Advertisement

Human Physiology

, Volume 44, Issue 8, pp 860–863 | Cite as

Atypical Clinical Cases of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

  • A. A. MorozEmail author
  • N. Yu. Abramycheva
  • E. O. Ivanova
  • R. N. Konovalov
  • S. L. Timerbaeva
  • S. N. Illarioshkin
Article
  • 1 Downloads

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary CNS disease with autosomal dominant inheritance caused by NOTCH3 gene mutations. Typically, CADASIL manifests with headaches, recurrent strokes, and progressive cognitive decline. Neuroimaging plays an important diagnostic role as it reveals multiple lacunar infarcts in the basal ganglia, brainstem, and cerebellum, as well as focal white matter lesions and diffuse leukoaraiosis-type changes. CADASIL can sometimes have other symptoms and mimic different phenotypes atypical of the disease. We hereby present two genetically confirmed CADASIL cases that manifested with predominantly cerebellar or essential tremor combined with cognitive and affective disturbances. The main principles of diagnosis of this disease characterized by clinical polymorphism are discussed.

Keywords:

CADASIL the NOTCH3 gene clinical manifestations atypical phenotypes neuroimaging diagnosis 

REFERENCES

  1. 1.
    Joutel, A., Corpechot, C., Ducros, A., et al., Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia, Nature, 1996, vol. 383, pp. 707–710. PMID 8878478. doi 10.1038/ 383707a0CrossRefGoogle Scholar
  2. 2.
    Tournier-Lasserve, E., Iba-Zizen, M.-T., Romero, N., et al., Autosomal dominant syndrome with stroke like episodes and leukoencephalopathy, Stroke, 1991, vol. 22, pp. 1297–1302. PMID 1926242. doi 10.1161/ 01.STR.22.10.1297CrossRefGoogle Scholar
  3. 3.
    Choi, J., Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a genetic cause of cerebral small vessel disease, J. Clin. Neurol., 2010, vol. 6, pp. 1–9. PMID 20386637. doi 10.3988/jcn.2010.6.1.1CrossRefGoogle Scholar
  4. 4.
    Dong, Y., Hassan, A., Zhang, Z., et al., Yield of screening for CADASIL mutations in lacunar stroke and leukoaraiosis, Stroke, 2003, vol. 34, pp. 203–205. PMID 12511775. doi 10.1161/01.STR.0000048162. 16852.88CrossRefGoogle Scholar
  5. 5.
    Abramycheva, N., Stepanova, M., Kalashnikova, L., et al., New mutations in the Notch3 gene in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), J. Neurol. Sci., 2015, vol. 349, pp. 196–201. PMID 25623805. http://dx.doi.org/10.1016/j.jns.2015.01.018CrossRefGoogle Scholar
  6. 6.
    Trojano, M. and Paolicelli, D., The differential diagnosis of multiple sclerosis: classification and clinical features of relapsing and progressive neurological syndromes, Neurol. Sci., 2001, vol. 22, pp. 98–102. PMID 11794488. http://dx.doi.org/10.1007/s100720100044CrossRefGoogle Scholar
  7. 7.
    Kalaria, R., Viitanen, M., and Kalimo, H., The pathogenesis of CADASIL: an update, J. Neurol. Sci., 2004, vol. 226, pp. 35–39. PMID 15537516. http:// dx.doi.org/10.1016/j.jns.2004.09.008CrossRefGoogle Scholar
  8. 8.
    Razvi, S., Davidson, R., Bone, I., et al., The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in the west of Scotland, J. Neurol. Neurosurg. Psychiatry, 2005, vol. 76, pp. 739–741. PMID 15834040. doi 10.1136/jnnp.2004.051847CrossRefGoogle Scholar
  9. 9.
    Illarioshkin, S.N., Slominskii, P.A., Shadrina, M.I., et al., Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): the first description of Russian family with NOTCH3 identified mutation, Ann. Klin. Eksp. Nevrol., 2008, vol. 2, no. 2, pp. 45–50.Google Scholar
  10. 10.
    Gunda, B., Herve, D., Godin, O., et al., Effects of gender on the phenotype of CADASIL, Stroke, 2012, vol. 43, pp. 137–141. PMID 22033996. doi 10.1161/ STROKEAHA.111.631028CrossRefGoogle Scholar
  11. 11.
    Illarioshkin, S.N., Genetics of cerebrovascular diseases, in Ocherki angionevrologii (Description of Angioneurology), Suslina, Z.A., Ed., Moscow: Atmosfera, 2005, pp. 327–345.Google Scholar
  12. 12.
    Chabriat, H., Joutel, A., Vahedi, K., et al., CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): clinical features and neuroimaging, Bull. Acad. Natl. Med., 2000, vol. 184, pp. 1523–1531. PMID 11261256Google Scholar
  13. 13.
    Kim, Y., Choi, E.J., Choi, C.G., et al., Characteristics of CADASIL in Korea: a novel cysteine-sparing Notch3 mutation, Neurology, 2006, vol. 66, pp. 1511–15w16. PMID 16717210. doi 10.1212/01.wnl.0000216259. 99811.50CrossRefGoogle Scholar
  14. 14.
    Yousry, T., 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), Am. J. Neuroradiol., 1999, vol. 20, pp. 91–100. PMID 9974062Google Scholar
  15. 15.
    Liem, M., Lesnik-Oberstien, S., Haan, J., et al., Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: progression of MRI abnormalities in prospective 7-year follow-up study, Radiology, 2008, vol. 249, pp. 964–971. PMID 18840792. http://dx.doi.org/10.1148/radiol. 2492080357CrossRefGoogle Scholar
  16. 16.
    Davous, P., CADASIL: a review with proposed diagnostic criteria, Eur. J. Neurol., 1998, vol. 5, pp. 219–223. PMID 10210836. doi 10.1046/j.1468-1331.1998.530219.xCrossRefGoogle Scholar
  17. 17.
    Park, S., Park, B., Kyung, K.M., and Ho, J.Y., Case report: bipolar disorder as the first manifestation of CADASIL, BMC Psychiatry, 2014, vol. 14, p. 175. PMID 24929957. doi 10.1186/1471-244X-14-175CrossRefGoogle Scholar
  18. 18.
    Valenti, R., Pescini, F., and Antonini, S., Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview, Acta Neurol. Scand., 2011, vol. 124, pp. 390–395. PMID 21428968. doi 10.1111/j.1600-0404.2011.01512.xCrossRefGoogle Scholar
  19. 19.
    Chabriat, H. and Bousser, M.-G., Neuropsychiatric manifestations in CADASIL, Dialogues Clin. Neurosci., 2007, vol. 9, pp. 199–208. PMID 17726918Google Scholar
  20. 20.
    Kesebir, S., Koca, E.K., and Kilicaslan, E.E., CADASIL syndrome presenting with bipolar disorder, J. Mood Disord., 2012, vol. 2, pp. 115–118. doi 10.5455/ jmood.20120412113716CrossRefGoogle Scholar
  21. 21.
    Vedeler, C. and Bindoff, L., A family with atypical CADASIL, J. Neurol., 2011, vol. 258, pp. 1888–1889. PMID 21465151. doi 10.1007/s00415-011-6023-zCrossRefGoogle Scholar
  22. 22.
    Yoon, W.T. and Lee, P.H., Unusual manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mimicking multiple system atrophy (MSA), Mov. Disord., 2014, vol. 29, suppl. 1, p. 261.CrossRefGoogle Scholar
  23. 23.
    Malandrini, A., Carrera, P., and Ciacci, G., Unusual clinical features and early brain MRI lesions in a family with cerebral autosomal dominant arteriopathy, Neurology, 1997, vol. 48, pp. 1200–1203. PMID 9153443CrossRefGoogle Scholar
  24. 24.
    Velizarova, R., Mourand, I., Serafini, A., et al., Focal epilepsy as first symptom in CADASIL, Seizure, 2011, vol. 20, pp. 502–504. PMID 21414809. doi 10.1016/ j.seizure.2011.02.006CrossRefGoogle Scholar
  25. 25.
    Ragno, M., Berbellini, A., and Cacchio, G., Parkinsonism is a late, not rare, feature of CADASIL. A study on Italian patients carrying the R1006C mutation, Stroke, 2013, vol. 44, pp. 1147–1149. PMID 23412372. doi 10.1161/STROKEAHA.111.000458CrossRefGoogle Scholar
  26. 26.
    Song, S.K., Lee, J.S., Choi, J.C., and Kang, J.H., Various phenotypes of parkinsonism in patients with CADASIL, Mov. Disord., 2012, vol. 27, suppl. 1, p. 1198.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • A. A. Moroz
    • 1
    Email author
  • N. Yu. Abramycheva
    • 1
  • E. O. Ivanova
    • 1
  • R. N. Konovalov
    • 1
  • S. L. Timerbaeva
    • 1
  • S. N. Illarioshkin
    • 1
  1. 1.Research Center of NeurologyMoscowRussia

Personalised recommendations