Introduction
Hereditary multiple cerebral infarction dementia(hereditary multi-infarct dementia) also known as autosomal dominant arteropathy with subcortical infarcts and leukoencephalopathy (CADASIL) Van Bogaert (1955) reports the onset of two sisters in middle age Rapidly advanced Binswanger subcortical encephalopathy, manifested as dementia, gait instability, pseudobulbar paralysis,epilepsyWith the loss of focal neurological function, the other two sisters in the family died at 36 and 43 years of age due to progressive dementia. Sourander et al (1977) first described familial cerebral vessels with hereditary multiple cerebral infarction dementia, Stevens et al., chronic familial vascular encephalopathy, which reported an autosomal dominant stroke family of unknown etiology. The disease is mainly caused by damage of the pia mater and deep small arteries of the brain. The thickening of the blood vessel wall causes blood flow reduction and occlusion.
Cause
(1) Causes of the disease
Tournier-Lasserve et al. (1993) linked the genes of two unrelated families and found that the genetic gene of this disease is located at chromosome 19q12. The microsatellite marker was used to localize the gene locus to the 2 cm region (Ducros et al, 1996), confirming that the cause of CADASIL is the Notch 3 gene mutation (Joutel et al, 1996).
(two) pathogenesis
17 cases of CADASIL pathological reports have been reported, except for mild uniform brain atrophy, the frontal parietal lobe is obvious, 2 cases of cerebellar atrophy are obvious, and 2 cases have large brain hematoma, no characteristic changes. The Willis ring may have mild atherosclerosis and small arteriosclerosis, with no occlusion of blood vessels. There are multiple lacunar lesions in the white matter, basal ganglia, thalamus, midbrain and pons around the ventricles. The subcortical white matter is usually better, and the ventricles are obviously dilated. A small number of 10 patients had coronary and aortic atherosclerotic plaques. Microscopic white matter myelin staining was diffuse and focally pale, deep white matter, inner capsule showed lacunar lesions and infarct macrophage response, mild to moderate gliosis, and senile plaques in rare cortical cases. The characteristic fibrinolytic proteins of the white matter and pia mater wall thicken the wall. Sourander reported 3 cases of extensive occlusive endovascular hyaline degeneration, 2 cases of vascular occlusion, and endometrial fibrinous necrosis. Vascular myocyte nuclear loss, spherical cells or scattered clear cytoplasmic balloon-like myocytes make the middle membrane a fuzzy grain-like appearance, Guttiierez-Molina et al. (1994) called small arterial granular degeneration (SAGD). Estes (1991) electron microscopy first discovered white matter and soft osmophilic material (GOM), and many scholars reported GOM. GOM consists of a large number of electron-dense extracellular particulate deposits, which are difficult to measure from 0.2 to 0.8 mm. GOM consists of vascular smooth muscle cells (VSMCs) composed of 10-15 nm granules. The VSMCs of the cerebral perforating branch and meningeal artery were obviously destroyed. The white matter, brain and cerebellar cortex, optic nerve and retinal VSMCs could not be recognized. The changes were observed in skin, muscle and nerve biopsy VSMCs. The nature of GOM has not been determined.
symptom
1. The average age of onset of this disease is 45 years old, no gender difference, no risk factors for stroke. The first symptom is different, 85% of patients have a stroke, and 30% to 90% of patients have dementia, which may be caused by differences in age. The course of disease lasts for 10 to 30 years. 30% of patients have a migraine with aura. Migraine attacks can be the earliest symptoms, mostly occurring at 30 years of age, possibly due to repeated ischemia or underlying vascular disease, leading to white matter lesions. Twenty percent of patients had severe affective disorder, and several families reported significant depression, mania, and suicidal tendencies during the course of the disease, presumably associated with caudate nucleus and ischemic injury. Repeated subcortical symptoms are the main manifestations of this disease, such as recurrent episodes of stroke with cognitive dysfunction, pseudobulbar paralysis, gait instability, pyramidal tract dysfunction, and sphincter dysfunction.
2. Cerebrospinal fluid examination is usually normal. Chabriat et al. (1995) reported an increase in the number of CSF oligoclonal bands and one CSF cell in 2 patients, and 2 cases of immunoglobulin disease in the reported family.
3. MRI is an important diagnostic tool for this disease. The punctate and nodular T2WI high signal can be seen around the lateral ventricle and at the center of the semi-oval, and the basal nucleus and pons are also visible. Most patients had no abnormalities in cerebral angiography. One patient was reported to have severe stenosis of the small arteries, and the other two patients had increased neurological signs after cerebral angiography. PET examination of only one manic patient with severe basal ganglia injury suggests a decrease in cortical metabolism. Skin biopsy is a new method for external brain examination. Skin biopsy has found important diagnostic value for the deposition of eosinophilic granules (GOM).
According to the disease of middle and early stage, clear cerebrovascular disease and family history of dementia, repeated episodes of TIA or stroke, early episodes of migraine, repeated episodes of focal cerebral ischemia, signs, progressive dementia, no stroke risk Factors, without hypertension and diabetes, MRI showed white matter atrophy and multiple cerebral infarction, manifested as non-specific leukoaraiosis, excluding atherosclerotic cortical encephalopathy and amyloidosis vascular disease. Notch 3 gene mutation examination and skin biopsy found that GOM can be diagnosed.
diagnosis
The neuropsymologist's alertness to CADASIL is the key to avoiding clinical misdiagnosis. Screening for young and middle-aged cases of cerebral infarction and dementia with aura of migraine attacks.
1.Binswanger disease is more than 60 years old, with a history of stroke, manifested as chronic progressive dementia, gait instability and urinary incontinence, and more with hypertension. Leukotropia is common in asymptomatic people over the age of 60. Patients with cognitive impairment, evidence of cerebrovascular disease, and risk factors should be identified.
2. Familial disease-related strokes must exclude all genetic factors of cerebral ischemia, such as coagulopathy, dyslipoproteinemia, Fabry disease, cerebral amyloid angiopathy, homocystinuria andMELAS syndrome (mitochondrial myopathy, lactic acidosis, and stroke-like episodes)Etc., these diseases have typical clinical manifestations and specificity tests.
complication
Can be associated with significant depression, mania and suicidal tendencies, pay attention to secondary lung infections, urinary tract infections and hemorrhoids.
treatment
(a) treatment
At present, there is no effective therapy for this disease, and the discovery of Notch 3 gene mutation has laid the foundation for the treatment of this disease.
(two) prognosis
It is closely related to the prognosis of vascular lesions in the brain. At the same time, the prognosis of dementia is also inconsistent due to different lesions and ranges. However, the process of total cognitive decline is irreversible and the progress rate is different.
prevention
Genetic diagnosis and treatment should be performed in patients with a clear genetic background. The treatment of nervous system genetic diseases is difficult, the effect is not satisfactory, and prevention is more important. Preventive measures include avoiding close relatives, conducting genetic counseling, carrier genetic testing, prenatal diagnosis, and selective abortion.
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