The role of clinical and neuroimaging features in the diagnosis of CADASIL

Abstract

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. Methods: Patients with lacunar stroke or TIA, were included in the present study. For each patient demographic and clinical data were collected.MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. Results: 128 patients (mean age 56.3±12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of all these factors together with familial history for stroke result in a higher positive predictive value and specificity. Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.

A large number of cerebral microbleeds in CADASIL patients presenting with recurrent seizures: A case report

“…Brain [10]. In CADASIL, the prevalence of cerebral microbleeds ranges from 34% to 75% [3][4][6][7][8].…”

“…Seizures are an uncommon symptom found in only 6% to 10% of cases [2][3][4]. The exact aetiology of epileptic seizures is not known.…”

“…The common MRI findings are T2-hyperintense lesions in the periventricular and subcortical white matter, especially the external capsule and anterior temporal lobes, which are more likely to be involved in this condition than in sporadic forms of small vessel diseases [5]. The prevalence of cerebral microbleeds ranges from 34% to 75% [3][4][6][7][8]. Common locations of cerebral microbleeds are in the thalamus, basal ganglia, subcortical white matter, brainstem, cerebellum and grey-white matter junction [7][8].…”

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

“…CADASIL is an inherited cerebrovascular disorder, whose main clinical features are migraine with aura, recurrent subcortical ischemic attacks, strokes, vascular dementia, cognitive impairment, psychiatric disturbances, and apathy [8][9][10][11][12][13][14][15][16]. Due to the rarity of the disease, CADASIL is often overlooked and misdiagnosed; nevertheless, the combined symptomatic and asymptomatic prevalence of CADASIL is estimated at least 10.7 per 100,000 adults [11,12,[17][18][19][20].…”

“…However, because affected family members may have been misdiagnosed [80] and de novo cases have been described [69,81], the lack of an apparent family history of CADASIL does not preclude the diagnosis. Several groups of clinicians [13,14,82] proposed suitable diagnostic strategies to be used in the clinical setting for the selection of patients to be subjected to NOTCH3 gene analysis. In fact, in order to establish a correct diagnosis, clinical signs, neuroimaging findings, and family history need to be evaluated.…”