neurological deficits

神经功能缺损
  • 文章类型: Journal Article
    电针(EA)已被证明可促进脑缺血再灌注(I/R)损伤后的功能恢复。然而,线粒体动力学对恢复的贡献尚不清楚.这项研究的目的是研究线粒体动力学是否参与EA对脑I/R损伤的影响。
    通过大脑中动脉阻塞/再灌注建立脑I/R损伤的大鼠。随后,电针应用于百会(GV20)和大珠(GV14)穴位,频率为2Hz/5Hz,强度为1.0mA,每次20分钟,一天一次,连续七天。通过改良的神经系统严重程度评分(mNSS)评估治疗结果,2,3,5-三苯基-氯化三唑(TTC)染色,和苏木精-伊红(HE)染色。在透射电镜下观察线粒体形态。使用ELISA评估三磷酸腺苷(ATP)含量和ATP合酶(ATP酶)活性以测量线粒体功能。最后,线粒体动力学相关分子,包括动力蛋白相关蛋白1(Drp1),裂变1(Fis1),mitofusin1(Mfn1),mitofusin2(Mfn2),和视神经萎缩1(OPA1),通过Westernblot和免疫荧光染色进行检测。
    脑I/R损伤引起的神经功能障碍,脑梗死和神经元损伤,所有这些都得到了EA的改善。EA改善了线粒体形态和功能。此外,EA改变了线粒体动力学的平衡。具体来说,数据显示Drp1和Fis1的表达显着降低,导致线粒体裂变的抑制。此外,Mfn1,Mfn2和Opa1与线粒体融合有关,电针治疗后得到有效推广。然而,假电针对脑I/R损伤大鼠未显示任何神经保护作用。
    总之,我们的研究表明,线粒体动力学的平衡对于EA治疗脑I/R损伤至关重要。
    UNASSIGNED: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury.
    UNASSIGNED: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining.
    UNASSIGNED: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA. And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury.
    UNASSIGNED: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury.
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  • 文章类型: Journal Article
    背景:小动脉闭塞(SAO)是一种常见的缺血性卒中亚型。然而,其临床结果可能比通常理解的更严重。SAO的严重程度可能会有所不同,范围从轻度到中度。铁沉积与中风的发生和进展有关。然而,其在SAO中的具体分布和与卒中严重程度的关系尚不清楚.本研究的目的是通过定量磁化率图(QSM)研究轻度SAO卒中(SAO-MiS)和中度SAO卒中(SAO-MoS)之间铁沉积的差异及其与神经功能缺损的关系。
    方法:根据美国国立卫生研究院卒中量表(NIHSS)评分,纳入初发24小时内的68名SAO参与者,并分为SAO-MiS和SAO-MoS。QSM帮助计算了磁化率图,反映大脑中的铁含量。使用逐体素统计分析来分析磁化率图,以比较SAO-MiS和SAO-MoS之间的铁沉积。然后,差异分布的铁沉积有助于使用支持向量机(SVM)方法区分轻度和中度中风。
    结果:与SAO-MiS相比,SAO-MoS描绘了左苍白球中铁沉积的升高,海马旁回,和额上回内侧区,右额上/中回和双侧补充运动区较低。基于铁沉积,SVM分类器的分析揭示了区分SAO-MoS和SAO-MiS的能力。此外,纤维蛋白原,甘油三酯(TG),总胆固醇(TC)与特定脑区的QSM值相关。
    结论:我们的研究首次揭示了SAO后的脑铁分布以及SAO-MiS和SAO-MoS中不同分布的铁沉积。结果表明,铁沉积可能在SAO的病理生理学中起作用,并与卒中严重程度相关。
    BACKGROUND: Small artery occlusion (SAO) is a common ischemic stroke subtype. However, its clinical outcome can be more severe than commonly understood. The severity of SAO can vary, ranging from mild to moderate. Iron deposition has been associated with the development and progression of stroke. However, its specific distribution and relationship with stroke severity in SAO remain unclear. The study\'s purpose is to investigate the differences in iron deposition between mild stroke with SAO (SAO-MiS) and moderate stroke with SAO (SAO-MoS) through quantitative susceptibility mapping (QSM) and its association with neurological deficits.
    METHODS: Sixty-eight SAO participants within 24 hours of first onset were enrolled and separated into SAO-MiS and SAO-MoS according to the National Institutes of Health Stroke Scale (NIHSS) scores. QSM helped calculate the susceptibility maps, reflecting the iron content within the brain. The susceptibility maps were analyzed using voxel-wise statistical analysis to compare the iron deposition between SAO-MiS and SAO-MoS. Then, differentially distributed iron deposition helped differentiate between mild and moderate stroke using support vector machine (SVM) methods.
    RESULTS: Compared with SAO-MiS, SAO-MoS depicted elevated iron deposition in the left pallidum, parahippocampal gyrus, and superior frontal gyrus medial region, and is lower in the right superior/middle frontal gyrus and bilateral supplementary motor area. Based on iron deposition, the SVM classifier\'s analysis revealed a high power to discriminate SAO-MoS from SAO-MiS. In addition, fibrinogen, triglyceride (TG), and total cholesterol (TC) were linked with QSM values in specific brain regions.
    CONCLUSIONS: Our study first revealed the brain iron distribution after SAO and differently distributed iron deposition in SAO-MiS and SAO-MoS. The results indicate that iron deposition could play a role in the pathophysiology of SAO and its correlation with stroke severity.
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  • 文章类型: Journal Article
    Cervical stenosis is a clinical picture that is regularly encountered by both hospital physicians and orthopedic surgeons in the daily clinical practice. While advanced cervical spinal canal stenosis may lead to myelopathic symptoms in cases of sufficient manifestation and spinal cord injury, neuroforaminal stenosis leads to radicular symptoms due to compression of the nerve roots. The clinical examination can provide initial clues as to the suspected cause of the patient\'s symptoms; however, reliable diagnostics are based only on sectional imaging of the cervical spine. Depending on the extent of the symptoms, the treatment options vary between nonsurgical treatment for moderate symptoms without neurological deficits and surgical decompression of the spinal cord or nerve roots. The surgical treatment can be performed from anterior or posterior depending on the findings. Surgery can lead to an improvement of the neurological symptoms; however, the primary aim of surgical treatment is to avoid deterioration of the neurological deficits.
    UNASSIGNED: Die zervikale Stenose ist ein Krankheitsbild, das sowohl dem im Krankenhaus tätigen Mediziner wie auch dem niedergelassenen Orthopäden im klinischen Alltag regelmäßig begegnet. Während die zervikale Spinalkanalstenose bei entsprechender Ausprägung und Rückenmarkschädigung zu myelopathischen Symptomen führt, kommt es im Falle einer Neuroforamenstenose aufgrund der im Vordergrund stehenden Wurzelkompression zu radikulären Symptomen. Die klinische Untersuchung kann erste Anhaltspunkte für die zu vermutende Ursache der Beschwerden des Patienten geben. Eine sichere Diagnostik gelingt jedoch nur mit einer Schichtbildgebung der Halswirbelsäule. Die Therapieoptionen variieren, abhängig vom Ausmaß der Symptomatik zwischen einer nichtoperativen Behandlung bei moderaten Beschwerden ohne neurologische Ausfallerscheinungen und einer operativen Dekompression von Myelon bzw. Nervenwurzeln. Die operative Therapie kann je nach Befundlage von ventral oder dorsal erfolgen. Nach einer Operation kann es zu einer Verbesserung der neurologischen Symptomatik kommen. Das primäre Ziel der operativen Versorgung stellt jedoch die Vermeidung einer Verschlechterung neurologischer Defizite dar.
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  • 文章类型: Case Reports
    中枢神经细胞瘤,一种罕见的颅内肿瘤,主要位于侧脑室和第三脑室,由于其不同的临床表现,提出了诊断和治疗的挑战。我们报告了一例53岁的男性,表现为右上下肢无力,头痛,视力模糊,和刺痛的感觉,导致中枢神经细胞瘤与相关脑积水的诊断。初步评估,包括磁共振成像(MRI)和随后的计算机断层扫描(CT)扫描,揭示了肿瘤的特征。病人接受了两阶段的外科手术,包括肿瘤切除和脑室腹膜分流术,术后因呼吸道并发症进行气管造口术。组织病理学检查证实诊断为中枢神经细胞瘤,促进多学科管理和进一步转诊以进行长期随访。这一案例凸显了综合评价的重要性,多学科合作,并继续研究优化中枢神经细胞瘤的诊断和治疗。
    Central neurocytoma, a rare intracranial tumor predominantly located in the lateral and third ventricles, presents a diagnostic and therapeutic challenge due to its varied clinical manifestations. We report the case of a 53-year-old male presenting with right upper and lower limb weakness, headaches, blurred vision, and tingling sensations, leading to the diagnosis of central neurocytoma with associated hydrocephalus. Initial evaluation, including magnetic resonance imaging (MRI) and subsequent computed tomography (CT) scans, revealed characteristic features of the tumor. The patient underwent a two-stage surgical intervention, including tumor excision and ventriculoperitoneal shunting, followed by a tracheostomy due to respiratory complications post-surgery. Histopathological examination confirmed the diagnosis of central neurocytoma, prompting multidisciplinary management and further referral for long-term follow-up. This case underscores the importance of comprehensive evaluation, multidisciplinary collaboration, and continued research in optimizing the diagnosis and management of central neurocytomas.
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  • 文章类型: Journal Article
    背景:脊柱转移需要手术的患者的年龄,主要是65岁以上的人,由于癌症治疗的改善而上升。手术干预的目标是急性神经功能缺损和不稳定。抗凝剂的使用越来越多,尤其是老年人,但在管理出血并发症方面构成挑战。该研究检查了术前抗凝/抗血小板使用与脊柱转移手术中出血风险之间的相关性。这对于优化患者预后至关重要。
    方法:在我科2010年至2023年的一项回顾性研究中,对脊柱肿瘤手术患者进行了分析。数据包括人口统计,神经状况,外科手术,术前抗凝血剂/抗血小板使用,术中/术后凝血管理,和再出血的发生率。凝血管理包括失血评估,凝血因子给药,和术后液体平衡监测。入院时记录实验室参数,preop,posop,和放电。
    结果:290例脊柱转移瘤患者接受手术治疗,主要是男性(63.8%,n=185),中位年龄为65岁。术前,24.1%(n=70)接受口服抗凝剂或抗血小板治疗。30天内,再出血率为4.5%(n=9),与术前抗凝状态无关(p>0.05)。术前神经功能缺损(p=0.004)与再出血风险和手术治疗水平之间存在相关性,与较少的水平与较高的术后出血发生率相关(p<0.01)。
    结论:无论患者的术前抗凝状态如何,脊柱转移癌的手术干预似乎都是安全的。然而,仍然必须为每位患者定制术前计划和准备,强调细致的风险-效益分析和优化围手术期护理。
    BACKGROUND: The age of patients requiring surgery for spinal metastasis, primarily those over 65, has risen due to improved cancer treatments. Surgical intervention targets acute neurological deficits and instability. Anticoagulants are increasingly used, especially in the elderly, but pose challenges in managing bleeding complications. The study examines the correlation between preoperative anticoagulant/antiplatelet use and bleeding risks in spinal metastasis surgery, which is crucial for optimizing patient outcomes.
    METHODS: In a retrospective study at our department from 2010 to 2023, spinal tumor surgery patients were analyzed. Data included demographics, neurological status, surgical procedure, preoperative anticoagulant/antiplatelet use, intra-/postoperative coagulation management, and the incidence of rebleeding. Coagulation management involved blood loss assessment, coagulation factor administration, and fluid balance monitoring post-surgery. Lab parameters were documented at admission, preop, postop, and discharge.
    RESULTS: A cohort of 290 patients underwent surgical treatment for spinal metastases, predominantly males (63.8%, n = 185) with a median age of 65 years. Preoperatively, 24.1% (n = 70) were on oral anticoagulants or antiplatelet therapy. Within 30 days, a rebleeding rate of 4.5% (n = 9) occurred, unrelated to preoperative anticoagulation status (p > 0.05). A correlation was found between preoperative neurologic deficits (p = 0.004) and rebleeding risk and the number of levels treated surgically, with fewer levels associated with a higher incidence of postoperative bleeding (p < 0.01).
    CONCLUSIONS: Surgical intervention for spinal metastatic cancer appears to be safe regardless of the patient\'s preoperative anticoagulation status. However, it remains imperative to customize preoperative planning and preparation for each patient, emphasizing meticulous risk-benefit analysis and optimizing perioperative care.
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  • 文章类型: Case Reports
    此案例报告描述了演示文稿,诊断,以及一名61岁女性的手术治疗,该女性被送往三级护理医院,有两个月的颈部疼痛和四肢无力病史。尽管没有明确的创伤史,详细检查显示颈部弯曲受限,椎旁肌痉挛,和神经缺陷。增强MRI显示C5-C6水平的椎体骨髓炎和椎间盘炎,怀疑有感染性病因,可能是结核性脊柱炎.患者接受了颈椎前路减压术,C5-C6全切术和C4-C7融合。术后管理包括静脉注射抗生素,物理治疗,和抗结核治疗。患者恢复令人满意,该病例强调了综合评估和及时干预治疗复杂脊柱感染的重要性。
    This case report describes the presentation, diagnosis, and surgical management of a 61-year-old female admitted to a tertiary care hospital with a two-month history of neck pain and weakness in all four limbs. Despite the absence of a clear history of trauma, a detailed examination revealed restricted neck flexion, paraspinal muscle spasm, and neurological deficits. Contrast-enhanced MRI indicated vertebral osteomyelitis and discitis at the C5-C6 level, with a suspected infective etiology, possibly tuberculosis spondylitis. The patient underwent anterior cervical decompression, corpectomy of C5-C6, and fusion of C4-C7. Postoperative management included intravenous antibiotics, physiotherapy, and anti-tubercular treatment. The patient exhibited satisfactory recovery, and this case underscores the importance of comprehensive evaluation and prompt intervention in managing complex spinal infections.
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  • 文章类型: Case Reports
    颈神经根病是一种常见病,其特征是颈部疼痛放射到上肢和下肢,经常伴有刺痛感,麻木,和弱点。我们介绍了一名32岁的男性,他患有左侧颈神经根病和神经功能缺损。临床检查显示左侧C5/C6/C7感觉减退,握力减弱,左上肢和下肢的力量降低,和一个积极的喘振测试。颈椎的磁共振成像(MRI)显示C4-C5和C5-C6水平的多节段颈椎间盘突出症,导致狭窄。患者在C5-C6水平下进行了颈前路椎间盘切除术,并进行了人工椎间盘置换(颈椎间盘置换术(CDA))。手术过程顺利,患者在术后两周内神经系统症状迅速缓解。手术后一周的随访X射线照片显示,在人造椎间盘原位的情况下,每个手术水平的运动范围保持不变。此病例强调了使用前路颈椎间盘切除术和人工椎间盘置换术成功治疗神经根型颈椎病伴神经功能缺损。及时的干预导致症状的解决和功能的恢复,证明了这种手术方法在减轻神经根症状和保持颈椎活动能力方面的功效。在这种情况下,需要进一步的研究和长期随访来验证人工椎间盘置换术的长期结果和耐久性。
    Cervical radiculopathy is a common condition characterized by neck pain radiating to the upper and lower limbs, often accompanied by tingling sensations, numbness, and weakness. We present the case of a 32-year-old male who presented with left-sided cervical radiculopathy and neurological deficits. Clinical examination revealed left C5/C6/C7 hypoesthesia, diminished grip strength, reduced power in the left upper and lower extremities, and a positive Spurling test. Magnetic resonance imaging (MRI) of the cervical spine revealed multilevel cervical disc herniations at C4-C5 and C5-C6 levels, resulting in stenosis. The patient underwent anterior cervical discectomies with artificial disc replacement (cervical disc arthroplasty (CDA)) at the C5-C6 level. The surgical procedure was uneventful, and the patient experienced prompt relief from neurological symptoms within two weeks postoperatively. Follow-up radiographs at one week post-surgery demonstrated a preserved range of motion at each operated level with the artificial disc in situ. This case highlights the successful management of cervical radiculopathy with neurological deficits using anterior cervical discectomy and artificial disc replacement. The timely intervention led to the resolution of symptoms and restoration of function, demonstrating the efficacy of this surgical approach in alleviating radicular symptoms and preserving cervical spine mobility. Further studies and long-term follow-up are warranted to validate the long-term outcomes and durability of artificial disc replacement in such cases.
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  • 文章类型: Journal Article
    研究甘油三酯-葡萄糖(TyG)指标与肥胖指标的关系与新发急性缺血性卒中的初始神经严重程度和短期预后。
    收集2021年11月至2023年10月北华大学附属医院卒中病房收治的急性缺血性卒中患者的数据。通过结合TyG和肥胖指数计算这两个指标:TyG体重指数(TyG-BMI)和TyG腰围(TyG-WC)。采用美国国立卫生研究院卒中量表(NIHSS)对入院24小时内出现神经功能缺损的患者进行评估和分组:轻度卒中(NIHSS≤5)和中重度卒中(NIHSS>5)。在出院时或疾病发作后14天使用改良的Rankin量表(mRS)评估短期预后,并将其分组:预后良好(mRS≤2)和预后不良(mRS>2)。根据TyG-BMI和TyG-WC的四分位数,将患者分为4组:Q1,Q2,Q3和Q4.采用多因素logistic回归分析评估TyG-BMI和TyG-WC与严重程度和短期预后的相关性。
    该研究包括456名患者。调整多个变量后,结果显示,与四分位数1相比,TyG-BMI四分位数4的患者发生中重度中风的风险降低[Q4:OR:0.407,95CI(0.185-0.894),P=0.025];TyG-BMI四分位数2、3和4的患者短期不良结局的风险依次较低[Q2:OR:0.394,95CI(0.215-0.722),P=0.003;Q3:OR:0.324,95CI(0.163-0.642),P=0.001;Q4:OR:0.158,95CI(0.027-0.349),P<0.001];TyG-WC四分位数3和4的患者发生中重度卒中的风险依次较低[Q3:OR:0.355,95CI(0.173-0.728),P=0.005;Q4:OR:0.140,95CI(0.056-0.351),P<0.001];TyG-WC四分位数3和4的患者短期不良结局的风险依次较低[Q3:OR:0.350,95CI(0.175-0.700),P=0.003;Q4:OR:0.178,95CI(0.071-0.451),P<0.001]。
    TyG-WC和TyG-BMI与新发急性缺血性卒中的严重程度和短期预后相关。随着TyG-WC和TyG-BMI的增加,卒中严重程度降低,短期结局更好.
    UNASSIGNED: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke.
    UNASSIGNED: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome.
    UNASSIGNED: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001].
    UNASSIGNED: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.
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  • 文章类型: Case Reports
    脊髓损伤(SCI)可引起神经源性休克,伴有心动过缓和低血压。如果之前没有明显的创伤性发作,并且神经系统检查因患者的智力障碍而复杂化,SCI可能会被忽视。一位63岁的智障人士到我们医院就诊。病人倒在地板上;然而,未观察到明显的头部或颈部外伤.在计算机断层扫描上确认没有颅内血肿后,患者返回家中。然而,患者因低血压和心动过缓而再次入院,和病态窦房结综合征被怀疑。由于表现为四肢运动无力和尿潴留,脊柱磁共振成像筛查显示颈髓损伤和颈椎病。怀疑与跌倒有关的宫颈SCI。颈椎减压手术和康复治疗有助于改善患者状况。在这里,我们报告了一例智障病例,其中SCI最初被忽视.在我们的病例中,患者之前的严重创伤性事件或智力残疾不会导致忽视SCI。临床医生应该对这种罕见的情况保持谨慎。
    Spinal cord injury (SCI) can cause neurogenic shock accompanied by bradycardia and hypotension. If no preceding traumatic episodes are apparent and the neurological examination is complicated by the patient\'s intellectual disability, SCI is likely to be overlooked. A 63-year-old man with intellectual disability presented to our hospital. The patient had fallen on the floor; however, no apparent head or neck trauma was observed. The patient returned home after confirming the absence of intracranial hematoma on computed tomography. However, the patient was re-admitted because of hypotension and bradycardia, and sick sinus syndrome was suspected. As the manifestations were motor weakness in the extremities and urinary retention, screening spinal magnetic resonance imaging revealed cervical cord injury and spondylosis. Cervical SCI related to a fall was suspected. Cervical decompression surgery and rehabilitation therapy contributed to the improved patient status. Herein, we report a case of intellectual disability in which SCI was initially overlooked. No severe preceding traumatic episode or intellectual disability of the patient could have led to overlooking SCI in our case. Clinicians should be cautious about this rare condition.
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  • 文章类型: Journal Article
    缺血性中风会导致神经损伤,炎症过程极大地促进了损伤的扩展和生长。受体相互作用蛋白激酶2(RIPK2)以其作为NOD1/2模式识别受体信号传导的专性激酶的作用而闻名,并与各种炎症的病理学有关。与假手术对照相比,缺血性卒中导致活动期急剧增加,磷酸化形式的RIPK2,表明RIPK2可能与中风损伤的反应有关。这里,我们评估了RIPK2的药理学抑制作用对实验性缺血性卒中小鼠卒中后结局的改善作用.我们发现在再灌注开始时用RIPK2抑制剂治疗,抑制RIPK2的磷酸化和激活,与在卒中后24小时评估的载体给药组相比,导致卒中后行为结局显著改善.RIPK2抑制剂治疗的小鼠显示梗死体积显著减少,同时减少对血脑屏障的损伤,同侧皮质中活性基质金属蛋白酶-9(MMP-9)水平降低和血源性白蛋白渗漏证明了这一点。探讨RIPK2抑制的保护机制,接下来,我们用RIPK2抑制剂或载体对小鼠进行预处理,并检查卒中后6小时缺血性脑中发生的转录组改变.我们观察到抑制剂治疗组的同侧皮质中的神经炎标记物的显着减少,同时还通过对受损皮质的大量RNA测序,对抑制剂治疗在大脑中发生的巨大转录组改变进行了全面的观察。总的来说,我们提供了重要的新证据,表明RIPK2可能是卒中后药物治疗和潜在的其他神经炎性疾病的可行靶点.
    Ischemic stroke induces a debilitating neurological insult, where inflammatory processes contribute greatly to the expansion and growth of the injury. Receptor-interacting protein kinase 2 (RIPK2) is most well-known for its role as the obligate kinase for NOD1/2 pattern recognition receptor signaling and is implicated in the pathology of various inflammatory conditions. Compared to a sham-operated control, ischemic stroke resulted in a dramatic increase in the active, phosphorylated form of RIPK2, indicating that RIPK2 may be implicated in the response to stroke injury. Here, we assessed the effects of pharmacological inhibition of RIPK2 to improve post-stroke outcomes in mice subjected to experimental ischemic stroke. We found that treatment at the onset of reperfusion with a RIPK2 inhibitor, which inhibits the phosphorylation and activation of RIPK2, resulted in marked improvements in post-stroke behavioral outcomes compared to the vehicle-administered group assessed 24 h after stroke. RIPK2 inhibitor-treated mice exhibited dramatic reductions in infarct volume, concurrent with reduced damage to the blood-brain barrier, as evidenced by reduced levels of active matrix metalloproteinase-9 (MMP-9) and leakage of blood-borne albumin in the ipsilateral cortex. To explore the protective mechanism of RIPK2 inhibition, we next pretreated mice with RIPK2 inhibitor or vehicle and examined transcriptomic alterations occurring in the ischemic brain 6 h after stroke. We observed a dramatic reduction in neuroinflammatory markers in the ipsilateral cortex of the inhibitor-treated group while also attaining a comprehensive view of the vast transcriptomic alterations occurring in the brain with inhibitor treatment through bulk RNA-sequencing of the injured cortex. Overall, we provide significant novel evidence that RIPK2 may represent a viable target for post-stroke pharmacotherapy and potentially other neuroinflammatory conditions.
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