Home / Deep Research / CADASIL Type 1

CADASIL Type 1

CADASIL Type 1 (NOTCH3-related) — Disease Characteristics Research Report

2026-05-08
Falcon MONDO:0007432 Model: Edison Scientific Literature 36 citations

CADASIL Type 1 (NOTCH3-related) — Disease Characteristics Research Report

1. Disease information

1.1 Concise overview

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset, autosomal dominant hereditary cerebral small-vessel disease that typically presents in mid-adulthood with ischemic strokes/transient ischemic attacks, migraine (often with aura), mood disturbance, and progressive cognitive impairment leading to vascular dementia. (cerfontaine2024associationofnotch3 pages 1-2, papakonstantinou2019notch3andcadasil pages 1-3, bersano2017cadasiltreatmentand pages 1-3)

A current mechanistic consensus is that CADASIL is “considered to be caused by accumulation of the mutant NOTCH3 extracellular domain (N3ECD)” with possible contribution from impaired Notch signaling; however, “the process leading to N3ECD accumulation and its association with canonical NOTCH3 signaling remain unknown.” (Mizuta et al., 2024-01-18) (mizuta2024progresstoclarify pages 1-2)

1.2 Key identifiers and synonyms (from retrieved evidence)

Not located in the retrieved sources for this run: MONDO ID, Orphanet ORPHA number, ICD-10/ICD-11 codes, MeSH ID. These identifiers should be added by consulting the corresponding terminologies (e.g., MONDO/Orphanet/WHO ICD/MeSH) because they are not directly available in the evidence retrieved here.

1.3 Source types for disease definition

2. Etiology

2.1 Disease causal factors

CADASIL is caused primarily by pathogenic NOTCH3 variants. The archetypal CADASIL-causing variants are heterozygous missense mutations in the NOTCH3 extracellular epidermal growth factor-like repeat (EGFr) region that alter the number of cysteines (creating an odd number), leading to misfolding/aggregation of the NOTCH3 extracellular domain and characteristic vessel-wall pathology. (hu2021notch3variantsand pages 1-2, mizuta2024progresstoclarify pages 1-2)

Direct abstract quote (mechanistic framing): “CADASIL … is adult-onset and considered to be caused by accumulation of the mutant NOTCH3 extracellular domain (N3ECD) and, possibly, by an impairment in Notch signaling.” (Mizuta et al., 2024-01-18) (mizuta2024progresstoclarify pages 1-2)

2.2 Risk factors (genetic and non-genetic modifiers)

Genetic (variant-position effects): NOTCH3 variant position in EGFr domains strongly influences phenotype severity; variants in EGFr 1–6 are repeatedly associated with more severe disease than EGFr 7–34, beyond effects of age/sex/vascular risk factors. (dupe2023phenotypicvariabilityin pages 1-2, kaisaridi2025determiningclinicaldisease pages 1-5, cao2024phenotypesassociatedwith pages 13-14)

Non-genetic modifiers: Large cohort analyses identify age, male sex, and vascular risk factors (notably hypertension, hypercholesterolemia; also smoking in progression modeling) as contributors to clinical severity/progression, in addition to NOTCH3 variant position. (dupe2023phenotypicvariabilityin pages 1-2, kaisaridi2025determiningclinicaldisease pages 1-5)

Hemorrhage-related treatment/risk factor signal: In a UK register/systematic review study, anticoagulation was associated with higher intracerebral hemorrhage (ICH) risk in CADASIL (see §11 and §12). (sukhonpanich2024prevalenceclinicalcharacteristics pages 1-2)

2.3 Protective factors and gene–environment interaction

No protective factors or explicit gene–environment interaction models were identified in the retrieved evidence.

3. Phenotypes (with suggested HPO terms)

3.1 Core phenotype spectrum

Across large cohort and registry/EMR studies, CADASIL commonly includes: - Migraine with aura (often early feature). Suggested HPO: HP:0002076 (Migraine); aura can be mapped to HP:0012378 (Aura) (phenotype label). (cerfontaine2024associationofnotch3 pages 1-2, bersano2017cadasiltreatmentand pages 1-3) - Ischemic stroke/TIA, typically lacunar subtype. Suggested HPO: HP:0001297 (Stroke); HP:0002326 (Transient ischemic attack). (cerfontaine2024associationofnotch3 pages 1-2, bersano2017cadasiltreatmentand pages 1-3) - Cognitive impairment/executive dysfunction → vascular dementia. Suggested HPO: HP:0100543 (Cognitive impairment); HP:0000726 (Dementia). (cerfontaine2024associationofnotch3 pages 1-2, bersano2017cadasiltreatmentand pages 1-3) - Psychiatric/mood disturbance (depression/apathy). Suggested HPO: HP:0000716 (Depression); HP:0000741 (Apathy). (cerfontaine2024associationofnotch3 pages 1-2, bersano2017cadasiltreatmentand pages 1-3) - Seizures (minority). Suggested HPO: HP:0001250 (Seizures). (bersano2017cadasiltreatmentand pages 1-3)

3.2 Quantitative phenotype frequencies from recent cohorts/case series

  • Brazilian genetically confirmed series (n=26): ischemic stroke first symptom 19/26; cognitive impairment 17/26; dementia 6/26; psychiatric manifestations 16/26; recurrent migraine 8/26, aura in 6/8 (75%). (Nogueira et al., online 2023-05-08) (nogueira2023clinicalandepidemiological pages 1-2)
  • TriNetX EMR network analysis (n=914): 596/914 (65.2%) had documented cerebrovascular events; among CADASIL-stroke patients, 89.4% had ischemic stroke; TIAs co-existed in 27.7%; hemorrhagic strokes 6.2%; first stroke ≤65 years in 71%. (Pan et al., 2023-07-14) (pan2023lifelongcerebrovasculardisease pages 1-2)

3.3 MRI phenotype (selected frequencies)

  • Brazilian series (n=26): temporal lobe WMH 20/22? reported as 20 patients (91%); external capsule WMH 15 (68%); lacunar infarcts 18 (82%); microbleeds 9 (41%); larger hemorrhages 2 (9%). (nogueira2023clinicalandepidemiological pages 1-2)
  • Chinese cohort excerpt (probands; MRI): external capsule involvement 77.8% and anterior temporal lobe involvement 37.0% in that cohort; skin biopsy GOM detected in 11/16 tested. (hu2021notch3variantsand pages 1-2)

4. Genetic/molecular information

4.1 Causal gene

4.2 Pathogenic variants and variant classes

Examples of common variants (systematic review): A 1996–2023 systematic review reported the six most common missense mutations globally as p.R75P, p.R133C, p.R141C, p.R169C, p.R182C, and p.R544C. (Boston et al., 2024-06-03) (boston2024mostcommonnotch3 pages 1-2)

4.3 Genotype–phenotype correlations

4.4 Modifier genes / epigenetics / chromosomal abnormalities

No robust modifier genes, epigenetic mechanisms, or chromosomal abnormalities were identified in the retrieved evidence for this run.

5. Environmental information

No CADASIL-specific environmental toxins or infectious triggers were identified in the retrieved evidence. Vascular risk factors (hypertension, dyslipidemia, smoking) are clinically relevant modifiers rather than primary environmental causes. (kaisaridi2025determiningclinicaldisease pages 1-5)

6. Mechanism / pathophysiology

6.1 Causal chain (current understanding)

1) Germline NOTCH3 EGFr cysteine-altering variant → 2) misfolding and accumulation/aggregation of NOTCH3 extracellular domain (N3ECD) in small-vessel walls → 3) granular osmiophilic material (GOM) deposition and co-aggregation with extracellular matrix/matrisome proteins → 4) progressive small-vessel dysfunction (vascular wall damage, impaired vascular reactivity/perfusion) → 5) chronic ischemic injury and MRI small-vessel disease markers (WMH, lacunes, microbleeds, atrophy) → 6) clinical manifestations (migraine, lacunar strokes/TIA, cognitive decline/dementia, mood symptoms). (papakonstantinou2019notch3andcadasil pages 1-3, kaisaridi2025determiningclinicaldisease pages 1-5, mizuta2024progresstoclarify pages 1-2)

6.2 Cellular/tissue context

CADASIL pathology is centered on vascular smooth muscle cells and pericytes of small arteries/arterioles and capillaries, where NOTCH3 is expressed and where N3ECD deposits and GOM are detected. (papakonstantinou2019notch3andcadasil pages 1-3)

Suggested Cell Ontology (CL) terms (label suggestions): - Vascular smooth muscle cell (e.g., “vascular associated smooth muscle cell”). - Pericyte.

6.3 Molecular pathways and processes (GO suggestions)

Evidence in this run most strongly supports processes related to: - Notch signaling (canonical pathway involvement uncertain in CADASIL relative to other NOTCH disorders). (mizuta2024progresstoclarify pages 1-2) - Protein aggregation / extracellular deposition, extracellular matrix interactions, and vascular wall remodeling. (kaisaridi2025determiningclinicaldisease pages 1-5)

GO term suggestions (label-level): Notch signaling pathway; extracellular matrix organization; protein aggregation; vascular smooth muscle cell differentiation/maintenance; response to hypoxia/ischemia.

6.4 Recent mechanistic emphasis (2024)

Mizuta et al. (2024) explicitly highlight that, despite extensive downstream studies, “the process leading to N3ECD accumulation and its association with canonical NOTCH3 signaling remain unknown,” underscoring an upstream mechanistic gap that is increasingly relevant for designing disease-modifying therapies. (mizuta2024progresstoclarify pages 1-2)

7. Anatomical structures affected

7.1 Organ/system level

Suggested UBERON terms (label suggestions): brain; cerebral cortex; white matter; basal ganglia; thalamus.

7.2 Tissue/cell level

7.3 Subcellular level

8. Temporal development

CADASIL is adult-onset with early manifestations such as migraine with aura potentially in young adulthood, while disabling motor/cognitive manifestations often occur later (often after age 50 in clinical descriptions). (bersano2017cadasiltreatmentand pages 1-3, akrich2024geneticdiagnosisof pages 1-2)

Disease progression is heterogeneous; modeling of longitudinal clinical scores identified an early-onset rapidly progressing subgroup vs a later-onset slower subgroup, with variant position (EGFr 1–6), male sex, education, hypertension, and smoking associated with more aggressive progression. (kaisaridi2025determiningclinicaldisease pages 1-5)

9. Inheritance and population

9.1 Inheritance

Autosomal dominant inheritance is consistently reported for classical CADASIL due to pathogenic NOTCH3 variants. (akrich2024geneticdiagnosisof pages 1-2)

9.2 Epidemiology and prevalence

9.3 Sex differences (real-world EMR data)

In TriNetX EMR data, males had higher associated risk of stroke onset (OR 1.37) and higher mortality risk (OR 2.72) compared with females, after adjustment. (pan2023lifelongcerebrovasculardisease pages 1-2)

10. Diagnostics

10.1 Genetic testing (current implementation)

Genetic testing is repeatedly described as the diagnostic gold standard for CADASIL in the retrieved evidence. (hu2021notch3variantsand pages 1-2, bersano2017cadasiltreatmentand pages 1-3)

A real-world diagnostic laboratory evaluation (680 referred samples; 1997 onward) showed a 14.7% mutation detection rate overall, and higher yield using a targeted NGS panel (15.8%) compared with limited Sanger strategies (10.8%), supporting broader sequencing approaches. (Dunn et al., 2020-01; Human Genomics) (dunn2020investigatingdiagnosticsequencing pages 1-2)

10.2 Skin biopsy / pathology

Presence of granular osmiophilic material (GOM) in skin vessels is a characteristic pathological hallmark and is used diagnostically in some workflows, particularly when genetic results are uncertain; in one cohort excerpt, skin biopsy found GOM in 11/16 tested. (papakonstantinou2019notch3andcadasil pages 1-3, hu2021notch3variantsand pages 1-2)

10.3 MRI and imaging markers

Characteristic MRI patterns include extensive white matter hyperintensities (WMH), lacunes, microbleeds, and brain atrophy, with involvement of anterior temporal pole and external capsule often considered suggestive. (bersano2017cadasiltreatmentand pages 1-3, nogueira2023clinicalandepidemiological pages 1-2)

A 2024 prospective study demonstrates trial-sensitive MRI outcomes over 2 years including diffusion MRI (MSMD), WMH volume, lacune volume, and brain parenchymal fraction; variant risk category stratifies progression rates. (cerfontaine2024associationofnotch3 pages 1-2)

Image evidence: Table 2 from Dupé et al. provides a structured summary of clinical and imaging features stratified by NOTCH3 EGFr 1–6 vs 7–34 (including WMH, lacunes, microbleeds, and brain parenchymal fraction), supporting genotype-informed interpretation of MRI patterns. (dupe2023phenotypicvariabilityin media cdee29b5)

11. Outcome / prognosis

CADASIL is progressive and leads to cumulative cerebrovascular injury and vascular cognitive impairment/dementia. (cerfontaine2024associationofnotch3 pages 1-2, bersano2017cadasiltreatmentand pages 1-3)

Recent quantitative prognosis-related signals include: - Two-year prospective worsening in disability, executive function, and multiple MRI measures (MSMD, WMH volume, lacune volume, brain parenchymal fraction), with faster progression in high-risk NOTCH3 variant categories. (cerfontaine2024associationofnotch3 pages 1-2) - ICH occurs in about ~2% of symptomatic cases in a large UK register estimate, with mean onset ~56.6 years and important associations with anticoagulation exposure. (sukhonpanich2024prevalenceclinicalcharacteristics pages 1-2)

12. Treatment

12.1 Current standard of care (symptomatic/risk management)

No disease-modifying therapy is established in the retrieved evidence; management is largely supportive and focused on symptom control and vascular risk factor management. A dedicated treatment review emphasizes that “no proven disease-modifying therapies exist” and management is empiric. (bersano2017cadasiltreatmentand pages 1-3)

12.2 Antithrombotic considerations (evidence relevant to practice)

ICH-focused evidence indicates anticoagulation is associated with increased ICH risk in CADASIL (20.0% vs 1.9% in the UK register comparison), whereas antiplatelet agents were not associated with increased risk in that study. This is relevant to clinical decision-making when considering anticoagulation indications in CADASIL patients. (Sukhonpanich & Markus, published online 2024-01-13) (sukhonpanich2024prevalenceclinicalcharacteristics pages 1-2)

12.3 Clinical trials and observational research (real-world implementation)

Although interventional disease-modifying trials were not identified in the retrieved clinicaltrials.gov set for this run, multiple observational/natural history efforts are active and support biomarker development and future trial readiness: - NCT05677880 (first posted 2023-01-10; recruiting): longitudinal observational study (“Unraveling the Early Phases…”) enrolling individuals with CADASIL family history and known NOTCH3 status; includes neurocognitive assessment, MRI, and biofluids including neurofilament light (NfL). URL: https://clinicaltrials.gov/study/NCT05677880 (NCT05677880 chunk 1) - NCT05072483 (first posted 2021-10-11; recruiting): NIH natural history study with deep phenotyping; may include skin biopsy and lumbar puncture; long follow-up. URL: https://clinicaltrials.gov/study/NCT05072483 (NCT05072483 chunk 1)

Suggested MAXO terms (label suggestions): genetic testing; magnetic resonance imaging; antiplatelet therapy; anticoagulation avoidance/risk assessment; rehabilitation therapy; cognitive assessment.

13. Prevention

No primary prevention strategies specific to CADASIL onset were identified in the retrieved evidence. Secondary/tertiary prevention in practice focuses on aggressive management of vascular risk factors and careful consideration of anticoagulation given ICH risk evidence. (kaisaridi2025determiningclinicaldisease pages 1-5, sukhonpanich2024prevalenceclinicalcharacteristics pages 1-2)

14. Other species / natural disease

No naturally occurring CADASIL-equivalent disease in non-human species was identified in the retrieved evidence.

15. Model organisms and experimental models

A 2024 mechanistic review notes that Notch signaling is conserved across species and that some Drosophila Notch lines harbor cysteine-altering mutations corresponding to CADASIL-causing mutations, but also states that “animal models of CADASIL other than rodent models have not been established,” potentially because Notch signaling is not impaired by most CADASIL-causing mutations. (mizuta2024progresstoclarify pages 1-2)

Recent quantitative findings (2023–2024)

Table (click to expand)
Study (first author, year) Design/Population Key quantitative results (include exact numbers) Interpretation/implication
Cerfontaine, 2024 Prospective 2-year single-center follow-up in genetically confirmed CADASIL; 162 patients total: high-risk (HR) n=90, moderate-risk (MR) n=67, low-risk (LR) n=5 Over 2 years, whole cohort showed progression in MSMD β=0.20 (95% CI 0.17–0.23; p=7.0×10⁻²⁴), normalized lacune volume β=0.13 (0.080–0.19; p=2.1×10⁻⁶), normalized WMH volume β=0.092 (0.075–0.11; p=8.8×10⁻²⁰), brain parenchymal fraction β=−0.22 (−0.26 to −0.19; p=3.2×10⁻²²), plus increased disability (p=0.002) and executive decline (β=−0.15; 95% CI −0.30 to −3.4×10⁻⁵; p=0.05). HR variants had higher 2-year incident stroke risk than MR variants: hazard ratio 4.3 (95% CI 1.4–13.5; p=0.011); also greater increase in MSMD β=0.074 (0.013–0.14; p=0.017) and lacune volume β=0.14 (0.034–0.24; p=0.0089). Significant MSMD progression was detectable even in young n=17 and premanifest n=24 subgroups. (cerfontaine2024associationofnotch3 pages 1-2) Strong evidence that NOTCH3 risk category predicts short-term clinical and radiologic worsening; supports MSMD as a trial-sensitive biomarker, including in premanifest disease.
Dupé, 2023 Large phenotyping study of 446 CADASIL patients assessing effects of NOTCH3 EGFr mutation location plus age, sex, and vascular risk factors The study confirmed that mutation location in EGFr 1–6 vs 7–34 strongly influences disease severity; effects were “mainly driven” by differential development of ischemic tissue lesions. The cohort analysis showed severity differences beyond the effects of aging, male sex, hypertension, and hypercholesterolemia. MRI outcomes included WMH, lacunes, microbleeds, and brain parenchymal fraction; mutation location was a major determinant of clinical/imaging profile. (dupe2023phenotypicvariabilityin pages 1-2, dupe2023phenotypicvariabilityin pages 2-3, dupe2023phenotypicvariabilityin media cdee29b5) Establishes variant position as one of the most important predictors of phenotype and a key stratifier for prognosis and trial design.
Sukhonpanich, 2024 Retrospective review of UK prospective CADASIL register plus systematic review; 516 symptomatic registry patients 10 ICH cases identified in the UK register, giving estimated point prevalence 1.9%. Systematic review added 119 cases, for 129 total cases and 142 ICH events. Mean age at ICH onset 56.6 ± 15.7 years; 57.4% male. ICH was the first manifestation in 32 patients (38.1%) and recurred in 16 (12.4%). Commonest sites were thalamus 58/142 (40.8%) and basal ganglia 34/142 (23.9%). Anticoagulation was associated with higher ICH risk (20.0% vs 1.9%; p=0.006), whereas antiplatelets were not. (sukhonpanich2024prevalenceclinicalcharacteristics pages 1-2) ICH is uncommon but clinically important in CADASIL; the anticoagulation signal is highly relevant to real-world management decisions.
Pan, 2023 TriNetX global health research network analysis; 914 CADASIL patients identified in US-based EMR data Median age 60 [IQR 50–69]; 61.3% female. 596/914 (65.2%) had documented cerebrovascular events. Among CADASIL-stroke patients, 89.4% had ischemic stroke, 27.7% had co-existing TIA, and 6.2% had hemorrhagic strokes. Initial stroke occurred at age ≤65 years in 71%. Male sex was associated with higher stroke risk (OR 1.37, 95% CI 1.01–1.86) and higher mortality (OR 2.72, 95% CI 1.53–4.84). (pan2023lifelongcerebrovasculardisease pages 1-2) Demonstrates a high lifetime cerebrovascular burden in real-world practice and suggests sex-specific risk stratification may be important.
Dunn, 2020 Clinical diagnostic sequencing evaluation; 680 patient samples, 764 tests across Sanger, targeted NGS panel, and WES Overall mutation detection rate was 14.7% (100/680). By method: Sanger 10.8% (44/407), targeted NGS panel 15.8% (56/354), and WES 1/3 identifying a likely non-NOTCH3 pathogenic variant. Sanger-positive variants clustered mainly in exon 4 (n=36), then exon 3 (n=3), exon 11 (n=3), exon 18 (n=1), exon 19 (n=1). (dunn2020investigatingdiagnosticsequencing pages 1-2) Supports current practice favoring broader NGS-based testing over limited exon-first Sanger approaches for CADASIL diagnostics.
Nogueira, 2023 Brazilian multicenter case series with genetic confirmation; 26 patients 16/26 female; mean disease onset 45 years. Ischemic stroke was first symptom in 19/26. Cognitive impairment occurred in 17/26, dementia in 6/26, psychiatric manifestations in 16/26. Recurrent migraine in 8/26, with aura in 6/8 (75%). MRI: temporal lobe WMH in 20 patients (91%), external capsule WMH in 15 (68%), lacunar infarcts in 18 (82%), microbleeds in 9 (41%), larger hemorrhages in 2 (9%). (nogueira2023clinicalandepidemiological pages 1-2) Confirms that core CADASIL clinical-radiologic patterns generalize to an admixed Brazilian cohort, while microbleed/hemorrhage rates may vary by population.
Mizuta, 2024 Mechanistic review of NOTCH3/CADASIL biology CADASIL is described as adult-onset and driven primarily by mutant NOTCH3 extracellular domain (N3ECD) accumulation, with possible contribution from impaired Notch signaling. The review emphasizes that all known causative mutations are in the EGFr domain, most are cysteine-altering missense variants, and that N3ECD accumulation with downstream vascular pathology remains the dominant current mechanistic framework. (mizuta2024progresstoclarify pages 1-2) Provides current expert consensus for the field: disease-modifying strategies will likely need to target early N3ECD aggregation/vascular injury, not just downstream stroke consequences.

Table: This table compiles recent quantitative and clinically actionable findings in CADASIL, emphasizing cohort sizes, exact effect estimates, and why each study matters for prognosis, diagnosis, and trial design.

Expert analysis and current gaps (2023–2024 emphasis)

1) Variant position and risk categorization are now central to prognosis and trial design. Large cohorts show EGFr 1–6 vs 7–34 effects on severity, and 2024 prospective data show that risk category predicts 2-year clinical and MRI progression (including incident stroke HR 4.3 for HR vs MR). (cerfontaine2024associationofnotch3 pages 1-2, dupe2023phenotypicvariabilityin pages 1-2) 2) A key upstream mechanistic gap remains: despite strong evidence that N3ECD aggregation and GOM are core to pathogenesis, the “process leading to N3ECD accumulation” remains unresolved, complicating rational targeting for disease-modifying therapies. (mizuta2024progresstoclarify pages 1-2) 3) Real-world diagnosis and early-stage identification are increasingly operationalized via NGS testing and longitudinal biomarker studies. Diagnostic laboratories report improved detection with targeted NGS panels, while large observational studies now recruit pre-symptomatic carriers to define early biomarkers and endpoints. (dunn2020investigatingdiagnosticsequencing pages 1-2, NCT05677880 chunk 1)

URLs and publication dates (from retrieved sources)

References

  1. (cerfontaine2024associationofnotch3 pages 1-2): Minne N. Cerfontaine, Remco J. Hack, Benno Gesierich, Marco Duering, Marie-Noëlle W. Witjes-Ané, Mar Rodríguez-Girondo, Gido Gravesteijn, Julie Rutten, and Saskia A.J. Lesnik Oberstein. Association of notch3 variant risk category with 2-year clinical and radiologic small vessel disease progression in patients with cadasil. Neurology, May 2024. URL: https://doi.org/10.1212/wnl.0000000000209310, doi:10.1212/wnl.0000000000209310. This article has 12 citations and is from a highest quality peer-reviewed journal.

  2. (papakonstantinou2019notch3andcadasil pages 1-3): Eleni Papakonstantinou, Flora Bacopoulou, Dimitrios Brouzas, Vasileios Megalooikonomou, Domenica D'Elia, Erik Bongcam-Rudloff, and Dimitrios Vlachakis. Notch3 and cadasil syndrome: a genetic and structural overview. EMBnet.journal, 24:e921, May 2019. URL: https://doi.org/10.14806/ej.24.0.921, doi:10.14806/ej.24.0.921. This article has 50 citations.

  3. (bersano2017cadasiltreatmentand pages 1-3): Anna Bersano, Gloria Bedini, Joshua Oskam, Caterina Mariotti, Franco Taroni, Silvia Baratta, and Eugenio Agostino Parati. Cadasil: treatment and management options. Current Treatment Options in Neurology, 19:1-15, Jul 2017. URL: https://doi.org/10.1007/s11940-017-0468-z, doi:10.1007/s11940-017-0468-z. This article has 58 citations and is from a peer-reviewed journal.

  4. (mizuta2024progresstoclarify pages 1-2): Ikuko Mizuta, Yumiko Nakao-Azuma, Hideki Yoshida, Masamitsu Yamaguchi, and Toshiki Mizuno. Progress to clarify how notch3 mutations lead to cadasil, a hereditary cerebral small vessel disease. Biomolecules, 14:127, Jan 2024. URL: https://doi.org/10.3390/biom14010127, doi:10.3390/biom14010127. This article has 25 citations.

  5. (hu2021notch3variantsand pages 1-2): Yacen Hu, Qiying Sun, Yafang Zhou, Fang Yi, Haiyun Tang, Lingyan Yao, Yun Tian, Nina Xie, Mengchuan Luo, Zhiqin Wang, Xinxin Liao, Hongwei Xu, and Lin Zhou. Notch3 variants and genotype-phenotype features in chinese cadasil patients. Frontiers in Genetics, Jul 2021. URL: https://doi.org/10.3389/fgene.2021.705284, doi:10.3389/fgene.2021.705284. This article has 39 citations and is from a peer-reviewed journal.

  6. (pan2023lifelongcerebrovasculardisease pages 1-2): Alan P. Pan, Thomas Potter, Abdulaziz Bako, Jonika Tannous, Sudha Seshadri, Louise D. McCullough, and Farhaan S. Vahidy. Lifelong cerebrovascular disease burden among cadasil patients: analysis from a global health research network. Frontiers in Neurology, Jul 2023. URL: https://doi.org/10.3389/fneur.2023.1203985, doi:10.3389/fneur.2023.1203985. This article has 13 citations and is from a peer-reviewed journal.

  7. (dupe2023phenotypicvariabilityin pages 1-2): Charlotte Dupé, Stéphanie Guey, Lucie Biard, Sokhna Dieng, Jessica Lebenberg, Lina Grosset, Nassira Alili, Dominique Hervé, Elisabeth Tournier-Lasserve, Eric Jouvent, Sylvie Chevret, and Hugues Chabriat. Phenotypic variability in 446 cadasil patients: impact of notch3 gene mutation location in addition to the effects of age, sex and vascular risk factors. Journal of Cerebral Blood Flow & Metabolism, 43:153-166, Oct 2023. URL: https://doi.org/10.1177/0271678x221126280, doi:10.1177/0271678x221126280. This article has 40 citations and is from a highest quality peer-reviewed journal.

  8. (kaisaridi2025determiningclinicaldisease pages 1-5): Sofia Kaisaridi, Dominique Herve, Aude Jabouley, Sonia Reyes, Carla Machado, Stéphanie Guey, Abbas Taleb, Fanny Fernandes, Hugues Chabriat, and Sophie Tezenas Du Montcel. Determining clinical disease progression in symptomatic patients with cadasil. Neurology, Jan 2025. URL: https://doi.org/10.1212/wnl.0000000000210193, doi:10.1212/wnl.0000000000210193. This article has 3 citations and is from a highest quality peer-reviewed journal.

  9. (cao2024phenotypesassociatedwith pages 13-14): Yuan Cao, Ding-Ding Zhang, Fei Han, Nan Jiang, Ming Yao, and Yi-Cheng Zhu. Phenotypes associated with notch3 cysteine-sparing mutations in patients with clinical suspicion of cadasil: a systematic review. International Journal of Molecular Sciences, 25:8796, Aug 2024. URL: https://doi.org/10.3390/ijms25168796, doi:10.3390/ijms25168796. This article has 7 citations.

  10. (sukhonpanich2024prevalenceclinicalcharacteristics pages 1-2): Nontapat Sukhonpanich and Hugh S. Markus. Prevalence, clinical characteristics, and risk factors of intracerebral haemorrhage in cadasil: a case series and systematic review. Journal of Neurology, 271:2423-2433, Jan 2024. URL: https://doi.org/10.1007/s00415-023-12177-0, doi:10.1007/s00415-023-12177-0. This article has 13 citations and is from a domain leading peer-reviewed journal.

  11. (nogueira2023clinicalandepidemiological pages 1-2): Renata Nogueira, Christian Marques Couto, Pérola de Oliveira, Bernardo José Alves Ferreira Martins, and Vinícius Viana Abreu Montanaro. Clinical and epidemiological profiles from a case series of 26 brazilian cadasil patients. Arquivos de Neuro-Psiquiatria, 81:417-425, May 2023. URL: https://doi.org/10.1055/s-0042-1758756, doi:10.1055/s-0042-1758756. This article has 10 citations and is from a peer-reviewed journal.

  12. (boston2024mostcommonnotch3 pages 1-2): Georgina Boston, Dan Jobson, Toshiki Mizuno, Masafumi Ihara, and Raj N Kalaria. Most common notch3 mutations causing cadasil or cadasil-like cerebral small vessel disease: a systematic review. Cerebral Circulation - Cognition and Behavior, 6:100227, Jun 2024. URL: https://doi.org/10.1016/j.cccb.2024.100227, doi:10.1016/j.cccb.2024.100227. This article has 31 citations.

  13. (akrich2024geneticdiagnosisof pages 1-2): Madeleine Akrich, Vololona Rabeharisoa, Florence Paterson, and Hugues Chabriat. Genetic diagnosis of individuals at risk of cadasil: prospect for future therapeutic development. Journal of Neurology, 271:6912-6922, Sep 2024. URL: https://doi.org/10.1007/s00415-024-12640-6, doi:10.1007/s00415-024-12640-6. This article has 4 citations and is from a domain leading peer-reviewed journal.

  14. (dunn2020investigatingdiagnosticsequencing pages 1-2): P. J. Dunn, N. Maksemous, R. A. Smith, H. G. Sutherland, L. M. Haupt, and L. R. Griffiths. Investigating diagnostic sequencing techniques for cadasil diagnosis. Human Genomics, Jan 2020. URL: https://doi.org/10.1186/s40246-019-0255-x, doi:10.1186/s40246-019-0255-x. This article has 23 citations and is from a peer-reviewed journal.

  15. (dupe2023phenotypicvariabilityin media cdee29b5): Charlotte Dupé, Stéphanie Guey, Lucie Biard, Sokhna Dieng, Jessica Lebenberg, Lina Grosset, Nassira Alili, Dominique Hervé, Elisabeth Tournier-Lasserve, Eric Jouvent, Sylvie Chevret, and Hugues Chabriat. Phenotypic variability in 446 cadasil patients: impact of notch3 gene mutation location in addition to the effects of age, sex and vascular risk factors. Journal of Cerebral Blood Flow & Metabolism, 43:153-166, Oct 2023. URL: https://doi.org/10.1177/0271678x221126280, doi:10.1177/0271678x221126280. This article has 40 citations and is from a highest quality peer-reviewed journal.

  16. (NCT05677880 chunk 1): Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Study. University of Wisconsin, Madison. 2022. ClinicalTrials.gov Identifier: NCT05677880

  17. (NCT05072483 chunk 1): Natural History Study of CADASIL. National Heart, Lung, and Blood Institute (NHLBI). 2022. ClinicalTrials.gov Identifier: NCT05072483

  18. (dupe2023phenotypicvariabilityin pages 2-3): Charlotte Dupé, Stéphanie Guey, Lucie Biard, Sokhna Dieng, Jessica Lebenberg, Lina Grosset, Nassira Alili, Dominique Hervé, Elisabeth Tournier-Lasserve, Eric Jouvent, Sylvie Chevret, and Hugues Chabriat. Phenotypic variability in 446 cadasil patients: impact of notch3 gene mutation location in addition to the effects of age, sex and vascular risk factors. Journal of Cerebral Blood Flow & Metabolism, 43:153-166, Oct 2023. URL: https://doi.org/10.1177/0271678x221126280, doi:10.1177/0271678x221126280. This article has 40 citations and is from a highest quality peer-reviewed journal.