Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

RU-Net: skull stripping in rat brain MR images after ischemic stroke with rat U-Net.

BACKGROUND: Experimental ischemic stroke models play a fundamental role in interpreting the mechanism of cerebral ischemia and appraising the development of pathological extent. An accurate and automatic skull stripping tool for rat brain image volumes with magnetic resonance imaging (MRI) are crucial in experimental stroke analysis. Due to the deficiency of reliable rat brain segmentation methods and motivated by the demand for preclinical studies, this paper develops a new skull stripping algorithm to extract the rat brain region in MR images after stroke, which is named Rat U-Net (RU-Net). METHODS: Based on a U-shape like deep learning architecture, the proposed framework integrates batch normalization with the residual network to achieve efficient end-to-end segmentation. A pooling index transmission mechanism between the encoder and decoder is exploited to reinforce the spatial correlation. Two different modalities of diffusion-weighted imaging (DWI) and T2-weighted MRI (T2WI) corresponding to two in-house datasets with each consisting of 55 subjects were employed to evaluate the performance of the proposed RU-Net. RESULTS: Extensive experiments indicated great segmentation accuracy across diversified rat brain MR images. It was suggested that our rat skull stripping network outperformed several state-of-the-art methods and achieved the highest average Dice scores of 98.04% (p < 0.001) and 97.67% (p < 0.001) in the DWI and T2WI image datasets, respectively. CONCLUSION: The proposed RU-Net is believed to be potential for advancing preclinical stroke investigation and providing an efficient tool for pathological rat brain image extraction, where accurate segmentation of the rat brain region is fundamental.

Improvement After Celecoxib Treatment in Patients with Thalamic Hemorrhage - A Case Report.

PURPOSE: Perihematomal edema of intracerebral hemorrhage (ICH) is caused by a hematoma-induced inflammatory reaction, which usually contributes to delayed deterioration of neurological function and poor outcomes. Celecoxib is a commonly used nonsteroidal anti-inflammatory drug that selectively inhibits cyclooxygenase-2. High-dose celecoxib (400 mg twice daily) for 14 days has been shown to reduce perihematomal edema and hematoma enlargement in patients with ICH, but without improvement in long-term functional outcome, which may be confounded by the heterogeneity of hematoma location. Low-dose celecoxib may be an effective management for symptoms caused by perihematomal edema in patients with ICH, particularly those involving the thalamus. CASE REPORT: We reported two patients with acute thalamic ICH; a common symptom between the two was delayed onset of drowsiness caused by perihematomal edema involving the thalamus. Their consciousness improved after low-dose celecoxib (200 mg once daily) administration for 3 and 2 days in case A and B, respectively. Furthermore, other symptoms that concomitantly improved included poor appetite caused by perihematomal edema involving the left hypothalamus in case A, and limb weakness caused by perihematomal edema of the internal capsule in case B. CONCLUSION: These cases revealed that low-dose celecoxib may be an effective management for symptoms caused by perihematomal edema in patients with ICH, particularly those involving the thalamus.

Concomitant Sympathetic and Parasympathetic Dysfunction after Acute Ischemic Stroke.

PURPOSE: Autonomic dysfunction is an underrecognized complication of acute ischemic stroke. The cortical regulation of sympathetic activation is predominantly lateralized to the right hemisphere and parasympathetic activation to the left hemisphere. However, prior evidence is lacking regarding ischemic lesions in unilateral hemisphere that concomitantly cause sympathetic and parasympathetic dysfunction. CASE REPORT: We present the case of a 73-year-old woman with acute ischemic stroke in the left middle cerebral artery territory, whose neurological symptoms improved significantly after thrombolysis and endovascular thrombectomy. She presented residual scattered small infarctions involving the left insula and lateral parietal cortex. However, she experienced obvious autonomic symptoms that included orthostatic hypotension, which is indicative of sympathetic dysfunction, and micturition difficulty with exaggerated reflex tachycardia, indicative of parasympathetic dysfunction. The sympathetic and parasympathetic functions sequentially resolved on days 10 and 20 after stroke onset, respectively. CONCLUSION: The case revealed insight into the phenomenon and recovery course of concurrent sympathetic and parasympathetic dysfunction associated with ischemic lesions in the left hemisphere.

Early recurrence of ischemic stroke in patients receiving endovascular thrombectomy.

BACKGROUND/PURPOSE: Endovascular thrombectomy (EVT) is effective in treating acute ischemic stroke associated with large vessel occlusion. Early recurrence of ischemic stroke (ERIS) after EVT, however, is a devastating event and could worsen the condition of patient. Current study aimed to investigate the prevalence and risk factors of ERIS after EVT. METHODS: The medical records of all patients receiving EVT at a single medical center were reviewed and analyzed. ERIS was defined as presentation of newly developed neurological deficits in previously recanalized vascular territory or another vascular territory that was not initially involved within 30 days of the index stroke. RESULTS: From January 2015 to September 2018, a total of 200 patients (71.6 ± 12.3 years, male 49%) had received EVT and 17 patients (8.5%) developed ERIS. Presence of valvular heart disease was the only clinical factor associated with ERIS (OR: 4.26, 95% CI: 1.16-17.7). Patients with ERIS had significantly worse modified Rankin scale at 3 months (common OR: 3.11, 95% CI: 1.18-8.73) and were independently associated with mortality (OR: 7.73, 95% CI: 2.00-30.6). Ten of 17 patients with ERIS had received repeated EVT and all achieved good recanalization without procedure-related complications or symptomatic intracerebral hemorrhage. CONCLUSION: ERIS in patients receiving EVT was not rare, especially in those with valvular heart disease, and was associated with worse outcome. Nevertheless, they could be safely treated by repeated EVT.

Segmentation of Rat Brains and Cerebral Hemispheres in Triphenyltetrazolium Chloride-Stained Images after Stroke.

Ischemic stroke is one of the leading causes of death among the aged population in the world. Experimental stroke models with rodents play a fundamental role in the investigation of the mechanism and impairment of cerebral ischemia. For its celerity and veracity, the 2,3,5-triphenyltetrazolium chloride (TTC) staining of rat brains has been extensively adopted to visualize the infarction, which is subsequently photographed for further processing. Two important tasks are to segment the brain regions and to compute the midline that separates the brain. This paper investigates automatic brain extraction and hemisphere segmentation algorithms in camera-based TTC-stained rat images. For rat brain extraction, a saliency region detection scheme on a superpixel image is exploited to extract the brain regions from the raw complicated image. Subsequently, the initial brain slices are refined using a parametric deformable model associated with color image transformation. For rat hemisphere segmentation, open curve evolution guided by the gradient vector flow in a medial subimage is developed to compute the midline. A wide variety of TTC-stained rat brain images captured by a smartphone were produced and utilized to evaluate the proposed segmentation frameworks. Experimental results on the segmentation of rat brains and cerebral hemispheres indicated that the developed schemes achieved high accuracy with average Dice scores of 92.33% and 97.15%, respectively. The established segmentation algorithms are believed to be potential and beneficial to facilitate experimental stroke study with TTC-stained rat brain images.

Determinants for Control of Status Epilepticus in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND: Treatment guideline for status epilepticus (SE) specifically in patients with anti-N-methyl- D-aspartate receptor (anti-NMDAR) encephalitis is insufficient. This study aimed to clarify the determinants for the control of SE in adult patients with anti-NMDAR encephalitis. METHODS: Medical records of all patients with anti-NMDAR encephalitis hospitalized between Jan. 2010 and Sep. 2019 were analyzed for the time sequence of seizures and treatments, and antiepileptic drug (AED) regimens related to SE. The outcomes were control of SE and seizures, and the discharge score of modified Rankin Scale (mRS). RESULTS: All eight patients had seizures and seven (87.5%) suffered from SE which lasted for 3.6 ± 3.9 days. Five patients (71.4%) had SE earlier than using IT, whose SE was controlled by AEDs alone (n = 4) or combined with teratomas resection (n = 1). Another two patients suffered from SE after receiving IT, and one of them had SE only for 1 hour. Moreover, all SE patients received increased types and dosages of AEDs at SE end. A shorter duration of refractory SE was associated with its later occurrence after seizure onset (p = 0.005) and longer duration of AEDs use before SE (p = 0.026). All cases achieved seizure freedom after receiving AEDs and IT. CONCLUSIONS: In these patients with anti-NMDAR encephalitis, all the SE which occurred before initiating IT was successfully controlled by AEDs alone or combined with teratoma resection, and later onset of refractory SE was associated with a shorter SE duration.

Factors for recurrent stroke among Asian patients with non-valvular atrial fibrillation under non-vitamin K antagonist oral anticoagulant therapy.

BACKGROUND/PURPOSE: Atrial fibrillation (AF) patients with a history of ischemic stroke or transient ischemic attack (TIA) carry excessive risk of recurrent stroke. Real-world data for the Asian population is scarce. This study aimed to investigate the thromboembolism and major bleeding risk of non-vitamin K antagonist oral anticoagulant (NOAC) therapy among Asian patients, and to identify the risk factors of recurrent stroke. METHODS: This retrospective study recruited AF patients aged over 20 years, who had a previous stoke or TIA, and received NOAC therapy. Thromboembolic events were recurrent ischemic stroke or TIA, and the major bleeding events were classified according to the PLATO (Platelet Inhibition and Patient Outcomes) criteria. RESULTS: A total of 361 patients (61.2% male) were enrolled for data analysis. The incidence rate for recurrent ischemic stroke or TIA was 3.6 (95% CI = 2.5 to 5.5) per 100 person-years, and 0.9 (95% CI = 0.4 to 1.7) per 100 person-years for major bleeding. Patients with recurrent ischemic stroke or TIA were more likely to have malignancy (hazard ratio [HR] for malignancy = 4.4, 95% CI = 1.9 to 10.3, p = 0.001) and concomitantly take enzyme inducing antiepileptic drugs (EIAED, HR = 8.1, 95% CI = 2.7 to 24.1, p < 0.001). CONCLUSION: Atrial fibrillation patients with underlying malignancy or concurrently use of EIAED may have increased risk of treatment failure in secondary stroke prevention.

Similar outcomes between vitamin K and non-vitamin K antagonist oral anticoagulants associated intracerebral hemorrhage.

BACKGROUND: The application of non-vitamin K antagonist oral anticoagulant (NOAC) reduces the risk of intracerebral hemorrhage (ICH) in comparison with vitamin K antagonist (VKA). However, the features and outcomes of NOAC-associated ICH are still unclear, especially for Asian populations. METHODS: We retrospectively analyzed 49 consecutive patients who had spontaneous ICH while using NOAC or VKA. We compared the clinical characteristics, ICH volume, 7-day and 3-month mortality, and functional outcomes at discharge and 3 months post-stroke using the modified Rankin Scale (mRS) between NOAC- and VKA-associated ICH. The clinical features, ICH volume, ICH location, and/or treatment methods were statistically adjusted. RESULTS: Among the 49 ICH patients, 15 (30.6%) were using NOAC and 34 (69.4%) were taking VKA. There were no significant differences in the initial ICH volume between groups (mean volume 34.2 ± 43.8 vs. 59.4 ± 46.5 mL, p = 0.061). The percentage of early mortality (within 7 days post-ICH) was significantly lower in the NOAC group (13.3% vs. 44.1%; p = 0.047), but the 3-month mortality was similar (33.3% vs. 47.1%; p = 0.294). The functional outcome was equally poor in both groups at discharge (p = 0.670) and 3 months post-ICH (mean mRS score 4.7 ± 1.3 vs. 4.6 ± 1.7, p = 0.766). CONCLUSION: There were no significant differences in initial ICH volume, 90-day mortality, or functional outcomes between NOAC and VKA-associated ICH in Asians.

Pathophysiology of Central Poststroke Pain: Motor Cortex Disinhibition and Its Clinical and Sensory Correlates.

Background and Purpose- Central poststroke pain (CPSP) is a disabling condition in stroke patients, and evidence suggests that altered corticospinal and motor intracortical excitability occurs in neuropathic pain. The objective of this study was to investigate changes in motor cortex excitability and sensorimotor interaction and their correlates with clinical manifestations and alterations in somatosensory systems in CPSP patients. Methods- Fourteen patients with CPSP but no motor weakness were compared with age- and sex-matched healthy controls for motor cortex excitability and sensorimotor interaction assessed by transcranial magnetic stimulation to measure resting motor thresholds, short-interval intracortical inhibition, intracortical facilitation, and afferent inhibitions. The sensory pathway was evaluated by quantitative sensory testing, contact heat evoked potential, and somatosensory evoked potentials. Clinical pain and quality of life were assessed with validated tools. Results- The duration of CPSP was 3.3±3.0 years (ranging 0.5-10 years), and pain significantly impaired quality of life. Compared with the unaffected hemisphere, the stroke hemisphere had higher thermal thresholds, lower contact heat evoked potential amplitudes, and prolonged cortical somatosensory evoked potential latencies. There was no difference in resting motor thresholds between the stroke and unaffected hemisphere or between patients and controls. CPSP patients had a reduction in short-interval intracortical inhibition in the stroke hemisphere compared with that in the unaffected hemispheres of patients and controls. No changes were noted in afferent inhibitions between the stroke and unaffected hemispheres. The short-interval intracortical inhibition of the stroke hemisphere was negatively correlated with self-rated health on a visual analog scale and positively correlated with cortical somatosensory evoked potential latencies. Conclusions- CPSP patients with intact corticospinal tracts showed reduced motor intracortical inhibition in the stroke hemisphere, suggesting defective gamma-aminobutyric acid-ergic inhibition. This disinhibition was associated with impaired quality of life and was related to dorsal column-medial lemniscus pathway dysfunction.

Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

Factors affecting serum concentration of dabigatran in Asian patients with non-valvular atrial fibrillation.

BACKGROUND/PURPOSE: Dabigatran is effective in preventing ischemic stroke and systemic embolism in patients with atrial fibrillation. Although the therapeutic window for dabigatran is wide, its pharmacokinetic properties can differ between specific populations. This study aimed to establish a real-life plasma dabigatran concentration database and investigate potential factors affecting this concentration in Asians. METHODS: Patients under dabigatran therapy were recruited. Plasma dabigatran concentration was determined in trough and peak blood samples by using ultra-high performance liquid chromatography with tandem mass spectrometry analysis. Factors affecting the dabigatran concentration were investigated. RESULTS: A total of 46 patients (33 male, 71.7%) were prospectively enrolled. Most of them were receiving a low dose regimen (110 mg twice daily, n = 38, 82.6%). The trough and peak concentrations were significantly correlated (p < 0.001), and the trough concentration was higher in patients aged ≥75 years, body weight ≤60 kg, creatinine clearance (CrCl) ≤50 mL/min, CHA2DS2-VASc score >3 points, and HAS-BLED score ≥3 points. Multiple linear regression analysis identified body weight and serum creatinine as key factors predicting trough concentration (p = 0.003 and 0.005, respectively). Importantly, drug adherence was the only independent factor associated with low trough concentration, defined as the lowest 20th percentile in our study cohort (n = 10, hazard ratio = 9.07; 95% CI, 1.12 to 73.22; p = 0.004). CONCLUSION: Dabigatran monitoring may be considered for patients at risk of overexposure, especially those with low body weight and renal insufficiency, and also for detecting those with extremely low drug concentration.

High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis.

BACKGROUND: D-dimer is a fibrin degradation product and a possible marker of thromboembolic events. The aim of this study was to investigate the relationship between D-dimer levels and outcome in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis. METHODS: This retrospective study included AIS patients who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and provided plasma D-dimer level within 24 h after stroke onset during 2009 and 2014 at a single medical center. Unfavorable outcome was defined as modified Rankin scale ≥3 at 3 months after stroke. Symptomatic intracerebral hemorrhage (ICH) was defined as a deterioration of at least 4 points on the National Institutes of Health Stroke Scale within 36 h post thrombolysis. RESULTS: Of 347 patients receiving intravenous rt-PA, 159 (mean age 67.6 ± 13.1 year, 59.7% male) fulfilled the inclusion criteria. In univariate analysis, patients with unfavorable outcome (n = 79) had significantly higher levels of D-dimer than those with favorable outcome (median ln D-dimer = 1.4 vs. 0.7 µg/ml, p < 0.001). After adjustment for clinical variables, a higher level of D-dimer remained significantly associated with an unfavorable outcome (OR 1.90, 95% CI 1.27-2.86, p = 0.002) and the occurrence of symptomatic ICH (OR 2.97, 95% CI 1.15-7.70, p = 0.025). CONCLUSION: The D-dimer level within 24 h after stroke onset can be an early outcome indicator in AIS patients receiving rt-PA therapy.

Improved performance of new prenotification criteria for acute stroke patients.

BACKGROUND/PURPOSE: We aim to evaluate the accuracy of the new prehospital notification criteria for patients with potential acute stroke in the prehospital setting. METHODS: We conducted a retrospective observational study from March 2011 to February 2013 of potential acute stroke patients prenotified using the new criteria which were: (1) positive Cincinnati Prehospital Stroke Scale (CPSS); (2) symptom onset within 3 hours; and (3) blood glucose level > 60 mg/dL. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the new criteria were calculated and outcomes of acute stroke patients were reported. Data of all patients with stroke or transient ischemic attack (TIA) transported to the destination hospital were also obtained to evaluate the compliance of emergency medical technicians. RESULTS: There were 2888 patients suspected of stroke by emergency medical technicians and 221 patients prenotified due to meeting the criteria. The PPV, NPV, sensitivity, and specificity of the new criteria were 76.9%, 96.6%, 64.9%, and 98.1%, respectively. Onset time > 3 hours (24/51, 47.1%) and seizure (27.5%) were the two most common conditions leading to false prenotification. Of all prenotified patients, 23.1% (51/221) received thrombolytic therapy. Hemorrhagic stroke or ischemic stroke with hemorrhagic transformation (53.8%) and minor symptoms or rapid recovery (26.9%) were the most common reasons excluding correctly prenotified patients from thrombolytic therapy. CONCLUSION: The accuracy of the new prehospital stroke criteria has higher PPV and specificity compared to previous CPSS validation studies.

Dural Arteriovenous Fistula Presenting with Status Epilepticus Treated Successfully with Endovascular Intervention.

PURPOSE: Status epilepticus was rarely reported as the initial manifestation of intracranial dural arteriovenous fistulas. Successful treatment with endovascular intervention has not been reported in the literature. CASE REPORT: We report three cases of dural arteriovenous fistulas initially presenting with various types of status epilepticus, including generalized tonic-clonic status epilepticus, complex partial status epilepticus, and nonconvulsive status epilepticus. The status epilepticus of these patients was successfully terminated through aggressive endovascular intervention in conjunction with antiepileptic drugs. CONCLUSION: These cases highlight the importance of intracranial dural arteriovenous fistulas in diagnosing patients with status epilepticus. Moreover, directly treating dural arteriovenous fistulas plays a crucial role in addition to anti-epileptic drugs therapy in controlling seizures in patients with dural arteriovenous fistulas related status epilepticus.

Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by SMASH-U classification system.

BACKGROUND AND PURPOSE: Pathogenetic classification of intracerebral hemorrhage (ICH), using systems such as SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy [CAA], systemic disease, hypertension, or undetermined), is important in predicting functional outcomes and mortality in patients with ICH. This study aimed to compare pathogenetic subtypes between the first and recurrent ICH. METHODS: This study obtained data related to 4578 consecutive acute patients with ICH from the National Taiwan University Hospital Stroke Registry during January 1995 to December 2013. Using the SMASH-U method, patients were classified into 6 subtypes. We then analyzed the outcomes of first-ever ICH cases and pathogenetic classification of recurrent ICH. RESULTS: Among 3785 patients who experienced first-ever ICH (male, 63.3%; mean age, 58.7±17.0 years), the most common cause was hypertensive angiopathy (54.9%), followed by CAA (12.2%), systemic disease (12.1%), undetermined (10.1%), structural vascular lesions (7.8%), and medication related (2.9%). In 185 cases of recurrent ICH, pathogenetic differences between the 2 ICH events were observed in 34 (18.4%) cases, most of which were CAA to hypertensive angiopathy (n=10) or vice versa (n=7). The rates of ICH recurrence were highest for systemic disease-related and CAA-related ICH at 1, 5, 10, and 15 years after the indexed ICH event. CONCLUSIONS: In approximately one fifth of the recurrent patients with ICH, pathogenetic differences were observed between initial and recurrent events, particularly among those with CAA. It is possible that some patients with ICH with concomitant hypertensive angiopathy and CAA may have been categorized as CAA by the SMASH-U method.

Association between plasma levels of hyaluronic acid and functional outcome in acute stroke patients.

BACKGROUND: Activation of hyaluronic acid (HA) and associated enzyme synthesis has been demonstrated in experimental stroke animal models. Our study aimed to investigate the plasma levels of HA in acute stroke patients and the associations between HA levels and functional outcome. METHODS: This was a multicenter case-control study. Acute stroke patients and age- and sex-matched non-stroke controls were recruited. Plasma levels of HA in acute stroke patients were determined at <48 hours and at 48 to 72 hours after stroke onset by standard ELISA. Favorable functional outcome was defined as modified Rankin scale ≤ 2 at 3 months after stroke. RESULTS: The study included 206 acute stroke patients, including 43 who had intracerebral hemorrhage and 163 who had ischemic stroke, and 159 controls. The plasma levels of HA in the acute stroke patients were significantly higher than those in the controls (219.7 ± 203.4 ng/ml for <48 hours and 343.1 ± 710.3 ng/ml for 48 to 72 hours versus 170.4 ± 127.9 ng/ml in the controls; both P < 0.05). For intracerebral hemorrhage patients, HA ≤ 500 ng/ml (<48 hours) was an independent favorable outcome predictor (P = 0.016). For ischemic stroke patients, an inverted U-shaped association between plasma HA (48 to 72 hours) and outcome was noted, indicating that ischemic stroke patients with too high or too low plasma HA levels tended to have an unfavorable outcome. CONCLUSION: HA plasma level was elevated in patients with acute stroke, and can predict 3-month functional outcome, particularly for patients with intracerebral hemorrhage.

Thrombolytic therapy is an only determinant factor for stroke evolution in large anterior choroidal artery infarcts.

BACKGROUND: Large anterior choroidal artery (AChA) infarcts are frequently associated with stroke evolution. This study aimed to investigate the major determinants for stroke evolution in patients with large AChA infarcts. METHODS: We studied 118 consecutive adult patients with acute large AChA infarcts. The diagnosis was confirmed as abnormal hyperintensities in 3 or more rostracaudal magnetic resonance imaging slices (5 mm thickness) using diffusion-weighted imaging within typical AChA vascular regions. Stroke evolution was defined as neurologic deterioration with an increase in National Institutes of Health Stroke Scale (NIHSS) score by at least 4 or an increase of NIHSS score in motor function by at least 2 in 7 days after stroke onset. RESULTS: Forty-seven (39.8%) patients developed stroke evolution. Thrombolytic therapy was inversely associated with the occurrence of stroke evolution (P = .004). Using multivariate analysis, thrombolytic therapy was the only protective determinant for stroke evolution (adjusted odds ratio, .08; 95% confidence interval, .01 to .67). Patients with large AChA infarcts receiving thrombolytic therapy had less unfavorable long-term functional outcome than those not receiving thrombolytic therapy (adjusted odds ratio, .11; 95% confidence interval, .02-.75). CONCLUSIONS: Thrombolytic therapy is an only determinant factor for stroke evolution in large AChA infarcts, which reduced the risk of stroke evolution and improved functional outcome.

Pin-point pupils with drowsiness as a presentation of Hashimoto's encephalopathy mimicking pontine infarction.

PURPOSE: Hashimoto's encephalopathy (HE) is an autoimmune-mediated encephalopathy with various manifestations. Pupil size change has never been previously reported as a presentation of HE. CASE REPORT: A 65-year-old woman without previous known thyroid disease presented with acute onset of drowsiness and blurred vision. Neurologically, she was drowsy and had bilateral pinpoint-sized pupils without a light reflex, which probably indicated a bilateral pontine lesion. Brain MRI showed two tiny infarctions at the left midbrain and left thalamus, but did not show a pontine lesion, and demonstrated patent vertebral/basilar arteries. Electroencephalography showed intermittent diffuse slowing. She had an elevated protein level (123 mg/dl) in cerebrospinal fluid without pleocytosis. Of note, she had elevated serum levels of anti-TG antibody (282 IU/mL) and anti-TPO antibody (117 IU/mL). Her symptoms improved spontaneously including gradually normalization of her pupil size in 3 days and clear consciousness in 6 days; therefore, corticosteroid was not administered. CONCLUSION: This case illustrates that physicians should be aware of the treatable condition of HE as a possible diagnosis in patients with bilateral pinpoint pupils and drowsiness but without corresponding MRI lesions.

Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis.

OBJECTIVE: Despite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified. METHODS: This study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR-A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC-1) culture to examine the direct effect of TTR-A97S protein on endothelial cells. RESULTS: In ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC-1 culture in which the expression of collagen IV was upregulated after exposure to TTR-A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p-selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv. INTERPRETATION: Microangiopathy with thromboinflammation is characteristic of advanced-stage ATTRv nerves, which provides an add-on mechanism and therapeutic target for nerve degeneration.