Posterior fossa pilocytic astrocytoma presenting with opisthotonus in an infant - A case report.

Opisthotonus as a presenting feature in neurosurgical patients is rare, with few reports describing such presentations. Only four reports of opisthotonos secondary to posterior fossa mass were identified. An unclear pathophysiology, and broad aetiology contribute to clinical misdirection. While posterior fossa lesions commonly present with signs of raised intracranial pressure, or cerebellar dysfunction, this case describes the presentation of an infant with opisthotonic posturing, ataxia and autonomic dysfunction secondary to a large pilocytic astrocytoma. Despite initial treatment of hydrocephalus, opisthotonus only resolved with complete surgical resection of the posterior fossa mass. At follow-up, the child remains well and without signs of hypertonicity or other signs or symptoms. Presentations involving opisthotonus are rare, and active exclusion of posterior fossa pathology is necessary. In this case, urgent surgical resection allowed for a positive patient outcome. Description of such a case may contribute to understanding of similar presentations in the neurosurgical context.

Diagnosis in subdural myeloid sarcoma.

Introduction A 74-year-old man presented to hospital with a headache, thrombocytopaenia and an acute deterioration in cognition on a background of acute monocytic leukaemia in remission. Method This is a case report with computed tomography (CT), magnetic resonance (MR) and histopathology imaging. Results Preoperative CT and limited MR demonstrated a subdural lesion with marked midline shift. Craniotomy performed for evacuation of the presumed subdural haematoma revealed a solid tumour-like lesion. Histopathology identified the presence of a myeloid sarcoma (chloroma). Postoperative MRI with contrast revealed the solid nature of the mass. Conclusion The use of contrast is critical in the assessment of intracranial lesions to distinguish myeloid sarcoma from subdural haematoma in the context of leukaemia and a neurologically deteriorating patient.

Anterior lumbar interbody fusion (ALIF) as an option for recurrent disc herniations: a systematic review and meta-analysis.

BACKGROUND: Recurrent intervertebral disc herniation is a relatively common occurrence after primary discectomy for lumbar intervertebral disc herniation. For recurrent herniations after repeat discectomies, a growing body of evidence suggests that fusion is effective in appropriately selected cases. Theoretically, anterior lumbar interbody fusion (ALIF) allows for comprehensive discectomy, less trauma to spinal nerves and paraspinal muscles and avoidance of the disadvantages of repeat posterior approaches. However, ALIF has also been associated with risk of vascular injury and retrograde ejaculation. This current systematic review and meta-analysis aims to assess the viability of ALIF as a surgical treatment for recurrent disc herniations. METHODS: Seven studies were identified from six electronic databases and secondary reference lists. Pre-defined endpoints were extracted from the included studies and meta-analyzed. RESULTS: For the 181 patients from included studies, ALIF resulted in significant average improvements in Oswestry Disability Index (ODI) scores (50.49%, P<0.001), Visual Analogue Scale (VAS) back pain scores (47.85%, P<0.001) and VAS leg pain scores (37.00%, P<0.001). Average blood loss was acceptable at 122 mL (P<0.001) and average operation duration was 89 minutes (P<0.001). Average hospital stay was 5.28 days (P<0.001). Only 22 perioperative complications were reported, with subsidence the most commonly reported complication. CONCLUSIONS: Pooled evidence suggests that ALIF is a feasible approach for the treatment of recurrent disc herniations, demonstrating significant improvements in back and leg pain and minimal complications. These findings warrant further investigation in large prospective registries and multi-center studies.

Systematic review of cortical bone trajectory versus pedicle screw techniques for lumbosacral spine fusion.

Fusion of the lumbosacral spine is a common surgical procedure to address a range of spinal pathologies. Fixation in lumbar fusion has traditionally been performed using pedicle screw (PS) augmentation. However, an alternative method of screw insertion via cortical bone trajectory (CBT) has been advocated as a less invasive approach which improves initial fixation and reduces neurovascular injury. There is a paucity of robust clinical evidence to support these claims, particularly in comparison to traditional pedicle screws. This study aims to review the available evidence to assess the merits of the CBT approach. Six electronic databases were searched for original published studies which compared CBT with traditional PS and their findings reviewed. Nine comparative studies were identified through a comprehensive literature search. Studies were classified as retrospective cohort, prospective cohort or case control studies with medium quality as assessed by the GRADE criteria. The available literature is not cohesive regarding outcomes and complications of CBT versus PT procedures. Most studies found no difference in operative time, but reported less blood loss during CBT. Radiological outcomes show no difference in slippage at one year although CBT is associated with greater bone-density compared to PT. Results for post-operative pain are inconclusive.

A systematic review and meta-analysis of outcomes in hybrid constructs for multi-level lumbar degenerative disc disease.

A systematic review and meta-analysis was performed to assess the effect of hybrid constructs which involve a total disc arthroplasty (TDA) with stand-alone anterior lumbar interbody fusion (ALIF) versus non-hybrid constructs including multi-level TDA, multi-level transforaminal lumbar interbody fusion (TLIF) with posterior transpedicular fixation or multi-level stand-alone ALIF as a surgical intervention for degenerative disc disease (DDD) in the lumbar spine. Primary outcomes analysed included the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for back pain. A systematic search of Medline, Embase, Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Google Scholar was undertaken by two separate reviewers and a meta-analysis of the outcomes was performed. Three studies met our search criteria. When comparing hybrid constructs to multi-level TDA or lumbar fusion (LF) improvements in back pain were found with a VAS back pain score reduction of 1.38 (P<0.00001) postoperatively and a VAS back pain score reduction of 0.99 points (P=0.0006) at 2-years follow-up. Results so far slightly favour clinically significant improved VAS back pain score outcomes postoperatively and at 2-years follow-up for hybrid constructs in multi-level lumbar DDD of the spine when compared with non-hybrid multi-level LF or TDA. It cannot however be concluded that a hybrid construct is superior to multi-level LF or TDA based on this meta-analysis. The results highlight the need for further prospective studies to delineate best practice in the management of degenerative disc disease of the lumbar spine.

Recommendations for the development and validation of flow cytometry-based receptor occupancy assays.

Receptor occupancy measurements demonstrate the binding of a biotherapeutic agent to its extra-cellular target and represent an integral component of the pharmacodynamic (PD) portfolio utilized to advance the development and commercialization of a therapeutic agent. Coupled with traditional pharmacokinetic (PK) assessments derived from serum drug concentration, receptor occupancy data can be used to model PK/PD relationships and validate dose selection decisions throughout the drug development lifecycle. Receptor occupancy assays can be even more challenging to develop than other flow cytometric methods (e.g. surface immunophenotyping). In addition to typical considerations regarding stability of the cell type of interest, stability of the target-bound therapeutic agent and stability of the target receptor must be taken into account. Reagent selection is also challenging as reagents need to be evaluated for the potential to compete with the therapeutic agent and bind with comparable affinity. This article provides technical guidance for the development and validation of cytometry-based receptor occupancy assays.

Role of receptor occupancy assays by flow cytometry in drug development.

The measurement of the binding of a biotherapeutic to its cellular target, receptor occupancy (RO), is increasingly important in development of biologically-based therapeutic agents. Receptor occupancy (RO) assays by flow cytometry describe the qualitative and/or quantitative assessment of the binding of a therapeutic agent to its cell surface target. Such RO assays can be as simple as measuring the number of cell surface receptors bound by an antireceptor therapeutic agent or can be designed to address more complicated scenarios such as internalization or shedding events once a receptor engages the administered therapeutic agent. Data generated from RO assays can also be used to model whether given doses of an experimental therapeutic agent and their administration schedules lead to predicted levels of receptor occupancy and whether the receptor is modulated (up or down) on cells engaged by the therapeutic agent. There are a variety of approaches that can be used when undertaking RO assays and with the ability to measure distinct subsets in heterogeneous populations, flow cytometry is ideally suited to RO measurements. This article highlights the importance of RO assays on the flow cytometric platform in the development of biotherapeutic agents.

Validation of a flow cytometry based chemokine internalization assay for use in evaluating the pharmacodynamic response to a receptor antagonist.

Pharmacodynamic assays are important in clinical trial design to investigate the relationship between drug concentration (pharmacokinetics) and drug "effect' or biological activity. Increasingly flow cytometry is being used to examine the pharmacodynamic effect of new drug entities. However, to date, the analytical validation of cytometry based assays is limited and there is no suitable guidance for method validation of flow cytometry-based pharmacodynamic assays. Here we report the validation of a flow cytometry-based chemokine internalization assay for use in evaluating the effect of a receptor antagonist in clinical trials. The assay method was validated by examining the stability of the reagent, assay robustness, sensitivity, repeatability and reproducibility precision. Experimental results show the assay reagent was stable over 26 weeks. The assay demonstrated a sensitivity to distinguish 0.005 microg/ml of a CCR2 antagonist with a %CV of 13.3%. The intra-assay repeatability was less than 15% with an inter-assay repeatability of less than 20%. In vivo study results demonstrated that the assay was consistent and a reliable measure of antagonist activity.