UNASSIGNED: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant inherited arterial disease, with lacunar infarction resulting from intracranial small vessel lesions being the most prevalent clinical manifestation of CADASIL. However, large-scale cerebral infarction caused by intracranial non-small vessels occlusion is relatively uncommon, and reports of vascular intervention and long-term antiplatelet drug treatment for patients with CADASIL and large-scale cerebral infarction are rarer.
UNASSIGNED: We reported a 52 year-old male who experienced a significant cerebral infarction due to an occlusion in the second segment of the left middle cerebral artery, 4 months subsequent to being diagnosed with CADASIL. Following the benefit and risk assessment, the patient underwent intracranial vascular thrombectomy and balloon dilation angioplasty. Subsequently, he was administered dual antiplatelet therapy for 3 months, followed by mono antiplatelet therapy.
UNASSIGNED: After undergoing intracranial vascular intervention and receiving antiplatelet therapy, significant improvement in the symptoms were observed. The National Institutes of Health Stroke Scale score decreased from 6 to 2 points, and no bleeding lesions were detected on the head computed tomography during regular follow-up visits after discharge.
UNASSIGNED: Our case highlights the possibility that patients with CADASIL may also encounter extensive cerebral infarction resulting from stenosis or occlusion of intracranial non-small vessels. Considering the specific circumstances of the patient, intravascular intervention and antiplatelet therapy can be regarded as viable treatment options for individuals with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare genetic disorder caused by mutations in the NOTCH3 gene, resulting in subcortical infarctions and leukoencephalopathy. It predominantly affects the brain\'s small blood arteries, resulting in repeated ischemic episodes including transient ischemic attacks and strokes leading to cognitive impairment and mental symptoms. We provide a case study of a 25-year-old patient suspected of having meningoencephalitis. CADASIL was diagnosed based on clinical examination, imaging investigations, and genetic analysis. Optimal patient care for this complicated illness requires early detection and proper management.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of cerebral small vessel disease, caused by a mutation in the NOTCH3 gene on chromosome 19. The main clinical features include migraine (often with aura), early onset, recurrent subcortical ischemic strokes, mood disturbances, and cognitive impairment, frequently leading to dementia and disability with a reduction in life expectancy. Cerebral chronic global hypoperfusion, due to impaired cerebrovascular reactivity, seems to play a primary role in CADASIL. Migraine is the most common early feature of the disease, and to date, there are no consensus guidelines for treatment. Given the vasomodulatory influence of many antimigraine drugs, there is concern about their use in this disease. In particular, the calcitonin gene-related peptide (CGRP) system serves as a vasodilatory protective mechanism during cerebral and cardiac ischemia. Blocking this system could exacerbate ischemic events. Herein, we describe two CADASIL patients who were treated with the calcitonin gene-related peptide (CGRP) receptor antagonist erenumab for chronic migraine, reporting a significant reduction in the frequency of attacks and intensity of pain, and an improvement in quality of life without adverse effects.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one kind of monogenic hereditary small-vessel disease in the brain caused by mutations in the NOTCH3 gene. However, it is rare for CADASIL to recur with different clinical manifestations in 1 patient, and some atypical clinical manifestations can easily lead to misdiagnosis by clinical physicians.
UNASSIGNED: A 34-year-old male presented with transient speech disorder accompanied by weakness in the left side of the body for 1 day in June 2020. Magnetic resonance imaging showed acute ischemic infarction in right centrum semiovale, along with multiple abnormal white matter hyperintensities in the brain. Genetic sequencing identified a heterozygous mutation in the NOTCH3 gene. The patient experienced recurrent episodes in 2021 and 2023, with varying clinical symptoms including visual blurring, abnormal limb sensation, and sudden cognitive dysfunction.
METHODS: The diagnoses of CADASIL is based on clinical manifestations, imaging results, and genetic reports.
UNASSIGNED: The patient was received symptomatic treatment including antiplatelet aggregation therapy, lipid regulation, and plaque stabilization, resulting in improved symptoms.
RESULTS: During the course of the disease, after medication treatment and rehabilitation exercise, the patient clinical symptoms have significantly improved. Currently, the patient is closely following up and regularly undergoing relevant examinations.
CONCLUSIONS: In this rare case, we found that CADASIL can recur multiple times in a patient with different clinical symptoms, which can easily lead to clinical misdiagnosis. Clinicians should consider the possibility of CADASIL in young patients with sudden typical neurological dysfunction.

BACKGROUND: CADASIL(Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)is an inherited small vessel disease caused by mutations in NOTCH3 gene. Although NOTCH3 has numerous hotspots of gene mutations, mutations in exons 9 are rare. The p.C484T gene mutation type associated with it has not been reported in any relevant cases yet. Furthermore, CADASIL patients rarely present with acute bilateral multiple subcortical infarcts.
METHODS: We report the case of a Chinese female patient with CADASIL who experienced \"an acute bilateral subcortical infarction\" because of\"hemodynamic changes and hypercoagulability\". In genetic testing, we discovered a new Cys484Tyr mutation in exon 9, which has also been found in the patient\'s two daughters.
CONCLUSIONS: It is important to note that this discovery not only expands the mutation spectrum of Notch3 mutations in CADASIL patients, but also examines the mechanism behind acute bilateral subcortical infarction in CADASIL patients via case reviews and literature reviews, in order to provide some clinical recommendations for early intervention, diagnosis, and treatment in similar cases in the future.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.
METHODS: A retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.
RESULTS: Ten cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).
CONCLUSIONS: ICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.

UNASSIGNED: Spontaneous coronary artery dissection (SCAD) is increasingly diagnosed as one of the infrequent causes of acute coronary syndrome. Almost no cause was identified in half of the cases. Here, we report a rare case of spontaneous coronary artery dissection with leucoencephalopathy (SCADLE) associated with a mutation of the thrombospondin Type 1 domain containing 1 (THSD1) gene.
UNASSIGNED: A 36-year-old lady who presented with ischaemic type chest pain for 4 h duration and found to have anterior ST elevation myocardial infarction. She was thrombolysed with tenecteplase and had good resolution. Her coronary angiogram revealed a spontaneous dissection in the left anterior descending artery (LAD) with TIMI 3 flow. Intra-vascular ultrasound study confirmed the LAD spiral dissection and intramural haematoma. She has had recurrent transient ischaemic attacks 5 years and 7 years ago, and there was a significant family history of young stroke. Her magnetic resonance imaging (MRI) brain showed peri-ventricular white matter hyper-intensities and lacunar infarcts suggestive of leucoencephalopathy. An association with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and SCAD was suspected, and exome gene sequencing followed by genetic analysis was performed. It identified a variant c.67°C > G (p. Arg224Gly) in the THSD1 gene with normal NOTCH gene.
UNASSIGNED: Thrombospondin Type 1 domain containing 1 gene encodes proteins involving in the extra-cellular matrix (ECM). This THSD1 mutation is inherited as an autosomal dominant fashion and associated with arterial dissections (rare), fibromuscular dysplasia, intra-cranial aneurysm, and subarachnoid haemorrhages. Therefore, SCADLE could be a result of arteriopathy secondary to dysfunction of ECM proteins in cerebral and coronary vasculature resulting in neurological manifestations and MRI features like in CADASIL and SCAD.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil.
We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation.
We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively.
The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.
Arteriopatia cerebral autossômica dominante com enfartes subcorticais e leucoencefalopatia (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, em inglês) é uma causa genética de acidente vascular cerebral (AVC) isquêmico e a forma mais comum de acidente vascular cerebral não aterosclerótico. Apesar de ser a doença vascular hereditária mais prevalente que há, os dados clínicos para a população brasileira são escassos. Considerando que o Brasil tem uma das constituições genéticas mais heterogêneas do mundo, o conhecimento sobre perfis genéticos e epidemiológicos é obrigatório. Este estudo teve como objetivo elucidar as características clínicas e epidemiológicas de pacientes com CADASIL no Brasil. MéTODOS:  Apresentamos uma série de casos envolvendo 6 hospitais de reabilitação no Brasil, e relatamos dados clínicos e epidemiológicos de prontuários de pacientes admitidos entre 2002 e 2019 com confirmação genética.
incluímos 26 pacientes (16 mulheres) em que as mutações nos éxons 4 e 19 eram as mais comuns. A idade média de início da doença foi de 45 anos. O AVC isquêmico foi o primeiro sintoma cardinal em 19 pacientes. Comprometimento cognitivo, demência e manifestações psiquiátricas foram detectados em 17, seis e 16 pacientes, respectivamente. Ao todo, 8 pacientes apresentavam enxaqueca, sendo com aura em 6 (75%) pacientes. Hiperintensidades de substância branca no polo temporal e na cápsula externa foram encontradas em 20 (91%) e 15 pacientes (68%), respectivamente. A pontuação mediana na escala de Fazekas foi de 2. Infartos lacunares, microssangramentos e macro-hemorragias foram observadas em 18 (82%), 9 (41%) e 2 (9%) pacientes, respectivamente. CONCLUSãO:  O presente estudo representa a mais extensa série de pacientes brasileiros com CADASIL publicada até o momento, e relatamos o primeiro caso de micro-hemorragia na medula espinhal de um paciente com CADASIL. A maior parte dos nossos dados clínicos e epidemiológicos está de acordo com as coortes europeias, exceto para micro-hemorragias e macro-hemorragias, para as quais as taxas se enquadram entre as das coortes europeias e asiáticas.

BACKGROUND: Cerebral autosomal dominant arteriosis with subcortical infarction and leukoencephalopathy (CADASIL) is a single-gene small-vessel disease of the brain characterized by migraine, recurrent ischemic stroke, psychiatric disorders, progressive cognitive decline, and occasional intracerebral hemorrhage.[1]NOTCH3 was identified as a pathogenic gene for CADASIL.[2] The NOTCH3 gene encodes a membrane-bound receptor protein, and to date, several different NOTCH3 gene mutations have been identified.[3] Here, we report a case of CADASIL with a heterozygous mutation c.931T > G (thymine > guanine) on the exon region of the NOTCH3 gene, resulting in an amino acid change p.C311G (cysteine > glycine).
METHODS: We report a case of a female patient with CADASIL whose genetic sequencing revealed a mutation in the NOTCH3 gene. However, this patient did not exhibit any of the typical clinical findings of CADASIL but the patient\'s cerebral magnetic resonance imaging was consistent with the characteristic findings of CADASIL.
CONCLUSIONS: This case reminds us that mutations caused by different mutation sites present different clinical symptoms.

The authors present a new paper examining the disturbances in ocular circulation and electrophysiological changes in the presence of neuro-ophthalmic manifestations in a patient with cerebral autosomal dominant arteriopathy with subcortical infracts and leucoencephalopathy (CADASIL). Symptoms reported by the patient included: transient vision loss (TVL), migraines, diplopia, bilateral peripheral visual field loss and convergence insufficiency. CADASIL was confirmed by the presence of NOTCH3 gene mutation (p.Cys212Gly), the presence of granular osmiophilic material (GOM) in cutaneous vessels in an immunohistochemistry test (IHC) and bilateral focal vasogenic lesions in the white matter of the cerebral hemisphere, with micro-focal infarct in the left external capsule on a magnetic resonance imaging test (MRI). Color Doppler imaging (CDI) confirmed decreased blood flow and increased vascular resistance in the retinal and posterior ciliary arteries, with reduced P50 wave amplitude on a pattern electroretinogram (PERG). An eye fundus examination and fluorescein angiography (FA) revealed the constriction of retinal vessels and a peripheral retinal pigment epithelium (RPE) atrophy with focal drusen. The authors suggest that the cause of TVL may be changes in the hemodynamics of the retinochoroid vessels associated with the narrowing of small vessels and the presence of druses in the retina-which is supported by a decrease in the amplitude of the P50 wave in PERG, changes in OCT correlating simultaneously with changes in MRI imaging and other neurological symptoms.