Objective To report filaminopathy with novel insertion mutation in a Chinese family.Methods Total 19 patients from successive 5 generations involved in an autosomal dominant family. The detailed clinical manifestations had been described (Chinese Journal of Neurology, 2008, 41:751-755).The filamin C gene sequencing was performed in 3 patients, 5 family members without symptoms and 50 normal persons. The amplified fragments of the exon 18 in filamin C gene were cloned into pBluesripts vectors, then sequenced and identified with capillary electrophoresis. Results 18-nucleotide deletion and 6-nucleotide insertion were identified in the exon 18 of filamin C gene. The mutation caused the disturbance of the seventh immunoglobulin-like domain in filamin C, leading to the instability of dimmers of filamin C.Another 2 patients in the family had same mutation while 5 family members without symptoms and 50 normal controls were normal. Conclusion The novel nucleotide deletion-insertion in exon 18 of filamin C gene causes filaminopathy. This disease can appear in non-Nordic race.

Objective To report the clinical, myopathological and genetic features in myofibrillar myopathy (MFM) with numerous cytoplasmatic-spheroid bodies. Methods Ten patients in 5 successive generations began to present progressive proximal limbs weakness at 35 to 40 years old. Additionally, 4 cases manifested diarrhea and 6 cases accompanied with cardiorespiratory symptoms. An open biopsy was performed on the proband. In addition to histological, enzymhistochemical staining and ultrastructural examination, immunohistochemical staining with antibody against tau, desmin, ubiquitin, dysferlin, dystrophin-C', dystrophin-N' and dystrophin-R were done. All the exons of the MYOT, CRYAB, DESMIN, LDB3, LMNA, SEPNI gene and the FLNC exon 48 were analysed. Results Cytoplasmatic bodies and spheroid bodies were found in the fibers. The deposited material were positive for tau, desmin, ubiquitin, dysferlin and dystrophin-R, dystrophin-C'. Electron microscope showed granular dense Z-disc material in the inclusions which were surrounded by thin filament. There was no mutation in the above exons of the 7 candidate genes. Conclusions Myofibrillar myopathy involves multiple system impairment. Cytoplasmatic and spheroid bodies contain microtubule and membrane associated protein. The disease might be induced by some unknown genetic abnormities.

Objective To describe the clinical, radiological and genetic features in a family with X-linked Charot-Marie-Tooth disease type 1 (CMT1X) with transient white matter lesions.Methods The proband is a 14-year-old boy who presented transient and recurrent dysarthria, mild numbness and weakness of the limbs for 2 years and 5 months.Later he developed leg weakness.His mother only presented pes cavus.MRI, electrophysiology and nerve biopsy were performed in the proband.Gap junction protein beta 1 (GJB1) gene was analyzed by PCR-sequencing on the proband, his parents and 50 non-illness control women.Results Electremyography showed marked reduced amplitude of the distal compound muscle action potentials and mild decrease of conduction velocities.MRI showed bilateral white matter lesions in centrum semiovale and corpus callnsum, which improved significantly after 6 months.Pathological examination revealed chronic axonal neuropathy and widened Schmidt-Lanterman incisures of myelinated fibers.I20T mutation in GJB1 gene was detected in the proband and his mother, but not in non-illness control women and his father.Conclusions Novel 120T mutation of GJBI maybe could result in CMT1X with predominant recurrent leucocncephalopathy.The white matter changes in MRI are reversibility.

BACKGROUND: Cerebral infarction is commonly associated with blood stasis syndrome. Abnormal alternation of blood rheology is generally manifested as increased blood viscosity and hematocrit (HCT). In isometric hemodilution, a certain amount of red blood cell (RBC) is shifted by bleeding and simultaneously, isometric diluter is supplemented to reduce whole blood viscosity.OBJECTIVE: To observe the improvement of astragalus injection, the Chinese herb for qi tonification and isometric hemodilution on blood rheology in blood stasis syndrome of cerebral infarction.DESIGN: Randomized controlled experiment and case-control analysis were designed.SETTING: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. PARTICIPANTS: In cerebral infarction group (infarction group), 64 inpatients of senile ischemic cerebral vascular disease were collected from Union Hospital Affiliated to Huazhong University of Science and Technology from March 2002 to March 2004. Al l of cases were aged over 60 years and were in conformity with the diagnostic criteria on blood stasis syndrome. According to random number table, routine treatment group (routine group) and the group of integrative therapy of Chinese and western medicine (experimental group) were divided, 32 cases in each one. 47 healthy people of similar age and diagnosed with routine physical examination were selected in normal control. METHODS: In routine group, cerebral infarction was treated with routine therapy, including extending capacity, reducing viscosity, resisting coagulation, blocking aggregation of platelet and dehydration and general symp tomatic supporting treatment. In experimental group, on basis of routine treatment, isometric hemodilution and astragalus injection, the Chinese herb for qi tonification were used. 10% of total blood amount (about 450-650 mL) was collected from vein, and colloid solution of same volume was injected intravenously. The treatment was applied once every 5 days, continuously for 3 times. Astragalus injection 50 mL mixed with physical saline 250 mL was intravenous dropped, once per day, continuously for 3 weeks. MAIN OUTCOME MEASURES: ① Comparison of indexes in bloodrheology before and after treatment in routine group and experimental group. ② Comparison of indexes in blood rheology between normal control and infarction group. RESULTS: According to intention management, 64 patients and 47 normal persons all entered result analysis. ① Comparison between infarction group and normal control: RVB, HCT and PFC (fibrinogen) were higher than normal control [(3.90±0.73), (3.40±0.28) mPa·s; (46.39±6.03) %,(42.61±2.91)%; (3.25±0.75), (3.08±0.46) g/L, P < 0.01, 0.05], MTIE (de formity index of RBC) was lower than normal control (0.958±0.006, 0.961 Shen H,Lu YD.Study on quantitative messurement of immunohistochemical ±0.004, P < 0.05). ② Comparison between routine group and experimental group: Difference in some indexes presented before the treatment. After treatment, RVB, HCT and PFC in experimental grou p were all lower than routine group [(3.90±0.52), (4.21±0.68) mPa·s; (43.80±3.29)%, (48.47±4.50)%; (3.31±0.60), (3.68±0.67) g/L, P < 0.01, 0.05]. CONCLUSION: Isometric hemodilution therapy and astragalus injection reduces blood viscosity, improves blood rheology and alleviates clinical svmptoms of blood stasis syndrome in senile cerebral infarction.

ObjectiveTo investigate expression distribution of mutant connexin 32 (Cx32) protein in human endothelial cells in patients with X-linked Charcot-Marie-Tooth disease type 1 ( CMTX1 ) .MethodsNerve biopsies were performed in 3 patients with CMTX1 and in 3 non-CMTX1 controls. Cx32 mutations of c. 379A ＞ T( I127F), c. 533A ＞ G(D178G) and c. 590C ＞ T(A197V) were identified in these 3 patients respectively.Immunofluorescent (IMF) staining of nerve blood vessel was processed with antibodies against Cx32, Yon Willebrand factor and Cx40. The mutant Cx32 was constructed in pEGFP-N plasmid (pEGFP-N1-Cx32) and was transfected in HeLa cells. Cx32 and GRP78, a marker of endoplasmic reticulum ( ER), were stained by IMF in HeLa cells to investigate expression of mutant Cx32. ResultsIn 3 control cases, Cx32 was visualized by IMF staining as dots along gap junction of vascular endothelial cells,and it was coexisted with Cx40.However, immunoreactivity of Cx32 in 3 patients was predominantly decreased and was not located in endothelial gap junction. The transfection of 3 Cx32 mutants into HeLa cells demonstrated thepathogenic changes.The cells withthemutationc. 379A ＞T found Cx32 accumulations in the cytoplasm; the cells with mutation c. 533A ＞G showed few staining positive dots surrounding the nuclear and the cells with c. 590C ＞ T showed dot-like expression of Cx32 both in the cytoplasmicand cell membrane. The mutant Cx32 was not overlapped with expression of the marker of ER.ConclusionsMutant Cx32 might cause dysfunction of endothelial gap-junctions due to the abnormal expression of Cx32 in level and location in the vascular endothelial cells of CMTX1 patients.

Sixty-six volunteers,including 24 subjects with normal glucose tolerance(NGT),18 patients with impaired glucose regulation (IGR),and 24 patients with type 2 diabetes mellitus ( T2DM ),underwent a test of continuous glucose monitoring.The data of continuous glucose monitoring were embedded into two-dimension Euclid space by Takens' embedding theory.Glycemic phase diagram was drawn by MATLAB.The area and center distance of glycemic phase diagram were calculated by computer.The distinction of glycemic variability and average glycemic level among different glucose regulation populations were analyzed.The results showed that there existed significant differences in body mass index,systolic blood pressure,diastolic blood pressure,low density lipoprotein-cholesterol,high density lipoprotein-cholesterol,triglyceride,total cholesterol,creatinine,and alanine aminotransferase among three groups( all P＜0.05 ).The levels of HbAIC,fasting plasma glucose( FPG ),postprandial 2 h plasma glucse (2hPG),area and center distance of glycemic phase diagram in T2DM group were higher than those in NGT and IGR groups( P＜0.01 ),and the levels of FPG,2hPG,area and center distance of glycemic phase diagram in IGR group were higher than those in NGT group( P＜0.01 ).The levels of FPG and 2hPG were correlated with area and center distance of glycemic phase diagram ( all P＜0.01 ).These results suggest that measuring the area and center distance of glycemic phase diagram is a good method to assess glycemic variability and average glycemic level during continuous glucose monitoring.

ObjectivesTo report pathological and genetic features of 6 Chinese families with Xlinked Charcot-Marie-Tooth disease type 1 ( CMTX1 ).Methods The index cases from 6 families with CMTX1 are males with onset of disease between 11 and 24 years old.All of them had distal leg muscle weakness,accompanied with areflexia and sensory loss in the feet.Additionally,the index 1 presented with recurrent encephalopathy and the index case 5 with cerebellar ataxia.Peripheral neuropathy was found in 12 family members,while other 7 members showed talipescavus and hyporeflexia.Sural nerve biopsies were performed in all index cases.Connexin 32(Cx32) gene was analyzed in the index cases,8 affected and 10unaffected family members as well as 50 healthy women control subjects.ResultsMild to moderate loss of myelinated fiber with axonal degeneration and regeneration clusters were found in all index cases. Thin myelin fibers were found in 5,small onion bulbs in 3 and inflammatory infiltrates in 2.Five novel mutations (I20T,I127F,D178G,A197V,403_404insT) and one L10L synonymous mutation were detected in the 6index cases and their affected family members.The same mutations,in heterozygous state,were detected in 4 female family members without clinical symptoms,but not found in 6 male unaffected family members.The same mutations were not found in healthy control subjects.ConclusionsThe CMTX1 patients in our study present predominantly axonal lesions.Frequent novel Cx32 gene mutations indicated that private mutations may be common in Chinese CMTX1 patients.

Objective To report the development of clinical symptoms in a Chinese family with autosomal dominant progressive external ophthalmoplegia(adPEO).Methods Electromyologram and muscle biopsy were performed in the proband and 4 family members with the disease.Results The proband was a 57 year-old woman,who developed bilateral ptosis after the age of 30,external ophthalmoplegia after the age of 35 years old,weakness of extremities at the age of 37 years old and bulb palsy with palmus at the age of 47 years old.In the family there were 20 male and female members from five generations.All of them complained about bilateral ptosis between 26—33 years old,external ophthalmoplegia(12/15)and weakness of all extremities(14/15)between 35—45,facial and masticatory weakness(9/9)as well as dysphagia(8/9)between 44—60,accompanied with heart lesions(4/7)after 50 years old.Some patients died due to cardiac impairment.Electromyologram showed myopathic abnormalities in the examined patients. The main myopathological changes were ragged red fibers,cytochrome c oxidase negative fibers and ragged blue fibers in succinate dehydrogenase staining.Conclusions The adPEO started from extra-ocular muscles to limbs,finally facial and bulbar muscles.Heart lesions were presented in late stage and lead to death in some members.The developing process of symptoms suggested that we should pay more attention to cardiac manifestations in this disease.

Objective To investigate the axonal lesion in chronic inflammatory demyelinating polyneuropathy(CIDP).Methods Eighteen patients had undergone sural nerve biopsy.The clinical and electrophysiological distinction based on the different pathological changes were analyzed.Results Five patients with demyelination predominance which presented myelinated fiber with thin myelin.Three of them showed also mild axonal degeneration.Eight patients with axonal lesion predominance which presented Wallerian degeneration and regeneration of myelinated fibers.Three patients with mixed myelin and axon lesion of myelinated fibers and two with mild lesion.There was no significant difference between CIDP predominantly with axonal lesion and demyelination.Electrophysiological examination shows both axonal lesion and demyelination feature in some of the 2 types patients at the same time.Conclusions Axonal lesion is a common pathological change in CIDP and should not be considered as an exclusive criterion in diagnosis of the disease.Infiltration of macrophages is a common change.

To summarize the clinical characters of optic neuritis caused by antituberculosis drugs, and to discuss the prevention countermeasures.
● METHODS: The clinical characters of optic neuritis caused by antituberculosis drugs among those outpatients and ward patients from January 2003 to January 2013 were reviewed and analyzed.
● RESULTS: Optic neuritis caused by antituberculosis drugs was rare ( 17 / 60000 ), while retrobulbar neuritis was common. The drugs inducing optical neuritis were mainly ethambutol, followed by isoniazid and streptomycin. The vision of patients would have different degrees of improvement via the following treatment after specific diagnosis, i. e. , timely stopping the tuberculosis medicine associated with optic neuritis, and taking vitamin supplements, dilating blood vessels and applying hormone therapy according to the illness.
●CONCLUSlON: We should pay attention to the change of the vision of patients during the usage of antituberculosis drugs. ln the case of sudden eyesight deterioration, ophthalmology examination and timely treatment are advised preventing blindness.