Migraines, Strokes, Depression and Dementia - Oh My... Multiple Sclerosis?

What do all of these things have in common (besides the brain)?  A genetic neurologic disorder often misdiagnosed as Multiple Sclerosis - CADASIL.

C - cerebral
A - autosomal
D - dominant
A - arteriopathy
S - (with) subcortical
I - infarcts
L - (and) leukoencephalopathy (destruction of white matter in the brain)

CADASIL is found in families, and it is a serious neurologic disease to have.  It is the most common form of hereditary stroke disorder, although it is still considered to be a rare disease.

It strikes when the patient is young - typically in the mid-thirties - often beginning as Migraine headaches (40%) usually with aura which may mimic TIA,  before progressing to depression, strokes and mini-strokes, apathy, motor function problems, and finally, dementia.  Usually by age 65 dementia has set in and other symptoms are quite noticeable.  Symptoms and the time of onset can vary widely however.  The neurological problems associated with CADASIL stem from vascular thickening of the small blood vessels in the white matter of the brain due to abnormal muscle cells in those vessels, which occludes bloodflow to the brain.  Due to the granulation deposits within the walls of small arterial vessels as well as degeneration of vascular smooth muscle cells which cause the narrowing of arteries, the brain essentially starves. Later on, other tissues in the body are damaged as well.  CADASIL was portrayed in a 2004 movie called "The Sea Inside".

Other symptoms of CADASIL include:

• lesions in white matter
• cognitive deterioration
• seizures
• vision problems
• psychiatric problems
• speech defects

There are more than 100 mutations that can cause CADASIL, but all cause a change in the amino acid of the Notch 3 receptor.  The gene associated with CADASIL is called NOTCH 3 and resides on chromosome 19.  This gene is inherited in a dominant fashion.  This means that if you have one of the genes, you will get the disease.  50% of the children of a carrier can be expected to be affected as well.

Unfortunately, there is a high affinity for misdiagnosis of CADASIL in patients and their relatives.  Unfortunately, many patients are misdiagnosed with Multiple Sclerosis which can appear in testing and imaging the same as CADASIL.   Both diseases usually begin in young adults with similar symptoms.

Testing for CADASIL includes genetic testing, skin biopsy which looks for granulation deposits but may also be negative, MRI which alone is not sufficient to diagnose this disease.

Because there are no treatments yet effective for CADASIL, it was hoped that an Alzheimer's Disease drug called Aricept might help these patients.  It was from a larger study on this medication that this smaller study (indicating MS is a frequent misdiagnosis) was a part of. Since there is no treatment, supportive care is given and can include Migraine medications (taking care not to use medications in the list below), depression medications, and a daily aspirin to help reduce the chance of stroke.  Lifestyle changes include stopping smoking which can exacerbate the condition.

Some medications should be avoided in CADASIL patients, and knowing if you have the genetic mutation is important as these drugs may be prescribed for symptoms the disease causes yet make the situation even worse.  These include:

++ Thrombolyisis & anticoagulant treatments like Warfarin used in TPA (Hughes Disease) and other diseases
++ Arteriography procedures
++ Vasoconstricting medicines (ergotamines and Triptans used as Migraine abortives)
++ products aimed at unblocking blood vessels (they increase the risk of a hemorrhage).
++ Warfarin, Coumadin
++ Contraceptive pills are a risk factor. It's recommended to use less than 50 mcgs of estrogen in birth control method.

Unfortuantely, Aricept was not found to affect CADASIL in any manner which was disappointing.  The authors of the study do state that groundwork in this field is "exploding" and great leaps toward understanding CADASIL have been made.  Before good treatments are developed, a disease must first be understood enough to develop new treatments.  From this perspective, there is great hope down the road for patients and their families.

Other studies are being done currently and include looking at an overreaction to hormones that can affect poor blood supply. Another was published that looked at CADASIL's increased vasoreactivity to L-argninine in the brain, and hopes are high that understanding this reactivity may lead to therapies in the future.

If you have a diagnosis of CADASIL, please consider donating your brain to the CADASIL Tissue Bank for research after your death.  There is a shortage of this tissue for researchers to use to help others in the future.   Researchers in fact need healthy brains for use in research as well, so anyone can donate and help the cause.  :)

For more in-depth reading on this important disease:
CADASIL Foundation
National Institute of Neurological Disorders and Stroke
Medical News Today

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