Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia:A case report

BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.

A Case of Cerebrospinal Drainage for Paraplegia Complicated by Acute Aortic Dissection (Stanford B) Followed by TEVAR in the Subacute Phase

The patient is 50-year-old man. He was admitted to our hospital with a strong back pain and diagnosed as an acute type B aortic dissection. On the second day of hospitalization, he developed symptoms of paraplegia, and we considered TEVAR, but we were concerned that TEVAR intervention in the acute phase might worsen the dissection, so we first placed a cerebrospinal drainage (CSFD) device, which resulted in improvement of his symptoms. Thereafter, although his lower limb mobility was fine, he underwent thoracic stent graft aortic repair (TEVAR) in the subacute phase due to worsening ULP. The patient had a good postoperative course and was discharged home unassisted. The initial placement of CSFD was effective in reducing the incidence of paraplegia as a complication of TEVAR and in bringing the timing of TEVAR intervention from the acute phase to the subacute phase.

以神经系统损伤为首发症状的2例原发性干燥综合征报道

目的·总结以神经系统损伤为首发症状的2例原发性干燥综合征(primary Sjögren's syndrome,pSS)患者的临床特点并复习相关文献。方法·对以神经系统受累为首发症状的2例pSS患者的临床表现、实验室检查结果、影像学检查结果、唇腺活检结果、治疗效果等进行总结和分析。结果·病例1,女性,自50岁起出现进行性行走不稳伴下肢远端感觉障碍,表现为痉挛步态、感觉性共济失调、传导束性感觉障碍和二便障碍;58岁起无法独立行走。实验室检查提示抗核抗体阳性(1∶1000着丝点型),抗干燥综合征抗原A(SSA)/Ro-52抗体、抗SSA/Ro-60抗体、抗着丝点抗体阳性;唇腺活检可见唾液腺组织、导管间及小叶内淋巴细胞浸润灶2个/4 mm^(2)(淋巴细胞>50个)。头颅磁共振成像可见“蛇眼征”;肌电图显示右侧腓神经运动纤维轴索损伤。在院期间予以大剂量糖皮质激素冲击、联合免疫抑制剂治疗后明显好转。3个月后可推助行器行走,日常生活基本自理。病例2,女性,自81岁起出现颈部不自主右斜,既往有轻度口干、眼干、伴膝关节疼痛1年。实验室检查提示抗SSA/Ro-52抗体、抗SSA/Ro-60抗体阳性,血红蛋白86 g/L;唇腺活检可见小唾液腺组织部分腺泡萎缩,间质内见淋巴细胞、浆细胞浸润灶2个/4 mm^(2)(淋巴细胞>50个)。周围神经电生理检查结果提示右侧正中神经传导速度减慢。经免疫抑制剂、解痉、肌松药物治疗后症状较前好转。结论·以复杂型痉挛性截瘫样表现、颈部肌张力障碍为首发症状的病例拓展了pSS的临床表型谱;临床上应注意鉴别继发于pSS的神经系统损伤与其他原发神经系统疾病;对于具有无明显原因的神经系统损伤症状的患者,应当筛查相关自身免疫抗体。

颅内破裂动脉瘤介入栓塞术后抗凝及抗血小板聚集药物应用下腰椎穿刺致急性椎管内血肿2例并文献复习

目的探讨腰椎穿刺(LP)导致椎管内血肿(ISH)形成的临床表现、诊断、治疗及预后。方法回顾性分析新乡医学院第一附属医院2020年7月—2020年10月收治的2例在使用抗血小板聚集及抗凝药物情况下LP导致急性ISH形成患者的临床资料,并复习相关文献。结果此2例均为脑动脉瘤破裂合并蛛网膜下腔出血患者,在支架辅助弹簧圈栓塞动脉瘤术后使用抗血小板聚集及抗凝药物预防支架内血栓形成。在行LP术后均出现急性ISH,并进一步行血肿清除及椎管减压术治疗,出院时均遗留不同程度的神经功能障碍。结论抗凝及抗血小板聚集药物的应用使LP导致ISH形成的可能性较前增加。其诊断主要依靠患者的临床表现、体征及影像学检查,治疗以外科手术减压为主,预后主要与发病时神经功能缺失的程度相关。

多参数MRI随访观察遗传性痉挛性截瘫5型患者脊髓微结构改变

目的评估多参数MRI随访观察遗传性痉挛性截瘫5型(SPG5)患者脊髓微结构改变的价值。方法前瞻性纳入11例接受颈胸段脊髓MR检查及痉挛性截瘫评价量表(SPRS)评分的SPG5患者,随访1年后进行第2次MR检查及SPRS评分,比较2次SPRS评分、脊髓整体结构及脊髓微结构变化。结果11例SPG5患者2次SPRS评分结果差异无统计学意义(P>0.05)。相比首次颈胸段脊髓MRI,第2次MRI显示脊髓萎缩程度加重;首次与第2次MRI所测C4右侧皮质脊髓束(CST)轴向弥散系数(AD)差异有统计学意义(t=3.987,P<0.01),C4其余参数差异均无统计学意义(P均>0.05);其余椎体脊髓白质、后索、左/右侧CST的各向异性分数(FA)、平均弥散系数(MD)、AD、径向弥散系数(RD)及T1值,以及C1~T9椎体截面积(CSA)、左右径及前后径差异均无统计学意义(P均>0.05)。第2次MRI显示颈段脊髓白质、后索及CST的FA均低于、而RD均高于首次(P均>0.05)。结论多参数MRI可用于随访观察SPG5患者脊髓微结构变化。

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

Decision-Making and Management of Self-Care in Persons with Traumatic Spinal Cord Injuries: A Preliminary Study

Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.

脑血管造影术后并发高位截瘫1例

造影剂脑病(CIE)是一种在血管内使用造影剂后出现神经功能缺损的罕见疾病,通常有自限性,不会产生严重的后遗症。本文报道1例CIE,51岁女性,有高血压病史,术前无明显神经功能缺损的症状,使用碘克沙醇造影剂行DSA后出现高位截瘫的严重并发症,病人四肢肌力进行性下降至0级,感觉丧失,但病人意识清楚,经过积极治疗后症状未见明显缓解。这是极其罕见的CIE,提示临床医生应该预防其发生。

针刺辅助治疗脊髓损伤性截瘫临床研究

目的:观察针刺辅助治疗脊髓损伤性截瘫的临床疗效及对肢体运动功能的影响。方法:采用随机数字表法将132例脊髓损伤性截瘫患者分为观察组、对照组各66例。2组均给予常规药物治疗,对照组在常规药物基础上给予康复训练治疗,观察组在对照组基础上给予针刺辅助治疗,2组均连续治疗3个月。比较2组临床疗效及治疗前后改良Barthel指数评定量表(MBI)、美国损伤分级(ASIA)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、世界卫生组织生存质量测定量表(WHOQOL-BREF)评分及血清神经生长因子(NGF)、脑源性神经生长因子(BDNF)、5-羟色胺(5-HT)水平。结果:治疗期间,对照组脱落3例,完成研究63例。治疗后,观察组总有效率95.45%,高于对照组84.13%(P<0.05)。2组治疗后BMI、ASIA、WHOQOL-BREF评分及血清NGF、BDNF、5-HT水平均较治疗前升高(P<0.05),HAMD、HAMA评分降低(P<0.05);观察组治疗后BMI、ASIA、WHOQOL-BREF评分及血清NGF、BDNF、5-HT水平高于对照组(P<0.05),HAMD、HAMA评分低于对照组(P<0.05)。结论:中医针刺辅助治疗脊髓损伤性截瘫疗效确切,能够通过调节患者神经递质水平来改善肢体运动功能,缓解患者负性情绪与提高生活质量。

微创脊柱创伤手术治疗脊柱创伤患者临床安全性探讨

目的 探讨微创脊柱创伤手术的安全性。方法 选取2021年6月—2022年6月本院收治的182例脊柱创伤患者作为研究对象,根据患者意愿分常规组(行传统手术)与微创组(行微创脊柱创伤手术),每组91例,比较两种手术临床安全性。结果 微创组患者手术时间、术中出血量、术后疼痛评分、住院时间、卧床时间各项指标均优于对照组(P<0.05);微创组患者术后不良反应发生率远低于常规组,两组数据存在明显差异(P<0.05);微创组治疗满意度远远高于常规组(P<0.05)。结论 采用微创脊柱创伤手术治疗脊柱创伤,具有较高的安全性,减少患者术后并发症的发生,对患者创伤较小,缩短住院时间,临床治疗满意度较高。

Rescue axonal defects by targeting mitochondrial dynamics in hereditary spastic paraplegias

Impaired axonal development and degeneration underlie debilitating neurodegenerative diseases including hereditary spastic paraplegia, a large group of inherited diseases. Hereditary spastic paraplegia is caused by retrograde degeneration of the long corticospinal tract axons, leading to progressive spasticity and weakness of leg and hip muscles. There are over 70 subtypes with various underlying pathophysiological processes, such as defective vesicular trafficking, lipid metabolism, organelle shaping, axonal transport, and mitochondrial dysfunction. Although hereditary spastic paraplegia consists of various subtypes with different pathological characteristics, defects in mitochondrial morphology and function emerge as one of the common cellular themes in hereditary spastic paraplegia. Mitochondrial morphology and function are remodeled by mitochondrial dynamics regulated by several key fission and fusion mediators. However, the role of mitochondrial dynamics in axonal defects of hereditary spastic paraplegia remains largely unknown. Recently, studies reported perturbed mitochondrial morphology in hereditary spastic paraplegia neurons. Moreover, downregulation of mitochondrial fission regulator dynamin-related protein 1, both pharmacologically and genetically, could rescue axonal outgrowth defects in hereditary spastic paraplegia neurons, providing a potential therapeutic target for treating these hereditary spastic paraplegia. This mini-review will describe the regulation of mitochondrial fission/fusion, the link between mitochondrial dynamics and axonal defects, and the recent progress on the role of mitochondrial dynamics in axonal defects of hereditary spastic paraplegia.

Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia

PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 （PLP1） gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.

A Patient with Malignant Spinal Epidural Lymphoma with Initial Rapidly Aggravating Paraplegia

We report the case of a 51-year-old female with rapid neurological deterioration as an initial presentation of non-Hodgkin’s lymphoma. Paraplegia occurred suddenly after a 4-day history of weakness and numbness of the lower extremity. MRI revealed a dorsal epidural mass from T10 to T11 that compressed the spinal cord. There was neither bone destruction nor a paravertebral mass. Emergency decompressive laminectomy and tumor resection were performed. Histological analysis of the surgical specimen indicated diffuse large B cell lymphoma. The clinical stage was IV on CT and complete remission was achieved by subsequent chemotherapy. Spinal cord compression occurs in the course of non-Hodgkin’s lymphoma in 0.1% - 6.5% of cases, but this situation usually develops in the late phase with bone destruction and/or a paravertebral mass. Cord compression and especially the severe symptoms such as paraplegia are rare as the initial presentation of lymphoma.

THE EFFECT OF ACUPUNCTURE ON URINARY BLADDER DYSFUNCTION OF PATIENTS WITH TRAUMATIC PARAPLEGIA

62 patients with traumatic paraplegia were treated with acupuncture(GovernorVessel electro-stimulation),according to the theories of TCM such as dredging the meridians,regu-lating vital energy and blood,improving blood circulation,reinforcing marrow and replenishing brain.The effect of acupuncture on urinary bladder disturbance was studied.The results indicated that totaleffect rate was 96.8%(Ⅰ—Ⅲ),marked effect rate was 66.1%(Ⅰ—Ⅱ).The marked effect rate incomplete paraplegia was significantly different from that in imcomplete paraplegia;it was 63.0% and87.5% respectively.Furthermore,the results suggested that the degree of spinal cord injury was veryimprotant factor that affected the effect of acupuncture therapy.

Novel ATL1 mutation in a Chinese family with hereditary spastic paraplegia: A case report and review of literature

BACKGROUND Hereditary spastic paraplegias (HSPs) refer to a group of heterogeneous neurodegenerative diseases characterized by lower limbs spasticity and weakness. So far, over 72 genes have been found to cause HSP (SPG1-SPG72). Among autosomal dominant HSP patients, spastic paraplegia 4 (SPG4/SPAST) gene is the most common pathogenic gene, and atlastin-1 (ATL1) is the second most common one. Here we reported a novel ATL1 mutation in a Chinese spastic paraplegia 3A (SPG3A) family, which expands the clinical and genetic spectrum of ATL1 mutations. CASE SUMMARY A 9-year-old boy with progressive spastic paraplegia accompanied by right hearing loss and mental retardation for five years was admitted to our hospital.Past history was unremarkable. The family history was positive, and his grandfather and mother had similar symptoms. Neurological examinations revealed hypermyotonia in his lower limbs, hyperreflexia in knee reflex, bilateral positive Babinski signs and scissors gait. The results of blood routine test, liver function test, blood glucose test, ceruloplasmin test and vitamin test were all normal. The serum lactic acid level was significantly increased. The testing for brainstem auditory evoked potential demonstrated that the right side hearing was impaired while the left was normal. Magnetic resonance imaging showed mild atrophy of the spinal cord. The gene panel test revealed that the proband carried an ATL1 c.752A>G p.Gln251Arg (p.Q251R) mutation, and Sanger sequencing confirmed the existence of family co-segregation. CONCLUSION We reported a novel ATL1 Q251R mutation and a novel clinical phenotype of hearing loss in a Chinese SPG3A family.

Apoptosis of motor neurons in the spinal cord after ischemia reperfusion injury delayed paraplegia in rabbits

Objective To clarify the pathologic change of the motor neuron on spinal cord ischemia reperfusion injury delayed paraplegia.Methods The infrarenal aorta of White New Zealand rabbits(n=24) was occluded for 26 minutes using two bulldog clamps.Rabbits were killed after 8,24,72,or 168 hours(n=6 per group),respectively.The clamps was placed but never clamped in sham-operated rabbits(n=24).The lumbar segment of the spinal cord(L5 to L7) was used for morphological studies,including hematoxylin and eosin staining,the expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry.The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end-labeling of DNA fragments(TUNEL) staining.Results Delayed paraplegia occurred in all rabbits of ischemia reperfusion group at 16-24 hours,but not in sham groups.Motor neurons were selectively lost at 7 days after transient ischemia.After ischemia,the positive expression of bcl-2 protein were in the sham controls but decreased significantly as compared with that of the IR group(P<0.01),especially in 72 hours reperfusion.The positive expression of bax protein were also in the sham controls, but increased in the IR group,especially in 72 hours reperfusion;In addition, TUNEL study demonstrated that no cells were positively labeled until 24 hours after ischemia,but nuclei of some motor neurons were positively labeled at peak after ischemia reperfusion at 72 hours.Conclusion Spinal cord ischemia in rabbits induces morphological and biochemical changes suggestive of apoptosis.These data raise the possibility that apoptosis contributes to neuronal cell death after spinal cord ischemia reperfusion.

Chinese Herbal Medicine and Acupuncture Used for Rehabilitation of the Impaired Urinary System in Patients with Paraplegia—A Report of 52 Cases

Infection of the urinary system is frequently seen in the paraplegic patients with urinary complications,which is one of the main reasons for the late death in such cases. The effects of the therapeutic method adopted for the urinary rehabilitation are directly related to the life quality and survival time of the paraplegic patients. Since 1999-2002, the authors had applied Chinese herbal medicine combined with acupuncture for the urinary rehabilitation in 52 paraplegic patients, with quite good therapeuticresults as reported in the following.

Clinical presentation of gastric Burkitt lymphoma presenting with paraplegia and acute pancreatitis:A case report

BACKGROUND The incidence of gastric Burkitt lymphoma(BL),presenting as paraplegia and acute pancreatitis,is extremely low.BL is a great masquerader that presents in varied forms and in atypical locations,and it is prone to misdiagnosis and missed diagnosis.The prognosis of BL remains poor because of the difficulty in early diagnosis and the limited advances in chemotherapy.CASE SUMMARY A 53-year-old man was referred to our hospital from the local county hospital due to abdominal pain for two weeks and weakness in the lower extremities for one day.Magnetic resonance imaging of the abdomen and lumbar spine showed a swollen pancreas and gallbladder,with peripancreatic exudation and liquid collection,indicating acute pancreatitis and acute cholecystitis.Additionally,we observed abnormally thickened lesions of the gastric wall,multiple enlarged retroperitoneal lymph nodes and a well-demarcated,posterolateral extradural mass lesion between T9 and T12,with extension through the spinal foramen and definite bony destruction,suggesting metastasis in gastric malignancy.Subsequent whole-body positron emission tomography/computed tomography examination showed multifocal malignant lesions in the stomach,pancreas,gallbladder,bone,bilateral supraclavicular fossa,anterior mediastinum,bilateral axillary and retroperitoneal lymph nodes.Gastroduodenal endoscopy revealed primary BL with massive involvement of the gastric body and duodenum.The patient refused chemotherapeutic treatment and died one week later due to upper gastrointestinal hemorrhage.Afterward,we reviewed the characteristics of 11 patients with BL involving the stomach,pancreas or spinal cord.CONCLUSION Clinicians should be aware that BL can be the potential cause of acute pancreatitis or a rapidly progressive spinal tumor with accompanying paraplegia.For gastric BL,gastroscopy biopsies and pathology are necessary for a definite diagnosis.

Paraplegia from spinal intramedullary tuberculosis:A case report

BACKGROUND Tuberculosis (TB) mostly attacks the lungs, and extrapulmonary TB involving thecentral nervous system is uncommon;among these cases, spinal intramedullaryTB is even more rare. The clinical manifestations of spinal intramedullary TB aresimilar to those of intramedullary spinal cord tumors. Therefore, it is necessary tomake a careful differential diagnosis of spinal intramedullary lesions to achievethe appropriate treatment and favorable prognosis. We report a rare case of ayoung male patient with paraplegia due to spinal intramedullary TB, which isuncommon and regrettable.CASE SUMMARY A 23-year-old male presented with fever accompanied by nausea and vomitinglasting for 2 mo and was then diagnosed with tubercular meningitis. After anti-TBtreatment, his symptoms were significantly improved. However, 2 mo after thediagnosis of tubercular meningitis, the patient felt numbness below the costal archlevel, which lasted for 1 wk, and he paid no attention to this symptom. Whatfollowed was paraplegia and urine/fecal incontinence. Magnetic resonanceimaging of the thoracic spine showed a ring-enhanced intramedullary cord lesionat T8-T9. Lesion exploration showed enlargement of the spinal cord at T8-T9, andthe lesion could be observed by incision. The lesion was adhered to the peripheraltissue and was grayish-white and tough with a poor blood supply and a diameterof approximately 0.8 cm. The lesion was resected completely. The results ofpathological examination by both hematoxylin-eosin staining and acid-fast bacillistaining confirmed TB, accompanied by acute and chronic suppurativeinflammation and granulation tissue formation. The patient was instructed tocontinue anti-TB treatment after the operation, but he did not follow the medicaladvice. Follow-up continued for ten years, the patient had persistent paraplegia,the numbness disappeared and urine/fecal sensation recovered.CONCLUSION Although TB is a kind of benign disease, some cases progress rapidly. Moreover,spinal intramedullary TB may seriously endanger quality of life and still needstimely diagnosis and proper treatment.

ACUPUNCTURE TREATMENT OF COMPLETE TRAUMATIC PARAPLEGIA——Analysis of 261 Cases

Traumatic paraplegia is commonly seenin cases with the spinal cord injured. Basedon the significant therapeutic effectivenessobtained from our acupuncture treatment offacial paralysis. monoplegia. hemiplegia andmultiple neuritis, we started to treattraumatic paraplegia with acupuncture in1963. From 1976 to 1993, 428 patients