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Objective:To investigate the genetic distribution of pathogenic genes of Charcot-Marie-Tooth diseases (CMT) in Chinese Han population, and compare the similarity and difference with the data in Peking University Third Hospital in 2013.Methods:Five hundred and twenty families with CMT and related diseases in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to March 2021 were collected. After peripheral myelin protein 22 (PMP22) gene duplication and deletion mutations were initially detected by multiple ligation probe amplification, the probands of these families were sequenced by next-generation sequencing (NGS) gene panel or whole exome sequencing, and validated by Sanger sequencing.Results:Among the 520 families, 336 CMT families were genetically confirmed, and the mutation detection rate increased from 48.6% (51/105) in 2013 to 64.6% (336/520) in 2021 (χ 2=9.54, P=0.003). Among them, 139 families had PMP22 gene duplication mutation (139/520, 26.7%), 46 families had gap junction beta-1 (GJB1) gene mutation (46/520, 8.8%), 26 families had mitofusin-2 (MFN2) gene mutation (26/520, 5.0%), 12 families had myelin protein zero (MPZ) gene mutation (12/520, 2.3%), 11 families had PMP22 gene point mutation (11/520, 2.1%), and 10 families had heat shock protein B1 gene mutation (10/520, 1.9%). There were 10 families with ganglioside induced differentiation associated protein 1 (GDAP1) gene mutation (10/520, 1.9%), 8 families with SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene mutation (8/520, 1.5%), 7 families with immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene mutation (7/520, 1.3%), 6 families with MORC family CW-type zinc finger 2 (MORC2) gene mutation (6/520, 1.2%), 5 families with sorbitol dehydrogenase (SORD) gene mutation (5/520, 1.0%), 16 families with very rare gene mutation (16/520, 3.1%) and 184 families without genetic diagnosis (184/520, 35.4%). Conclusions:Compared with the results in 2013, the 3 most common genes affecting CMT were still PMP22, GJB1 and MFN2 genes, but the proportion difference of patients with MPZ gene mutation gradually decreased with other genes such as SH3TC2 and GDAP1 genes. The proportion of newly discovered CMT genes, such as MORC2 and SORD genes, was similar with IGHMBP2 gene, which should be paid more attention. NGS greatly improved the detection rate of CMT, especially for patients with autosomal recessive-CMT.
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Objective To explore the diagnostic value of tremor analysis in patients with coexisting essential tremor (ET) and Parkinson's disease (PD).Methods A cross-sectional survey was conducted to collect 30 patients with PD,30 patients with ET and 20 patients with ET + PD in Peking University Third Hospital from January 2015 to December 2017.Tremor analysis was performed in all the patients.Results There were statistically significant differences in age (63.0(54.8,68.0),49.0(26.5,58.5),57.0(50.0,66.0) years,H=21.336,P＜0.05),disease course (12.0(8.0,13.3),36.0(12.0,87.0),22.0(11.5,33.0) years,H=18.233,P＜0.05) and Unified Parkinson's Disease Rating Scale score (21.13± 8.85,8.00± 3.68,24.35±9.14,F=36.443,P＜0.05) among the PD,ET and ET+PD groups.The average tremor frequencies in PD,ET and ET+PD groups at rest were (5.46±0.77),(7.11 ± 1.80) and (6.18± 1.55) Hz,respectively,with statistically significant differences among the three groups (F=5.77,P=0.006).The average tremor frequencies in the three groups at posture were (6.19±2.21),(8.23± 1.96) and (6.49± 1.23) Hz,respectively,with statistically significant differences (F=9.673,P＜0.01).There was no statistically significant difference in tremor amplitude among the three groups at rest and posture position.In the PD,ET and ET+PD groups,the proportion of electromyography alternating contractions of the active and antagonistic muscles was 76.9％(20/26),0/6 and 5/15 at rest (x2=17.192,P＜0.01),and 53.8％ (14/26),20.0％ (6/30) and 4/15 at posture (x2=7.564,P=0.023),both with statistically significant differences.Conclusions The clinical manifestations of patients with ET+PD have both characteristics of PD and ET,but they have their own characteristics.Tremor analysis can objectively identify the bilaterally synchronous or alternate discharges of electromyography at rest,which are different from those of typical PD and ET.Tremor analysis is helpful for the identification of this disease.
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The clinical and imaging data in 6 patients with corticobasal syndrome were retrospectively analyzed. Six patients presented asymmetric clinical symptoms, including 5 with cognitive impairment, 6 with emotional disorders, 2 with cortical sensory deficit, 5 with lalopathy, and 4 with apraxia. All patients developed limb dystonia and limb or trunk stiffness, 4 with tumble, 4 with bradykinesia, and 2 with tremor. Brain magnetic resonance imaging (MRI) showed that 4 patients had unilateral cerebral atrophy and 2 had mild atrophy of bilateral hippocampus. Localized low glucose metabolism in the unilateral cerebral lobe was seen in four patients by positron emission computed tomography (PET) examination, suggesting that PET is helpful for the diagnosis of corticobasal syndrome.
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To explore clinical characteristics,electrophysiological findings and treatment response in diabetic patients with chronic inflammatory demyelinating polyradiculoneuropathy (DM-CIDP). Thirty-six CIDP patients were identified, 10 were DM-CIDP and 26 were non-DM-CIDP. Clinical medical records, electrophysiological data and treatment were retrospectively reviewed.DM-CIDP patients were significantly older than non-DM-CIDP patients [(56.7 ± 10.0) years old vs. (40.4 ± 16.9) years old, P=0.001]. However, clinical characteristics and abnormalities of electrophysiological tests in both groups were comparable. DM-CIDP subjects responded to corticosteroids or intravenous immunoglobulin, thus with better prognosis.
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Objective To investigate the clinical and radiological features of medullary infarction (MI), and to compare the clinical characteristics of lateral medullary infarction (LMI) and medial medullary infarction (MMI).Methods Patients diagnosed as acute MI who were treated from January 2009 to December 2014 in Department of Neurology, Peking University Third Hospital, were retrospectively enrolled in the study and data were analyzed including risk factors, clinical features, laboratory findings, radiological characteristics, etiology and outcomes.Results A total of 62 cases of MI were enrolled with 48 cases of LMI and 14 cases of MMI , including 2 cases of bilateral MMI.The mean onset age of LMI and MMI was 60.2 ± 12.3 and 56.9 ± 14.2, respectively.The frequently affected location of LMI was the middle and upper part of medulla [40 cases (83.3％)].The common symptoms and signs of LMI were dizzy (38 cases ,79.2％), sensory disturbance (33 cases ,68.8％), dysarthria (32 cases ,66.7％), dysphagia (30 cases ,62.5％), diminished pharyngeal reflex (30 cases, 62.5％), Homer's sign (29 cases, 60.4％), ataxia (26 cases, 54.2％) and nausea or vomiting (25 cases, 52.1％).The frequently affected location of MMI was the upper part of medulla (13 cases, 92.9％).The common symptoms and signs of MMI were motor dysfunction (12 cases, 85.7％), sensory disturbances (11 cases, 78.6％), dizzy (10 cases, 71.4％) and dysarthria (10 cases, 71.4％).Infarctions caused by atherosclerosis were found in 35 cases of LMI (72.9％) and 12 cases of MMI (85.7％).Five cases (10.4％) of LMI died in hospital, while 1 case (7.1％) of MMI died in hospital.No lesion was found in 16 cases (25.8％) by MRI-DWI within the first 24 hours of onset.Conclusions Our study showes that the mean onset age of LMI is older than that of MMI.The lesion of LMI is frequently located in the upper and middle medulla, whereas the lesion of MMI is mostly in the upper medulla.The prognosis of LMI is worse than that of MMI.Atherosclerosis of the vertebral arteries is the predominant vascular pathology in MI.
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Objective To characterize the clinical,electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM).Methods We retrospectively analyzed the clinical,electrophysiology,neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014).Results Among these 4 patients,2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months.Two patients were with acute onset and 2 with chronic onset.All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration.One patient had interstitial lung disease.The anti-signal recognition particle antibodies were strong positive in all 4 patients.Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients.Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients.However,very few inflammatory cells were detectable in patients.One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs.Conclusions IMNM is characterized by heterogeneity at disease onset,severity and ilnvolvement of muscles with,however,similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation.Corticosteroid and/or immunosuppressant is effective for patients.
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Objective To summarize the clinical features,electrophysiology and neuropathological characteristics of peripheral nerves in patients with vasculitic neuropathy.Methods We retrospectively analyzed the clinical,electrophysiology and neuropathological characteristics of 15 patients with vasculitic neuropathy who underwent electrophysiology and sural nerve biopsy in our department from January 2009 to June 2013.Results There were 8 males and 7 females,aged from 38 to 82 years old,with a peripheral neuropathy course ranged from 0.5 month to 60 months.In the total of 15 patients,3 patients were diagnosed as nonsystemic vasculitic neuropathy,while the other 12 patients were diagnosed as systemic vasculitis neuropathy (SVN) including 5 cases of primary systemic vasculitis and 7 cases of secondary systemic vasculitis.In patients diagnosed as primary systemic vasculitis,there were 2 cases of Churg-Strass syndrome (CSS) and 3 cases of ANCA associated vasculitis.In patients diagnosed as secondary systemic vasculitis,there were 1 case of systemic lupus erythematosus (SLE),2 cases of sicca syndrome (SS),3 cases of rheumatoid arthritis (RA),1 case of Behcet' s disease associated with thyroid papillary carcinoma,1 case of hepatitis B and 1 case of RA-associated SS.For the pathological features of vasculitic neuropathy,type 1 lesion was found in 4 patients,type 2 lesion in 2 patients,and type 3 lesion in 9 patients.Axon degeneration was observed in 8 patients,while 7 patients manifested as axon degeneration associated with demyelination and local thickening of the perineurium was found in 2 patients.Conclusion Multiple mononeuropathy and asymmetric polyneuropathy are the common clinical presentations of vasculitic neuropathy.Electrodiagnostic testing almost always reveals the evidence of a predominantly axonal and sensorimotor process with associated demyelination presented in some cases.Sural nerve biopsy showes changes indicative of an axonopathy.
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Objective To investigate the correlation of CAGs repeat size and age of onset in patients with Kennedy's Disease (KD).Methods We detected the number of CAG repeats in the androgen receptor genes in 30 patients with KD.The correlation of CAGs repeat size with age of onset was analyzed.At the same time,the Appel scale that could represent the degree of motor functional impairment was scored in every patient.The correlation of Appel scale with CAGs repeat size and the course of disease were analyzed.Results Significant correlation was found between the number of CAGs with age of onset (r= -0.671,P <0.01 ).There was also correlation between the Appel score and the course of disease (r=0.855,P<0.01 ),but no correlation between the Appel score and the number of CAGs (r =0.100,P =0.601 ).Conclusions It is found that in Kennedy' disease,as well as in other CAG repeat diseases,the length of polyglutamine tract determines the age of onset ,but has no correlation with the severity of the disease.