Objective:To investigate the phenotypic heterogeneity and gene penetrance of a dopa-responsive dystonia (DRD) family.Methods:The clinical data of a four-generation DRD family (including 3 patients) admitted to Department of Neurology, China-Japan Friendship Hospital in November 2015 were retrospectively analyzed. The proband underwent whole exon sequence, and the genetic result was verified by Sanger sequencing. Sanger sequencing was performed in the other 14 subjects in the family; the genotypes and clinical manifestations were analyzed.Results:In 15 subjects underwent genetic testing, 7 had heterozygous mutations c.284G>A (p.P95L) in GCH1 gene; the penetrance of GCH1 gene mutation in this family was 0.43 (3/7), the gene penetrance in male was 0.25 (1/4), and the gene penetrance in female was 0.67 (2/3). Three subjects in the DRD family had clinical symptoms; the clinical symptoms of the two female patients were more severe than those of the male patient; the severity of clinical symptoms differed greatly between the 2 female patients. Conclusion:There is a wide intrafamilial phenotypic heterogeneity in DRD family members carrying the same gene mutation, and the phenotype is gender-related; the gene penetrance in male is lower than that in female, and the clinical phenotype is often milder.

ABSTRACT : Objective To investigate the neurophysiological characteristics of nitrous oxide-induced neuropathy. Methods Clinical manifestation ,laboratory examinations ,cervical-thoracic vertebra M RI and nerve conduction studies of 15 patients with nitrous oxide (N2 O )-induced neuropathy were retrospectively collected from Department of Neurology ,China-Japan Friendship Hospital from July 2015 to M arch 2018. In the control group ,44 patients (including 23 cases of limb-girdle muscular dystrophy ,5 cases of lipid storagemyopathy ,8 cases of hypokalemic periodic paralysis and 8 cases of neuromyelitis optica ) underwent nerve conduction examination. T he nerve conduction velocity and action potential amplitude were in the normal range and peripheral neuropathy was excluded in the control group. Nerve conduction studies were done in 29 median nerves ,22 ulnar nerves ,25 peroneal nerves and 32 tibial nerves w hich were normal for control. Results 15 patients manifested as weakness and numbness in four limbs ;motor and sensory impairments were more severe in lower limbs than upper limbs. T2-weighted M RI scans showed hyperintensity lesions shaped inverted ‘V’ -sign at the posterior column of the spinalcad from the second cervical to thoracic vertebrae level in 8 patients. Compared with the control group ,the mean motor conduction velocity (MCV) of the median nerve ,ulnar nerve , peroneal nerve and tibial nerve decreased by 14.1%,11.1%,18.3% and 21.5% respectively ,and the amplitude of distal compound muscle action potential (CM AP ) decreased by 29.6%, 19.5%, 63.6% and 82.5%, respectively ,all with significant difference (all P ＜ 0.05 ) . Compared with the control group , the sensory conduction velocity (SCV ) of upper and lower limbs and the amplitude of sensory nerve action potential (SNAP) of lower limbs in the lesion group decreased significantly (all P ＜ 0.05 ) . CM AP were not detected in 7 peroneal nerve and 3 tibial nerve. M otor nerve conduction block were detected in 2 patients. Conclusions Neurological impairment induced by N2 O abuse often results in cervicothoracic posterior cord lesions and peripheral neuropathy. Peripheral neuropathy caused by N2 O abuse can involve both motor and sensory fibers , including axonal degeneration and demyelination. The degree of damage in lower limbs is more severe than that in upper limbs. Motor axons are more vulnerable than sensory axons. Motor conduction block may occur in the affected nerves.

OBJECTIVE:To study the clinical and electrophysiological characteristics of carpal tunnel syndrome (CTS) with cervical spondylotic radiculopathy (CSR) and simple-CTS, and compare the effect of double crush with that of simple entrapment on a nerve and investigate the association between CTS and CSR.METHOD:From January 2011 to August 2014, clinical data from 96 patients with double crush syndrome (DCS, CTS with CSR) and 165 patients with simple-CTS were examined, and the electrophysiologic parameters of median nerve in patients with DCS were compared with that in patients with simple-CTS.RESULTS:In 96 patients with DCS, most of them were female; neck and shoulder pain or simultaneously accompanied by numbness and pain of upper limb was observed in 34 patients, upper limb symptoms and hand weakness and muscle atrophy were observed in the other 62 patients, 124 median nerves with abnormal conduction were found in these DCS patients, including 68 cases with unilateral abnormalities and 28 cases with bilateral abnormalities. Cervical radiculopathies of the C5-7 mainly involved in patients with DCS.223 median nerves with abnormal conduction found in the 165 patients with simple-CTS, including 107 cases with unilateral abnormalities and 58 cases with bilateral abnormalities. The average sensory nerve conduction velocity (SCV), motor nerve conduction velocity (MCV) and distal motor latency (DML) of median nerve for DCS and simple-CTS were (32±7) m/s vs (35±5) m/s, (55±7) m/s vs (57±5) m/s and (4.6±1.6) ms vs (4.0±0.8) ms, respectively, and their corresponding amplitudes were 6.4 µV vs 9.5 µV, 10.9 mV vs 13.1 mV and 11.3 mV vs 14.1 mV, respectively. The SCV, MCV and DML and their corresponding amplitude of DCS were significantly greater decreased than that of simple-CTS (P<0.01).CONCLUSION:DCS is a common clinical syndrome, and patients with DCS may have neck and shoulder symptoms in addition to the common manifestations of simple-CTS. Abnormal conduction of median nerve of CTS with CSR is more severe than that of simple-CTS, which neurophysiologically proves the association between CTS and CSR and supports double crush hypothesis.

Objective To summarize the clinical,imaging,electroencephalogram and pathological characteristics of insulinoma which presented with seizures and disturbances of cognition.Methods A case of insulinoma presenting with seizures and disturbances of cognition was reported and relevant literatures were reviewed.Results The patient was a Chinese woman aged 49.She presented with various kinds of seizures and continuous disturbances of cognition.When she suffered from a seizure,the blood glucose was always less than 1.7 mmol/L.The MRI of brain showed a lesion in the splenium of the corpus callosum.EEG presented with sharp waves in areas of the left temporal-occipital lobe and generalized slow waves.A pancreatic head and neck tumor with rich blood supply was showed by CT scan.After the operation,the pathology showed an insulinoma.The patient never has a seizure after operation but is left with a sequelae of disturbances of cognition.Conclusions We should highly pay attention to a patients with atypical refractory seizures and hypoglycemia to find whether he has,insulinoma then the best treatment can be adopted to avoid the sequelae.

Objective To summarize electromyographic features of external anal sphincter(EAS) in patients with motor neuron disease(MND).Methods EAS-EMG was performed in 20 MND patients with different subtypes,as well as 22 negative controls(cases with neither symptoms nor signs of bowel and bladder dysfunction).Electromyographic characteristics of the two groups were recorded and analyzed statistically.Results Significantly prolonged mean duration [(12.21±2.26) ms vs.(14.55±2.27)ms,P=0.000] and increased area of motor unit potentials(MUPs) [(512.89±363.55)(ms·μV)vs.(718.47±236.57)(ms·μV),P=0.05] were shown in the MND group,when comparing with the negative control group(P≤0.05).No significant differences were found in the amplitude,percentage of polyphasic wave and turns of MUPs between the two groups(P0.05).Conclusions Asymptomatic or subclinical neurogenic lesion may occur in EAS of MND patients.Mean duration and area of MUPs are the most sensitive parameters exhibiting MUPs characters.

目的 探讨Kennedy病的临床、神经电生理及病理特征.方法 报道2例经基因确诊的Kennedy病患者,分析其临床症状、体征、肌电图和神经传导检查和神经病理等特点.结果 两例患者均中年发病,进展缓慢.神经系统表现为以肢体近端无力和延髓受累为主的下运动神经元瘫痪.血清性激素水平正常,但有男性乳腺发育等雄激素功能低下表现.血清肌酸激酶轻度升高.肌电图呈广泛神经源性损害,神经传导检查提示感觉神经动作电位波幅减低,H反射异常,神经活检提示大的有髓纤维减少.雄激素受体基因编码区CAG重复数大于40.结论 Kennedy病有相对独特的临床、电生理及病理特征,确诊有赖于雄激素受体基因编码区CAG重复数的检测.

目的探讨周围髓鞘蛋白22（PMP22）基因重复突变阳性的夏科-马里-图斯病（CMT）lA亚型患者临床和神经电生理改变特点。方法总结21例PMP22基因重复突变阳性的CMTlA患者的临床特点,并分析其神经电生理特征。结果 21例患者中,10例临床特征符合四肢远端萎缩无力的典型CMTl型表现,另外11例呈不典型性,如仅有头晕、合并听力障碍、上肢姿势性震颤、反复发作性肢体无力、伴有小脑性共济失调及癫疒间等。10例患者肌电图出现纤颤电位和（或）正锐波,15例患者运动单位电位时限延长。神经传导存在广泛异常,所有患者被检的运动或感觉神经传导速度存在不同程度的减慢或消失。结论 PMP22重复突变阳性的CMTlA患者具有较高的临床异质性,其电生理特点为肌电图呈神经源性损害,感觉神经病变重于运动神经,下肢受累程度重于上肢,神经电生理检查对CMT1A的诊断很重要。

Objective: To study the therapeutic method for patients with acute stroke and blood sugar metabolism anomalies and its effect on prognosis.Methods: From March 2011 to January 2012,74 cases of patients with acute stroke and secondary glucose metabolism abnormal in our hospital were selected as the object of study.According to the inhospital time order,all patients were divided into the control group and the experimental group.34 patients in the control group were given conventional treatments,and 40 patients in the experimental group were given the novolin,Xueshuantong injection and ozagrel combination therapy.After 1 to 2 months of fol-low-up for all patients,we compared the clinical curative effect and the fasting blood sugar changes of the two groups.Results: Before treatment,the fasting blood sugar value showed no statistically significant differences between the two groups(p0.05);After treatment,the fasting blood sugar value of the experimental group(5.76 ±1.09) was lower than those of the control group(9.36 ±1.66),with statis-tically significant difference(P0.05).Between the two groups,the total effective rate of the experimental group was 97.5%,which was higher than those in the control group(88.2%);the difference was statistically significant(P0.05).Of the experimental group,the neural function defect score(NDS) was 39.4±2.4,Glasgow coma scale(GCS) was 9.2±1.6 and daily life activities(ADL) was 5.4±1.2,all of which were higher than those in the control group(27.7±1.4,6.4±1.2,3.8±1.3 respectively);the difference were statistically significant(P0.05).Conclusion: The novolin,Xueshuantong injection and ozagrel combination therapy for acute stroke combined with glucose metabolism abnormal can effectively improve the blood sugar metabolism change and brain function.

患者女,38岁,因"行走不稳,视物模糊3个月"入院.患者入院前3个月,于一次"河滩拾花生"后骑车回家时,突发独立行走困难,骑自行车易摔倒,扶自行车可勉强行走.3d后行走不稳加重,伴双眼视物模糊.2个月前出现言语含混,声音变粗,语速变慢.

Objective:To evaluate the diagnostic value of second lumbrical and interossei distal motor latency difference(2LIDMLD)in diagnosing carpal tunnel syndrome(CTS).Methods:2LIDMLD was standardized in 50 hands of age-matched healthy controls.Subjects with clinically diagnosed CTS were prospectively evaluated with 2LIDMLD in addition to another standard diagnostic test.Sensitivities of these two tests were compared in patients with CTS.Results:Eighty-four hands of 55 patients met the clinical criteria for CTS.The mean values of 2LIDMLD of healthy controls and CTS group were 0.13 ±0.07ms and 1.07 ±0.55ms,respectively.The prolonged 2LIDMLD for the CTS patients had significant differences as compared with that of normal subjects(P0.01).Sensitivity of 2LIDMLD and conventional median sensory conduction velocity(SCV)in diagnosing CTS were 85.71% and 63.09%,respectively.Conclusion:2LIDMLD is a sensitive,also simple and convenient measurement in confirming the electrophysiologic diagnosis of CTS.

Objective:To explore the electrophysiological diagnostic efficacy of nerve conduction studies in lumbosacral radiculopathy.Methods:Retrospectively analyzing nerve conduction data of 82 patients with lumbosacral radiculopathy,including nerve conduction velocity,H-reflex,F-wave,and comparing these data with references of normal records.Totally 102 posterior tibial nerves and 102 peroneal nerves were tested.Results:Of the posterior tibial nerves,52% had changes in H-reflex,such as diminished amplitude and delayed latency or absent of H-reflex,and 8% showed abnormal F-wave with prolonged latency.While the peroneal nerves,4% had slightly decreased amplitude of compound motor action potential.All motor and sensory conductive velocities of posterior tibial and peroneal nerves were normal.In cases with abnormal H-reflexes,amplitude abnormality(49%) was significantly more common than latency abnormality(26%,P<0.01).Conclusion:H-reflex is more efficient in detecting radiculopathy than F-wave,especially its amplitude change,and nerve conductive velocity is the least sensitive.

<正>患者男性,54岁,主因"四肢渐进性无力5年,加重半年"入院。5年前无明显诱因出现四肢无力,表现为蹲起困难,双上肢上抬、梳头、持物困难,双下肢行走吃力,该症状持续至半年前患者自觉双下肢无力加重,蹲下后不能自行站立,需借助外力,起立后尚可自行行走,但行走不稳,为

<正>干燥综合征(sjogren syndrome,SS)是累及外分泌腺为主的慢性炎性自身免疫病,当病变隐袭、多系统受累,而口、眼干症状不显著时极易漏诊[1~3]。患者女性,63岁。因"双腿痛3年,腰背痛1年"入院。患者入院前3年无明显诱因出现右足背胀痛,渐出现双

Objective To investigate the clinical,pathological and genetic features of the patients from a pedigree of autosomal dominant inherited centrunuclear myopathy(CNM).Methods Clinical examinations were performed in patients and unaffected members of the pedigree.Muscular enzymes and EMG were checked in the patients.Muscle biopsy was performed in proband.The specimen was used for histological and histochemical staining.Reported mutations of dynamin 2(DNM2)genes were scanned in family members.Results The initial symptom was weakness of lower extremities.Muscular atrophy was also prominent.Serum creatine kinase was slightly elevated in proband.The EMG of 2 patients showed myopathy change.The most prominent histopathological features included the high frequency of centrally located nuclei in a large number of the extrafusal muscle fibers,radial arrangement of sarcoplasmic strands around the central nuclei and predominant and hypotrophy of type Ⅰ fiber.Exon 8 and 11 of DNM2 were analyzed by PCR and sequencing,and 1105C→T mutation was revealed.Conclusions This pedigree is verified as CNM clinical,pathological and genetic researches.DNM2 gene mutation is confirmed in Asian autosomal dominant inherited CNM pedigree.

脂肪酸β-氧化代谢是将二碳单位由长链脂肪酸上水解下来后进入三羧酸循环或酮体生成途径分解产能.体内脂肪酸根据所含C原子的多少,分为短链(2～4碳),中长链(4～12碳),及长链(12碳以上).人体完成脂肪酸β氧化代谢的器官有线粒体和过氧化物体两种,线粒体主要完成≤20个碳单位的脂肪酸代谢.到目前为止,人们已发现25种参与脂肪酸β氧化的酶或转运蛋白,此环节中的任何一个出现异常均可导致脂肪酸分解和能量生成障碍,出现神经系统、骨骼肌、心、肝、肾、消化道等的功能异常.1973年人们首次报道了2例脂肪酸代谢异常患者;目前至少发现了22种影响骨骼肌和/或其它组织β氧化的先天性异常[1～3].

OBJECTIVE:To investigate the effect of z-DEVD-fmk, a caspase-3 inhibitor on the neuronal apoptosis in ischemia-reperfusion region (IRR) of rat cerebral cortex.METHODS:Rats prepared by middle cerebral artery occlusion and reperfusion were used as the research model. The animals were divided into A group (untreated), B group (DMSO control) and C group (treated with z-DEVD-fmk). Before reperfusion, z-DEVD-fmk (7 microg/kg) was injected into the ischemic side of ventriculus cerebri of C group rats. The expression and activation of caspase-3, expression and cleavage of poly (ADP-ribose) polymerase (PARP), and apoptotic neurons in the temporal-parietal cortex IRRs (SPAB method) of all the rats were studied using Western blotting, in situ apoptotic detection (TUNEL method) and immunohistochemistry.RESULTS:In the cerebral IRRs of A, B, C groups reperfused for 1 h and 24 h, the quantities of caspase-3 precursor were 16.7 +/- 3.0, 11.5 +/- 3.0 and 47.5 +/- 3.5, and 76.1 +/- 3.5, 71.3 +/- 6.4 and 88.2 +/- 5.5, respectively; the caspase-3 fragments (12,000) 8.2 +/- 2.3, 9.4 +/- 1.2 and 4.3 +/- 1.6, and 59.0 +/- 6.3, 60.5 +/- 7.2 and 17.3 +/- 2.8, respectively; the PARP 12.6 +/- 3.0, 13.9 +/- 2.0 and 53.7 +/- 4.1, and 67.5 +/- 8.6, 61.1 +/- 6.6 and 93.6 +/- 4.1, respectively; the PARP fragments (24,000) 6.0 +/- 0.7, 6.6 +/- 1.2, 3.6 +/- 1.1, and 27.4 +/- 2.6, 25.8 +/- 3.2, 12.1 +/- 2.8 (relative quantity, x+/- s); the densities of apoptotic neurons 83.3 +/- 7.5, 84.3 +/- 5.7 and 45.7 +/- 4.0, and 197.4 +/- 11.8, 185.2 +/- 11.2 and 99.1 +/- 5.8 (cell number/0.1 mm(2), x+/- s). These results showed that in the cerebral IRRs of both A and B groups, all caspase-3 expression and activation, PARP expression and cleavage, and neuronal apoptosis were increased relevantly along with prolongation of the reperfusion time (P < 0.05 - 0.001). At each time point of the reperfusion, caspase-3 activation, PARP cleavage and neuronal apoptosis in the cerebral IRR of C group were significantly less than those of the former two groups (P < 0.05 - 0.001). The variations of the 5 parameters of A, B and C groups correlated positively with one another (r = 0.630 - 0.942, P < 0.01). The cells expressing PARP were mainly neurons in the cerebral IRRs of all the animals, but the difference of their number was not distinct among the 3 groups.CONCLUSIONS:It is an important mechanism resulting in apoptosis of the injured neurons in the cerebral IRR that caspase-3 expression and activation abnormally increased by the reperfusion have more PARP rapidly inactivated by over-cleavage. z-DEVD-fmk may decrease PARP cleavage by inhibiting activity and auto-activation of caspase-3, and prevent the injured neurons from apoptosis.

OBJECTIVE:To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitability and neurofunction after cerebral ischemia-reperfusion injury.METHODS:After determined awake resting motor threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion injury, then rTMS were applied to rTMS group (n=10) at different time, while control group (n=10) received no stimulation. A week later, MT and MEPs were evaluated again, as well as neurological deficits and infarct volume. The effects of rTMS and MCAO reperfusion injury on these parameters were analyzed.RESULTS:After MCAO reperfusion, both MT level and neurological deficit scores increased, distinct focal infarction formed, and latency of MEP elongated. Compared with the control group, the increased extent of MT and neurological scores of rats receiving rTMS were significantly lower (P < 0.05), as well as the infarct volumes reduced significantly (P < 0.05). But MEP was not affected by rTMS obviously. There was a positive linear correlation between postinjury MT and infarct volume (r = 0.64, P < 0.05).CONCLUSION:rTMS may facilitate neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could provide prognostic information after MCAO reperfusion injury.

经颅磁刺激技术(transcranial magnetic stimulation,TMS)出现于1985年,通过时变磁场(time-varying)产生感应电流直接刺激皮层神经元而改变后者功能.单脉冲TMS、重复TMS(rTMS)、配对TMS、围刺激期时间直方图等与其他检查方法联合应用,可描述不同脑区的功能,不同脑区之间或内部和(或)投射纤维之间的联系和变化及继发行为改变.尤为人们关注的rTMS技术出现于1992年,其不仅影响刺激局部和功能相关的远隔皮层功能,实现皮层功能区域性重建,而且产生的生物学效应可持续到刺激停止后一段时间,已成为研究神经网络功能重建的良好工具,并用于某些神经心理疾病的发病机制和治疗效果的探讨[1,2].现就近年来rTMS的研究及应用进展综述如下.