Routine sectioning of the C2 nerve root and ganglion for C1 lateral mass screw placement in children: surgical and functional outcomes

Purpose

Adult studies have shown that sectioning the C2 nerve root and ganglion may facilitate placement of C1 lateral mass screws and lead to decreased operative time and blood loss. We report the functional outcomes and complications following routine sectioning of the C2 nerve root and ganglion, which have not been reported in pediatric patients.

Methods

Fifteen consecutive pediatric patients underwent C1 lateral mass screw insertion and bilateral C2 nerve root and ganglion sectioning. Clinical and radiographic assessments were performed at follow-up. Numbness in the C2 distribution and/or occipital neuralgia, operative times, estimated blood loss (EBL), length of stay (LOS), and complications were recorded.

Results

Average follow-up time was 35.7 months. Overall mean operative time was 250.5 min, LOS was 8.46 days, and EBL was 337 cc. When considering only atlantoaxial fusions, mean operative time was 180.7 min and EBL was 97.1 cc. There were no intraoperative complications, and no patient reported new onset occipital neuralgia or numbness in the C2 distribution that would interfere with daily living. Of the patients, 93 % achieved Lenke fusion grade A; one achieved Lenke fusion grade B.

Conclusions

Routine C2 nerve root sectioning and ganglionectomy enhanced surgical exposure of the C1 lateral mass and C1–2 facet joint, potentially maximizing fusion rate and minimizing intraoperative complications. This technique may yield favorable operative times, EBL, and LOS in children undergoing C1 lateral mass screw insertion without negatively affecting functional outcome.     

Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation

We examined the immune response to DBY, a model H-Y minor histocompatibility antigen (mHA) in a male patient with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant from a human histocompatibility leukocyte antigen (HLA)-identical female sibling. Patient peripheral blood mononuclear cells were screened for reactivity against a panel of 93 peptides representing the entire amino acid sequence of DBY. This epitope screen revealed a high frequency CD4(+) T cell response to a single DBY peptide that persisted from 8 to 21 mo after transplant. A CD4(+) T cell clone displaying the same reactivity was established from posttransplant patient cells and used to characterize the T cell epitope as a 19-mer peptide starting at position 30 in the DBY sequence and restricted by HLA-DRB1*1501. Remarkably, the corresponding X homologue peptide was also recognized by donor T cells. Moreover, the T cell clone responded equally to mature HLA-DRB1*1501 male and female dendritic cells, indicating that both DBY and DBX peptides were endogenously processed. After transplant, the patient also developed antibodies that were specific for recombinant DBY protein and did not react with DBX. This antibody response was mapped to two DBY peptides beginning at positions 118 and 536. Corresponding DBX peptides were not recognized. These studies provide the first demonstration of a coordinated B and T cell immune response to an H-Y antigen after allogeneic transplant. The specificity for recipient male cells was mediated by the B cell response and not by donor T cells. This dual DBX/DBY antigen is the first mHA to be identified in the context of chronic GVHD.     

Attachment characteristics and treatment outcome following inpatient psychotherapy: Results of a multisite study

Abstract

Existential suffering may contribute to treatment-resistant depression. The “VITA” treatment model was designed for such patients with long-standing depression accompanied by existential and/or religious concerns. This naturalistic effectiveness study compared the VITA model (n = 50) with a “treatment as usual” comparison group (TAU; n = 50) of patients with treatment-resistant depression and Cluster C comorbidity. The TAU patients were matched on several characteristics with the VITA patients. The VITA model included existential, dynamic, narrative and affect-focused components. The VITA group had significantly greater improvement on symptom distress and relational problems during treatment and from pre-treatment to 1-year follow-up. Patients in the VITA, at follow-up, were more likely to be employed and less likely be using psychotropic medications.     

The role of mast cells in neuroinflammation

Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin and well known for their pathogenetic role in allergic and anaphylactic reactions. In addition, they are also involved in processes of innate and adaptive immunity. MCs can be activated in response to a wide range of stimuli, resulting in the release of not only pro-inflammatory, but also anti-inflammatory mediators. The patterns of secreted mediators depend upon the given stimuli and microenvironmental conditions, accordingly MCs have the ability to promote or attenuate inflammatory processes. Their presence in the central nervous system (CNS) has been recognized for more than a century. Since then a participation of MCs in various pathological processes in the CNS has been well documented. They can aggravate CNS damage in models of brain ischemia and hemorrhage, namely through increased blood–brain barrier damage, brain edema and hemorrhage formation and promotion of inflammatory responses to such events. In contrast, recent evidence suggests that MCs may have a protective role following traumatic brain injury by degrading pro-inflammatory cytokines via specific proteases. In neuroinflammatory diseases such as multiple sclerosis, the role of MCs seems to be ambiguous. MCs have been shown to be damaging, neuroprotective, or even dispensable, depending on the experimental protocols used. The role of MCs in the formation and progression of CNS tumors such as gliomas is complex and both positive and negative relationships between MC activity and tumor progression have been reported. In summary, MCs and their secreted mediators modulate inflammatory processes in multiple CNS pathologies and can thereby either contribute to neurological damage or confer neuroprotection. This review intends to give a concise overview of the regulatory roles of MCs in brain disease.     

Cytoskeletal changes during development and aging in the cortex of neurofilament light protein knockout mice

The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprising the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age compared with age‐matched wild‐type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF‐P, NF‐DP), the medium NF subunit (NFM), and the intermediate filament α‐internexin (INT) at P4. At 5 months, NF‐DP, NFM, and INT remained significantly lower in knockouts. At 12 months, NF‐P was again significantly decreased, and INT significantly increased, in KOs compared with wild type. In addition, protein levels of class III neuron‐specific β‐tubulin and microtubule‐associated protein 2 were significantly increased in NFL KO mice at P4, 5 months, and 12 months, whereas β‐actin levels were significantly decreased at P4. Immunocytochemical studies demonstrated that NF‐DP accumulated abnormally in the perikarya of cortical neurons by 5 months of age in NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin‐immunolabeled nonpyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs. J. Comp. Neurol. 521:1817–1827, 2013. © 2012 Wiley Periodicals, Inc.     

Toll-like receptor 4 contributes to microvascular inflammation and barrier dysfunction in thermal injury

Systemic and microvascular inflammation plays a key role in the development of multiple organ failure after infection, sepsis, and traumatic injury. Toll-like receptors (TLRs) regulate host responses to pathogens and sterile, injury-associated inflammatory responses. We investigated whether TLR-4 contributes to microvascular dysfunction during thermal injury in vivo in anesthetized wild-type or TLR-4 (-/-) mice receiving either a 25% total body surface area full-thickness scald burn or sham treatment on the dorsal skin. Using intravital microscopy, we assessed the hemodynamics and leukocyte dynamics in the mesenteric microvasculature as representative of the splanchnic microcirculation at a site remote from the burn wound. The transvascular flux of fluorescein isothiocyanate-albumin across mesenteric venules was measured as an indicator of microvascular permeability. Furthermore, cultured microvascular endothelial cell models were used to evaluate the endothelial-specific mechanisms involved in TLR-4-mediated barrier dysfunction. The results showed significantly elevated microvascular permeability in wild-type mice after burn, whereas this response was markedly attenuated in TLR-4 (-/-) mice. Burn injury also increased leukocyte adhesion in mesenteric venules of wild-type mice, and a blunted leukocyte response was seen in the TLR-4 mice. Treatment of endothelial cell monolayers with burn plasma induced a rapid reduction in the transendothelial electrical resistance measured by electric cell-substrate impedance sensing, indicative of endothelial cell-cell adhesive barrier dysfunction. Reducing expression of TLR-4 with siRNA treatment attenuated this response. Taken together, these data indicate that TLR-4 plays an important role in microvascular leakage and leukocyte adhesion under the inflammatory condition associated with nonseptic thermal injury.