Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Prevalence, clinical characteristics, and risk factors of intracerebral haemorrhage in CADASIL: a case series and systematic review

“…Thirty studies were eligible, including 21 case reports [ 16 – 36 ], 7 case series [ 13 , 14 , 37 – 41 ], and 2 observational studies [ 11 , 15 ], comprising 119 CADASIL patients with history of ICH. Half of the studies were published in Asia, which consisted of 98 cases (76.0%).…”

Palliative care in CADASIL: diagnosis is only the first step

“…We read with interest the article published by Nogueira et al 1 titled “Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients.” We congratulate the authors for their very descriptive case series.…”

Pro‐Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property

“…21 The NOTCH3 p.R75P mutation has been identified in patients with CADASIL in South Korea and China, but not in non-East Asian people, such as British, French, Finnish, Swedish, German, and Brazilian, indicating that different NOTCH3 mutations are associated with distinct CADASIL phenotypes between East Asian and white European populations. 17,18,[22][23][24][25][26] Additionally, the cysteine-altering NOTCH3 p.R544C mutation was evaluated for its association with ICH, because it is an East Asian-specific mutation, but the result was negative. 6 Intriguingly, the first report of the NOTCH3 p.R75P mutation from South Korea showed a high frequency of this mutation among CADASIL patients with CMB.…”