From: deputyfife23x@gmail.com   
      
   Welcome to CADASIL Together We Have Hope Non-Profit Organization   
      
       
   What is CADASIL?   
      
   CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts   
   and Leukoencephalopathy) is a hereditary autosomal dominant disease affecting   
   all the small cerebral arteries. It causes subcortical infarcts and damages   
   the white matter (   
   leukoencephalopathy) and it is due to various mutations of the Notch3 gene   
   situated on chromosome 19.   
      
   Epidemiology   
   Initially described in Europe, the disease has now been observed in families   
   with very different ethnic backgrounds, on all continents. At present, there   
   are more than four hundred families in Europe. There has not yet been any real   
   epidemiological study    
   of CADASIL in France. The authors of a study carried out in the West of   
   Scotland in 2002 listed 22 patients with CADASIL from seven families out of a   
   population of 1,418,990. Considering the relatives of these patients, who risk   
   being carriers of the    
   mutated gene, the researchers estimated the prevalence to be 4.15/100,000   
   inhabitants. It is, though, likely that the frequency of the disease is as yet   
   underestimated.   
      
   Clinical description   
   The initial clinical signs, which are observed in 20% to 30% of patients, are   
   the onset of migraine with aura starting between the ages of 20 and 40.   
   Cerebral infarcts (ischemic strokes) are observed in 70% to 80% of patients   
   with onset usually around    
   the age of 50. There are also cognitive disorders (difficulties with   
   concentration and attention, memory loss), to a greater or lesser extent.   
   These difficulties occur very early in the development of the disease but do   
   not become significant until the    
   50 to 60 years age span. These cognitive difficulties may lead to a change in   
   social life and, eventually, to almost constant dementia in the terminal phase   
   of the illness, combined with difficulties in walking and balance. In 10% to   
   20% of cases, there    
   are also psychiatric disorders and, in 5% to 10% of patients, there are   
   epileptic seizures.   
      
   Migraines with aura (i.e. migraines accompanied by neurological signs) are   
   reported by one in four patients The frequency of the migraines is extremely   
   variable, ranging from twice a week to one every 3 or 4 years. Symptoms of the   
   aura are, in order of    
   frequency, visual, sensory, aphasic or motor. A visual aura manifests itself   
   in various forms, most frequently as a scintillating scotoma and less often as   
   blurring of vision or as a homonymous lateral hemianopsia. Speech disorders   
   during attacks of    
   migraine with aura can often be summarised as difficulties in expressing   
   oneself, with reduced verbal fluency.   
      
   More than one-half of patients suffer migraine with atypical aura i.e.   
   sudden-onset migraines with aura, << basilary >> migraine or << hemiplegic >>   
   migraine. In a few cases, the migraines may be extremely severe such as those   
   seen with familial    
   hemiplegic migraine. They produce episodes of confusion, lack of vigilance,   
   coma and hyperthermia (possibly lasting for several hours or several days).   
      
   Some 70% to 85% of patients report the occurrence of an ischemic event which   
   can be a neurological deficiency of sudden onset resolving in less than 24   
   hours (TLA transient ischaemic attack) or a permanent neurological deficiency.   
   In most cases these    
   signs indicate a minor stroke resulting in traditional signs (lacunar syndrome   
   caused by the occlusion of a small artery: pure sensory deficit, pure motor   
   deficit, or sensorimotor deficit of one side of the body or ataxic   
   hermiparesis). These cerebral    
   infarcts can occur in the absence of any of the usual vascular risk factors   
   (arterial hypertension, diabetes, or hypercholesterolemia).   
      
   Mood disturbance are observed in one in five patients. They may be early (up   
   to 10% of patients), sometimes inuagural and lead to an error or delay in   
   diagnosis. Some patients describe symptoms of severe depression suggesting   
   melancholia, alternating, in    
   a few cases, with episodes of mania (this can lead to the presumptive   
   diagnosis of bipolar disorder). Apathy (loss of motivation) is a frequent sign   
   of the disease, depending on the location of the brain lesions. It is not   
   always secondary to depression.   
      
   Cognitive disorders (difficulties with executive functions, attention and   
   memory) are extremely frequent but of variable severity during the course of   
   the illness. Alteration of the executive functions (planning, anticipation,   
   adjustment, self-correction    
   and mental flexibility) is the earliest symptom most frequently observed and   
   it can be almost imperceptible for many years. Damage to the executive   
   functions is frequently associated with attention and concentration disorders.   
   Gradually, with age, the    
   decline becomes more acute with the onset of apathy, often the most observable   
   feature, and deficiencies in motor functions (tasks such as drawing or writing   
   done using external resources), suggestive of diffuse cerebral damage.   
   However, there is very    
   rarely any severe aphasia (language difficulties), apraxia (difficulties with   
   voluntary behaviors) or agnosia (difficulty with the recognition of objects,   
   people or places with visual difficulties), all features frequently observed   
   in Alzheimer's disease.   
    Semantic memory (linked to knowledge) and recognition are often maintained.   
   Cognitive decline commonly appears gradually, often in the absence of any   
   ischaemic events. This development may therefore suggest a degenerative   
   disease. Sometimes, the patient    
   suddenly worsens, in stages.   
      
   Dementia (cognitive difficulties that affect the patient's everyday life and   
   lead to a loss of independence) is observed in one-third of patients,   
   especially after the age of 60. Its frequency increases with age and   
   approximately 60% of patients over the    
   age of 60 have dementia. It is often associated with other signs of the   
   gravity of the disease e.g. difficulty with walking, urinary incontinence and,   
   sometimes, a pseudo-bulbar palsy (difficult swallowing, spasmodic laughter or   
   crying).   
      
   Despite the diffuse damage to small arteries in all organs, the clinical   
   manifestations of the disease are only neurological and restricted to the   
   brain.   
      
   Clinical course and prognosis   
      
   [continued in next message]   
      
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