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.

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.

Evaluation of Therapeutic Effect of Maneuver-Dominated Method in 30 Cases of Cervical Spondylotic Myelopathy

Thirty cases of cervical spondylotic myelopathy (CSM) were treated by a maneuver-dominated non-surgical therapy. Eighteen cases were recovered to grade E according to the criteria set by the American Spinal Injury Association. The effect was definite. Indications and contraindications of the maneuver were proposed on the basis of the pathogenesis of CSM and the principles of this manual method.

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.

Influence of hinge position on the effectiveness of open-door expansive laminoplasty for cervical spondylotic myelopathy

Objective： To assess the influence of different hinge positions on clinical results of expansive open-door laminoplasty （EOLP） for cervical spondylotic myelopathy （CSM）.Methods： A total of 102 CSM patients who underwent EOLP from February 2006 to February 2007 were enrolled in this randomized controlled trial. Using a random digits table,57 patients with the hinge located at the inner margin of the lateral mass were classified as wide-open group, while 45 patients with the hinge positioned at the lamina margin served as narrow-open group. All patients were observed over 24 months, and the clinical and radiological results were analyzed statistically.Results： There were no significant differences in operation duration, intraoperative bleeding volume, Japanese Orthopaedic Association （JOA） scores, cervical curvature index, range of motion and neural function recovery rate.The neural functions were satisfactorily improved after surgery in both groups, while the severity of axial symptoms was significantly lower in the narrow-open group than in the wide-open group （P=0.003）. The incidence of C5 palsy in the wide-open group was higher than that in the narrowopen group （5.3% vs 0）, even though the difference did not reach statistical significance （one tailed Fisher＇s exact test,P=0.17）.Conclusions： Proper inward shift of the hinge can ensure effectiveness of surgical decompression, avoid an excessive backward shift of the spinal cord, decrease the incidence of C5 palsy and alleviate the severity of axial symptoms.

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