A Novel Mutation Associated with Familial Idiopathic Basal Ganglia Calcification and Analysis of the Genotype-Phenotype Association in Chinese Patients / 中华医学杂志(英文版)

<p><b>Background</b>Idiopathic basal ganglia calcification (IBGC) is a genetic disorder characterized by bilateral basal ganglia calcification and neural degeneration. In this study, we reported a new SLC2OA2 mutation of IBGC and reviewed relevant literature to explore the association between phenotypes and genotypes in Chinese IBGC patients.</p><p><b>Methods</b>Clinical information of the proband and her relatives were collected comprehensively. Blood samples of both the patient and her father were obtained, and genetic screening related to IBGC was performed using second generation sequencing with their consent. Findings were confirmed by Sanger sequencing. Polyphen-2 was used to predict the potential association between mutations and disease. Then, we retrieved literatures of Chinese IBGC patients and explored the association between phenotype and genotype.</p><p><b>Results</b>A novel mutation was identified through genetic testing, and it is suggested to be a damage mutation predicted by Polyphen-2. Through literature review, we found that SLC20A2 mutation is the most common cause for IBGC in China. Its hot spot regions are mainly on the 1 and 8 exons; the second common one is PDGFB where the hot spot covered a length of 220-230 bp localized on the 2 exon; moreover, Chinese IBGC patients featured early-onset, more severe movement disorder and relatively mild cognitive impairment compared with those in other countries.</p><p><b>Conclusions</b>There is significant heterogeneity both in phenotype and genotype in Chinese IBGC patients. Further research of pathogenic mechanism of IBGC is required to eventually develop precise treatment for individuals who suffered this disease.</p>

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study / 中华医学杂志(英文版)

Background@#Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.@*Methods@#TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).@*Results@#Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.@*Conclusions@#Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.@*Trial Registration@#ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice.</p><p><b>METHODS</b>Data including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables.</p><p><b>RESULTS</b>Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups.</p><p><b>CONCLUSION</b>The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.</p>

Recurrent Fisher-Bickerstaff syndrome: report of a Chinese case / 中华医学杂志(英文版)

Fisher-Bickerstaff syndrome (FBS) was recently proposed to help to diagnose the conditions that overlap Fisher syndrome and Bickerstaff’s brainstem encephalitis, as well as the unclassified conditions that had ophthalmoplegia and ataxia with clear consciousness, flexor plantar response and preserved tendon reflexes. Recurrences are exceptional with Guillain-Barré syndrome and its variants. Here we reported a patient with diagnosis of recurrent FBS. The patient presented with recurrent drowsiness, unsteady gait, diplopia and reduced deep tendon reflexes, which met the diagnostic criteria for FBS. The interval was eight months. He was treated with intravenous immunoglobulins during each episode and got good recovery. To our knowledge, this is a relatively early report about recurrent FBS case that had central and peripheral involvement during each episode in China.

Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multiple sclerosis (MS) is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation (ASCT) has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS.</p><p><b>METHODS</b>Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide, melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months (range, 6 to 59 months).</p><p><b>RESULTS</b>No death occurred following the treatment. The overall confirmed progression free survival rate was 77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation (P = 0.000). Thirteen patients (59%) had remarkable improvement in neurological manifestations, four (18%) stabilized their disability status and five (23%) showed clinical recurrence of active symptoms.</p><p><b>CONCLUSIONS</b>ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.</p>

Hearing impairment in patients with mild cognitive impairment and Alzheimer's disease / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the relationship between the degrees of peripheral auditory dysfunction and clinical dementia rating (CDR) in the patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD).</p><p><b>METHODS</b>Pure-tone thresholds (PT), word recognition scores (WRS), acoustic immittance and auditory brain-stem responses (ABR) were done to evaluate the auditory function in 24 cases of the patients with MCI and in 31 cases of the patients with AD and in 50 subjects of the control group. Clinical dementia rating (CDR) questionnaire was used to define the dementia degree of the subjects.</p><p><b>RESULTS</b>Twenty-four MCI patients and 31 AD patients were selected, with average age of 72.0 +/- 6. 5 and 73.1+/-7. 5 of whom 70.8% and 67.7% were female separately. There was no significant difference in PTT and WRS between the MCI and AD groups (P > 0.05). In order to ascertain the relationship between hearing level and degree of dementia, all subjects were divided into 4 groups according their hearing loss (PTA <25 dB:0, 25-30 dB:1, 31-35 dB:2, >35 dB:3) to compare their CDR scores (the control:0, MCI:0. 5, mild AD:1). The more the CDR scores have, the more hearing impairment after controlling the confounder factors (Kendalls tau b = - 0.285, P = 0.018). No significant difference was found between the two groups in audiometry reliability, acoustic immittance and ABR (P > 0.05).</p><p><b>CONCLUSION</b>The positive relationship was founded the peripheral hearing impairment and the score of CDR questionnaire in less than 0.5 score of CDR groups and mild AD patients.</p>