Invasion of lesion territory by regenerating fibers after spinal cord injury in adult macaque monkeys.

In adult macaque monkeys subjected to an incomplete spinal cord injury (SCI), corticospinal (CS) fibers are rarely observed to grow in the lesion territory. This situation is little affected by the application of an anti-Nogo-A antibody which otherwise fosters the growth of CS fibers rostrally and caudally to the lesion. However, when using the Sternberger monoclonal-incorporated antibody 32 (SMI-32), a marker detecting a non-phosphorylated neurofilament epitope, numerous SMI-32-positive (+) fibers were observed in the spinal lesion territory of 18 adult macaque monkeys; eight of these animals had received a control antibody infusion intrathecally for 1month after the injury, five animals an anti-Nogo-A antibody, and five animals received an anti-Nogo-A antibody together with brain-derived neurotrophic factor (BDNF). These fibers occupied the whole dorso-ventral axis of the lesion site with a tendency to accumulate on the ventral side, and their trajectories were erratic. Most of these fibers (about 87%) were larger than 1.3μm and densely SMI-32 (+) stained. In the undamaged spinal tissue, motoneurons form the only large population of SMI-32 (+) neurons which are densely stained and have large diameter axons. These data therefore suggest that a sizeable proportion of the fibers seen in the lesion territory originate from motoneurons, although fibers of other origins could also contribute. Neither the presence of the antibody neutralizing Nogo-A alone, nor the presence of the antibody neutralizing Nogo-A combined with BDNF influenced the number or the length of the SMI-32 (+) fibers in the spinal lesion area. In summary, our data show that after a spinal cord lesion in adult monkeys, the lesion site is colonized by fibers, a large portion of which presumably originate from motoneurons.

Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy?

Dominant mutations in the receptor calcium channel gene TRPV4 have been associated with a family of skeletal dysplasias (metatropic dysplasia, pseudo-Morquio type 2, spondylometaphyseal dysplasia, Kozlowski type, brachyolmia, and familial digital arthropathy) as well as with dominantly inherited neuropathies (hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy). While there is phenotypic overlap between the various members of each group, the two groups were considered to be totally separate with the former being strictly a structural skeletal condition and the latter group being confined to the peripheral nervous system. We report here on fetal akinesia as the presenting feature of severe metatropic dysplasia, suggesting that certain TRPV4 mutations can cause both a skeletal and a neuropathic phenotype. Three cases were detected on prenatal ultrasound because of absent movements in the second trimester. Case 4 presented with multiple joint contractures and absent limb movements at birth and was diagnosed with "fetal akinesia syndrome". Post-interruption and post-natal X-rays showed typical features of metatropic dysplasia in all four. Sequencing of the TRPV4 gene confirmed the presence of de novo heterozygous mutations predicting G78W (Case 1), T740I (Cases 2 and 3), and K276E (Case 4). Although some degree of restriction of movements is not uncommon in fetuses with skeletal dysplasia, akinesia as leading sign is unusual and suggests that certain TRPV4 mutations produce both chondrodysplasia and a peripheral neuropathy resulting in a severe "overlap" phenotype.

Incidence and management of pulmonary embolism following spinal surgery occurring while under chemical thromboprophylaxis.

Patients undergoing spinal surgery are at risk of developing thromboembolic complications even though lower incidences have been reported as compared to joint arthroplasty surgery. Deep vein thrombosis (DVT) has been studied extensively in the context of spinal surgery but symptomatic pulmonary embolism (PE) has engaged less attention. We prospectively followed a consecutive cohort of 270 patients undergoing spinal surgery at a single institution. From these patients, only 26 were simple discectomies, while the largest proportion (226) was fusions. All patients received both low molecular weight heparin (LMWH) initiated after surgery and compressive stockings. PE was diagnosed with spiral chest CT. Six patients developed symptomatic PE, five during their hospital stay. In three of the six patients the embolic event occurred during the first 3 postoperative days. They were managed by the temporary insertion of an inferior vena cava (IVC) filter thus allowing for a delay in full-dose anticoagulation until removal of the filter. None of the PE patients suffered any bleeding complication as a result of the introduction of full anticoagulation. Two patients suffered postoperative haematomas, without development of neurological symptoms or signs, requiring emergency evacuation. The overall incidence of PE was 2.2% rising to 2.5% after exclusion of microdiscectomy cases. The incidence of PE was highest in anterior or combined thoracolumbar/lumbar procedures (4.2%). There is a large variation in the reported incidence of PE in the spinal literature. Results from the only study found in the literature specifically monitoring PE suggest an incidence of PE as high as 2.5%. Our study shows a similar incidence despite the use of LMWH. In the absence of randomized controlled trials (RCT) it is uncertain if this type of prophylaxis lowers the incidence of PE. However, other studies show that the morbidity of LMWH is very low. Since PE can be a life-threatening complication, LMWH may be a worthwhile option to consider for prophylaxis. RCTs are necessary in assessing the efficacy of DVT and PE prophylaxis in spinal patients.

Fast Blue and Diamidino Yellow as retrograde tracers in peripheral nerves: efficacy of combined nerve injection and capsule application to transected nerves in the adult rat

Capsule application of Diamidino Yellow (DY) to the cut end of the sciatic nerve immediately followed by capsule application of Fast Blue (FB) resulted in approximate to 95% double-labelled dorsal root ganglion neurones (DRGn) and motoneurones (Mn). Nerve injection of DY followed either immediately or 2 months later by capsule application of FB resulted in approximate to 90% double-labelled DRGn and Mn, indicating that DY and FB label similar populations of DRGn and Mn, and that insignificant DY fading occurred during this period. Inversing the order of application, however, i.e. nerve injection of FB followed immediately by capsule application of DY, resulted in double labelling in only approximate to 10% of the DRGn and Mn. These percentages increased to 70% of the DRGn and 60% of the Mn when the FB injection was followed 1 or 2 months after by the DY application, indicating that DY uptake is blocked by recent administration of FB. The results indicate that DY and FB might be useful for sequential labelling before and after nerve injury as a tool to investigate the accuracy of sensory and motor regeneration.

Single stage transforaminal retrojugular tumor resection: The spinal keyhole for dumbbell tumors in the cervical spine.

BACKGROUND: Dumbbell tumors are defined as having an intradural and extradural component with an intermediate component within an expanded neural foramen. Complete resection of these lesions in the subaxial cervical spine is a challenge, and it has been achieved through a combined posterior/anterior or anterolateral approach. This study describes a single stage transforaminal retrojugular (TFR) approach for dumbbell tumors resection in the cervical spine. METHODS: This is a retrospective review of a series of 17 patients treated for cervical benign tumors, 4 of which were "true" cervical dumbbell tumors operated by a simplified retrojugular approach. The TFR approach allows a single stage gross total resection of both the extraspinal and intraspinal/intradural components of the tumor, taking advantage of the expanded neural foramen. All patients were followed clinically and radiologically with magnetic resonance imaging (MRI). RESULTS: Gross total resection was confirmed in all four patients by postoperative MRI. Minimal to no bone resection was performed. No fusion procedure was performed and no delayed instability was seen. At follow up, one patient had a persistent mild hand weakness and Horners syndrome following resection of a hemangioblastoma of the C8 nerve root. The other three patients were neurologically normal. CONCLUSIONS: The TFR approach appears to be a feasible surgical option for single stage resection in selective cases of dumbbell tumors of the cervical spine.

Magnetic resonance imaging findings of disc-related epidural cysts in nonsurgical and postoperative microdiscectomy patients

OBJECTIVE: To demonstrate five discal cysts with detailed magnetic resonance imaging findings in nonsurgical and following postoperative microdiscectomy. MATERIALS AND METHODS: Five discal cysts in four patients who underwent magnetic resonance imaging were found through a search in our database and referral from a single orthopedic spine surgeon. Computed tomography in two cases and computed tomography discography in one case were also performed. RESULTS: Five discal cysts were present in four patients. Three patients had no history of previous lumbar surgery and the other patient presented with two discal cysts and recurrent symptoms after partial laminectomy and microdiscectomy. All were oval shaped and seated in the anterior epidural space. Four were ventrolateral, and the other one was centrally positioned in the anterior spinal canal. One showed continuity with the central disc following discography. Three were surgically removed. CONCLUSION: Magnetic resonance imaging can easily depict an epidural cyst and the diagnosis of a discal cyst should be raised when an homogeneous ventrolateral epidural cyst contiguous to a mild degenerated disc is identified.

Spinal cord compression in cattle after the use of an oily vaccine

An outbreak of compressive myelopathy in cattle associated with the improper use of an oil vaccine is described. Neurological signs were observed in 25 out of 3,000 cattle after 60 days of being vaccinated against foot and mouth disease. The clinical picture was characterized by progressive paralysis of the hind limbs, difficulty in standing up, and sternal recumbency during the course of 2-5 months. A filling defect between the L1 and L3 vertebrae was seen through myelography performed in one of the affected animals. A yellow-gray, granular and irregular mass was observed in four necropsied animals involving the spinal nerve roots and epidural space of the lumbar (L1-L4) spinal cord; the mass was associated with a whitish oily fluid. This fluid was also found in association with necrosis of the longissimus dorsi muscle. Microscopic changes in the epidural space, nerve roots, and spinal musculature were similar and consisted of granulomas or pyogranulomas around circular unstained spaces (vacuoles). These spaces were located between areas of severe diffuse hyaline necrosis of muscle fibers and resembled the drops of oil present in the vaccine.

Assessment of the diagnostic value of diffusion tensor imaging in patients with spinal cord compression: a meta-analysis

We investigated the diagnostic value of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging (DTI) in patients with spinal cord compression (SCC) using a meta-analysis framework. Multiple scientific literature databases were exhaustively searched to identify articles relevant to this study. Mean values and standardized mean differences (SMDs) were calculated for the ADC and FA in normal and diseased tissues. The STATA version 12.0 software was used for statistical analysis. Of the 41 articles initially retrieved through database searches, 11 case-control studies were eligible for the meta-analysis and contained a combined total of 645 human subjects (394 patients with SCC and 251 healthy controls). All 11 studies reported data on FA, and 9 contained data related to the ADC. The combined SMDs of the ADC and FA showed that the ADC was significantly higher and the FA was lower in patients with SCC than in healthy controls. Subgroup analysis based on the b value showed higher ADCs in patients with SCC than in healthy controls at b values of both ≤500 and >500 s/mm2. In summary, the main findings of this meta-analysis revealed an increased ADC and decreased FA in patients with SCC, indicating that DTI is an important diagnostic imaging tool to assess patients suspected to have SCC.

The Effects of Subarachnoid Administration of Preservative-Free S(+)-Ketamine on Spinal Cord and Meninges in Dogs

BACKGROUND: The N-methyl-D-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs.METHODS: Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equine root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein).RESULTS: No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups.CONCLUSION: A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg-1 dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model. (Anesth Analg 2012;114:450-55)

Anestesia epidural com ropivacaína, lidocaína ou associação de lidocaína e xilazina em cães: efeitos cardiorrespiratório e analgésico

Este estudo investigou o efeito da ropivacaína, da lidocaína e da associação de lidocaína e xilazina na anestesia epidural de cães. Trinta cães foram tranqüilizados com acepromazina intravenosa, distribuídos em três grupos e submetidos à anestesia epidural no espaço lombo-sacro, com lidocaína 2% com vasoconstrictor (GL), ropivacaína 1% (GR) ou com xilazina associada à lidocaína (GXL). Mensuraram-se as freqüências cardíaca (FC) e respiratória (f), a pressão arterial sistólica (PAS), a concentração final expirada de CO2 (EtCO2), o volume minuto (VM) e a temperatura retal (T). Para avaliação da analgesia somática, utilizou-se o teste do panículo e o teste térmico a 55°C. Os protocolos produziram anestesia da região retro-umbilical, sendo que a associação XL produziu bloqueio anestésico mais cranial, porém causou bradicardia moderada. A duração da anestesia foi mais prolongada nos animais dos grupos GXL (240 min) e GR (250 min), quando comparada as do grupo GL (120 min).

Injeção epidural de morfina ou cetamina em cães: avaliação do efeito analgésico pelo emprego de filamentos de von Frey

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analgesia of Epidural Tramadol in Dogs Submitted to Orchiectomy

Epidural tramadol in veterinary medicine has been studied in only a few instances. In this case, 36 dogs submitted to orchiectomy received 6.0 mg/kg of lidocaine combined with 1.0 mg/kg of tramadol, 0.1 mg/kg of morphine or 0.01 ml/kg of 0.9% NaCl by epidural route. Analgesia was assessed at 4, 8, 12, 18 and 24 hours after surgery. There were no differences between morphine and tramadol over the time of evaluation within these groups, and no complementary analgesia was necessary. In the NaCl group, analgesia was needed at 4, 8 and 12 hours. Epidural tramadol provides an analgesic effect comparable to that of morphine during the first 12 hours post-surgery.

Uso da lidocaína isolada ou associada à quetamina ou ao butorfanol, em anestesia epidural em cães: avaliação cardiorrespiratória e analgésica

Pós-graduação em Anestesiologia - FMB

Efeitos da injeção epidural de cetamina ou da sua associação com ifenprodil na mediação nociceptiva somática e visceral em equinos

Pós-graduação em Cirurgia Veterinária - FCAV

Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)