CADASIL: a new differential diagnosis for vascular dementias Author: André Mascarenhas Oliveira - Pathology Resident Mayo Clinic, Rochester, MN - USA

Introduction

CADASIL is the English acronym for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

Recognized more than a decade ago as a new cerebral vasculopathy ⁽¹⁾, and maybe reported 40 years ago by Van Bogaert as an aggressive form of Binswanger’s disease ⁽²⁾, CADASIL has been continously diagnosed in the last years, with more than 50 affected families reported ⁽³⁾.

Pathogenesis

CADASIL still has an unknown pathogenesis but alterations in the q12 region of chromosome 19 have been detected in some cases ⁽⁴⁾. Histopathologically, a characteristic eosinophilic granular deposit of an unknown composition has been present in the media of the small penetrating cerebral arteries. This seems to cause vascular obliteration and, consequently, multiple infarcts, mainly in the white matter, basal ganglia and leptomeninges ⁽⁵⁾. Extracerebral vascular abnormalities have also been noted ⁽⁶⁾.

Photo 1. (click here to zoom) CADASIL: arterial thickening secondary to an eosinophilic deposit of unknown origin (H&E, 160X). Courtesy of Dr. J. Parisi (Mayo Clinic, Rochester, MN).

Photo 2. (click here to zoom) CADASIL: the arterial deposit shows PAS (Periodic Acid-Schiff) positivity,40X. Courtesy of Dr. J. Parisi (Mayo Clinic, Rochester, MN).

Clinical Manifestations

CADASIL first appears after the third decade of life with multiple episodes of migraine (usually associated with aura), and progresses in one decade with recurrent cerebral infarcts in patients without important risk factors for cerebrovascular disease. Dementia becomes evident 20 years after the onset of symptoms. Other manifestations include pseudobulbar paralysis, mood disturbances, neuro-sensorial hearing loss and seizures ^(3,5).

Diagnosis

The use of magnetic resonance imaging is required for the diagnosis. Subcortical and white matter alterations compatible with subcortical infarcts and demyelination, respectively, are the most common findings but nonspecific ⁽³⁾.

Binswanger’s disease is the most important differential diagnosis. It differs from CADASIL because patients with Binswanger’s disease usually have a history of arterial hypertension. Furthermore, the familial occurrence and the history of migraine with aura in CADASIL help to differentiate both illnesses. Other differential diagnosis include vascular and nonvascular dementias ^(3,7).

Treatment

The treatment is nonspecific and the use of platelet aggregation inhibitors has been evaluated ⁽⁸⁾.

CADASIL is still an underdiagnosed disease and its prevalence is probably higher than what is estimated. Therefore, the notion of CADASIL existence is required because it can be an important cause of vascular dementia in a near future.

CADASIL - To remember: