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Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with genetic and clinical heterogeneity characterized by spasticity and weakness of the lower limbs. It includes four genetic inheritance forms: autosomal dominant inheritance (AD), autosomal recessive inheritance (AR), X-linked inheritance, and mitochondrial inheritance. To date, more than 82 gene loci have been found to cause HSP, and SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs) with a thin corpus callosum (TCC), presents with early cognitive impairment and slowly progressive leg weakness. Here, we reported a homozygous pathogenic variant in ZFYVE26. A 19-year-old Chinese girl was admitted to our hospital presenting with a 2-year progressive bilateral leg spasticity and weakness; early cognitive impairment; corpus callosum dysplasia; chronic neurogenic injury of the medulla oblongata supplied muscles; and bilateral upper and lower limbs on electromyogram (EMG). Based on these clinical and electrophysiological features, HSP was suspected. Exome sequencing of the family was performed by high-throughput sequencing, and an analysis of the patient showed a ZFYVE26 NM_015346: c.7111dupA p.(M2371Nfs*51) homozygous mutation. This case reported a new ZFYVE26 pathogenic variant, which was different from the SPG15 gene mutation reported earlier.
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RATIONALE: Few reports of idiopathic hypereosinophilic syndrome exist presenting as ischemic cerebrovascular disease, and the majority are watershed infarction. We report the first case of idiopathic hypereosinophilic syndrome that has clinical features of capsular warning syndrome lasting 6 weeks. PATIENT CONCERNS: A 26-year-old man complained of recurrent right limb weakness, accompanying slurred speech, and right facial paresthesia. DIAGNOSES: The patient was diagnosed with idiopathic hypereosinophilic syndrome (IHES). INTERVENTIONS: Adequate glucocorticoid and anticoagulant treatments were given. OUTCOMES: The patient's motor ability improved, and he was discharged 2 weeks later. Muscle strength in the right-side extremities had fully recovered at a 3-month follow-up after discharge. LESSONS: This case suggests that idiopathic hypereosinophilic syndrome should be considered as a cause of capsular warning syndrome, and the dose of glucocorticoid and the efficacy evaluation index needs to be reevaluated for the treatment of ischemic cerebrovascular disease associated with idiopathic hypereosinophilic syndrome.
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Líquidos Corporales , Trastornos Cerebrovasculares , Síndrome Hipereosinofílico , Masculino , Humanos , Adulto , Glucocorticoides/uso terapéutico , Síndrome Hipereosinofílico/complicaciones , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/tratamiento farmacológico , AnticoagulantesRESUMEN
Vascular cognitive impairment (VCI) is the most common type of dementia after Alzheimer's disease (AD). Effective treatments for VCI are currently lacking. MicroRNA (miR)- 140-5p is associated with cerebral ischemia and poststroke depression, but its relationship with VCI remains unknown. A VCI model was established by bilateral common carotid artery occlusion (BCCAO) for 17 min in mice. Neurogenesis was evaluated by immunostaining for Nestin/bromodeoxyuridine (BrdU), NeuN/BrdU, and doublecortin (DCX)/BrdU. Neuroplasticity was assessed by quantifying synapsin-I and postsynaptic density protein 95 (PSD-95) protein levels. Predicted target genes were screened and verified using the dual luciferase reporter gene system. MiR-140-5p was upregulated in the hippocampus of the BCCAO mice 2 weeks following ischemia. Compared with control groups, the AAV-miR-140-5p group exhibited poorer cognitive performance alongside lower numbers of DCX/BrdU and NeuN/BrdU and less synapsin-I and PSD-95 in the dentate gyrus (P < 0.05). MiR-140-5p overexpression decreased the predicted target gene Prox1. Dual luciferase reporter system confirmed that Prox1 was a direct target site for miR-140-5p. In conclusion, our results suggest that miR-140-5p inhibits neurogenesis and neuroplasticity via downregulation of Prox1 and aggravates VCI. Our findings highlight that miR-140-5p is involved in the pathological process of VCI and provides information for the development of new treatments, which may need further inhibition tests to verify.
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Isquemia Encefálica , Disfunción Cognitiva , MicroARNs , Animales , Isquemia Encefálica/metabolismo , Disfunción Cognitiva/metabolismo , Hipocampo/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Neurogénesis/fisiologíaRESUMEN
BACKGROUND: Many studies among different ethnic populations suggested that angiotensin converting enzyme (ACE) gene polymorphisms were associated with susceptibility to Alzheimer's disease (AD). However, the results remained inconclusive. In the present meta-analysis, we aimed to clarify the effect of ACE polymorphisms on AD risk using all available relevant data. METHODS: Systemic literature searches were performed using PubMed, Embase, Alzgene and China National Knowledge Infrastructure (CNKI). Relevant data were abstracted according to predefined criteria. RESULTS: Totally, 82 independent cohorts from 65 studies were included, focusing on five candidate polymorphisms. For rs1799752 polymorphism, in overall analyses, the insertion (I) allele conferred increased risk to AD compared to the deletion (D) allele (I vs. D: OR = 1.091, 95% CI = 1.007-1.181, p = 0.032); while the I carriers showed increased AD susceptibility compared with the D homozygotes (II + ID vs. DD: OR = 1.131, 95% CI = 1.008-1.270, p = 0.036). However, none of the positive results passed FDR adjustment. In subgroup analysis restricted to late-onset individuals, the associations between rs1799752 polymorphism and AD risk were identified using allelic comparison (OR = 1.154, 95% CI = 1.028-1.295, p = 0.015, FDR = 0.020), homozygotes comparison, dominant model and recessive model (II vs. ID + DD: OR = 1.272, 95% CI = 1.120-1.444, p < 0.001, FDR < 0.001). Nevertheless, no significant association could be revealed after excluding studies not in accordance with Hardy-Weinberg equilibrium (HWE). In North Europeans, but not in East Asians, the I allele demonstrated increased AD susceptibility compared to the D allele (OR = 1.096, 95% CI = 1.021-1.178, p = 0.012, FDR = 0.039). After excluding HWE-deviated cohorts, significant associations were also revealed under homozygotes comparison, additive model (ID vs. DD: OR = 1.266, 95% CI = 1.045-1.534, p = 0.016, FDR = 0.024) and dominant model (II + ID vs. DD: OR = 1.197, 95% CI = 1.062-1.350, p = 0.003, FDR = 0.018) in North Europeans. With regard to rs1800764 polymorphism, significant associations were identified particularly in subgroup of European descent under allelic comparison (T vs. C: OR = 1.063, 95% CI = 1.008-1.120, p = 0.023, FDR = 0.046), additive model and dominant model (TT + TC vs. CC: OR = 1.116, 95% CI = 1.018-1.222, p = 0.019, FDR = 0.046). But after excluding studies not satisfying HWE, all these associations disappeared. No significant associations were detected for rs4343, rs4291 and rs4309 polymorphisms in any genetic model. CONCLUSIONS: Our results suggested the significant but modest associations between rs1799752 polymorphism and risk to AD in North Europeans. While rs4343, rs4291 and rs4309 polymorphisms are unlikely to be major factors in AD development in our research.
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Enfermedad de Alzheimer/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Alelos , Predisposición Genética a la Enfermedad , HumanosRESUMEN
OBJECTIVE: This study aimed to explore the correlation between white matter hyperintensity (WMH) and post-stroke depression (PSD) at 3 months, and to further investigate sex differences in the pathogenesis of PSD. METHODS: A total of 238 consecutive patients with acute cerebral infarction were recruited. PSD was assessed at 2 weeks and at 3 months after stroke onset. All stroke cases were divided into four subgroups according to the diagnosis of depression at two time nodes: continuous depression; depression remission; late-onset PSD; and continuous non-depression. The Fazekas and Scheltens visual rating scales were adopted to assess WMH. RESULTS: Logistic regression revealed that the presence of periventricular white matter hyperintensity (PVWMH) at baseline in male patients was an independent risk factor for PSD at 3 months. Further subgroup analysis revealed that PVWMH was associated with late-onset PSD in males, but not with continuous depression 3 months after stroke. Male acute stroke patients with PVWMH at baseline were more likely to develop PSD at 3 months, especially late-onset PSD. CONCLUSION: Our data suggest that sex differences may influence the pathogenesis of PSD.
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PURPOSE: To explore the relationship between the monocyte-to-lymphocyte ratio (MLR) and depression three months after acute ischemic stroke. PATIENTS AND METHODS: From May 2013 to September 2014, 203 patients with acute ischemic stroke were recruited within 7 days post-stroke from Shanghai Ruijin Hospital and blood samples were collected after admission. The Hamilton Depression Scale and Clinical Review were evaluated at 3 months after stroke. Based on the Diagnostic and Statistical Manual of Mental Disorders-IV diagnostic criteria, we divided patients into post-stroke depression (PSD) and non-PSD groups. We analyzed the intergroup difference in MLR and the contributing factors. Moreover, dynamic changes in monocytes, lymphocytes and MLR at four different time intervals for all the stroke patients and their relationship with PSD patients were also studied. RESULTS: The NIHSS scores and MLR in the PSD group were significantly higher than in the non-PSD group (p<0.05). Logistic regression analysis revealed MLR was an independent risk factor for PSD (odds ratio: 18.020, 95% confidence interval: 1.127â288.195, p=0.041). MLR correlated negatively with cholesterol and low-density lipoprotein (r=-0.160 and -0.165, respectively, p<0.05). Within 7 days post-acute ischemic stroke, monocytes gradually increased while lymphocytes remained unchanged for all the stroke patients. The MLR value was significantly higher in the PSD group than in the non-PSD group within 24 h post-stroke (p<0.05), but there was no difference in the other three time-intervals between the two groups. CONCLUSION: The admission MLR, particularly within 24 h post-stroke, was associated with PSD at 3 months, implying that the MLR might be involved in the PSD inflammatory mechanism.