Objective:To analyze the key differentially expressed genes and related pathways in patients with de-layed cerebral ischemia(DCI)occurring after aneurysmal subarachnoid hemorrhage(aSAH)based on gene expression database(GEO)datasets.Methods:Gene datasets meeting the study requirements were screened from the GEO data-base and divided into a patient group with DCI after aSAH and a control group without DCI,and differentially expressed genes(DEGs)analysis,gene ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and gene set enrichment analysis(GSEA)were performed by using R software to find rele-vant genes and pathways.Results:A total 140 differentially expressed genes were identified.KEGG analysis showed that there were 10 significantly enriched signaling pathways(P＜0.05),mainly related to hypoxia-inducible factor-1(HIF-1)signaling pathway,glutamatergic synapses,cell adhesion molecules,and chemokine signaling pathways,etc.Twenty-six significantly enriched entries were obtained according to the functional analysis of GO,which involved entries in three categories,namely,biological processes,cellular components,and molecular functions.GSEA analysis showed that two pathways,extracellular matrix receptor interactions as well as peroxisomes,had significant enrichment differ-ences between the patient group and the control group.Conclusion:The development of DCI after aSAH involves sever-al genes such as COL17A1,RPL11,FCAMR,GNB2L1,HIF1A,and can affect the development of DCI through various pathways such as vascular dysfunction,inflammatory response,neurological injury,and oxidative stress.

Objective:To summarize the clinical and genetic characteristics in patients with transthyretin familial amyloid polyneuropathy (TTR-FAP).Methods:Fourteen unrelated TTR-FAP patients diagnosed at Xuanwu Hospital, Capital Medical University from September 2014 to February 2022 were retrospectively reviewed. The clinical manifestation, electrophysiology, cardiac function, biopsy and gene mutation were analyzed.Results:In the 14 patients (13 males, 1 female) diagnosed as TTR-FAP, the mean age at onset was 53.9 years (range: 33.0-71.0 years), with a mean course from symptom-onset to diagnosis of 4.1 years. The late-onset type occurred in 9 cases. Seven patients had a family history of TTR-FAP. Distal paresthesia of lower limbs was the commonest initial symptom (8 cases), with sensorimotor neuropathy and autonomic dysfunction seen initially in 4 and 2 cases, respectively. Cardiac involvement occurred in 6/8 of the patients. Nerve conduction studies indicated extremely axonal impairment with demyelinating features. Sural nerve biopsies showed moderate to severe axonal loss of myelinated fibers and the positive rate of Congo red staining was 8/14. Of 8 different TTR mutations detected, V50M was the most common (appearing in 5 cases). No obvious neuropathy progression was seen in the 5 patients who received tafamidis and 2 patients died of dyscrasia. Conclusions:TTR-FAP is more common in males, with sensorimotor axonal polyneuropathy, autonomic dysfunction and cardiac subclinical damage as the predominant symptoms. V50M is the commonest mutation. Tafamidis can delay the progression of disability.

Objective:To describe clinical characteristics, genetic mutation and therapeutic response of a family diagnosed as slow-channel congenital myasthenia syndrome (SCCMS) and analyze the factors of the efficacy of channel blockers therapy.Methods:Clinical data and therapeutic response in three patients from a family of SCCMS from Department of Neurology, Xuanwu Hospital, Capital Medical University in May 2017 were collected. The clinical data, mutations and response to therapy of all literature SCCMS cases in the English database of Pubmed and Chinese database of Wanfang until December 31, 2018 were analyzed statistically.Results:The proband was a 48-year-old female who referred to Xuanwu Hospital for limb weakness for 40 years. The proband′s elder daughter presented with onset of the birth and delayed motor milestones, scoliosis and difficulty in walking. The younger daughter was born healthy with normal motor milestones, while fatigue and weakness gradually appeared. The antibodies of myasthenia gravis were negative. No repetitive compound muscle action potentials (CMAP) were detected in three patients. Repetitive nerve stimulation showed decrements. Gene test revealed heterozygous mutation of CHRNE p.εV279F, a known pathogenic mutation of SCCMS. Seventeen SCCMS cases were reported in literature. A total of 20 patients with SCCMS were described in terms of clinical manifestation, mutation, drug therapy and efficacy in detail. According to the literature description, they were divided into significant benefit group and mild to modest benefit group to channel blocker therapy. The age of onset in 10 patients with significant benefit was 1.50 (0.75, 28.25) years from birth to 43 years, and that in 10 patients with mild to modest benefit was 2.50 (0, 6.25) years from birth to 11 years. There was no significant difference between the two groups. The age at the initial channel blocker therapy in the group with significant benefit was (23.40±13.29) years from 12 to 43 years, whereas that in the group with mild to modest benefit was (34.10±13.43) years from 20 to 62 years, and there was no significant difference between the two groups. The delay time of treatment (age at the beginning of treatment with channel blockers-age of onset) in patients with significant benefit was 13.0 (10.25, 15.00) years, which was 32.50 (19.25, 38.00) years in patients with mild to modest benefit ( Z=-3.374, P=0.000). According to the response of cholinesterase inhibitor, eight patients were in the effective group, 10 patients were in the ineffective group and two patients were without cholinesterase inhibitor. The age of onset in the effective group was 0 (0, 4.75) years, while that in the ineffective group was 6.50 (1.00, 28.25) years ( Z=-2.315, P=0.021).The age of treatment with channel blockers was (27.90±12.99) years in the effective group and (32.00±13.21) years in the ineffective group, and there was no significant difference between the two groups. The delay time of channel blocker treatment in effective group was (30.25±11.07) years, while that in ineffective group was (14.30±9.60) years ( t=-3.274, P=0.005). Conclusions:In SCCMS, the effect of channel blockers was related to the delay time of treatment. Channel blocker was more effective the sooner it was started after the onset of symptoms. The average age of onset of SCCMS patients with positive responses to cholinesterase inhibitor was younger, but the delay time of channel blocker therapy was longer, resulting in poor therapeutic effect.

Objective To strengthen the recognition of atypical POEMS syndrome in order to improve diagnosis rate of rare cases of POEMS syndrome. Methods The diagnosis and treatment of a rare case of POEMS syndrome coexisting with Castleman disease but without M protein in serum, urine and bone marrow who was admitted to Xuanwu Hospital, Capital Medical University in November 2017 were retrospectively analyzed with review of the literature. Results The elder male was suspected with a diagnosis of POMES syndrome, but absence of monoclonal plasma cell disease that made it difficult to diagnose. Systemic PET-CT found an active metabolic lesion in left iliac bone. Although the lymph node biopsy had been performed for a diagnosis of Castleman disease, a bone biopsy was also done for a definite diagnosis. Pathological result indicated a plasmacytoma which confirmed a diagnosis of POEMS syndrome without M protein in serum, urine and bone marrow. Literature review suggested that the application of immunofixation electrophoresis was helpful to improve the diagnostic rate of POEMS syndrome. For patients with a suspected diagnosis of POEMS syndrome, bone biopsy, flow cytometry and systemic PET-CT may assist in the search for monoclonal plasma cell. Periphery neuropathy, bone lesion and treatment response were helpful in distinguishing Castleman disease coexisting with POEMS syndrome from Castleman disease without POEMS syndrome. Conclusions When a mandatory major criterion of POEMS syndrome is not sufficient, it should be actively sought, especially for patient with a suspected diagnosis of POEMS syndrome. For patients with multiple lesions, multi-site biopsies are necessary to assist in diagnosis.

Objective To investigate the clinical manifestation and electrophysiological, muscle imaging and pathological, molecular features of oculopharyngodistal myopathy (OPDM). Methods The clinical electrophysiological, muscle imaging and pathological, molecular data was collected from a case of OPDM. Data analysis was conducted together with a literature. Results The onset age of the patient was 25 years old. The sequential order of involved muscle was upper eyelid muscle, external ocular, laryngopharyngeal, facial, distal limb muscle and proximal upper limb. Serum creatine kinase was mildly elevated. Electromyography revealed myogenic changes with demyelinating peripheral neuropathy. Myopathological findings showed myopathic changes with rimmed vacuoles . Muscle image showed that fatty replacement of was more severe in lower legs than in thigh. Posterior muscle was severely involved in lower legs. All known genes responsible for distal and myofibrillar myopathies, vacuolar myopathies, and muscular dystrophies were excluded by targeted next-generation sequencing. Conclusion The case is a sporadic case. OPDM is a disease with a unique phenotype which not only affects muscle but also involves multiple system (demyelinating peripheral neuropathy、heart disease and so on).

The 28th International Conference on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Boston from December 8 to 10, 2017. The conference covered 23 topics, 102 special topics and 446 papers. This article briefly introduces some topics of the conference, involving basic research, clinical research and clinical trials. Among these, basic studies include genetics, cell biology and pathology, and superoxide dismutase1 gene ALS related pathology; clinical studies include the progression of ALS disease, cognitive behavioral disorders, and biological markers.

Myasthenia gravis is an autoimmune disease involving the acquired neuromuscular junction.Vast majority of patients with myasthenia gravis after conventional treatment (acetylcholinesterase inhibitors,plasmapheresis,gammaglobulin,and immunosuppressants) has significantly improved prognosis;but,there is still a small portion of patients had refractory myasthenia gravis,they did not have effective treatment,and their prognosis is poor.Some recent studies suggest that novel immunomodulatory agents,secondary thymus expand dissection,hematopoietic stem cell transplantation may be in force.

ObjectiveTo explore the clinical features and diagnosis of one Kennedy's disease.MethodsOne patient was clinically diagnosed as Kennedy's disease on the basis of the clinical features including slowing progression of disease, symptoms, nervous system signs, electromyography and nerve conduction velocity results and family history. His CAG number from the repetitive CAG sequence in the first exon of androgen receptor gene was determined using PCR.ResultsThe progression of Kennedy's disease is usually much slower. The CPK and testosterone levels increased in patient. EMG revealed neurogenic injury. The numbers of CAG region of the first exon of androgen receptor gene were 51 in the patient.ConclusionDespite its relatively typical manifestations, the definite diagnosis of Kennedy's disease should be made by detecting the number of CAG from the repetitive CAG region in the first exon of androgen receptor gene.

Objective To investigate the clinical characteristics of methylmalonic academia in adolescence cases. Methods 4 cases were diagnosed methylmalonic academia by gas chromatography- masss pectrogram whose clinical, manifestations and treatment process were analyzed. Results The main clinical manifestations in 4 cases with methylmalonic academia were intellect impairment,epilepsy, pyramid signs; 2 of them suffered with hypopsia and optic atrophy, one of them suffered with papilledema. Symptoms were improved after treated with cobamamide and L-carnitine in all the 4 cases 1 months later. Conclusions The main clinical characteristics of methylmalonic academia in adolescence were intellect impairment, epilepsy and pyramid signs. The symptoms could be improved after treatment.

Objective To investigate the clinical manifestions, pathological features and diagnosing methods of Lafora disease. Methods The chnical and pathological features of 5 patients with Lafora disease who were diagnosed by axillary biopsies were systemically studied. The specimen were stained by HE, PAS and AB-PAS methods. Results Four of 5 cases had an onset during adolescence and 1 during adulthood. All cases presented with progressive generalized tonic-clonic seizure, myoclonus and dementia. Emotional disturbance, dysarthria and ataxia appeared in the early course of the disease. Lafora bodys were identified in myoepithelial cells and duct cells of both eccrine sweat glands and apecrine sweat glands in the biopsies of axillary skin. Conclusions Lafora disease could be confirmed by round and oval periodic acid-Schiff- positive inclusions in skin biopsy specimen combined with the proper clinical settings. Both axillary and other skins can be chosen as the sites of biopsy.