Known C/O CADASIL. Sibling is also affected.
Past
H/O multiple strokes. Now C/O memory impairment with gait ataxia.
Findings:
There are diffuse hyperintense areas on the PD, T2W and
FLAIR images in the periventricular white matter bilaterally, both external
capsules, right lateral aspect of the pons and in the subcortical and deep white
matter in the temporo-fronto-parietal regions bilaterally. These lesions appear
hypointense to normal white matter on the T1W images. Lacunar infarcts are
seen in the body of the corpus callosum, lentiform nuclei, thalami, corona
radiata and centrum semiovale bilaterally. There is fullness of the
ventricles and presence of atrophy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) usually affects middle-aged people. The mode of transmission appears to be autosomal dominant and the disease locus has been assigned to chromosome 19q12.
Clinical Features:
CADASIL patients present with recurrent neurologic episodes that are initially transient motor and sensory disturbances. The initial symptom may be migraine. Eventually the neurologic deficits become permanent and patients develop a stepwise deterioration that may lead to spastic quadriparesis, pseudobulbar palsy, incontinence and dementia. Death generally occurs in the seventh decade. However, linkage analysis is only possible when large families with several affected members can be investigated. In patients with no known family history, the diagnosis can only be suggested by the presence of typical clinical symptoms and neuroradiologic findings, in the absence of arterial hypertension. In patients from smaller families, an exact description of the pattern of lesions seen on brain MR images could be of significant help in the diagnosis.
Pathology:
Histopathology reveals an angiopathy of small and middle-sized arteries. The angiopathy involves duplication and splitting of the internal elastic lamina, hypertrophy of the media and adventitial hyalinosis and fibrosis. Basophilic granular material replaces or destroys the smooth muscle cells of the media, although there are no appreciable atherosclerotic changes or amyloid depositions. Eosinophilic granular deposits have been noted in the media, not confined to the muscular cell layer but extending into the adventitia in the form of coarse, occasionally coalescent, masses. The cerebral arteries affected most are those supplying the white matter, basal ganglia, thalamus, leptomeninges, cerebral cortex, and cerebellum. These are the areas in which high lesion load and volumes may be seen on MR images.
MRI:
MRI shows extensive involvement of the subcortical and periventricular white matter. Typical patterns are:
There is a reasonable correlation between the severity of the clinical syndrome and the degree of brain involvement as seen on MRI.
Differential Diagnosis:
Other conditions may also be characterized by recurrent strokes and
leukoencephalopathy. Binswanger disease causes both focal and widespread signal
changes in the white matter. However, it presents later, is associated with
hypertension and does not have a familial pattern of occurrence. Various other
rare familial conditions are associated with recurrent strokes, such as
hereditary dyslipoproteinemias, thrombotic disorders, homocystinuria and Fabry
disease. These all also have characteristic clinical features that allow them to
be distinguished from CADASIL.