Mild malformation of cortical development with oligodendroglial hyperplasia: a new pathological subtype of frontal lobe epilepsy / 中华神经科杂志

Objective To analyze the clinical and histology characteristics of a patient with frontal lobe epilepsy diagnosed with mild malformation of cortical development with oligodendroglial hyperplasia, and to recognize the new neuropathological entity. Methods Clinical history, seizure types, neuroimaging, electroencephalography as well as macroscope, histology and immunohistochemistry characteristics were collected from a frontal lobe epilepsy patient and were compared with cases from literature. Results It was a female patient aged 16 years with 12 years history of epilepsy. The seizures manifested as episodes of conscious loss with automatism including grope and voice lasting for seconds. About 10 episodes a day were found and sometimes with secondary generalized tonic-clonic seizures. MRI showed blurring of grey-white matter interface in left orbital frontal cortex. Video-encephalography revealed left frontal lobe origin of seizures. So left prefrontal lobe was removed. Histology showed almost normal cortex neuropil and neurons. Blurring of grey-white interface in some area with patches of proliferation of oligodendrocytes in the corresponding sub-cortical white matter was found. The density of oligodendrocytes was significantly higher in sub-cortical than in deep white matter both shown in HE and Oligo-2 staining. Obvious oligodendrocytes increase and satellite phenomenon in deep cortical layer as well as increased ectopic neurons in sub-cortical white matter were found in the lesion. In proliferation area, there were some nuclei stained with Ki-67, but not as high as tumor. Subsequent follow up for two years proved the operation efficacy and benign prognosis. Conclusions There are special and undiscovered histopathological entities in epilepsy etiology. Although known as grey matter disease, white matter pathology plays an important role in epilepsy pathophysiology which needs further research.

Clinical and muscle pathological study of 21 juvenile myositis patients with perifascicular atrophy changes / 中华神经科杂志

Objective To describe the clinical and muscle pathological characters of juvenile myositis patients with perifascicular atrophy (PFA).Methods A series of 21 consecutive muscle biopsies with clinically and pathologically confirmed juvenile myositis were studied.All biopsies had PFA of muscle fibers.Results Clinical manifestation:11/21 had typical dermatomyositis rash,9/21 possible dermatomyositis because of atypical rash,1/21 mixed connective tissue disease;9/21 had weakness complaint;9/21with normal creatine kinase (CK) level,4/21 low grade rise,8/21 apparently elevated,10/ 11 definite dermatomyositis patients with normal or low grade level;6/21 combined with interstitial lung disease,2 with EB virus infection,1 with cytomegalo virus infection.Muscle pathology:4 specimens with atypical PFA also had enzyme abnormality in nicotinamide adenine dinucleotide,succinate dehydrogenase and cytochrome c oxidase staining,9/12 cases had membrane attack complement deposition intramuscular capillaries,and they had prominent regional mitochondrial abnormalities,protrude PFA and focal muscle damage.Skin biopsy of one case showed perivasculitis in dermis.Conclusions PFA could be seen in juvenile dermatomyositis and mixed connective tissue disease,and PFA could not increase the CK level.The capillary and intermediate-sized vessels damage may cause chronic ischemia,which could explain the PFA with mitochondrial abnormalities.

Clinical manifestations and gene diagnosis of collagen type Ⅵ related myopathy / 中华神经科杂志

Objective To summarize the clinical presentations, the findings of lab tests and procedures and the genetic investigation of collagen type Ⅵ related myopathy, and to help clinicians recognize and diagnose this rare disease.Methods Seven familiar or spontaneous collagen type Ⅵ related myopathy patients diagnosed by gene detection were analyzed.We emphasized on the features of clinical manifestations, serum creatine kinase level, electromyography, lower-limb muscle MRI, muscle biopsy and correlation between genotype and pZenotype.Results Among 7 patients, 3 were caused by COL6A1 mutation, 1 was caused by COL6A2 mutation and 3 were caused by COL6A3 mutation.Two patients were familiar wZile 5 were spontaneous.HigZligZted clinical presentations were proximal weakness in lower limbs and joint contrature.Serum creatine kinase level was sligZtly elevated.ElectromyograpZy sZowed sligZt myogenic damage.Muscle MRI of tZigZ sZowed distinct pattern of muscle involvement.Muscle patZology revealed dystropZic myogenic cZanges with proliferation of connective tissue between muscle fibers.Conclusions Neurologists should recognize the features of collagen type Ⅵ related myopathy, such as progressive weakness, early-onset joint contraetures, slightly elevated serum creatine kinase and selective muscle involvement on leg MRI scan, and then perform next-generation sequencing based genetic test on suspected patients.This approach would improve the diagnostic rate of the disease.

Microarray-captured next-generation sequencing as a diagnostic platform for detecting small mutations in Duchenne muscular dystrophy / 中华神经科杂志

Objective To set up a new diagnostic platform based on microarray exon-capture and next-generation sequencing for detecting small mutations in dystrophin gene.The sensitivity and specificity of the method were assessed in clinical settings and the distribution of small mutations in Chinese Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) patients were also analyzed.Methods Forty-one DMD/BMD patients diagnosed by the clinical criteria without large deletion or duplication (≥ 1exon) were recruited from Peking Union Medical College Hospital consecutively.Genomic DNA was extracted from blood samples.The libraries were prepared.Then exon and intron-exon flanking sequences of DMD gene were captured by custom microarray.Targeted next-generation sequencing and Sanger Sequencing were conducted.The patients who were not detected any disease-causing mutation were performed muscle biopsy.Results Thirty-eight subjects were detected small mutations in DMD gene.All single nucleotide variants (SNVs) and insertion & deletions (INDELs) were validated by Sanger sequencing.Twenty-one novel mutations were reported.The distribution of SNVs and INDELs was similar to other international DMD databases.Upon immunohistochemistry staining of dystrophin protein,1 of 3 mutation-undetected patients was diagnosed as DMD,2 of them were excluded.The specificity of the method was 100％,while the sensitivity was 97.4％.Conclusions Our microarray-captured next-generation sequencing assay could detect SNVs and INDELs with high sensitivity and specificity.Its advantages are economic,time-saving and stable.The platform is suitable for clinical gene diagnosis.

The diagnostic significance of superficial peroneal nerve and peroneus brevis muscle biopsy: a clinicopathological report of 15 cases / 中华神经科杂志

ObjectiveIn an attempt to clarify the usefulness of combined nerve and muscle biopsy in the diagnosis of neuromuscular disease when compared with traditional sural nerve biopsy.Methods Fifteen biopsies of superficial peroneal nerve (SPN) and peroneus brevis muscle ( PBM ) by one incision performed within one neurological clinic were reviewed.All patients had peripheral neuropathy while 3 of them had myopathy clinically.The diagnostic significance of SPN and PBM biopsies were classified into 3 grade: essential,helpful,no value.ResultsOf 15 SPN and PBM biopsies,7 showed essential pathological findings whichreachedthe etiologicaldiagnosis, including 5definitevasculitis, 1inflammatory demyelinating polyneuropathy and 1 amyloid neuropathy.Five biopsies are helpful for etiological diagnosis,including demyelinating neuropathy,mild inflammation,and microvascular lesion,et al.Three biopsies are of no value for etiological diagnosis which only have nonspecific change such as type 2 fiber atrophy,neurogenic atrophy and axonal degeneration et al. Finally,SPN and PBM biopsies made the definite etiological diagnosis possible in 12 patients.ConclusionsSPN and PBM biopsy improved the yield of specific pathological and etiological diagnosis of neuropathy and myopathy such as vasculitis and amyloidosis with minor trauma and side effect.Further clinical and pathological studies will be necessary for a better practice of combined nerve and muscle biopsy.

The clinical and muscular pathological study of dermatomyositis with perifascicular atrophy changes / 中华内科杂志

ObjectiveTo investigate the clinical and pathological characteristics of dermatomyositis with muscular perifascicular atrophy (PFA).MethodsA series of 104 consecutive patients clinically and pathologically diagnosed as dermatomyositis by muscle biopsy in our laboratory from December,2003 to August,2011,were enrolled in this study. Muscle biopsy of all the enrolled patients had shown PFA of muscle fibers.ResultsAmong the 104 patients,34 were males and 70 were females with a mean age of 45 years old.Among them,8 cases had normal electromyogram;42 had normal serum creatine kinase level;11 were diagnosed as carcinoma;75 were found to be combined with interstitial lung disease (ILD).Based on morphologic changes of muscle biopsy,they were divided into pure PFA group with 54 cases and PFA plus focal damage group with 50 cases.Compared with the pure PFA group,there was prominent mononuclear cell infiltration into perimysial intermediate sized vessels and membrane attack complement (MAC) deposition in the intramuscular capillaries in the PFA plus group.Skin biopsy had been taken in 12 cases together with muscle biopsy and had shown the border effectof both PFA and interface dermatitis in muscle and skin.ConclusionsOur study suggests that chronic immune vascular damage and insufficiency in dermatomyositis may cause ischemia and focal myofiber damage in watershed regions. The incidence of ILD in our dermatomyositis patients with PFA is high.

Diagnosis of intracranial germinoma by cerebrospinal fluid cytology: a report of 8 cases / 中华神经科杂志

Objective To investigate the value of the cerebrospinal fluid ( CSF ) cytology in diagnosis of intracranial germinomas by reviewing the outcomes of CSF cytology of 8 patients with intracranial germinomas. Methods Eight patients with positive CSF cytology at our clinic from January 2006 to June 2009 were reviewed. Conventional cytology and immunocytochemistry of CSF were performed. The relevant literature on the subject was reviewed. Results The patients, including 7 male and 1 female, developed endocrinological or neurological symptoms at the age of 13 to 25, and the typical neurological presentation included vertigo, headache, mental and behavior disorders, double vision and weakness of legs. The CSF cell count ranged from 0 to 300 leukocytes per cubic and elevated in 7 cases, typically lymphocytic inflammation. CSF level of human chorionic gonadotropin was 3.2-1087.0 mIU/ml, higher than the individual serum level. On CSF cytology studies, typical tumor cells of germinima were found, which had positive particles in cytoplasm on periodic acid Schiff stain. All presents had lymphocyte inflammation ( small lymphocyte predominant ). On immunocytochemical studies of CSF, the tumor cells were positive on placental alkaline phosphatase and Ki-67 stains. Conclusions CSF cytology is clinically useful for diagnosis of primary intracranial germinoma. Further clinical and cytological studies will be necessary for a better understanding of the biology of these tumors.

Clinical and pathological features of 20 patients of glycogen storage disease type Ⅱ / 中华神经科杂志

Objective To summarize the clinical and pathological features of glycogen storage disease (GSD) type Ⅱ. Methods The clinical and pathological data of the 20 GSD type Ⅱ patients were reviewed. Results One patient with infantile-onset mainly presented hypotonia, muscle weakness, feeding difficulties, pulmonary infection and cardiomyopathy insufficiency and increase of serum creatine kinase (778 IU/L) and echographic evidence of hypertrophic cardiomyopathy were detected. Electromyography studies indicated a definite myopathy. Nineteen cases were late-onset, presenting a slowly progressive proximal myopathy with truncal involvement or with symptoms dominated by respiratory insufficiency. Not all muscles were equally affected. Increase of serum creatine kinase (208-2600 IU/L) was detected in 14 patients and normal level in 1 patient. Electromyography studies indicated a definite myopathy in 9 patients,with abnormal irritability in 1 patient and susceptible in 4 patients and myotonic discharge in 1 patient and no abnormalities in 2 patients. Echographic evidence of thickening of the interventricular septum and pulmonary hypertension were detected in 2 patients respectively. The common light microscopic feature of all case was a vacuolar myopathy with high glycogen content and acid phosphatase activity in the vacuoles. Conclusions GSD type Ⅱ often presents slowly progressive myopathy which often affect the toro and respiratory muscles.In most patients the serum creatine kinase level is elevated slightly. Muscle biopsy is of use to make the definite diagnosis of this disease.

Single nucleotide polymorphism associated with Chinese sporadic amyotrophic lateral sclerosis patient / 中华神经科杂志

Objective Amyotrophic lateral sclerosis(ALS)is a progressive paralytic disorder resulting from the degeneration of upper and lower motor neurons.Sporadic ALS(SALS)accounm for majority of patients.ALS is a kind of complex disorder.There were several single nucleotide polymorphism (SNP)reported to be associated with SALS in recently published genome-wide association(GWA)study,but there are few data from Asia ALS population and no report focus on SNP which may associated with SALS of Chinese origin.Our study is to screen and add the SNPs related to the risks of SALs in Chinese.Methods Eighty-six individuals with SALS and 94 matched controls were recruited for our study and genomic DNA from blood samples was extracted.Genotypes were determined by a matrix assisted laser desorption/ionization time of flisht mass spectrometry based approach followed by association analysis. Results Individual genotype data for 8 SNPs,rs6700125,rs10260404, rs1942239,rs2279812,rs2405657,rs558889,rs6922711 and rs935 1470 in Chinese population showed no significant association with sporadic ALS.Combining genotype data from published GWA,rs1942239 gained in strength of allelic association(P value decreased to 9.07×10-5 from 1.48×10-4),and rs558889 deviated Hardy-Weinberg equilibrium at ALS case group which may be associated with susceptibility.Conclusions SNP rs1942239 and rs558889 may contribute to susceptibility of sporadic ALS in Chinese patient.The larger sample studies are warranted to confirm the association.

Immunohistochemistry and Western blot for diagnosis of benign muscular dystrophy related with dystrophin / 中华神经科杂志

Objective To investigate the value of the immunohistochemistry and Western blot in the diagnosis of the benign muscular dystrophy with abnormal dystrophin expression.Methods The medical histories and clinical manifestations of 4 patients were collected.In addition to routine histological and histochemical studies,expression of dystrophin in muscle fibets was observed by immunohistochemical reaction(dys-N,dys-R and dys-C)and Western blot to anti-dystrophin antibody.Results Two patients had muscular weakness while another 2 patients had only muscular pain and elevated creatine kinase blood levels without muscular weakness.Histochemical stains showed atrophy,hypertrophy and fiber splitting in 2 patients,while only variation in fiber size was presented in anothor 2 patients.One patient had no reaction for dys-N,but had immunostains for dys-C and dys-R in the sarcolemma of muscle fibers.Western blot confirmed that the band of dys-C and dys-R was partly deficient,and the band of dys-N was absent compared with control.Three patients had no reaction for dys-R,but had immunostains for dys-C and dys-N.Compared with control,Western blot confirmed that the band of dys-R was absent,and the band of dys-C and dys-N were truncated.Conclusion The immunohistochemistry is stained with three anti-dystrophin antibodies to avoid diagnostic errors.Western blot is essential to further determine the type of dystrophin protein.

Screening of mutations in superoxide dismutase 1 gene in Chinese with familiar amyotrophic lateral sclerosis / 中华神经科杂志

Objective To identify the mutations in Cu/Zn superoxide dismutase ( SOD1 ) gene in three Chinese kindreds with amyotrophic lateral sclerosis ( ALS), compare the genotypes with those found in other ethnic groups and to analyze the clinical characteristics.Methods The diagnosis of ALS met El Escorial ALS diagnostic criteria.Genomic DNA was extracted from peripheral blood in ALS patients using standard procedure.PCR amplifications of five exons of SOD1 were performed using primers as described in the previous publication.The PCR products were directly sequenced.Results A heterozygous mutation H46R was found in four affected members in a family with middle age onset and slowly progressive ALS.A heterozygous mutation of G72C was identified in a 20-year-old male who died of respiratory failure after two years of ALS.His father carried the same mutation without clinical phenotype.In the third family with 20affected members with middle age onset and rapidly progress, a mutation of E13V was identified in 5 affected subjects.Conclusions This study is the first large screening of SOD1 mutation in Chinese familiar ALS patients.H46R has previously been found only in Japanese and Pakistanis; this is the first report in Chinese, suggesting H46R may be specific to Asians.The family with mutation G72C presented decreased penetrance, therefore screening SOD1 mutation in sporadic cases and unaffected family members is necessary.E133V is the first reported mutation and needs more study to investigate its effect on the disease.

Diagnosis of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes / 中华神经科杂志

Objective The clinical,laboratory,and neuroradiologic features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) were analyzed and early clinical diagnosis was proposed.Method The various presentations of 34 MELAS patients were summarized to identify the specific symptoms and signs.The appropriate interpretation of the ancillary examinations,including lactic acid levels of blood and cerebral spinal fluid,neuroradiology,muscle biopsy and genetic test,was emphasized.the diagnostic significance and limitations of clinical,laboratory and neuroradiologic features were pointed out.Result The most common clinical presentations were listed in order of frequency:seizures,headache,mental decline,stroke-like episode,development abnormality,muscle weakness,fatigue,and ophthalmoplegia.Raised fasting or post-exercise blood lactic acid levels were found in 23 patients (67.6%).The most common lesions were located in the occipital lobe,parietal lobe,temporal lobe,basal ganglion,frontal lobe,cerebellum and deep white matter of 32 patients.Ragged red fibers were found in 24 patients (75%),and 8 other patients had negative muscle biopsy.Fourteen patients underwent genetic test,of which 9 patients had point mutation at 3243.Conclusion It is feasible to have early recognition of the various presentations of MELAS and make an early diagnosis even before the stroke like episodes.

Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients / 中华神经科杂志

Objective To investigate whether the polymorphism of rs10260404 in DPP6 gene in Chinese Han origin is associated with sporadic amyotrophic lateral sclerosis (SALS). Methods The genomic DNA was extracted from the leukocytes of whole blood samples in 58 Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was processed in the presence of an unlabeled probe that contained the rs10260404 locus. The product was genotyped on light scanner and some was confirmed with sequencing. Results Two single nucleotide polymorphism, rs10260404 that was reportedly consistently strongly associated with susceptibility to SALS in different populations of European and American ancestry, rs10260404 were genotyped, but not strongly associated with ALS in Chinese patients(SALS:C:12.94%,T:87.06%;health controls:C:10.58%,T:89.43%;χ2=0.29,OR=1.256,95%CI 0.549-2.872, P>0.05). Conclusion The rs10260404 is not associated with ALS susceptibility in Chinese people.

Effect of pregnancy and spontaneous delivery on the morphology of levator ani muscle and expression f vaginal nerve fibers / 中华妇产科杂志

Objective To investigate the effect of pregnancy and spontaneous delivery on the morphologic characteristics of the levator ani muscle and innervation of the vaginal mucosa. Methods Eight nullipara without pelvic floor dysfunction (PFD) and 64 normal primipara undergoing spontaneous delivery were enrolled in this study during July to December 2006 in Peking Union Medical College Hospital. Biopsy specimens of levator ani muscle (LAM) and anterior and posterior vaginal walls were obtained from the puerpera as well as from the 8 nullipara undergoing vaginal operation. The structures of LAM were examined with histological techniques. Vaginal mucosa specimens were examined using immunohistochemistry staining for protein gene product 9. 5 ( PGP 9. 5), vasoactive intestinal poptide (VIP) and ne uropeptide Y ( NPY),and the positive stained nerve fibers were calculated respectively. Results The LAMs of the puerpera undergoing spontaneous delivery presented myogenetic and neurogenetic changes, both acute and chronic.Type Ⅰ muscular fibers were predominant(79% )with both types increasing in diameters [ (86±9)μm and (79±15) μm]. Significantly different ( P < 0. 05 ) innervation of PGP 9. 5, VIP, and NPY nerve fiberswas observed between epithelial lamina of anterior vaginal wall(5.9±3. 3, 7. 6±3. 1 and 8. 2±3. 2, respectively) and that of posterior vaginal wall (3. 8±2. 9, 5.9±3. 1 and 6. 0±3.0, respectively), with the nerve fibers being more in epithelial lamina of anterior vaginal wall, while no difference in the innervation of nerve fibers was observed in the lamina propria. Significantly different( P <0. 05 ) innervation of PGP 9. 5 and VIP nerve fibers was observed in the lamina propria of the anterior vaginal wall in puerperal undergoing vaginal delivery (6.9±3.2 and 4.9±2. 1) compared with those in nullipara (3.9±3.6 and 3. 1±1.2). Conclusions Pathologic changes occur in LAMs and pelvic floor nerves during labor and delivery. LAM fibers become hypertrophy to adapt to the physiological changes during pregnancy. Richer innervation of PGP 9. 5 and VIP nerve fibers in the lamina propria of the anterior vaginal wall in puerpera undergoing spontaneous delivery is beneficial for dilation of the blood vessels and smooth muscles and makes preparation for delivery.

Skin nerve biopsy in the diagnosis of peripheral neuropathy / 中华神经科杂志

Objective To find out a reference range of epidermal nerve fiber density in normal humans and compare the concordance between clinical features, electrophysiology and the results of skin biopsy. Methods Fifty-one patients with peripheral neuropathy and 10 normal controls were studied. Skin biopsies were obtained from distal leg and/or proximal leg and nerves identified using immunohistochemistry with antibody against protein gene product (PGP) 9. 5. Forty-one in 51 performed routine nerve conduction vdocity and electromyography, 21 in 51 performed sympathetic skin response(SSR). The concordance of the consequences was compared. Results Intraepidermal nerve fiber density (IENFD) was (21.4 + 2. 7) /mm in thigh and (15.4±2. 2) /mm in the distal part of the leg in normal controls. IENFD was (15.0± 6. 3)/mm and (8. 1±5.9) /mm in patients. The intraepidermal nerve fiber density was significantly lower in the patients than in the normal controls both in proximal (t = 2. 976, P = 0.004) and distal legs (t= 3.191, P=0.002). Forty-eight out of 51 patients showed abnormalities in skin biopsy, among which 33 patients had length-dependent neuropathy. In the group of abnormal skin biopsy, 41 received routine electrophysiology, among which 21 (51.2%) were abnormal and they were performed SSR, turning out that 17 (81.0%) were abnormal. In 29 patients who had only small fiber neuropathy, 27(93. 1%) showed abnormalities in skin biopsy, out of whom 20 were performed routine electromyography, and it identified that 6 (30. 0%) were abnormaL In 14 receiving SSR, 11 were abnormal. Conclusion Skin biopsy is safe and tolerable, which has a higher sensitivity especially in small fiber neuropathy.

Study of morphological changes in levator ani muscle of patients with stress urinary incontinence or pelvic organ prolapse / 中华妇产科杂志

0. 05) . The muscular fiber density of levator ani muscles in SUI and POP groups was decreased, fibers were arranged in disorder and separated by large quantities of dense connective tissues with infiltrating inflammatory cells. The muscle fiber fascicles showed obvious grouped denervative atrophy, fiber type grouping and angular in shape. And also there was myopathic degeneration such as centrally located nuclei, peripheral phagocytosis and vacuolated necrosis. Conclusions There are both neurogenic and myopathic alterations in levator ani muscle's structure in patients with SUI and POP. The presence of both acute and chronic abnormalities indicates that the weakness of pelvic floor is a consequence of prolonged denervation.

Evaluation of lipid accumulation in muscle fibers in inflammatory myopathies / 中华神经科杂志

Objective To study the frequency and correlate factors of lipid accumulation in muscle fibers in inflammatory myopathies Methods Muscle biopsy specimens were routinely processed for histopathological and histochemical studies Excepting inflammatory changes, lipid droplets were observed by ORO staining According to the amount of lipid droplets in the muscle fibers, these cases were separated into two groups, and then the differences in muscle power, serum CK level, morphologic changes of muscle, courses and corticosteroids administration between two groups were compared Results 37 7% specimens showed lipid accumulation in muscle fibers distinctly As compare with the lipid normal group, in the lipid increasing group, the generalized muscle fiber degenerating were more common and muscle weakness were more prominent Although more patients have long term therapy with steroid in lipid increasing group, there were no significant differences between these two groups Conclusions Lipid accumulation in muscle fibers was present in some patients with inflammatory myopathies Increasing of lipid droplets might result from the muscle fiber degenerating and might turn to impair the muscle function reversely