The Natural History of CADASIL
To the Editor:
I read with much interest the article by Desmond et al1 about the natural history of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). Similar work I conducted previously was published 1 year ago2 and unfortunately ignored by the authors. The methods we used were similar: making a review of the literature on MEDLINE and collecting documented cases on pathological or genetical bases. A preliminary communication of this work was presented at the 8th meeting of the European Neurological Society held in Nice in June 1998.3 During the same session, Dichgans et al presented the work they later published,4 which was not included in our own review submitted in 1997. Similarly, the cohort described by Chabriat et al5 was not included in our work. Our own data included all the references listed by Desmond et al up to References 27 to 36, which appeared later. A few documented pathological cases, either familial or apparently sporadic, were included in our review and not in that of Desmond et al.
Our data, including 134 documented cases, showed similar results, with a mean age at onset of 40.3±13.8 years. Major initial symptoms were stroke, transient ischemic attacks, or strokelike episodes in 36.5% of the cases and migraine in 34.6%, with a significant difference of age at onset (24.8±11.6 years versus 43.9±9.8 years for stroke and 47±7.8 years for transient ischemic attacks). Other initial symptoms, including depression, dementia, and other psychiatric or neurological presentations, were much less frequent (each <10%). We found similar data about the duration of the disease (mean 13.6±10.7 years) and age at death (56.7±10.9 years), much lower than those published in the cohorts of Chabriat et al5 and Dichgans et al4 (21.5 and 23.3 years for mean duration of the disease and 64.5 and 61 years for mean age at death, respectively). It was suggested in our study2 that stroke or transient ischemic attacks were a little less frequent (70%) than as published in the French and German cohorts (84% and 87%, respectively), a result confirmed (67%) by Desmond et al.1
Additional data were collected from our review about causes of death, showing stroke in 26 documented cases to be the most frequent cause (32%), followed by bronchopneumonia and other decubitus complications. One of the diagnostic criteria of CADASIL is the absence of vascular risk factors related to the pathology, particularly hypertension. In the 79 cases screened in the literature for such factors, we showed that 11 patients (14%) had a mild hypertension. Signs or symptoms of any other vascular disease were unusual, but myocardial infarction occurring at a young age, sometimes antedating the neurological signs, was documented in 7.5%.
From our review, we suggested diagnostic criteria for probable and possible forms of CADASIL in order to give to clinicians guidelines for identification of the patients on clinical and imaging bases for further genetic analysis. Alternative etiologies were presented, with the diagnoses of multiple sclerosis and vascular dementia being the most frequently encountered. We conclude that the work of Desmond et al, although subject to the same methodological weakness as ours, was not unique, as they assumed, but instead a valuable confirmation of previously published data. However, in the context of expansion of the spectrum of genetically determined cerebral arteriopathies, the confirmative data of the natural history of CADASIL by 2 independent studies looks worthwhile.
- Copyright © 1999 by American Heart Association
We regret that we failed to acknowledge the related study of Dr DavousR1 in our article,R2 but we did not know of its existence because the journal in which it was published is not referenced in MEDLINE. In addition, that journal is not a part of the otherwise extensive holdings of the Health Sciences Library of Columbia University, and his article was not referenced in any of the previous publications on CADASIL that we reviewed. Finally, it should be noted that the abstract cited by Dr Davous,R3 which was published after our initial presentation of our findings at the 50th annual meeting of the American Academy of Neurology in 1998,R4 summarized his important proposal of operationalized criteria for the diagnosis of CADASIL but made no reference to any formal pooled analysis of previously published cases relevant to the clinical characteristics and natural history of that disorder. We are pleased to recognize the consistencies between the findings of our 2 studies, however, and it is our hope that future collaborative efforts crossing national boundaries will help us to gain an increased understanding of the features of CADASIL and move toward the development of an effective therapy.
Davous P. CADASIL: a review with proposed diagnostic criteria. Eur J Neurol.. 1998;5:219–233.
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;30:1230–1233.
Davous P. CADASIL: proposed diagnostic criteria. J Neurol.. 1998;245:344. Abstract.
Desmond DW, Moroney JT, Lynch T, Chan S, Chin SS, Mohr JP. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): a meta-analysis of previously published cases. Neurology. 1998;50(suppl 4):A441–A442. Abstract.