyloid precursor protein revealed the same expression pattern for tight junction and MMP proteins. Consistent with reduced tight junction and increased MMP expression and activity, permeability was increased in brain microvessels from human amyloid precursor protein mice compared with microvessels from wild-type controls. CONCLUSIONS: Our findings indicate that Aß contributes to changes in brain microvessel tight junction and MMP expression, which compromises BBB integrity. We conclude that Aß causes BBB leakage and that assessing BBB permeability could potentially help characterize CAA progression and be a surrogate marker for treatment response.