Progress in the generation of spinal cord organoids over the past decade and future perspectives

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord: Analysis of 21 cases

BACKGROUND： Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE： To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN： Case analysis. SETTING： Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS： A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5 - 108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS： Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187 - 1 059 ng/L and normal value of serum homocysteine was 5 - 15μ mol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES： （1） Levels of blood routine, serum vitamin B12 and homocysteine; （2） results of neuroelectrophysiological examination; （3） results of MRI examination of spinal cord; （4） prognosis. RESULTS： Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. （1） Clinical manifestations： All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs （5 cases）, unstable gait （3 cases）, limb asthenia （4 cases）, limb numbness combined with light asthenia （5 cases）, limb numbness combined with unskillful activity （3 cases）, and limb numbness combined with unstable gait （1 case）. （2） Experimental results： Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of bomocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. （3） Results of neuroelectrophysiological examination： Among all patients, 95% （20/21） patients had abnormal sensory-evoked potential, 89% （8/9） patients had abnormal motor evoked potential, 67% （10/15） patients had abnormal nerve conduction, 13% （2/15） patients had neurogenic muscle injury showed by electromyography （EMG）, 70% （7/10） patients had abnormal brain-stem auditory evoked potential, and 40% （4/10） patients had abnormal visual evoked potential. （4） Results of MRI examination of spinal cord： MRI examination demonstrated that 40% （6/15） patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B I2 therapy. CONCLUSION： Nervous system lesion caused by vitamin B 12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin BI2. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.

Spinal dural arteriovenous fistula 8 years after lumbar discectomy surgery: A case report and review of literature

BACKGROUND Spinal dural arteriovenous fistula(SDAVF)is an extremely rare vascular malformation of the central nervous system that is often confused with degenerative spinal disorders due to similar early symptoms and clinical features.Here,we report a case of SDAVF recurrence 8 years after lumbar spine surgery and summarize relevant literature.CASE SUMMARY A 54-year-old male was admitted to our hospital complaining of lower back pain,numbness in both lower extremities and intermittent claudication.Subsequent imaging identified lumbar spinal stenosis.Following surgical treatment,the patient’s symptoms significantly resolved,and he was able to perform daily activities.However,similar symptoms appeared 8 years later,followed by confirmation of SDAVF diagnosis.The patient underwent neurosurgery 7 mo after symptom onset.The follow-up period lasted 14 mo,and the patient remains with marginal neurological symptoms.CONCLUSION This case highlights the importance of prompt SDAVF diagnosis.Due to its nonspecific clinical presentation,the clinical experience of the surgeon and definitive imaging examination are indispensable.Additionally,timely neurosurgery is effective and may significantly improve patient outcomes.

Spontaneous conus infarction with"snake-eye appearance"on magnetic resonance imaging:A case report and literature review

BACKGROUND Infarction of the conus medullaris is a rare form of spinal cord infarction.The first symptom is usually acute non-characteristic lumbar pain,followed by lower limb pain,saddle numbness,fecal incontinence,and sexual dysfunction.Spontaneous conus infarction with"snake-eye appearance"on magnetic resonance imaging has rarely been reported.CASE SUMMARY We report a 79-year-old male patient with spontaneous conus infarction who had acute lower extremity pain and dysuria as the first symptoms.He did not have any recent history of aortic surgery and trauma.Magnetic resonance imaging revealed a rare"snake-eye appearance."In addition,we reviewed the literature on 23 similar cases and summarized the clinical features and magnetic resonance manifestations of common diseases related to the"snake-eye sign"to explore the etiology,imaging findings,and prognosis of spontaneous conus infarction.CONCLUSION We conclude that acute onset of conus medullaris syndrome combined with"snake-eye appearance"should be strongly suspected as conus medullaris infarction caused by anterior spinal artery ischemia.This special imaging manifestation is helpful in the early diagnosis and treatment of conus infarction.

Tenosynovial giant cell tumor involving the cervical spine: A case report

BACKGROUND Tenosynovial giant cell tumors(TGCTs)are a frequent benign proliferative disease originating from the synovial membrane.However,TGCTs rarely occur in the spine.The purpose of this paper is to report a case of TGCT occurring in the cervical spine.Although the disease is rare,it is essential to consider the possibility of TGCT in axial skeletal lesions.Awareness of spinal TGCTs is important because their characteristics are similar to common spinal tumor lesions.CASE SUMMARY A 49-year-old man with a 2-year history of neck pain and weakness in both lower extremities was referred to our ward.Imaging revealed a mass extending from the left epidural space to the C4-5 paravertebral muscles with uneven enhancement.The tumor originated in the synovium of the C4-5 lesser joint and eroded mainly the C4-5 vertebral arch and spine.Puncture biopsy was suggestive of a giant cellrich lesion.The patient had pulmonary tuberculosis,and we first administered anti-tuberculosis treatment.After the preoperative requirements of the antituberculosis treatment were met,we used a posterior cervical approach to completely remove the mass after fixation with eight pedicle screws.The mass was identified as a TGCT by postoperative immunohistochemical analysis.Recurrence was not detected after 1 year of follow-up.CONCLUSION Spinal TGCTs are often misdiagnosed.The radiological changes are not specific.The ideal treatment comprises complete excision with proper internal fixation,which can significantly reduce postoperative recurrence.

Neck pain and absence of cranial nerve symptom are clues of cervical myelopathy mimicking stroke:Two case reports

BACKGROUND Cervical myelopathy is a potential stroke imitator,for which intravenous thrombolysis would be catastrophic.CASE SUMMARY We herein present two cases of cervical myelopathy.The first patient presented with acute onset of right hemiparesis and urinary incontinence,and the second patient presented with sudden-onset right leg monoplegia.The initial diagnoses for both of them were ischemic stroke.However,both of them lacked cranial nerve symptom and suffered neck pain at the beginning of onset.Their cervical spinal cord lesions were finally confirmed by cervical computed tomography.A literature review showed that neck pain and absence of cranial nerve symptom are clues of cervical myelopathy.CONCLUSION The current report and the review remind us to pay more attention to these two clues in suspected stroke patients,especially those within the thrombolytic time window.

Application of A-line autoregressive model with exogenous input index during the wake-up test in spinal surgery under propofol-remifentanil anaesthesia

Paraplegia is a rare but terrible complication following major spinal operation. Intraoperative monitoring should be used to detect the neurological compucauons early so that they can be surgically revised.1 The common procedures for spinal cord monitoring are intraoperative wake-up test and neurophysiological methods. The latter includes somatosensory evoked potentials （SSEP） and motor evoked potentials （MEP）. The wake-up test has been routinely used to monitor voluntary motor function of the lower limbs during corrective spinal surgery.

Current status of full-endoscopic techniques in the surgical treatment of disk herniations and Spinal Canal stenosis

Degenerative constrictions of the spinal canal with compression of neural elements arise as a result of bony,disk,capsular or ligament structures.The most frequent causes are disk herniations and spinal stenoses.The lumbar and cervical spine is the most prominent cause.After conservative treatments have been exhausted,surgical intervention may be necessary.Today,microsurgical or microscopically-assisted decompression is regarded as the standard procedure for disk herniation and spinal stenosis in the lumbar region,while in the cervical spine,microsurgical or microscopically-assisted anterior decompression and fusion are standard.Both procedures demonstrate good clinical results but present problems associated with the operation.Decompressions in the area of the spine must be carried out under continuous visualization and must entail the possibility of adequate bone resection.Taking this into account,completely new endoscopes and instrument sets has been developed for full-endoscopic operations in tandem with the development of the lateral transforaminal and interlaminar approaches for the lumbar spine and the posterior,contralateral and anterior approaches for the cervical spine.The possibilities and results of comparable and established standard procedures have been used as a benchmark in the course of clinical validation.The development of surgically created approaches and the new rod lens endoscopes combined with appropriate instrument sets have laid the technical foundations for full-endoscopic operation in the lumbar spine on all primary and recurrent disk herniations inside and outside the spinal canal and on spinal stenoses.This development has also permitted resection of soft disk herniations in the cervical spine.The use of the relevant approaches depends on anatomical and pathological inclusion and exclusion criteria.The clinical results of standard procedures are achieved,which must be regarded as a minimum criterion for the introduction of new technologies.On the basis of evidence-based medicine(EBM) criteria,it can be established that using the full-endoscopic techniques developed,adequate decompression is achieved in the defined indications with reduced traumatization,improved visibility conditions and positive cost benefits.Today,fullendoscopic operations may be regarded as an expansion and alternative within the overall concept of spinal surgery.

Primary spinal intradural hydatidosis： a case report

Hydatid disease is a parasitic infestation by a .tapeworm of the genus echinococcus. Spinalhydaticiosis occurs in 1% of all cases with hydatidosis and is most commonly located in the dorsal spine.1 It is a rare cause of neurological signs and symptoms. Spinal hydatid disease should be considered in the differential diagnosis of spinal cord compression syndrome in endemic areas. There are no characteristic signs or symptoms. Misdiagnosis is easily to be made preoperatively. Most diagnosis are made intraoperatively, which increases the risk of future recurrences.

Profiles of and correlation between objective and subjective outcome assessments following open-door laminoplasty for cervical spondylotic myelopathy

Background Open-door laminoplasty is widely used in the treatment of cervical spondylotic myelopathy （CSM）. This study aimed to investigate the profiles of and correlation between objective and subjective short-term outcome assessments after open-door laminoplasty for CSM. Methods We retrospectively analyzed surgical outcomes in 129 consecutive CSM patients who underwent open-door laminoplasty in Peking University Third Hospital from February 2008 to November 2011. Both objective and subjective assessments were evaluated before surgery, 3 months after surgery, and 1 year after surgery. We then analyzed the profiles of and correlation between objective and subjective short-term outcomes. Results The Modified Japanese Orthopaedic Association （mJOA） score was significantly improved at 3 months （P〈0.01） and 1 year （P〈0.01） after surgery. Bivariate Logistic regression showed that sensory improvement contributed more to the recovery rate than motor function improvement at 3 months after surgery, while motor function contributed more to the recovery rate at 1 year after surgery. On the subjective assessment （the short form （SF）-36）, there was no significant improvement at 3 months after surgery （P〉0.05）, while physical function （PF）, role-physical （RP）, and social function （SF） were notably improved at 1 year after surgery （P〈0.01）. Improved mJOA score correlated with improvements in PF, RP, bodily pain, general health （GH）, vitality （VT）, and SF （P〈0.05） at 3 months after surgery; PF, GH, VT, and SF were associated with improved mJOA scores at 1 year after surgery. Conclusions Patients benefit from surgery by postoperative restitution of neurological function with early recovery of sensory function, followed by a gradual transition to motor function improvement. At the early stage of recovery, improvement in the mJOA score essentially correlated with improvements in the physical domains of the SF-36, while at the later stage, mJOA score improvement was associated with improvements in both mental and physical domains of the SF-36.Chin med J 2014;127（14）：2659-2663