Spinocerebellar ataxia
Introduction
Introduction to spinocerebellar ataxia Spinocerebellar ataxia mainly refers to Friedreich ataxia, a degenerative disease of the spinal cord and cerebellum. Friedreich ataxia is an autosomal recessive disorder. The main clinical manifestations are ataxia, arched foot, optic atrophy, scoliosis, and cardiomyopathy. Spinocerebellar ataxia (SCA) is a major type of hereditary ataxia, including SCA1-21. Adult onset, autosomal dominant inheritance, and ataxia are common features of the disease, and are manifested in advanced age and severity of disease (inherited early). Levodopa relieves extrapyramidal symptoms such as tonicity, and physostigmine or citicoline promotes acetylcholine synthesis. Chloranilide can reduce sputum, amantadine can improve ataxia, and ataxia with myoclonus is preferred. Neurotrophic drugs such as ATP, Coenzyme A, inosine and vitamin B can be tried. basic knowledge The proportion of the disease: the incidence rate is about 0.001% -0.002%, more common in alcoholics Susceptible people: no special people Mode of infection: non-infectious Complications: Cardiomyopathy, valvular heart disease, malnutrition, heart failure
Cause
Spinal cerebellar ataxia
The biochemical changes in this disease are still unknown. Some patients have defects in pyruvate oxidation. Spinocerebellar ataxia (SCA) is the main type of hereditary ataxia, and its common feature is the incidence of young and middle-aged. Vascular disease, occupying disease, autosomal dominant inheritance, and ataxia, confirmed by CT scan to rule out other changes involving the cerebellum and brainstem.
Autosomal dominant cerebral cerebral ataxia has genetic heterogeneity, and the most characteristic gene defect is the amplified CAG trinucleotide repeat encoding polyglutamine channel, which is in unclear protein and P/Q-type calcium channel DA subunit found on nerve endings; other types of mutations include CTG trinucleotide (SCA8) and ATTCT tetranucleotide (SCA10) repeat amplification, which is amplified in many cases The size of the fragment is related to the severity of the disease, and the younger the age, the heavier the condition. SCAs mutations alter the nature of the protein, and the substance cannot be processed normally. The abnormally processed fragment is bound to a ubiquitin which is involved in the non-lysosomal degradation, and is transported to the nucleus in the form of a proteasome conformation. Intranuclear protein aggregation can affect the function of the nucleus. Each SCA subtype gene is located on a different chromosome, with different sizes and gene mutations. For example, the SCA1 gene is located on chromosome 6q22-23, the genome span is 450Kb, the cDNA is 11Kb long, contains 9 exons, and encodes 816 amino acid residues. The base consists of the ataxia-1 protein, which is located in the nucleus. The CAG mutation is located in exon 8 and the amplified copy number is 40-83, and the normal person is 6-38. SCA3 (MJD) is the most common SA subtype in China. The gene is located at 14q24..3-32. It contains at least 4 exons and encodes 960 amino acid residues to form the ataxia-3 protein. In the distributed cell, the CAG mutation is located. Exon 4, the amplified copy number is 61-89, and the normal person is 12-41. Although SCA has a common genetic mutation mechanism, resulting in similar clinical manifestations of different subtypes, there are still differences, such as with ophthalmoplegia, and some with retinitis pigmentosa, pathological lesions and extent are different, suggesting that in addition to polygeneration In addition to the toxic effects of glutamyl, other factors may also be involved in the onset of the disease.
Prevention
Spinocerebellar ataxia prevention
The disease is a congenital genetic disease. The use of DNA diagnosis for timely prenatal diagnosis and selective abortion is a fundamental measure to prevent and treat this disease.
Complication
Spinal cerebellar ataxia complications Complications cardiomyopathy, valvular heart disease, malnutrition, heart failure
Typical Friedreich ataxia is more common before the age of 25 years. Symptoms gradually worsened, loss of mobility 9 to 16 years after onset, and most died of repeated infections or cardiomyopathy. Heart valve disease, myocardial malnutrition, heart block and heart failure can be the cause of sudden death.
Symptom
Spinal cerebellar ataxia symptoms common symptoms ataxia disorders limb movement incoordination sensory ataxia gait closed eyes standing can not be limited dystonia sputum reflexes divergence diplopia ocular hyperopia eye muscle paralysis hyperreflexia
1, SCA common symptoms and signs, 30-40 years old insidious onset, slow progress, there are also children and 70-year-old onset; lower limb ataxia is the first symptom, showing walking shaking, sudden fall and speech ambiguity, As well as clumsy hands, intentional tremor, nystagmus, dementia and distal muscle atrophy; examination showed dystonia, hyperreflexia, pathological signs, gait gait, tuning fork vibration sense and loss of proprioception. Usually can not walk 10-20 years after onset.
2, in addition to the common clinical manifestations, each subtype has its own characteristics, such as SCA1 ophthalmoplegia, upper eye can not be more obvious; SCA2 upper limb paralysis reflexes weakened or disappeared, eyeball slow saccade movement is more obvious; SCA3 muscle atrophy, facial muscles and Tongue muscle fibrillation, eyelid retraction to form a convex eye; SCA8 often has difficulty in pronunciation; SCA5 disease progresses very slowly, mild symptoms; SCA6 early thigh muscle spasm, lower tremor, diplopia and positional vertigo; SCA10 pure cerebellum sign and epilepsy Attack; SCA7 vision loss or loss, retinitis pigmentosa, heart damage is also prominent.
Examine
Spinal cerebellar ataxia
1, CT or MRI showed cerebellar atrophy is very obvious, sometimes brain stem atrophy; brain stem evoked potential can be abnormal, EMG shows peripheral nerve damage; cerebrospinal fluid examination is normal.
2, confirmed SCA and differentiated subtypes of feasible PCR analysis, using peripheral blood leukocytes to detect the corresponding gene CAG amplification, to prove the genetic defects of SCA.
Diagnosis
Diagnosis and differentiation of spinocerebellar ataxia
1, diagnosis
According to typical common symptoms such as ataxia, dysarthria, and pyramidal tract signs, as well as manifestations of ocular paralysis, extrapyramidal symptoms, and retinitis pigmentosa, combined with MRI, cerebellum and brain stem atrophy are found, and other cerebellum involvement is excluded. Brain stem degeneration can be diagnosed clinically. However, clinical diagnosis is still inaccurate based on the characteristic symptoms and signs of each subtype (except SCA7). The number of continents and CAG amplification can be accurately determined by PCR method for gene diagnosis.
2, differential diagnosis
Atypical cases need to be differentiated from ataxia caused by multiple sclerosis, CJD, etc.
