Objective To investigate the correlation of plasma interleukin ( IL)-17 level and IL-17 receptor (IL-17R) expression in the thymus of patients with myasthenia gravis (MG).Methods The blood samples of 63 patients (38 with glucocorticoid treatment, 25 with thymus removal) who admitted to Henan Provincial People′s Hospital between 2010 and 2014 were collected at three different stages: pre-treatment, 1 week post-treatment and 1 month post-treatment.The blood samples of 42 healthy controls were also collected.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-17 in plasma.Twenty-five thymus tissues from MG patients and another 12 thymus tissues from patients with congenital heart disease who had surgery therapy were also collected.Reverse transcription polymerase chain reaction was used to evaluate the mRNA levels of IL-17R.The possible correlation between the expression of IL-17 and IL-17R with MG was analyzed.Results Before treatment, the levels of IL-17 in the plasma were much higher in all the MG patients ( both ocular and generalized) when compared to the healthy controls ( controls (3.2 ±0.7) pg/ml, MG patients (8.5 ±1.7) pg/ml, t =2.450, P <0.01; generalized type patients (9.7 ±1.4) pg/ml, t =2.532, P <0.01).In the patients with glucocorticoid treatment, IL-17 levels began to reduce after 1 week treatment and a statistically significant difference was found when compared to the pre-treatment samples (pre-treatment (8.3 ±1.2) pg/ml, 1 week after treatment (6.3 ±0.7) pg/ml, t=2.052, P<0.05) and healthy controls (t =1.933, P<0.05).One month after the glucocorticoid treatment, the levels of IL-17 decreased to the normal level (1 month after treatment (3.9 ±0.6) pg/ml, t=2.630, P <0.01, compared to the pre-treatment; t =1.395, P >0.05, compared to the healthy controls).In the surgery therapy cases, the IL-17 levels were also reduced after the thymus removal ( pre-surgery (8.8 ±1.4) pg/ml, 1 week after surgery (5.3 ±0.7) pg/ml, t=1.950, P<0.05;1 month after surgery (3.0 ±0.4) pg/ml, t=2.683, P<0.01).In the thymus tissues of the MG patients, the mRNA levels of IL-17R were much higher than that of the controls ( relative level 2.31 folds, t =2.682, P <0.01).Meanwhile, a positive correlation was found between the plasma IL-17 levels and the relative IL-17R levels in thymus tissues ( r =0.945 4, P <0.01 ).Furthermore, IL-17 was positively correlated with quantitative myasthenia gravis scores (QMGS) either pre-treatment (r =0.798 1, P <0.01) or post-treatment (r=0.906 5, P<0.01).And IL-17R was positively correlated with QMGS pre-treatment (r=0.775 5, P<0.01).Conclusions IL-17 is increased in the plasma of MG patients (both ocular and generalized) , and is decreased upon the glucocorticoid treatment or surgery therapy, suggesting that it can be used as a parameter to determine the therapeutic effects.IL-17R is increased in the thymus tissues of MG patients, suggesting that it can potentially be used as a pathological diagnosis parameter.

Objective To explore the walking ability and cognitive function changes in normal pressure hydrocephalus patients after cerebrospinal fluid ( CSF ) tap test for helping clinicians choose evaluation time and methods.Methods Twenty-seven patients with probable normal pressure hydrocephalus in Peking Union Medical College Hospital from 2013 to 2014 were included.All patients were evaluated using Minimum Mental State Examination, the Montreal Cognitive Assessment, Ability of Daily Life, and Idiopathic Normal Pressure Grade Scale, underwent 1.5 T head MRI scan and had ventriculo-peritoneal shunt after informerd consent.A lumbar tap with removal of 30 ml of CSF was performed in all patients.Evaluations included the 10 m walking time and steps, Trail Making Test A, number code and Stroop test.Those tests were performed 1 day before and 4, 8, 24, 72 hours after CSF tap test.The walking test and neuropsychological test results were compared between those before and after the CSF tap test.Correlation analysis was conducted between the normal pressure hydrocephalus featured MRI characters and CSF tap test responses including Evan′s index, callosum corpus angle, mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure associated with ventriculomegaly . Results Compared with 0 h walking time (23.56(14.00) s), the 10 m walking time on the 8 hours and 24 hours after CSF tap test, which were 19.41 ( 9.00 ) s and 19.67 ( 11.00 ) s respectively, were significantly improved ( Z values in Wilcoxon signed ranks test were -3.416 and -3.443 respectively,both P<0.01).There were no statistically significant differences on every evaluation time point.The neuropsychological tests changings were significant on 24 hours and 72 hours.Compared with 0 h neuropsychological test z scale (-10.28(21.60)), the z scale on the 24 hours and 72 hours after CSF tap test, which were -6.29 (26.72), -3.37(36.15)respectively, were significantly improved (Z values in Wilcoxon signed ranks test were -3.506,-2.701 respectively, both P<0.01).The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure were not statistically correlated with the response of CSF tap test.Conclusions Walking ability in normal pressure hydrocephalus patients was improved after the CSF tap test.The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure might not be correlated with the response of CSF tap test.

Objective To explore the effect of miniAd-ATP7B-GFP on the copper metabolism of skin fibroblasts of Wilson′s disease ( WD ) patients under high concentration copper medium.Methods Firstly, mini-adenovirus carrier containing human ATP7B gene was built and the mutations of 8 WD patients were detected.Fibroblasts from primary culture of skin of WD patients and normal human were cultivated 72 h in basic medium and medium with the copper concentration of C1(22.3μmol/L), C2(89.2μmol/L), C3 (156.1 μmol/L), C4 (245.3 μmol/L).Then the concentration of copper and protein was detected and copper/protein ratio was calculated.Secondly, miniAd-GFP ( miniAd-GFP group) and miniAd-ATP7B-GFP ( miniAd-ATP7B-GFP group ) were added into WD patients skin fibroblasts respectively, Wilson non-transfection group and normal group were set up as control, and C4 medium was used to culture the cells of four groups for 72 h and 96 h.Then the concentration of copper and protein was detected and copper/protein ratio was calculated.Results Five kinds of mutations were detected from 8 WD patients.The copper/protein ratio of WD patients and normal human in basic medium and the C1 -C3 groups had no statistically significant difference, but in C4 group (WD (1 871.6 ±209.2) ng/mg, normal group (1 267.2 ±188.3) ng/mg) the difference was statistically significant (t=6.075, P<0.01).C3((816.3 ±113.9) ng/mg) and C4 groups had statistically significant difference compared with the basic medium group ( ( 159.2 ± 38.6) ng/mg;WD:χ2 =31.493, normal group:χ2 =30.708, both P<0.01).The copper/protein ratio of 96 h group was higher than 72 h group.Compared with WD non-transfection (96 h:(2 731.2 ±188.7) ng/mg,72 h:(1 901.7 ±219.5) ng/mg) and normal groups, miniAd-ATP7B-GFP group had statistically significant difference both in 96 h ( ( 2 071.0 ±171.8 ) ng/mg ) and 72 h groups ( ( 1 495.5 ±161.4 ) ng/mg;72 h:F=20.130, 96 h: F=51.496,P<0.01).Conclusion MiniAd-ATP7B-GFP has partial improvement on copper metabolism of skin fibroblasts of WD patients under high concentration copper medium.

Objective To study the clinical and electrophysiological features of the patients with hereditary neuropathy with liability to pressure palsy ( HNPP) diagnosed by gene analysis.Methods Seven patients from two HNPP families were assessed on medical history, physical examination, electrophysiology findings and gene analysis.Results A clinical manifestation of acute, painless, recurrent peripheral nerve palsies was typical for HNPP.Median, ulnar and peroneal nerves were usually affected.Electrophysiology study revealed that prolonged distal motor latency and slowing nerve conduction velocity were prominent.Gene studies exhibited a deletion of the peripheral myelination protein 22 gene in all the seven patients.Conclusions HNPP usually affects areas where nerves are subject to entrapment, and many episodes are preceded by minor compression on the affected nerve.As a reliable screening tool in detecting HNPP, the electrophysiological study shows that segmental demyelination is most commonly seen at common nerve entrapment sites.

Objective To investigate the clinical features, the video electroencephalography ( V-EEG) and synchronous electrocardiography ( ECG) changes in non-epileptic seizures and the significance of ECG monitoring in the diagnosis of epilepsy.Methods We collected 3 patients who came in a chief complaint of“episodes of unconsciousness with limbs twitch”, whose clinical features and EEG, ECG in longterm VEEG monitoring were analyzed.The 3 patients were followed up for at least 6 months.Results The 3 patients were all diagnosed as epilepsy in other hospital,and during the 24-hour VEEG monitoring in our hospital,2 patients showed abnormal cardiac rate and arrest during the attack and corresponding EEG changes after cerebral ischemia and hypoxia.After consultation with the department of cardiology, they were diagnosed as cardiac syncope episode and no attack showed up after the placement of pacemaker.The Q-T interval was prolonged in the other patient during the longterm ECG monitoring, after the coherence check who was diagonsed as severe hypocalcemia combined with myocardial damage due to a lower parathyroid function and had no attack after symptomatic treatment.Conclusions The synchronous ECG monitoring during the attack is of great significance in the differential diagnosis of epileptic and non-epileptic seizures. The ECG changes in patients with longterm VEEG monitoring should be focused on.It is necessary to add the early warning function to prevent the occurrence of accidents.

Objective To discuss the clinical and radiological features of congenital absence of the internal carotid artery.Methods Four patients of the congenital absence of the internal carotid artery were reported and the clinical and radiological features were summarized by a review of the literature.Results Four patients were shown subarachnoid hemorrhage ( SAH) , transient ischemic attack ( TIA) , epilepsy and headache, respectively.All of the four patients presented the absence of unilateral or bilateral carotid arteries in cervical computed tomography angiography ( CTA) or magnetic resonance angiography ( MRA).Carotid canal was absent in all the patients in CT base of skull and multiple intracranial vascular dysplasia was shown in all the patients.Basilar or posterior communicating artery was presented as dolichoectasia in 3 patients.There were 2 patients who suffered aneurysm.Conclusions The onset of the congenital absence of the internal carotid artery can be presented in any age.Sudden severe headache as initial symptom caused by SAH is showed more common in children and adolescents.TIA is commonly seen in the elderly.CT shows carotid canals are absent in the base of skull.Unilateral or bilateral carotid arteries are shown absent in CTA or MRA.Multiple intracranial vascular dysplasia is shown in CTA or MRA.Carotid artery CTA has been considered as the optimal imaging method of showing the congenital absence of the internal carotid artery.

Objective To investigate the clinical features and pathogenic genes of a familial hypokalemic periodic paralysis ( HOKPP).Methods PCR amplification and DNA sequencing were used to screen candidate genes of the HOKPP family members (CACNA1S, SCN4A, KCNE3), and the clinical features were carefully analyzed at the same time.Results The sequencing analyses of the SCN4A gene in the proband identified three nucleotide sequence mutations, which influenced the amino acid sequence of the skeletal sodium channel.One of the mutations was identified as a C/T heterozygous pattern at the 2111th nucleotide position in exon 13, resulting in a change from Thr to Met at the 704th amino acid position of the sodium channel protein.All affected patients carried the Thr704Met mutation, whereas unaffected family members did not.Clinical symptoms in this family followed an autosomal dominant inheritance pattern.Muscles weakness, pain and hypokalemia in the period between attacks were seen in all patients.Paralytic symptoms occurred early, lasted longer and recurred frequently, while cold was the main predisposing factor.With the progress of the disease, patients represented persistent weakness and atrophy in proximal muscles.Conclusions Mutation (Thr704Met) in the SCN4A gene should be responsible for this family.This mutation causes severe HOKPP and progressive muscle atrophy.

Objective To describe the clinical, neuroimaging and genetic profiles of amyotrophic lateral sclerosis with frontotemporal lobe degeneration ( ALS-FTLD).Methods From August 2011 to May 2015, patients with FTLD or other types of neurodegenerative dementia were physically examined in detail and electromyography was performed to those with suspected dysarthria, limb atrophy or weakness.Cognitive and behavioral screenings were performed to all ALS patients.Patients with ALS-FTLD entered further analysis of neuroimaging and genetics.Results Among the 8 patients diagnosed as ALS-FTLD, 4 patients began with personality change or amnesia, while diseases in the remaining 4 cases began with limb weakness or dysarthria.Dementia type of 7 cases was behavioral variant FTLD ( bvFTD) and 1 case was diagnosed as semantic dementia.Electromyography of all the 8 patients showed diffuse neurogenic changes.Constructional neuroimaging of 6 patients showed cerebral atrophy predominantly in frontal and temporal lobes.Fluorodeoxyglucose-positron emission tomography was conducted in 5 patients, indicating hypometabolism mainly in frontal and ( or) temporal lobes.NeuroQ analysis revealed that bilateral frontal lobes were the most hypometabolic areas for ALS-FTLD.Among 4 patients who underwent genetic screening, 1 patient was C9ORF72 mutation carrier.Conclusions bvFTD is the major type of dementia in the context of ALS.Metabolic neuroimaging could assist accurate diagnosis, and it reveals that bilateral frontal lobes are the most hypometabolic areas for ALS-FTLD.C9ORF72 gene mutation is an important pathogenic mutation for ALS-FTLD, although it is rare in Chinese population.

Objective To summarize clinical phenotypes and pathological characteristics in myopathies with tubular aggregates (TAs).Methods We reviewed 5 697 patients who performed muscle biopsies in our department between January 2001 and July 2015.We collected the cases with TAs and made classification based on their clinical diagnoses and pathological changes.Results Fifty-seven patients (1.00％) showed TAs in muscle specimens,including 50 (87.72％) males and 7 (12.28％) females.According to clinical,neurophysiological,pathological and genetic analysis,the diagnoses included 23 (40.35％) cases of periodic paralysis,7 (12.28％) cases of chronic alcohol intoxication,6 (10.53％) cases of congenital myasthenic syndrome,5 (8.77％) cases of exercise-induced cramps,3 (5.26％) cases of necrotizing myopathy,1 (1.75％) case of stromal interaction molecule 1-associated myopathy,limbgirdle muscular dystrophy 2E,myotonic dystrophy,myotonia congenita,paramyotonia congenitia,hypothyroid myopathy respectively.Other cases of unknown cause included unclassified distal myopathy,external ophthalmoplegia,white matter lesions,mental retardation,stroke,early onset weakness,pulmonary arterial hypertension.Besides TAs,pathological changes also included necrosis of muscle fibers (3 cases,5.26％),neurogenic changes (3 cases,5.26％) and muscular dystrophic changes (1 case,1.75％).Conclusions Our results indicated that TAs are usually found in males and could present in many types of hereditary or acquired neuromuscular disease as independent or accompanying changes.Periodic paralysis,chronic alcohol intoxication and congenital myasthenic syndrome are 3 major diseases causing myopathies with TAs.

Objective To observe the characteristics of midbrain hyperechogenicity of amyotrophic lateral sclerosis (ALS) patients by transcranial sonography (TCS).Methods A total of 107 ALS patients,enrolled from January to July 2015 in Beijing University Third Hospital,with the diagnosis of possible or definite ALS according to revised E1 Escorial criteria were examined by transcrinal B-mode sonography.The area of midbrain and substantia nigra and the area ratio of hyper-substantia nigra/midbrain (S/M) were measured and compared between ALS and 40 age-and gender-matched controls.Results There were 29.0％ (31/107) of ALS patients and 7.5％ (3/40) of controls who displayed abnormal midbrain hyperechogenic areas for groups comparison (x2 =22.708,P ＜ 0.01).The hyperechogenic substantia nigra area and S/M were (0.40 ± 0.14) cm2 and 9.5％ (6.0％,13.0％) in ALS group,whereas (0.20 ± 0.06) cm2 and 5.0％ (2％,6.0％) in control group respectively,the difference between the two groups being statistically significant (t =12.727,Z =16.545,both P ＜0.01).No correlations of hyperechogenic area sizes in ALS patients were found in regard to age,gender,ALS duration or ALS Functional Rating Scale score (r=0.043,-0.088,0.018,0.202;P=0.251,0.512,0.894,0.190).However,there was significant correlation between TCS severity and ALS subtype (bulbar vs spinal form,r =0.386,P ＜ 0.01).Conclusion Hyperechogenicity of the substantia nigra was found in patients with sporadic ALS with a frequency higher than in controls.