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.

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.

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.

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 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.

Objective To investigate the clinical features of patients with acute ST-segment elevation myocardial infarction (STEMI) comorbid with diabetes mellitus (DM) and to analyze the prognosis within 12 months after primary percutaneous coronary intervention (pre-PCI). Methods A total of 375 STEMI patients were divided into the diabetes group (n=140) and the normal blood glucose group(n=235) according to whether they met the diagnostic criteria of DH. The clinical data,characteristics of coronary artery lesions,type of stent implant,rate of coronary slow flow or no-reflow after pre-PCI, and the prognosis within 12 months after PCI of the two groups were investigated.Results Patient in the diabetes group presented with higher mean age ,higher comorbid rates of hypertension , hyperlipidemia and heart function of Killip class Ш and above than patients in the normal blood glucose group (all P<0.05). patients in the diabetes group had higher rates of slow reflow /no-reflow after PCI(12.9% vs.5.5%,P=0.013),higher percentages of 3-ressel disease(40.7% vs. 28.9%,P=0.019)and lef t main lesions(13.6% vs. 7.2%,P=0.044). The in-hospital mortality rates(6.4% vs.1.7%,P=0.020),revascularization rates within 12 months(7.9% vs.0.9%,P=0.001)and incidence of heart failure(7.9% vs. 2.6%,P=0.017)were all higher in the diabetes group. Conclusions STEMI patients comorbid with DM were relatively older, had higher comorbidities of hypertension,hyperlipidemia, three-vessel disease, left main coronary lesions and higher mortality during hospitalization. No significant increase in cardiac death and recurrent myocardial infarction were deserved during the follow-up period. These patients may benefit more from early intervention.

Humans ; Hemolysis ; Lymphoma, Large B-Cell, Diffuse/complications* ; Rituximab ; Pancreatic Neoplasms/complications*