Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To investigate the long-term outcome of deep brain stimulation (DBS) in patients with KMT2B gene-related dystonia. Methods:Seven patients with KMT2B gene-related dystonia who were treated at Peking Union Medical College Hospital from April 2018 to December 2020 were enrolled. Whole-exome sequencing was used to detect genetic variations, and clinical phenotypes were summarized. All patients underwent DBS surgery and were followed up at 6 months, 3 years, and 5 years post-surgery. The therapeutic effects of DBS were evaluated by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), including BFMDRS Motor Subscale (BFMDRS-M) and Disability Subscale (BFMDRS-D). Results:The preoperative BFMDRS-M and BFMDRS-D scores were 60.43±27.12 and 17.00±6.24, respectively. The most significant improvements were observed at 6 months post-surgery, with the BFMDRS-M and BFMDRS-D scores being 20.64±5.50 and 9.57±1.72, reflecting improvements of 65.8% and 43.7%, respectively, both with statistically significant differences ( t=4.342, P=0.005; t=2.828, P=0.030). At 3 years post-surgery, the BFMDRS-M and BFMDRS-D scores were 26.20±8.68 and 10.50±2.74, representing improvements of 56.7% ( t=3.045, P=0.029) and 38.2% ( t=2.012, P=0.100), respectively. At 5 years post-surgery, the BFMDRS-M and BFMDRS-D scores were 27.80±14.87 and 11.00±2.83, with improvements of 54.0% ( t=1.824, P=0.142) and 35.3% ( t=1.933, P=0.125), respectively. At the 5-year postoperative follow-up, the patients′ cervical dystonia improved by 78.9%, while the upper limbs, lower limbs, and trunk dystonia improved by 57.8%, 56.6%, and 58.0%, respectively. However, only 1 patient showed significant improvement in the language function. Conclusions:DBS showed good therapeutic effects on KMT2B gene-related dystonia, but the efficacy declined over time. Significant improvements were observed in patients′ cervical, limb and trunk dystonia, but the improvement in language function was not significant.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To investigate the long-term outcome of deep brain stimulation (DBS) in patients with KMT2B gene-related dystonia. Methods:Seven patients with KMT2B gene-related dystonia who were treated at Peking Union Medical College Hospital from April 2018 to December 2020 were enrolled. Whole-exome sequencing was used to detect genetic variations, and clinical phenotypes were summarized. All patients underwent DBS surgery and were followed up at 6 months, 3 years, and 5 years post-surgery. The therapeutic effects of DBS were evaluated by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), including BFMDRS Motor Subscale (BFMDRS-M) and Disability Subscale (BFMDRS-D). Results:The preoperative BFMDRS-M and BFMDRS-D scores were 60.43±27.12 and 17.00±6.24, respectively. The most significant improvements were observed at 6 months post-surgery, with the BFMDRS-M and BFMDRS-D scores being 20.64±5.50 and 9.57±1.72, reflecting improvements of 65.8% and 43.7%, respectively, both with statistically significant differences ( t=4.342, P=0.005; t=2.828, P=0.030). At 3 years post-surgery, the BFMDRS-M and BFMDRS-D scores were 26.20±8.68 and 10.50±2.74, representing improvements of 56.7% ( t=3.045, P=0.029) and 38.2% ( t=2.012, P=0.100), respectively. At 5 years post-surgery, the BFMDRS-M and BFMDRS-D scores were 27.80±14.87 and 11.00±2.83, with improvements of 54.0% ( t=1.824, P=0.142) and 35.3% ( t=1.933, P=0.125), respectively. At the 5-year postoperative follow-up, the patients′ cervical dystonia improved by 78.9%, while the upper limbs, lower limbs, and trunk dystonia improved by 57.8%, 56.6%, and 58.0%, respectively. However, only 1 patient showed significant improvement in the language function. Conclusions:DBS showed good therapeutic effects on KMT2B gene-related dystonia, but the efficacy declined over time. Significant improvements were observed in patients′ cervical, limb and trunk dystonia, but the improvement in language function was not significant.

Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

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.

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.

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.

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.

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.