Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.

Thoracic Anterior Spinal Cord Herniation: Treatment and Prognosis Outcome of Seven Patients.

BACKGROUND: This study aimed to investigate the diagnosis and treatment of thoracic anterior spinal cord herniation, a rare condition. METHODS: Clinical data of 7 patients diagnosed with thoracic anterior spinal cord herniation were analyzed. All patients were diagnosed with a complete preoperative examination and scheduled for surgical treatment. In addition, regular follow-up was performed after the surgery, and the operation's efficacy was evaluated according to clinical symptoms, imaging findings, and improvement in neurologic function. RESULTS: All patients underwent spinal cord release with an anterior dural patch. Notably, no severe postoperative surgical complications were observed. All patients were followed up for 12-75 months, with an average duration of approximately 46.5 months. Post-operative pain symptoms were controlled, neurological dysfunction and related symptoms improved to varying degrees, and anterior spinal cord herniation did not recur. The modified Japanese Orthopedic Association score at the last follow-up was significantly higher than the preoperative score. CONCLUSIONS: Clinicians should avoid misdiagnosing patients with thoracic anterior spinal cord herniation with intervertebral disc herniation, arachnoid cysts, and other related diseases, and patients should undergo surgical treatment as early as possible. In addition, surgical treatment can protect the neurologic function of patients and effectively prevent the aggravation of clinical symptoms.

Spinal nerve root sleeve cysticercosis: a case report and review of the literature.

BACKGROUND: Neurocysticercosis is a parasitic infection of the central nervous system by tapeworm larvae. Spinal cysticercosis is thought to be relatively rare, and spinal nerve root sleeve cysticercosis have not been reported previously. CASE PRESENTATION: A 46-year-old Chinese Han female patient presented with low back pain and radicular pain of the right lower limb. The visual analog scale was 6. Magnetic resonance imaging showed a subarachnoid cyst at the S1 level, with a slight enhanced rim. The patient underwent surgical treatment. During surgery, we found the cyst located mainly in the subarachnoid space and partly in a sacral nerve root sleeve. Cysticercosis was also confirmed by postoperative pathological examination. Postoperative drug therapy was performed after cysticercosis was confirmed. Postoperatively, the patient was treated with oral albendazole (15 mg/kg) for 1 month. Only mild sensory impairment was left when she was discharged. After 3 years of follow-up, the visual analog scale reduced from 6 to 2, and the patient's sensory function completely recovered. Magnetic resonance imaging showed no recurrence of cysticercosis. CONCLUSION: Subarachnoid cysticercosis may extend to nerve root sleeve causing back pain and radiculopathy, which may present with similar magnetic resonance imaging manifestations to Tarlov cysts. Hence, spinal subarachnoid cysticercosis should be considered as an important differential diagnosis of arachnoid cyst and sacral Tarlov cyst. Combined treatment with surgical removal and drug therapy is effective to manage spinal subarachnoid cysticercosis.

An Effective Surgical Method for Terminal Syringomyelia: Terminal Ventriculostomy-Associated "V"-Type Ostomy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: We aimed to evaluate the effectiveness of terminal ventriculostomy in treating tethered cord syndrome (TCS) combined with terminal syringomyelia (TS) and describe "V"-type ostomy as an effective surgical method to avoid relapsing syringomyelia based on terminal ventriculostomy. METHODS: We retrospectively analyzed the clinical and radiological data of 28 patients admitted to the Department of Neurosurgery, PLA General Hospital who had been diagnosed with TCS combined with TS and underwent terminal ventriculostomy-associated "V"-type ostomy between January 2011 and January 2016. We classified patients' clinical outcomes into 4 levels according to the Spinal Bifida Neurological Scale: markedly improved, improved, stable, and deteriorated. The size of the syrinx cavity was quantified using the syrinx index, and there was a difference in syrinx cavity size between pre-operation and post-operation. RESULTS: Twenty-eight patients were followed up for 36 months. We found that each syrinx cavity shrunk by at least 50%. More than 90% of patients had achieved "markedly improved" and "improved" outcomes during the follow-up visit. Moreover, no patient relapsed for up to 36 months post-surgery. CONCLUSION: Terminal ventriculostomy has a beneficial effect on TS, particularly on the syrinx cavity extending to the filum terminale. For this special cavity, we advocate the use of terminal ventriculostomy-associated "V"-type ostomy to avoid potential relapse. As a safe, convenient, and persistently effective approach, terminal ventriculostomy-associated "V"-type ostomy can be considered a promising alternative method for treating TCS combined with TS in clinical practice.

Gestational age-specific reference standards of low-lying conus medullaris level in fetuses: a prospective cohort study.

PURPOSE: To explore the position change of fetal conus medullaris by ultrasound, and to propose gestational age-specific references for the lower limits of fetal conus medullaris level. METHODS: We prospectively collected the imaging and clinical data of fetuses whose mothers accepted routine prenatal ultrasonic follow-ups in the Department of Medical Ultrasonics, Chinese PLA General Hospital, between November 2020 and April 2021. By assigning to the conus medullaris levels, calculating statistical data, and performing linear regression analysis, we determined the correlation between the conus medullaris level and gestational week, as well as between the 95th percentile of the conus medullaris level, i.e., the lower limit of the conus medullaris level, and gestational week. RESULTS: We included 1202 different fetuses at 17-40 gestational weeks in the study. Both the conus medullaris level and the 95th percentile of the conus medullaris level were linearly correlated with gestational week. We calculated the adjusted values of the lower limits of fetal conus medullaris levels, that is, the theoretical references of the lower limits, according to the linear regression equation, and composed a comparison table. CONCLUSION: The fetal conus medullaris position continues changing cranially with gestational weeks during the whole pregnancy. The conus medullaris of a term fetus should not lie below the L2 vertebra level at birth. We proposed reference criteria of fetal low-lying conus medullaris for each gestational week from 17 to 40 weeks of gestational age, which potentially help prompt diagnosis and improve prognosis of fetal tethered cord syndrome.

Fetal magnetic resonance imaging in the diagnosis of spinal cord neural tube defects: A prospective study.

Objective: This study aimed to evaluate the value of fetal magnetic resonance imaging (MRI) in the prenatal diagnosis of spinal neural tube defects. Methods: From August 2018 to January 2021, 56 fetuses with suspected spinal cord neural tube defects were treated by prenatal ultrasound in the Neurosurgery Department of the First Medical Center of the People's Liberation Army General Hospital. Fetal MRI was performed within 72 h after ultrasound diagnosis. Forty singleton fetuses were selected. Magnetic resonance examination was performed within 1 month after birth, and the diagnostic coincidence rates of prenatal ultrasound and fetal magnetic resonance examination in the prenatal diagnosis of spinal cord neural tube defects were compared and analyzed using postnatal magnetic resonance examination as the standard. Results: The coincidence rates of prenatal ultrasound and fetal MRI for the prenatal diagnosis of spina bifida were 71.4% (20/28) and 39.2% (11/28), respectively, and the difference was statistically significant. The coincidence rates of prenatal ultrasound and fetal MRI in the diagnosis of intraspinal lipoma were 52.6% (10/19) and 73.7% (14/19), respectively, and the difference was statistically significant. Conclusion: Fetal MRI has an advantage over prenatal ultrasound in detecting intraspinal lipoma. Prenatal ultrasound has an advantage over fetal MRI in detecting spina bifida.

Filum Terminale: A Comprehensive Review with Anatomical, Pathological, and Surgical Considerations.

The conus medullaris is the distal tapering end of the spinal cord, and the filum terminale (FT) is regarded as a bundle of nonfunctional fibrous tissue; therefore, some scholars call it the spinal ligament, while others describe the human FT as "remnants of the spinal cord." It was later found that in the human spinal cord, the FT is composed of an intradural segment and an epidural segment, and the end of the FT is connected to the coccyx periosteum. Because some nerve tissue is also found in the FT, as research progresses, FT may have the potential for transplantation. A lack of exhaustive overviews on the FT in the present literature prompted us to conduct this review. Considering that a current comprehensive review seemed to be the need of the hour, herein, we attempted to summarize previous research and theories on the FT, elucidate its anatomy, and understand its pathological involvement in various diseases.

Ruptured Spinal Dermoid Cysts with Lipid Droplets into the Syrinx Cavity : Reports of Fourteen Cases.

OBJECTIVE: Dermoid cysts are uncommon in spinal cord tumors, and the phenomenon of their spontaneous rupture into the syrinx cavity is quite rare. We aimed to analyze the imaging characteristics and etiologies, and propose some surgical strategies, for this uncommon phenomenon. METHODS: We retrospectively reviewed 14 cases with spinal dermoid cysts that ruptured into the cervical and thoracic syrinx cavity. There were six male and eight female cases, aged 21 to 46 years, who had lipid droplets in the syrinx cavity from C1 to L3. The dermoid cysts were always located at the conus. Based on patients' complaints, clinical manifestations, and imaging results, we adopted tumor excision and/or syrinx cavity aspiration in one stage or multiple stages. RESULTS: Three patients had only a syrinx cavity aspiration surgery due to a history of dermoid cyst excision. Eight patients had dermoid cyst resection and syrinx cavity aspiration in one stage. One patient was operated upon in two stages due to the development of new symptoms at nine months follow-up. Two patients underwent only tumor resection since they did not show similar symptoms or signs caused by the cervicothoracic syrinx. The axial magnetic resonance imaging indicated that the lipid droplets were always not at the center but were eccentric. The clinical effect was satisfactory during the follow-up period in this group. CONCLUSION: The lipid droplets filled the spinal syrinx cavity, not entirely confined to the central canal. Based on the chief complaints and associated signs, we adopted different surgical strategies and had satisfactory clinical results.

Early Surgical Intervention with Antibiotic Treatment for Congenital Dermal Sinus with Central Nervous System Infection: A Retrospective Study of 20 Cases.

OBJECTIVE: To investigate the efficacy of surgical intervention with antibiotic treatment for congenital dermal sinus (CDS) with central nervous system infection. METHODS: Clinical data of 20 patients with CDS and central nervous system infection were retrospectively analyzed. All patients received early surgical treatment combined with postoperative antibiotic therapy after the diagnosis was confirmed. The infection control effect was evaluated according to the clinical symptoms, laboratory examination results, and improvement of neurological function. RESULTS: All 20 patients were treated with complete resection of the CDS and postoperative antibiotic therapy. No severe surgical complications occurred. Patients were followed for 3-81 months with a median follow-up time of 37.5 months. Postoperative infection was effectively controlled with no recurrence. Neurological dysfunction and related symptoms improved to varying extents after treatment, and the Spina Bifida Neurological Scale score at the final follow-up significantly increased. CONCLUSIONS: Patients with CDS and central nervous system infection should receive surgical management at an early stage with antibiotic treatment. This treatment algorithm was effective for control infection and protection of neurological function.

Type 1.5 Split Cord Malformation : A New Theory of Pathogenesis.

To report two cases of type 1.5 split cord malformation (SCM), a subtype of SCM with combined characteristics of types I and II and to review the relevant literature and propose a new possible pathogenetic theory for type 1.5 SCM. A 52-year-old woman had hemicords within a single dural sac with a dorsal bony septum at the L5 level. A 9-year-old boy had hemicords within a single dural sac with a ventral bony septum and fibrous extension at the L3 level. Both patients underwent microsurgical treatments for removing the bony septum, detethering the spinal cord, and sectioning the filum terminale. The surgical procedure revealed an extradural partial bony septum and hemicords within an intact single dural sac in each patient. Both patients were discharged from the hospital without de novo nerve dysfunction. Published cases have validated that types I and II SCM can overlap. We recommend recent type 1.5 SCM as a normative terminology for this overlapping SCM and report two rare cases of this SCM. We propose an associated pathogenesis consisting of uneven distribution and regression to explain type 1.5 SCM. Furthermore, we postulate that the amount of condensing meninx primitiva might determine whether the left bony septum has fibrous extensions to the opposite dura in type 1.5 SCM.

Determination of the normal conus medullaris level in term infants: the role of MRI in early infancy.

OBJECTIVE: This study aimed to explore the migration process of the conus medullaris (CM) in early infancy using infant MRI and to evaluate the application of MRI for locating the infant CM level. METHODS: The authors retrospectively analyzed the CM level on the lumbosacral MR images of 26 term infants aged < 3 months who were classified into three groups according to age. The authors numbered the CM level in each patient and analyzed the range and average of the CM level of the cohort. The authors studied the linear correlation between CM level and postnatal days with linear regression analysis, 1-way ANOVA, and the least significant difference test. RESULTS: The CM level ranged from the superior border of the L1 vertebra to the top third of the L3 vertebra. About 96.2% of infants had CM higher than the superior border of the L3 vertebra. On average, CM was located between the L1-2 intervertebral disc and the inferior border of the L2 vertebra (mean ± SD score 1.64 ± 1.14). The three groups had no significant statistical difference in CM level (F = 1.071 and p = 0.359; groups 1 and 2, p = 0.408; groups 1 and 3, p = 0.170; groups 2 and 3, p = 0.755). CM level had no linear regression correlation with postnatal days within the first month (r2 = 0.061, F = 0.654, p = 0.438) or within the first 3 months (r2 = 0.002, F = 0.056, p = 0.816). CONCLUSIONS: The CM level reaches the normal adult level by birth in term infants and does not ascend during childhood. On average, the CM was between the L1-2 intervertebral disc and the inferior border of the L2 vertebra in term infants. Considering the possibility of physiologically low-lying CM, the authors agree that normal CM is located above the L3 level in term infants and CM at the L3 level could be equivocal and should be investigated with other clinical data. The study data suggest that MRI is an accurate and valuable method for determining the CM level in term infants.

Conus medullaris migration during the third trimester: A retrospective study.

OBJECTIVE: To explore the migration process of the conus medullaris (CM) and propose a normal range of CM levels during the third trimester. METHOD: We retrospectively collected the ultrasonographic and clinical data of 588 fetuses during the third trimester. We located the CM and assigned scores. One-way analysis of variance and linear regression analyses were used to statistically analyze CM migration. Statistical significance was set at p < 0.05. RESULTS: The CM levels were statistically different among the different gestational weeks of the third trimester. The CM level showed a linear regression correlation with the gestational weeks. On an average, the CM migrated from the top third of the L2 vertebra to the L1/2 intervertebral disc level. CONCLUSION: The CM continues to migrate, from the top third of the L2 vertebra to the L1/2 intervertebral disc level, during the third trimester. The term infant could have the CM at the normal adult level at birth. At the beginning of the third trimester, a CM located above the L2/3 intervertebral disc level could be normal; the CM location at the L3 vertebra level could be physiological and needs follow-up; and a CM presenting below the L3 vertebra level might indicate tethered cord syndrome. The fetus with a CM significantly above the L1/2 intervertebral disc level may have caudal regression syndrome.

Intramedullary metastasis in medulloblastoma: a case report and literature review.

BACKGROUND: Cerebellar medulloblastomas are the most common malignant tumors of the posterior fossa in childhood that frequently metastasize. Leptomeningeal dissemination and distant metastasis have been associated with medulloblastomas; however, intramedullary metastases are rare with very few case reports in the literature available. METHODS: We present a case of a 3-year-old girl with a medulloblastoma who underwent surgical resection of spinal intramedullary metastases. Histopathology revealed the tumor to be an anaplastic medulloblastoma similar to the intracranial lesions. The patient subsequently underwent postoperative chemotherapy followed by radiotherapy. RESULTS: Following the surgery and subsequent follow-up, the patient showed a good recovery without any new neurological dysfunction. CONCLUSIONS: Intramedullary metastasis of medulloblastoma remains a rare disease. Surgical resection could play a possible role in the management in addition to radiation and chemotherapy.

Feasibility of commonly used fluorescent dyes and viral tracers in aqueous and solvent-based tissue clearing.

OBJECTIVE: To study the compatibility of traditional tracers and viral tracers with tissue clearing technology and to provide guidance in choosing suitable tracing methods for a specific tissue clearing technique. METHOD: Experiment 1: In this study, two different types of representative tracers, namely fluorescent dye tracers (Fluoro-Gold and Fluoro-Ruby) and viral tracers carrying fluorescent proteins (rAAV9-hSyn-mCherry-WPRE-pA and rAAV9-hSyn-EGFP-WPRE-pA), were selected to trace the cerebrospinal tract of the animals by microinjection. Furthermore, we presented the signal changes after using the three representative transparentizing methods, which included FRUIT (aqueous tissue clearing), 3DISCO (solvent-based tissue clearing), and uDISCO (solvent-based tissue clearing), were compared after slicing. Experiment 2: Based on the research mentioned above, Fluoro-Ruby was microinjected unilaterally into the primary motor cortex of rats, directly tracing the pyramidal tract to the spinal cord. Then, the entire brain and spinal cord were collected for tissue transparency using the 3DISCO method, after which three-dimensional imaging was performed using optical microscopic imaging equipment. RESULTS: Experiment 1 indicated that Fluoro-Gold and Fluoro-Ruby displayed better compatibility with the three transparent methods. The viral tracer exhibited higher compatibility with the FRUIT method, while its compatibility with 3DISCO and uDISCO was low. Furthermore, GFP was quenched more quickly and seriously than cherry protein under the same experimental conditions. Experiment 2: The Fluoro-Ruby tag displayed the presence of long-distance axons. For microscopic imaging, light sheet microscopy and two-photon microscopy were both used to identify the signals of tracers in transparent tissue. RESULTS: Both Fluoro-Gold and Fluoro-Ruby displayed excellent compatibility with tissue clearing technology, which, with dehydration and delipidation at its core, lead to quenching of fluorescence proteins, while exhibiting poor compatibility with viral tracers. In combination with tissue clearing technology and optical microscopy, the anterograde tracer Fluoro-Ruby could stereoscopically display the complete neural conduction pathway.

Anterior Sacral Meningocele: A New Classification and Treatment Using the Dorsal Transsacral Approach.

STUDY DESIGN: Retrospective case series. OBJECTIVE: Anterior sacral meningocele (ASM) is a rare disorder. We reviewed 11 cases of congenital ASM and classified them into three types based on the anatomy and relationship between the cyst and sacral nerve roots. SUMMARY OF BACKGROUND DATA: The cohort with ASM is relatively large; the classification is novel and has not been previously reported. METHODS: Eleven consecutive patients with ASM who underwent surgery between February 2014 and January 2019 were retrospectively analyzed. They included four males and seven females. The dorsal transsacral approach was adopted in all cases. The follow-up time was at least 3 months. RESULTS: We attempted to classify ASM into three types. Of the 11 cases, six were caudal type, two were paraneural type, and three were nerve-root type. The meningocele was ligated after exploring no nerve involvement, in Type I and II. For Type III, the herniating sac and involved nerve roots were ligated when the nerve roots were indicated as nonfunctional on neurophysiological monitoring; otherwise, the sacral nerve roots were protected and imbricated on the residual sac like a hand-in-glove, and sutured to reconstruct the nerves sleeve. Eight cases were accompanied by tethered cord syndrome (TCS); spinal cord detethering was done with one-stage operation. Ten patients' presenting symptoms improved at 3 to 6 months' follow-up; notably, constipation significantly improved. Only one case accompanied by an epidermoid cyst had a second laparoscopic surgery by a general surgeon. CONCLUSION: Aim of surgical treatment is to obliterate the communication between the subarachnoid space and herniated sac, detether the spinal cord, and resect the congenital tumor. The new classification helps to recognize the relationship between the meningocele and sacral nerve roots, and subsequently adopt different surgical strategies. We consider the dorsal transsacral approach relatively feasible, safe, and with lower complication. LEVEL OF EVIDENCE: 4.

Intramedullary Thoracic Meningioma: A Rare Case Report and Review of the Literature.

BACKGROUND: Quite a few cases of intramedullary meningioma have been described in previously reported studies. We have presented a rare case of intramedullary thoracic meningioma, which was quite different from subdural extramedullary meningioma, and the preliminary diagnosis was mistakenly given as hemangioblastoma. CASE DESCRIPTION: A 46-year-old man with complaints of gait problems and pain in the right lower extremity was admitted to our hospital. The neurological examination revealed 3 of 5 motor strength, spastic paraparesis, hyperreflexia, increased tone, and sensory deficits in the right lower extremity. Contrast-enhanced images showed a T6-T7 intramedullary lesion and an evident and homogeneously enhanced lesion with clearly defined borders on the sagittal, coronal, and axial views. The preliminary diagnosis was hemangioblastoma. However, he underwent tumor resection, and the histopathological examination findings confirmed the diagnosis of intramedullary meningioma. CONCLUSION: Intramedullary thoracic meningiomas are extremely rare and differ from the common subdural extramedullary meningiomas. Clinicians should be aware of this when diagnosing intramedullary tumors. Gross total resection using a microsurgical technique will be the best treatment strategy.

Microsurgical efficacy in 326 children with tethered cord syndrome: a retrospective analysis.

Tethered cord syndrome is a progressive disease with a typically insidious onset in infants and children, and which can lead to persistent progress of neurological deficits and a high rate of disability without timely intervention. The purpose of this study was to investigate the curative effect of microsurgery in children with different types of tethered cord syndrome. In this study, we analyzed 326 patients with tethered cord syndrome, aged from 2 months to 14 years old, who were followed for 3-36 months after microscopic surgery. Based on clinical manifestations and imaging findings, these patients were classified into five types: tight filum terminale (53 cases), lipomyelomeningocele (55 cases), lipomatous malformation (124 cases), postoperative adhesions (56 cases), and split cord malformation (38 cases). All patients underwent microsurgery. Curative effects were measured before and 3 months after surgery by Spina Bifida Neurological Scale based on sensory and motor functions, reflexes, and bladder and bowel function. The results showed that Spina Bifida Neurological Scale scores improved in all five types after surgery. Overall effective rates in these patients were 75%. Effective rates were 91% in tight filum terminale, 84% in lipomyelomeningocele, 65% in lipomatous malformation, 75% in postoperative adhesion, and 79% in split cord malformation. Binary logistic regression analysis revealed that types of tethered cord syndrome (lipoma-type or not) and symptom duration before surgery were independent influencing factors of surgical outcome. These results show that therapeutic effect is markedly different in patients with different types of tethered cord syndrome. Suitable clinical classification for tethered cord syndrome will be helpful in predicting prognosis and guiding treatment. This trial has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800016464).