Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

SAMHD1 compound heterozygous rare variants associated with moyamoya and mitral valve disease in the absence of other features of Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome (AGS) is an autosomal recessive inflammatory syndrome that manifests as an early-onset encephalopathy with both neurologic and extraneurologic clinical findings. AGS has been associated with pathogenic variants in nine genes: TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR, IFIH1, LSM11, and RNU7-1. Diagnosis is established by clinical findings (encephalopathy and acquired microcephaly, intellectual and physical impairments, dystonia, hepatosplenomegaly, sterile pyrexia, and/or chilblains), characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes), or the identification of pathogenic/likely pathogenic variants in the known genes. One of the genes associated with AGS, SAMHD1, has also been associated with a spectrum of cerebrovascular diseases, including moyamoya disease (MMD). In this report, we describe a 31-year-old male referred to genetics for MMD since childhood who lacked the hallmark features of AGS patients but was found to have compound heterozygous SAMHD1 variants. He later developed mitral valve insufficiency due to recurrent chordal rupture and ultimately underwent a heart transplant at 37 years of age. Thus, these data suggest that SAMHD1 pathogenic variants can cause MMD without typical AGS symptoms and support that SAMHD1 should be assessed in MMD patients even in the absence of AGS features.

Cognitive outcomes in Susac syndrome: A 2-year neuropsychological follow-up study.

BACKGROUND AND PURPOSE: Susac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long-term neuropsychological outcomes of patients with SuS. METHODS: Thirteen patients with SuS (mean [SD] age 39.5 [11.1] years) were enrolled at the Ghent University Hospital by their treating neurologist. The cognitive functioning and emotional well-being of each patient was evaluated by means of a thorough neuropsychological test battery at baseline and after 2 years. Follow-up testing after 2 years was performed in 11 patients (mean [SD] age 42.2 [11.5] years). RESULTS: Patients showed normal neuropsychological test results at a group level, both at baseline and follow-up testing. Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency. Individual test results showed interindividual variability at baseline, with most impairments being in attention, executive functioning and language, which improved after a 2-year period. In addition, patients reported significantly lower mental and physical well-being, both at baseline and follow-up testing. CONCLUSIONS: Our results suggest that neuropsychological dysfunction in SuS is limited at a group level and improves over time. Nonetheless, individual test results reveal interindividual variability, making cognitive screening essential. Furthermore, a high psycho-emotional burden of the disease was reported, for which screening and follow-up are necessary.

Clinical and subclinical findings in heterozygous ABCC6 carriers: results from a Belgian cohort and clinical practice guidelines.

BACKGROUND: Biallelic pathogenic variants in the ATP-binding cassette subfamily C member 6 (ABCC6) gene cause pseudoxanthoma elasticum, a multisystemic ectopic calcification disorder, while heterozygous ABCC6 variants are associated with an increased risk of cardiovascular and cerebrovascular disease. As the prevalence of pathogenic ABCC6 variants in the general population is estimated at ~1%, identifying additional ABCC6-related (sub)clinical manifestations in heterozygous carriers is of the utmost importance to reduce this burden of disease. Here, we present a large Belgian cohort of heterozygous ABCC6 carriers with comprehensive clinical, biochemical and imaging data. Based on these results, we formulate clinical practice guidelines regarding screening, preventive measures and follow-up of ABCC6 carriers. METHODS: The phenotype of 56 individuals carrying heterozygous pathogenic ABCC6 variants was assessed using clinical (eg, detailed ophthalmological examinations), biochemical, imaging (eg, cardiovascular and abdominal ultrasound) and genetic data. Clinical practice guidelines were then drawn up. RESULTS: We found that ABCC6 heterozygosity is associated with distinct retinal alterations ('comet-like') (24%), high prevalence of hypercholesterolaemia (>75%) and diastolic dysfunction (33%), accelerated lower limb atherosclerosis and medial vascular disease, abdominal organ calcification (26%) and testicular microlithiasis (28%), though with highly variable expression. CONCLUSION: In this study, we delineated the multisystemic ABCC6 heterozygosity phenotype characterised by retinal alterations, aberrant lipid metabolism, diastolic dysfunction and increased vascular, abdominal and testicular calcifications. Our clinical practice guidelines aimed to improve early diagnosis, treatment and follow-up of ABCC6-related health problems.

Mutations in RNU7-1 Weaken Secondary RNA Structure, Induce MCP-1 and CXCL10 in CSF, and Result in Aicardi-Goutières Syndrome with Severe End-Organ Involvement.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a type I interferonopathy usually characterized by early-onset neurologic regression. Biallelic mutations in LSM11 and RNU7-1, components of the U7 small nuclear ribonucleoprotein (snRNP) complex, have been identified in a limited number of genetically unexplained AGS cases. Impairment of U7 snRNP function results in misprocessing of replication-dependent histone (RDH) pre-mRNA and disturbance of histone occupancy of nuclear DNA, ultimately driving cGAS-dependent type I interferon (IFN-I) release. OBJECTIVE: We performed a clinical, genetic, and immunological workup of 3 unrelated patients with uncharacterized AGS. METHODS: Whole exome sequencing (WES) and targeted Sanger sequencing of RNU7-1 were performed. Primary fibroblasts were used for mechanistic studies. IFN-I signature and STAT1/2 phosphorylation were assessed in peripheral blood. Cytokines were profiled on serum and cerebrospinal fluid (CSF). Histopathology was examined on brain and kidney tissue. RESULTS: Sequencing revealed compound heterozygous RNU7-1 mutations, resulting in impaired RDH pre-mRNA processing. The 3' stem-loop mutations reduced stability of the secondary U7 snRNA structure. A discrete IFN-I signature in peripheral blood was paralleled by MCP-1 (CCL2) and CXCL10 upregulation in CSF. Histopathological analysis of the kidney showed thrombotic microangiopathy. We observed dysregulated STAT phosphorylation upon cytokine stimulation. Clinical overview of all reported patients with RNU7-1-related disease revealed high mortality and high incidence of organ involvement compared to other AGS genotypes. CONCLUSIONS: Targeted RNU7-1 sequencing is recommended in genetically unexplained AGS cases. CSF cytokine profiling represents an additional diagnostic tool to identify aberrant IFN-I signaling. Clinical follow-up of RNU7-1-mutated patients should include screening for severe end-organ involvement including liver disease and nephropathy.

IRF2BPL Is Associated with Neurological Phenotypes.

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadly detected, including in the nervous system. Complete loss of pits is lethal early in development, whereas partial knockdown with RNA interference in neurons leads to neurodegeneration, revealing a requirement for this gene in proper neuronal function and maintenance. The identified IRF2BPL nonsense variants behave as severe loss-of-function alleles in this model organism, and ectopic expression of the missense variants leads to a range of phenotypes. Taken together, our results show that IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

Alemtuzumab in multiple sclerosis: A retrospective analysis of occult hemorrhagic magnetic resonance imaging lesions and risk factors.

BACKGROUND AND PURPOSE: Alemtuzumab, a monoclonal CD52 antibody, is a high-efficacy disease-modifying-therapy in relapsing-remitting multiple sclerosis (RRMS). Recently, intracerebral hemorrhage (ICH) was reported as a possible treatment-related adverse event. Arterial hypertension during infusion was suggested as a potential cause, although platelet or endothelial dysfunction may also contribute. This study aimed to screen for occult hemorrhagic cerebral lesions after alemtuzumab treatment and to further elucidate risk factors. METHODS: We included 30 RRMS patients who received alemtuzumab treatment at Ghent University Hospital or Sint-Jan Bruges Hospital. Retrospective data concerning vital signs, adverse effects and thrombocyte levels during treatment were collected. The occurrence of occult intracranial hemorrhagic lesions was assessed by magnetic resonance imaging with susceptibility-weighted imaging (SWI). RESULTS: The mean (standard deviation [SD]) systolic blood pressure (SBP) during the morning, afternoon and evening was 120 (3.38) mmHg during first administration and 114 (4.40) mmHg during second administration (N = 13). There was no significant increase in SBP when comparing morning, afternoon and evening per day, nor was there a significant difference in daily mean SBP between consecutive administration days. Thrombocyte count during treatment cycles ranged between 107 × 109 /L and 398 × 109 /L, with a mean (SD) absolute reduction of 59.3 × 109 /L (50.65) or a mean (SD) relative reduction of 25.0 (12.84)% (N = 20). No patient had ICH, nor did SWI show any cerebral microbleeds or other hemorrhagic lesions post-treatment (N = 23). CONCLUSIONS: In our patient population, alemtuzumab treatment was not associated with arterial hypertension, ICH or occult microbleeds. Possible differences in administration regimen (ambulatory vs. in-hospital setting) and patient population (cardiovascular risk) might explain an increased risk in different populations.

Dysarthria following acute ischemic stroke: Prospective evaluation of characteristics, type and severity.

BACKGROUND: Dysarthria is a common symptom following stroke and represents an important cause of functional impairment in stroke patients. A better characterization of dysarthria could facilitate differential diagnosis and optimize healthcare service distribution. AIM: To determine the speech characteristics, dysarthria type and severity in the acute phase following ischemic stroke in a comprehensive stroke centre. METHODS & PROCEDURES: First-ever ischemic stroke patients consecutively admitted to the Stroke Unit of Ghent University Hospital were included in this prospective clinical study between March 2018 and October 2019. All participants admitted to the Stroke Unit were screened for dysarthria by a speech-language pathologist within 72 h after admission. When dysarthria was identified, speech characteristics were evaluated via auditory-perceptual assessment and objective measurement of acoustic parameters. Dysarthria type was determined based on the Mayo Classification System. Severity of impairment was scored at function and activity level using the Radboud Dysarthria Assessment and the evaluation of speech intelligibility at sentence level using the Dutch Speech Intelligibility Assessment. In addition, dysarthria recovery was separately evaluated in all participants using the National Institutes of Health Stroke Scale (NIHSS) at hospital admission, day 3 ± 2 and day 7. OUTCOMES & RESULTS: A total of 67 out of 151 participants (44%; mean age = 69 years; SD = 13; 28 females) were diagnosed with dysarthria in the acute phase following stroke. Standardized assessments were possible in 72% (48/67) of participants. Imprecise articulation of consonants, harsh voice quality and audible inspiration were the most frequent observed speech characteristics. The acoustic parameters maximum phonation time and maximum loudness deviated most from normative values. Unilateral upper motor neuron (UUMN) was the main dysarthria type present in 52% (25/48) of participants. A total of 58% (28/48) and 71% (34/48) of participants had no/minimal/mild difficulties at the functional and activity levels, respectively. Speech intelligibility was mildly impaired (median = 91%; IQR = 73-97). According to the NIHSS, sub-item speech score at hospital admission, 46% (70/151) of participants had dysarthria, of which half recovered completely from their dysarthria within 1 week after stroke symptom onset. CONCLUSIONS & IMPLICATIONS: UUMN was the dominant dysarthria type, and the majority of participants had a mild dysarthria. Half the participants showed complete recovery within 1 week following symptom onset. The observed speech characteristics mainly reflect impairments in the subsystem's articulation, phonation and respiration. Objective measurements of acoustic parameters corroborate these findings. Future research should focus on longitudinal assessment to investigate recovery of symptoms and the long-term impact of dysarthria on social participation. What this paper adds What is already known on the subject There are few data concerning the presentation of dysarthria following acute ischemic stroke. Moreover, previous research did not include objective measurements of speech characteristics and dysarthria severity. There was a need to determine prospectively speech characteristics, dysarthria type and severity in a stroke population using standardized assessments. What this paper adds to existing knowledge The findings of this study show a high prevalence of dysarthria following acute ischemic stroke. This study confirms previous findings that the speech of dysarthric patients following acute ischemic stroke was mostly characterized by imprecise articulation of consonants, a harsh voice quality and audible inspiration. The results of the objective measures confirm these findings. We added evidence that UUMN is the most prevalent dysarthria type in a stroke population, and that the majority of participants had mild dysarthria. A high rate of dysarthria recovery was seen in the first week following symptom onset. What are the potential or actual clinical implications of this work? The findings of this study contribute to the limited research performed regarding post-stroke dysarthria. The results can help optimize the distribution of healthcare resources. The majority of participants have a mild dysarthria, making the identification of the specific needs of this group an important area of concern. The evaluation of impaired speech subsystems and characteristics, especially supplemented with objective measures of acoustic parameters, and the classification of the type and severity of dysarthria can be helpful to monitor early progress in the acute phase post-stroke.

A new dimension in patent foramen ovale size estimation.

BACKGROUND: Detailed multidimensional assessment of patent foramen ovale (PFO) size with transesophageal echocardiography (TOE) may help to determine PFO pathogenicity in cryptogenic stroke patients. We explored the potential additive value of Live xPlane and three-dimensional (3D) TOE anatomical PFO sizing techniques. METHODS: Imaging data of 45 patients who underwent a 3D TOE-assisted percutaneous PFO closure were studied. The two-dimensional (2D) PFO separation distance and right-to-left (RL) contrast shunt magnitude were assessed on preprocedural TOE recordings. Peri-procedural measurements of the triangular anatomical PFO opening (base, height, and area) were performed after positioning of a stiff guidewire (SW) through the PFO, using Live xPlane imaging and 3D Zoom mode. RESULTS: The PFO SW base appeared on average 5 times larger than the preprocedural 2D PFO separation (median difference [IQR] = 13[5] mm; P < .001). For a same PFO separation, the width of the PFO base may vary significantly. The PFO SW base was significantly larger in patients with a large versus a small-to-moderate PFO RL contrast shunt (18 vs 15 mm; P = .007) and in those with a spontaneous versus a provoked shunt (18 vs 14 mm; P = .003). CONCLUSION: Live xPlane and 3D Zoom TOE allow peri-procedural measurement of the largest dimension of a PFO, which is the PFO base. Patients with a large or spontaneous RL contrast shunt appear to have a larger PFO base. The anatomical PFO base dimension may be taken into account for optimization of device and patient selection strategies.

Evolution of surgical treatment of carotid artery stenosis: a single center observational study.

Background: In 2009 and 2011 respectively ESVS and AHA/ASA guidelines recommended to operate patients with a symptomatic carotid artery stenosis within 14 days. This study aimed primarily to determine if an academic hospital has implemented these international guidelines about indication and timing of surgical treatment of carotid stenosis. Second, the influence of referral from another hospital on time from symptoms to surgery and the influence of time between neurological event and surgery on 30-day complication rate was studied. Third, the number of asymptomatic carotid artery lesions treated surgically was also evaluated in both periods.Methods: Retrospective study to compare patients with significant atherosclerotic carotid stenosis who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) in 2005-2006 versus patients treated in 2014-2016. Demographic data, treatment characteristics, interval between symptom and surgery and 30-day outcomes were collected.Results: In 2005-2006 38.1% (59/155) of the patients were treated for symptomatic carotid artery stenosis, in 2014-2016 this increased to 66.5% (121/182) (p < .001, 95% CI: 0.179-0.383). Median time from neurological symptom to surgery in symptomatic patients decreased from 30 to 13 d (p <.001, 95% CI: 1.476-2.763). Early surgery did not increase the 30-day postoperative complications (p = .19, 95% CI: 0.987-1.003). Referral from another hospital almost doubled the time interval between symptoms and surgery in 2014-2016 (p <.001, 95% CI: 1.386-2.827).Conclusions: Since the publication of the international guidelines, patients with symptomatic carotid artery stenosis were preferably surgically treated within 2 weeks at an academic institution. The number of treated asymptomatic carotid stenoses was drastically reduced.

Category specific recall in acute stroke: a case with letter speech.

Category selective recall in spontaneous speech after stroke has been reported only rarely. We recently described three cases demonstrating transient number speech in the acute stage of left hemispheric stroke and hypothesized a link with multilingualism and mathematical proficiency. In this report, we describe a similar case with a transient episode of utterances of randomly selected letters. Like in the three previous cases, this episode was preceded by a brief stage of mutism and ultimately evolved to Wernicke's aphasia over a period of days. This phenomenon is reviewed with reference to linguistic models and neuroanatomic and neurophysiological correlates.

The combined impact of dependency on caregivers, disability, and coping strategy on quality of life after ischemic stroke.

BACKGROUND: To estimate the additional impact of coping and of being dependent on caregivers, over and above the large effects of disability on utility after ischemic stroke. METHODS: A total of 539 patients were recruited into an observational, retrospective study when returning for a check-up between 3 and 36 months after an ischemic stroke. Patients' modified Rankin Scale (mRS), dependency on caregivers, the Brandtstädter and Renner Coping questionnaire (with summary scores: Tenacity of Goal Pursuit (TGP) and Flexible Goal Adjustment (FGA) coping styles), EQ-5D-3 L and co-morbidities were evaluated. RESULTS: In multivariable regression, greater disability (mRS) resulted in large utility losses, between 0.06 for mRS 1 to 0.65 for mRS 5 (p < 0.0001). Dependency on caregivers caused an additional dis-utility of 0.104 (p = 0.0006) which varied by mRS (0.044, 0.060, 0.083, 0.115, 0.150 and 0.173 for mRS 0-5). The effect of coping on utility varied by coping style, by the disability level of the patient and by his or her dependency on caregivers. FGA coping was associated with additional increases in utility (p < 0.0001) over and above the effect of disability and dependency, whereas TGA had no significant impact. FGA coping was associated with larger utility changes among more disabled patients (0.018 to 0.105 additional utility, for mRS 0 to mRS 5 respectively). Dependent patients had more to gain from FGA coping than patients who function independently of caregivers: utility gains were between 0.049 and 0.072 for moderate to high levels of FGA coping. In contrast, the same positive evolution in FGA coping resulted in 0.039 and 0.057 utility gain among independent patients. Finally, we found that important stroke risk factors and co-morbidities, such as diabetes and atrial fibrillation, were not predictors of EQ-5D utility in a multivariable setting. CONCLUSIONS: This study suggests that treatment strategies targeting flexible coping styles and decreasing dependency on caregivers may lead to significant gains in quality of life above and beyond treatment strategies that solely target disability.

Cognate effects and cognitive control in patients with parallel and differential bilingual aphasia.

BACKGROUND: Until today, there is no satisfying explanation for why one language may recover worse than another in differential bilingual aphasia. One potential explanation that has been largely unexplored is that differential aphasia is the consequence of a loss of language control rather than a loss of linguistic representations. Language control is part of a general control mechanism that also manages non-linguistic cognitive control. If this system is impaired, patients with differential aphasia could still show bilingual language activation, but they may be unable to manage activation in non-target languages, so that performance in another language is hindered. AIMS: To investigate whether a loss of cognitive control, rather than the loss of word representations in a particular language, might underlie differential aphasia symptoms. METHODS & PROCEDURES: We compared the performance of seven bilinguals with differential and eight bilinguals with parallel aphasia with 19 control bilinguals in a lexical decision and a flanker task to assess bilingual language co-activation and non-linguistic control respectively. OUTCOMES & RESULTS: We found similar cognate effects in the three groups, indicating similar lexical processing across groups. Additionally, we found a larger non-linguistic control congruency effect only for the patients with differential aphasia. CONCLUSIONS & IMPLICATIONS: The present data indicate preserved language co-activation for patients with parallel as well as differential aphasia. Furthermore, the results suggest a general cognitive control dysfunction, specifically for differential aphasia. Taken together, the results of the current study provide further support for the hypothesis of impaired cognitive control abilities in patients with differential aphasia, which has both theoretical and practical implications.

Rehabilitation of visuospatial neglect by prism adaptation: effects of a mild treatment regime. A randomised controlled trial.

Closely examining the effects, optimal regime and time window of prism adaptation (PA) promotes guidelines for effective rehabilitation practice. The effects of short-term repetitive PA on spatial neglect manifestations were evaluated in patients with heterogeneous post-stroke delays, using a digital Visuospatial Neglect Test Battery. Subsequently, potential differences in PA effects between acute, subacute or chronic neglect were explored. A multicentre randomised controlled trial was conducted in 43 right-hemisphere neglect patients. They were treated with a mild PA regime: seven sessions of experimental or placebo prism training over 7-12 days. The outcome measures were diverse neglect variables related to peripersonal navigation, visual extinction, visuospatial memory, bisection, cancellation, drawing and visual search. The treatment effects were assessed after a short and a long time interval. Two to 24 hours after PA, conventional effects were found for drawing and centred bisection, and novel effects for peripersonal visuospatial navigation, visual extinction, and non-motor memory (with caution). No effects were found for visual search times and cancellation. The assessments after three months were still indicative of PA benefits for navigational, drawing and memory functions. PA did not prove to be more effective in acute, subacute or chronic patients. The extension of effects is theoretically framed within the debate about the levels of cognitive processing that are impacted by PA. Clinical suggestions are formulated regarding PA implementation in neglect treatment.

Unruptured Brain Arteriovenous Malformations: Primary ONYX Embolization in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Patients.

BACKGROUND AND PURPOSE: In light of evidence from ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), neurovascular specialists had to reconsider deliberate treatment of unruptured brain arteriovenous malformations (uBAVMs). Our objective was to determine the outcomes of uBAVM treated with primary embolization using ethylene vinyl alcohol (ONYX). METHODS: Patients with uBAVM who met the inclusion criteria of ARUBA and were treated with primary Onyx embolization were assigned to this retrospective study. The primary outcome was the modified Rankin Scale score. Secondary outcomes were stroke or death because of uBAVM or intervention and uBAVM obliteration. RESULTS: Sixty-one patients (mean age, 38 years) were included. The median observation period was 60 months. Patients were treated by embolization alone (41.0%), embolization and radiosurgery (57.4%), or embolization and excision (1.6%). Occlusion was achieved in 44 of 57 patients with completed treatment (77.2%). Forty-seven patients (77.1%) had no clinical impairment at the end of observation (modified Rankin Scale score of <2). Twelve patients (19.7%) reached the outcome of stroke or death because of uBAVM or intervention. Treatment-related mortality was 6.6% (4 patients). CONCLUSIONS: In uBAVM, Onyx embolization alone or combined with stereotactic radiosurgery achieves a high occlusion rate. Morbidity remains a challenge, even if it seems lower than in the ARUBA trial.

Fibromuscular dysplasia - results of a multicentre study in Flanders.

BACKGROUND: Fibromuscular dysplasia (FMD) is an idiopathic, non-inflammatory, non-atherosclerotic vascular disease, resulting in focal narrowing of small and medium-sized arteries. Systematic recording of clinical data in central databases as in the US and France provided new insights into FMD. The main objectives of this multicentre study were to explore the epidemiology, pattern of vascular involvement, clinical manifestations, and management of FMD patients in Flanders. PATIENTS AND METHODS: Multicentre, retrospective registry of patients diagnosed with FMD based on medical imaging. RESULTS: Hundred-twenty-three FMD patients (83.7 % female) were included. Mean age at FMD diagnosis was 57.3 years (SD 15.8). More than half of patients (59.5 %) were hypertensive at the time of diagnosis. Neurological complaints such as headache (26.4 %) and dizziness (23.1 %) were also frequently reported. FMD was discovered incidentally in 10 patients (8.3 %). Nearly one quarter (22.8 %) of patients experienced a cerebrovascular event. Aneurysms were found in one-fifth (20.3 %) of patients and 11.4 % had an arterial dissection. FMD affected most frequently the renal (85.3 %), carotid (74.7 %), and vertebral (39.8 %) arteries. Renovascular FMD was more prevalent in men, whereas cerebrovascular FMD was more frequent in women. Multiple affected sites were documented in 25 of 61 (41.0 %) patients, having two or more vascular beds imaged. Digital subtraction angiography was most frequently used for detecting FMD. One third (32.9 %) of patients received an interventional treatment, mainly patients with renovascular FMD (32.8 % underwent percutaneous transluminal angioplasty) and patients with an intracranial carotid aneurysm (36.4 % were treated by means of coiling). CONCLUSIONS: Although differences existed, results of the Flemish registry were broadly in line with the US and French registries. Patient databases help to learn more about the natural history, progression, and management of FMD, based on real life clinical evidence.

Transcervical Carotid Stenting With Dynamic Flow Reversal Demonstrates Embolization Rates Comparable to Carotid Endarterectomy.

PURPOSE: To evaluate a series of patients treated electively with carotid endarterectomy (CEA), transfemoral carotid artery stenting with distal filter protection (CASdp), and transcervical carotid stenting with dynamic flow reversal (CASfr) monitored continuously with transcranial Doppler (TCD) during the procedure to detect intraoperative embolization rates. METHODS: Thirty-four patients (mean age 67.6 years; 24 men) with significant carotid stenosis underwent successful TCD monitoring during the revascularization procedure (10 CEA, 8 CASdp, and 16 CASfr). Ipsilateral microembolic signals were segregated into 3 phases: preprotection (until internal carotid artery cross-shunted or clamped if no shunt was used, filter deployed, or flow reversal established), protection (until clamp/shunt was removed, filter retrieved, or antegrade flow reestablished), and postprotection (after clamp/shunt or filter removal or restoration of normal flow). RESULTS: CASdp showed higher embolization rates than CEA or CASfr in the preprotection phase (p<0.001). In the protection phase, CASdp was again associated with more embolization compared with CEA and CASfr (p<0.001). In the postprotection phase, no differences between the revascularization therapies were observed. CASfr and CEA did not show significant differences in intraoperative embolization during any of the phases. CONCLUSION: TCD recordings demonstrated a significant reduction in embolization to the brain during transcervical carotid artery stent placement with the use of dynamic flow reversal compared to transfemoral CAS using distal filters. No significant differences in microembolization could be detected between CEA and CASfr. The observed lower embolization rates and lack of adverse events suggest that transcervical CAS with dynamic flow reversal is a promising technique and may be the preferred method when performing CAS.

Perioperative Embolization Load and S-100ß Do Not Predict Cognitive Outcome after Carotid Revascularization.

BACKGROUND: Cognitive changes after carotid revascularization have been reported in 10-20% of patients. The etiology of cognitive impairments remains largely unknown. This study evaluates the predictive value of S-100ß serum values and perioperative microembolization on cognition after carotid revascularization. METHODS: Forty-six patients with significant carotid stenosis underwent carotid endarterectomy (CEA, n = 26), transfemoral carotid artery stenting with distal protection (CASdp, n = 10), or transcervical carotid stenting with dynamic flow reversal (CASfr, n = 10). Twenty-six matched vascular patients without carotid stenosis were recruited as controls. All patients underwent comprehensive cognitive testing on the day before and 1 month after carotid revascularization. S-100ß analysis was performed in 31 cases pre-, peri-, and 2, 6, and 24 hr after carotid surgery, and in 25 patients transcranial Doppler monitoring was done during surgery. RESULTS: In the 3 treatment groups similar transient increases in S-100ß values were observed. CASdp was associated with a higher embolic load than CEA and CASfr, while CEA was also associated with less microembolization than CASfr. Cognitive improvement or deterioration could not be predicted by S-100ß or perioperative embolic load for any of the investigated cognitive domains. CONCLUSIONS: Cognitive deterioration could not be predicted using perioperative embolic load and S-100ß changes. A similar inverted u-curve of the S-100ß levels was observed in the 3 groups and may be caused by impairment in the blood-brain barrier during intervention, and not due to cerebral infarction. Distal protection CAS is associated with a higher embolic load than transcervical CAS using dynamic flow reversal and CEA, but the long-term impact of this higher embolic load is yet unknown. Perfusion-related measures seem promising in their ability to predict cognitive decline.