Aseptic meningitis associated with primary Sj?gren′s syndrome: a case report / 中华神经科杂志

Sj?gren′s syndrome is a chronic autoimmune inflammatory disease characterized by exocrine gland and extraglandular involvement. Cases of Sj?gren′s syndrome-associated aseptic meningitis (SS-AM) are relatively rare, and a case of recurrent aseptic meningitis with leukopenia and mild anemia associated with primary Sj?gren′s syndrome is reported, whose symptoms basically disappeared after treatment with prednison and hydroxychloroquine. The purpose of reporting this case is to raise awareness of SS-AM among fellow clinicians.

Screening for NOTCH2NLC gene dynamic mutation in patients with essential tremor / 基础医学与临床

Objective To identify the pathogenic variants in 110 patients with essential tremor(ET).Methods Clinical data and peripheral blood samples of ET patients were collected from the Department of Neurology of Peking Union Medical College Hospital and then the genomic DNA was extracted.Dynamic mutation detection of NOTCH2NLC was performed in patients with essential tremor by triplet repeat primed PCR(TP-PCR).Since ET is as-sociated with multiple mechanisms of neuro-degeneration,the next generation sequencing(NGS)panel targeting neu-rodegenerative associating genes were performed to check pathogenic variants in additional genes.Results A total of 110 ET patients and 187 matched control individuals were recruited.The age of onset in the current ET group was(36.30±17.64)years,and 74.8%patients had a family history.No abnormal trinucleotide repeat expansion in NOTCH2NLC was identified.The repeat number of(GGC)n lied within normal ranges between 10－47(average 18.6±5.4).Variants burden analysis showed association of ET with PLA2G6.Three rare variants in four patients in PLA2G6 were identified with unknown significance.Conclusions Dynamic mutations of NOTCH2NLC are uncom-mon in ET patients and that suggests need of more researches for further exploring the genetic mechanism of ET.

Long-term outcome of deep brain stimulation in chorea-acanthocytosis / 中华神经科杂志

Objective:To summarize genotype-phenotype features and explore the long-term outcome of bilateral globus pallidus interna deep brain stimulation (DBS) in chorea-acanthocytosis (ChAc) patients.Methods:Seven patients who diagnosed with ChAc were included in this study from April 2016 to April 2018 at Peking Union Medical College Hospital. Whole-exome sequencing was used for gene analysis of the patients, and the genotype-phenotype features of these patients were recorded. All patients underwent the DBS surgery, and long term follow-up was conducted before surgery, 3 months, 6 months, 1 year, 3 years, and 5 years after surgery. Patients were scored using the Unified Huntington Disease Rating Scale (UHDRS) to evaluate the long-term efficacy of DBS surgery.Results:The main clinical manifestations in all 7 patients were oro-faciol-ingual dyskinesia, limb chorea, dystonia, and dysarthria. Genetic testing found that all patients had VPS13A gene pathogenic variation, but the type of variation was different. The UHDRS motor score before bilateral pallidal DBS surgery was 37.00±16.68, which significantly improved to 19.67±5.99 at 1 year post-surgery, with average improvement of 46.8% ( t=5.20, P=0.003), to 23.86±8.99 at 3 years post-surgery, with average improvement of 35.5% ( t=3.08, P=0.022), and to 29.00±14.97 at 5 years post-surgery, with average improvement of 21.6% ( t=1.41, P=0.217). The symptoms of patients were most significantly improved in limb chorea and oro-facio-lingual dyskinesia. However, at the 5-year follow-up, severe dystonia and gait difficulties reoccurred in 3/7 and 4/7 of the patients, respectively. The patient′s dysarthria had not been effectively improved. Conclusions:The clinical manifestations of patients with ChAc are relatively consistent, but there is significant genetic heterogeneity. Bilateral pallidal DBS therapy is effective for patients with ChAc, but the long-term efficacy decreases with disease progression.

The clinical features and etiology analysis of superficial siderosis of the central nervous system / 中华神经科杂志

Objective:To summarize the clinical manifestation and imaging of superficial siderosis of the central nervous system and explore the potential etiology.Methods:The clinical and imaging data of 7 patients diagnosed as superficial siderosis of the central nervous system in Peking Union Medical College Hospital from May 2013 to November 2019 were retrospectively reviewed. The etiology and follow-up prognosis through phone call were analyzed.Results:There were 7 patients included (3 male and 4 female) with an average age of 53 years (41-58 years). The cardinal manifestations were sensorineural deafness (all 7 cases), cerebellar ataxia (all 7 cases) and pyramidal signs (all 7 cases). Dizziness (6 cases), bladder disturbance (5 cases), headache (3 cases), double vision (2 cases) and congnitive impairment (1 case) could also happen. Magnetic resonance imaging showed symmetrical well-defined curvilinear homogeneous low signal on T 2 or blood-sensitive sequences (T 2* gradient echo or susceptibility-weighted imaging) over the superficial surface of cerebellar, brain stem, and spinal cord or cranio-cervical junction. All the 7 patients showed cerebellar atrophy especially the upper vermis. The potential causes included trauma history in 3 cases, intraspinal fluid-filled collection which indicated dural defect or duropathologies in 3 cases, intraspinal mass in 1 case and vertebral and disc degeneration in all 7 patients. The 5 patients who successsfully got follow-up showed exacerbation of variable degree. Conclusions:Classical superficial siderosis of the central nervous system is a rare disease with cardinal manifestation of progressive ataxia, sensorineural deafness and pyramidal signs. T 2WI of magnetic resonance imaging showing low signal over the superficial surface of cerebellar, brain stem, and spinal cord could indicate the diagnosis, and blood-sensitive sequences such as T 2* gradient echo or susceptibility-weighted imaging were more sensitive. Duropathologies or dural defect may be the most probable causes of the disease and should be examined and treated carefully.

Reliability of rating scales for dystonia by using standardized video / 中风与神经疾病杂志

@#Objective To investigate the reliability of using standardized generalized and craniocervical dystonia video to score the dystonia scale.Methods Standardized videos of 12 patients with dystonia （4 patients with generalized dystonia，4 patients with blepharospasm and 4 patients with spasmodic torticollis）were evaluated by 5 dyskinesia doctors from different hospitals in China.Burke Fahn Marsden Dystonia Scale （BFMDRS），Jankovic Scale （JRS），and West Toronto Spastic Tortico Scale （TWSTRS） were scored，respectively.The intra class correlation coefficient（ICC）was used to calculate the inter-rater reliability and intrarater reliability of total scales and each subitems.Results The ICC of inter-rater reliability of BFMDRS，JRS and TWSTRS were 0.96，0.91 and 0.92，respectively. The ICC of intra-rater reliability were 0.97，0.94 and 0.99，respectively. The inter-rater reliability and intra-rater reliability of the three scales all reached the excellent standard.Conclusion There are good inter-rater reliability and intra-rater reliability of using standardized video to score BFMDRS，JRS and TWSTRS.Standardized video has clinical application value.

Safety and efficacy of botulinum toxin type A made in China for treatment of post-stroke upper limb spasticity: a randomized double-blind controlled trial / 中华神经科杂志

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Clinical and radiological features in patients with DYT6 dystonia / 中华神经科杂志

Objective To summarize the clinical and radiological features of DYT6 dystonia with mutations based on the data of our patient cohort as well as the report by others.Methods Clinical data of the 11 patients with DYT6 dystonia in Peking Union Medical College Hospital from June 2009 to May 2012 were retrospectively reviewed and analyzed.Clinical data included gender,onset age,initiative symptom of onset,the sites of involvemet,family history,etc.All patients were examined for brain MRI scan,6 patients were examined for DTI.Results Of the eleven gene-confirmed DYT6 dystonia patients,7 were male and 4 were female,with an onset-age ranged from 5 years to 36 years,the mean age of onset was 19.4years.Eight patients had a family history.There were 10 patients with early onset dystonia and only 1 patient with late onset dystonia.The most common site of onset was the neck (7/11),and the next was the right arm,1-5 body areas were affected at the time of neurological assessment,the average amount was 2.8,and the most frequently affected anatomical site was the neck (10/11),next came lower face,jaw and tongue.Among all the patients,6 patients presented with segmental dystonia,4 patients presented with focal dystonia,only 1 patient presented with generalized dystonia.All the patients with thanatos-associated protein domain-containing apoptosis-associated protein (THAP) domain affected had a family history,but the patients with the same mutant gene varied with clinical manifestation.Only 1 patients with non-THAP domain affected had a family history,but in most families,there were adult asymptomatic mutant gene carriers.Mutations within the THAP domain were associated with an earlier age of onset than non-THAP domain (17.3 and 21.8 years old).Routine MRI of all patients were normal and DTI of 6 patients showed that fractional anisotropy values in the bilateral sensorimotor area in DYT6 dystonia were reduced.A detailed description of a patient with TOR1A and THAP1 gene mutations was given.Conclusions Early onset dystonia is the main manifestation in patients with DYT6 dystonia in China.The most common site of onset is the neck,and the next is the right arm.The most frequently affected anatomical site is the neck,next come lower face,jaw and tongue.Laryngeal dystonia is absent.The patients with same mutant gene show high heterogeneity in the clinical manifestations,mutations within the THAP domain of THAP1 tend to manifest at an earlier age and higher penetration than mutations localized to non-THAP domain.Reduction of fractional anisotropy values indicates that the axonal integrity and coherence in the region of sensorimotor area is damaged in DYT6 dystonia.

Analysis of the risk factors for benign essential blepharospasm / 中华神经科杂志

Objective To explore the risk factors of benign essential blepharospasm( BEB) and each factor' s intensity.Methods Totally 100 patients with BEB including Meige and cranial-cervical without other neurological abnormalities were recuited from the outpatient clinic of Department of Neurology, Peking Union Medical College Hospital from April 2009 to March 2010 as case group.At the same time, 100 outpatients diagnosed with idiopathic hemifacial spasm ( HFS) and 40 healthy controls without extrapyramidal diseases or other neurological diseases were recuited from the same outpatient clinic.All the cases and controls were investigated by questionnaires about general conditions, social behavioral factors, environmental factors, phychiatrical factors, genetic factors, previous diseases.The data was analysed by Logistic regression model with the statistical software SPSS 11.0.Results Multivariate analysis indicated that eye disease (OR = 5.818, 95% CI 2.510-13.486), anxiety (OR=3.433, 95% CI 1.548-7.610) and depression (OR =2.894, 95% CI 1.091-7.681) were positively related with BEB, whereas coffee drinking (OR = 0.251, 95% CI 0.080-0.784) had a negative relationship with BEB ( all P ＜ 0.05 ).Conclusions The risk factors of BEB are eye diseases, anxiety and depression.Coffee drinking is protective for BEB.The results suggest that local injury and phychiatrical factors may be more important than genetic factor in the aetiology of BEB.