Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Case contributed by Dr Rajalakshmi Ramesh

Presentation

40 year-old female presenting with new onset diffuse headaches. Nil focal neurological deficits.

Patient Data

Age: 40
Gender: Female

Represented within the frontal and parietal lobe white matter bilaterally, in a fairly symmetrical distribution, numerous well circumscribed and irregularly marginated zones of T2 hyperintense signal are appreciated extending well up to the vertex, many being distributed within the watershed distribution of the frontal lobes bilaterally, and also at the capsular margins. Overall findings are well in keeping with areas of old subcortical and deep white matter infarcts/leuko-encephalopathy. None of these lesions demonstrate restricted diffusion on DWI sequence. No true periventricular white matter signal change is seen. No posterior fossa abnormality is seen. Sulcal, cistern and ventricular anatomy of the anterior and posterior circulation throughout. The right vertebral artery is dominant with normal junction point being demonstrated. Normal calibre of the basilar artery seen. The carotid syphons are normal bilaterally and no supraclinoid disease is seen. There is no evidence of AVM or aneurism.

Conclusion: The findings are well in keeping with a diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). No acute infarct is seen on this occasion.

The patient was managed conservatively and remained under radiological annual surveillance. Here most recent MRI is shown below. 

Moderately extensive foci of increased FLAIR and T2 signal evident within the periventricular white matter and subcortical white matter in the frontal and parietal lobes and sub insular white matter unchanged in comparison to the previous scan from two years prior. Small foci are evident within the basal ganglia and the largest confluent area is laterally on the right frontal lobe. Further FLAIR hyperintensity is evident in the subcortical white matter of the anterior temporal lobes, a more specific feature of CADASIL. There is no evidence of restricted diffusion. No critical intracranial vascular stenosis.

 

Impression: Stable appearances and features suspicious for CADASIL.

Case Discussion

This case illustrates radiological findings most consistent with a diagnosis of CADASIL in a patient with a positive family history. 

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral angiopathy1 . It is a non-amyloid type of small vessel arterial disease caused by mutation NOTCH3 gene on chromosome 19q122. The NOTCH3 gene encodes a transmembrane protein expressed in vascular smooth muscle 1,3. This protein dictates maturation of smooth muscle cells and is thereby required for maintenance of the structural and functional integrity of small arteries. Mutations of the NOTCH3 gene result in mural fibrosis and subsequent loss of vasomotor reactivity in small blood vessel walls.  There is resultant dysfunctional arterial autoregulation, cerebral hypoperfusion and ischemic infarction 3.

Clinical hallmarks of CADASIL include migraine with aura, stroke, mood disturbances and cognitive impairment 4. The first clinical manifestations of the disease often start in patients during the 3rd decade, and death often occurs in patients during the 6th decade 2.

The main neuroimaging findings of CADASIL are 1-4:

  • White matter regions of high signal intensities on T2 weighted images and FLAIR sequences. These white matter hyperintensities are usually found in the periventricular region and deep white matter. There is a predelication for the frontal, parietal, and anterior temporal, followed by external capsule areas of the brain.
  • Lacunar infarcts, most commonly of the in the semioval center, thalamus, basal ganglia, and pons.
  • Cerebral microbleeds most sensitive on Gradient echo planar T2* MRI and common to the cortical/subcortical areas, white matter, thalamus and brainstem. 

Case courtesy of Associate Professor Pramit Phal.

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Case information

rID: 41018
Case created: 12th Nov 2015
Last edited: 12th Nov 2015
Inclusion in quiz mode: Included

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