Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury.

BACKGROUND: After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK) in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX) to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1) positive fibers (mostly C- and Adelta-fibers) and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI), and observed spinal microglial changes 2 days later. RESULTS: SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+) were microglia (Iba1+). Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord. CONCLUSION: (1) Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers) is not enough to prevent nerve injury-induced spinal microglial activation. (2) Peripheral input from large myelinated fibers is important for microglial activation. (3) Microglial activation is associated with mechanical allodynia.

Recovery of paraplegia after type B dissection due to spinal collateral recruitment.

Acute paraplegia could be a symptom of aortic dissection due to sudden compromise of arterial spinal cord blood supply. Complete spontaneous neurologic recovery is possible and was observed in the present case 3 hours after symptom onset. Spontaneous spinal cord reperfusion after acute type B dissection was probably due to two main mechanisms. Reperfusion of false lumen and collateral vascular network recruitment, recently confirmed by anatomic animal studies, serve as potential explanations. Favorable evolution of acute paraplegia after aortic dissection exists, but prognosis is uncertain, probably due to individual variable anatomic distribution of spinal cord blood supply.

The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition.

Peripheral inflammation induces persistent central sensitization characterized by mechanical allodynia and heat hyperalgesia that are mediated by distinct mechanisms. Compared to well-demonstrated mechanisms of heat hyperalgesia, mechanisms underlying the development of mechanical allodynia and contralateral pain are incompletely known. In this study, we investigated the distinct role of spinal JNK in heat hyperalgesia, mechanical allodynia, and contralateral pain in an inflammatory pain model. Intraplantar injection of complete Freund's adjuvant (CFA) induced bilateral mechanical allodynia but unilateral heat hyperalgesia. CFA also induced a bilateral activation (phosphorylation) of JNK in the spinal cord, and the phospho JNK1 (pJNK1) levels were much higher than that of pJNK2. Notably, both pJNK and JNK1 were expressed in GFAP-positive astrocytes. Intrathecal infusion of a selective peptide inhibitor of JNK, D-JNKI-1, starting before inflammation via an osmotic pump, reduced CFA-induced mechanical allodynia in the maintenance phase but had no effect on CFA-induced heat hyperalgesia. A bolus intrathecal injection of D-JNKI-1 or SP600126, a small molecule inhibitor of JNK also reversed mechanical allodynia bilaterally. In contrast, peripheral (intraplantar) administration of D-JNKI-1 reduced the induction of CFA-induced heat hyperalgesia but did not change mechanical allodynia. Finally, CFA-induced bilateral mechanical allodynia was attenuated in mice lacking JNK1 but not JNK2. Taken together, our data suggest that spinal JNK, in particular JNK1 plays an important role in the maintenance of persistent inflammatory pain. Our findings also reveal a unique role of JNK1 and astrocyte network in regulating tactile allodynia and contralateral pain.

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.

Influence of the morphology of the dural sac on surgical decision making in lumbar spinal stenosis

Introduction: Surgical decision making in lumbar spinal stenosis (LSS) takes into account primarily clinical symptoms as well as concordant radiological findings. We hypothesized that a wide variation of operative threshold would be found in particular as far as judgment of severity of radiological stenosis is concerned. Patients and methods: The number of surgeons who would proceed to decompression was studied relative to the perceived severity of radiological stenosis based either on measurements of dural sac cross sectional area (DSCA) or on the recently described morphological grading as seen on axial T2 MRI images. A link to an electronic survey page with a set of ten axial T2 MRI images taken from ten patients with either low back pain or LSS were sent to members of three national or international spine societies. Those 10 images were randomly presented initially and re-shuffled on a second page including this time DSCA measurements in mm2, ranging from 14 to 226 mm2, giving a total of 20 images to appraise. Morphological grades were ranging from grade A to D. Surgeons were asked if they would consider decompression given the radiological appearance of stenosis and that symptoms of neurological claudication were severe in patients who were otherwise fit for surgery. Fisher's exact test was performed following dichotomization of data when appropriate. Results: A total of 142 spine surgeons (113 orthopedic spine surgeons, 29 neurosurgeons) responded from 25 countries. A substantial agreement was observed in operating patients with severe (grade C) or extreme (grade D) stenosis as defined by the morphological grade compared to lesser stenosis (A&B) grades (p<0.0001). Decision to operate was not dependent on number of years in practice, medical density in practicing country or specialty although more neurosurgeons would operate on grade C stenosis (p<0.005). Disclosing the DSCA measurement did not alter the decision to operate. Although 20 surgeons only had prior knowledge of the description of the morphological grading, their responses showed no statistically significant difference with those of the remaining 122 physicians. Conclusions: This study showed that surgeons across borders are less influenced by DSCA in their decision making than by the morphological appearance of the dural sac. Classifying LSS according to morphology rather than surface measurements appears to be consistent with current clinical practice.

Preoperative assessment of neurovesical function in children with anorectal malformation: association with vertebral and spinal malformations.

PURPOSE: We preoperatively assessed neurovesical function and spinal cord function in children with anorectal malformations. In cases of neurovesical dysfunction we looked for an association with vertebral malformation or myelodysplasia. MATERIALS AND METHODS: We prospectively evaluated 80 children with anorectal malformations via preoperative urodynamics and magnetic resonance imaging of the spine. Bladder compliance and volume, detrusor activity and vesicosphincteric synergy during voiding allowed urodynamic evaluation. Results were reported according to Wingspread and Krickenbeck classifications of anorectal malformations. RESULTS: Urodynamic findings were pathological in 14 children (18%). Pathological evaluations did not seem related to type of fistula or level of anorectal malformation. Vertebral anomalies were seen in 34 patients (43%) and myelodysplasia in 16 (20%). Neither vertebral anomaly nor myelodysplasia seemed associated with type of fistula or severity of anorectal malformation. Of 14 children with pathological urodynamics no vertebral anomaly or myelodysplasia was found in 7. Of 66 children with normal urodynamics 40 presented with vertebral or spinal malformation. CONCLUSIONS: Lower urinary tract dysfunction is common in patients with anorectal malformations. Normal spine or spinal cord does not exclude neurovesical dysfunction. Myelodysplasia or vertebral anomaly does not determine lower urinary tract dysfunction. Thus, we recommend preoperative urodynamic assessment of the bladder and magnetic resonance imaging of the spine in children with anorectal malformations.

Cross-cultural adaptation, reliability, internal consistency and validation of the Spinal Function Sort (SFS) for French- and German-speaking patients with back complaints.

Introduction Functional subjective evaluation through questionnaire is fundamental, but not often realized in patients with back complaints, lacking validated tools. The Spinal Function Sort (SFS) was only validated in English. We aimed to translate, adapt and validate the French (SFS-F) and German (SFS-G) versions of the SFS. Methods Three hundred and forty-four patients, experiencing various back complaints, were recruited in a French (n = 87) and a German-speaking (n = 257) center. Construct validity was estimated via correlations with SF-36 physical and mental scales, pain intensity and hospital anxiety and depression scales (HADS). Scale homogeneities were assessed by Cronbach's α. Test-retest reliability was assessed on 65 additional patients using intraclass correlation (IC). Results For the French and German translations, respectively, α were 0.98 and 0.98; IC 0.98 (95% CI: [0.97; 1.00]) and 0.94 (0.90; 0.98). Correlations with physical functioning were 0.63 (0.48; 0.74) and 0.67 (0.59; 0.73); with physical summary 0.60 (0.44; 0.72) and 0.52 (0.43; 0.61); with pain -0.33 (-0.51; -0.13) and -0.51 (-0.60; -0.42); with mental health -0.08 (-0.29; 0.14) and 0.25 (0.13; 0.36); with mental summary 0.01 (-0.21; 0.23) and 0.28 (0.16; 0.39); with depression -0.26 (-0.45; -0.05) and -0.42 (-0.52; -0.32); with anxiety -0.17 (-0.37; -0.04) and -0.45 (-0.54; -0.35). Conclusions Reliability was excellent for both languages. Convergent validity was good with SF-36 physical scales, moderate with VAS pain. Divergent validity was low with SF-36 mental scales in both translated versions and with HADS for the SFS-F (moderate in SFS-G). Both versions seem to be valid and reliable for evaluating perceived functional capacity in patients with back complaints.

Video-assisted thoracic surgery diagnosis of thoracic spinal tuberculosis.

Tuberculous spondylitis is rare in economically well-developed countries. MRI is the most sensitive radiologic method of diagnosis. CT-guided fine needle aspiration can be an appropriate method for obtaining samples for culture, with positive cultures in 25 to 89% of cases. However, it can take >6 weeks for specimens to grow, and it is essential to have adequate culture and sensitivity studies for the diagnosis and treatment of mycobacterial diseases. We propose a minimally invasive diagnostic approach that ensures that adequate surgical specimens are obtained prior to initiating treatment.

Spinal epidural abscess from group A Streptococcus after varicella infection: a case report and review of the literature.

INTRODUCTION: Spinal epidural abscess (SEA) is a very rare condition in pediatric patients. Varicella zoster infection could be a predisposing factor, and SEA should be suspected in patients with signs of secondary bacterial infection and even mild neurological signs. CLINICAL CASE: We describe here a case of a 30-month-old girl with a history of remitting varicella infection, diagnosed for a lumbar epidural abscess and sacro-ileitis, secondary to group A Streptococcus (GAS). DISCUSSION: This is the third case of SEA from GAS reported in the literature in a pediatric population with varicella infection. We discuss here the clinical presentation and the diagnostic challenges for SEA in childhood through a review of the literature.

Community-wide plasmid gene mobilization and selection.

Plasmids have long been recognized as an important driver of DNA exchange and genetic innovation in prokaryotes. The success of plasmids has been attributed to their independent replication from the host's chromosome and their frequent self-transfer. It is thought that plasmids accumulate, rearrange and distribute nonessential genes, which may provide an advantage for host proliferation under selective conditions. In order to test this hypothesis independently of biases from culture selection, we study the plasmid metagenome from microbial communities in two activated sludge systems, one of which receives mostly household and the other chemical industry wastewater. We find that plasmids from activated sludge microbial communities carry among the largest proportion of unknown gene pools so far detected in metagenomic DNA, confirming their presumed role of DNA innovators. At a system level both plasmid metagenomes were dominated by functions associated with replication and transposition, and contained a wide variety of antibiotic and heavy metal resistances. Plasmid families were very different in the two metagenomes and grouped in deep-branching new families compared with known plasmid replicons. A number of abundant plasmid replicons could be completely assembled directly from the metagenome, providing insight in plasmid composition without culturing bias. Functionally, the two metagenomes strongly differed in several ways, including a greater abundance of genes for carbohydrate metabolism in the industrial and of general defense factors in the household activated sludge plasmid metagenome. This suggests that plasmids not only contribute to the adaptation of single individual prokaryotic species, but of the prokaryotic community as a whole under local selective conditions.

Percutaneous radiofrequency ablation of primary intraosseous spinal glomus tumor.

The glomus tumor is a rare, benign, but painful vascular neoplasm arising from the neuromyoarterial glomus. Primary intraosseous glomus tumor is even rarer, with only about 20 cases reported in the literature so far, 5 of which involved the spine. Surgical resection is currently considered the treatment of choice. We herewith present an uncommon case of primary intraosseous spinal glomus tumor involving the right pedicle of the eleventh thoracic vertebra (T11). To our knowledge, this is the first case of primary intraosseous spinal glomus tumor successfully treated by percutaneous CT-guided radiofrequency ablation (RFA).

Secular changes of spinal canal dimensions in Western Switzerland: a narrowing epidemic?

STUDY DESIGN: Computed tomography-based anatomical study. OBJECTIVE: To study the secular changes in lumbar spinal canal dimensions. SUMMARY OF BACKGROUND DATA: Development of symptomatic lumbar spinal stenosis, among other factors, is related to the dimensions of the bony canal. The canal reaches its adult size early on in life. Several factors, including protein intake, may influence its final dimensions. As with increases in human stature from improvements of socioeconomic conditions, we hypothesized that adult bony canal size has also grown larger in recent generations. METHODS: This study analyzes computed tomographic reconstructions from 184 subjects performed for either trauma (n = 81) or abdominal pathologies (n = 103) and born either between 1940 and 1949 (n = 88) or 1970 and 1979 (n = 96). The cross-sectional area of the bony canal was digitally measured at the level of the pedicle (i.e., at a level not influenced by degenerative changes) for each lumbar vertebra. Intra- and interobserver reliability was assessed. RESULTS: Intra- and interobserver measurement reliability were excellent (interclass correlation coefficient = 0.87) and good (interclass correlation coefficient = 0.61), respectively. Contrary to our hypothesis, the 1940-1949 generation patient group exhibited larger lumbar canals at all levels as compared with the 1970-1979 group. Statistically this difference was highly significant (P < 0.001) and particularly pronounced in the trauma subgroup. CONCLUSION: Given that human stature evolution has stabilized and adult height is established during the first 2 years of long bone growth, it is possible that antenatal factors are responsible for this surprising finding. Maternal smoking and age may be possible explanations. This finding may have significant implications. An increasing number of patients may emerge with lumbar spinal stenosis as degenerative changes develop, putting a strain on health resources. Further studies in different population groups and countries will be important to further confirm this trend. LEVEL OF EVIDENCE: 3.

Pilomyxoid astrocytoma of the spinal cord in an adult.

We report a 45-year old woman with a pilomyxoid astrocytoma (PMA) of the cervical spinal cord with a rapid clinical course and fatal outcome. Moreover, two family members of the patient were reported to have brainstem tumours with similar histopathological features. This may be the first report of familial PMAs.