Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous diseases caused by mutations affecting neuromuscular transmission. Even if the first symptoms mainly occur during childhood, adult neurologists must confront this challenging diagnosis and manage these patients throughout their adulthood. However, long-term follow-up data from large cohorts of CMS patients are lacking and the long-term prognosis of these patients is largely unknown. We report the clinical features, diagnostic difficulties, and long-term prognosis of a French nationwide cohort of 235 adult patients with genetically confirmed CMS followed in 23 specialized neuromuscular centres. Data were retrospectively analysed. Of the 235 patients, 123 were female (52.3%). The diagnosis was made in adulthood in 139 patients, 110 of whom presented their first symptoms before the age of 18. Mean follow-up time between first symptoms and last visit was 34 years (SD = 15.1). Pathogenic variants were found in 19 disease-related genes. CHRNE-low expressor variants were the most common (23.8%), followed by variants in DOK7 (18.7%) and RAPSN (14%). Genotypes were clustered into four groups according to the initial presentation: ocular group (CHRNE-LE, CHRND, FCCMS), distal group (SCCMS), limb-girdle group (RAPSN, COLQ, DOK7, GMPPB, GFPT1), and a variable-phenotype group (MUSK, AGRN). The phenotypical features of CMS did not change throughout life. Only four genotypes had a proportion of patients requiring intensive care unit (ICU) admission that exceeded 20%: RAPSN (54.8%), MUSK (50%), DOK7 (38.6%) and AGRN (25.0%). In RAPSN and MUSK patients most ICU admissions occurred before age 18 years and in DOK7 and AGRN patients at or after 18 years of age. Different patterns of disease course (stability, improvement and progressive worsening) may succeed one another in the same patient throughout life, particularly in AGRN, DOK7 and COLQ. At the last visit, 55% of SCCMS and 36.3% of DOK7 patients required ventilation; 36.3% of DOK7 patients, 25% of GMPPB patients and 20% of GFPT1 patients were wheelchair-bound; most of the patients who were both wheelchair-bound and ventilated were DOK7 patients. Six patients died in this cohort. The positive impact of therapy was striking, even in severely affected patients. In conclusion, even if motor and/or respiratory deterioration could occur in patients with initially moderate disease, particularly in DOK7, SCCMS and GFPT1 patients, the long-term prognosis for most CMS patients was favourable, with neither ventilation nor wheelchair needed at last visit. CHRNE patients did not worsen during adulthood and RAPSN patients, often severely affected in early childhood, subsequently improved.

Diagnostic Accuracy of Posterior/Anterior Periventricular WMH Ratio to Differentiate CAA From Hypertensive Arteriopathy.

BACKGROUND: Periventricular white matter hyperintensities (PVWMHs) in cerebral amyloid angiopathy (CAA) have been reported posterior predominant using semiautomated segmentation method and logarithmic transformation. We aimed to compare PVWMH extent and posterior/anterior distribution between patients with CAA and patients with hypertensive arteriopathy with radiological tools available in daily practice. METHODS: We retrospectively analyzed confluent PVWMH directly adjacent to lateral ventricles on axial FLAIR (fluid-attenuated inversion recovery) from 108 patients with CAA and 99 patients with hypertensive arteriopathy presenting with hemorrhage-related symptoms consecutively recruited in our stroke database (Nîmes University Hospital, France) between January 2015 and March 2022. For each of the left (L), right (R), anterior (A), and posterior (P) horns of lateral ventricles, the maximal distance between the outer PVWMH border and ventricle border was measured. The sum of anterior left PVWMH and anterior right PVWMH, and posterior left PVWMH and posterior right PVWMH resulted in anterior and posterior extent, respectively. RESULTS: Compared with hypertensive arteriopathy, patients with CAA were older (median, 77 versus 71; P=0.0010) and less frequently male (46% versus 64%; P=0.012) and had less frequent hypertension (45% versus 63%; P=0.013) and more chronic hemorrhages (P<0.0001). CAA showed slightly more extensive anterior right PVWMH (median, 6.50 versus 5.90 mm; P=0.034), far more extensive (all P<0.0001) posterior left PVWMH (median, 13.95 versus 6.95 mm), posterior right PVWMH (median, 14.15 versus 5.45 mm), posterior (median, 27.95 versus 13.00 mm), and total (median, 39.60 versus 24.65 mm) PVWMH, and higher posterior/anterior ratios (median, 1.82 versus 1.01). Age-/sex-adjusted model predicting CAA incorporating total PVWMH extent and posterior/anterior ratios for the given score (-4.3683+0.0268×PVWMH-T+0.3749×posterior/anterior PVWMH ratio+0.0394×age+0.3046 when female) showed highest area under the curve (0.76 [0.70-0.83]), with a 72% [62.50-80.99] sensitivity and 76% [67.18-84.12] specificity. Values above the optimal threshold of 0.22 for the score showed a crude relative risk of 2.75 (2.26-2.37; P<0.0001). CONCLUSIONS: Severe posterior PVWMH and high posterior/anterior PVWMH ratio assessed by radiological tools used in daily practice are associated with probable CAA versus hypertensive arteriopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05486897.

Real-life effectiveness 1 year after switching to avalglucosidase alfa in late-onset Pompe disease patients worsening on alglucosidase alfa therapy: A French cohort study.

INTRODUCTION: Late-onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α-glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long-term treatment results vary. Avalglucosidase alfa demonstrated non-inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa. METHODS: Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow-up. Respiratory (forced vital capacity [FVC]) and motor functions (Six-Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values. RESULTS: Twenty-nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: -1 m/year on the 6MWT after the switch versus -63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different. DISCUSSION: At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening. CONCLUSION: Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.

From Sensors to Digital Twins toward an Iterative Approach for Existing Manufacturing Systems.

Digital twin technology is a highly valued asset in the manufacturing sector, with its unique capability to bridge the gap between the physical and virtual parts. The impact of the rapid increase in this technology is based on the collection of real-world data, its standardization, and its widespread deployment on an existing manufacturing system. This encompasses sensor values, PLC internal states, and IoT, as well as how the means of linking these data with their digital counterparts. It is challenging to implement digital twins on a large scale due to the heterogeneity of protocols and data structuring of subsystems. To facilitate the integration of the digital twin into existing manufacturing architectures, we propose in this paper a framework that enables the deployment of scalable digital twins from sensors to services of digital twins in an iterative manner.

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.

Unilateral subcortical extensive dilated perivascular spaces associated with superior sagittal sinus perivenous dilated spaces.

We present the MRI of a 70-year-old patient showing unilateral subcortical extensive dilated perivascular spaces with surrounding fluid-attenuated inversion recovery hyperintensities associated with the presence of small cysts and tubular hypointensities in and near the superior sagittal sinus co-locating with draining cortical veins on gadolinium-enhanced T1-weighted imaging representing probably (dilated) spaces between pial sheath and cortical vein walls. These (peri)venous superior sagittal sinus cysts seem to represent either hydrops cause (by blocking interstitial fluid flow in perivenous subpial space, via meningeal lymphatics) or consequence (where cysts might have been formed due to subpial fluid flow obstruction by unknown cause).

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.

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.

Association of symptomatic atherosclerotic carotid arteries with plaque areas showing low densities on computed tomographic angiography.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage is a key feature of vulnerable carotid atherosclerotic plaque (CAP), associated with low densities (<25 Hounsfield units [HU]) on computed tomographic angiography (CTA). This study aimed to analyze CAP on routine CTA performed in patients with symptomatic and asymptomatic carotid stenosis undergoing carotid endarterectomy (CEA) by assessing HU of the CAP area showing the lowest density (CAPALD) using radiological tools available in daily clinical practice, and to compare CAPALD values between symptomatic and asymptomatic carotids. METHODS: We retrospectively screened preoperative CTA scans of 206 consecutive adult patients undergoing CEA for symptomatic or asymptomatic stenosis. CAPALD values were compared between symptomatic and asymptomatic carotids. Asymptomatic carotids included arteries contralateral to the symptomatic CEA artery, and asymptomatic stenotic arteries undergoing CEA and their contralateral arteries. Carotids were excluded when there was <30% stenosis, or when CAP could not be identified or CAPALD could not be measured. RESULTS: In total, 95 symptomatic and 112 asymptomatic carotids (derived from 174 patients) were analyzed. In multivariate analysis, symptomatic arteries showed more severe stenosis (median 70% vs. 67%, p = 0.0228) and lower CAPALD values (median 17 vs. 25 HU, p = 0.049), whereas degree of stenosis and CAPALD values were not correlated (rho = -0.02, p = 0.77). HU values of <25 were more frequent in symptomatic than asymptomatic carotids (68% vs. 47%, p = 0.0022). CONCLUSIONS: On CTA, symptomatic carotids are associated with CAP areas with low densities. CTA analysis of CAP may be interesting to help identify vulnerable plaques at risk for future stroke, especially in patients lacking strict indications for CEA based on the current guidelines.

Symmetrical isolated globus pallidus infarction due to bilateral carotid artery dissection.

A 43-year-old woman presented 1 day after whiplash injury with behavior change, hypersomnia, and abulia. MRI showed symmetrical globus pallidus infarction and bilateral watershed hypoperfusion. Magnetic resonance angiography (MRA) showed bilateral carotid artery dissection. To our knowledge, isolated symmetrical globus pallidus infarction related to bilateral carotid dissection has never been reported earlier.

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.

Finger-Like Projections in Lobar Haemorrhage on Early Magnetic Resonance Imaging Is Associated with Probable Cerebral Amyloid Angiopathy.

BACKGROUND: Recently, finger-like projections (FLP) and subarachnoid haemorrhage extension (SAHE) of lobar intracerebral haemorrhage (LH) on acute CT together with ApoE4 genotype have been used in a prediction model for histopathologically proven cerebral amyloid angiopathy (CAA). Our aim was to analyse FLP and SAHE on acute/early subacute magnetic resonance imaging (MRI) and to assess the association with probable CAA diagnosis according to modified Boston criteria. METHODS: We retrospectively studied MRI scans (and CT if available) performed <7 days in a cohort of consecutive acute LH patients >55 years. RESULTS: Forty-six patients (24 men and 22 women; mean age 73; 28 probable and 18 possible CAA patients) were analysed. Mean symptom onset-MRI delay was 1.3 days (including 26 patients with MRI <24 h). Both probable and possible CAA groups were comparable regarding age, sex, time MRI and CT performance, MRI field strength, and LH volume. On MRI, both FLP and SAHE were observed more frequently in probable than in possible CAA (FLP 43 vs. 6%, p = 0.0073; SAHE 79 vs. 44%, p = 0.027), and associated with larger LH volumes (FLP, p = 0.011; SAHE, p = 0.047). FLP was associated with earlier performed MRI (mean 0.3 vs. 1.75 days, p = 0.025). In the subgroup of 35 patients with available CT (performed a mean of 2.2 days before or after MRI), FLP presence on CT was observed more frequently in probable than in possible CAA (57 vs. 7%, p = 0.0039). Concordance of MRI and CT for FLP presence/absence was 89%. CONCLUSIONS: In acute LH patients, FLP and SAHE on acute/early subacute phase MRI are associated with probable CAA diagnosis. Larger LH volumes are associated with FLP and SAHE on MRI, and early performed MRI with FLP.

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.

Small obliquely oriented cortical cerebellar infarctions are associated with cardioembolic stroke.

BACKGROUND: A revised classification of cerebellar infarctions (CI) may uncover unrecognized associations with etiologic stroke subtypes. We hypothesized that obliquely oriented small cortical cerebellar infarction (SCCI) representing end zone infarctions on MRI would be associated with cardiac embolism. METHODS: We retrospectively analyzed consecutive stroke patients recruited between January-December 2016 in our center. Analyzed baseline characteristics: sex, age, cardiovascular risk factors, history of stroke or atrial fibrillation (AF). TOAST classification was used for determining stroke subtype. Acute infarction location (anterior/posterior/mixed anterior-posterior circulation), acute uni- or multiterritorial infarction, and acute or chronic CI/SCCI/non-SCCI were assessed by MRI, and vertebrobasilar stenosis/occlusion by vessel imaging. Pre-specified analysis was also performed in patients without known high cardioembolic risk (known AF history or acute multiterritorial infarction). RESULTS: We included 452 patients (CI in 154, isolated SCCI in 55, isolated non-SCCI in 50, and mixed SCCI/non-SCCI in 49). Both SCCI and non-SCCI were associated with AF history (SCCI, p = 0.021; non-SCCI, p = 0.004), additional acute posterior circulation infarction (p < 0.001 both CI-subtypes), multiterritorial infarctions (SCCI, p = 0.003; non-SCCI, p < 0.001) and cardioembolic more frequent than large-artery atherosclerosis origin (p < 0.001 for both CI-subtypes). SCCI was associated with older age (p < 0.001), whereas non-SCCI was associated with stroke history (p = 0.036) and vertebrobasilar stenosis/occlusion (p = 0.002). SCCI were older (p = 0.046) than non-SCCI patients, had less frequently prior stroke (p < 0.001), and more frequent cardioembolic infarction (p = 0.025). In patients without known high cardioembolic risk (n = 348), SCCI was strongly associated with subsequent cardioembolism diagnosis (OR 3.00 [CI 1.58-5.73, p < 0.001]). No such association was present in non-SCCI. CONCLUSIONS: Acute or chronic SCCI are strongly associated with a cardioembolic origin.

Inflammatory facioscapulohumeral muscular dystrophy type 2 in 18p deletion syndrome.

Facioscapulohumeral muscular dystrophy (FSHD) has been shown to be related to genetic and epigenetic derepression of DUX4 (mapping to chromosome 4), a gene located within a repeat array of D4Z4 sequences of polymorphic length. FSHD type 1 (FSHD1) is associated with pathogenic D4Z4 repeat array contraction, while FSHD type 2 (FSHD2) is associated with SMCHD1 variants (a chromatin modifier gene that maps to the short arm of chromosome 18). Both FSHD types require permissive polyadenylation signal (4qA) downstream of the D4Z4 array.

Infratentorial Cerebral Microbleeds in Patients with Cerebral Amyloid Angiopathy.

BACKGROUND: Cerebral microbleeds (CMBs) observed in hypertension-related arteriolosclerosis tend to occur in the supratentorial deep gray matter, whereas those in cerebral amyloid angiopathy (CAA) typically show a supratentorial lobar distribution. Recently, superficial spontaneous cerebellar intracerebral hemorrhage has been shown to be associated with strictly lobar CMBs. Few data exist on infratentorial CMBs in CAA. The purpose of this study was to describe the incidence, number, and characteristics of infratentorial CMBs in patients with CAA. METHODS: We performed a retrospective analysis of data derived from a prospectively recruited cohort of patients with possible or probable CAA according to the Boston criteria. RESULTS: A total of 115 patients with CAA (59% with CMBs) were analyzed. Eighteen percent of all patients with CAA had at least 1 infratentorial CMB. For patients with CMBs, presence and median CMB number were as follows: brainstem, 8% and 1; deep cerebellum, 4% and 1; superficial cerebellum, 10% and 1.5. Brainstem or deep cerebellum CMB was associated with the presence of and with higher numbers of supratentorial deep gray matter CMBs (P < .001 for both) and with hypertension (P = .048), whereas superficial cerebellar CMB was associated with the presence of and with higher numbers of supratentorial lobar CMBs (P < .001 for both). CONCLUSIONS: Based on our study, superficial cerebellar CMBs (in low numbers when present) seem to be a CAA-related phenomenon observed in a minority of patients who have CAA with a relatively high supratentorial lobar CMB load.