Diagnostic Value of Ultrastructural Skin Biopsy Studies in Cadasil

Malandrini, Alex; Gaudiano, Caterina; Gambelli, Simona; Berti, Gianni De; Serni, Giovanni; Bianchi, Silvia; Federico, Antonio; Dotti, Maria Teresa

doi:10.1212/01.wnl.0000264018.46335.c8

Cited by 48 publications

(28 citation statements)

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“…In this series, nearly 50 % of clinically suspected cases were found not to have a mutation in exons 2 to 23. In Caucasians, skin biopsy was found to have a high specificity but fair sensitivity (45-75 %) [7,16]. We have previously demonstrated a low sensitivity of skin biopsy in 5 cases of genetically proven CADASIL in our hands [13].…”

Section: Discussionmentioning

confidence: 63%

Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

et al. 2009

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Section: Discussionmentioning

confidence: 63%

Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

et al. 2009

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“…These deposits are thought to be a diagnostic hallmark of CADASIL, as are GOM deposits [1,4,30,31]. Although the few studies of CADASIL patients that utilized immunohistochemical staining of Notch3 demonstrated higher sensitivity of that technique compared with electron microscopic examination of GOM, ranging from 45 to 90 % [23,32,33], Lesnik Oberstein et al [31] reported almost 10 % false-negative results for the immunohistochemical staining of Notch3 with formalin-fixed, paraffin-embedded skin biopsy specimens. In the present study, we observed clear granular deposits of Notch3 on the walls of the skin's blood vessels in all 16 CADASIL patients with confirmed NOTCH3 mutations.…”

Section: Discussionmentioning

confidence: 99%

Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014

Ueda¹,

Ueda

Nagatoshi³

et al. 2015

J Neurol

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This study elucidates the genotypic and phenotypic spectrum and histopathological findings related to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Japan. For this single-center retrospective observational study, we enrolled 215 patients who were clinically suspected of having CADASIL and were examined at Kumamoto University from 1997 to 2014, and we diagnosed CADASIL in 70 patients. We found 19 different NOTCH3 mutations in the patients, with the NOTCH3 Arg133Cys mutation being found most frequently. We also found the Arg75Pro mutation, a cysteine-sparing NOTCH3 mutation. CADASIL patients with this Arg75Pro mutation were frequently found throughout Japan, and fewer patients with the Arg75Pro mutation showed MRI hyperintensity in the anterior temporal pole compared with patients with other NOTCH3 mutations. Significantly more CADASIL patients with the NOTCH3 Arg133Cys mutation had hyperintensity in the external capsule compared with CADASIL patients with the other mutations not including the NOTCH3 Arg75Pro mutation. We also showed postmortem pathological findings of the first Japanese CADASIL case with the NOTCH3 Arg133Cys mutation, and histopathological findings of fresh frozen skin biopsy specimens of CADASIL patients. In conclusions, the spectrum of NOTCH3 mutations in Japanese CADASIL patients may be partially explained by founder effects. Genotype-phenotype correlations may exist in CADASIL, which should be considered so as to make an accurate diagnosis of CADASIL in each population. Fresh frozen skin biopsy specimens may aid detection of Notch3 deposits on vascular walls for an improved diagnosis of CADASIL.

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“…Presence of multiple deposits of GOM at ultrastructural examination of brain or skin vessels is the pathognomonic hallmark of CADASIL [1,8,11], with 100% specificity and 96% sensitivity [7]. Nevertheless, the origin, chemical nature and function of GOM deposits are still not clear.…”

Section: Abstract: Cadasil Notch3 Granular Osmiophilic Material Gmentioning

confidence: 99%

Letter to Editors Are granular osmiophilic material deposits an epiphenomenon in CADASIL?

Erro¹,

Moccia²,

Cervasio³

et al. 2015

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Diagnostic Value of Ultrastructural Skin Biopsy Studies in Cadasil

Cited by 48 publications

References 0 publications

Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014

Letter to Editors Are granular osmiophilic material deposits an epiphenomenon in CADASIL?

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