Immunobiology of spinal cord injuries and potential therapeutic approaches.

The incidence of spinal cord injuries (SCI) is high every year. As the spinal cord is the highway that allows for the brain to control the rest of the body, spinal cord injuries greatly impact the quality of life of the patients. The SCI include the primary response consisting of the initial accident-induced damage and the secondary response that is characterized by damage due to inflammation and biological responses. Astrocytes are the first to act at the site of the injury, forming a glial scar and attracting immune cells. The immune system plays a role in cleaning out the debris caused by the injury, as well as preventing neurons to grow and heal. The secondary injury caused by the inflammatory response is the major target to combat SCI. This article critically reviews the key players in the inflammatory SCI response and potential therapies, specifically targeting astrocytes, neutrophils, and macrophages. These cells are both beneficial and detrimental following SCI, depending on the released molecules and the types of cells infiltrated to the site of injury. Indeed, depending on the subtype of macrophages, M1 or M2, beneficial or detrimental response could be incited. Therapeutic strategies to regulate and manipulate the immune cells via increasing or decreasing their recruitment to the site of injury could be developed together with upregulating and downregulating the release of certain chemicals from the infiltrated cells.

The danger zone: Systematic review of the role of HMGB1 danger signalling in traumatic brain injury.

BACKGROUND: Traumatic brain injuries (TBI) are associated with complex inflammatory pathways that lead to the development of secondary injuries such as cerebral ischaemia, elevated intracranial pressure and cognitive deficits. The association between intracellular danger signalling involving nuclear chromatin-binding factor, high mobility group box-1 (HMGB1) and inflammatory pathways following TBI has not yet been fully understood. PRIMARY OBJECTIVE: To comprehensively review the available literature regarding the potential diagnostic, prognostic and therapeutic use of HMGB1 in TBI. METHODS: A systematic literature review of studies available in PubMed using human and animal subjects was performed. A total of eight studies were included in the results. CONCLUSIONS: A comprehensive review of these reports demonstrated that, following TBI, HMGB1 is released from damaged neurons and is elevated in patient's serum and CSF. Furthermore, these studies showed the potential for HMGB1 to serve as a prognostic biomarker and therapeutic target in patients with TBI. Thus, HMGB1 is a prospective candidate for future studies as it shows promise in treating and/or predicting the sequelae of TBI.

Hippocampal Transections for Epilepsy.

Multiple hippocampal transection (MHT) is a novel surgical procedure that serves to disrupt seizure propagation fibers within the hippocampus without impairing verbal memory or the loss of stem cells. Given the paucity of literature regarding the utility and long-term outcome of MHT, a review is presented of the current literature to support the utility of this procedure in the treatment of intractable temporal lobe epilepsy. Long-term outcome analysis of this technique has been reported by 2 independent groups. Both groups used intraoperative electrocorticography. All patients underwent multiple subpial transection on the neocortex and MHT on the hippocampus.

Intraventricular tissue plasminogen activator for intraventricular hemorrhage caused by an arteriovenous malformation.

The use of thrombolytics delivered through an external ventricular drain has improved outcomes in intraventricular hemorrhage, a disease with a poor prognosis; however, presence of an arteriovenous malformation is generally considered a contraindication to thrombolytic use. Due do the high mortality with the current standard of care, thrombolytics should be considered as an acceptable treatment option despite the presence of an arteriovenous malformation in certain clinical situations. We review the available literature and present an additional patient to make the case for the use of thrombolytics for intraventricular hemorrhage from an arteriovenous malformation.

Long term follow-up after multiple hippocampal transection (MHT).

PURPOSE: Multiple hippocampal transection (MHT) is a new surgical procedure which disrupts seizure propagation within the hippocampus without impairing verbal memory or the loss of stem cells. Since there are very few papers on this procedure, the authors are presenting their long term results to increase the database on this procedure. METHOD: Long term outcome in 15 consecutive patients who had MHT for unlilateral temporal lobe epilepsy, had intra-operative electro-corticography (ECoG) and have a minimum follow-up of at least 2 years is presented. The male/female ratio is 2/1; follow-up is 24-60 months (median of 41 months); and ages between 25 and 60 years. All patients had multiple subpial transection (MST) on the neocortex and MHT on the hippocampus. Amygdalectomy was done if seizure focus was present in the amygdala (10 patients). Temporal tip (1.5-2.5 cm in length) was resected (11 patients) when it was resistant to MST, based on intraoperative EEG recordings. RESULTS: There was no permanent neurological complication. Fourteen patients (94.7%) are seizure free (Engel's Class I) and 1 (5.3%) has rare seizures (Class II). Neuropsychological studies showed that verbal memory was preserved. CONCLUSION: The results show that the seizure outcome with MHT is equal or better than those reported with standard temporal lobectomy. Furthermore verbal memory is preserved. The study also shows that intraoperative ECoG is important in order to conclude adequacy of the procedure. Based on the result of this study the authors feel that this procedure needs to be persued as an alternate to hippocampectomy.

Intraoperative image fusion to ascertain adequate lead placement.

BACKGROUND: In order to view the position of the deep brain stimulator (DBS) lead in relation to the stereotactic target on 3-tesla magnetic resonance (3T-MR) images prior to the conclusion of the procedure, intraoperative postimplantation computed tomography (CT) images were fused with preoperative 3T-MR images. The method to do this is described and discussed in this paper. METHODS: Over the last year, this method was used for 8 procedures: 6 for subthalamic nucleus and 2 for ventral-intermediate nucleus of the thalamus. The procedures were done on the CT table in a stereotactic frame. CT and MR images plus coordinates from the Schaltenbrand atlas were used to plan the target. After the lead had been placed at the target, intraoperative CT images were obtained and fused with preoperative 3T-MR images prior to the conclusion of the procedure. If error was detected in the lead position, it was corrected. RESULTS: Errors in the x-coordinate were detected in 2 patients. These errors were corrected prior to the conclusion of the procedures. CONCLUSION: This is a simple method to intraoperatively visualize DBS lead position on high-quality 3T-MR images. It gives the surgeon the capability to detect errors and correct them prior to the conclusion of the procedure.

A modified stereotactic frame as an instrument holder for frameless stereotaxis: Technical note.

BACKGROUND: In order to improve the targeting capability and trajectory planning and provide a more secure probe-holding system, a simple method to use a stereotactic frame as an instrument holder for the frameless stereotactic system was devised. METHODS: A modified stereotactic frame and BrainLab vector vision neuronavigation sys¬tem were used together. The patient was placed in the stereotactic head-holder to which a reference array of the neuronavigation system was attached. The pointer of the frameless system was placed in the probe-holder of the frame. An offset in distances was kept between the radius of the arch of the frame and the tip of the pointer so that the pointer was always outside the head during navigation. The offset correction was made on the BrainLab monitor so that the center of the arc of the frame was at the tip of the probe line on the monitor. Then, using the frame's coordinate adjuster system, the center of the arc was positioned on the target. This method was used to insert depth electrodes (seven procedures) and gain access to the temporal horn (three procedures). RESULTS: Post-operative scans showed that the accuracy was within 2.5 mm in all three planes for depth electrode placement, and easy access to the temporal horn was obtained in two other patients. CONCLUSION: This is a simple method to use a stereotactic frame to improve coordinate and trajectory adjustments and provides a better method to stabilize the pointer and the probe-holder during frameless stereotactic procedures.

Computed tomography-guided vertebroplasty using a stereotactic guidance system (stereo-guide).

BACKGROUND: In order to make it easy to perform computed tomography (CT)-guided vertebroplasty a stereotactic guidance system called the "stereo-guide" was designed. A method to perform CT-guided vertebroplasty using this system is described. METHODS: The device is a rectangular flat plastic block. One of the flat surfaces of the block has deeply grooved protractor markings at 5-degree intervals; ranging from 0 to 30 degrees. The procedure is performed on the CT table. Based on distances and angle measurements obtained from CT images the device is placed on an appropriate location on the back of the patient and the needle is advanced to the target through the pedicle guided by the grooves on the device. Ten procedures were performed in nine patients with lumbar and thoracic pathology. RESULTS: The system was easy to use and proved to be accurate. No complication resulted from the procedure. CONCLUSION: The stereo-guide proved to be simple and easy to use. Intraoperative scans helped to plan the trajectory and follow the injection of the cement.

Stereotactic approach to the trigeminal ganglion using a stereotactic frame and intraoperative computed tomography scans: technical note.

OBJECTIVE: In this paper, a technique to place a probe at the trigeminal ganglion using a stereotactic frame and intraoperative computed tomography (CT) scans is described. METHOD: The procedure is performed on the CT table using a stereotactic frame. After the coordinates have been obtained and then adjusted, the target is probed using the frame. In this study, intraoperative scans were obtained to confirm the accuracy of probe placement. After successful stimulation studies, radiofrequency lesions were made. Thirty-two procedures were performed on 26 patients. RESULTS: Twenty patients were free of pain at a follow-up which lasted a median of 30 months. There was no permanent complication from the procedure. CONCLUSIONS: The technique is straightforward, accurate and safe. It also enables the surgeon to obtain intraoperative confirmation of accurate probe placement on CT images.

Nonresective hippocampal surgery for epilepsy.

INTRODUCTION: Clinical experience with a new surgical procedure called multiple hippocampal transections is described. In this procedure, seizure circuits within the hippocampus are disrupted by making multiple cuts parallel to the hippocampal digitations; while the vertical functional fibers are preserved. METHODS: Ten patients with temporal lobe epilepsy are described. The male/female ratio is 6:4, the ages of the patients were 20-53 years, and follow-up periods were 10-34 months, with a median of 21 months. Five patients had no hippocampal sclerosis, two had minimal sclerosis, and three had significant sclerosis. Six patients had surgery on the dominant side and five had failed the Wada test. Multiple hippocampal transections were made at 4-mm intervals. The neocortex was then treated with multiple subpial transections. In addition, six patients had resections of the temporal tip. RESULTS: There were no permanent neurologic complications: seven patients are seizure-free, two have rare seizures, and one has 60% decrease in seizure frequency. Eight patients had both pre- and postoperative memory testing. Among these eight patients, five had improved verbal memory, three had improved visual memory, and three had a slight drop in visual memory. CONCLUSION: This is a small series with a short follow-up period. However, the results are encouraging enough to warrant further trials. In addition, this may be an effective alternative procedure for those who fail the Wada test and do not have significant temporal lobe sclerosis or who have seizures originating from the dominant side.

Direct anatomical localization of the subthalamic nucleus on CT with comparison to Schaltenbrand-Wahren atlas.

Stimulation of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms of Parkinson's disease. Generally, localization of the target is based on stereotactic atlas coordinates and magnetic resonance (MR) images. In this paper a method of direct anatomical localization of the STN on computed tomography (CT) images is described and compared with the Schaltenbrand-Wahren atlas. Serial CT scans were obtained at 1.5-mm interval and scan thickness of 3 mm, with the CT gantry and glabella-inion plane of the patient's head vertical. The STN was identified as a dense structure medial to the inner semicircular border of the internal capsule in the subthalamic region. Its visibility was increased by changing the window and level settings on the CT workstation computer. The center of the STN in relationship to the intercommissural line, determined by this technique, was similar to those found on standard atlases.

Improving the lives of patients with medically refractory epilepsy by electrical stimulation of the nervous system.

Vagal nerve stimulation proved effective in animal models of epilepsy, and in open and double-blinded trials, in over 450 patients. Seizure reduction improved for at least 2 years. Almost 50% of treated patients achieve at least a 50% reduction in seizure frequency. Other advantages include termination of a seizure and improved alertness. Benefits were demonstrated in children, partial and generalized epilepsies, and in specific neurologic syndromes.

Is epilepsy surgery on both hemispheres effective?

BACKGROUND: Patients with bilateral independent seizure foci are poor candidates for conventional resective epilepsy surgery. The authors have therefore used minimally invasive procedures to treat such patients. In this paper, the result of a large series of patients treated by this approach is examined to determine the effectiveness of this approach. MATERIALS AND METHODS: The series had 61 patients. The range of follow-up was 15-90 months. The mean follow-up was 41.5 months with a median of 37 months. Patients' ages at the time of surgery ranged from 3 to 54 years, with a mean of 11.3 and median of 6. Male to female ratio was 39/22. Fifty patients had complex partial seizures, 3 had Lennox-Gastaut syndrome, 4 had myotonic seizures, 2 had infantile spasm, and 2 had myoclonic seizures. Preoperative evaluation included: video electroencephalogram (EEG) monitoring using scalp electrodes, neuropsychological evaluation, magnetic resonance scans, positron emission topography and/or single photon emission computed tomography scans, magnetoencephalogram, Wada test and video EEG recording using subdural electrodes. Multiple subpial transection (MST) was the principle procedure. This procedure was supplemented (17 patients) with minimal cortical resection when intraoperative electroencephalogram indicated that an area failed to respond to MST. When an additional epileptogenic focus was present in the amygdala-hippocampus complex (5 patients), it was treated with stereotactic amygdala-hippocampotomy. The eloquent cortex was treated in 51 patients. The number of lobes treated was 2 in 5 patients, 3 in 5 patients, 4 in 10 patients, 5 in 2 patients, 6 in 38 patients and 8 in 1. RESULTS: Seizure outcome based on Engel's modified classification was as follows: 32 patients (52.45%) were class I, 5 (8.2%) were class II, 15 (24.59%) were class III, 3 (4.9%) were class IV and 6 (9.83%) were class V. There was no statistical difference between those who were operated on of the first half of the series and those who were operated on of the second half of the series (p = 0.1636). Similarly, there was no statistical difference between this series and two large series in which MST had been performed on one hemisphere (p values of 0.6863 and 0.7337). There was no statistical difference between those who had MST alone and those who had MST plus minimal cortical resection (p = 0.1698). There was no permanent neurological complication in this series. CONCLUSION: Patients with intractable epilepsy with independent seizure foci in both hemispheres can be safely treated with the approach described in this paper, and seizure control achieved by this approach is fairly satisfactory and similar to that reported in patients with surgery on one hemisphere.

Single-unit artificial intervertebral disc.

OBJECT: The authors describe a new type of artificial disc called a single-unit artificial disc (SUAD). It is a single-unit disc without components, and there is no fixation system with which to maintain it in the disc space. It is theorized that its shape, hardness, and surface consistency, together with the compressive force exerted by the body's axial load, should be adequate to maintain the position of the disc in the disc space. In this paper the authors present their results of the kinematic tests in which the stability and integrity of the SUADs was tested. METHODS: Panorobot was used for kinematic test fixture for fatigue testing for different types of SUAD. The test was performed after placing the disc between the C-5 and C-6 vertebral bodies (VBs) obtained from a cadaver. Eight pounds of weight was placed on the top of the container housing the C-5 VB to account for the weight of the head. The robot performed the following movements: 1) flexion-extension, 4.7 degrees each; 2) lateral left-right bending, +/- 2.1 degrees; and 3) coupled rotation, +/- 3.8 degrees. Two flat discs (FDs) of 85 durometer (D), four 30D FD, two recess-edged discs (REDs) of 85D, and four custom-designed discs (CDDs) (custom molded to the disc space) of 30D were tested. None of the discs showed cracks or breakage at the end of the study. After 1 million cycles of excursions all 85D and 30D FD, and both 85D REDs showed weight loss. The 30D CDDs showed minimal weight gain at 1 million cycles. One of the CDDs, tested up to 5 million cycles, did lose weight at 5 million cycles. One 85D FD was extruded after 0.2 million cycles and one 85D RED rotated within the disc space. All other discs maintained their position in the disc space. Dimensional changes were minimal. Scanning electron microscopy of particles collected from one 30D CDD sample after 1 million cycles showed rough irregular granular particles 1 to 600 microm in diameter. CONCLUSIONS: These findings show that a 30D SUAD can maintain its position in the disc space without any anchoring device. Furthermore, at 1 million cycles of testing of 30 D SUAD, FDs did as well as the CDDs. This may be because softer discs mold to changes in dimension of the disc space. In addition the softer discs tend to wear less than the harder ones. Further fatigue study of 10 million cycles is needed to determine long-term efficacy, and the effects of wear on particles surrounding the joints need to be studied.