脑健黄瘤病2021/3/241授课：XXXCase 1 A 44-year-old man presented with progressive cerebellar ataxia and spastic paraparesis. Gait difficulties had started at age 16 years, and at age 42 years bilateral cataracts were diagnosed. His cognitive function progressively declined, and seizures repeatedly occurred. Neurology 2005;64;14762021/3/242授课：XXX A 47 years old white man which symptoms began at 20 years old. He presented progressive walking difficulty, becoming unable to walk fast at 40 years old. He presented delay of the psychomotor development .He had a history of chronic diarrhea during the childhood. His mother denied other family members with similar symptoms, except for the patients younger brother. Case 2Arq Neuropsiquiatr 2004;62(4):1085-10892021/3/243授课：XXX In the neurological examination, he presented mild mental retardation, mild bilateral facial palsy without other findings in cranial nerves. His muscular strength was IV in superior limbs (SL) and IV- in inferior limbs (IL). We noted moderate spasticity in IL, increased deep tendon reflexes with bilateral Babinski sign. The sensibility was preserved . The patient presented symmetrical dismetry and disdiadococinesy in SL. He had also gait ataxia and walked with support.Arq Neuropsiquiatr 2004;62(4):1085-10892021/3/244授课：XXX A, 40 years old white man, case twos brother, which according to the mothers information, presented learning difficulty since childhood, unable to read or to write. He did not finish the basic school. At 35 years of age he began with progressive difficulty to walk .He also presented chronic diarrhea and was submitted to a bilateral cataracts surgery in the childhood. Case 3Arq Neuropsiquiatr 2004;62(4):1085-10892021/3/245授课：XXX In the neurological exam he presented mild mental retardation, visual handicap and facial palsy without other abnormalities in cranial nerves. The muscle strength was V in SL and IV+ in IL. Other findings were spasticity in IL, increased deep tendon reflexes with bilateral Babinski and Hoffman signs. Sensibility was preserved. He had walking disturbance with ataxia and spasticity in IL. Arq Neuropsiquiatr 2004;62(4):1085-10892021/3/246授课：XXX 患者男性,52 岁。以“头痛、发热、声音嘶哑1 周”入院。入院前1 周无明显诱因出现头痛,为后枕部跳痛,呈阵发性并持续加重,伴有发热,体温最高达38.8 , 咳嗽,无痰,声音嘶哑。入院后患者出现尿潴留,饮水呛咳并逐渐出现进食饮水困难。患者13 岁双眼曾患白内障,25岁行白内障手术;1990 年开始逐渐出现痉挛性截瘫和智能障碍。入院查体:体温37.8 ,血压130/70 mmHg 。神志清楚,声音嘶哑,反应淡漠,计算力差,左侧软腭抬举无力,咽反射消失,左侧声带麻痹,伸舌左偏,双上肢肌力级,肌腱反射对称,双下肢肌力级,双侧膝反射及跟腱反射活跃,双侧踝阵挛阳性,双侧巴宾斯基征阳性。家系调查:患者妹妹也呈痉挛性步态,无白内障和明显智能障碍,父母无类似病史。病例 4中国神经免疫学和神经病学杂志2007 年14 卷2 期2021/3/247授课：XXX本病的共同特点：小脑性共济失调锥体束受损脑干受累智力障碍白内障、腹泻家族史2021/3/248授课：XXX2021/3/249授课：XXX2021/3/2410授课：XXXCase 12021/3/2411授课：XXXCase 2-32021/3/2412授课：XXXCase 2-32021/3/2413授课：XXXCerebrotendinous Xanthomatosis(CTX)脑腱黄瘤病2021/3/2414授课：XXX 脑腱黄瘤病（）是一种常染色体隐性遗传的脂肪代谢障碍性疾病，致病基因位于常染色体，导致固醇羟化酶缺乏，使胆固醇合成胆酸受阻，引起不同组织胆固醇代谢障碍。2021/3/2415授课：XXX 多系统损害： 肌腱黄瘤(71%) 青少年白内障(92%) 早发的动脉硬化 神经系统损害(100%) 小脑性共济失调 进行性智能减退(81%) 进行性下肢痉挛性瘫痪 延髓麻痹 周围神经病2021/3/2416授课：XXX 诊断线索1）infantile-onset diarrhea Chronic diarrhea from infancy may be the earliest clinical manifestation. 2021/3/2417授课：XXX2）childhood-onset cataract In about 75% of affected individuals, cataracts are the first finding, often appearing in the first decade of life. 2021/3/2418授课：XXX3）adolescent- to young adult-onset tendon xanthomas Xanthomas appear in the second or third decade; they occur on the Achilles tendon.2021/3/2419授课：XXX4）adult-onset progressive neurologic dysfunction dementia with slow deterioration in intellectual abilities occurs in the 20s in over 50% of individuals. Neuropsychiatric symptoms such as behavioral changes, hallucinations, agitation, aggression, depression, and suicide attempts may be prominent. Pyramidal signs (i.e., spasticity) and/or cerebellar signs are almost invariably present between 20 and 30 years of age. Other findings include extrapyramidal manifestations (dystonia and atypical parkinsonism), seizures, and peripheral neuropathy. 2021/3/2420授课：XXX肌腱黄瘤2021/3/2421授课：XXX肌腱黄瘤2021/3/2422授课：XXX肌腱黄瘤2021/3/2423授课：XXX肌腱黄瘤2021/3/2424授课：XXX肌腱黄瘤2021/3/2425授课：XXX肌腱黄瘤2021/3/2426授课：XXX肌腱黄瘤2021/3/2427授课：XXX脑腱黄瘤病的MRI表现 Conventional MRI studies have shown focal/ diffuse white matter abnormalities and different degrees of cerebral and cerebellar atrophy in the brain of patients with CTX. The bilateral nonhomogenous, hyperintense magnetic resonance signal in dentate nuclei and surrounding cerebellar white matter, can be considered as a neuroradiological feature suggestive of CTX and could become an important diagnostic marker.2021/3/2428授课：XXX脑腱黄瘤病的MRI表现2021/3/2429授课：XXX脑腱黄瘤病的MRI表现2021/3/2430授课：XXX脑腱黄瘤病的MRI表现2021/3/2431授课：XXX脑腱黄瘤病的MRI表现2021/3/2432授课：XXX脑腱黄瘤病的MRI表现2021/3/2433授课：XXX脑腱黄瘤病的MRI表现2021/3/2434授课：XXX脑腱黄瘤病的MRI表现2021/3/2435授课：XXX脑腱黄瘤病的诊断临床表现家族史MRI血浆胆甾烷醇升高、固醇27-羟化酶活性下降基因检查: mutations in the sterol 27-hydroxylase gene (CYP 27 gene) 病理检查:肌腱内发现腱黄瘤细胞或胆固醇结晶2021/3/2436授课：XXX脑腱黄瘤病的治疗 Several modes of treatment have been tried for CTX. Since 1975, chenodeoxy cholic acid (CDCA)(鹅脱氢胆酸 ) 750 mg daily has been commonly used as the standard therapy, There is a considerable decrease in the serum cholestanol and a sharp decline in the excretion of urine bile alcohols. But a combination of CDCA with 3-hydroxy 3-methyl glutaryl coenzyme A (HMG COA) reductase inhibitors such as pravastatin or simvastatin (10-40 mg daily) is found to be more effective in lowering the serum cholestanol levels. Long-term treatment may arrest or even reverse the progression of the disease. 2021/3/2437授课：XXX2021/3/2438授课：XXX谢谢!2021/3/2439授课：XXX2021/3/2440授课：XXXThank you!2021/3/2441