Voltage-gated potassium channel-complex antibodies associated clinical syndromes with myasthenia gravis complicated with thymoma: analysis of 2 cases and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

Clinical, neuroimaging and gene mutation characteristics of McLeod syndrome and literature review / 中华神经科杂志

Objective:To study the characteristics of clinical, laboratory, imaging, genetic and differential diagnosis of McLeod syndrome.Methods:The clinical characteristics of 2 cases of McLeod syndrome confirmed by gene detection in Qilu Hospital (Qingdao) on June 27, 2018 and in Qilu Hospital of Shandong University on September 11, 2019 were analyzed retrospectively. And the characteristics of patients of McLeod syndrome reported in China were analyzed in combination with literature review.Results:Both of the 2 patients were adult male, aged 57 and 61 years, respectively, with a slowly progressive course, beginning with gradually involuntary movement of trunk and extremities, involving involuntary biting of the tongue and dysphagia. Two patients had mild cognitive impairment; one patient had emotional agitation. Imaging study showed atrophy of caput nuclei caudate. Neuroelectrophysiological examination of case 1 showed sensory axon neuropathy in both upper limbs with severe damage to the left ulnar nerve. Creatine kinase (CK) was mildly elevated in 2 patients. The peripheral blood smear of 1 patient showed increased acanthocytes, accounting for 13%, the other patient showed no increased acanthocyte. McLeod syndrome related gene was tested in the 2 patients, case 1 with deletion mutation of exon 2 of XK gene, and case 2 with hemizygotic mutation of XK gene c.898delC p.L300 *. Conclusions:The clinical manifestations of McLeod syndrome are various and the differential diagnosis is crucial. For elderly male with cephalic facial chorea, elevated CK level and neuromuscular diseases, the possibility of McLeod syndrome should be screened.

Clinical characteristics of orobuccal involuntary movements induced by anticholinergic agents in patients with Parkinson′s disease and literature review / 中华神经科杂志

Objective:To study the clinical characteristics of orobuccal involuntary movements (OB) induced by anticholinergic agents.Methods:The clinical characteristics of patients with OB induced by anticholinergic agents in Qilu Hospital (Qingdao) from April 2018 to October 2021 and cases reported in the literature were analyzed in combination with literature review.Results:Seven patients in Qilu Hospital (Qingdao) and 10 cases in the literature were analyzed. Of these 7 patients, 6 were elderly female, with involuntary, repetitive, stereotypical movements of the lips, tongue, and sometimes of the jaw after intake of anticholinergic medication with the latency 21-60 days and the involuntary movements improved 7-30 days after discontinuation of anticholinergic medication. Of 10 cases reported in the literature, 7 were elderly female and 8 only with OB and 2 patients had extremities dyskinesia plus OB. Involuntary movements appeared after latency of 3-93 days following the introduction of anticholinergic drugs and resolved after latency of 2-60 days following their withdrawal.Conclusions:OB induced by anticholinergic agents mostly occur sub-acutely during the treatment of Parkinson′s disease, and can resolve in a short time after withdrawal, which is independent of the dose of levodopa and anticholinergic agents. The aging, female, and anxiety and depression may be the risk factors.

Clinical analysis of type Ⅱ Alexander disease and literature review / 中华神经科杂志

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.

Clinical and radiological analysis of patients with diplopia after acute lacunar infarction / 实用放射学杂志

Objective To analyze the clinical,radiological features and risk factors of diplopia in patients with acute lacunar infarction (ALI).Methods Retrospectively retrieved patients of ALI (lesion diameter was less than 1.5 cm in DWI sequence)diagnosed by MR and clinical.We further summarized 13 ALI patients with diplopia and randomly selected 13 ALI patients without diplopia as the control group. SPSS22.0 statistical software was used for statistical analysis.The general clinical data such as sex and age was compared by Ch-i square test and t-test.The risk factors were primarily analyzed by one-way ANOVA and then the risk factors with statistical significance were brought into the logistic regression model for multivariate analysis.Results The incidence of diplopia in ALI patients was about 2.7%(13/489). The infarct sites were all located in the brain stem of the oculomotor-related brain nucleus and the dorsolateral medulla oblongata.Hypertension and hematocrit were negatively correlated with diplopia after infarction (P＜0.05 ).Conclusion The incidence of diplopia is low in ALI patients.The medial longitudinal tract of the dorsolateral medulla is an important area causing diplopia.Hypertension and hematocrit are non-risk factors for diplopia after ALI.

Clinical analysis of three cases of listerial rhombencephalitis / 中华神经科杂志

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.

A case of fragile-X-associated tremor/ataxia syndrome in China / 中华神经科杂志

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder occuring in male carriers of a premutation expansion (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. However, no FXTAS cases have been reported in China. We report a 67-year old male who presented clinically with orthostatic tremor, intention tremor, resting tremor and ataxic gait. Magnetic resonance imaging showed lesions in the bilateral middle cerebellar peduncles. Gene test showed premutation (101 CGG repeats) of the FMR1 gene and confirmed the diagnosis of FXTAS.

Guanosine diphosphate-mannose pyrophosphorylase-B gene mutations causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome / 中华神经科杂志

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 .

Effect of transplantation of mouse marrow stromal cells through injection into cerebrospinal fluid on Cu/Zn superoxide dismutase 1 transgenic mice / 中华神经科杂志

Objective To investigate the effect of transplantation of mouse marrow stromal cells (mMSCs) on Cu/Zn superoxide dismutase 1 (SOD1) transgenic mice through cerebrospinal fluid (CSF) injection.Methods We delivered 5 × 105 mMSCs into SOD1 transgenic mice by single injection to CSF at the age of 8 weeks or by multiple injections at the age of 8,10 and 12 weeks.Neurologic phenotype observation,weight measurement,hanging wire test and motor neuron counts were used to assess disease progression of SOD1 mice.Results Single transplantation of mMSCs didn' t show beneficial effect on SOD1 mice.Compared with vehicle-treated mice,SOD1 transgenic mice with multiple transplantations of mMSCs demonstrated attenuated weight loss,improved motor performance,decreased motor neuron loss,and importantly,prolonged survival by 17 days ((157 ± 15) d vs (140 ± 11) d; x2 =7.56,P ＜ 0.01).Conclusion Intrathecal injection could be an effective route of cell transplantation,and multiple transplantations of mMSCs are needed to achieve the therapeutic effect on SOD1 mice.

Fasting plasma obestatin levels in patients with different glucose tolerance and its association with lipid metabolism / 中华老年医学杂志

Objective To investigate whether fasting obestatin level is different in patients with impaired glucose tolerance or type 2 diabetes, and to explore the association between obestatin and lipid metabolism. Methods Eighty-four subjects without known diabetes were divided into three groups: normal glucose tolerance(NGT), impaired glucose tolerance (IGT) and type 2 diabetes (DM) Plasma obestatin levels were measured with a radioimmunoassay. The relationship between fasting obestatin levels and metabolic parameters was also analyzed. Results Fasting obestatin levels were lower in DM group [(2.82±0.78)ng/ml] and IGT group [(3.25±0.29)ng/ml] than in NGT group[(3.55±0.57) ng/ml, P＜0.01]. Triglycerides and low density lipoprotein cholesterol levels gradually increased among the three groups (P＜0.05). Multiple linear regression analysis revealed fasting obestatin level was independently associated with waist-to-hip ratio, triglyeride and low density lipoprotein cholesterol. The regression equation was obestatin=6.953-3.412×W/H-0.175×TG-0.123×LDL-C. Conclusions The decreased obestatin may be associated with IGR and T2DM, and obestatin level may be associated with lipid metabolism.

Effect of human mesenchymal stem cells intracardiac transplantation on superoxide dismutase 1-G93A mice / 中华神经科杂志

Objective To study the changes of life span and pathology in superoxide dismutase 1 (SOD1)-G93A mice after intracardiac transplantation of human mesenchymal stem cells (hMSCs).Methods hMSCs were isolated from bone marrow cells obtained from healthy donors and cultured.The purity and morphology were assessed by flow cytometry (FCM).hMSCs (3×10~6) resuspended in 0.2 ml DMEM was injected into the heart of 8 week-old SOD1-G93A mice.In non-transplantion control SOD1-G93A mice, only DMEM was injected.The mice were evaluated for signs of motor deficit with 4-point scoring system previously described by Weydt et al.The age of onset and life span in mice were assessed.The pathological change including number of motor neurons was investigated by Nissl staining.Immunofluorescence staining with specific human nuclear antibody was used to confirm the transplant of hMSCs in mice.Results The onset symptoms in untreated SOD1-G93A mice appeared at (156.56±3.60) days of age and the average life span was (188.32±3.51) days.hMSCs transplantation delayed the onset of ALS type symptoms about 16 days (x~2=10.888, P=0.001) and prolonged the life span about 14 days compared to the untreated SOD1-G93A littermates((202.19±4.09) days vs (188.32±3.51) days, x~2=3.917, P=0.04).The loss of motor neurons in untreated mice was earlier and more severe than in hMSCs transplanted mice.At 20 weeks, the number of motor neurons in transplanted mice was significantly higher than those in untreated mice.Human specific nuclear antigen in brain and spinal cord was detected in transplanted SOD1-G93A mice.Conclusion hMSCs can be implanted for a long-term into central nervous system by intracardiac transplantation and the transplantation can prolong life span, and delay the onset of the disease and motor neuron loss in SOD1-G93A mice.

Effectiveness and pathologic changes of transplantation of human mesenchymal stem cells in SOD1-G93A mouse model of familial amyotrophic lateral sclerosis / 中国病理生理杂志

AIM:To study intravenous transplantation of human mesenchymal stem cells (hMSCs) on the life span and pathological change of SOD1-G93A amyotrophic lateral sclerosis (ALS) mice. METHODS:hMSCs were cultured and expanded from heparinized bone marrow cells from healthy donors and the purity and features were identified with FCM. hMSCs (3×10~6) resuspended in 0.3 mL DMEM or 0.3 mL DMEM only were injected into the tail vein of genotyped SOD1-G93A ALS mice. The mice were evaluated for signs of motor deficit with 4-point scoring system according to Weydt and the onset and life span were assessed. The pathological change was observed with Nissl staining and number of motor neuron was counted. RESULTS:The onset symptoms in untreated SOD1-G93A ALS mice appeared at (156.6±3.6) d of age and the average life span was (188.3±3.5) d. hMSCs transplantation delayed the onset of ALS type symptoms about 14 d and prolonged the life span about 18 d compared to the untreated SOD1-G93A littermates. The loss of motor neurons in untreated mice was much faster and severer than that in hMSCs transplanted mice. At 16 th week and 20 th week,motor neurons of untreated mice were significantly fewer than those of transplanted mice. β-globin gene in brain was detected in transplanted ALS mice. CONCLUSION:hMSCs migrate to central nervous system after intravenous transplantation,prolong the life span and delay the onset and motor neuron loss in SOD1-G93A ALS mice.

Hypertriglyceridemia and insulin resistance in the obese elderly / 中华老年医学杂志

Objective To study the changes of circulating triglyceride (TG) in the obese elderly, and to investigate the effect of hypertriglyceridemia on the development of insulin resistance. Methods A total of 82 subjects were divided into simple obesity group, obesity with IGT group, obesity with T2DM group and normal control group. The body height, body weight, blood pressure, fasting plasma glucose (FPG) and insulin(FPI), circulating TG and total cholesterol (TC) were measured. The homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. Results The levels of serum TG were significantly higher in the simple obesity group ( 1.3 ± 0. 6) mmol/L, obesity with IGT group (1.9 ± 0.9)mmol/L and obesity with T2DM group (2.1±0.7) mmol/L than in the normal controls [(1.0±0.2)mmol/L, all P<0. 05], Furthermore, the levels of TG, FPG, FPI, HOMA-IR and systolic pressure were significantly higher(all P<0. 05) in obesity with IGT group and obesity with T2DM group than in simple obesity group. There were significantly positive correlations between TG and body mass index (BMI), FPG, HOMA-IR, TC, systolic pressure respectively (all P < 0.05). Multiple linear regression analysis indicated that FPG and HOMA-IR were the independent factors affecting TG (both P < 0. 05 ). Conclusions Hypertriglyceridemia may play an important role in the development of insulin resistance.

Noninvasive measuring the new indexes of cardiac functions by echocardiography / 中华超声影像学杂志

Objective　To establish the method of noninvasive measuring the new indexes of cardiac functions by echocardiography and illustrate the diagnostic values of the indexes.Methods　By use of simultaneous screen display of echocardiography, phonocardiography and electrocardiography and synchronously monitoring blood pressure (BP) technique, the values of LV end-systolic and end-diastolic long and short- axis dimensions, wall thickness and area sizes,and synchronous BP were measured in the patients with myocardial infarction (MI) of defferent sites and area sizes before and during BP were altered to defferent degrees. The values of maximum elasticity (Emax) and average maximum myocardial elasticity stiffness (maxEav) and ejection blood fraction (EF) were calculated through computer programmed process.Results　The order of values of Emax,maxEav and EF among MI patients of defferent sites was control group>inferior MI group>anterior MI subgroup>multi-wall MI subgroup. Their order among MI patients of defferent area sizes was control group > small area MI subgroup > larger MI subgroup. Emax was associated with the MI parts and 　maxEav was associated better with the MI area sizes.Conclusions　The study has established a noninvasive method of examining cardiac function by use of echocardiography and reflected the special diagnostic values of Emax,maxEav and EF in MI patients of defferent parts and area sizes.

EFFECTS OF MODIFIED DECOCTION FOR INVIGORATING YANG ON NERVOUS FUNCTIONAL RECOVERY AFTER PERIPHERAL NERVOUS INJURY / 中药新药与临床药理

Rat models with common peroneal nerve injury were treated with modified Decoction for Invigorating Yang orally to observe its effect on the nervous functional recovery after peripheral nerve injury. The result showed that the motor nerve conduction velocity of the drug group during the whole observation period was higher than that of the control group (p