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OBJECTIVE@#To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7).@*METHODS@#A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed.@*RESULTS@#The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7.@*CONCLUSION@#Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.
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Male , Female , Humans , Membrane Transport Proteins/genetics , Neuronal Ceroid-Lipofuscinoses/diagnosis , Retrospective Studies , Atrophy , MutationABSTRACT
Objective:To investigate the clinical, pathological and genetic characteristics of myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).Methods:The detailed clinical data, muscle biopsy pathology and molecular results of 4 patients with genetically confirmed myopathy-type VLCADD admitted to Henan Provincial People′s Hospital and Xuanwu Hospital, Capital Medical University from June 2014 to November 2019 were retrospectively analyzed.Results:All of the 4 patients were late-onset myopathy-type VLCADD. The onset age ranged from 13 to 16 years, with a mean age of 14.5 years. The age at diagnosis ranged from 21 to 54 years, with a mean age of 42.5 years. The main clinical manifestation was repeated rhabdomyolysis, including myalgia, weakness and dark urine. Obvious somnolence was observerd in 1 patient. Muscle biopsy pathology revealed mild lipid accumulation, without vacuoles. Six ACADVL variations were detected in the 4 patients, including c.1283G>A (p.R428H), c.1532G>A (p.R511Q), c.833_835delAGA (p.K278del), c.1843C>T (p.R615 *), c.1748C>T (p.S583L) and c.1391C>T (p.T464I),among which c.1391C>T (p.T464I) was a novel variation, predicted to be likely pathogenic. Other 5 variations were reported pathogenic variations. Conclusions:Myopathy-type VLCADD is characterized by paroxysmal rhabdomyolysis and can be associated with somnolence. There is no specificity in muscle pathology. There are ACADVL variations, among which c.1391C>T is a novel variation.
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Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.
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Vascular cognitive impairment (VCI), one of the most common causes of cognitive impairment, severely influences the lifetime and daily life abilities in the elder population. Cognitive reserve (CR) can compensate the damage caused by aging and brain pathology. The risk factors of CR include intelligence quality, education, occupation achievement, leisure activities, bilingualism, traumatic brain injury and vascular risk factors. Single proxy indicator and questionnaire composed of several different proxy indicators have been developed to measure CR. Cognitive Reserve Index Questionnaire is the most commonly used scale of CR. CR is not only associated with the severity of post-stroke cognitive impairment, but also the rapid cognitive recovery early after stroke. CR also plays a great role in the cognitive impairment related to small cerebral vessel diseases. Many problems on CR exist among the clinical application and clinical research, such as the underlying biological mechanisms, excessively emphasizing socioeconomic indicators in the CR questionnaire and unclear weighting score of single indicators in the CR questionnaire. More attention should be paid to mechanism research and relationship between CR and VCI.
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Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the recovery of neurological functioning and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and inflammatory factors after ischemic stroke.Methods:Sixty-four C57BL/6J mice were randomly divided into a normal control group, a model group, a sham stimulation group and an observation group, each of 16. All mice except those of the normal control group received middle cerebral artery occlusion using the suture method to model an ischemic stroke. After the modeling the observation group was given 1Hz rTMS daily for 7 consecutive days, while the sham stimulation group was given sham rTMS. After the intervention, Zea-Longa scores were used for all of the groups, and the size of the cerebral infarct was measured using triphenyltetrazolium chloride staining. The expression of NLRP3 around the cerebral infarction was detected using immunofluorescence, while that in the brain tissue was measured using Western blotting. The expression of interleukin-1β and IL-18 in the brain tissue was detected using enzyme-linked immunosorbent assays.Results:Compared with the normal control group, a significant increase was observed in the other groups′ average neurological function impairment scores. Expression of NLRP3, IL-1β and IL-18 in the model and sham stimulation groups also increased, with large cerebral infarcts in the cortex and hippocampus. Compared with the sham stimulation and model groups, there was a significant decrease in the average neurological dysfunction scores, the area of cerebral infarction in the cortex and hippocampus, as well as the expression of NLRP3, IL-1β and IL-18 in the observation group.Conclusions:Low-frequency rTMS can promote the recovery of damaged nerve function after an ischemic stroke, at least in mice. It can reduce the size of cerebral infarction, and inhibit neuronal pyroptosis, which is closely related to the down-regulation of NLRP3, IL-1β and IL-18 expression.
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Objective:To report 8 patients of sporadic Creutzfeldt-Jakob disease (sCJD) with real-time quaking-induced conversion (RT-QuIC) positive and analyze their clinical characteristics.Methods:The medical records of patients discharged from Henan Provincial People′s Hospital from January 2018 to May 2021 who were diagnosed with clinically probable sCJD and had RT-QuIC test were retrospectively analyzed. General information (gender, age, initial symptom, main clinical manifestations), accessory examination [brain magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid 14-3-3 protein, prion protein gene, antibodies related to autoimmune encephalitis and paraneoplastic syndrome] were collected. By a telephone-based follow-up survey, data about morality and total duration of course were collected. The patients were divided into two groups according to electroencephalogram, 14-3-3 protein, duration of disease and MRI results, and the differences of fluorescence peak time and fluorescence peak value in RT-QuIC results between groups were compared.Results:Among 8 patients, 7 patients had subacute onset and 1 patient had chronic onset. Main clinical manifestations included progressive cognitive decline (8/8), pyramid sign (5/8), walking instability (4/8), mental and behavior disorder (4/8), myoclonus (4/8), akinetic mutism (4/8), dizziness (3/8), limb shaking (2/8), dysarthria (2/8), visual hallucination (1/8), impaired vision (1/8). All cases had abnormal electroencephalogram and typical periodic sharp slow compound waves (PSWCs) were observed in 5 cases. Brain MRI showed high signal intensity in the cerebral cortex and/or basal ganglia on diffusion-weighted imaging in 7 cases, of which 6 cases involved bilateral basal ganglia. Cerebrospinal fluid 14-3-3 protein was positive in 2 cases, and RT-QuIC was positive in all cases. The fluorescence peak time of RT-QuIC was shorter in patients with PSWCs [(7.617±2.164) h vs (10.602±2.247) h, t=2.84, P=0.010] and high total MRI score [ (7.600±1.907) h vs (9.760±2.457) h, t=2.26, P=0.032]. Conclusions:RT-QuIC detection is a reliable method for early diagnosis of sCJD. RT-QuIC results were related to PSWCs and degree of MRI involvement.
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common single gene hereditary cerebral small vessel disease in adults. With the development of gene sequencing technology and imaging, the disease is more and more recognized by people. In this paper, according to the research progress in recent years, the mutation types of NOTCH3 gene in CADASIL patients, the hot spot regions and sites of mutation in different populations, and the relationship between genotype and phenotype were summarized from the perspective of genetics. The future gene therapy of the disease was prospected.
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Objective:To report the clinical and genetic features of a pedigree with familial encephalopathy with neuroserpin inclusions bodies (FENIB) and to enhance the understanding of the disease.Methods:The proband was admitted to Department of Neurology, Henan Provincial People′s Hospital in June 2020 due to cognitive impairment and epilepsy. Detailed medical history inquiry, physical examinations, and neuroimaging examination of the family were conducted. The proband completed the examination of brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid examinations. Whole exome sequencing and Sanger sequencing were used to screen the genetic variations in the proband. Sanger sequencing was performed in some family members to verify the mutation. Through literature review, the characteristics of the disease were summarized.Results:The proband was a 23-year-old young female with progressive cognitive impairment, epilepsy as the main manifestations. Brain MRI indicated moderate atrophy of bilateral cerebral cortex. Genetic sequencing revealed a heterozygous missense mutation (c.1013A>G; p.H338R) of SERPINI1 gene encoding the neuroserine protease inhibitor protein. The proband′s mother and brother had similar clinical symptoms in adolescence. Both of them passed away several years later. This mutation was a proven pathogenic mutation for FENIB. The clinical phenotype was consistent within the family. Genotype and clinical phenotype were co-segregated.Conclusion:FENIB due to SERPINI1 gene mutations should be considered in young cases of cognitive decline, epilepsy and myoclonus.
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Objective:To evaluate the efficacy and safety of fasudil on vasospasm caused by subarachnoid hemorrhage in elderly patients.Methods:A total of 100 elderly patients with subarachnoid hemorrhage admitted to our hospital from January 2015 to May 2018 were enrolled as research objects.They were randomly divided into the Fasudil group(n=50, receiving the Rho kinase inhibitor Fasudil therapy)and the Nimodipine group(n=50, receiving Nimodipine therapy). The cerebral vasospasm and cerebral infarction lesions, the ability of daily life, clinical prognostic score, the incidence of symptomatic cerebral vasospasm and adverse reactions during treatment were evaluated and compared between the two groups.Results:After treatment, the incidences of cerebral vasospasm and cerebral infarction in Fasudil group were 2.04%(1/49)and 6.12%(3/49), respectively, which were lower than those in the Nimodipine group[12.50%(6/48)and 20.83%(10/48), respectively]( χ2=6.134 and 6.794, P=0.047 and 0.033). The scores of daily living ability was better in the Fasudil group than in the Nimodipine group(16.09±1.06 vs.22.91±1.66, t=7.721, P=0.026). The incidence of adverse reactions was lower in the Fasudil group than in the Nimodipine group(4.08% or 2/49 vs.16.7% or 8/48, χ2=6.362, P=0.040). There was no statistically significant difference in the proportion of patients with good prognosis between Fasudil group and Nimodipine group. Conclusions:Rho kinase inhibitor Fasudil can effectively prevent and improve cerebral vasospasm caused by subarachnoid hemorrhage, which is beneficial for improving the clinical prognosis and quality of life of the elderly patients with subarachnoid hemorrhage.
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Objective:To analyze the clinical phenotype, imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene (TREM2).Methods:Clinical data were collected from a patient with early-onset dementia. Then whole exome sequencing was performed for the proband, followed by Sanger sequencing for the family members.Results:The clinical manifestations of the proband (a 49-year-old female) was personality changes, mental and behavioral abnormalities, memory loss, ataxia, and seizures. Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2, namely c.154C>T (p.R52C) heterozygosity in four family members, and one patient with similar clinical manifestations was deceased. The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy, bilateral white matter hyperintensity, thin corpus callosum. No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions:A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia, epilepsy, but without bone cysts. This mutation is probably pathogenic. This research highlights the importance of TREM2 gene mutation screening in early-onset dementia, especially in those with atypical presentations.
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Objective:To explore whether there were changes in midbrain morphology related to motor function in patients with cerebral small vessel disease (CSVD).Methods:The study was conducted on a subset of patients with CSVD registered at the Department of Neurology of Peking Union Medical College Hospital from 2010 to 2018. All magnetic resonance imaging images were taken with a 3.0 T nuclear magnetic resonance imager. The measurement of anteroposterior diameter of the mesencephalon and the tegmentum of mesencephalon was performed on a personal computer with the image processing software RadiAnt DICOM Viewer. Several clinical manifestations of dyspraxia, dysphagia, dysarthria and dysuria were evaluated by interviewing the patient and family members living with the patient. Kinect depth camera combined with self-developed software platform was used to conduct quantitative evaluation of patients′ motor function. Three parameters, namely walking speed, walking time of three meters and time of standing up and sitting down, were selected from the obtained parameters. SPSS 17.0 software was used for statistical analysis.Results:A total of 176 patients were included, aged 30-88 (64.16±11.57) years. One hundred and fifteen patients were males, accounting for 65.34%. In patients with CSVD, anteroposterior diameter of the mesencephalon and the tegmentum of mesencephalon were negatively correlated with age ( B=-0.032, P<0.001; B=-0.020, P=0.006). The anteroposterior diameter of the mesencephalon was negatively correlated with symptoms of dyskinesia ( OR=0.006, 95% CI 0-0.135, P=0.001), even when the age and gender were adjusted ( OR=0.014,95% CI 0-0.416, P=0.013). The anteroposterior diameter of the mesencephalon was negatively correlated with symptoms of dysuria ( OR=0.046,95% CI 0.002-0.936, P=0.045), but no longer correlated when the age and gender were adjusted. The anteroposterior diameter of tegmentum of mesencephalo was also negatively correlated with symptoms of dyskinesia ( OR=0.035,95% CI 0.002-0.684, P=0.027), but no longer correlated after adjusting for age and gender. Video recording and evaluation of motor function were performed on 87 patients. Spearman correlation analysis showed that none of the three motor function scores was correlated with age or gender. The anteroposteric diameter of the midbrain was positively correlated with walking speed ( r=0.231 ,P=0.040) and negatively correlated with walking time of three meters ( r=-0.304, P=0.005), but not with standing up and sitting down time, while the anteroposteric diameter of tegmentum of mesencephalo was not correlated with all of them. Conclusion:There are changes in mesencephalon morphology in patients with CSVD, structural parameters of mesencephalon are related to motor function and urination function, and mesencephalon atrophy may be an independent related factor for symptoms of dyskinesia in patients with CSVD.
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Objective:To evaluate the clinical value of temporal pole and external capsule white matter hyperintensities (WMHs) on the diagnosie of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by meta-analysis.Methods:PubMed, Cochrane, Embase, VIP database, China Biomedical Literature database, CNKI, Wanfang Data Service Platform were retrieved. The relevant literature of temporal pole and external capsule WMHs for the diagnosis of CADASIL was collected. The retrieval time limit was from the establishment of the databases to April 1, 2020. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of literature. Stata 15.1 software was used for statistical analysis. The fitted Summary Receiver Operating Characteristic (SROC) curve and combined diagnostic effect size were used to evaluate the diagnostic value of temporal pole and external capsule WMHs for CADASIL.Results:A total of 9 articles involving 10 studies were enrolled, including 880 patients. The combined sensitivities of temporal pole and external capsule WMHs for CADASIL were 0.67 (95% confidence interval [ CI] 0.54-0.78) and 0.84 (95% CI 0.72-0.91) respectively, the combined specificities were 0.64 (95% CI 0.47-0.78) and 0.44 (95% CI 0.36-0.53) respectively, the combined positive likelihood ratios were 1.9 (95% CI 1.4-2.6) and 1.5 (95% CI 1.2-1.8) respectively, the combined negative likelihood ratios were 0.51 (95% CI 0.42-0.63) and 0.37 (95% CI 0.20-0.69) respectively, the odds ratios of combined diagnosis were 4 (95% CI 3-5) and 4 (95% CI 2-9) respectively, and the area under the SROC curves were 0.71 (95% CI 0.66-0.74) and 0.62 (95% CI 0.58-0.66) respectively. Conclusions:The temporal pole and external capsule WMHs have limited diagnostic value for CADASIL, and other factors need to be comprehensively considered in the clinical diagnosis process.
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Objective@#To determine the effect of transplanting bone marrow mononuclear cells (BMMCs) on the expression of glial fibrillary acidic protein (GFAP) and Nogo-A around the ischemic foci after focal cerebral ischemia and reperfusion, and to study any role of BMMCs in nerve function recovery.@*Methods@#BMMCs were isolated from the bone marrow of Sprague-Dawley rats. Cerebral ischemia and reperfusion was performed using a nylon thread to occlude the right middle cerebral artery for 2h followed by 24h of reperfusion. The qualified models were selected according to the Longa scale. The 48 models selected were randomly divided into a model group and an observation group, each of 24. Each group was further divided into 7d, 14d and 21d subgroups. 100μl of BMMCs (5×106 /ml) were slowly injected into the ischemic lateral striata of the observation group. The rats in the model group were similarly injected, but with buffered saline solution. The rats were evaluated using the Longa scale after 7d, 14d and 21d. The rats were then sacrificed and the brain was resected. Immunohistochemical assays quantified the expression of GFAP and Nogo-A around the ischemic foci.@*Results@#Compared with the model group, the rats in the observation group showed less neurological deficit on the 21st day, significantly greater expression of GFAP and significantly less Nogo-A expression on days 14 and 21. Nogo-A expression on the 21st day was also significantly lower than on the 14th day in the observation group.@*Conclusion@#BMMC transplantation can promote recovery from nerve damage after focal cerebral ischemia, which is probably related to enhanced expression of GFAP and restrained expression of Nogo-A in the brain tissues surrounding ischemic lesions.
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Objective:To determine the effect of transplanting bone marrow mononuclear cells (BMMCs) on the expression of glial fibrillary acidic protein (GFAP) and Nogo-A around the ischemic foci after focal cerebral ischemia and reperfusion, and to study any role of BMMCs in nerve function recovery.Methods:BMMCs were isolated from the bone marrow of Sprague-Dawley rats. Cerebral ischemia and reperfusion was performed using a nylon thread to occlude the right middle cerebral artery for 2h followed by 24h of reperfusion. The qualified models were selected according to the Longa scale. The 48 models selected were randomly divided into a model group and an observation group, each of 24. Each group was further divided into 7d, 14d and 21d subgroups. 100μl of BMMCs (5×10 6 /ml) were slowly injected into the ischemic lateral striata of the observation group. The rats in the model group were similarly injected, but with buffered saline solution. The rats were evaluated using the Longa scale after 7d, 14d and 21d. The rats were then sacrificed and the brain was resected. Immunohistochemical assays quantified the expression of GFAP and Nogo-A around the ischemic foci. Results:Compared with the model group, the rats in the observation group showed less neurological deficit on the 21st day, significantly greater expression of GFAP and significantly less Nogo-A expression on days 14 and 21. Nogo-A expression on the 21st day was also significantly lower than on the 14th day in the observation group.Conclusion:BMMC transplantation can promote recovery from nerve damage after focal cerebral ischemia, which is probably related to enhanced expression of GFAP and restrained expression of Nogo-A in the brain tissues surrounding ischemic lesions.
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Objective:To summarize the clinical and imaging features of five patients of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with cysteine-sparing NOTCH3 gene missense mutations and explore potential pathogenicity of gene mutations.Methods:The clinical data from five patients who were admitted to the People′s Hospital of Zhengzhou University from March 2017 to November 2018 were collected. The patients were found to carry cysteine-sparing NOTCH3 gene mutations through genetic testing and diagnosed pathologically. They were probands confirmed from five unrelated family and all five patients were performed full exon detection and skin biopsy.Results:Genetic testing identified five patients with cysteine-sparing NOTCH3 gene missense mutations, a total of five different mutations, including p.R75Q, p.D80G, p.V237M, p.S1418L and p.R1761H. The first three mutations were found in the epidermal growth factor-like repeats (EGFr), the latter two mutations near the transmembrane domain. Granular osmiophilic material was identified in all cases examined with skin biopsy. The age at initial symptom onset of these five cases was ranged from 22 to 58 years and three cases presented cardiovascular risk factors. The primary clinical manifestations included migraine in one case, ischemic stroke in three cases, psychiatric disturbances in four cases, cognitive dysfunction in five cases, while gait disturbance, pseudobulbar palsy, and seizures accounted for only one case each. Magnetic resonance imaging of five patients all showed white matter hyperintensities (WMLs) and lacunar infarcts, and WMLs involved the anterior temporal pole and external capsules in three cases separately. According to the criteria proposed by Mui?o et al for evaluating the pathogenicity of cysteine-sparing NOTCH3 mutations, all five mutations are potentially pathogenic.Conclusions:Most characteristics of CADASIL patients with cysteine-sparing NOTCH3 gene mutations are similar to those of CADASIL patients with cysteine NOTCH3 gene mutations. Mutations not involving the EGFr may also have potential pathogenicity, and the specific mechanism still needs further study.
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Objective:To investigate the clinical, myopathological and genetic mutation characteristics in two Chinese families with paramyotonia congenita (PMC).Methods:Clinical manifestations, electrophysiology, muscle pathology and gene sequencing of two Chinese families with PMC were analyzed retrospectively.Results:Family 1 involved 12 patients in 4 consecutive generations and family 2 involved only 1 patient in 3 generations. The onset of symptoms in all patients started at early childhood. Both probands presented with myotonia triggered by cold and paroxysmal weakness. However, the other 11 patients in family 1 only manifested cold-induced myotonia. Serum creatine kinase (CK) was slightly elevated between attacks of weakness in the 2 probands, and was even greater than 10 000 U/L during the episodes of weakness in the second proband, whose lower limb MRI revealed edema in bilateral medial gastrocnemius. Electromyography showed diffuse myotonia discharge and myogenic impairment in both probands, and myotonia discharge in the first proband′s mother. Muscle pathology of both probands showed mild myopathic changes, and tube aggregation was occasionally observed in the second one. Genetic testing revealed a maternally inherited heterozygous R1448H mutation of SCN4A gene in the first proband and part of his family. A novel heterozygous R1448G mutation of SCN4A gene was reported in the second proband.Conclusions:Cold-triggered myotonia with or without paroxysmal weakness are the common characteristics of PMC. Myotonic potential and myogenic impairment can be tested in electromyography. The p.R1448G mutation is a new missense mutation.
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Objective:To investigate the effect of Donepezil treatment on the expression of high mobility group box 1 protein(HMGB1)in serum and cerebrospinal fluid in Alzheimer's disease patients.Methods:This is a single-center observational stady.A total of 120 Alzheimer's disease patients admitted in our hospital from March 2017 to may 2019 were randomly divided into the control group receiving the routine drug therapy(n=60)and the Donepezil group receiving Donepezil hydrochloride(5 mg/d)as an add-on to medicine of control group(n=60). The expression levels of HMGB1 in serum and cerebrospinal fluid, Alzheimer's disease assessment scale(ADAS-Cog), mini-mental state examination(MMSE)scores, activities of daily living(ADL)and neuropsychiatric inventory(NPI)were compared before versus after 1 month of treatment.Results:After the Donepezil treatment, the ADAS-Cog score was lower, MMSE score was higher, ADL score was higher and NPI score was lower in the Donepezil group than in the control group(25.2± 2.7 vs.33.4± 3.6, 23.3± 2.1 vs.19.4±1.9, 56.3±2.1 vs.46.9±1.6, 16.2±2.3 vs.22.3± 2.6, P<0.05). After the Donepezil treatment, the levels of HMGB1 in serum[(45.3±5.3)μg/L vs.(56.3±4.4)μg/L]and in cerebrospinal fluid[(39.2±3.3)μg/L vs.(47.1±3.9)μg/L]were lower in the Donepezil group than in the control group(all P<0.05). Conclusions:Donepezil treatment can downregulate the HMGB1 expression levels in serum and cerebrospinal fluid in Alzheimer's disease patients, which may related to the improvement of cognitive function in Alzheimer's disease patients.
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Objective@#To analyze the clinical data of a family with early-onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family.@*Methods@#The clinical data of a proband who was clinically diagnosed as early-onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3.@*Results@#The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta-amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy.@*Conclusions@#The study identified the pathogenic mutation of the beta-amyloid precursor protein gene p.V717I in six patients of a family with early-onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early-onset Alzheimer′s disease in Chinese population.
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Objective@#To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy.@*Methods@#Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband.@*Results@#The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c. 341G>A (p.G114D) mutation in exon 2 of the INF2 gene.@*Conclusion@#The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c. 341G>A mutation of the INF2 gene.
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Objective To study changes in hepatic and renal function,serum lipids and homocysteine levels in patients with multiple system atrophy(MSA),and to explore the relationship of serum biochemical indexes with MSA and its severity.Methods A total of 86 hospitalized patients with MSA at our department from January 2014 to June 2017 were retrospectively analyzed.Eightyfive healthy subjects undergoing health physical examinations at our hospital during the same period were enrolled as a control group.Serum lipid levels and liver and renal function were compared between the two groups.After stratified by gender,the correlations of liver and renal function,serum lipids and homocysteine levels with MSA and its severity were analyzed.Results Serum levels of total cholesterol,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were lower in the MSA group than in the control group(P＜0.01).Serum levels of total cholesterol,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were lower in male patients with MSA than in male healthy controls(P＜0.01).Serum levels of uric acid were lower in female patients with MSA than in female healthy controls (P ＜ 0.05).Serum levels of total cholesterol and low-density lipoprotein cholesterol were lower in MSA patients aged under 60 years than in healthy controls aged under 60 years (P ＜ 0.01).Serum levels of total cholesterol (r =0.34,P ＜ 0.01),high-density lipoprotein cholesterol(r =-0.27,P ＜ 0.01),low-density lipoprotein cholesterol(r =0.32,P ＜ 0.01)and uric acid(r =0.15,P ＜ 0.05)were correlated with MSA,but they were not independent risk factors.Serum levels of total cholesterol(r =0.27,P ＜0.05) and low-density lipoprotein cholesterol (r =0.23,P ＜0.05)were correlated with the severity of MSA,but they were not independent risk factors (r =-0.381,P ＞0.05).Conclusions Serum levels of lipids and urea are associated with MSA,but they are not independent risk factors for MSA or its severity.Gender may affect the occurrence of MSA,but it needs to be further confirmed.