Andersen-Tawil综合征的临床特点(附1例报告)

目的探讨Andersen-Tawil综合征(ATS)的临床特点。方法回顾性分析1例ATS患者的临床资料。结果本例患者女,42岁,主要表现为小下颌、低位耳、高弓足和跟腱挛缩,四肢近端为主的肌无力,双侧腓肠肌肥大。血钾降低,餐后2 h血糖和促甲状腺激素轻度升高;尿糖强阳性,尿重碳酸盐升高。诱发运动试验示运动后60 min和120 min运动神经波幅降低,多发运动神经远端波幅降低。ECG示频发室性期前收缩。17号染色体KCNJ2基因发现杂合突变:c.431GC(p.G144A)。诊断为ATS,近端肾小管损伤,糖耐量受损,多发神经病,亚临床甲状腺功能减低。经补钾治疗,肌力和ECG恢复正常。结论 ATS可以伴随三联征外的其他表现。     

Ⅰ型唾液酸沉积症一例

目的探讨Ⅰ型唾液酸沉积症的临床特点及诊断。方法分析1例Ⅰ型唾液酸沉积症患者的临床资料及基因检测。结果患者为12岁女童,10岁时出现肢端疼痛,随后出现进行性行走不稳、视力下降及抽搐发作;眼底检查提示黄斑樱桃红斑。无家族史。应用二代测序方法对全外显子测序,发现患者携带NEU1基因c. 239 CT(p.P 80 L)和c.544AG(p.S 182 G)复合杂合突变,分别来自其表型正常母亲和父亲。结论Ⅰ型唾液酸沉积症具有共济失调、肌阵挛发作、视力下降的特点,基因检测对于明确诊断具有重要意义。     

临床运动诱发试验在低钾型周期性瘫痪诊断中的价值

目的 通过观察运动诱发试验后小指外展幅度和肌电图复合肌肉动作电位(compound muscle action potential,CMAP)变化的特点,建立一种在非发作期诊断低钾型周期性瘫痪的新方法.方法 收集确诊为低钾型周期性瘫痪的患者59例,以非周期性瘫痪患者38例作为对照,对小指展肌进行运动诱发试验测定(低钾型周期性瘫痪患者选择发作间期),观察120 min,测定运动诱发前后肌电图CMAP波幅变化的百分比,同时观察小指展肌肌力的变化以及小指外展幅度的变化.结果 在运动结束后120 min,患者组和对照组CMAP波幅下降的百分比[M50(M25,M75)]分别为54.1%(43.1%,66.3%)和11.1%(2.0%,21.3%),差异有统计学意义(Z=6.731,P=0.000);小指外展幅度下降百分比[M50(M25,M75)]分别为39.4%(26.3%,48.9%)和7.8%(1.3%,13.7%),差异有统计学意义(Z=5.519,P=0.000).运动后小指展肌肌力小于Ⅳ级者在两组分别为96.3%(52/54)和8.6%(3/35,x2=69.2,P=0.000).当采用小指外展幅度下降百分比＞20%作为界值时,诊断周期性瘫痪的敏感度为87.5%,特异度为90.5%.结论 临床运动诱发试验有助于低钾型周期性瘫痪的诊断.     

低钾型周期性麻痹基因型与临床表型相关性的研究进展

原发性低钾型周期性麻痹和甲状腺毒性周期性麻痹是由于编码某些离子通道的基因发生突变,导致反复发作肌无力伴血清钾降低,为离子通道相关周期性麻痹,突变位点不同,临床表型亦不相同,且存在种族差异性。近年来对低钾型周期性麻痹基因型-临床表型相关性的研究日益受到重视,并取得一定进展。     

发作性运动障碍1例报告

发作性运动障碍是一类罕见的神经系统疾病 ,其临床特点是反复发作的不自主运动 ,不伴意识障碍。根据诱因、发作持续时间及病因等将本病分为四型 :发作性运动诱发的异常运动(PKD) ;发作性非运动诱发的异常运动 (PNKD) ;发作性持续运动诱发的肌张力障碍 (PED ) ;夜间发作性肌张力障碍(HPD)。现将笔者遇到的 1例PKD报告如下。1　临床资料　　患者女性 ,3 5岁。 17年前无明显诱因下出现右侧上下肢不自主扭动 ,在惊吓或紧张时易发 ,每次持续 1～ 2min ,无意识丧失 ,缓解时肢体活动正常 ,睡眠时不发作 ,但惊醒后易发作 ,患者开始时每天发作…     

吉兰-巴雷综合征疾病谱:用新的标准重新分类

目的回顾分析2015—2019年在北京同仁医院出院诊断为吉兰-巴雷综合征(GBS)或相关的疾病40例,依据新的临床分类及其诊断标准将病例重新分类;描述重新分类后各疾病表型的临床特点。方法收集40例来自2015—2019年北京同仁医院出院诊断为GBS或相关疾病的患者的临床资料[其中米勒-费舍综合征(MFS)6例,可能的MFS 7例,GBS 17例,可能的GBS 3例,GBS脑神经型2例,可能的GBS脑神经型3例,GBS叠加MFS 2例],出院诊断根据2010年中国吉兰-巴雷综合征诊治指南的标准建立。依据2014年Wakerley等提出的新的GBS疾病谱临床分类及其诊断标准对40例病例重新分类;描述重新分类后各表型的临床特点(性别、年龄、病前感染史)、脑脊液表现、免疫治疗情况;与经典GBS表型患者对比分析相比其他表型患者的脑脊液表现及临床预后情况。结果上述40例患者依据新的分类及诊断标准重新分类诊断为:经典GBS 3例(7.5%),下肢瘫痪型GBS 1例(2.5%),经典GBS叠加其他表型6例(15.0%),包括叠加眼外肌麻痹2例及叠加面肌无力、咽-颈-臂型无力/MFS/面肌无力、急性咽型无力/MFS、急性咽型无力/面肌无力/眼外肌麻痹各1例;下肢瘫痪型GBS叠加其他表型3例(7.5%),包括叠加眼外肌麻痹2例、叠加面肌无力1例;急性咽型无力叠加眼外肌麻痹1例(2.5%);经典MFS 4例(10.0%);急性眼外肌麻痹14例(32.5%);急性眼睑下垂1例(2.5%);经典MFS叠加面肌无力2例(5.0%);急性眼外肌麻痹叠加其他表型5例(15.0%),包括叠加面肌无力2例,叠加急性瞳孔散大3例。关于脑脊液表现和临床预后,其余表型与经典GBS表型相比,差异均无统计学意义(均P0.05)。结论依据GBS疾病谱的新的临床分类及其诊断标准,可以将既往临床表现不典型的但又有证据支持属于GBS疾病谱的疾病表型得到较为准确的诊断分型,避免漏诊。     

发作性运动诱发性运动障碍临床表型分析

研究背景发作性运动诱发性运动障碍是一组由突然动作诱发的非随意性运动障碍性疾病,表现为反复发作的短暂性肌张力障碍或舞蹈样动作,具有高度临床和遗传异质性。本研究旨在总结中国发作性运动诱发性运动障碍临床表型特点。方法采集195例原发性发作性运动诱发性运动障碍患者临床资料,采用自行设计的发作性运动诱发性运动障碍登记表记录并整理,分析和总结发作性运动诱发性运动障碍临床表型特点,并比较家族性与散发性患者临床表型差异。结果 195例发作性运动诱发性运动障碍患者男女比例为4.42∶1,平均发病年龄为(12.32±3.49)岁,单纯型162例(83.08%)、复杂型33例(16.92%),16例(8.21%)合并特发性震颤,144例(73.85%)发作前有先兆,发作形式包括肌张力障碍(134例,68.72%)、舞蹈样动作(8例,4.10%)和二者混合形式(53例,27.18%),134例(68.72%)发作时面部受累,115例(58.97%)发作频率10次/d、54例(27.69%)10~20次/d、26例(13.33%)20~30次/d,117例(60%)发作持续时间10 s、58例(29.74%)10~30 s、20例(10.26%)30~60 s,散发性131例(67.18%)、家族性64例(32.82%),78例(40%)未服用药物,117例(60%)服用抗癫药物患者中106例症状完全控制、8例偶有发作、3例未见明显缓解。其中,家族性组发病年龄低于(t=2.376,P=0.019)、发作持续时间短于(χ~2=7.731,P=0.021)散发性组。结论通过大样本临床数据分析和总结中国发作性运动诱发性运动障碍临床表型特点,以期为临床诊断与治疗提供帮助。     

糖皮质激素冲击治疗诱发重症肌无力危象临床特点和危险因素分析

目的探讨糖皮质激素冲击治疗诱发重症肌无力危象之临床特点和危险因素。方法共59例次重症肌无力患者分别于入院时和糖皮质激素冲击治疗第4、7、14、21、28天时采用临床绝对评分判断病情严重程度、临床相对评分评价病情变化,并分析危象发作危险因素。结果在糖皮质激素冲击治疗过程中约69.49%(41/59)患者出现短暂性肌无力,重症肌无力危象组患者治疗第4天时临床绝对评分短暂性升高(37.63±1.80;t=4.410,P=0.028),第7天开始下降(32.94±2.29),至第14天(22.19±1.75)低于入院时(31.31±2.07;t=12.701,P=0.000);非重症肌无力危象组患者治疗后临床绝对评分下降,第14天(12.37±1.11)低于入院时(21.27±1.39;t=5.740,P=0.000),与临床表现改善程度一致。重症肌无力危象组患者治疗第7天临床相对评分逐渐增加[(-0.06±0.06)%],至第28天[(0.82±0.03)%]高于第4天[(-0.23±0.05)%;t=28.232,P=0.000];非重症肌无力危象组患者治疗后临床相对评分亦逐渐增加,至第21天[(0.53±0.04)%]高于第4天[(0.03±0.04)%;t=4.312,P=0.000]。Logistic回归分析提示,高龄、临床绝对评分增加、感染、延髓肌麻痹、合并其他自身免疫性疾病均可诱发危象,但以高龄为主要诱发因素。结论糖皮质激素冲击治疗过程中通过筛查危险因素、密切观察病情变化,可以及时发现危象病例,经呼吸机辅助通气和静脉注射免疫球蛋白可以缓解病情,挽救患者生命。     

低钾型周期性瘫痪患者运动诱发试验中肌力和肌电图改变与血钾的关系

目的 通过长时运动诱发试验,观察低钾型周期性瘫痪患者肌力和肌电图的变化与血钾之间的关系.方法 收集确诊为低钾型周期性瘫痪患者78例,对小指展肌进行运动诱发试验测定,以拇短展肌作为对照,观察120 min,测定运动诱发前后尺神经/小指展肌和正中神经/拇短展肌复合肌肉动作电位(compound muscle action potential,CMAP)波幅变化,同时观察患者小指外展和小指内收肌力以及拇短展肌肌力的变化,部分患者测定运动前后血钾水平.分析运动后不同肌肉的肌力、CMAP波幅与血钾之间的关系.结果 在小指外展运动后,78例患者尺神经CMAP波幅运动后比运动前明显下降,分别为(4.6±2.7)、(9.6±3.2)mV(t=16.047,P=0.000),而正中神经CMAP波幅在小指外展运动后与运动前相比无明显差异,分别为(10.9±4.2)、(11.2±3.9)mV(t=0.673,P=0.822).在运动后,76例小指外展肌力下降;有41例小指外展肌力小于Ⅲ级,但同侧小指内收和拇短展肌肌力仍为V级,对其中10例患者在运动前和运动后测定血钾,结果无明显差异,分别为(3.8±0.3)、(3.9±0.4)mmol/L(t =0.395,P=0.702).结论 在低钾型周期性瘫痪患者进行运动诱发试验时,血钾并非影响肌力和CMAP波幅变化的关键因素.     

糖皮质激素治疗重症肌无力早期致病情加重的临床观察

目的观察甲基强的松龙冲击疗法(MPPT)治疗重症肌无力(MG)早期导致一过性肌无力加重的作用.方法对MPPT治疗的36例MG患者于治疗前及治疗后肌无力加重时分别进行临床评分、低频重复电刺激、血清AChRAb滴度检查.结果MPPT治疗MG后,1周时临床显效率58%,4周时临床显效率为78%,有效率为94%;部分患者出现一过性肌无力加重;加重后低频重复电刺激波幅递减幅度较加重前明显增加(P<0.05),而血清AChRAb滴度无明显变化(P>0.05).结论MPPT治疗MG,56%患者早期可出现不同程度的一过性肌无力加重,其中轻～中度加重占65%,重度加重占35%,14%累及呼吸肌,6%出现MG危象;加重多出现于治疗后的1～7(3±2)d,持续时间1～18(4±3)d;早期一过性肌无力加重可能与激素直接抑制神经-肌接头处传递有关.     

Do polio survivors have a higher risk of epilepsy?

We planned this study to investigate the frequency of epilepsy in paralytic polio survivors. We analyzed the clinical data of 91 paralytic polio survivors. Patients who had been diagnosed with epilepsy were examined by electroencephalography and brain magnetic resonance imaging. 11 of the 91 patients had epilepsy (12%). The mean age at which the patients were exposed to acute poliomyelitis was 5.3±3.8 years (age range: 1-13). The mean age of epilepsy onset was 17±5.6 (age range: 4-25) in the epileptic patients. Our findings suggest that paralytic polio survivors may be at a higher risk for epilepsy compared to normal subjects.     

A case of hypokalemic periodic paralysis: utility of exercise test for the assessment of therapeutic efficacy]

We report a 14-year-old male with hypokalemic periodic paralysis. He noticed periodic paralysis at the age of 11. Any complication did not accompany the symptom. At the age of 12, hypokalemia was found during an episode of paralysis, and he was diagnosed as hypokalemic periodic paralysis. The frequency of paralytic attack increased around April 2000. Although long-acting oral potassium (32 mEq/day) was administered, it did not give favorable effect. Therapeutic spironolactone trial also failed. After the reconfirmation of the diagnosis of periodic paralysis by an exercise test, oral acetazolamide (750 mg/day) was started. In subsequent exercise test, the increment of the CMAP amplitude of abductor digiti minimi during exercise became smaller and the decrement of CMAP amplitude after exercise disappeared thereafter, which was assumed to be related with clinical improvement. The noninvasive exercise test is useful not only to diagnose periodic paralysis but also to evaluate therapeutic efficacy.     

Abnormal salivary cortisol levels in social phobic patients in response to acute psychological but not physical stress.

BACKGROUND: Little is known about the hypothalamic-pituitary-adrenal axis response to acute stressful behavioral challenges in patients with social phobia. METHODS: Eighteen patients with social phobia and 17 normal volunteers participated in two behavioral stressors: a speech task and physical exercise. RESULTS: Normal volunteers (n = 14) demonstrated a significant 50% increase in salivary cortisol levels to the speech task. Three nonresponding normal volunteers demonstrated a 17% decrease. In contrast, patients with social phobia demonstrated dichotomous changes. Seven social phobia patients demonstrated a significantly higher 90% increase in salivary cortisol to the speech task, whereas the remaining patients (n = 11) were nonresponders demonstrating a 32% decrease in cortisol. Both patient groups were significantly more anxious than the normal volunteers. In contrast to the response to a speech task, social phobics showed a cortisol response to physical exercise of similar magnitude as normal volunteers. CONCLUSIONS: The results indicated dichotomies in magnitude and in distribution of the cortisol response to a speech task between social phobia patients and normal volunteers. Social phobia patients responded differently than normal volunteers to a stressor associated with social evaluation but not to physical exercise. These results suggest adaptation of distinct biological processes specific to different stressful conditions in social phobia.     

Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica

OBJECTIVES: Patients with paralysis periodica paramyotonica exhibit a clinical syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associated with hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have been previously reported. Phenotypic variations of mutations in SCN4A, however, have not been described yet. The present study aimed to evaluate genetic variations in a family with clinical and electrophysiological characteristics of paralysis periodica paramyotonia. METHODS: Seven members of a family affected with symptoms of paralysis periodica paramyotonia were studied by electrophysiological and genetic analyses. There were increased serum potassium concentrations in four members during paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried out in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of SCN4A were performed on one patient and a normal control to identify polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then performed at the identified polymorphic sites. RESULTS: Electrophysiological studies showed both exercise sensitivity and temperature sensitivity. Compound motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests after cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses showed that all affected patients carried the Thr704Met mutation, whereas unaffected family members and a normal control did not. CONCLUSION: Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family affected with paralysis periodica paramyotonia.     

Familial hypokalaemic periodic paralysis in Finland.

Seven families with familial hypokalaemic periodic paralysis were found in Finland. Nine of the 103 asymptomatic family members studied had abnormal results on a potassium exercise test. The overall prevalence of familial hypokalaemic periodic paralysis in Finland was 0.4/100,000. Carbohydrate intake and hard exercise were the most important triggers of paralytic attacks. Half of the patients reported having attacks at least once a month. Seven patients reported cardiac symptoms (especially bradycardia) during attacks. Permanent muscular weakness was not prominent.     

The short exercise test is normal in proximal myotonic myopathy.

OBJECTIVES: Proximal myotonic myopathy (PROMM) is a multisystem disorder that may mimic myotonic dystrophy (MD). Previously we demonstrated that the 60 s exercise test was normal in two siblings with PROMM. The test enabled distinction of PROMM from MD, as there is a well documented immediate post-exercise compound muscle action potential (CMAP) amplitude decline in MD. METHODS: We now performed exercise testing using several exercise durations in 8 PROMM patients from 6 kinships, and one MD patient, extending our previous observations. Repetitive stimulation and needle electromyography findings were also recorded. RESULTS: The 10 (n = 8), 30 (n = 5), and 60 (n = 5) s, and the 5 min (n = 1) exercise tests were normal in all PROMM patients. Specifically, the maximum post-exercise CMAP amplitude decline was 8%. In contrast, the MD patient had CMAP amplitude declines of 48% (10 s exercise test) and 26% (30 s exercise test). The distribution of repetitive stimulation and motor unit duration abnormalities were variable and less diagnostically useful. CONCLUSIONS: The 10, 30, and 60 s exercise tests help distinguish PROMM from MD. As the 10 s exercise test is rapid and easily tolerated, we recommend this test for clinical testing.     

Idiopathic hypokalemic periodic paralysis presenting peculiar insulin secretion

A 24-year-old male was admitted to our hospital because of the paralytic attack. He was well until he went to bed the day before, and he found his limbs unmovable in the morning. The initial attack occurred at age 11 and subsequently he had two episodes of the reversible generalized weakness which always appeared in the morning and continued for about one day at age 14 and 21, respectively. The provocative factors were uncertain. There was no family history of paralytic attacks nor thyroid diseases. On the neurologic examination he presented flaccid tetraparesis without the facial and respiratory involvements. The laboratory studies showed that the serum potassium was 2.4 mEq/l and the thyroid function was normal. The oral and intravenous potassium chloride was given and within two days the serum potassium turned back to the normal level, and he has recovered completely from the paralysis. An oral 75g glucose load was performed. The serum immunoreactive insulin (IRI) was elevated from the basal level to 289 microU/l, showing the prominent peak response at 30 min after the load, and both the serum potassium and the grasping power decreased significantly, although the blood glucose fluctuated within the normal level. After the prophylactic treatment with acetazolamide 2,000 mg daily for 7 days, this markedly elevated initial insulin response has disappeared and moreover the weakness of grip was milder, however, the serum potassium decreased notedly. This case revealed that in the idiopathic hypokalemic periodic paralysis the attack was possibly induced by the extraordinarily secreted insulin which was supported by the acetazolamide treatment.     

Cost-effectiveness of mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in austria.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen). The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity. The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost. Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58, 787 and ATS 61,851 per patient respectively. Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant. In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.     

Clinical features and long exercise test in Chinese patients with Andersen‐Tawil syndrome

Introduction: Andersen‐Tawil syndrome (ATS) is a rare multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, and developmental dysmorphology. There are few reports concerning ATS in the Chinese population. We analyzed clinical features and evaluated the long exercise test as a tool for diagnosis of periodic paralysis in ATS. Methods: Direct sequencing of KCNJ2 was performed in 12 subjects from mainland China with suspected ATS. Clinical features, therapeutic responses, and long exercise tests (LET) were retrospectively analyzed. Results: Twelve patients were genetically confirmed to have ATS. A small mandible and clinodactyly were demonstrated in all patients. Premature ventricular contractions were the most prevalent form of cardiac arrhythmia. The LET revealed an early amplitude decrement. Conclusions: Chinese ATS patients shared some common clinical features with reported subjects in other countries. An early amplitude decrement in LET may be useful for diagnosis of ATS. Muscle Nerve 54 : 1059–1063, 2016