Safety and Efficacy of Cangrelor in Acute Stroke Treated with Mechanical Thrombectomy: Endovascular Treatment of Ischemic Stroke Registry and Meta-analysis.

BACKGROUND AND PURPOSE: Rescue therapies are increasingly used in the setting of endovascular therapy for large-vessel occlusion strokes. Among these, cangrelor, a new P2Y12 inhibitor, offers promising pharmacologic properties to join the reperfusion strategies in acute stroke. We assessed the safety and efficacy profiles of cangrelor combined with endovascular therapy in patients with large-vessel-occlusion stroke. MATERIALS AND METHODS: We performed a retrospective patient data analysis in the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France from July 2018 to December 2020 and conducted a systematic review and meta-analysis using several data bases. Indications for cangrelor administration were rescue strategy in case of refractory intracranial occlusion with or without intracranial rescue stent placement, and cervical carotid artery stent placement in case of cervical occlusion (tandem occlusion or isolated cervical carotid occlusion). RESULTS: In the clinical registry, 44 patients were included (median initial NIHSS score, 12; prior intravenous thrombolysis, 29.5%). Intracranial stent placement was performed in 54.5% (n = 24/44), and cervical stent placement, in 27.3% (n = 12/44). Adjunctive aspirin and heparin were administered in 75% (n = 33/44) and 40.9% (n = 18/44), respectively. Rates of symptomatic intracerebral hemorrhage, parenchymal hematoma, and 90-day mortality were 9.5% (n = 4/42), 9.5% (n = 4/42), and 24.4% (n = 10/41). Favorable outcome (90-day mRS, 0-2) was reached in 51.2% (n = 21/41), and successful reperfusion, in 90.9% (n = 40/44). The literature search identified 6 studies involving a total of 171 subjects. In the meta-analysis, including our series data, symptomatic intracerebral hemorrhage occurred in 8.6% of patients (95% CI, 5.0%-14.3%) and favorable outcome was reached in 47.6% of patients (95% CI, 27.4%-68.7%). The 90-day mortality rate was 22.6% (95% CI, 13.6%-35.2%). Day 1 artery patency was observed in 89.7% (95% CI, 81.4%-94.6%). CONCLUSIONS: Cangrelor offers promising safety and efficacy profiles, especially considering the complex endovascular reperfusion procedures in which it is usually applied. Further large prospective data are required to confirm these findings.

Systematic prolonged video-electroencephalograms identify electrographic seizures in 5% of acute stroke patients with aphasia.

In stroke units, diagnosing seizures may be difficult, especially in aphasic patients. We discuss herein our systematic 4-hour video EEG monitoring of 61 patients with aphasia within the first 72hours after the onset of ischaemic stroke. Five electrographic seizures were identified in 3 patients, with no clinical signs apparent on the video and no symptoms reported by patients. We did not record status epilepticus nor generalized seizure. Comparative analyses disclosed a higher risk of early seizures in patients with haemorrhagic transformation. Video EEG monitoring detected electrographic seizures in 5% of stroke patients with aphasia. This monitoring could be useful for selected patients, especially those with haemorrhagic transformation.

Early neurological deterioration following thrombolysis for minor stroke with isolated internal carotid artery occlusion.

BACKGROUND AND PURPOSE: Better understanding the incidence, predictors and mechanisms of early neurological deterioration (END) following intravenous thrombolysis (IVT) for acute stroke with mild symptoms and isolated internal carotid artery occlusion (iICAo) may inform therapeutic decisions. METHODS: From a multicenter retrospective database, we extracted all patients with both National Institutes of Health Stroke Scale (NIHSS) score <6 and iICAo (i.e. not involving the Willis circle) on admission imaging, intended for IVT alone. END was defined as ≥4 NIHSS points increase within 24 h. END and no-END patients were compared for (i) pre-treatment clinical and imaging variables and (ii) occurrence of intracranial occlusion, carotid recanalization and parenchymal hemorrhage on follow-up imaging. RESULTS: Seventy-four patients were included, amongst whom 22 (30%) patients experienced END. Amongst pre-treatment variables, suprabulbar carotid occlusion was the only admission predictor of END following stepwise variable selection (odds ratio = 4.0, 95% confidence interval: 1.3-12.2; P = 0.015). On follow-up imaging, there was no instance of parenchymal hemorrhage, but an intracranial occlusion was now present in 76% vs. 0% of END and no-END patients, respectively (P < 0.001), and there was a trend toward higher carotid recanalization rate in END patients (29% vs. 9%, P = 0.07). As compared to no-END, END was strongly associated with a poor 3-month outcome. CONCLUSIONS: Early neurological deterioration is a frequent and highly deleterious event after IVT for minor stroke with iICAo, and is of thromboembolic origin in three out of four patients. The strong association with iICAo site-largely a function of underlying stroke etiology-may point to a different response of the thrombus to IVT. These findings suggest END may be preventable in this setting.

Large vessel stroke in six patients following SARS-CoV-2 infection: a retrospective case study series of acute thrombotic complications on stable underlying atherosclerotic disease.

BACKGROUND AND PURPOSE: Ischaemic stroke has been described in association with COVID-19. Several pathophysiological mechanisms have been suggested, i.e. prothrombotic state, cardiac injury etc. It was sought to assess the potential association between ischaemic stroke associated with SARS-CoV-2 infection and underlying atherosclerotic lesions. METHODS: A retrospective analysis of stroke related to large vessel occlusion was conducted amongst patients with SARS-CoV-2 infection and underlying mild atherosclerotic disease, between 19 March and 19 April 2020 in six different stroke centers in the Île-de France area, France. RESULTS: The median age was 52 years, median body mass index was 29.5 kg/m2 . All patients displayed previous vascular risk factors such as high blood pressure, diabetes, dyslipidemia or body mass index > 25. The delay between the first respiratory symptoms of COVID-19 and stroke was 11.5 days. At baseline, all had tandem occlusions, i.e. intracerebral and extracerebral thrombus assessed with computed tomography or magnetic resonance imaging. Cases displayed a large thrombus in the cervical carotid artery with underlying mild non-stenosing atheroma, after an etiological workup based on angio-computed tomography or magnetic resonance imaging and/or cervical echography. CONCLUSION: Our study should alert clinicians to scrutinize any new onset of ischaemic stroke during COVID-19 infection, mainly in patients with vascular risk factors or underlying atherosclerotic lesions.

Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review.

INTRODUCTION: Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive cerebral angiomatous-like microangiopathy characterized by diffuse and asymmetric white-matter lesions associated with multiple calcifications and cysts. The disease is caused by SNORD118 mutations. The entire clinical spectrum of LCC is not yet fully determined. MATERIAL AND METHODS: To define the clinical spectrum of LCC, we analyzed data from recently diagnosed cases and from the litterature. Both clinical and imaging features from our five LCC cases harboring compound heterozygous SNORD118 mutations were presented and all cases reported in the litterature reviewed. RESULTS: Ninety-two LCC cases including our five patients were identified. Consanguinity was rare (4%), and 97% of cases were symptomatic. Mean age of first clinical manifestations was 16.1±16.1 years (range 1 month-71 years) and was earlier in men (10.3±14.3 years) than in women (20.2±22.8 years) (P=0.02). The main inaugural symptoms were seizures (36%; mean age at onset: 5.2±9.5 years) and progressive neurological symptoms including ataxia, dystonia and spasticity (26%; 27.8±23.6 years). Intracranial hypertension was less frequently observed (14%), mostly in adults (mean age 31.5±13.2 years). Ischemic or hemorrhagic strokes were inaugural symptoms in two adults (2%). During follow-up, most patients developed progressive extrapyramidal, cerebellar and pyramidal signs (83%), cognitive decline (56%), seizures (37%), intracranial hypertension (30%) or stroke (2%). CONCLUSION: In LCC, the clinical spectrum is largely heterogeneous and the course of the disease appears highly variable in contrast to other hereditary cerebral small vessel diseases.

Epilepsy after stroke: Definitions, problems and a practical approach for clinicians.

Stroke, whether ischemic or hemorrhagic, is the main etiology of epilepsy in the elderly. However, incidences and outcomes differ according to stroke subtype and delay of onset following the stroke. While the medical literature is extensive, it is not always consistent, and many questions still remain regarding risk factors and management of vascular epilepsy. Thus, the present report here is an overview of the clinical aspects of vascular epilepsy using a practical approach that integrates data from meta-analyses and the more recently published expert recommendations.

Central retinal thickness assessment in a real life setting after cataract surgery in diabetic patients.

PURPOSE: To assess in a real life setting the progression of central retinal thickness (CRT) during the first month after surgery in diabetic patients without previous diabetic macular edema (DME) and to identify potential risk factors for DME leading to increased postoperative follow-up. METHODS: We conducted a prospective study of diabetic patients without history of DME who underwent uncomplicated cataract surgery. Best-corrected visual acuity (BCVA) and SD-OCT were performed 7 days and 1 month after surgery. We assumed absence of preoperative DME when there was no edema of SD-OCT at D7. Our primary endpoint was the central retinal thickness (CRT) variation between 7 days and 1 month after cataract surgery in patients without previous history of DME. RESULTS: We included 55 eyes of 42 patients. BCVA was 0.57±0.72 logMar (20/80) prior to surgery and increased significantly to 0.11±0.17 (20/25) at one month (P=0.001) post-surgery. The mean baseline CRT was 209±35µm and 229±69µm (P=0.06) one month after surgery. Four eyes (7.4%) developed macular edema at one month. We found no linear correlation between HbA1C and CRT. DISCUSSION/CONCLUSION: We found no link between a high level of HbA1C and postoperative increase in CRT. We found that cataract surgery in diabetic patients without previous DME has no negative impact on CRT, and visual outcomes are good. We suggest that in diabetic patients without complete visual recovery at 1-month post-cataract surgery, OCT examination should be performed in order to detect an early stage of DME.

Fundus autofluorescence in retinal artery occlusion: A more precise diagnosis.

IMPORTANCE: Retinal artery occlusion (RAO) is a medical emergency associated with a high risk of cerebral vascular accident and other cardiovascular events. Among patients with non-arteritic RAO, a retinal embolus is observed in approximately 40% of cases. Fundus examination and retinography are not reliable to predict the nature of the emboli. OBSERVATIONS: We report three consecutive cases of central and branch RAO that were investigated with fundus autofluorescence, fluorescein angiography and color retinal photographs. All patients underwent complete neurological and cardiovascular workups, with brain imaging, cardiac Doppler ultrasound, carotid Dopplers and Holter ECG's, to determine the underlying mechanism of retinal embolism. In the three cases, aged 77.7±4 years (2 women and 1 man), fundus autofluorescence demonstrated hyperautofluorescent emboli. In two cases, it allowed visualization of emboli that were not detected with fundus examination or retinography. The cardiovascular work-up demonstrated atheromatous carotid or aortic plaques in all patients. In one case, it permitted the diagnosis of RAO. Two of the three cases were considered to be of atherosclerotic origin and one of undefined origin. CONCLUSION AND RELEVANCE: Fundus autofluorescence may help to detect and characterize retinal emboli. Since lipofuscin, which is present in large quantity in atherosclerotic plaques, is the main fluorophore detected with fundus autofluorescence, this non-invasive and simple examination may give information about the underlying mechanism of retinal embolism, and thus impact the etiologic assessment of RAO. Additional studies are necessary to confirm this potential role of autofluorescence.

Ictal speech and language dysfunction in adult epilepsy: Clinical study of 95 seizures.

PURPOSE: To analyze the semiological characteristics of the language and speech disorders arising during epileptic seizures, and to describe the patterns of language and speech disorders that can predict laterality of the epileptic focus. METHOD: This study retrospectively analyzed 95 consecutive videos of seizures with language and/or speech disorders in 44 patients admitted for diagnostic video-EEG monitoring. Laterality of the epileptic focus was defined according to electro-clinical correlation studies and structural and functional neuroimaging findings. Language and speech disorders were analyzed by a neurologist and a speech therapist blinded to these data. RESULTS: Language and/or speech disorders were subdivided into eight dynamic patterns: pure anterior aphasia; anterior aphasia and vocal; anterior aphasia and "arthria"; pure posterior aphasia; posterior aphasia and vocal; pure vocal; vocal and arthria; and pure arthria. The epileptic focus was in the left hemisphere in more than 4/5 of seizures presenting with pure anterior aphasia or pure posterior aphasia patterns, while discharges originated in the right hemisphere in almost 2/3 of seizures presenting with a pure vocal pattern. No laterality value was found for the other patterns. CONCLUSION: Classification of the language and speech disorders arising during epileptic seizures into dynamic patterns may be useful for the optimal analysis of anatomo-electro-clinical correlations. In addition, our research has led to the development of standardized tests for analyses of language and speech disorders arising during seizures that can be conducted during video-EEG sessions.

Thrombolysis in Stroke Patients with Isolated Aphasia.

BACKGROUND: Data about evolution of aphasia following stroke are rare and controversial especially following fibrinolysis. The aim of this study was to describe the early clinical patterns of isolated aphasia in consecutive stroke patients with or without thrombolysis. METHODS: Clinical and radiological data of consecutive stroke patients were routinely entered in prospective registry. Patients were considered aphasic when NIHSS (National Institutes of Health Stroke Scale) item 9 >0. 'Isolated aphasia' was defined by aphasic patients without motor limb deficit. We created a 'composite language score' obtained by summing the NIHSS items 1b, 1c and 9, which reflects language-processing ability. Recovery of functions was evaluated as measured by global NIHSS, composite language score and language screening test (LAST) at baseline, H24 and day 7 (D7). 'Mild deficit' was defined as global NIHSS <5. RESULTS: A total of 100 consecutive patients met study criteria for isolated aphasia. Twenty-five underwent thrombolysis and 75 did not. There was no difference between the 2 groups concerning demographic characteristics, involved territories and presence of arterial occlusion, initial median NIHSS, composite language and LAST scores at entrance. Evolution was significantly better in thrombolysed patient for the 3 testings: NIHSS, composite language score and LAST at D7 (respective p = 0.0002; p = 0.01 and p = 0.004). Similar results were found when we focused on the subgroups of patients with initial 'mild' deficits (p = 0.01; p = 0.0003 and p = 0.007). No symptomatic hemorrhagic transformation occurred following thrombolysis. CONCLUSION: These data strongly suggest that thrombolysis is safe and effective in patients with 'isolated aphasia,' even if the global NIHSS score is <5.

Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene.

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures.

[LAST-Q: Adaptation and normalisation in Quebec of the Language Screening Test]. / LAST-Q: adaptation et normalisation franco-québécoises du Language Screening Test.

The goal of the present study was to adapt and to establish normative data for the recently developed Language Screening Test (LAST; Flamand-Roze et al., 2011) in the French-Canadian population according to age and level of education. After an adaptation process, 100 French-Canadian speakers were evaluated with the LAST-Q. As expected, a perfect score of 15/15 was obtained for all high level education participants, and a score of 14/15 was obtained for all participants with a lowest level of education or aged 80 years or more. Thanks to this adaptation, LAST-Q can be used in acute patients in stroke unit in Quebec.

Occurrence of multiple Cerebral Cavernous Malformations in a patient with Neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis 1 (NF1) belongs to the autosomal dominant neurocutaneous disorders' group, which mainly includes NF1 and NF2, tuberous sclerosis, von Hippel-Lindau disease and Cerebral Cavernous Malformations (CCMs). NF1 has a major impact on the nervous system, eye, skin, bone or cardiovascular system. Cerebrovascular lesions have been reported in NF1 including aneurysm, pseudoaneurysm, arteriovenous malformations, vascular stenosis or occlusion and Moya moya syndrome. OBJECTIVE: To report a case of an NF1 patient with multiple CCMs. OBSERVATION: A 47-year-old man with café-au-lait skin lesions, countless cutaneous neurofibromas, short stature and scoliosis was admitted for progressive spinal cord compression due to histologically proven neurofibroma. Systematic cerebral MRI screening including gradient echo sequences showed multiple asymptomatic CCMs. Screening of CCM1, CCM2 and CCM3 genes was negative while a deleterious frameshift mutation was identified in NF1 gene. CONCLUSION: While single CCM can occur in NF1 patients following radiation exposure, they are only rarely reported in non-irradiated NF1 brain. Even if it could be a fortuitous association, plausible links and explanations exist. If cerebral MRI can be systematic in NF1 to detect asymptomatic gliomas, used protocols in neuroradiology do not usually include gradient echo sequences, the most sensitive test for CCM detection, leading possibly to failure to detect these vascular lesions. More reports having this combination and further investigations of NF1 families will certainly provide a better understanding of links between these 2 phakomatoses, as recently reported with "multiple meningiomas" phenotype associated with multiple CCMs in patients with CCM3 gene mutations or café-au-lait skin lesions in CCM1 mutation carriers.

Significance of acute multiple infarcts in multiple cerebral circulations on initial diffusion weighted imaging in stroke patients.

OBJECTIVES: We attempted to assess the frequency, clinical and neuroradiological features of concomitant Acute Multiple Infarcts in Multiple Cerebral Circulations (AMIMCC) and to classify their causes. SUBJECTS AND METHODS: Consecutive patients treated for MR DWI-confirmed infarcts were included in this cohort. We retrospectively analyzed all patients with AMIMCC of our prospective database, studying clinical and radiological features. Causes of stroke were classified using TOAST and ASCO system (atherosclerosis, small vessel disease, cardiac source, other causes). RESULTS: Eighty AMIMCC were identified out of 824 consecutive patients with MR DWI-confirmed infarcts (9.7%). Compared with single infarct patients, AMIMCC patients presented similar age and risk factors. Only 24 AMIMCC patients (30%) presented symptoms suggesting multiple lesions before MRI. Cardiac origin existed in 39 of 80 patients (49%) including atrial fibrillation in 25 patients. Other sources of AMIMCC were hematologic diseases or coagulopathies such as intravascular coagulation in relation with cancer (n = 6; 7,5%) and vasculitis or systemic disorders (n = 5;6,5%). AMIMCC also appeared to originate from unilateral carotid diseases or intracranial stenosis, mostly atheromatous, in association with anatomic variations(n = 9;11%). In 21 patients, no cause was identified despite extensive investigations (26%). According to TOAST classification, 62% had a definite source for infarcts, 67% according to ASCO grade 1 classification. MRI data did not permit to orientate etiological explorations according to DWI appearance, associated leucoaraiosis or previous infarcts on FLAIR or microbleeding on gradient-echo sequences. CONCLUSIONS: AMIMCC are not rare and mostly need MRI to be detected. Multiple and various etiologies are implicated, including cardioembolic diseases in half of them, but also hematologic disorders and angeitis.

CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas.

Mutations of CCM3/PDCD10 cause 10-15% of hereditary cerebral cavernous malformations. The phenotypic characterization of CCM3-mutated patients has been hampered by the limited number of patients harboring a mutation in this gene. This is the first report on molecular and clinical features of a large cohort of CCM3 patients. Molecular screening for point mutations and deletions was used to identify 54 CCM3-mutated index patients. Age at referral and clinical onset, type of inaugural events and presence of extra-axial lesions were investigated in these 54 index patients and 22 of their mutated relatives. Mean age at clinical onset was 23.0 ± 16 years. Clinical onset occurred before 10 years in 26% of the patients, and cerebral hemorrhage was the initial presentation in 72% of these patients. Multiple extra-axial, dural-based lesions were detected in 7 unrelated patients. These lesions proved to be meningiomas in 3 patients who underwent neurosurgery and pathological examination. This 'multiple meningiomas' phenotype is not associated with a specific CCM3 mutation. Hence, CCM3 mutations are associated with a high risk of early-onset cerebral hemorrhage and with the presence of multiple meningiomas.

Short-term evolution of spinal cord damage in multiple sclerosis: a diffusion tensor MRI study.

INTRODUCTION: The potential of diffusion tensor imaging (DTI) to detect spinal cord abnormalities in patients with multiple sclerosis has already been demonstrated. The objective of this study was to apply DTI techniques to multiple sclerosis patients with a recently diagnosed spinal cord lesion, in order to demonstrate a correlation between variations of DTI parameters and clinical outcome, and to try to identify DTI parameters predictive of outcome. METHODS: A prospective single-centre study of patients with spinal cord relapse treated by intravenous steroid therapy was made. Patients were assessed clinically and by conventional MRI with DTI sequences at baseline and at 3 months. RESULTS: Sixteen patients were recruited. At 3 months, 12 patients were clinically improved. All but one patient had lower fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values than normal subjects in either inflammatory lesions or normal-appearing spinal cord. Patients who improved at 3 months presented a significant reduction in the radial diffusivity (p = 0.05) in lesions during the follow-up period. They also had a significant reduction in the mean ADC (p = 0.002), axial diffusivity (p = 0.02), radial diffusivity (p = 0.02) and a significant increase in FA values (p = 0.02) in normal-appearing spinal cord. Patients in whom the American Spinal Injury Association sensory score improved at 3 months showed a significantly higher FA (p = 0.009) and lower radial diffusivity (p = 0.04) in inflammatory lesion at baseline compared to patients with no improvement. CONCLUSION: DTI MRI detects more extensive abnormalities than conventional T2 MRI. A less marked decrease in FA value and more marked decreased in radial diffusivity inside the inflammatory lesion were associated with better outcome.