CADASIL: case report

Silva, Julio Cesar Vasconcelos da; Gasparetto, Emerson L.; Engelhardt, Eliasz

doi:10.1590/S1980-57642012DN06030013

ABSTRACT

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary cerebral arteriopathy caused by mutations in the Notch-3 gene. The diagnosis is reached by skin biopsy revealing presence of granular osmiophílic material (GOM), and/or by genetic testing for Notch-3. We report a case of a 52-year-old man with recurrent transient ischemic attacks (TIA), migraine, in addition to progressive sensory, motor and cognitive impairment. He was submitted to a neuropsychological assessment with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery along with other tests, as well as neuroimaging and genetic analysis for Notch-3, confirming the diagnosis. Executive function, memory, language and important apraxic changes were found. Imaging studies suggested greater involvement in the frontal lobes and deep areas of the brain.

Key words:
CADASIL; Notch3; cognition; neuropsychology

Resumo

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) é uma arteriopatia cerebral hereditária causada por mutações no gene Notch-3. O diagnóstico é feito através de biópsia da pele onde se verifica presença de material osmiofílico granular (GOM) e/ou por teste genético para Notch-3. É relatado o caso de um homem de 52 anos, com ataques isquêmicos transitórios (AIT) recorrentes, enxaqueca e comprometimento sensitivo e motor, e cognitivo progressivo. Foi submetido à avaliação neuropsicológica através da bateria CERAD (Consortium to Establish a Registry for Alzheimer's Disease) e outros testes, exames de neuroimagem e análise genética para Notch-3, que confirmou o diagnóstico. Foram encontradas alterações em função executiva, memória, linguagem e importante comprometimento apráxico. Exames de imagem sugerem um maior envolvimento dos lobos frontais e áreas profundas do cérebro.

Palavras-chave:
CADASIL; Notch-3; cognição; neuropsicologia

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REFERENCES

Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383(6602):707-710.
Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995;346 (8980):934-939.
Tournier-Lasserve E, Joutel A, Melki J, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 1993;3:256-259.
Chabriat H, Levy C, Taillia H et al. Patterns of MRI lesions in CADASIL. Neurology 1998;51:452-457.
Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategies in CADASIL. Neurology 2002;59:1134-1138.
Tomimoto H, Ohtani R, Wakita H, Lin JX, Miki Y, Mizuno T. [Distribution of ischemic leukoaraiosis in MRI: a difference from white matter lesions in CADASIL]. No To Shinkei. 2005;57:125-130.
Schultz A, Santoianni R, Hewan-Lowe K. Vasculopathic changes of CADASIL can be focal in skin biopsies. Ultrastruct Pathol 1999;23:241-247.
Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989;39: 1159-1165.
Bertolucci PHF, Okamoto IH, Toniolo Neto J, Ramos LR, Brucki SMD. Desempenho da população brasileira na bateria neuropsicológica do Consortion to Establish a Registry for Alzheimer´s Disease (CERAD). Rev Psiq Clin 1998;25:80-83.
Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. 2. ed. Tucson, AZ: Neuropsychology Press; 1993:912.
Watson YI, Arfken CL, Birge SJ. Clock completion: an objective screening test for dementia. J Am Geriatr Soc 1993;41:1235-1240.
Barbize J, Duizabo P. Manual de Neuropsicologia. São Paulo: Ed. Masson do Brasil; 1985:158.
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412-2414.
Montano MB, Ramos LR. [Validity of the Portuguese version of Clinical Dementia Rating]. Rev Saude Publica 2005;39:912-917.
Silva, JCV, Emerson, L, Gasparetto, André C. Cognitive and neuroimaging profile of a Brazilian family with CADASIL. Arq Neuropsiquiatr 2011; 69:436-440.
Charlton RA, Morris RG, Nitkunan A, Markus HS. The cognitive profiles of CADASIL and sporadic small vessel disease. Neurology 2006;66: 1523-1526.
Amberla K, Waljas M, Tuominen S, Almkvist O, Poyhonen M, Tuisku S, Kalimo H, Viitanen M. Insidious cognitive decline in CADASIL. Stroke 2004;35:1598-1602.
Buffon F, Porcher R, Hernandez K, Kurtz A, Pointeau S, Vahedi K, et al. Cognitive profile in CADASIL. J Neurol Neurosurg Psychiatry 2006;77: 175-180.
Peters N, Opherk C, Danek A, Ballard C, Herzog J, Dichgans M. The pattern of cognitive performance in CADASIL - a monogenic condition leading to subcortical ischemic vascular dementia. Am J Psych 2005; 162:2078-2085.
Basso A, Faglioni P, Luzzatti C. Methods in neuroanatomical research and experimental study of limb apraxia. In: Roy EA (editor). Neuropsychological studies of apraxia and related disorders. Amsterdam: North-Holland;1985:179-202.
Ragno M, Fabrizi GM, Cacchiò G, et al. Two novel Italian CADASIL families from Central Italy with mutation CGC-TGC at codon 1006 in the exon 19 Notch3 gene. Neurol Sci 2006;27:252-256.
Trojano L, Ragno M, Manca A, Caruso G. A kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A 2-year neuropsychological follow-up. J Neurol 1998;245:217-222.
Peter P. Pramstaller and C. David Marsden. The basal ganglia and apraxia. Brain 1996;119:319-340.
Yousry TA, Seelos K, Mayer M, et al. Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). AJNR Am J Neuroradiol 1999;20:91-100.
Liem MK, Lesnik Oberstein SA, Haan J, et al. MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study. Neurology 2009;72:143-148.

Publication Dates

Publication in this collection
Jul-Sep 2012

History

Received
08 June 2012
Accepted
15 Aug 2012

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383(6602):707-710.

[2] Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995;346 (8980):934-939.

[3] Tournier-Lasserve E, Joutel A, Melki J, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 1993;3:256-259.

[4] Chabriat H, Levy C, Taillia H et al. Patterns of MRI lesions in CADASIL. Neurology 1998;51:452-457.

[5] Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategies in CADASIL. Neurology 2002;59:1134-1138.

[6] Tomimoto H, Ohtani R, Wakita H, Lin JX, Miki Y, Mizuno T. [Distribution of ischemic leukoaraiosis in MRI: a difference from white matter lesions in CADASIL]. No To Shinkei. 2005;57:125-130.

[7] Schultz A, Santoianni R, Hewan-Lowe K. Vasculopathic changes of CADASIL can be focal in skin biopsies. Ultrastruct Pathol 1999;23:241-247.

[8] Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989;39: 1159-1165.

[9] Bertolucci PHF, Okamoto IH, Toniolo Neto J, Ramos LR, Brucki SMD. Desempenho da população brasileira na bateria neuropsicológica do Consortion to Establish a Registry for Alzheimer´s Disease (CERAD). Rev Psiq Clin 1998;25:80-83.

[10] Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. 2. ed. Tucson, AZ: Neuropsychology Press; 1993:912.

[11] Watson YI, Arfken CL, Birge SJ. Clock completion: an objective screening test for dementia. J Am Geriatr Soc 1993;41:1235-1240.

[12] Barbize J, Duizabo P. Manual de Neuropsicologia. São Paulo: Ed. Masson do Brasil; 1985:158.

[13] Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412-2414.

[14] Montano MB, Ramos LR. [Validity of the Portuguese version of Clinical Dementia Rating]. Rev Saude Publica 2005;39:912-917.

[15] Silva, JCV, Emerson, L, Gasparetto, André C. Cognitive and neuroimaging profile of a Brazilian family with CADASIL. Arq Neuropsiquiatr 2011; 69:436-440.

[16] Charlton RA, Morris RG, Nitkunan A, Markus HS. The cognitive profiles of CADASIL and sporadic small vessel disease. Neurology 2006;66: 1523-1526.

[17] Amberla K, Waljas M, Tuominen S, Almkvist O, Poyhonen M, Tuisku S, Kalimo H, Viitanen M. Insidious cognitive decline in CADASIL. Stroke 2004;35:1598-1602.

[18] Buffon F, Porcher R, Hernandez K, Kurtz A, Pointeau S, Vahedi K, et al. Cognitive profile in CADASIL. J Neurol Neurosurg Psychiatry 2006;77: 175-180.

[19] Peters N, Opherk C, Danek A, Ballard C, Herzog J, Dichgans M. The pattern of cognitive performance in CADASIL - a monogenic condition leading to subcortical ischemic vascular dementia. Am J Psych 2005; 162:2078-2085.

[20] Basso A, Faglioni P, Luzzatti C. Methods in neuroanatomical research and experimental study of limb apraxia. In: Roy EA (editor). Neuropsychological studies of apraxia and related disorders. Amsterdam: North-Holland;1985:179-202.

[21] Ragno M, Fabrizi GM, Cacchiò G, et al. Two novel Italian CADASIL families from Central Italy with mutation CGC-TGC at codon 1006 in the exon 19 Notch3 gene. Neurol Sci 2006;27:252-256.

[22] Trojano L, Ragno M, Manca A, Caruso G. A kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A 2-year neuropsychological follow-up. J Neurol 1998;245:217-222.

[23] Peter P. Pramstaller and C. David Marsden. The basal ganglia and apraxia. Brain 1996;119:319-340.

[24] Yousry TA, Seelos K, Mayer M, et al. Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). AJNR Am J Neuroradiol 1999;20:91-100.

[25] Liem MK, Lesnik Oberstein SA, Haan J, et al. MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study. Neurology 2009;72:143-148.

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