CADASIL presenting with spontaneous intracerebral hemorrhage: report of a case and description of the first family in Northern Greece

Abstract

Introduction: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), the most common inherited cause of stroke and dementia in adults, has been described in six Greek families. Common presenting manifestations include migraine with aura, brain ischemia, mood disorders and cognitive decline. Spontaneous intracerebral hemorrhage (SICH) rarely occurs in CADASIL and only exceptionally as the first clinical manifestation.

Case description: We have previously reported the sixth Greek family with CADASIL and in particular, two brothers in whom the genetic testing documented a classic mutation of the NOTCH3 gene (Arg169Cys). In this report, we describe the 30-year-old son of the second brother, who suffered a thalamic SICH as the presenting manifestation of CADASIL, in the absence of arterial hypertension or antiplatelet drug use.

Conclusion: Patients with acute subcortical infarcts, leukoencephalopathy, a history of migraine, mood disorders, and dementia, should always raise the suspicion of CADASIL. However, a SICH, even in the absence of classical risk factors for hemorrhage, is possible and should not exclude the diagnosis of CADACIL. Hippokratia 2016, 20(1): 76-79.

Keywords: CADASIL; NOTCH3 gene; intracerebral hemorrhage.

Figure 1. Α) Computing tomography imaging of the 30-yearold man with sudden headache and numbness of the right hand, upon admission indicating intracerebral hemorrhage in the left thalamus. B) Magnetic resonance imaging (MRI, FLAIR-1.5 Tesla, axial) one month later showing, along with the deep hemorrhage, periventricular leukoencephalopathy and lacunes in the basal ganglia (arrows). C) MRI (STIR-3 Tesla, axial) three months later clearly depicting the multiple asymptomatic lacunar lesions (arrows). D) T2- gradient echo sequence at the same time documenting the hemorrhage and the absence of cerebral microbleeds.

Figure 2. A) Magnetic resonance imaging (MRI) of the 50-year-old man who suffered from left hemiparesis in 2011: Diffusion restriction in the right internal capsule, indicating acute infarction (arrow). B) MRI (FLAIR, axial, year 2011): Abnormal MR signal periventricularly and in the external capsules, most obvious on the left (arrow). C) MRI (DWI, year 2015) indicating the new acute infarction in the left semioval center (arrow). D) MRI (FLAIR, axial, year 2015) showing the typical lacune in the right internal capsule (arrow), which corresponds to the lesion depicted in A four years earlier.

Figure 3. Abnormal magnetic resonance signal (FLAIR, axial) in both the anterior temporal lobes (more prominent on the left), in the basis pontis (A, arrow) and in the ventral midbrain (B, arrow). The leukoencephalopathy extends periventricularly, to the basal ganglia and the external capsules (C, arrow). Notice multiple big subcortical gliotic areas suggestive of old ischemic strokes, especially next to the body of the right lateral ventricle (D, arrows).

Figure 4. Pedigree tree of the Greek family with CADASIL. I. The grandfather of Patient 1 died of myocardial infarction at the age of 63 and the grandmother died of undetermined "stroke" also at the age of 63. II. The older sisters of Patients 1 and 2 live in Canada and are possibly asymptomatic. All other individuals in the tree are currently asymptomatic.