Transcript CADASIL

CADASIL
Cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy
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
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 multiinfarct dementia, subcortical vascular dementia and
familial encephalophaty
CADASIL
The histopathology of small arteries and mediumsized 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.
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
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 (www.orpha.net)
The disease prevalence of CADASIL is unknown.
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.
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)
Initial examination: Conducted study of intracranial arteries by MRI
angiography for diagnostic investigation which revealed no vascular
changes
CADASIL
Intracranial venous phase were normal
CADASIL
The FLAIR sequence performed by MRI showed multiple hyperintense
lesions affecting the white matter predominantly to the temporal
lobe and bilaterally symmetrical
CADASIL
MRI axial T1 sequence after the use of intravenous contrast with
gadolinium showed no uptake in the lesions
CADASIL
MRI axial T2 sequence at the level of the midbrain
demonstrating hyperintense subcortical white matter bi-temporal
CADASIL
T2 * gradient sequence showed no changes
CADASIL
Diffusion technique without restriction of water molecules
CADASIL
Proton spectroscopy demonstrated increased peak of choline
and NAA
CADASIL
Studies show that blood flow is reduced in demyelinating lesions compared
to normal values in normal white matter due to hypoxicischemic events in vascular occlusion observed in this pathology
CADASIL
Intrafamilial comparative study
We observed the temporal lobes bilaterally symmetrical and its clinical
symptoms reported
CADASIL
23 y (daughter)
Headaches
52 y (mother)
Seizures
71 y(grandmother)
Advanced cognitive deficit
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)
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)
52 y (mother)
71 y(grandmother)
Impairment of deep white matter in the region
of high curvature of the semi-oval centers and peri-Rolandic
CADASIL
23 y (daughter)
52 y (mother)
71 y(grandmother)
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)
52 y (mother)
71 y(grandmother)
Sagittal FLAIR sequence shows extensive involvement of the
corpus callosum (blue arrows) in older patientswith
clinical lush cognitive impairment, difficulty walking, psychiatric
disorders
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
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
First examination in 1985
Control held in 2009
Worsening mental statu
First diagnosed as
Multiple Sclerosis
on this MRI performed
in 1985
Difficulty in walking
Cognitive deficit
Incontinence
sphincter
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
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
• Sporadic
subcortical atherosclerotic encephalopathy
• MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis
and stroke-like episodes
• Primary CNS angiitis
• Binswanger's disease
• Hypercoagulable state
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;218:443-451
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;218:443-451
©2001 by Radiological Society of North America
Comparison of statistical
parametric mapping group of
patients with CADASIL
and sporadic subcortical
atherosclerotic encephalopat
hy without (A, C) and (B, D)
correction of the
group threshold
Auer D P et al. Radiology 2001;218:443-451
©2001 by Radiological Society of North America
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;182:1537-1541
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
1. Sourander, P. and J. Walinder, Hereditary multi-infarct dementia. Lancet,
1977. 1(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, 2001. 218(2): p. 443-451
3. O'Sullivan, M., et al., MRI hyperintensities of the temporal lobe and external
capsule in patients with CADASIL. Neurology, 2001. 56(5): p. 628-634
4. Davous, P., CADASIL: a review with proposed diagnostic criteria. Eur J
Neurol, 1998. 5(3): p. 219-233
5. Jouvent, E., et al., Brain atrophy is related to lacunar lesions and tissue
microstructural changes in CADASIL. Stroke, 2007. 38(6): p. 1786-1790.
6. Oberstein L et al: Incipient CADASIL. Arch Neurol
60:707-712,2003