Homogeneous clinical subgroups in children with Tourette syndrome

The existence of two clinically homogeneous subgroups in Tourette syndrome, depending upon the presence or absence of migraine or a family history of migraine, is suggested. Patients with Tourette syndrome who have migraine (n = 18) were found to have a significantly higher prevalence of disorders of arousal--particularly sleepwalking and night terrors--as well as a higher prevalence of motion sickness than patients without migraine (n = 27). They were also significantly more likely to exhibit a co-occurrence of associated features (two or more) than the patients without migraine. Patients with Tourette syndrome who have not had migraine headaches but in whom there is a family history for migraine (n = 20) were shown to have an intermediate prevalence of associated symptoms. It is suggested that the differential association for these symptoms in patients with Tourette syndrome may reflect an underlying abnormality in function of two different neurotransmitter systems.     

Tourette综合征儿童主观生活质量研究

目的：探讨Tourette综合征（TS）儿童的主观生活质量状况,为其综合干预提供理论依据。方法：选取儿童保健科就诊的174例TS患儿（≥8岁）作为病例组,选取儿童保健科门诊的正常体检儿童186例(≥8岁)为对照组。采用病例对照研究的方法探讨TS儿童的主观生活质量状况。结果：TS儿童主观生活质量总分（156.6±21.1）低于对照组（164.2±21.2）（P<0.01）,家庭生活、学校生活、认知成分、抑郁体验和焦虑体验得分（19.1±3.5,24.1±4.4,90.6±13.3,24.0±4.6,23.8±4.4）亦低于对照组（20.7±3.0,26.6±3.2,97.9±15.3,25.1±3.1,24.7±3.5）（P<0.05）。相关分析发现TS儿童主观生活质量总分与患儿年龄、病程、症状严重程度、儿童行为总分及家庭矛盾性呈负相关 (r=-0.432,-0.213,-0.869,-0.137, -0.257;均P＜0.01),而与家庭娱乐性呈正相关(r=0.084,P＜0.01)。多元逐步回归分析显示TS儿童主观生活质量的影响因素是症状严重程度、患儿年龄、家庭矛盾性和娱乐性(β′=-0.787,-0.171,-0.109,0.106;P<0.01)。结论：TS儿童主观生活质量不佳;为提高患儿主观生活质量,尽早控制临床症状与改善家庭环境是必要的。     

Factors influencing diagnosis delay in children with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is a chronic disorder characterized by motor and vocal tics. Previous studies reported a substantial lag period between disease onset and diagnosis ranging from 3 to 11.9 years. AIMS: To determine the lag period and factors associated with diagnosis delay of TS. METHODS: All files of 185 children with TS attending one neuropediatric unit in Jerusalem were reviewed. Lag time between disease onset, according to DSM criteria, and diagnosis was determined and the contributions of the disease course, comorbidities and epidemiological factors were assessed. RESULTS: A relatively short lag to diagnosis following the onset of diagnosable TS was documented (mean 13.2+/-15.9 months, median 6 months). A relatively longer gap was associated with older age at TS onset (r=0.161, p<0.05) and vocal tics as the first manifestation rather than motor or combined motor and vocal tics (mean=20.3+16.3 months vs 11.9+16.5 and 12.6+15.2, respectively, p<0.05). A relatively shorter gap was associated with tic severity (r=0.13, p<0.05) and presence of comorbid obsessive-compulsive disorder (OCD) (9.5+14.7 months vs. 14.1+16 without OCD, p<0.05). CONCLUSIONS: Lag time to diagnosis is relatively short in our population. Factors associated with a shorter lag (early age of TS onset, motor tics as the first manifestation, greater tics severity and the presence of OCD) may be perceived as disruptive, prompting patient and families to seek medical care. Conversely, vocal tics as the first manifestation, associated with a longer lag, may be misdiagnosed as features of common pediatric conditions, thus delaying diagnosis.     

儿童抽动秽语综合征中免疫紊乱的新证据

近年来抽动秽语综合征(Tourette syndrome,TS)患病率逐渐增高,但发病机制仍不清楚.一些研究提示TS患儿存在非特异和特异性免疫的异常,如辅助性T细胞亚群Th1和Th2紊乱,以及所分泌的细胞因子水平的变化、自然杀伤细胞和自身抗体表达的改变等.免疫系统的动态平衡和适度的免疫应答对维持机体正常生理功能发挥重要作用.该文对TS患儿免疫特点进行综述,探讨免疫功能紊乱对TS患儿发病的影响,为临床诊断及治疗提供理论依据.     

Tourette syndrome in children: an updated review

Tourette syndrome (TS) is a common neuropsychiatric disorder in children characterized by multiple motor and vocal tics that fluctuate in severity and lasting for at least 1 year. Boys are more commonly affected than girls. Symptoms usually begin with simple motor or vocal tics which then evolve into more complex motor and vocal tics over time. Premonitory sensory urges are common in children over the age of 8 years, and these urges help distinguish tics from symptoms of other movement disorders. Common comorbidities of TS include attention deficit hyperactivity disorder, obsessive-compulsive disorder and learning difficulties. Several genes have been assessed as candidate genes for TS; environmental factors such as stress and streptococcal infections might also contribute to its etiology. The pathophysiology of TS mainly involves dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. A thorough history assessment and neurological examination are important for the correct diagnosis and differentiation from other movement disorders. Treatment for TS should focus on improving the patient's social functioning, minimizing the impairment from cormobid disorders, and controlling tics, if they are severe. Commonly used medications for TS include a2-adrenergic agonists and atypical neuroleptics. Habit reversal therapy is an effective option for TS, and repetitive transcranial magnetic stimulation may be a promising approach for severe cases.     

抽动-秽语综合征患儿听觉事件相关电位P300研究

目的：听觉事件相关电位是测定人脑认知加工功能或心理活动的客观指标,应用听觉事件相关电位检测,以探讨抽动-秽语综合征(TS)患儿的认知功能。方法：对30例TS患儿进行听觉事件相关电位P300测定,并与30例健康对照组儿童比较。结果：TS患儿听觉事件相关电位P300潜伏期明显延长、波幅明显降低,与健康对照组相比差异有显著性意义(P＜0.01＝。结论：听觉事件相关电位作为电生理检查,可客观反映TS患儿认知功能障碍,亦可作为治疗效果的评价指标。 ［中国当代儿科杂志,2004, 6(4): 321-322］     

儿童和青少年Tourette综合征治疗现状

Tourette综合征(TS)是一种儿童期发病的神经发育障碍性疾病,主要临床表现为多种运动和至少1种发声抽动。TS发病可能由多种遗传和环境因素引起,大多共患其他精神障碍性疾病,如注意力缺陷多动障碍、强迫症等。TS的治疗方式包括行为干预、药物干预、外科手术、经颅磁刺激等。文章综述儿童和青少年TS治疗的研究进展。     

盐酸托莫西汀治疗大年龄抽动障碍患儿的临床分析

儿童抽动障碍（tic disorder, TD）是起病于儿童和青少年时期的一种神经精神疾病,主要表现为不自主、反复、快速的一个部位或多部位肌肉运动抽动或发声抽动,TD患儿常伴有诸多心理行为障碍,如注意缺陷多动障碍（ADHD）、强迫障碍（OCD）、睡眠障碍及情绪障碍等[1-4]。随着TD患儿年龄的增大,大部分患儿病情逐渐好转,但仍有部分患儿病情顽固,症状长期存在,对患儿的自尊产生很大的影响,同时也对其学习、社会心理等方面造成不良影响。目前TD临床上多用氟哌啶醇、硫必利等抗精神类药物治疗,但通常药物不良反应较大,因此患儿服药的依从性较差,导致最终的疗效欠佳。近年来有学者报告采用盐酸托莫西汀治疗TD患儿有一定的效果,不良反应少[5-6]。但盐酸托莫西汀治疗TD患儿的疗效报道在国内还并不多见,且既往研究之研究对象的年龄范围大（7~17岁）,本研究特别针对大年龄患儿（10~18岁）进行观察分析,探讨盐酸托莫西汀对大龄TD患儿的治疗效果及不良反应,对大年龄TD患儿的治疗具有参考性。     

Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome

BACKGROUND: Brain imaging studies have revealed anatomical anomalies in the brains of individuals with Tourette syndrome (TS). Prefrontal regions have been found to be larger and the corpus callosum (CC) area smaller in children and young adults with TS compared with healthy control subjects, and these anatomical features have been understood to reflect neural plasticity that helps to attenuate the severity of tics. METHOD: CC white matter connectivity, as measured by the Fractional Anisotropy (FA) index from diffusion tensor images, was assessed in 20 clinically well-defined boys with Tourette syndrome and 20 age- and gender-matched controls. RESULTS: The hypothesis that children with TS would show reduced measures of connectivity in CC fibers was confirmed for all subregions of the CC. There was no significant interaction of TS and region. Reductions in FA in CC regions may reflect either fewer interhemispheric fibers or reduced axonal myelination. FA values did not correlate significantly with the severity of tic symptoms. Group differences in measures of connectivity did not seem to be attributable to the presence of comorbid ADHD or OCD, to medication exposure, or group differences in IQ. CONCLUSION: Our findings of a reduced interhemispheral white matter connectivity add to the understanding of neural connectivity and plasticity in the brains of children who have TS.     

Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is characterized by both motor and phonic tics. One half to two thirds of children with TS experience a reduction or complete resolution of tic symptoms during adolescence. At least one third of adults with TS have comorbid obsessive-compulsive disorder (OCD). OBJECTIVES: To clarify the clinical course of tic and OCD symptoms in children with TS and determine if baseline clinical measurements in childhood are associated with future symptom severity in late adolescence and early adulthood. DESIGN: Prospective cohort study. SETTING: Yale Child Study Center tic and OCD outpatient specialty clinic. PARTICIPANTS: Forty-six children with TS who received a structured clinical evaluation prior to age 14 years. MAIN OUTCOME MEASURES: Expert-rated tic and OCD symptom severity at follow-up interview an average of 7.6 years later (range, 3.8-12.8 years). RESULTS: Eighty-five percent of subjects reported a reduction in tic symptoms during adolescence. Only increased tic severity in childhood was associated with increased tic severity at follow-up. The average age at worst-ever tic severity was 10.6 years. Forty-one percent of patients with TS reported at one time experiencing at least moderate OCD symptoms. Worst-ever OCD symptoms occurred approximately 2 years later than worst-ever tic symptoms. Increased childhood IQ was strongly associated with increased OCD severity at follow-up. CONCLUSION: Obsessive-compulsive disorder symptoms in children with TS became more severe at a later age and were more likely to persist than tic symptoms.     

小剂量氟哌啶醇结合心理干预治疗Tourette综合征疗效观察

为探讨Tourette综合征（TS）的治疗方法，采用小剂量氟哌啶醇结合心理干预治疗26例TS患儿，并与28例常规剂量治疗组作对照。结果发现两组疗效比较相近（P＞0．05），而药物毒副反应观察组显著低于对照组（P＜0．05）。提示小剂量氟哌啶醇结合心理干预是TS一个疗效好且安全的治疗方法。     

阿立哌唑治疗Tourette综合征患儿的多中心对照研究

目的 探讨阿立哌唑治疗Tourette综合征患儿的疗效和安全性.方法 采用前瞻性多中心病例对照研究方法,最终纳入研究的195例5～17岁Tourette综合征患儿分为阿立哌唑组98例,剂量5～25 mg/d;硫必利组97例,剂量100～500 mg/d;疗程12周.于基线(0周)及治疗第2、4、8、12周末,采用耶鲁综合抽动严重程度量表(YGTSS)评定临床疗效,采用不良反应症状量表、血生化指标和心电图检查评定药物不良反应.结果 从治疗第2周末开始阿立哌唑组和硫必利组YGTSS运动抽动分、发声抽动分、功能损害分和总分与治疗前比较均有明显下降(P＜0.0001),且治疗第2周末时阿立哌唑组的功能损害分显著低于硫必利组(P＜0.05).治疗第12周末阿立哌唑组YGTSS总分从基线的(53.74±15.71)分降至(24.36±16.38)分,平均减分29.38分;硫必利组YGTSS总分从基线的(51.66±13.63)分降至(23.26±15.31)分,平均减分28.40分;两组平均减分差值的差异无统计学意义(P＞0.05).第12周末时阿立哌唑组和硫必利组的有效率分别为60.21%和63.92%,差异无统计学意义(P＞0.05).阿立哌唑组和硫必利组均无严重不良反应,不良反应的发生率分别为29.6%和27.8%,差异无统计学意义(P＞0.05).结论 阿立哌唑治疗Tourette综合征患儿的疗效与硫必利相当,不良反应较少,其为临床治疗儿童抽动障碍提供了一种新的药物选择.

Abstract：

Objective To evaluate the efficacy and safety of aripiprazole in the treatment of children with Tourette syndrome. Method A prospective, multi-center, controlled clinical trial was conducted in 195 children aged 5-17 years with Tourette syndrome. The patients were assigned to two groups: aripiprazole group (n =98) and tiapride group (n =97), with the treatment dosage of 5-25 mg/d and 100-500 mg/d,respectively. After 12 weeks treatment, the clinical efficacy was assessed by the Yale Global Tic Severity Scale (YGTSS) score, and adverse reactions were observed by side effects symptoms scale, blood biochemical indexes, and electrocardiography. Result Significant pre- and post-treatment differences were ascertained for motor tic, phonic tic, function damage and total scores of YGTSS in the both groups from the second week of treatment (P ＜0. 0001 ). Compared with the tiapride group, the aripiprazole group showed a more significantly decreased function damage score of YGTSS by the second week of treatment ( P ＜ 0. 05 ).After 12 weeks treatment, total scores of YGTSS in the aripiprazole group decreased from 53.74 + 15.71 at baseline to 24. 36 + 16. 38, while in the tiapride group from 51.66 + 13.63 to 23.26 + 15. 31. The mean reduction scores of YGTSS were 29. 38 in the aripiprazole group and 28.40 in the tiapride group at the end of treatment, and the clinical response rates were 60. 21% and 63.92%, respectively. There were no significant differences between the 2 groups ( P ＞ 0. 05 ). The incidence of adverse reactions was similar in the aripiprazole and tiapride groups, with 29.6% and 27.8% respectively. There were no significant differences in the incidence of adverse reactions between aripiprazole and tiapride groups and no severe adverse events were found in either group. Conclusion The results showed that aripiprazole showed similar therapeutic effect to tiapride in treatment of children with Tourette syndrome. Aripiprazole was safe and well tolerated in Chinese population, and can be considered as a new valid option for the treatment of tic disorders.     

An open-label,prospective study of levetiracetam in children and adolescentes with Tourette syndrome

ObjectivesTo evaluate the usefulness of levetiracetam (LEV) for the treatment of tics in patients with Tourette syndrome (TS) by means of a prospective, open-label, 12-week study.Material and methodsTwenty-nine patients with TS who received LEV to control their tics were admitted to the study.The authors recorded the following variables: initial status (Yale Global Tic Severity Scale – YGTSS – and the scale of Modified Clinical Global Impression –MCGI), the clinical status at 3 months using the same scales, and clinical/medical impression of improvement.ResultsThe mean age of the patients studied was 12 years; 25 males (86%) and 4 females (14%). Participants received 800–2000 mg/day of LEV. Of the 29 patients, 21 children (72%) improved according to YGTSS and MCGI scores. Mean YGTSS Total Tic Score at baseline and after treatment with LEV were 67 and 44, respectively. The statistical analysis confirmed a significant improvement with a p-value of <0.001 on the YGTSS and MCGI. In 3 cases, treatment was suspended due to adverse effects.ConclusionsTreatment with LEV can constitute a treatment option for tics in patients with TS. Double-blind trials of longer duration are needed in larger samples in order to establish both the benefit, as well as what patients are eligible for treatment.     

Neurological soft signs and EEG findings in children and adolescents with Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a childhood-onset neuropsychiatric disorder, characterized by multiple motor and vocal tics. The presence of EEG abnormalities and neurological soft signs are reported in patients with GTS. In this study, conducted on 40 children and adolescents, non-specific EEG abnormalities and neurological soft signs were detected in 12 and 57.5 percent of cases, respectively. These findings are analyzed in comparison with other neuropsychological test results. A statistically significant association between EEG abnormalities, neurological soft signs and low-performance IQ results was detected.