Hereditary Multi-Infarct Dementia

Sonninen, V.; Savontaus, Marja‐Liisa

doi:10.1159/000116158

Cited by 57 publications

(20 citation statements)

References 6 publications

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“…10 This mean age is very similar to those reported from elsewhere, eg, 49.3 years among French patients 2 and 46.1 years among German-Austrian patients, 3 although the age at the first-ever stroke in CADASIL is highly variable. Among the Finnish heterozygous R133C patients, 1 patient had a stroke at 30 and another at 32 years of age.…”

Section: Discussionsupporting

confidence: 86%

“…9 In Finland, the first family with CADASIL was identified and published as hereditary multi-infarct dementia in 1987. 10 After the gene test became available, 15 new, apparently different families with approximately 100 patients or presymptomatic carriers of the gene defect have been identified in Finland. Fourteen of the 16 families identified in Finland carry the same C475T transition mutation of the Notch3 gene, which leads to substitution of the 133 arginine by cysteine (R133C).…”

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confidence: 99%

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Phenotype of a Homozygous CADASIL Patient in Comparison to 9 Age-Matched Heterozygous Patients With the Same R133C Notch3 Mutation

Tuominen

Juvonen

Amberla

et al. 2001

Stroke

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Background and Purpose-CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein.We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. Methods-The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. Results-The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. Conclusions-Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.

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Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

Phenotype of a Homozygous CADASIL Patient in Comparison to 9 Age-Matched Heterozygous Patients With the Same R133C Notch3 Mutation

Tuominen

Juvonen

Amberla

et al. 2001

Stroke

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“…247 - 10 No mention had been made of the skin in previous reports. In the only article specifically mentioning the smooth muscle arteries, these were said to be normal.…”

Section: To the Editormentioning

confidence: 99%

“…In the case of cerebral infarction, ischemia may account for both seizures and stroke, or a silent ischemic lesion could be responsible for seizures occurring before a symptomatic stroke. 9 - 10 Obviously, neither explanation can directly relate epileptic seizures to hemorrhage. Cortical iron injection causes acute epileptiform activity in experimental models, 11 and this finding has been claimed to account for posttraumatic and poststroke epilepsy.…”

Section: Marie-magdeleine Ruchoux MD Phdmentioning

confidence: 99%

Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL.

Mm¹,

Chabriat²,

Bousser³

et al. 1994

Stroke

134

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ResponseWe are grateful to Drs Norris and Bladin for their interest in our review of the relative merits of ticlopidine and aspirin, 1 but we are not sure whether there is a baby in the bathwater at all. We feel less confident than they do that the point estimate of the overall advantage of ticlopidine over aspirin (8% with 3500 patients) would remain the same with greater numbers and would then reach statistical significance. This is what 95% confidence intervals (-4% to 19%) are all about: we simply don't know. By the way, we could not find a P of <.OO7 in the paper about the Ticlopidine Aspirin Stroke Study (nor indeed any significant difference for any outcome event that included more than stroke alone) 2 ; is this perhaps a subgroup analysis that did not survive the final stages of publication? What the report does contain is a table of side effects, totalling 62% in the ticlopidine group and 53% in the aspirin group (with 1300 mg!). These proportions have not been weighted for severity, but this uncertainty can be interpreted both ways, as it can for efficacy.

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“…This may be a form of inherited Binswanger's disease or perhaps a defect in white matter metabolism. 29 In 1987 Sonninen and Savontaus 30 reported a 51-member family (16 affected) with an inherited form of multi-infarct dementia. Examination of 14 patients showed a mean age of onset of 46 years and mean disease duration of 10.6 years.…”

Section: Familial Strokementioning

confidence: 99%

Genetic aspects of cerebrovascular disease.

Alberts

1991

Stroke

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Hereditary Multi-Infarct Dementia

Cited by 57 publications

References 6 publications

Phenotype of a Homozygous CADASIL Patient in Comparison to 9 Age-Matched Heterozygous Patients With the Same R133C Notch3 Mutation

Phenotype of a Homozygous CADASIL Patient in Comparison to 9 Age-Matched Heterozygous Patients With the Same R133C Notch3 Mutation

Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL.

Genetic aspects of cerebrovascular disease.

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