Ran Harel

Spine metastases: current treatments and future directions.

Spinal metastases are the most frequently encountered spinal tumour and can affect up to 50% of cancer patients. Both the incidence and prevalence of metastases are thought to be rising due to better detection and treatment options of the systemic malignancy resulting in increased patient survival. Further, the development and access to newer imaging modalities have resulted in easier screening and diagnosis of spine metastases. Current evidence suggests that pain, neurological symptoms and quality of life are all improved if patients with spine metastases are treated early and aggressively. However, selection of the appropriate therapy depends on several factors including primary histology, extent of the systemic disease, existing co-morbidities, prior treatment modalities, patient age and performance status, predicted life expectancy and available resources. This article reviews the currently available therapeutic options for spinal metastases including conventional external beam radiation therapy, open surgical decompression and stabilisation, vertebral augmentation and other minimally invasive surgery (MIS) options, stereotactic spine radiosurgery, bisphosphonates, systemic radioisotopes and chemotherapy. An algorithm for the management of spine metastases is also proposed. It outlines a multidisciplinary and integrated approach to these patients and it is hoped that this along with future advances and research will result in improved patient care and outcomes.

Invasive group A streptococcal infections in a large tertiary center: epidemiology, characteristics and outcome.

AbstractBackground: Invasive group A streptococcal (GAS) infections are increasing alarmingly worldwide. Patients and Methods: To determine the clinical and epidemiologic characteristics of invasive GAS in a large tertiary medical center, we retrospectively surveyed microbiology and medical records of patients with invasive GAS infections (isolation of Group A Streptococcus from a normally sterile site) treated in our hospital from January 1995 to December 1997. Results: 70 patients with a median age of 48 years (range 2 months–88 years) were identified. Of the 70 identified, 53 (76%) were adults (age ≥ 19 years). The most common co-morbid diseases for invasive GAS in adults were diabetes mellitus, congestive heart failure (CHF), malignancy and immunosuppression. A probable port of entry was identified in 31 (44%) of the cases. In children, varicella lesions were the major port of entry. Overall mortality rate was 17%: The difference in mortality between pediatric and adult cases was significant (0/17 vs 12/53, respectively; p = 0.03). Toxic shock syndrome (TSS) and necrotizing fasciitis were identified in 8.6% and 5.7% of the cases, respectively, with mortalities of 83.3% and 25%. Hyponatremia and hypocalcemia were more frequently observed among the severely ill. Conclusion: Invasive GAS infections tend to have an unexpected course and a broad clinical spectrum, ranging from local skin or pharyngeal involvement to deeply invasive fasciitis with TSS and high mortality. The elderly and those with underlying medical conditions are at utmost risk for invasive GAS. Clear-cut guidelines for early therapeutic strategy, i. e. antibiotic administration and preemptive hospital admission are needed for community-based physicians.

Coordinate Transformation is First Completed Downstream of Primary Motor Cortex

It was suggested previously that the transformation of action to muscle-based coding is completed in the primary motor cortex (M1). This is consistent with a predominant direct pathway leading from M1 to motoneurons. Accordingly, spinal segmental interneurons that are located downstream to M1 are expected to show muscle-like coding properties. We addressed this hypothesis using simultaneous recording of cortical and spinal activity in primates performing an isometric wrist task with multiple targets and two hand postures. Here we show that while the motor cortex follows an intermediate coordinate frame, spinal interneurons already follow a muscle-like coordinate frame. We thus suggest that the final steps in coordinate transformation of motor commands take place downstream of M1 via corticospinal interactions.

Connected Corticospinal Sites Show Enhanced Tuning Similarity at the Onset of Voluntary Action

Corticospinal (CS) pathways provide the structural foundation for executing voluntary movements. Although the anatomy of these pathways is well explored, little is known about spinal decoding of parametric information transmitted via this route during voluntary movements. We addressed this question by simultaneously recording cortical and spinal activity in primates performing an isometric wrist task with multiple targets while measuring CS interactions. Single-pulse cortical stimulation effectively produced a short-latency (presumably monosynaptic) spinal response and thus revealed functionally connected CS sites. Spinal and cortical neurons recorded from connected CS sites showed alignment of directional-torque tuning that peaked at torque onset, consistent with the enhanced cortical drive active during this period. This increased tuning similarity was accompanied by an increased trial-to-trial covariability of firing. Whereas functional CS interactions were dynamic, the efficacy of cortical stimulation was unaffected by the motor state. These results suggest that around the onset of motor action there is a period of facilitated information transfer during which cortical command has greater efficacy in recruiting spinal neurons with matching tuning properties. Dynamic alignment of response properties may form the basis for a spinal readout mechanism of descending motor commands in which directional-torque is a parameter that is preserved across interacting CS sites.

Spine instrumentation failure after spine tumor resection and radiation: Comparing conventional radiotherapy with stereotactic radiosurgery outcomes

OBJECTIVE To evaluate whether stereotactic spine radiosurgery (SRS) results in lower rates of instrumentation failure or higher rates of fusion compared with surgical decompression and stabilization combined with conventional fractionated radiation (XRT) in patients with spine tumors. METHODS The Cleveland Clinic Spine Tumor board database was retrospectively reviewed. Only patients who underwent spine surgery with instrumentation followed by either SRS or XRT and who had at least 6 months of clinical and imaging follow-up were included. RESULTS The primary inclusion criteria were met by 15 instrumented and irradiated patients (8 SRS and 7 XRT). In the XRT group, 43% had instrumentation failure versus 0% instrumentation failure in the SRS group (P = 0.08). Excluding patients with no bone graft, fusion rates were 50% in the SRS group versus 17% in the XRT group (not significant). CONCLUSIONS SRS precisely delivers ionizing radiation to tumors, while sparing the surrounding organs or vital structures. This study poses the question of whether a fusion site should also be considered a structure or organ at risk and whether SRS rather than XRT is more ideal in the postoperative setting. This relatively small series shows a trend toward higher fusion rates and a lower incidence of instrumentation failure with SRS and suggests that larger prospective studies are warranted.

Interleukin-8 secretion following cardiopulmonary bypass in children as a marker of early postoperative morbidity.

Background: Interleukin (IL)‐8, an 8 kDa peptide, is the first chemoattractant identified as being specific for neutrophils. Its possible association with early postoperative morbidity following cardiopulmonary bypass (CPB) in infants and children is unknown. This prospective cohort study sought possible roles of IL‐8 in the inflammatory response to CPB and investigated if changes in IL‐8 levels and clinical course and outcome were related.

Functional Organization of Information Flow in the Corticospinal Pathway

Transmission of information in the corticospinal (CS) route constitutes the fundamental infrastructure for voluntary actions. The anatomy of this pathway has been studied extensively, but there is little direct evidence regarding its functional organization. Here we explored the areal specificity of CS connections by studying two related questions: the functional significance of the parallel, motor, and premotor CS pathways; and the way in which finger-related motor commands are handled by this pathway. We addressed these questions by recording from primary motor (M1) and premotor cortical sites in primates (Maccaca fascicularis) performing a motor task, while measuring the evoked intraspinal unit response to single pulse cortical stimulation. Stimulation in M1 evoked spinal neuronal responses more frequently than stimulation in premotor cortex. The number of muscles excited by M1 stimulation was higher than the number excited by premotor stimulation. Within subregions of M1 finger-related sites were sparsely connected with intermediate zone interneurons and tended to affect the ventrally located motoneurons directly. These results suggest that, despite the parallel anatomical organization, the flow of motor commands is predominantly relayed via M1 to downstream elements. The functional impact of premotor cortex is weak, possibly due to inhibitory systems that can shape the flow of information in the CS pathway. Finally, the difference in spinal processing of finger versus wrist-related motor commands points to a different motor control strategy of finger versus wrist movements.

Metabolic and clinical markers of prognosis in the era of CT imaging in children with acute epidural hematomas

Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children <16 years old with head trauma and isolated AEH. Treatment followed a standard advanced trauma life support protocol. A medical history was obtained, and all patients underwent neurosurgical and physical evaluations. CT scans were performed, as were laboratory tests which included arterial blood gases, glucose, electrolytes (K+, Na+), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.

Spine radiosurgery for spinal metastases: indications, technique and outcome

Abstract Early diagnosis, better imaging, and advanced treatment of cancer patients extend survival and increase the incidence of symptomatic spine metastases. The treatment algorithm for spine metastases has shifted to a more aggressive approach in recent years. Spine stereotactic radiosurgery (SRS) is a relatively new tool utilizing advanced imaging systems, planning software, image-guided localization, and intensity-modulated dose delivery. Radiosurgery of spine metastases yields high rates of pain- and tumor control, and offers both the patients and the treating physicians an effective noninvasive alternative. This review presents the indications and outcomes for SRS and describes current techniques.

Computation in spinal circuitry: lessons from behaving primates.

Performing voluntary motor actions requires the translation of motor commands into a specific set of muscle activation. While it is assumed that this process is carried out via cooperative interactions between supraspinal and spinal neurons, the unique contribution of each of these areas to the process is still unknown. Many studies have focused on the neuronal representation of the motor command, mostly in the motor cortex. Nonetheless, to execute these commands there must be a mechanism that can translate this representation into a sustained drive to the spinal motoneurons (MNs). Here we review different candidate mechanisms for activating MNs and their possible role in voluntary movements. We discuss recent studies which directly estimate the contribution of segmental INs to the transmission of cortical command to MNs, both in terms of functional connectivity and as a computational link. Finally, we suggest a conceptual framework in which the cortical motor command is processed simultaneously via MNs and INs. In this model, the motor cortex provides a transient signal which is important for initiating new patterns of recruited muscles, whereas the INs translate this command into a sustained, amplified and muscle-based signal which is necessary to maintain ongoing muscle activity.