Rare association between CADASIL and multiple system atrophy: a report of three Brazilian cases and literature review

Case presentation: Report of 3 cases of patients with association between CADASIL and MSA-C. Case 1: Woman, 58 years old, symptoms for 18 years, clinical presentation of imbalance, dysarthria and left crural hemiplegia. Progressing to urinary incontinence, short-term memory and language impairment, as well as dysphagia. Severe dependence on daily activities. Case 2: A 75-year-old woman, with pathology for 8 years, has been presenting with imbalance, short-term memory changes, left crural hemiparesis. 1 year ago the condition progressed to cognitive decline (moderate bradypsychism), urinary incontinence and dysphagia. Moderate dependence on daily activities. Case 3: Male, 55 years old. Clinical condition for 5 years, characterized by imbalance, bradykinesia, generalized decrease in muscle strength, bradypsychism and urinary incontinence. Intense paresthesia in the upper limbs and tongue region, denies dysphagia. Independent living. For all cases, secondary causes were ruled out and neuroimaging studies demonstrated typical CADASIL changes, as well as the “sign of the cross” in the pons and atrophy of the cerebellum and peduncles. NOTCH3 mutation gene was found in all cases. Discussion: CADASIL (Autosomal Dominant Cerebral Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an autosomal dominant pathology caused by mutations in the NOTCH 3 gene. Multiple System Atrophy - MSA is a group of neurodegenerative syndromes characterized by cerebellar ataxia, parkinsonism and dysautonomia. In this work, 3 cases of association of these 2 chronic pathologies were reported. All individuals were followed up on an outpatient basis according to radiological criteria compatible with the 2 pathologies, CADASIL and MSA-C (cerebellar form). MRIs were performed to assess the progression of structural degeneration and leukoencephalopathy. Final comments: This is a very rare association between CADASIL and MSA. Currently, only one post-mortem case has been described in the literature. All three forms had cerebellar involvement (MSA-c). The three cases presented cognitive impairment in several domains, with little response to the proposed medications. The association between CADASIL and MSA may be associated with some types of mutations in the NOTCH3 gene.