Figure 1
Axial FLAIR MR image.
Axial FLAIR MR image shows extensive confluent white matter hyperintensities in the subcortical white matter of temporal lobes.
A Familial Case of CADASIL
SectionNeuroradiology
Case TypeClinical Cases
AuthorsKamvysis D., Lachanis S., Prasouli A., Kyriakoulis D., Karapostolakis G.
Connected authors
40 years, female
Clinical History
40 year-old female suffering from transient ischemic attacks and migraine
episodes.
Imaging Findings
A 40 year-old female was admitted to the hospital suffering from migraine episodes and transient
ischemic attacks. Laboratory tests showed no pathologic results except for elevated ANA levels. MRI investigation revealed extensive diffuse signal abnormalities, mainly affecting the centrum
semiovale, the external capsule, thalamus, basal ganglia and temporal lobes. These MR findings along with the clinical history of the patient alerted diagnostic thought of the presence of a
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL); a detailed familial history was obtained to reveal that the patient’s mother suffered
from similar neurological symptoms, that were attributed to central nervous system lupus erythematous, with the latter been considered as the cause of death 15 years earlier. An MR study of the
mother was revised and an MR investigation of the patient’s asymptomatic sister was performed, both demonstrating similar findings as mentioned above.
Discussion
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare inherited microangiopathy caused by mutations in the NOTCH3 gene on chromosome 19q12.
Histopathologic study has shown abnormalities of white matter and leptomeningeal arteries (also involving non-CNS vessels) consisting of concentric thickening of the media and adventitia and luminal
narrowing caused by granular material (basophilic, PAS-positive granules) and loss of smooth muscle cells. Clinical manifestations of the disease include transient ischemic attacks, strokes,
progressive subcortical dementia, migraine with aura and mood disturbances. The onset of clinical symptoms usually occurs in the fourth decade; nevertheless, a number of patients remain asymptomatic.
CADASIL has a poor prognosis, with severe cognitive decline and physical disability preceding death within about 20 years. Magnetic Resonance Imaging in patients with CADASIL typically reveals
diffuse white matter areas with abnormal signal intensity (hyperintensity on T2 and hypointensity on T1 sequences) and lacunar infarcts in the centrum semiovale, the corpus callosum, the external
capsule, thalamus basal ganglia and pons. White matter lesions tend to be symmetrical and bilateral and commonly involve frontal and temporal lobes. The latter distribution is considered a hallmark
of the disease, along with the lacunar infarcts. Microbleeds and subcortical lacunar lesions can also be regarded as radiological features of CADASIL. Diffusion tensor measurements have revealed
increased diffusivity and concomitant loss of diffusion anisotropy in CADASIL patients that can be correlated with clinical impairment. This diffusional abnormality is hypothesized to be the result
of neuronal loss and demyelination. The above MR findings have been correlated with the age of the patients; in the younger of them (in the 3rd-4th decades) cerebral
abnormalities usually include areas of hyperintensity and subcortical lacunar lesions while lacunar infarcts and microbleeds are superimposed on the radiological disease pattern later (during
4th-6th decades). In most patients with CADASIL, the diagnosis is relatively clear in those with early onset lacunar stroke, often complex migraine and a typical MRI scan. In
the majority of cases there is a clear autosomal pattern of inheritance, with stroke or dementia occurring in relatives at a young age; nevertheless, diagnosis is confirmed by the demonstration of
mutations in the NOTCH3 gene. The differential diagnosis is obviously from other disorders presenting with multiple recurrent subcortical infarctions or other lesions. CADASIL should be mainly
differentiated from sporadic subcortical arteriosclerotic encephalopathy (Binswanger disease) and cerebral amyloid angiopathy. Other familial disorders in which stroke may be a prominent symptom are
the dyslipoproteinemias (eg familial hypercholesterolemia), disorders of connective tissue (Ehlers-Danlos s., Marfan s.), hyperhomocysteinemia and mitochondrial encephalopathies. Recurrent strokes in
young adults may also be due to cerebral vasculitis, drug abuse (cocaine), cardiac diseases etc. Familial hemiplegic migraine can be confused with CADASIL in its early stages. Rarely, CADASIL may be
presented as an acute unexplained reversible encephalopathy.
Differential Diagnosis List
Cerebral
Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Final Diagnosis
Cerebral
Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
References
[1] Coulthard A, Blank SC, Bushby K, Kalaria RN, Burn DJ. Distribution of cranial MRI abnormalities in patients with symptomatic and subclinical CADASIL. Br J Radiol, 73 (2000), 256-265. (PMID: 10817040)
[2] Auer D, Pütz B, G怀ssl C, Elbel GK, Gasser T, Dichgans M. Differential Lesion Patterns in CADASIL and Sporadic Subcortical Arteriosclerotic Encephalopathy: MR Imaging Study with Statistical Parametric Group Comparison. Radiology 2001; 218:443-451. (PMID: 11161160)
[3] van den Boom R, Lesnik Oberstein SAJ, van Duinen SG, Bornebroek M, Ferrari MD, Haan J, van Buchem MA. Subcortical Lacunar Lesions: An MR Imaging Finding in Patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. Radiology 2002; 224:791-796. (PMID: 12202716)
[4] van den Boom R, Lesnik Oberstein SAJ, Ferrari MD, Haan J, van Buchem MA. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: MR Imaging Findings at Different Ages 3rd-6th Decades. Radiology 2003; 229:683-690. (PMID: 14593195)
Case information
| URL: | https://www.eurorad.org/case/4821 |
| DOI: | 10.1594/EURORAD/CASE.4821 |
| ISSN: | 1563-4086 |
Figure 2
Axial FLAIR MR image, at the level of basal ganglia.
Axial FLAIR MR image, at the level of basal ganglia, shows confluent white matter changes at the external capsule and frontal white matter.
Figure 3
Coronal T2-w MR image.
Coronal T2-w MR image at the level of basal ganglia shows hyperintensities of the subcortical white matter and basal ganglia.
Figure 4
Axial T2-w MR image of the patient’s mother.
Mother’s MRI (T2-w) shows extensive confluent white matter hyperintensities in the subcortical white matter of temporal lobes.
Figure 5
Axial T2-w MR image of the patient’s sister.
Sister’s MRI (T2-w) shows similar white matter hyperintensities in the external capsules.
Figure 6
Axial T2-w MR image of the patient’s sister.
Sister’s MRI (T2-w) shows similar white matter hyperintensities in the subcortical white matter of the temporal lobes.
Axial FLAIR MR image.
Axial FLAIR MR image shows extensive confluent white matter hyperintensities in the subcortical white matter of temporal lobes.
Axial FLAIR MR image, at the level of basal ganglia.
Axial FLAIR MR image, at the level of basal ganglia, shows confluent white matter changes at the external capsule and frontal white matter.
Coronal T2-w MR image.
Coronal T2-w MR image at the level of basal ganglia shows hyperintensities of the subcortical white matter and basal ganglia.
Axial T2-w MR image of the patient’s mother.
Mother’s MRI (T2-w) shows extensive confluent white matter hyperintensities in the subcortical white matter of temporal lobes.
Axial T2-w MR image of the patient’s sister.
Sister’s MRI (T2-w) shows similar white matter hyperintensities in the external capsules.
Axial T2-w MR image of the patient’s sister.
Sister’s MRI (T2-w) shows similar white matter hyperintensities in the subcortical white matter of the temporal lobes.