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 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.

OBJECTIVETo explore the strategy of pediatric intractable epilepsy surgery.

METHODSThe clinical data of 96 pediatric cases with intractable epilepsy and epilepsy syndromes underwent surgical treatment from April 2004 to April 2006 were retrospectively analyzed.

RESULTSThe surgical treatments were performed based on the results of comprehensive data from neurological, neurosurgical and pediatric departments. Among of them, 78 cases were performed with curative procedure, 17 cases with palliative procedure and 1 case with stereotactic damage procedure. The surgical effect was judged with Engel's standard, 58 cases had no seizure during 14 to 26 months follow-up, 26 cases had significantly improved in seizure control and the total efficiency was 87.5%. 81 cases had improvements in neuropsychological tests. 22 cases had postoperative complications such as neuro-dysfunctions and 15 cases were gradually recovered after the period of follow-up ended, 1 case died of CSF over drainage after operation 3 months.

CONCLUSIONSPediatric patients with symptomatic epilepsy and epilepsy syndromes are suitable to surgical treatment, the results are satisfactory in seizure control and neuropsychological function tests.

Adolescent ; Child ; Child, Preschool ; Epilepsy ; surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Retrospective Studies ; Treatment Outcome

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.

Objective To assess retinal arteriole stenosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to evaluate the relationship between retinal arteriole stenosis with cranial MRI changes and clinical features. Methods Sixteen CADASIL patients (mean age was (43.4±8.1)years, mean duration was(4.7±3.4)years)and sixteen age matched healthy individuals were enrolled. Mini-Mental State Examination (MMSE) and modified Rankin scale scoring were performed in 16 patients. Cranial MRl with Coulthard scores was assessed on CADASIL patients as well. Retinal examinations for arteriole stenosis were done for each subject. Bivariate correlations (Kendall's tau-b) were used to assess the relationship among the grade of retinal stenosis, MMSE, modified Rankin seale, cranial MRI with Coulthard scores and age. Results Retinal arteriole stenosis presented in 15 cases. in whom 4 cases showed mild arterio-venous nicking. while it only presented in 2 controls. Grade 0.Ⅰ, and Ⅲ of retinal arteriole stenosis are noted in 1/16,4/16,7/16 and 4/16cases respectively. Coulthard scores of cerebral MRl were 6.0.19.0.25.1 and 29.8 respectively from Grade 0 toⅢ of retinal arteriole stenosis. The correlation coefficient of retinal arteriole stenosis and cranial MRI scores was 0.743(P＜0.001＝,MMSE-0.429(P＜0.05＝,modified Rankin scale 0.437(P＞0.05).and age 0.299(P＞0.05).Conclusion Retinal arteriole stenosis is significantly correlated with lesion in cranial MRI and dementia.

Objectives To report clinical,electrophysiological and pathological features of myopathy with tubular aggregates.Methods The onset of the disease was between 5-50 years old in the 6 sporadic male cases.Skeletal muscle biopsy was performed for all cases.Specimens were examined histochemically,enzymhistochemically and electromicroscopically.Results Case 1 and 2 presented with limb girdle myasthenic syndrome.The case 1 developed exercise-induced cramps in the late stage.Case 3 complained about persistent weakness and Dopa-responsive dystonia.Case 4 and 5 were characterized by periodic paralysis.Case 6 showed exercise-induced cramps.Serum potassium was normal in all patients. Slight elevation of serum creatine kinase appeared in 3 cases.Electromyography showed neurogenic pattern in case 1 and 6,myogenic changes in case 4 and 5,and no abnormality in other 2 cases.Marked decrement of active potential amplitude was noted with low frequency repetitive nerve stimuli in case 1 and 2.Four percent to forty percent of muscle fibers showed focal material accumulation in the fibers,which involved mainly type 2 fibers in all cases.The material was stained bright red material with modified gomori trichrome,intensive staining with nicotinamide adenine dinucleotide-tetrazolium reductase,lack activity of succinate dehydrogenase and ATPase.Electron microscopy confirmed bundles of parallel micro-tubular structure in the muscle fiber.Conclusions Myopathy with tubular aggregates has various clinical subtypes and electromyographic pattern.Dystonia or other systemic symptoms could be noted in this disease.The limb girdle myasthenic syndrome can also be accompanied with exercise-induced cramps.

Objective To describe the changes of cell development associated contracture and structure proteins in vascular smooth muscle cells (VSMCs) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods The clinical manifestation of probands in 6 families showed the recurrent cerebral ischemic event. A part of patients showed dementia. The genetic analysis in all probands showed Notch3 gene mutation. All probands received the sural nerve biopsy. The primary antibodies against α-smooth muscle actin, smooth muscle myosin heavy chain, desmin and vimenfin were used in immunohistochemistry staining on all of them. Results VSMCs showed hypertrophy or atrophy in the arterioles with different caliber. The granular osmiophilic material (GOM) could be found within the basal lamina of arteriole VSMCs in all of the probands. The expressions of α-smooth muscle actin and smooth muscle myosin heavy chain were partly lost, negative or unevenly distributed in the VSMCs in the arteriole. The expression of desmin showed also unregular distribution or partial loss. The expression of vimentin was partly enhanced. Conclusions The VSMCs show the physiological features of synthetic configuration, indicating the hypoplasia of VSMCs in the arterioles of CADASIL. The VSMCs of the larger arteriole were more severely involved.

Objective To report the clinical, pathological and genetic features in a Chinese family with distal hereditary motor ueuropathy type Ⅴ (dHMN-Ⅴ). Methods Four men and 5 women in 4 generations were involved. The onset of disease was from 13 to 40 years old. Six of them showed predominantly weakness of low extremities. Two women had only weakness and atrophy of hand muscle and 1 woman presented additionally pyramidal signs. The proband, a 20 year-old girl, presented asymmetrical atrophy and weakness of both hands since 13 years old. She had weakness of low extremities after 15 years old. Neurogenic changes were observed in the electromyography. Amplitude of compound muscle action potentials were markedly reduced, while the motor nerve conduction velocity were mildly decreased. Sensory nerve conduction velocity and amplitude of action potential were within the normal range. Sural nerve biopsy was performed in the proband. Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene were sequenced in the proband and other 4 patients. Results Nerve biopsy showed mild loss of myelinated fibers with a few regeneration cluster of myelinated fibers. DNA analysis revealed a heterozygons 263A→G mutation in exon 3 of BSCL2 gene. Conclusions dHMN-V has been genetically and clinically confirmed in this family. The phynotype is obviously heterogeneous in onset time and clinical symptoms within the same family. The patients present mild pyramidal tract signs and axonal lesions in the sensory nerve.

Objective To report clinical,myopathological and genetic features in a family with oculopharyngeal muscular dystrophy(OPMD).Methods The proband,a 60 year-old man,presented proximal weakness of both lower limbs since 50 years old.He developed dysphagia and dysarthria after 53 years old and mild exophthalmos with ptosis after 57 years old.The serum creatine kinase was mildly elevated.Electromyography showed neurogenic involvement and the nerve conduction velocity decreased 20%-143%.Other 5 members in 3 generations developed also dysathria after 45 years old.followed by ptosis 4-20 years afterwards.Three of them showed mild limb weakness.Muscle was biopsied in the proband and specimen was examined with histological,enzymhistochemical,immunohistochemical stainings (first antibody were anti.desmin and ubiquitin antibedies) and ultrastructural examination.PABPN1 gene was sequenced in the proband and 18 family members.Results Rimmed vacuoles with ubiquitin positive material appeared in the muscle fibers.Additionally.there were a few angular atrophic fibers in small groups,COX negative fibers and desmin positive regenerative fibers.Intranuclear palisading filamentous inclusions were observed electromicroscopically in 3% of the nuclears.(GCG)6in PABPN1 was expanded to (GCG)9 in the proband and 11 members.Conclusions The onset symptoms is pharyngeal weakness in OPMD due to heterozygous expanding of PABPNl(GCG)9,accompanied with demyelinating neuropathy.Intranuclear inclusions are also identified in Chinese patient.

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.