1. CADASIL Cerebral autosomal dominant arteriopathy with
André Spenzieri C. de Mendonça, MD Valério Ribeiro de Oliveira, MD Flávia Aparecida de Sousa Ribeiro, MD St. Helena Hospital – Goiânia - Goiás
CADASIL
Cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy

2. Purpose CADASIL Define
To describe three cases of CADASIL in the same family
Discuss the main findings of the MRI image
Pathological features
Evolution and Prognosis
Differential diagnoses
Demonstrate current perspectives of treatment

3. Definitions
CADASIL
Hereditary small-vessel disease due to mutations in
Notch3 gene on chromosome 19, which causes stroke in young adults
It is also known by the names of hereditary multi-infarct dementia, subcortical vascular dementia and familial encephalophaty

4. Pathological features
CADASIL
The histopathology of small arteries and medium-sized leptomeningeal and long perforating arteries of the brain revealed luminal narrowing or even obliteration caused by deposition of electron-dense granular material in the membrane of vascular smooth muscle cells, and loss of smooth muscle cells vessel walls.

5. Etiology
CADASIL
Two types of lesions affecting small cerebral arteries compromising cerebral hemodynamics   
Reduction of the arterial lumen by fibrous thickening of artery walls   
Destruction of the wall smooth muscle cells of blood vessels can impair the vasodilator response to hypoxia secondary

6. Epidemiology
CADASIL
The CADASIL disease has a worldwide distribution distribution, there are few published hundreds of families being referred to this issue as a bibliographic study of 500 Orphanet ( The disease prevalence of CADASIL is unknown.

7. Presentation
The patient was a previously healthy 23 y female with occasional headache of recent onset diagnosed as migraine without aura, without neuropsychiatric disorders with onset of first symptoms at the age of 22. She had no cognitive impairment, epilepsy, peripheral neuropathy, ocular abnormalities or other neurological disorders.
There was no clinical criteria to suggest multiple sclerosis or other demyelinating disease. However, family history showed that the mother of 52 years had onset of seizures and grandmother had debilitating demyelinating disease being defined without a previous diagnosis.

8. Imaging findings CADASIL
The central nervous system lesions have an age of onset and the rate of progression varies widely. Can be identified even in asymptomatic individuals. In most patients, these lesions are located in the subcortical white matter, but can also be found in other locations central nervous system (brain stem and subcortical gray matter)

9. Imaging findings CADASIL
Initial examination: Conducted study of intracranial arteries by MRI angiography for diagnostic investigation which revealed no vascular changes
CADASIL

10. Imaging findings
Intracranial venous phase were normal
CADASIL

11. Imaging findings CADASIL
The FLAIR sequence performed by MRI showed multiple hyperintense lesions affecting the white matter predominantly to the temporal lobe and bilaterally symmetrical
CADASIL

12. Imaging findings CADASIL
MRI axial T1 sequence after the use of intravenous contrast with gadolinium showed no uptake in the lesions
CADASIL

13. Imaging findings CADASIL
MRI axial T2 sequence at the level of the midbrain demonstrating hyperintense subcortical white matter bi-temporal
CADASIL

14. Imaging findings
T2 * gradient sequence showed no changes
CADASIL

15. Imaging findings CADASIL
Diffusion technique without restriction of water molecules
CADASIL

16. Imaging findings CADASIL
Proton spectroscopy demonstrated increased peak of choline and NAA
CADASIL

17. Imaging findings CADASIL
Studies show that blood flow is reduced in demyelinating lesions compared to normal values ​​in normal white matter due to hypoxic-ischemic events in vascular occlusion observed in this pathology
CADASIL

18. Imaging findings CADASIL
Intrafamilial comparative study We observed the temporal lobes bilaterally symmetrical and its clinical symptoms reported
CADASIL
23 y (daughter) y (mother) y(grandmother)
Headaches Seizures Advanced cognitive deficit

19. Imaging findings CADASIL
The same image looks predominantly at the tips of the temporal lobes in the left picture patient of 23 y, the middle image patient of 52 y and the image on the right patient with 77 y all of the same family and female
CADASIL
Hyperintense on FLAIR compromising the temporal lobes (white arrows)

20. Imaging findings CADASIL
FLAIR sequence showing multiple hard hyperintense foci of deep white matter  affecting the peri-ventricular level in accordance with the progressive age of the patients still noting brain volume reduction
CADASIL
23 y (daughter) y (mother) y(grandmother)

21. Imaging findings CADASIL
Impairment of deep white matter in the region of high curvature of the semi-oval centers and peri-Rolandic
CADASIL
23 y (daughter) y (mother) y(grandmother)

22. Imaging findings CADASIL
Bilateral and symmetric temporal lobe is an important feature in the imaging findings. The brain atrophy is a sign of disease progression and often found to be related to cognitive impairment and functional
CADASIL
23 y (daughter) y (mother) y(grandmother)

23. Imaging findings CADASIL
Sagittal FLAIR sequence shows extensive involvement of the corpus callosum (blue arrows) in older patientswith clinical lush cognitive impairment, difficulty walking, psychiatric disorders
CADASIL

24. Imaging findings CADASIL
Corpus Callosum preserved in patients 23 y and 52 y (left and center) compared with the diffuse involvement of the corpus callosum in the oldest patient (right)
CADASIL

25. Imaging findings
T2 sequence at the basal ganglia of older patients showing disease progression observed here in the latest scan on the right with important involvement of white matter cortical / subcortical sparing the subcortical fiber in "U"
1985
2009

26. Imaging findings First examination in 1985 Control held in 2009
Worsening mental status
First diagnosed as Multiple Sclerosis on this MRI performed in 1985
Difficulty in walking
Cognitive deficit
Incontinence sphincter

27. Pathological features
CADASIL
Geneva Foundation for Medical Education and Research
Reduction of the arterial lumen by fibrous thickening of artery walls Destruction of the wall smooth muscle cells of blood vessels can impair the vasodilator response to hypoxia

28. Natural History & Prognosis
CADASIL
The CADASIL disease has a progressive course and a final very debilitating and disabling. There is great variability within and between families. There is the description of individuals who remained asymptomatic until the seventh decade of life. In the final phase of the disease, most patients have dementia with pseudobulbar palsy and sphincter incontinence

29. DIFFERENTIAL DIAGNOSIS
Sporadic subcortical atherosclerotic encephalopathy
MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
Primary CNS angiitis
Binswanger's disease
Hypercoagulable state

30. DIFFERENTIAL DIAGNOSIS
Images obtained in patients with biopsy-proven CADASIL (top row) and sporadic subcortical atherosclerotic encephalopathy (bottom row) showing the different involvement of white matter and frontal temporo-polar with marked symmetry of lesions
Auer D P et al. Radiology 2001;218:

31. DIFFERENTIAL DIAGNOSIS
Volume display color-coded pixels with significantly increased signal intensity in CADASIL compared with sporadic subcortical atherosclerotic 
encephalopathy
Auer D P et al. Radiology 2001;218:
©2001 by Radiological Society of North America

32. DIFFERENTIAL DIAGNOSIS
Comparison of statistical parametric mapping group of patients with CADASIL and sporadic subcortical atherosclerotic encephalopathy without (A, C) and (B, D) correction of the group threshold
Auer D P et al. Radiology 2001;218:
©2001 by Radiological Society of North America

33. DIFFERENTIAL DIAGNOSIS
Comparison between CADASIL patient in 71 y with an extension of the lesions to the subcortical region and MELAS in a patient of 35 y (Literature File)
CADASIL
Millar, W. S. et al. Am. J. Roentgenol. 2004;182:

34. TREATMENT GUIDELINES CADASIL
There is no effective therapy. These patients are usually monitored in child neurology, but with the progression of the disease need to have a multidisciplinary team, where the psychological support of patients and their families should not be forgotten. Thus, treatment is provided only symptomatic relief. Migraine headaches are treated with analgesia. 
The efficacy and safety of triptans are uncertain. The frequent and disabling attacks may require prophylactic drug therapy in the long term. Depression and mood disorders are treated with conventional antidepressants. The crises of emotional lability benefit from the administration of serotonin reuptake inhibitors

35. References
1. Sourander, P. and J. Walinder, Hereditary multi-infarct dementia. Lancet,
(8019): p. 1015
2. Auer, D.P., et al., Differential lesion patterns in CADASIL and sporadic
subcortical arteriosclerotic encephalopathy: MR imaging study with statistical
parametric group comparison. Radiology, (2): p
3. O'Sullivan, M., et al., MRI hyperintensities of the temporal lobe and external
capsule in patients with CADASIL. Neurology, (5): p
4. Davous, P., CADASIL: a review with proposed diagnostic criteria. Eur J
Neurol, (3): p
5. Jouvent, E., et al., Brain atrophy is related to lacunar lesions and tissue
microstructural changes in CADASIL. Stroke, (6): p
6. Oberstein L et al: Incipient CADASIL. Arch Neurol
60: ,2003