[32] The vast majority of migraine sufferers with CADASIL, 80-90%, have migraine with aura.[27, 32] Rates of migraine without aura appear to be similar to the general population.[22] When migraine with aura is present, it is often the presenting symptom, and almost all migraine cases become symptomatic by age 38.[27] Aura characteristics are typical in 44% of cases, while 56% of cases also experience atypical features,
including aura without headache, brainstem aura, hemiplegic aura, prolonged Dasatinib order aura, or acute onset aura.[33] Severe attacks associated with fever, confusion, meningitis, or coma have also been reported.[34, 35] The frequency of attacks can be highly variable, and triggering factors are often typical for migraine headaches.[29] Subcortical ischemic events, whether transient ischemic events or completed infarctions, are the most frequent clinical manifestation of CADASIL, occurring in 65-85% of BGB324 manufacturer patients.27-29 The average incidence of
stroke in CADASIL patients is 10.4 per 100 person-years.[36] The age of onset of ischemic events is usually in the fifth decade of life, and most patients have recurrent ischemic events. Two-thirds of strokes correspond to classic lacunar syndromes, with the remainder representing mostly small deep infarctions.[22] Large artery infarcts are usually absent, although large vessels may occasionally be involved in CADASIL.[37] Traditional vascular risk factors are usually not present, although hypertension, high cholesterol, and smoking have been reported in case series.27-29 Cognitive dysfunction is the second most frequent clinical manifestation of CADASIL, being reported in 40-60% of patients in some case series.[27, 28, 38] Cognitive dysfunction typically is slowly progressive, and patients demonstrate a stepwise deterioration, typical for vascular dementia.[27, 29] It is by nature subcortical, and many patients have frontal lobe features, 上海皓元医药股份有限公司 such
as disinhibition, perseveration, and apathy. Most develop gait disturbance, urinary urgency, and pseudobulbar palsy as the disease progresses.27-29 One of the earliest signs of cognitive dysfunction is impairment in executive function and processing speed, almost universally present by age 50 in 1 case series of 42 symptomatic patients. Frank dementia appears later in the course of the disease, with 75% of demented patients being older than 60 years.[39] Mood disturbances are present in 20-30% of patients with CADASIL and most frequently present as episodes of severe depression, although manic episodes have also been described. Mood disturbances are rarely the presenting feature of the disorder, often developing as the disease progresses.27-29 Apathy, perhaps as a manifestation of frontal lobe symptoms seen with the development of dementia in these patients, has been described in 41% of patients and can occur independently from depression.