Arterial Recanalization During Interhospital Transfer for Thrombectomy.

BACKGROUND: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes. METHODS: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis. RESULTS: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization. CONCLUSIONS: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

Clinical change during inter-hospital transfer for thrombectomy: Incidence, associated factors, and relationship with outcome.

BACKGROUND: Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome. METHODS: We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately. RESULTS: A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59-3.71; p < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37-0.98; p = 0.044). CONCLUSION: Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

Acute phase supra-aortic intraluminal thrombus signal changes on magnetic resonance angiography: A case series: Intraluminal thrombus signal changes on MRA.

BACKGROUND AND OBJECTIVES: Intraluminal thrombus (ILT) is a relatively rare cause of stroke. MRI/MRA is increasingly used for stroke patients eligible for acute treatment. Radiological ILT characteristics have never been studied systematically on MRA. We aimed to analyse signal changes and other radiological characteristics of ILT in the acute phase on MRA in a case series of ILT patients. MATERIALS AND METHODS: Consecutive stroke patients registered in our stroke database between January 2013 and September 2022 were screened for supra-aortic ILT on MRA, in whom MRA was the first supra-aortic vessel imaging performed. Twelve patients were included for analysis. Radiological analysis on MRA included ILT localisation, diameter of the free-floating ILT component, total ITL length, degree of stenosis caused by ILT, and ILT signal intensity. RESULTS: Median age was 65 years and 92% were men. Median time interval between stroke onset and MRA was 0.5 days. Atherosclerosis was the underlying ILT aetiology in half of the patients. The most frequent ILT localisation was the internal carotid artery, always involving the C1 segment. Median ILT diameter was 4.35 mm, median length 20.9 mm, median stenosis 65%, and with a homogeneous hypointensity of the ILT in 67% and a mixed hypo-hyperintensity in 33% (with ILT showing central hyperintensity surrounded by peripheral hypointensity). DISCUSSION: When observed on MRA, ILT showed a homogeneous hypointensity in two-thirds and a mixed hypo-hyperintensity in one third of patients. In future studies, follow-up MRA scans should be performed to analyse whether these signal changes are time-related or influenced by antithrombotic treatment for ILT.

Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy on 1.5T T2*-Weighted Imaging.

BACKGROUND: Cerebellar superficial siderosis (SS) has been recently reported to be present in about 10% of both hereditary and sporadic cerebral amyloid angiopathy (CAA) on 3T MRI using primarily susceptibility-weighted imaging. OBJECTIVES: Our aim was to assess cerebellar SS in sporadic CAA patients using 1.5T T2*-weighted MRI and to evaluate possible underlying mechanisms. METHOD: We retrospectively screened MRI scans of sporadic probable CAA patients initially presenting with intracerebral hemorrhage-, acute subarachnoid hemorrhage- or cortical SS-related symptoms between September 2009 and January 2022 registered in our stroke database. Patients with familial CAA were excluded. On 1.5T T2*-weighted MRI, cerebellar SS (including kappa statistics for interobserver agreement) was assessed together with typical CAA hemorrhagic features and with the presence of supratentorial macrobleed and cortical SS adjacent to the tentorium cerebelli (TC) and TC hemosiderosis. RESULTS: We screened 151 patients and finally included 111 CAA patients (median age 77) with cerebellar SS observed in 6 (5%) patients. Cerebellar SS presence was associated with a higher number of supratentorial macrobleeds (median n = 3 vs. n = 1, p = 0.0012), presence of supratentorial macrobleed adjacent to the TC (p = 0.002), and TC hemosiderosis (p = 0.005). CONCLUSIONS: Cerebellar SS in CAA patients can be identified on 1.5T T2*-weighted imaging. Associated MRI characteristics suggest contamination from supratentorial macrobleeds.

Brain hemorrhage on 24h-CT and functional outcome in stroke patients with cerebral amyloid angiopathy features on pre-thrombolysis MRI treated with intravenous thrombolysis: A case series.

BACKGROUND AND OBJECTIVES: In stroke patients treated with intravenous thrombolysis (IVT), presence and high number of strictly lobar cerebral microbleeds (compatible with cerebral amyloid angiopathy, CAA) seems to be associated with increased risk of hemorrhagic transformation, symptomatic hemorrhagic transformation, remote hemorrhage, and poor functional outcome. Some of these CAA patients with cerebral microbleeds also have chronic lobar intracerebral hemorrhage. Few data are available on IVT-treated CAA patients showing cortical superficial siderosis. There are no reports studying factors associated with brain hemorrhagic complication or functional outcome in IVT-treated CAA patients. We present a case series study of IVT-treated stroke patients with CAA features on pre-IVT MRI in whom we have evaluated brain hemorrhagic complications on 24 h-CT and functional outcome after IVT. MATERIAL AND METHODS: In our stroke center, IVT decision in patients with CAA MRI features is at the physician's discretion. We retrospectively screened our stroke database between January 2015 and July 2022 for pre-IVT imaging of 959 consecutive IVT-treated stroke patients without ongoing anticoagulation therapy for probable CAA MRI features defined by modified Boston criteria. After exclusion of 119 patients with missing MRI (n = 47), MRI showing motion artefacts (n = 49) or with alternative chronic brain hemorrhage cause on MRI (n = 23), 15 IVT-treated patients with probable CAA on pre-IVT MRI were identified. In these 15 patients, clinical, biological and MRI characteristics were compared between patients with vs. without post-IVT hemorrhage and between patients with poor (MRS 3-6) vs. good (MRS 0-2) functional outcome at discharge. RESULTS: Two patients showed brain hemorrhage on 24 h-CT and both died after 40 and 31 days respectively. The remaining patients had no brain hemorrhage and showed very good outcome except one. Atrial fibrillation (p = 0.029) and Fazekas scale (p = 0.029) were associated with brain hemorrhage whereas atrial fibrillation (p = 0.0022), NIHSS (p = 0.027), blood glucose level (p = 0.024), CRP (p = 0.022) and DWI ASPECT (p = 0.016) were associated with poor outcome. DISCUSSION: Consequences of IVT in CAA patients can be dramatic. Larger studies are needed to compare IVT risks and outcome between CAA and non-CAA patients, also including CAA patients with chronic intracerebral hemorrhage or cortical superficial siderosis. In addition, future studies should try to identify clinical, biological and radiological features at high risk for brain hemorrhage and poor outcome in order to assess the risk-benefit ratio for IVT in CAA. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT05565144.

Primary acute convexity subarachnoid hemorrhage in older patients: analysis of baseline, clinical and MRI characteristics including quantitative surface study and topographical probabilistic mapping of convexity subarachnoid hemorrhage.

OBJECTIVES: Primary acute convexity subarachnoid hemorrhage (cSAH) in older patients can be observed in cerebral amyloid angiopathy (CAA) or idiopathic (with cSAH as potential initial manifestation of suspected CAA). We aimed to analyze baseline, clinical and MRI (including quantitative cSAH surface analysis and topographical probabilistic cSAH mapping) characteristics in elderly cSAH patients with CAA. MATERIALS AND METHODS: Baseline/clinical/MRI characteristics of 50 consecutive primary acute cSAH patients ≥ 55 years with suspected/possible/probable CAA were retrospectively analyzed. RESULTS: Median age was 74, with 26% of patients showing suspected, 22% possible and 52% probable CAA. Transient focal neurological episode (TFNE) was observed in 78%, with spreading symptoms in 79% (median spreading speed five minutes), a median of two episodes before cSAH diagnosis, and similar symptoms in 91% when multiple TFNE, with a median duration of 15 min. Motor/sensory/speech/visual symptoms were observed in 85%/69%/46%/8%, respectively, and brachiofacial/brachial was the most frequent distribution for sensory-motor symptoms. Positive clinical-radiological correlation was observed in 84%, headache in 22%, and antiepileptics started in 78%. MRI showed chronic intracerebral hemorrhage in 10%, cortical superficial siderosis in 68%, cerebral microbleeds in 48%, median total Fazekas score of 3, lacunes in 6% and DWI lesion (all unique/cortical/ < 10 mm) in 6%. cSAH involved a median of 1 sulcus, with central sulcus as most frequently (47.5%) involved followed by precentral sulcus (17%). Median cSAH surface was 2170 mm2. No baseline, clinical or MRI characteristics were associated with cSAH surface extent in multivariate analysis. CONCLUSIONS: Baseline, clinical, or MRI features seem not to influence CAA-related cSAH extent. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT04825808.

Association between brain metabolism and clinical course of motor functional neurological disorders.

Features of resting brain metabolism in motor functional neurological disorder are poorly characterized. This study aimed to investigate the alterations of resting brain metabolism in a cohort of patients experiencing a first episode of motor functional neurological disorder with recent symptom onset and their association with persistent disability after 3 months. Patients eligible for inclusion were diagnosed with first episode of motor functional neurological disorder, were free from bipolar disorder, substance use disorder, schizophrenia, psychogenic non-epileptic seizure or any chronic or acute organic neurological disorder. Exclusion criteria included current suicidal ideation, antipsychotic intake and previous history of functional neurological disorder. Nineteen patients were recruited in Psychiatry and Neurology departments from two hospitals. Resting brain metabolism measured with 18F-fluorodeoxyglucose positron emission computed tomography at baseline and 3 months was compared to 23 controls without neurological impairment. Disability was scored using Expanded Disability Status Scale and National Institutes of Health Stroke Scale score at baseline and 3 months. Correlations were calculated with Spearman correlation coefficient. Hypometabolism was found at baseline in bilateral frontal regions in patients versus controls, disappearing by 3 months. The patients with Expanded Disability Status Scale score improvement showed greater resting state activity of prefrontal dorsolateral cortex, right orbito-frontal cortex and bilateral frontopolar metabolism at 3 months versus other patients. The resting state metabolism of the right subgenual anterior cingular cortex at baseline was negatively correlated with improvement of motor disability (measured with Expanded Disability Status Scale) between inclusion and 3 months (r = -0.75, P = 0.0018) and with change in motor symptoms assessed with the National Institutes of Health Stroke Scale (r = -0.81, P = 0.0005). The resting state metabolism of the left subgenual anterior cingular cortex at baseline was negatively correlated with improvement in Expanded Disability Status Scale and National Institutes of Health Stroke Scale scores between inclusion and 3 months (r = -0.65, P = 0.01 and r = -0.75, P = 0.0021, respectively). The negative association between the brain metabolism of the right subgenual anterior cingular cortex at baseline and change in National Institutes of Health Stroke Scale score remained significant (r = -0.81, P = 0.0414) after correction for multiple comparisons. Our findings suggest the existence of metabolic 'state markers' associated with motor disability and that brain markers are associated with motor recovery in functional neurological disorder patients.

Brain Infarction MRI Pattern in Stroke Patients with Intracardiac Thrombus.

BACKGROUND: Acute infarction patterns have been described in cardioembolic stroke, mainly with atrial fibrillation (AF) or patent foramen ovale. We aimed to analyse acute infarction magnetic resonance imaging (MRI) characteristics in stroke patients with intracardiac thrombus (ICT) compared with stroke patients with AF. METHODS: We performed a retrospective study analysing brain MRI scans of consecutive acute symptomatic cardioembolic infarction patients associated with ICT or AF who were recruited and registered in the stroke database between June 2018 and November 2019. Diffusion-weighted imaging performed within 1 week after symptom onset, intra-/extracranial vessel imaging, echocardiography, and ≥24-h ECG monitoring were required for inclusion. Baseline, biological, and echocardiography characteristics were assessed. Analysed MRI characteristics were infarction location (anterior/middle/posterior cerebral artery territory; anterior/posterior/mixed anterior-posterior circulation; multiterritorial infarction; brainstem; cerebellum; small cortical cerebellar infarctions [SCCIs] or non-SCCI; cortical/subcortical/cortico-subcortical), lesion number, subcortical lesion size (> or <15 mm), and total infarction volume. RESULTS: We included 28 ICT and 94 AF patients presenting with acute stroke. ICT patients were younger (median age 66 vs. 81 years, p < 0.001), more frequently male (79 vs. 47%, p = 0.003), and smokers (39 vs. 17%, p = 0.013), had more frequent history of diabetes (36 vs. 18%, p = 0.049) and ischaemic heart disease (57 vs. 21%, p < 0.001), and had lower HDL cholesterol levels (0.39 vs. 0.53 g/L, p < 0.001). On MRI, SCCI was more frequent in the ICT group (25 vs. 5%, p = 0.006) in the absence of other differences in infarction localisation, number, size, or volume on MRI. On multivariate analysis, younger age (p < 0.001), history of ischaemic heart disease (p < 0.001), and low HDL cholesterol levels (p = 0.01) were significantly associated with ICT. Results approaching statistical significance were observed for SCCI (more frequent in the ICT group, p = 0.053) and non-SCCI (more frequent in the AF group, p = 0.053) on MRI. CONCLUSIONS: ICT-related stroke is associated with acute SCCI presence on MRI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT04456309.

Chronic Small Cortical Cerebellar Infarctions on MRI are Associated with Patent Foramen Ovale in Young Cryptogenic Stroke.

BACKGROUND: In acute infarction patients, small cortical cerebellar infarctions (SCCI) on MRI (assessed on diffusion-weighted imaging, with SCCI often chronic and asymptomatic) are associated with acute cardioembolic infarction. In young cryptogenic stroke patients, patent foramen ovale (PFO) is thought to be a potential source of cardioembolic infarction. We hypothesize that SCCI on MRI would be associated with PFO in young cryptogenic stroke patients. METHODS: A total of 321 consecutive young (≤50 years) stroke patients admitted between January 2015 and July 2019 were screened. Of these patients, 287 patients had diagnostic work-up including early-phase MRI, intra- and extracranial vessel imaging, contrast transoesophageal or contrast transthoracic echocardiography, and ≥24 h ECG-monitoring. We retrospectively analyzed MRI scans of the 112 patients with cryptogenic stroke, including 63 with and 49 without PFO. Between both groups, we compared baseline characteristics (including cardiovascular risk factors and history of stroke), MRI characteristics of acute symptomatic infarction (cortical/subcortical localization, arterial territory, lesion number, and lesion size in case of subcortical infarction), atrial septum aneurysm (ASA) presence, and acute and chronic SCCI and non-SCCI lesions assessed on diffusion-weighted imaging. RESULTS: Groups with and without PFO were comparable in regard to performed vessel imaging and echocardiography modalities, baseline characteristics, and acute infarction characteristics, except for more frequent current smoking (67 vs. 44%, p = 0.022) and multiterritorial infarction (14 vs. 0%, p = 0.0024) and less frequent ASA (10 vs. 48%, p < 0.001) in the group without PFO. Risk of Paradoxal Embolism score was >6 in 76% of patients with PFO. SCCI was more frequent in patients with than without PFO (33 vs. 10%, p = 0.0061; OR 4.4, 95% CI 1.5-12.7), with chronic and asymptomatic SCCI in the vast majority of cases. No difference was observed for non-SCCI lesions. CONCLUSIONS: Chronic SCCI are strongly associated with PFO in young cryptogenic stroke patients. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT04043559.

A Clinico-Radiological Study of Cerebral Amyloid Angiopathy-Related Inflammation.

OBJECTIVE: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). METHODS: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. RESULTS: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. CONCLUSION: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.

Cerebral Amyloid Angiopathy and Cerebral Amyloid Angiopathy-Related Inflammation: Comparison of Hemorrhagic and DWI MRI Features.

BACKGROUND: Cerebral amyloid angiopathy (CAA) can be associated with primary vasculitis of small/medium-sized leptomeningeal and cortical arteries, called CAA-related inflammation (CAA-ri). OBJECTIVE: To compare hemorrhagic and diffusion-weighted imaging (DWI) MRI features in CAA and CAA-ri. METHODS: We prospectively scored in a consecutive CAA and CAA-ri cohort: presence/number of chronic intracerebral hemorrhage (ICH), cerebral microbleeds (CMB), and cortical superficial siderosis (CSS) on initial T2*-weighted imaging, and DWI lesions on both initial and follow-up imaging. In a subgroup, ApoE, CSF, and 18F-florbetaben-positron emission tomography (FBB-PET) were also analyzed. RESULTS: In CAA-ri, CMB presence was more frequent (100% versus 40%, p < 0.001) and CMB numbers higher (mean 137 versus 8, p < 0.001). No difference was observed for chronic ICH or CSS. DWI lesions were more frequent in acute compared to chronic CAA-ri (p = 0.025), whereas no such difference was observed between acute and chronic CAA (p = 0.18). Both ApoE4 (genotyping available in 22 CAA-ri and 48 CAA patients) carriers and homozygosity were more frequent in CAA-ri (48% versus 19% [p = 0.014] and 32% versus 2% [p < 0.001] respectively). CSF biomarker analyses (performed in 20 CAA-ri and 45 CAA patients) showed lower Aß42 levels in CAA-ri compared to CAA (median 312 versus 422 pg/mL, p = 0.0032). FBB-PET (performed in 11 CAA-ri and 20 CAA patients) showed higher standardized uptake value ratios in CAA-ri compared with CAA, only significant when the pons was used as reference (p = 0.037). CONCLUSION: Compared to CAA, CAA-ri was associated with higher CMB numbers, more frequent ApoE4 carriers and homozygotes, lower CSF Aß42 levels, and more severe amyloid load on FBB-PET.

Monocentric Prospective Study into the Sustained Effect of Incobotulinumtoxin A (XEOMIN®) Botulinum Toxin in Chronic Refractory Migraine.

Refractory chronic migraine is a disabling disorder impacting quality of life. BOTOX® (Onabotulinumtoxin A) is approved as a prophylactic treatment of chronic migraine in patients unresponsive to at least three prior preventive treatments. The objective of this study was to determine the prophylactic effect of 145 U XEOMIN® (Incobotulinumtoxin A) injected at 31 specific sites in adult patients with refractory chronic migraine. Sixty-one patients (8 men and 53 women, mean age 50) with migraine were recruited, including 20 patients with isolated chronic migraine, 18 patients with chronic migraine associating tension-type headache, 12 patients with migraine associating medication overuse headache, and 11 patients with episodic disabling migraine. The mean number of injections and duration of treatment per patient was 3.5 (range 2⁻13) and 21 (6⁻68) months, respectively. From baseline to first injection, 44 patients (73%) had >50% reduction in frequency of migraine episodes, 29 patients (48%) showed >50% reduction in number of headache days, and 28 patients (46%) had a >50% reduction in drug intake. Stable response for all three parameters was observed after the last injection. XEOMIN® thus seems to represent an effective and sustained prophylactic treatment of chronic migraine.

Cerebrospinal Fluid, MRI, and Florbetaben-PET in Cerebral Amyloid Angiopathy-Related Inflammation.

BACKGROUND: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is associated with a cerebrospinal fluid (CSF) biomarker profile similar to that observed in CAA. Few CAA-ri patients have been studied by fibrillar amyloid-ß (Aß) imaging (using 11C-Pittsburgh compound B and 18F-florbetapir, but not 18F-florbetaben). OBJECTIVE: To describe CSF biomarkers, magnetic resonance imaging (MRI), and 18F-florbetaben (FBB)-positron emission tomography (PET) changes in CAA-ri patients. METHODS: CSF levels of total tau, phosphorylated tau, Aß1-42, and Aß1-40, MRI (cerebral microbleeds count on susceptibility-weighted imaging and semi-quantitative analysis of fluid-attenuation inversion recovery white matter hyperintensities), and FBB-PET (using both cerebellar cortex and pons to calculate standardized uptake value ratios) were analyzed in nine consecutive CAA-ri patients. RESULTS: A median number of 769 cerebral microbleeds/patient were counted on MRI. When using the pons as reference region, amyloid load on FBB-PET was very strongly correlated to CSF Aß1-40 levels (rho = -0.83, p = 0.008) and moderately correlated to cerebral microbleed numbers in the occipital lobes (rho = 0.59, p = 0.001), while comparisons with other CSF biomarkers were not statistically significant (total tau, rho = -0.63, p = 0.076; phosphorylated tau, rho = -0.68, p = 0.05; Aß1-42, rho = -0.59, p = 0.09). All correlations were weaker, and not statistically significant, when using the cerebellum as reference region. A non-significant correlation (rho = -0.50, p = 0.18) was observed between CSF Aß1-40 levels and cerebral microbleed numbers. CONCLUSION: In CAA-ri, CSF Aß1-40 levels correlated well with amyloid load assessed by FBB-PET when the pons was used as reference, and to a lesser degree with cerebral microbleeds count on MRI. This confirms earlier data on CSF Aß1-40 as an in vivo marker for CAA and CAA-ri.

Radiologically Isolated Cerebral Amyloid Angiopathy-Related Inflammation.

In amyloid ß-related angiitis of the central nervous system (also called cerebral amyloid angiopathy-related inflammation), cerebral amyloid angiopathy occurs in association with primary vasculitis of small- and medium-sized leptomeningeal and cortical arteries. To avoid brain biopsy, clinicoradiological criteria (including clinical features due to inflammation-related uni/multifocal white matter hyperintensities) for the diagnosis of cerebral amyloid angiopathy-related inflammation have been validated recently. We report 3 cases with acute symptoms directly related to cerebral amyloid angiopathy in the presence of asymptomatic cerebral amyloid angiopathy-related inflammation hyperintensities on initial magnetic resonance imaging. Recognizing radiological features of cerebral amyloid angiopathy-related inflammation in patients with cerebral amyloid angiopathy is important because radiological isolated cerebral amyloid angiopathy-related inflammation may become symptomatic and immunosuppressive treatment is often effective in cerebral amyloid angiopathy-related inflammation, although optimal treatment regimen is yet unknown. In contrast, apart from hypertension treatment, few therapeutic options exist in cerebral amyloid angiopathy.