About CADASIL Our Program CADASIL studies at the Memory & Aging Program Other CADASIL research How to support CADASIL research About living with CADASIL CADASIL research areas    


CADASIL RESEARCH:
GENERAL RESEARCH

Background: The Clinical Picture
Article Summaries

Links to Abstracts & Articles: General Topics and Review Articles

Background: The Clinical Picture
Migraine with aura is often the earliest symptom of CADASIL, occurring in one third of patients and beginning in the third or fourth decade. By this age MRI usually shows early white matter changes. Recurrent stroke and TIA events are the most common symptoms of CADASIL, usually starting in the late 40's, and are often accompanied by the beginning of a gradual cognitive decline. Twenty to thirty percent of patients experience mood disorders, most commonly depression. The mean age of death is about 65 years. By the time of death almost all CADASIL patients have dementia. These facts notwithstanding, there is considerable variability among patients, even within the same family, in the course of the disease, and the duration from onset of symptoms to death has been observed to range from 3 to 43 years.

Article Summaries

Peters N et al.
A two-year clinical follow-up study in 80 CADASIL subjects: progression patterns and implications for clinical trials.
Stroke. 2004;35:1603-1608.   Abstract   Free Full Text Article

Eighty subjects from 56 CADASIL families were followed for 24 to 31 months to evaluate clinical progression, stroke incidence, and prognostic variables. The authors also aimed to determine the number of patients necessary to perform clinical trials. The patients underwent physical and neurologic assessment, neuropsychological evaluation, and stroke risk factor evaluation. At follow-up, investigators gathered information regarding TIAs, strokes, cognitive worsening, migraines, seizures, psychiatric disturbances and other neurologic symptoms. The authors report variable progression. Patients deteriorated on all clinical scores; however, the speed of deterioration was variable. Some patients declined in a stepwise fashion while others had a more gradual progression. Disability appeared to be tied to new strokes. Age and MRI lesion burden best predicted disease progression. The authors also noted a trend toward increased new stroke events in patients with elevated blood pressure and fibrinogen levels. Based on the frequency of clinical events observed in this study the authors estimate that a clinical trial will have to include 650 patients to demonstrate a clinical effect.

Back to Contents

Opherk C et al.
Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients.
Brain
. 2004;127:2533-9.   Abstract
The authors identified 411 subjects with a definite diagnosis of CADASIL. The median age at onset for stroke was 50.7 years in men and 52.5 years in women. The median ages at onset for inability to walk without assistance (men 58.9 and women 62.1), bedriddenness (men 62.1 and women 66.5); and death (men 64.6 and women 70.7) were significantly lower in men than in women . The median survival time of men but not women was significantly shorter than expected. At onset of the cause of death, 78% of the subjects were completely dependent and 63% were confined to bed. Pneumonia was the most frequent cause of death (38%), followed by sudden unexpected death (26%) and asphyxia (12%). The authors' findings also suggest possible genotype–phenotype correlations with regard to disease progression.

Dichgans M et al.
The phenotypic spectrum of CADASIL: clinical findings in 102 cases.
Ann Neurol. 1998;44:731-739.   Abstract
This study evaluated 102 CADASIL patients from 29 affected families to assess patterns of disease course. Patients underwent clinical evaluation, neuropsychiatric evaluation, and headache classification. 87% of subjects suffered ischemic episodes, 59% demonstrated cognitive defects, and 38% had migraines. Psychiatric disturbances included mood disorders, delusions, and mania as well as adjustment disorders due to disease manifestations. Epileptic seizures occurred in a pattern most consistent with post-stroke seizures. Onset of disability at a mild level was found in 25% of patients 40-44 years old, while 63% of patients older than 65 were so disabled that they were unable to walk. Disease duration from time of symptom onset to death ranged from 10-25 years.

Chabriat H et al.
Clinical spectrum of CADASIL: a study of 7 families.
Lancet. 1995;346:934-939.   Abstract
148 members of seven CADASIL families were evaluated. Among the 45 subjects who were clinically symptomatic, investigators found recurrent stroke or TIA in 84%, progressive or stepwise subcortical dementia in 31%, migraine with aura in 22% and mood disorders in 20%. Strokes were most consistent with lacunar infarct syndromes. The dementia observed consisted of problems with attention, apathy, memory problems, gait problems and motor weakness. All clinically affected subjects had white matter changes on MRI as well as 19 family members without clinical symptoms.

Back to Contents

Links to Abstracts and Articles: General Topics and Review Articles

Lesnik Oberstein SA, Haan J. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Panminerva Med. 2004 Dec;46(4):265-76.
Abstract

Kalaria RN, Viitanen M, Kalimo H, Dichgans M, Tabira T; CADASIL Group of Vas-Cog. The pathogenesis of CADASIL: an update. J Neurol Sci. 2004 Nov 15;226(1-2):35-9.
Abstract

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(Pt 11):2533-9.
Abstract

Singhal S, Bevan S, Barrick T, Rich P, Markus HS. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004 Sep;127(Pt 9):2031-8.
Abstract

Peters N, Herzog J, Opherk C, Dichgans M. A two-year clinical follow-up study in 80 CADASIL subjects: progression patterns and implications for clinical trials. Stroke. 2004 Jul;35(7):1603-8.
Abstract   Free Full Text Article

Chabriat H, Bousser MG. CADASIL. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Adv Neurol. 2003;92:147-50.
Abstract

Kalaria RN, Low WC, Oakley AE, Slade JY, Ince PG, Morris CM, Mizuno T. CADASIL and genetics of cerebral ischaemia. J Neural Transm Suppl. 2002;(63):75-90.
Abstract

Ruchoux MM, Brulin P, Brillault J, Dehouck MP, Cecchelli R, Bataillard M. Lessons from CADASIL. Ann N Y Acad Sci. 2002 Nov;977:224-31.
Abstract

Dichgans M. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: phenotypic and mutational spectrum. J Neurol Sci. 2002 Nov 15;203-204:77-80.
Abstract

Kalimo H, Ruchoux MM, Viitanen M, Kalaria RN. CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia. Brain Pathol. 2002 Jul;12(3):371-84.
Abstract

Back to Contents

Dichgans M. CADASIL: a monogenic condition causing stroke and subcortical vascular dementia. Cerebrovasc Dis. 2002;13 Suppl 2:37-41.
Abstract

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.
Abstract

Thomas NJ, Morris CM, Scaravilli F, Johansson J, Rossor M, De Lange R, St Clair D, Nicoll J, Blank C, Coulthard A, Bushby K, Ince PG, Burn D, Kalaria RN. Hereditary vascular dementia linked to notch 3 mutations. CADASIL in British families. Ann N Y Acad Sci. 2000 Apr;903:293-8.
Abstract

Viitanen M, Kalimo H. CADASIL: hereditary arteriopathy leading to multiple brain infarcts and dementia. Ann N Y Acad Sci. 2000 Apr;903:273-84.
Abstract

Kalimo H, Viitanen M, Amberla K, Juvonen V, Marttila R, Poyhonen M, Rinne JO, Savontaus M, Tuisku S, Winblad B. CADASIL: hereditary disease of arteries causing brain infarcts and dementia. Neuropathol Appl Neurobiol. 1999 Aug;25(4):257-65.
Abstract

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.
Abstract   Free Full Text Article

Davous P. CADASIL: a review with proposed diagnostic criteria. Eur J Neurol. 1998 May;5(3):219-233.
Abstract

Salloway S, Hong J. CADASIL syndrome: a genetic form of vascular dementia. J Geriatr Psychiatry Neurol. 1998 Summer;11(2):71-7.
Abstract

Dichgans M, Mayer M, Uttner I, Bruning R, Muller-Hocker J, Rungger G, Ebke M, Klockgether T, Gasser T. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998 Nov;44(5):731-9.
Abstract

Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep;56(9):947-64.
Abstract

Chabriat H, Vahedi K, Iba-Zizen MT, Joutel A, Nibbio A, Nagy TG, Krebs MO, Julien J, Dubois B, Ducrocq X, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995 Oct 7;346(8980):934-9.
Abstract

Bousser MG, Tournier-Lasserve E. Summary of t
he proceedings of the First International Workshop on CADASIL. Paris, May 19-21, 1993. Stroke. 1994 Mar;25(3):704-7.
Abstract

Back to Contents

Memory and Aging Program
Butler Hospital
345 Blackstone Blvd.
Providence, RI 02906


401-455-6403
Fax: 401-455-6405
memorydisorder.org

 

 

Website: Thea Brennan-Krohn
email: theabk@yahoo.com