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Ommaya reservoir implantation is generally used in the treatment of hydrocephalus and intraventricular drug administration. Ommaya reservoir implantation in the subarachnoid space of the spinal cord for the intrathecal drug administration has not been carried out in China, and only several reports can be retrieved from PubMed. About 60%-90% of untreated patients with spinal muscular atrophy type 2 (SMA2) who survive to adulthood often have complex scoliosis and joint deformities. Nusinersen is an effective drug for the treatment of SMA2. And the route of administration is intrathecal injection, which is difficult for patients with severe scoliosis. This article summarizes the process of Ommaya reservoir implantation and postoperative drug administration in a patient with complex scoliosis type SMA2, which provides a new method for clinical treatment of this disease.
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ObjectiveTo investigate the association between spontaneous portosystemic shunt (SPSS) and hepatorenal syndrome (HRS) in patients with liver cirrhosis. MethodsA retrospective analysis was performed for 93 patients with SPSS from Dezhou Hospital, Qilu Hospital of Shandong University, from January 2015 to January 2022, and the patients were followed up for 12 months with the onset of HRS as the observation endpoint. According to the presence or absence of HRS, the 93 patients with SPSS were divided into HRS group with 38 patients (40.86%) and non-HRS group with 55 patients (59.14%), and the two groups were compared in terms of clinical data, laboratory data, complication, and shunt diameter. Based on the maximum shunt vein diameter of 1.5 cm, the 93 patients with SPSS were divided into high shunt group with 52 patients (55.91%) and low shunt group with 41 patients (44.09%), and with the onset of HRS as the observation endpoint, the two groups were compared in terms of the incidence rate of HRS and survival time curve. The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was used to predict cut-off values, the Kaplan-Meier curve was used for comparison of survival time, and the Log-rank test was used to compare the differences in survival curves. The multivariate Cox regression analysis was used to investigate risk factors. ResultsCompared with the non-HRS group, the HRS group had significant increases in Child-Pugh score, Child-Pugh class, MELD score, serum creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, maximum shunt vein diameter, the incidence rates of hepatic encephalopathy and spontaneous bacterial peritonitis, and the degree of ascites, as well as significant reductions in main portal vein diameter, serum sodium and albumin (all P<0.05). Compared with the low shunt group, the high shunt group had a significant increase in the incidence rate of HRS (51.92% vs 26.83%, χ²=5.974, P=0.015) and a significant reduction in the time to the onset of HRS (Log-rank P=0.033). A maximum shunt vein diameter of >1.5 cm (hazard ratio [HR]=1.123, 95% confidence interval [CI]: 1.041 — 1.211, P=0.003), an increase in MELD score (HR=1.205, 95%CI: 1.076 — 1.437, P=0.039), a reduction in serum albumin (HR=0.890, 95%CI: 0.814 — 0.974, P=0.011), an increase in the degree of ascites (HR=2.099, 95%CI: 1.066 — 4.130, P=0.032), and spontaneous bacterial peritonitis (HR=2.259, 95%CI: 1.020 — 5.003, P=0.045) were independent risk factors for the onset of HRS in SPSS patients. ConclusionThere is an association between SPSS and HRS, and shunt diameter >1.5 cm was an independent risk factor for HRS in SPSS patients, which should be taken seriously and require early intervention in clinical practice.
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Objective:To report a family of Zellweger spectrum disorders (ZSD) caused by mutations in the PEX10 gene and to increase the level of awareness of the disease among clinicians. Methods:The clinical and genetic data of a brother-sister co-morbidity family with ZSD due to PEX10 gene mutation admitted to the Department of Neurology, Qilu Hospital of Shandong University in July 2022 were collected and a literature review was performed. Results:The proband was a 24-year-old female who was admitted to the Qilu Hospital of Shandong University due to unstable walking for 8 years and aggravated for 1 year with squatting effort. Cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography suggested peripheral neuropathy with motor and sensory involvement, and pure tone hearing threshold measurement showed neurogenic deafness. The 15-year-old brother of the proband presented with "unsteadiness in walking and difficulty in squatting for 2 years". His cranial MRI and electromyography were similar to those of the proband, and his laboratory results suggested abnormal liver function. The whole exon sequencing results of the proband suggested a compound heterozygous mutation in the PEX10 gene with c. 992G>A(p. R331Q) and c. 988T>C(p. C330R) mutations and both were likely pathogenic mutations and respectively from her parents. And her brother also carried the above variants. A total of 9 case reports in English literature (1 of which was published by domestic scholars) were retrieved from major domestic and international databases on PEX10 gene mutations causing ZSD, with a total of 15 patients, most of whom had childhood and adolescent onset. The most common initial symptom was slowly progressed ataxia. The majority of patients showed cerebellar atrophy on cranial MRI and peripheral neuropathy was found in the most patients.The 2 patients were suggested to have phytic acid-free food, at the same time, they bagan taking L-arginine and ursodeoxycholic acid. Fortunately,both the ataxia symptom and liver function of them were dramatically alleviated 3 months later. Conclusions:For the patients with unexplained ataxia with polyneuropathy and abnormal liver function,the possibility of ZSD should be considered. Phytic acid-free food, L-arginine and ursodeoxycholic acid supplement may be beneficial for the ZSD patients.
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Objective:To evaluate the relationship between CCL21 and triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling pathways in the spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Thirty-two SPF healthy male C57BL/6J mice, weighing 18-22 g, aged 8-10 weeks, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), CCL21 neutralizing antibody group (group anti-CCL21), remifentanil + incisional pain group (group R+ I), and CCL21 neutralizing antibody + remifentanil + incisional pain group (group anti-CCL21+ R+ I).A CCL21 neutralizing antibody 0.3 μg (diluted to 10 μl in normal saline) was intrathecally injected in anti-CCL21 and anti-CCL21+ R+ I groups twice a day.Normal saline 10 μl was intrathecally injected at the same time point twice a day in C and R+ I groups.Fifteen min after intrathecal injection, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at an interval of 15 min in C and anti-CCL21 groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was injected via the caudal vein for 4 consecutive times at an interval of 15 min in R+ I and anti-CCL21+ R+ I groups.The tail-flick latency (TFL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before remifentanil or normal saline injection (T 0) and 3, 6, 24 and 48 h after stopping injection of remifentanil or normal saline (T 1-4).The mice were sacrificed after the last measurement of pain threshold, and L 4-6 segments of the spinal cord were removed for determination of the expression of TREM2 and DAP12 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). Results:Compared with group C, TFL was significantly shortened and MWT was decreased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was up-regulated in group R+ I and R+ I+ anti-CCL21 ( P<0.05), and no significant change was found in the parameters mentioned above in group anti-CCL21 ( P>0.05).Compared with group R+ I, TFL was significantly prolonged and MWT was increased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was down-regulated in group anti-CCL21+ R+ I ( P<0.05). Conclusions:CCL21 is involved in remifentanil-induced hyperalgesia by activating TREM2/DAP12 signaling pathways in the spinal dorsal horn of mice with incisional pain.
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Objective:To investigate the clinicopathological features and imaging differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) in the central nervous system (CNS).Methods:A case of CNS IVLBCL with multiple intracerebral microbleeds (CMBs) diagnosed in the Department of Neurology, Qilu Hospital of Shandong University in 2017 was reported. The clinical and imaging data, histological and immunohistochemical markers were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 31-year-old woman presented with headache and seizures. Cranial magnetic resonance imaging (MRI) showed multifocal lesions involving mainly the cortical and subcortical white matter (bilateral cerebral hemisphere and right cerebellar hemisphere), hyperintense signal on T 2-weighted and fluid-attenuated inversion recovery images, with hypointense signal on T 1-weigthed and diffusion-weighted images and contrast enhancement in some lesions. The susceptibility weighted imaging revealed multifocal cortical or subcortical hypointense lesions, involving mainly the subcortical white matter. Brain magnetic resonance angiography was normal. Brain magnetic resonance venography showed left side transverse sinus was hypoplastic. Cranial magnetic resonance spectroscopy showed decreased N-acetylaspartylglutamate peak, elevated choline peak and inverted lipid double peak. Her symptoms and the lesions once improved after starting steroid treatment. However, CNS recurrence occurred after 1 week of steroid withdrawal. She underwent the biopsy of the right frontotemporal lobe. The pathological examination showed multiple microscopic hemorrhages and edema scattered in the brain tissue. A large number of heterologous mononuclear cells were aggregated in small blood vessels in the parenchyma and meninges. Immunohistochemical analysis revealed that the tumor was negative for Epstein-Barr virus encoded small RNAs, CD 3, CD 10, cytokeratin and CD 138, and positive for CD 20, CD 79α, B-cell lymphoma (BCL)-2, BCL-6, myelocytomatosis oncogene (C-myc) and multiple myeloma oncogene-1 (MUM-1). The Ki67 proliferation index was about 70%. The diagnosis of IVLBCL was confirmed. Conclusions:IVLBCL in CNS is a rare and swiftly progressive disease with poor prognosis. Its clinical symptoms and imaging are nonspecific. Early diagnosis and treatment is critical. Biopsy is the gold standard for diagnosis. Random skin biopsy may be helpful for the early diagnosis. Furthermore, regarding the cause of multiple CMBs, the possibility of IVLBCL should be considered in the differential diagnosis, in addition to the common causes, such as primary angiitis of the CNS and cerebral amyloid angiopathy.
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Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.
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Congenital Myasthenic syndrome (CMS) is a group of partially treatable genetic disorders characterized by dysfunction of neuromuscular junction signaling.With the popularization of high-throughput sequencing and in-depth understanding of the disease in recent years, more than thirty pathogenic genes have been discovered and there is a correlation between genotype and clinical phenotype.Misdiagnosis and missed diagnosis are common in clinical practice. This paper summarized the molecular mechanisms, clinical features, electrophysiologic, pathological features and treatment of main subtypes of CMS to deepen the understanding of the disease.
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Objective:To analyze the clinical features, imaging findings and gene test of patients with type Ⅱ Alexander disease.Methods:All the clinical data of three cases with type Ⅱ Alexander disease from August 2018 to June 2020 in the Department of Neurology, Qilu Hospital of Shandong University (Qingdao) and Qilu Hospital of Shandong University were collected, and their clinical and imaging findings were analyzed retrospectively.Results:All the three patients were middle aged and old men with a chronic progressive course, beginning with weakness of one or both lower limbs, followed by dizziness, dysarthria, dysphagia, sphincteral disturbances, constipation and orthostatic hypotension. Three patients all experienced misdiagnosis (hydrarthrosis, cerebral vascular disease, alcoholism, respectively) at early stage of the disease. Cranial magnetic resonance imaging (MRI) showed mild supratentorial periventricular leukodystrophy, which was not specific. Sagittal cranial MRI demonstrated medulla oblongata and upper cervical cord atrophy called “tadpole atrophy”, which had high suggestive value. The results of gene analysis showed heterozygous mutation of glial fibrillary acidic protein gene, which had been reported as pathogenic gene; c.1091C>T (p.A364V) in exon 6, c.722C>T (p.R258C) in exon 4 and c.197G>A (p.R66Q) in exon 1, respectively.Conclusions:Type Ⅱ Alexander disease is an autosomal dominant disease, most with point mutations, rarely with deletion mutations. Type Ⅱ Alexander disease should be suspected when a patient had signs of lower brainstem involvement such as dizziness, ataxia, pyramidal sign, autonomic dysfunction, especially when cranial MRI showed mild supratentorial leukodystrophy, and medulla oblongata and upper cervical cord atrophy.
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Background& AimsThe Coronavirus Disease 2019 (COVID-19) has become a global epidemic and has caused a lasting and huge loss of life security, economic development and social stability in more than 180 countries around the world. Unfortunately, there is still no specific treatment for COVID-19 till now, therefore, at this point, all potential therapies need to be critically considered. LL-37 is one of the best-studied human antimicrobial peptide (AMPs) that has a broad-spectrum activity against bacteria and viruses. The use of living, genetically modified organisms (GMOs) is an effective approach for delivery of therapeutic proteins. The aim of this study was to determine the safety and efficacy of the Lactococcus lactis which has been genetically modified to produce the therapeutic human antimicrobial peptide LL-37 (herein after referred to cas001) in the patients of COVID-19. MethodsFirstly we constructed genetically modified food-grade probiotic, Lactococcus lactis, with sequence of seven tandem repeats of mature human LL-37 under control of the nisin-inducible nisA promoter to produce the cas001. A total of 20 healthy SD rats, half male and half female (There were five male and five female in the control group, the same in treatment group) were used to observe the acute toxic reaction and death after daily administration of cas001 for three weeks, which helps to provide necessary reference basis for clinical dose selection, verificaition of toxic reaction and possible target organs. According to the estimated clinical dosage of 1 x 108CFU /kg/day, considering the conversion of body surface area, the dose for rats should be multiplied by 6.17 to 6 x 108 CFU/kg/day. We administrated 100 times higher dose at 6 x 1010 CFU/ /kg/day to rats. In order to investigate the pharmacokinetics of cas001, male SD rats (body weight 250-300g, 1 x 1010 /animal, n=3) were given oral administration of LL-37 bacteria powder. The concentration of LL-37 in the blood before and after gavage was detected by ELISA kit (Hycult biotechnology Cat# HK321). Human clinical study was approved by Ethics committee of Chinese PLA General Hospital (S2020-074-04) and a total of 11 patients with mild symptoms were enrolled in Wuhan hankou hospital and Huoshenshan hospital. They were enrolled voluntarily and all patients signed informed consent. Among them, there were 5 males and 6 females, aged 55 {+/-} 12 (36-70) years old, and the duration from onset to medication enrollment was 35 {+/-} 19 (5-68) days. 6 patients were nucleic acid positive and 5 patients were nucleic acid negative when they were enrolled. All patients received the oral drug cas001 treatment according to requirement(1 x 109 CFU/capsule, 3 capsules/time, three times a day for 3weeks), with an average follow-up time of 33 {+/-} 15 days (see table 1 for the results). O_TBL View this table: org.highwire.dtl.DTLVardef@1845d29org.highwire.dtl.DTLVardef@1004b38org.highwire.dtl.DTLVardef@4a741aorg.highwire.dtl.DTLVardef@c73d5org.highwire.dtl.DTLVardef@188b563_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSerum biochemical detection in rats two weeks after gavage Serum biochemistry detection of rats at the end of two weeks (Vehicle[male] v.s. LL-37[male], n=5; Vehicle[female] v.s. LL-37[female], n=5). *represent p value<0.05. C_TABLECAPTION C_TBL FindingsWestern blot analysis shows that reasonable amount of LL-37 were induced by different concentrations of nisin, which means we have successfully constructed cas001. In the pre-clinical safety evaluation test, after three weeks administration of cas001, no adverse effects were observed on the rats body weight, food and water intake, hematological or serum biochemical parameters. The results showed that the LD50 of cas001 was higher than that of the 100 times of the expected clinical dose of 6 x 1010 CFU/day. These results showed that cas001 could be safe in animal experiments. In addition, rat pharmacokinetics results showed that the serum concentration of LL-37 reached peak 2 hours after gavage of cas001 and returned to basal level 6 hours after gavage. During study period, the volunteers did not feel any discomfort while taking the cas001 capsules, and two hours after oral administration, the concentration of LL-37 were increased in healthy volunteers. cas001 shows definite effect in the improvement of gastrointestinal symptoms and is possible to have effects in improving the systemic symptoms and respiratory symptoms and may play a role in the improvement of results of nucleic acid test and lung CT test. 11 patients enrolled showed good compliance, tolerance, subjective feeling and actively interacted with the doctors. None of the patients had any adverse reactions. ConclusionsBased on above observations, we conclude here that as an oral anti-viral agent, cas001 displayed good safety profiles. It is very hard to reach conclusion of clinical outcomes related to the cas001, although changes of several symptoms indicate encouraging findings.
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Inborn errors of metabolism (IEMs) are defined as genetically enzymatic deficiencies or defects in polypeptide or protein involved in cellular metabolism,which include nearly a thousand kinds of genetic-definite disease entities up to now and could develop symptoms and signs at any age,and those whose onset-age is more than 1 years old are named as late-onset IEMs.More than 80% of IEMs could involve the nervous system,also called IEMs of the nervous system,and most of the late-onset IEM patients will go to the Deparment of Neurology firstly.The treatment aim of IEMs is to correct the metabolic deficiency.The main therapeutic strategies include substrate-limitted intake,enzyme replacement therapy,clearance of the toxic metabolites,cofactor supplement,gene therapy and sympatomatic and support treatment.Many kinds of late-onset IEMs of the nervous system are treatable,and could be healthy living if treated early and correctly.Therefore,it is important to strengthen the understanding of neurologists on the late IEMs of the nervous system,which should not be ignored.
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Objective To describe the features of clinical,imaging and cerebral spinal fluid (CSF) of listerial rhombencephalitis to improve the understanding of this disease in clinical practice.Methods All the clinical data of three cases of listerial rhombencephalitis from April to August 2017 in Qilu Hospital were collected and analyzed retrospectively.Results All the three cases were healthy adult women before,with a rapidly progressive course,beginning with fever (38.2-40 ℃),headache accompanied by nausea and vomiting,followed by cranial paralysis,dysphagia and paralysis of the limbs on the 2nd to 5th day of onset,and developed to acute respiratory failure and unconsciousness on the 5th to 8th day of onset.All the three patients were diagnosed with CSF culture positive for Listera monocytogenes on the 3rd to 5th day after admission.The initial CSF lactic acid increased significantly,representing 12.3,12.0 and 10.0 mmol/L respectively;CSF white blood cells were 416× 106/L,760× 106/L and 793× 106/L,respectively,and the protein levels were 0.76 g/L,0.57 g/L and 1.47 g/L,respectively.Brain images showed brain stem was involved in all the three patients,therein cases 1 and 3 with cerebellar hemisphere involved,case 2 with upper cervical spinal cord involved,and case 1 with supratentorial hydrocephalus involved.After treatment with sensitive antibiotics,case 1 recovered,case 2 died,and case 3 lived with dysphagia.Conclusions Listerial rhombencephalitis should be suspected when a patient started with fever and headache,rapidly progressed to cranial nerve paralysis,brainstem symptoms,and acute respiratory failure,especially when the brain imaging suggested brainstem involved with increased white blood cells and apparently elevated lactic acid level of CSF.The earlier the sensitive antibiotics initiated,the better the patients' prognosis.
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Objective To explore the clinical characteristics of late-onset ornithine carbamoyltransferase deficiency (OTCD) in order to improve the clinicians' understanding of this disease.Methods The clinical,therapeutic and follow-up data of two patients with late-onset OTCD diagnosed in the Department of Neurology,Qilu Hospital of Shandong University from November 2017 to February 2018 were collected and analyzed.Results Case 1 is a 17-year-old male who was admitted into Qilu Hospital with recurrent dizziness and vomiting for 4 months,sudden mental abnormality and convulsion for 3 days.The liver dysfunction,respiratory alkalosis and hyperammonemia (434 μmol/L) had been found before his admission.His blood ammonia fluctuated obviously from 180 μ mol/L to 2998 μmol/L,though he was given hemodialysis and arginine infusion,and died on the fourth day after admission.Case 2 is a 15-year-old male,complained with recurrent dizziness,vomiting,bluntness and somnolence for 20 days.He was found with hyperammonemia (600 μmol/L) and liver dsyfunction in a local hospital.He was getting better after intravenous administration of arginine and liver protective drugs.After admission,the blood ammonia,liver function and amino acids,acylcarnitine profiling in dried blood spots,and organic acid analysis in urine were normal,and he has not recurred since restriction of protein diet.Brain magnetic resonane imaging of both patients showed cytotoxic edema of bilateral frontal lobe and insular cortex,and their genetic detection both showed c.119G>A(p.R40H) hemizygous pathogenic mutation of OTC gene inherited from their respective mothers.Conclusion Unexplained hyperammonemia and acute encephalopathy with insular and frontal cortical involvement should be on the alert to the urea cycle disorders,especially OTCD.Early diagnosis and reasonable treatment are the key to changing the prognosis.
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Objective To summarize the clinical , pathological and genetic characteristics of three patients with caveolin-3 associated myopathy and review the literatures .Methods The clinical data of three patients with caveolin-3 associated myopathy were investigated .With informed consent , we performed muscle biopsy and genetic analysis of CAV 3 and PTRF genes.Results All the three patients presented with percussion/pressure-induced rapid contraction , percussion-induced muscle mounding and mechanically induced muscle rippling.Besides, case 1 had weakness and atrophy of hand muscles .Case 2, who manifested with muscle hyperexcitability at onset , developed weakness and atrophy of distal part of lower limbs.Case 3 showed normal muscle strength and tone .All of them had myalgia or tenderness .Muscle biopsy revealed mild myogenic changes in two patients and a muscular dystrophic pattern in one . Immunohistochemical staining of caveolin-3 revealed an even deficiency in case 1 and a mosaic deficiency in cases 2 and 3.Gene analysis revealed a missense mutation ( c.80G>A, p.R27Q) in CAV3 gene of case 1. No mutations were identified in cases 2 and 3.Conclusions There is phenotypic variability in patients with caveolin-associated myopathy , including limb-girdle syndrome , rippling muscle disease , distal myopathy , muscle hypertrophy , idiopathic hyperCKemia and cardiomyopathy .Muscle biopsy and caveolin-3 staining should be performed for the above patients with muscle rippling .
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Objective To report four patients with secondary α-dystroglycanopathy caused by guanosine diphosphate-mannose pyrophosphorylase-B ( GMPPB ) gene mutations and review the literature aiming to analyze the clinical manifestations , muscle image , molecular pathology and genetic characteristics of the disease.Methods The medical history , physical examination , electromyography and other clinical data of four patients with secondary α-dystroglycanopathy from two families were collected and retrospectively reviewed from 2009 to 2017.Case 1 ( proband of pedigree 1) and case 2 ( proband of pedigree 2) were then further analyzed with muscle imaging , muscle pathology and targeted next generation gene sequencing (NGS).Results Four patients came from two families (three from the same pedigree), two males and two females, with an onset age of 17 -18 years.All four cases presented as limb-girdle muscular dystrophy (LGMD) overlapping with congenital myasthenic syndrome (CMS) characterized by evident proximal limb weakness in early adulthood and fluctuating muscle weakness .They all had delayed motor milestone and did not perform well in physical education since childhood . Serum creatine kinase was elevated markedly (1877-5275 U/L).Myogenic changes on electromyography and marked attenuation on three Hz repetitive nerve stimulation were observed in all patients .Muscle MRI showed prominent involvement of bilateral hamstrings in case 1 and case 2.Muscular dystrophic patterns were demonstrated on muscle biopsies . Targeted NGS revealed two compound heterozygous missense mutations in GMPPB for each case .Case 1 carried c.860G>T (p.R287L)/c851T>C (p.V284L).Case 2 and his two affected sisters (case 3 and case 4) carried c.1097A >G ( p.N366S)/c.589G >T ( p.V197F) .All of these mutations were novel variants and pedigree analysis suggested that the two mutations were from parents .Compared with normal controls, immunohistochemistry and Western blotting showed significantly decreased expression of α-dystroglycan in the muscle tissue from case 1 and case 2.The myasthenic symptoms of all four patients were improved to varying degrees after treatment with pyridostigmine bromide . Conclusions Mutations in GMPPB can lead to dysfunction both in muscle and in neuromuscular transmission causing overlapping between LGMD and CMS phenotypes . Cholinesterase inhibitors can partly improve the symptoms of myasthenia in such patients .
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Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.
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Objective To investigate the clinical and electrophysiological characteristics of anti-myelin-associated glycoprotein (MAG)-associated peripheral neuropathy, as well as its antibody detection methods, treatment and prognosis. Methods Six cases of IgM paraproteinemia and anti-MAG antibody-associated peripheral neuropathy were summarized. All of the patients came from Peking Union Medical College Hospital and Qilu Hospital since April 2014 to February 2018. The clinical features, electrophysiological characteristics, and auxiliary examinations including anti-MAG antibody results were analyzed, and the treatment and prognosis were followed. Results Of the six patients, five were male and one was female. The age of onset was 50-77 years and the duration was three months to six years. All the six cases suffered from numbness of distal limbs and gradually progressed to the proximal limbs, of which three cases had muscle weakness. Walking instability occurred in five cases. One patient had electricity-like pain in the lower extremities. Reflexes in the four limbs decreased in five cases, and gloves and socks-like deep sensation decreased in six cases. Five patients underwent lumbar puncture and the cerebral spinal fluid protein ranged from 0.75 to 1.33 g/L. Serum monoclonal proteins were found in six patients, of which four were IgM kappa and two were IgG kappa and IgM kappa biclonal. Four cases were diagnosed with monoclonal gammopathy of undetermined significance and two cases were diagnosed with Waldenstr?m's macroglobulinaemia. Abnormal electromyography was detected in all the six cases, suggesting demyelinating peripheral nerve damage with secondary axonal damage, which was sensory predominant and more severe in lower limbs than upper limbs. In all the six cases, anti-MAG-IgM antibodies were all positive by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues. After the diagnosis, three patients underwent RCD (rituxima + dexamethasone + cyclophosphamide) chemotherapy. One patient improved (the modified Rankin scale (mRS) score was 3 before treatment and 2 three years after treatment), one patient was stable, and one patient was still in follow-up. One patient was treated with rituxima, and the condition improved (the mRS score was 3 before treatment and 1 one year after treatment). Conclusions MAG-associated peripheral neuropathy can present a slow progressed distal symmetric sensomotor peripheral neuropathy with predominant sensory symptoms. Electromyography shows demyelinating change. Monoclonal protein is usually IgM kappa. MAG-IgM antibodies detection by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues can support the diagnosis. RCD chemotherapy may be effective.
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Objective To investigate the CT manifestations and pathology features of solitary fibrous tumors of the pleural (SFTP),to improve diagnostic accuracy of this disease.Methods CT manifestations of 12 cases with SFTP confirmed by surgery were analyzed retrospectively by comparison with the pathological findings.Results The CT images of the 12 cases showed intrathoracic soft-tissue shadow with well-defined margin which was widely connected with pleural.There were 4 cases with mound like and mushroom shape,3 cases with round or oval shape,2 cases with irregular shape growing into the pleural space,3 cases with large mass filling unilateral thoracic cavity,9 cases with pleural tail sign and 1 case with pleural pedicle sign.The plain CT showed homogeneous density in 7 cases,high-low mixed density in 4 cases and with internal calcification in 1 case.After contrast enhancement,5 cases were map like heterogeneous and progressive enhancement,and 4 cases have strip distorted vessel inside or on the edge of the lesion.Conclusion CT manifestations of SFTP have certain characteristics,such as broad base,shaping growth and pleural tail sign,which could be helpful to improve the diagnostic accuracy of SFTP by analyzing carefully.
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Objective To investigate the clinical and pathological features of Guillain-Barré syndrome with treatment-related fluctuations (GBS-TRF).Methods Clinical data were obtained from medical records of patients with GBS-TRF during the period 1999 to 2014 in our Hospital.Sural nerve specimens were collected and summarized retrospectively (two cases).Results Eight of 868 cases with GBS had at least one TRF including three chronic hepatitis B patients.The onset of disease was ranged in age from six to 63 years, averaging 34 years.It is more common in men than in women in a ratio of seven to one.Triggering infections occurred in three patients.The initial symptom included weakness of the lower limbs (five cases) and upper extremities (three cases).Sensory symptom was presented in six patients.Five patients had associated respiratory paralysis.None of them had cranial nerve palsy or autonomic dysfunction.The examination of cerebrospinal fluid showed protein and cell separation.Five patients had two attacks, one had three attacks and two had six attacks.The interval between attacks ranged between 14 days and 46 days (mean 23 days).The striking pathologic finding was the presence of sectional selective nerve fiber degeneration (SNFD) with evidence of demyelination.Conclusions Patients with GBS-TRF show similar onset age, preceding infection, cerebrospinal fluid findings, and electrophysiologic characteristics comparing to patients with GBS,while there are more male patients than female patients.SNFD found in sural nerve biopsy reveals ischemic neuropathy, which predicts that injury of arterioles might play an important role in the pathogenesis of GBS-TRF.
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Objective To investigate the clinical and pathological features of Guillain-Barré syndrome with treatment-related fluctuations ( GBS-TRF ).Methods Clinical data were obtained from medical records of patients with GBS-TRF during the period 1999 to 2014 in our Hospital.Sural nerve specimens were collected and summarized retrospectively ( two cases ).Results Eight of 868 cases with GBS had at least one TRF including three chronic hepatitis B patients.The onset of disease was ranged in age from six to 63 years, averaging 34 years.It is more common in men than in women in a ratio of seven:one.Triggering infections occurred in three patients.The initial symptom included weakness of the lower limbs ( five cases ) and upper extremities ( three cases ).Sensory symptom was presented in six patients.Five patients had associated respiratory paralysis.None of them had cranial nerve palsy or autonomic dysfunction.Five patients had two attacks , one had three attacks and two had six attacks.The interval between attacks ranged between 14 days and 46 days ( mean 23 days ).The striking pathologic finding was the presence of sectional selective nerve fiber degeneration ( SNFD ) with evidence of demyelination.Conclusions Patients with GBS-TRF shows similar onset age , preceding infection , cerebrospinal fluid findings, and electrophysiologic characteristics comparing to patients with GBS ,while there are more male patients than female patients.SNFD found in sural nerve biopsy reveals ischemic neuropathy , which predicts that injury of arterioles might play an important role in the pathogenesis of GBS -TRF.
RESUMEN
BACKGROUND AND PURPOSE: The wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). METHODS: Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. RESULTS: Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The transcriptional activities of β-catenin/Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. CONCLUSIONS: Our findings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fibrosis.