舞蹈症-棘红细胞增多症的早期识别和筛查

目的：探讨舞蹈症-棘红细胞增多症（chorea-acanthocytosis,ChAc）临床特点,为该病早期诊断提供思路和方法。方法：通过回顾性研究,总结ChAc临床特点。结果：符合舞蹈样运动障碍的患者中,ChAc占29%,确诊时间中位值为5.5年。患者的发病年龄为（33.57±12.23）岁;7例（100%）均有口腔运动障碍,4例（57%）出现癫痫（全面强直阵挛发作）,6例（86%）出现腱反射减弱或消失,5例（71%）肌酸激酶增高;头颅磁共振可见尾状核尤其尾状核头（57%）和豆状核（29%）萎缩,侧脑室前角扩大（57%）;正电子发射断层显像（positron emission tomography,PET）-电子计算机断层扫描（computed tomography,CT）可见双侧基底节区低代谢表现（43%）。所有患者均可见棘红细胞比例大于3%,基因测序29%可发现责任基因VPS13A突变。结论：ChAc的确诊时间长,口腔运动障碍、肌酸激酶增高有助于尽早识别。建议舞蹈症患者常规进行2次以上的外周血涂片,进而再进行基因检测确立诊断。     

Testing for acanthocytosis

Abstract The presence of acanthocytosis in peripheral blood smears remains the hallmark of the clinical diagnosis of most neuroacanthocytosis syndromes, such as chorea-acanthocytosis (ChAc) and McLeod syndrome. Genetic analyses and/or specific laboratory tests are available only for a minority of these disorders. Testing for acanthocytosis is hampered by the lack of data on normal amounts of acanthocytes assessed by a standardized method. We report a prospective reader-blinded study designed to establish control values for abnormally shaped erythrocytes in healthy volunteers and patients with movement disorders (MDs) using light microscopic assessment of erythrocyte morphology in standard EDTA and isotonically diluted blood samples. We investigated a total of 100 patients fulfilling clinical criteria of specific MDs, 31 patients with MDs not matching any clinical criteria, and 37 healthy controls. In patients with diagnosed MDs and healthy controls, acanthocytes in dry blood smears were significantly more frequent following isotonic dilution compared with standard EDTA blood. In unfixed wet blood preparations of both EDTA blood and isotonically diluted blood, acanthocyte levels were significantly higher than in standard dry blood smear preparations. There were no statistical differences of acanthocyte levels in all test conditions between diagnosed MDs and healthy volunteers. There was no significant correlation of acanthocyte levels in all blood samples and preparations with age, sex or diagnosis. Thus, normal values were defined as the 99th percentile of combined results of the two groups of volunteers. Diluted blood combined with wet blood preparation showed high specificity (0.98) and the highest sensitivity of all test procedures (all genetically confirmed ChAc patients were detected). The reported method is cheap, readily available, and provides high specificity and sensitivity in respect to clinically relevant acanthocytosis. The use of isotonically diluted blood samples combined with unfixed wet blood preparation with a normal range of <6.3% of total erythrocytes is recommended to search for significant acanthocytosis in movement disorders.     

Clinical and molecular research of neuroacanthocytosis

Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated "acanthocytic" red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington’s disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.     

伴精神症状的舞蹈病-棘红细胞增多症1例并文献复习

目的加强对伴精神症状的舞蹈病-棘红细胞增多症(chorea-acanthocytosis, ChAc)的临床表现、检查及诊断的认识,并对治疗进行初步探讨。方法通过回顾性分析湖南省脑科医院2019年收治的伴精神症状的ChAc患者的诊疗过程,检索并分析伴精神症状的ChAc的病例报道,总结其临床表现、检查及本例中西医治疗方法。结果本例患者表现为头面部不自主运动伴精神症状,外周血棘红细胞增多、肌酸激酶增高,VPS13A基因突变。检索结果提示伴精神症状的ChAc患者以舞蹈样不自主运动为主要临床表现,以外周血棘红细胞增多、肌酸激酶增高及尾状核萎缩为特点,基因检测可作为有效的诊断手段。抑郁为最常见的精神症状,可使用氢溴酸西酞普兰进行改善。根据患者症状及体征,属中医学"百合病"范畴,予以百合地黄汤加减联合治疗后,患者症状明显改善。结论精神症状是ChAc较为常见的临床表现,对疑似病例应及时行外周血涂片等检查,以减少漏诊、误诊。中西医结合治疗可取得较好疗效。     

神经棘红细胞增多症(附1例报告)

目的通过舞蹈-棘红细胞增多症(ChAc)的临床资料分析,提高对ChAc的认识。方法对收治的1例ChAc病例的诊断过程进行分析,结合文献复习对神经棘红细胞增多症(NA)的遗传方式、影像学和实验室检查等特点进行总结。结果NA临床症状复杂多样,其发病特点与广泛的非特异性神经系统病变、棘红细胞增多密切相关。NA治疗以对症支持为主。结论NA是一种罕见的神经退行性疾病,预后差;早发现、早诊断、早治疗可改善预后。     

Chorea-acanthocytosis in monozygotic twins: clinical findings and neuropathological changes as detected by diffusion tensor imaging,FDG-PET and <Superscript>123</Superscript>I-<Emphasis Type="Italic">β</Emphasis>-CIT-SPECT

Abstract We report on two 33 years old monozygotic twins with chorea-acanthocytosis (ChAc) misdiagnosed as schizophrenia and Tourette syndrome, respectively. Although the patients shared several clinical similarities, there were also some clear differences: twin 1 presented initially with an acute episode of a paranoid schizophrenia, while twin 2 suffered from generalized epileptic seizures. In both twins, MRI demonstrated caudate nucleus atrophy and an increased apparent diffusion coefficient (ADC) in the striatum bilaterally with right sided predominance. ¹⁸F-FDG PET showed bilaterally reduced glucose utilization in the striatum with clearly pronounced reduction on the right side compared to the left and in twin 1 compared to twin 2. Ratios of binding to striatal dopamine transporters (DAT) and serotonin transporters in the hypothalamus midbrain area as determined using ¹²³I-β-CIT-SPECT fell within the normal ranges. However, in twin 1 a significant difference in binding to presynaptic DAT with marked reduction on the right hemisphere was observed. Right hemispheric accentuated changes measured by MRI, FDG-PET, and ¹²³I-β-CITSPECT correspond to more severe hyperkinetic movements on the left part of the body in both twins. Different neuro-psychiatric features in this monocygotic twin pair suggest that not only genetic but also environmental factors contribute to the clinical symptomatology. Our findings suggest that the main neuropathological process in ChAc is located in the striatum, involving microstructural alterations, and disturbance of metabolism and dopaminergic neurotransmission.