脊髓小脑性共济失调3型一家系的临床及电生理特征分析

发布时间：2018-03-26 14:14

本文选题：脊髓小脑性共济失调　切入点：基因　出处：《福建医科大学》2014年硕士论文

【摘要】：目的：调查一脊髓小脑性共济失调3型（spinocerebellar ataxia type3，SCA3）家系的遗传谱系、临床及电生理特征。方法：对福建地区一疑诊为SCA3家系的11名家系成员进行基因检测、影像学及神经电生理检查，并结合文献分析SCA3的临床及电生理特征。结果：1.在11名家系成员中，8名成员的基因检测显示CAG三核苷酸重复次数超出正常范围：5名成员为现患者，CAG三核苷酸重复次数范围为70～75次，平均（72.0±2.0）次，确诊为SCA3；另3名成员虽无临床症状，但CAG三核苷酸重复次数范围为70～72次，平均（71.0±1.0）次，为未到发病年龄的SCA3症状前患者；其余3名成员CAG三核苷酸重复次数均在正常范围。 2.家系4代22名成员中共有9例发病，每代均有患者，男女均受累，存在遗传早现的现象。现患者平均发病年龄为（41.0±2.9）岁，以进行性共济失调为突出表现，如步态不稳、动作笨拙（100%），且累及上、下运动神经元：上运动神经元受累主要表现为病理征阳性（100%）、腱反射活跃（80%）、肌张力增高（60%），下运动神经元受累主要表现为肢体肌肉萎缩（80%）、肌无力（40%）。世界神经病联合会国际协作共济失调评估量表(ICARS)评分在32～83分之间，临床症状越严重，评分越高。 3.SCA3现患者颅脑MRI显示小脑及脑干明显萎缩，症状前患者颅脑MRI则无明显异常。 4.SCA3存在体感神经传导通路、脑干听觉传导通路及视觉传导通路的障碍，诱发电位提示该病具有中枢性及周围性损害；体感诱发电位（SSEP）在疾病早期即可出现异常；神经电图检查(NCSs)以感觉运动性轴索性损害为主，感觉纤维受累更为显著，神经传导速度多在正常范围；常规肌电图（EMG）主要表现为神经源性损害，并在肌肉萎缩明显时可出现广泛的纤颤波或束颤波等自发电位，与运动神经元病(MND)的EMG类似。结论：1.本家系经研究证实，为SCA3合并运动神经元受累（MNS）。 2.SCA3家系的外显率高，患病者的CAG三核苷酸重复次数与正常人存在显著差别，CAG三核苷酸重复次数检测可为疾病的基因诊断及症状前诊断提供依据。 3.SCA3神经电生理表现具有一定特征性：SCA3诱发电位提示中枢性及周围性损害；SSEP可能是SCA3早期电生理改变的敏感指标，发现亚临床损害；NCSs以感觉运动性轴索性损害为主；EMG主要表现为神经源性损害。
[Abstract]:Objective: to investigate the genetic pedigree, clinical and electrophysiological characteristics of a family of spinocerebellar ataxia type 3 (SCA3) with cerebellar ataxia. Imaging and neuroelectrophysiological examination, The clinical and electrophysiological characteristics of SCA3 were analyzed in combination with literature. Results: 1.The gene tests of 8 out of 11 family members showed that the number of trinucleotide repeats of CAG exceeded the normal range of CAG trinucleotide repeats in 5 members of the family. The frequency ranges from 70 to 75, The mean number of CAG trinucleotide repeats was 72.0 卤2.0 times and 71.0 卤1.0 times respectively, and the other 3 members had no clinical symptoms, but the number of CAG trinucleotide repeats was 71.0 卤1.0 times. The number of CAG trinucleotide repeats in the other 3 members were within normal range. 2. There were 9 cases of disease in 22 members of 4 generations in the family, each generation had patients, both men and women were involved, and there was an early occurrence of heredity. The average onset age of the present patient was 41.0 卤2.9 years old, with progressive ataxia as a prominent manifestation, such as gait instability, The clumsy movements involved, Inferior motor neurons: the involvement of upper motor neurons is mainly manifested as pathological sign positive, tendon reflex is active, muscle tension is increased, muscle tension is increased, and inferior motor neurons are mainly manifested as limb muscle atrophy, myasthenia and myasthenia. The World Federation of Neuropathy. The ICARS score of the International Cooperative ataxia Assessment scale (ICARS) was between 32 and 83, The more severe the clinical symptoms, the higher the score. Craniocerebral MRI showed cerebellar and brainstem atrophy in present 3.SCA3 patients, but no significant abnormality in craniocerebral MRI in patients with 3.SCA3 before symptoms. In 4.SCA3, somatosensory nerve conduction pathway, brainstem auditory conduction pathway and visual conduction pathway were obstructed, and evoked potential showed central and peripheral damage, and somatosensory evoked potential (SSEP) was abnormal in the early stage of the disease. NCSs were mainly sensorimotor axonal damage, sensory fiber involvement was more significant, nerve conduction velocity was mostly in normal range, and routine electromyogram (EMG) showed neurogenic damage. A wide range of spontaneous potentials such as fibrillation wave or beam fibrillation wave can occur when muscle atrophy is obvious, which is similar to the EMG of motor neuron disease (MND). Conclusion [WT5HZ] [WT5BZ] [WT5 "HZ] [WT5BZ] [WT5" HZ] [WT5BZ] [WT5BZ]. The frequency of CAG trinucleotide repeats in 2.SCA3 families was significantly different from that in normal controls. The detection of 2.SCA3 trinucleotide repeats could provide evidence for gene diagnosis and pre-symptomatic diagnosis of the disease. The electrophysiological characteristics of 3.SCA3 suggested that central and peripheral lesions might be sensitive to early electrophysiological changes in SCA3. It was found that NCSs were mainly sensorimotor axonal damage and EMG was mainly neurogenic.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R744.7

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