From: deputyfife23x@gmail.com   
      
   Cerebral Autosomal Dominant Arteriopathy with Subcortical Infacts and   
   Leukoencephalopathy (CADASIL)   
      
   Before we go into detail about CADASIL, let's break down its complex name so   
   that we understand what it means. Although complex the name is s   
   lf-explanatory and gives an exact medical description regarding the location,   
   mode of inheritance, causative    
   factors and the pathological outcome.   
      
   Cerebral: relating to the brain; thus implying that order systems in the body   
   are relatively unaffected   
   Autosomal dominant: a method of inheritance, whereby a single abnormal copy of   
   a gene causes disease, despite the fact that the other good copy of the gene   
   is present.   
   Arteriopathy: disease of the arteries, usually medium to small size arteries   
   Subcortical: relating to the portion of the brain immediately below the   
   cerebral cortex. White matter and the deep gray structures constitute the   
   subcortical region. They play an important part in most higher functions such   
   as sensation, voluntary muscle    
   movement, thought, reasoning, memory, etc.   
   Infarcts: areas of tissue that have undergone a type of cell death (called   
   necrosis), as a result of loss of blood supply.   
   Leukoencephalopathy: a disease of the brain caused by damage to the white   
   matter.   
   What is the cause of CADASIL?   
   CADASIL is a inherited disorder caused by mutations in a gene called Notch 3,   
   which is a protein that is involved in determining cell fate during fetal   
   development. For example, it might determine whether a particular cell will   
   ultimately be a smooth    
   muscle cell in the wall of a blood vessel, or it will be a liver cell. Post   
   developmental function of Notch 3 includes maintaing the integrity of the   
   arterial vessel wall.   
   Mutation in Notch 3 causes the arterial wall to disintegrate, which leads to a   
   loss of blood supply in the region supplied by that blood vessel. The abnormal   
   Notch 3 protein accumulated in blood vessels of the brain as well as in other   
   parts of the body.    
   The white matter and deeper parts of the brain are predominantly affected   
   leading to infarcts.   
   CADASIL is an autosomal dominant disease, which means that a single abnormal   
   copy of the Notch3 gene overrides the other "good" copy, producing disease   
   (see our Genetic Inheritance fact sheet for more information). This means that   
   if a parent is affected,   
    every child of that parent has a 50% chance of having the disorder as well.   
   If the child receives theabnormal copy, the child has a 100% chance of   
   developing CADASIL.   
   What are the symptoms of CADASIL?   
   Initial symptoms of CADASIL, in the twenties or thirties, include migraine (a   
   type of headache) and mood disorders, which may occur in 30-40% of patients.   
   MRI abnormalities can be seen in the twenties and thirties as well. Strokes   
   occure in the 40's and    
   50's. Over the next few decades as the disease advances, strokes and dementia   
   are common symptoms. Death generally occurs 10-20 years after the onset of   
   strokes and dementia.   
   The most common symptoms of CADASIL include:   
   Migraine with aura: a migraine is a vascular headache resulting from changes   
   in the sizes of the arteries in the brain. An aura refers to an abnormal   
   sensation that the migraine is going to occur.   
   Psychiatric disturbance: any number of mood disorders can occur as a result of   
   CADASIL, including depression   
   Ischemic episodes: Loss of blood flow to the brain, causing symptoms similar   
   to those of a stroke.   
   Cognitive deficits: these might include deficits in memory,attention,   
   multi-tasking and personality; the cognitive abilities generally decline as   
   the disease worsens.   
   Progressive memory loss and dementia   
   Multiple strokes leading to hemiparesis (paralysis of one side of the body),   
   walking difficulty and visual impairment   
   Rarely, epileptic seizures   
   How can CADASIL be diagnosed?   
   Currently, the most reliable method of diagnosis is sequencing the Notch 3   
   gene. This method can diagnose >95% of cases of CADASIL with certainty. The   
   method involves a blood test sent to a specialized laboratory. Availability of   
   the test result makes    
   diagnosis of other family members relatively easy.   
   Prior to availability of the gene tests, skin biopsy was used to diagnose   
   CADASIL. A technique called electron microscopy was used to look for the   
   characteristic accumulations of granular material (called granular osmiophilic   
   material, or GOM) commonly    
   seen in CADASIL. Presence of the material can positively diagnose CADASIL,   
   though a negative result does not necessarily mean that the disease is not   
   present. Additionally, a skin biopsy tissue can be tested for the accumulation   
   of Notch 3, using a    
   molecule that specifically detects this protein. The accumulation occurs well   
   before any symptoms and therefore it can be used to diagnose other family   
   members. At this time, skin biopsy may be used to confirm doubtful cases.   
   Magnetic Resonance Imaging (MRI) may show charactristic alterations in the   
   brain, but the alterations do not appear to be specific only to CADASIL.   
   Therefore, brain MRI should not be considered as a single diagnostic tool.   
   How is CADASIL treated?   
   In a CADASIL patient, migraine should be treated like most other patients of   
   migraine, except the use of a group of medications called triptans (e.g.   
   Imitrex) is usually contraindicated due to increased risk of stroke.   
   Several medications are used to prevent migraine in patients who have frequent   
   and/or severe migraine attacks and these should be used as recommended by the   
   neurologist. Some examples of preventative medications are valproic acid,   
   topiramate, gabapentin,    
   propranolol and tricyclic anti-depressants. Acetazolamide has been used in the   
   past due to its property of dilating blood vessels.   
   Most neurologists agree to the use of low dose daily asprin in patients with   
   CADASIL. Asprin is used in patients who have other risk factors for stroke   
   such as diabetes and heart disease as a prophylactic (preventative) medication.   
      
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