Distal Spinal Cord Research Articles

Alterations of functional connectivity between thalamus and cortex before and after decompression in cervical spondylotic myelopathy patients: a resting-state functional MRI study.

Cervical spondylotic myelopathy is regarded as a chronic, special incomplete spinal cord injury, so the sensory components transmitted to thalamus decreased after distal spinal cord injury, which lead the disturbance of thalamus-cortex circuits, which might explain the alterations of clinical function of cervical spondylotic myelopathy patients. However, for lack of effective methods to evaluate the disturbance circuits and how the relative mechanism adapt to the recovery of cervical spondylotic myelopathy patients after decompression. Therefore, this study aim to explore how the possible mechanism of thalamus-cortex circuits reorganization adapt to the recovery of clinical function. Regard thalamus as the interest area, we evaluate the brain functional connectivity within 43 pre-operative cervical spondylotic myelopathy patients, 21 post-operative (after 3 months) cervical spondylotic myelopathy patients and 43 healthy controls. Functional connectivity difference between pre-/post-operative cervical spondylotic myelopathy group and healthy controls group were obtained by two independent samples t-test, and difference between pre-operative cervical spondylotic myelopathy and post-operative cervical spondylotic myelopathy group were obtained by paired t-test. Clinical function was measured via Neck Disability Index and Japanese Orthopaedic Association scores. Furthermore, Pearson correlation were used to analyse the correlation between functional connectivity values and clinical scores. Compared with healthy controls group, pre-operative cervical spondylotic myelopathy group showed increased functional connectivity between left thalamus and bilateral lingual gyrus/cuneus/right cerebellum posterior lobe (Voxel P-value <0.01, Cluster P-value <0.05, GRF corrected); post-operative cervical spondylotic myelopathy group manifested decreased functional connectivity between right thalamus and bilateral paracentral lobe/precentral gyrus but significantly increased between right thalamus and pons/superior temporal gyrus. In comparison with pre-operative cervical spondylotic myelopathy group, post-operative cervical spondylotic myelopathy group showed increased functional connectivity between bilateral thalamus and posterior cingulate lobe, angular gyrus, medial prefrontal, but significantly decreased functional connectivity between bilateral thalamus and paracentral lobe/precentral gyrus. The functional connectivity between left thalamus and bilateral lingual gyrus/cuneus/right cerebellum posterior lobe in pre-operative cervical spondylotic myelopathy group have a significantly positive correlation with sensory Japanese Orthopaedic Association scores (r = 0.568, P < 0.001). The functional connectivity between thalamus and paracentral lobe/precentral gyrus in post-operative cervical spondylotic myelopathy group have a significantly positive correlation with upper limb movement Japanese Orthopaedic Association scores (r = 0.448, P = 0.042). Pre- or post-operative cervical spondylotic myelopathy patients showed functional connectivity alteration between thalamus and cortex, which suggest adaptive changes may favor the preservation of cortical sensorimotor networks before and after cervical cord decompression, and supply the improvement of clinical function.

Exercise training modulates glutamic acid decarboxylase-65/67 expression through TrkB signaling to ameliorate neuropathic pain in rats with spinal cord injury.

Neuropathic pain is one of the most frequently stated complications after spinal cord injury. In post-spinal cord injury, the decrease of gamma aminobutyric acid synthesis within the distal spinal cord is one of the main causes of neuropathic pain. The predominant research question of this study was whether exercise training may promote the expression of glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67, which are key enzymes of gamma aminobutyric acid synthesis, within the distal spinal cord through tropomyosin-related kinase B signaling, as its synthesis assists to relieve neuropathic pain after spinal cord injury. Animal experiment was conducted, and all rats were allocated into five groups: Sham group, SCI/PBS group, SCI-TT/PBS group, SCI/tropomyosin-related kinase B-IgG group, and SCI-TT/tropomyosin-related kinase B-IgG group, and then T10 contusion SCI model was performed as well as the tropomyosin-related kinase B-IgG was used to block the tropomyosin-related kinase B activation. Mechanical withdrawal thresholds and thermal withdrawal latencies were used for assessing pain-related behaviors. Western blot analysis was used to detect the expression of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-REB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. Immunohistochemistry was used to analyze the distribution of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord dorsal horn. The results showed that exercise training could significantly mitigate the mechanical allodynia and thermal hyperalgesia in post-spinal cord injury and increase the synthesis of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. After the tropomyosin-related kinase B signaling was blocked, the analgesic effect of exercise training was inhibited, and in the SCI-TT/tropomyosin-related kinase B-IgG group, the synthesis of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord were also significantly reduced compared with the SCI-TT/PBS group. This study shows that exercise training may increase the glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67 expression within the spinal cord dorsal horn through the tropomyosin-related kinase B signaling, and this mechanism may play a vital role in relieving the neuropathic pain of rats caused by incomplete SCI.

BIRTH DEFECTS OF HUMAN SPINAL COLUMN

Various anomalies of spinal column development have common clinical manifestations. However, each defect has certain features that affect the nature of the deformity, the rate of its progression, the function of the spinal cord and the possibility of developing neurological disorders. An increase in deformation in the anomaly zone can lead to segmental instability at this level, which further cause disturbance of the biomechanics of the spine in general. The cervical section is the most mobile section of the spine, which is provided by the structure of the Atlantic-axial complex and functional mobility of the subaxial section. The detected anomaly should be evaluated in terms of the likelihood of developing instability. Mechanical instability is manifested by the displacement of vertebrae beyond the physiological range of movements. Neurological instability is mostly manifested in the subaxial section of the spine, as the reserve space of the spinal canal is extremely small. Congenital abnormalities of the thoracic spine that lead to deformity are the most common defects against the ground of impaired formation of vertebral bodies. Children with congenital kyphosis are motionless, and dyspnea occurs while walking fast or jogging. Surgical treatment of kyphotic deformities of the thoracic and lumbar spine is one of the most difficult problems in modern orthopedics, the relevance of which is stipulated by a relatively high frequency of unsatisfactory results of treatment. Lumbarisation is a congenital malformation of the spine, accompanied by the formation of an additional lumbar vertebra, which is formed from the superior sacral vertebra that has not fused into a single bone with the other sacral vertebrae. The frequency of occurrence is unknown, because lumbarisation in some cases is asymptomatic and undiagnosed. Depending on the nature of anatomical changes and the peculiarities of the influence on the dynamic and static functions of the spine, unilateral and bilateral lumbarisation are distinguished. Both unilateral and bilateral forms can be bone, cartilage and joint. The development of pain is characteristic only of the joint form of lumbarisation. Caudal regression syndrome is a rare severe congenital malformation of the distal spine and spinal cord. Clinically the disease is accompanied by hypoplasia of the lower half of the trunk and extremities due to a gross defect in the development of the caudal spine and spinal cord. Depending on the level and severity of the lesion of the latter there is a different stage of neurological deficit. In most observations, caudal regression syndrome is combined with defects in other organs and systems. Depending on the level of damage to the spine, coccyx, sacral, lumbar and even lower thoracic vertebrae may be absent, which determines the variant of the defect. An extremely severe form of caudal regression is called sirenomelia, or "mermaid syndrome". A sign of this anomaly is the fusion of the lower extremities. The fusion can be osseous or within soft tissue. In most cases with sirenomelia renal agenesis is observed, the colon ends blindly, the external and internal genitalia are absent, a single umbilical artery and anus atresia are detected. The quality of life prognosis for patients with caudal regression syndrome depends on the severity of spinal and spinal cord defects, the severity of neurological disorders, and urological complications. Children need constant medical rehabilitation.

The Distal Spine: Normal Embryogenesis and Derangements Leading to Malformation.

The spine and spinal cord are composed of multiple segments initiated by different embryologic mechanisms and advanced under different systems of control. In humans, the upper central nervous system is formed by primary neurulation, the lower by secondary neurulation, and the intervening segment by junctional neurulation. This article focuses on the distal spine and spinal cord to address their embryogenesis and the molecular derangements that lead to some distal spinal malformations.

Spinal Column Shortening for Secondary Tethered Cord Syndrome in Children: 2-Dimensional Operative Video.

Tethered cord syndrome is a constellation of signs and symptoms involving sensory and motor dysfunction of the lower extremities, bladder, and bowel. The pathophysiology may be from a mechanical stretch of the distal spinal cord causing deleterious changes in blood supply and metabolism. The standard of care for tethered cord syndrome has been tethered cord release. However, drawbacks of traditional tethered cord release include neurological injury, cerebrospinal fluid leak, and intradural scarring and retethering of the spinal cord (secondary tethering). As such, spinal column shortening was described to avoid these risks.1 We applied spinal column shortening to children and transitional adults with secondary tethered cord syndrome.1 As shown in cadaveric biomechanical studies, the objective of surgery is to shorten by the spinal column by 1.5 to 2.5 cm, to obtain the equivalent relief of traction on the spinal cord and nerve roots as direct circumferential untethering.2 In this video, we present the case of an 11-yr-old boy with a history of VATERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) and tethered cord syndromes manifest as bladder dysfunction. Our patient had segmentation and formation anomalies of the lumbosacral junction, imperforate anus, and leg length discrepancy. He had already undergone multiple tethered cord releases with no durable improvement in bladder function. After discussion of the advantages and disadvantages of spinal column shortening with the patient and his father, we decided to proceed with this treatment alternative. At 9 mo after surgery, the patient has satisfactory clinical and radiographic outcomes. Informed consent was obtained from the parents of the patient.

Histopathological lesions in reproductive organs, distal spinal cord and peripheral nerves of horses naturally infected with Trypanosoma equiperdum

BackgroundDourine, a venereal transmitted trypanosomosis caused by Trypanosoma equiperdum, has different clinical signs related to the reproductive and nervous system. Pathologic tissue changes associated with the disease are poorly described. The present study describes the histopathological lesions in naturally T. equiperdum-infected horses in the chronical stage of dourine.ResultsFour chronically dourine diseased horses underwent a post-mortem examination. They were Woo test negative, but CATT/T. evansi positive, had a low packed cell volume (PCV) and exhibited obvious clinical signs of dourine. Post-mortem examination did not reveal gross lesions in the organs assumed to be responsible for the symptomatology. On histopathology, genital organs were affected, with mononuclear cell infiltration and erosions and degeneration of seminiferous tubules and perivascular lymphoplasmacytic cuffing in the uterus. In the nervous system, mononuclear cell infiltration was located in peripheral nerves, ganglia and in the spinal cord, leading to axonal degeneration. Real-time PCR using ITS primer revealed the presence of trypanosomes in these organs and conventional PCRs using maxicircle and RoTat1.2 primers further confirmed the involvement of T. equiperdum since the DNAs from the vagina, testicle, distal spinal cord, sciatic and obturator nerves found to be positive for maxicircle and negative for RoTat 1.2.ConclusionsThe histopathological lesions in the spinal cord and peripheral nerves explain the incoordination of the hind legs in T. equiperdum-infected horses, whilst its presence in the genital tract exemplifies the venereal transmission.

Spinal Cord Injury in Rats Disrupts the Circadian System.

Spinal cord injury (SCI) perturbs many physiological systems. The circadian system helps maintain homeostasis throughout the body by synchronizing physiological and behavioral functions to predictable daily events. Whether disruption of these coordinated daily rhythms contributes to SCI-associated pathology remains understudied. Here, we hypothesized that SCI in rats would dysregulate several prominent circadian outputs including glucocorticoids, core temperature, activity, neuroinflammation, and circadian gene networks. Female and male Sprague Dawley rats were subjected to clinically relevant thoracic 9 moderate contusion SCI (or laminectomy sham surgery). Diurnal measures-including rhythms of plasma corticosterone (CORT), body temperature, and activity (using small implanted transmitters), and intraspinal circadian and inflammatory gene expression-were studied prior to and after surgery. SCI caused overall increases and disrupted rhythms of the major rodent glucocorticoid, CORT. Presurgery and sham rats displayed expected rhythms in body temperature and activity, whereas rats with SCI had blunted daily rhythms in body temperature and activity. In parallel, SCI disrupted intraspinal rhythms of circadian clock gene expression. Circadian clock genes can act as transcriptional regulators of inflammatory pathways. Indeed, SCI rats also showed dysregulated rhythms in inflammatory gene expression in both the epicenter and distal spinal cord. Our data show that moderate SCI in rats causes wide-ranging diurnal rhythm dysfunction, which is severe at acute time points and gradually recovers over time. Normalizing post-SCI diurnal rhythms could enhance the recovery of homeostasis and quality of life.

Tethered Cord Syndrome

Tethered cord syndrome (TCS) is a clinical condition of various origins, which comprises of progressive neurological, urological, and orthopaedic dysfunction, because of congenital fixation or tethering of the distal spinal cord by the terminal filum. It is believed that, if the filum elasticity is compromised by either fatty infiltration or abnormal thickening, the spine movement may cause stress upon the conus, resulting in TCS.Patients with symptomatic TCS can present with a wide variety of signs and symptoms in combination with cutaneous, orthopaedic, spinal, anorectal, and urological abnormalities. The common clinical presentations include the presence of cutaneous signs associated with open septal defects, neurogenic bladder with incontinence or urinary tract infection, leg or foot weakness, numbness and/or spasticity, differences in leg or foot length, deformities of the foot, spinal deformities, and back and leg pain.Neuroimaging is used to confirm when there is suspicion of TCS. Magnetic resonance imaging is the modality of choice in visualizing the level of the conus medullaris and for identifying a thickened and/or fatty filum.The fundamental goals of surgical intervention in TCS are to prevent future deficits in the asymptomatic patient and to improve or stabilize deficits in the symptomatic patient. These two goals are based on the fact that sectioning of the terminal filum can be done safely with minimal risk and a very low rate of morbidity. The reported complications of surgery are cerebrospinal fluid leakage (most common), wound infection, meningitis, bladder dysfunction, and neurological injury.

Tethered Cord Syndrome

Tethered cord syndrome (TCS) is a clinical condition of various origins, which comprises of progressive neurological, urological, and orthopaedic dysfunction, because of congenital fixation or tethering of the distal spinal cord by the terminal filum. It is believed that, if the filum elasticity is compromised by either fatty infiltration or abnormal thickening, the spine movement may cause stress upon the conus, resulting in TCS.Patients with symptomatic TCS can present with a wide variety of signs and symptoms in combination with cutaneous, orthopaedic, spinal, anorectal, and urological abnormalities. The common clinical presentations include the presence of cutaneous signs associated with open septal defects, neurogenic bladder with incontinence or urinary tract infection, leg or foot weakness, numbness and/or spasticity, differences in leg or foot length, deformities of the foot, spinal deformities, and back and leg pain.Neuroimaging is used to confirm when there is suspicion of TCS. Magnetic resonance imaging is the modality of choice in visualizing the level of the conus medullaris and for identifying a thickened and/or fatty filum.

NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

F69. Longitudinal follow-up of traumatic cauda equina/conus medullaris injuries – Neurological, neurophysiological and funsctional outcomes

Introduction Traumatic cauda equina/conus medullaris injuries lead to complex neurological syndromes that can compromise motor, sensory and autonomic functions of the lower limbs and pelvic organs. Some patients attain partial recovery of lower limb function and can accomplish independent ambulation. Standardized measures based on the neurological and functional evaluations are used to predict ambulation in spinal cord injuries. As distal spinal cord elements and cauda equina are composed mostly of peripheral nervous system structures, nerve conduction studies and electromyography (EMG), which are useful to quantify axonal loss, could help predict motor and functional outcomes. Methods 55 patients with trauma to the distal spinal cord due to thoracolumbar injuries, were submitted to a thoroughly evaluation in two distinct occasions - before the rehabilitation program (2–3 months after the injury) and after a long follow-up of at least 2 years. A longitudinal evaluation of neurological (ASIA/American Spinal Injury Association - Lower Extremity Motor Score-LEMS), functional (SCIM – Spinal Cord Independence Measure) and neurophysiological (EMG scores- EMGs) function was performed. The primary outcome was independent ambulation at the second year after the injury (SCIM item 12). A repeated-measures design with analysis of covariance (ANCOVA) was used to demonstrate the difference of pertinent parameters in the groups (complete X incomplete lesions) considering the baseline values, due to multiple confounders. Multiple regression and binary logistic regression analysis were used to determine the relevant importance of predictors. This work received local ethics board approval. Results From 55 patients (46 men, 18–53 years), 24 (43.6%) presented with an incomplete injury. Firearm injuries (63.6%) were the most frequent etiology, followed by motor vehicle accidents (20%) and falls (16.4%). There were no differences in demographic data between the groups (complete X incomplete injuries). All patients independently improved from motor function scores measured by LEMS and EMGs (p Conclusion The prognosis for neurological and functional recovery in traumatic cauda equina/conus medullaris injuries seems to be related to injury extension and to the initial improvement in motor function. The improvement in LEMS and EMGs, that were significantly correlated, suggests that the recovery of motor function might be related mostly to potential regrowth and regeneration of spinal roots.

Radial Glia and Cell Heterogeneity Across The Lizard Central Nervous System: Distal Spinal Cord Rupture Does Not Induce a System‐Wide Response

Radial glia are resident neural stem/progenitor cells of the central nervous system of many non‐mammalian species. Radial glia are capable of spontaneously generating new neurons, and are considered to be crucial for both brain development and injury‐mediated regeneration. Recently, radial glia have also been identified in the tail spinal cord of the lizard Eublepharis macularius (the leopard gecko), a species capable of tail spinal cord regeneration. Here, we investigated whether similar populations of radial glia were present within the body spinal cord (bSC) and brain. Using a bromodeoxyuridine pulse‐chase strategy, we determined that label‐retaining cells were found throughout the bSC and the forebrain following a 20‐week chase. Next, we established that populations of cells lining the central canal (of the bSC) and ventricular system (of the brain) express a panel of radial glia markers, including the transcription factor SOX2 and the intermediate filaments GFAP and Vimentin. However, Vimentin expression was conspicuously absent from the diencephalon (except for the hypothalamic eminence), as well as the midbrain and hindbrain. Further, cell populations lining the central canal of the bSC include both radial glia and cells with a neuronal phenotype (as evidenced by expression of the neuronal marker HuCD). An identical diversity of cell types is also reported for in the regeneration‐competent tail spinal cord. Finally, we determined that constitutive proliferation by cells lining the central canal (of the bSC) and the ventricular system (of the forebrain) are essentially unaltered in response to distal central nervous system injury (tail spinal cord rupture as a result of tail loss). Combined, our data demonstrates that radial glia are present throughout the central nervous system of the gecko, that the bSC is essentially identical to that of the tail, and that the bSC and forebrain are resilient to distal spinal cord injuries.Support or Funding InformationNatural Sciences and Engineering Research Council Discovery Grant 400358 (MKV), Canadian Foundation for Innovation Leaders Opportunity Fund 25371(MKV)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Unusual paediatric spinal myxopapillary ependymomas: Unique molecular entities or pathological variations on a theme?

Ependymomas are the commonest type of spinal glioma which represent a group of relatively benign tumours. Myxopapillary ependymoma (MPE) is a common variant found within the distal spinal cord around the conus. These two entities are clearly differentiated on the basis of their characteristic histological and molecular features. Rare variants of MPE’s are described in the literature to have the propensity to metastasise and grow in extraspinal locations despite appearing histologically identical to their more benign relatives. Here, we describe two unusual cases of MPE and utilise DNA methylation analyses to compare their molecular signatures with known molecular subtypes of ependymoma in an attempt to distinguish whether these tumours represent a unique subset of disease.

Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury

Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integration between host astrocytes and graft Schwann cells, allowing for robust growth, especially of catecholaminergic axons, through the graft and back into the distal spinal cord. In the absence of aFGF+ChABC fewer catecholaminergic axons entered the graft, no axons exited, and Schwann cells and astrocytes failed to integrate. In sharp contrast with the acutely bridge-repaired cord, in the chronically repaired cord only low levels of serotonergic axons regenerated into the graft, with no evidence of re-entry back into the spinal cord. The failure of axons to regenerate was strongly correlated with a dramatic increase of SOCS3 expression. While regeneration was more limited overall than at acute stages, our combinatorial strategy in the chronically injured animals prevented a decline in locomotor behavior and bladder physiology outcomes associated with an invasive repair strategy. These results indicate that PNG+aFGF+ChABC treatment of the chronically contused spinal cord can provide a permissive substrate for the regeneration of certain neuronal populations that retain a growth potential over time, and lead to functional improvements.

Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury

After spinal cord injury (SCI), severed axons in the adult mammalian CNS are unable to mount a robust regenerative response. In addition, the glial scar at the lesion site further restricts the regenerative potential of axons. We hypothesized that a combinatorial approach coincidentally targeting these obstacles would promote axonal regeneration. We combined (1) transplantation of a growth-permissive peripheral nerve graft (PNG) into an incomplete, cervical lesion cavity; (2) transduction of neurons rostral to the SCI site to express constitutively active Rheb (caRheb; a Ras homolog enriched in brain), a GTPase that directly activates the growth-promoting pathway mammalian target of rapamycin (mTOR) via AAV-caRheb injection; and (3) digestion of growth-inhibitory chondroitin sulfate proteoglycans within the glial scar at the distal PNG interface using the bacterial enzyme chondroitinase ABC (ChABC). We found that expressing caRheb in neurons post-SCI results in modestly yet significantly more axons regenerating across a ChABC-treated distal graft interface into caudal spinal cord than either treatment alone. Excitingly, we found that caRheb+ChABC treatment significantly potentiates the formation of synapses in the host spinal cord and improves the animals' ability to use the affected forelimb. Thus, this combination strategy enhances functional axonal regeneration following a cervical SCI.

Improving the regenerative potential of olfactory ensheathing cells by overexpressing prostacyclin synthetase and its application in spinal cord repair

BackgroundOlfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent.ResultsCultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10–12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40–60% of AdPGIS-OEC transplanted SCI rats.ConclusionsEnhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.

Multisystemic anomalies in conjoined twins: The role of imaging in management

Conjoined twins (CT) represent one of the rarest and most challenging congenital malformations arising as an unfortunate complication of monozygous twinning, with an estimated incidence ranging from 1 in 50,000 to 100,000 pregnancies, with an overall true incidence of about 1 in 200,000 live births with around 60% of them being stillborn. The types of the twins may differ depending on the site of fusion or nonseparation. The most commonly encountered types are thoraco-omphalopagus (28%), thoracopagus (18%), omphalopagus (10%), parasitic twins (10%), pygopagus (6-19%), and craniopagus (6%), with the pygopagus twins having the highest survival rate. Because of the highly variable and complex anatomy and associated malformations, skilled clinical assessments aided by detailed radiological studies, appropriate planning, and teamwork are required for the successful separation of the CT. The role of imaging in the diagnosis and management of missed diagnosed intrauterine case of pygopagus type CT was presented. At delivery, they were found to have sacral fusion on radiography with distal, rectal fusion on limited barium enema. Magnetic resonance imaging demonstrated distal spinal cord fusion with vascular anomaly found on computed tomography angiography. The surgical separation of the patients was successful with satisfactory postoperative lives.

MRI of Conus Medullaris, Cauda Equina, and Filum Terminale Lesions

Cauda equina is the Latin name for horse's tail because the cauda equina resembles a horse tail. The cauda equina is a set of 10 paired dorsal and ventral nerve roots (20 nerve roots in total), corresponding to four lumbar (second to fifth), five sacral, and one coccygeal segments that originate from the conus medullaris. These nerve roots are contained by the thecal sac, which is an enclosed space formed by dura mater and arachnoid extending from the head to the sacrum. The conus medullaris is an expansion of the terminating distal thoracic spinal cord, typically located at the T12-L1 level.

In vivo bioluminescence imaging for leptomeningeal dissemination of medulloblastoma in mouse models.

BackgroundThe primary cause of treatment failure in medulloblastomas (MB) is the development of leptomeningeal dissemination (seeding). For translational research on MB seeding, one of the major challenges is the development of reliable experimental models that simulate the seeding and growth characteristics of MBs. To overcome this obstacle, we improved an experimental mouse model by intracisternal inoculation of human MB cells and monitoring with in vivo live images.MethodsHuman MB cells (UW426, D283 and MED8A) were transfected with a firefly luciferase gene and a Thy1.1 (CD90.1) marker linked with IRES under the control of the CMV promoter in a retroviral DNA backbone (effLuc). The MB-effLuc cells were injected into the cisterna magna using an intrathecal catheter, and bioluminescence images were captured. We performed histopathological analysis to confirm the extent of tumor seeding.ResultsThe luciferase activity of MB-effLuc cells displayed a gradually increasing pattern, which correlated with a quantitative luminometric assay. Live imaging showed that the MB-effLuc cells were diffusely distributed in the cervical spinal cord and the lumbosacral area. All mice injected with UW426-effLuc, D283-effLuc and MED8A-effLuc died within 51 days. The median survival was 22, 41 and 12 days after injection of 1.2 × 106 UW426-effLuc, D283-effLuc and MED8A-effLuc cells, respectively. The histopathological studies revealed that the MB-effLuc cells spread extensively and diffusely along the leptomeninges of the brain and spinal cord, forming tumor cell-coated layers. The tumor cells in the subarachnoid space expressed a human nuclei marker and Ki-67. Compared with the intracerebellar injection method in which the subfrontal area and distal spinal cord were spared by tumor cell seeding in some mice, the intracisternal injection model more closely resembled the widespread leptomeningeal seeding observed in MB patients.ConclusionThe results and described method are valuable resources for further translational research to overcome MB seeding.

24. IOM in tethered spine surgery

Tethered cord syndrome (TCS) is a disorder in which the distal spinal cord is tethered caudally to an immovable boney structure. This results in dysfunction of the lower spinal cord and cauda equina, manifest as lower extremity weakness, sensory loss, bowel and bladder dysfunction and occasionally musculoskeletal deformities. Surgery for TCS involves releasing the tethering structure and correcting the musculoskeletal abnormalities. Because the neural elements of the cauda equina are in close proximity, there is potential for damage to these structures during surgery. Neurophysiologic intraoperative monitoring (NIOM) can help prevent injury to these structures. NIOM for TCS surgery can include monitoring free running and stimulated electromyography (EMG), anal sphincter EMG, tibial nerve somatosensory evoked potentials (SEP), motor evoked potentials, bulbocavernosus reflex and pudendal nerve SEP. These monitoring modalities will be discussed.