Further Outpatient Care

Patients with CADASIL should be followed routinely by a neurologist or a vascular neurologist to monitor their degree of disability and rate of progression. Management is primarily symptom-based and addressing rehabilitation needs is paramount. Routine psychiatric follow-up is also reasonable if the patient suffers from a complex mental disorder.

Further Inpatient Care

Inpatient care of patients with CADASIL depends on the reason for admission. Inpatient care of patients with CADASIL who present with a stroke is not entirely different than patients without CADASIL who have a stroke (see Acute Stroke Management). However, safety and efficacy of recombinant tissue plasminogen activator (rtPA) in patients with CADASIL who present with an acute cerebral infarction within the therapeutic window has not been systematically assessed.

Inpatient & Outpatient Medications

See Medication.

Prognosis

Exact mortality rate in patients with CADASIL is unknown.

Age at onset for stroke is 45-50 years.

Mean age at death has been reported to be 61 years after a mean disease duration of approximately 23 years.^[6]

Close to 80% of patients are completely dependent immediately before death.^[7]

Genetic counseling

Because CADASIL has an autosomal dominant inheritance, patients and their families should be counseled on the nature of the disorder and the probability of developing or transmitting it.

Questions

Sourander P, Walinder J. Hereditary multi-infarct dementia. Morphological and clinical studies of a new disease. Acta Neuropathol. 1977 Aug 31. 39(3):247-54. [QxMD MEDLINE Link].
Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet. 1993 Mar. 3(3):256-9. [QxMD MEDLINE Link].
Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 1996 Oct 24. 383(6602):707-10. [QxMD MEDLINE Link].
Peters N, Freilinger T, Opherk C, Pfefferkorn T, Dichgans M. Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL. J Neurol Sci. 2007 Sep 15. 260(1-2):100-5. [QxMD MEDLINE Link].
Meschia JF, Brott TG, Brown RD Jr. Genetics of cerebrovascular disorders. Mayo Clin Proc. 2005 Jan. 80(1):122-32. [QxMD MEDLINE Link].
Dichgans M, Mayer M, Uttner I, Bruning R, Müller-Hocker J, Rungger G, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998 Nov. 44(5):731-9. [QxMD MEDLINE Link].
Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004 Nov. 127:2533-9. [QxMD MEDLINE Link].
Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep. 56(9):947-64. [QxMD MEDLINE Link].
Arboleda-Velasquez JF, Lopera F, Lopez E, Frosch MP, Sepulveda-Falla D, Gutierrez JE, et al. C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke. Neurology. 2002 Jul 23. 59(2):277-9. [QxMD MEDLINE Link].
Hartley J, Westmacott R, Decker J, Shroff M, Yoon G. Childhood-onset CADASIL: clinical, imaging, and neurocognitive features. J Child Neurol. 2010 May. 25(5):623-7. [QxMD MEDLINE Link].
Davous P. CADASIL: a review with proposed diagnostic criteria. Eur J Neurol. 1998 May. 5(3):219-233. [QxMD MEDLINE Link].
Desmond DW, Moroney JT, Lynch T, Chan S, Chin SS, Mohr JP. The natural history of CADASIL: a pooled analysis of previously published cases. Stroke. 1999 Jun. 30(6):1230-3. [QxMD MEDLINE Link].
Harris JG, Filley CM. CADASIL: neuropsychological findings in three generations of an affected family. J Int Neuropsychol Soc. 2001 Sep. 7(6):768-74. [QxMD MEDLINE Link].
Gunda B, Hervé D, Godin O, Bruno M, Reyes S, Alili N, et al. Effects of Gender on the Phenotype of CADASIL. Stroke. 2012 Jan. 43(1):137-41. [QxMD MEDLINE Link].
Chabriat H, Bousser MG. Neuropsychiatric manifestations in CADASIL. Dialogues Clin Neurosci. 2007. 9(2):199-208. [QxMD MEDLINE Link].
Choi JC, Kang SY, Kang JH, Park JK. Intracerebral hemorrhages in CADASIL. Neurology. 2006 Dec 12. 67(11):2042-4. [QxMD MEDLINE Link].
Bentley P, Wang T, Malik O, Nicholas R, Ban M, Sawcer S. CADASIL with cord involvement associated with a novel and atypical NOTCH3 mutation. J Neurol Neurosurg Psychiatry. 2011 Jan 8. [QxMD MEDLINE Link].
Ito D, Tanahashi N, Murata M, Sato H, Saito I, Watanabe K, et al. Notch3 gene polymorphism and ischaemic cerebrovascular disease. J Neurol Neurosurg Psychiatry. 2002 Mar. 72(3):382-4. [QxMD MEDLINE Link].
Peters N, Opherk C, Bergmann T, Castro M, Herzog J, Dichgans M. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. Arch Neurol. 2005 Jul. 62(7):1091-4. [QxMD MEDLINE Link].
Pescini F, Nannucci S, Bertaccini B, Salvadori E, Bianchi S, Ragno M, et al. The Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Scale: a screening tool to select patients for NOTCH3 gene analysis. Stroke. 2012 Nov. 43(11):2871-6. [QxMD MEDLINE Link].
Chabriat H, Levy C, Taillia H, Iba-Zizen MT, Vahedi K, Joutel A, et al. Patterns of MRI lesions in CADASIL. Neurology. 1998 Aug. 51(2):452-7. [QxMD MEDLINE Link].
Lesnik Oberstein SA, van den Boom R, Middelkoop HA, Ferrari MD, Knaap YM, van Houwelingen HC, et al. Incipient CADASIL. Arch Neurol. 2003 May. 60(5):707-12. [QxMD MEDLINE Link].
Dichgans M, Filippi M, Bruning R, Iannucci G, Berchtenbreiter C, Minicucci L, et al. Quantitative MRI in CADASIL: correlation with disability and cognitive performance. Neurology. 1999 Apr 22. 52(7):1361-7. [QxMD MEDLINE Link].
O'Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001 Mar 13. 56(5):628-34. [QxMD MEDLINE Link].
Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategies in CADASIL. Neurology. 2002 Oct 22. 59(8):1134-8. [QxMD MEDLINE Link].
Jouvent E, Viswanathan A, Mangin JF, O'Sullivan M, Guichard JP, Gschwendtner A, et al. Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL. Stroke. 2007 Jun. 38(6):1786-90. [QxMD MEDLINE Link].
Lesnik Oberstein SA, van den Boom R, van Buchem MA, van Houwelingen HC, Bakker E, Vollebregt E, et al. Cerebral microbleeds in CADASIL. Neurology. 2001 Sep 25. 57(6):1066-70. [QxMD MEDLINE Link].
Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet. 2001 Dec 15. 358(9298):2049-51. [QxMD MEDLINE Link].
LaPoint SF, Patel U, Rubio A. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Adv Anat Pathol. 2000 Sep. 7(5):307-21. [QxMD MEDLINE Link].
Malandrini A, Gaudiano C, Gambelli S, Berti G, Serni G, Bianchi S, et al. Diagnostic value of ultrastructural skin biopsy studies in CADASIL. Neurology. 2007 Apr 24. 68(17):1430-2. [QxMD MEDLINE Link].
Kusaba T, Hatta T, Kimura T, Sonomura K, Tanda S, Kishimoto N, et al. Renal involvement in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Clin Nephrol. 2007 Mar. 67(3):182-7. [QxMD MEDLINE Link].
Oh JH, Lee JS, Kang SY, Kang JH, Choi JC. Aspirin-associated intracerebral hemorrhage in a patient with CADASIL. Clin Neurol Neurosurg. 2008 Apr. 110(4):384-6. [QxMD MEDLINE Link].
Dichgans M, Markus HS, Salloway S, Verkkoniemi A, Moline M, Wang Q. Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL. Lancet Neurol. 2008 Apr. 7(4):310-8. [QxMD MEDLINE Link].
Forteza AM, Brozman B, Rabinstein AA, Romano JG, Bradley WG. Acetazolamide for the treatment of migraine with aura in CADASIL. Neurology. 2001 Dec 11. 57(11):2144-5. [QxMD MEDLINE Link].
Weller M, Dichgans J, Klockgether T. Acetazolamide-responsive migraine in CADASIL. Neurology. 1998 May. 50(5):1505. [QxMD MEDLINE Link].
Huang L, Yang Q, Zhang L, Chen X, Huang Q, Wang H. Acetazolamide improves cerebral hemodynamics in CADASIL. J Neurol Sci. 2010 May 15. 292(1-2):77-80. [QxMD MEDLINE Link].
Park SA, Yang CY, Choi SS, Kim WH. Assessment of cerebral hemodynamics to acetazolamide using brain perfusion SPECT in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Clin Nucl Med. 2011 Feb. 36(2):158-9. [QxMD MEDLINE Link].

Media Gallery

FLAIR MRI of the brain showing hyperintensities involving the temporal poles in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (Reprinted with permission from Mayo Clin Proc, Meschia, 2005.)
FLAIR MRI of the brain showing hyperintensities involving bilateral external capsules in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (Reprinted with permission from Mayo Clin Proc, Meschia, 2005.)

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Author

Reza Behrouz, DO, FACP Department of Neurology, UT Health San Antonio

Reza Behrouz, DO, FACP is a member of the following medical societies: American Academy of Neurology, American College of Physicians, Neurocritical Care Society, Society for Vascular Medicine, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University in St Louis School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Abbott Laboratories, advisory group.

Additional Contributors

Paul E Barkhaus, MD, FAAN, FAANEM Professor of Neurology and Physical Medicine and Rehabilitation, Chief, Neuromuscular and Autonomic Disorders Program, Director, ALS Program, Department of Neurology, Medical College of Wisconsin

Paul E Barkhaus, MD, FAAN, FAANEM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Neurological Association

Disclosure: Nothing to disclose.