Sanjay Budhdeo1,2, Anderson Rodrigues Brandão de Paiva3,4, Charles Wade2, Laura Cardia Gomes Lopes5, Bruno Della-Ripa3, Indran Davagnanam6, Leandro Lucato7, Catherine J Mummery8, Fernando Kok3,9, Henry Houlden10, David J Werring11, David S Lynch12,13. 1. Department for Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK. 2. National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. 3. Neurology Department, Neurogenetics Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 4. Neurology Department, Hospital São Rafael-Rede D'Or São Luiz, Salvador, Brazil. 5. Department of Neurology, Psychology and Psychiatry, Universidade Estadual de São Paulo (UNESP), Botucatu, SP, Brazil. 6. Lysholm Department of Neuroradiology, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK. 7. Diagnostic Neuroradiology Section, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 8. Dementia Research Centre, Department of Neurodegenerative Disease, National Hospital for Neurology and Neurosurgery, London, UK. 9. Mendelics Genomic Analysis, São Paulo, Brazil. 10. Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London, UK. 11. Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK. 12. National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. david.lynch.13@ucl.ac.uk. 13. Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London, UK. david.lynch.13@ucl.ac.uk.
Abstract
BACKGROUND: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is a rare monogenic cause of cerebral small vessel disease. To date, fewer than 15 patients with CARASAL have been described, all of common European ancestry. METHODS: Clinical and imaging phenotypes of two patients are presented. Genetic variants were identified using targeted Sanger and focused exome sequencing, respectively. RESULTS: Both patients carried the same pathogenic p.Arg325Cys mutation in CTSA. One patient of Chinese ethnicity presented with migraine, tinnitus and slowly progressive cognitive impairment with significant cerebral small vessel disease in the absence of typical cardiovascular risk factors. She later suffered an ischaemic stroke. A second patient from Brazil, of Italian ethnicity developed progressive dysphagia and dysarthria in his 50s, he later developed hearing loss and chronic disequilibrium. Magnetic resonance imaging in both cases demonstrated extensive signal change in the deep cerebral white matter, anterior temporal lobes, thalami, internal and external capsules and brainstem. CONCLUSIONS: CARASAL should be considered in patients with early onset or severe cerebral small vessel disease, particularly where there are prominent symptoms or signs related to brainstem involvement, such as hearing dysfunction, tinnitus or dysphagia or where there is significant thalamic and brainstem involvement on imaging.
BACKGROUND: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is a rare monogenic cause of cerebral small vessel disease. To date, fewer than 15 patients with CARASAL have been described, all of common European ancestry. METHODS: Clinical and imaging phenotypes of two patients are presented. Genetic variants were identified using targeted Sanger and focused exome sequencing, respectively. RESULTS: Both patients carried the same pathogenic p.Arg325Cys mutation in CTSA. One patient of Chinese ethnicity presented with migraine, tinnitus and slowly progressive cognitive impairment with significant cerebral small vessel disease in the absence of typical cardiovascular risk factors. She later suffered an ischaemic stroke. A second patient from Brazil, of Italian ethnicity developed progressive dysphagia and dysarthria in his 50s, he later developed hearing loss and chronic disequilibrium. Magnetic resonance imaging in both cases demonstrated extensive signal change in the deep cerebral white matter, anterior temporal lobes, thalami, internal and external capsules and brainstem. CONCLUSIONS: CARASAL should be considered in patients with early onset or severe cerebral small vessel disease, particularly where there are prominent symptoms or signs related to brainstem involvement, such as hearing dysfunction, tinnitus or dysphagia or where there is significant thalamic and brainstem involvement on imaging.
Authors: Marianna Bugiani; Sietske H Kevelam; Hannah S Bakels; Quinten Waisfisz; Chantal Ceuterick-de Groote; Hans W M Niessen; Truus E M Abbink; Saskia A M J Lesnik Oberstein; Marjo S van der Knaap Journal: Neurology Date: 2016-09-24 Impact factor: 9.910
Authors: Yun Tae Hwang; Rahul Lakshmanan; Indran Davagnanam; Andrew G B Thompson; David S Lynch; Henry Houlden; Nin Bajaj; Sofia H Eriksson; Doris-Eva Bamiou; Jason D Warren Journal: Neurol Genet Date: 2017-07-06
Authors: Rhea Y Y Tan; Matthew Traylor; Karyn Megy; Daniel Duarte; Sri V V Deevi; Olga Shamardina; Rutendo P Mapeta; Willem H Ouwehand; Stefan Gräf; Kate Downes; Hugh S Markus Journal: Neurology Date: 2019-11-12 Impact factor: 9.910