Defining the Interval between the Development of New Lesion on Follow Up Study and 1st Gamma Knife Radiosurgery without Whole-Brain Radiation Therapy in the Management of Brain Metastases

The aim of this retrospective study is to define the interval between the development of new lesion on follow up study and 1st gamma knife radiosurgery (GKS) without whole brain radiation therapy (WBRT) in the management of brain metastases. Between May 1992 and January 2006, 378 patients (207 males and 174 females) with brain metastases were treated with radiosurgery at the Yonsei University Medical Center. Reviewing the follow up study was available in 357 (81.7%) cases, and new lesions were found in 83 (23.2%) cases. We classified the development of new lesions after 1st GKS as missed, invisible, true new and undetermined lesions；missed lesions are those which were visible on MRI at the time of 1st GKS retrospectively, but omitted；invisible lesions, too small to be visualized on MRI at the time of 1st GKS, may be less than 1mm in size at that time and will be new lesions, visible on MRI within 4months after 1st GKS；true new lesions, newly metastasized to brain after GKS, developed 8 months after 1st GKS； undetermined lesions, new lesions developed 5 to 7 months after 1st GKS. There were 12 patients (18.18%) of missed lesions, and the number of those lesions was 17；10 patients (15.15%) of invisible, and the number, 51；25 patients (37.88%) of undetermined, and the number, 166；19 patients (28.79%) of true new lesions, and the number, 100. The incidence of new lesion development was high between 5th and 7th months after GKS, and after that, it decreased suddenly. And that low incidence was even after 7th months. GKS without adjuvant WBRT showed good effect, however, strict MRI follow up at 4 and 7months after GKS is necessary to detect and treat the invisible and missed lesions.ope

Analysis of the Non-diagnostic Results after Stereotactic Biopsy

Objective: Although stereotactic brain biopsy has played an important role in the diagnosis and management of brain lesions, there is a significant number of patients in whom a histologic diagnosis is not achieved. The non-diagnostic result of stereotactic biopsy poses a management dilemma. The goal of this study was to analyze the non-diagnostic results after stereotactic biopsy, subsequent management, progress and final diagnosis. Methods: The authors reviewed the clinical and radiological records of 158 patients who underwent stereotactic brain biopsies using Leksell stereotactic frame. We included 138 patients who were followed more than 6 months in this study. Results: The results were diagnostic in 118 cases and the overall diagnostic yield of the procedure was 85.6%. A definite histological diagnosis was not made in 20 patients: gliosis in 10, normal white matter in 5, necrosis in 2, infiltration of inflammatory cell in 2, and insufficient material in 1. The subsequent managements, progress and their final diagnoses were described. Conclusion: Stereotactic biopsy has evolved as a powerful and safe tool to provide tissue diagnoses with minimal disruption of normal functioning brain. Multiple serial biopsy, intraoperative histological diagnosis, and updated imaging-guided biopsy should be tried to minimize the sampling error. Clinical and radiological follow-up are essential for further diagnosis and management in non-diagnostic cases.ope

Surgical Management of Central Neuropathic Pain Using the Neuroablative Procedures of Brain

Central pain is defined as pain initiated or caused by a primary lesion or dysfunction within the central nervous system and has proved the most difficult pain to control. Many intracranial ablative procedures have been tried, including stereotactic cingulotomy, thalamotomy, and mesencephalotomy, which have been described to be effective in about 50% to 60% although the relief of pain is faded out with time. Anterior cingulotomy is effective for the relief of cancer pain and noncancer chronic pain. Although few side effects are potential benefits of cingulotomy, the effectiveness for central pain is not yet established. Mesencephalotomy is particular value in central denervation pain, cancer pain involving the head, neck but its use is limited due to significant morbidity. The value of thalamotomy for treatment of central pain is not documented. Trigeminal tractotomy and nucleotomy are beneficial for vagoglossopharyngeal neuralgia, geniculate neuralgia, and the caudalis DREZ is beneficial for atypical facial pain, postherpetic neuralgia. Recently neurostimulation is recommended for the treatment of central pain or neuropahic pain rather than neuroablation. The use of destructive central procedures for central pain and noncancer chronic pain has not yet been well defined. With the potential benefit being less certain, priority might be given to a procedure with less risk.ope

Treatment Strategy of Multiple Hemangioblastomas

Objective：Hemangioblastomas are highly vascular and benign neoplasm of the central nervous system(CNS). They can often be found as multiple lesions, as is commonly observed in von Hippel-Lindau(VHL) disease. The aim of this study is to determine the proper management for multiple hemangioblastomas. Methods：Since 1990, 78cases of hemangioblastoma have been encountered. Among these, 9cases were multiple hemangioblastomas that were treated with surgical resection with or without radiosurgery. The medical, radiological, surgical and histological records were reviewed retrospectively and analyzed statistically. Results：Nine patients presented with multiple hemangioblastomas and were diagnosed as VHL disease. The mean follow-up duration was 75.7months (6.6~159.2months) after the first surgical treatment. Three patients were treated with surgical resection alone and six patients were treated by both surgical resection and radiosurgery. Twenty-one surgical procedures (13 surgical resections and 8 radiosurgery) were performed. One patient required ventriculoperitoneal shunt and a posterior fossa decompressive craniectomy because of post-radiation brain swelling. Another patient refused additional treatment for the newly developed lesions after the successful treatment of initial lesions. The other patient who presented with numerous lesions in the whole brain and spine underwent cranio-spinal irradiation. Remaining patients showed good results. Conclusion：The surgical outcomes for the patients with a single lesion of the CNS hemangioblastoma are favorable. However, the treatment of multiple hemangioblastoma is more difficult, and should be treated by surgical resection and radiosurgery with careful consideration.ope

Characteristics of Trigeminal Evoked Potential and It’s Pathway in the Rat

Objective：There are some advantages of trigeminal evoked potential(TEP) recording compared to other somatosensory evoked potential(SSEP) recordings. The trigeminal sensory pathway has a pure sensory nerve branch, a broader receptive field in cerebral cortex, and a shorter pathway. Despite these advantages, there is little agreement as to what constitutes a normal response and what wave forms truly characterize the intraoperative TEP. This study presents the normative data of TEP recorded on the epidural surface of the rat with a platinum ball electrode. Materials & Methods：Under general anesthesia with urethane, the adult Sprague-Dawley male rats(300-350g) were given electrical stimulation with two stainless steel electrodes which were inserted into the subcutaneous layer of the area around whiskers. A reference electrode was positioned in the temporalis muscle ipsilateral to the recording site. Results：TEPs were recorded in the Par I area of somatosensory cortex and recorded most apparently on the pointof 2mm posterior from the bregma and 6mm lateral from the midline. The typical wave form consisted of 5 peaks(N1-P1-N2-P2-N3 according to emerging order, upward negativity). Each latency to corresponding peaks was not influenced by the different intensities of stimulation, especially from 1 to 5mA. Average latencies of 5 peaks were in the following order；7.7, 11.1, 15, 22.3, 29.4ms. There was also no significant difference between latencies before and after administration of muscle relaxant(pancuronium). For the electrophysiological localization of recorded waves, the action potential of a single unit was recorded with glass microelectrode(filled with 2M NaCl, 3- 5MΩ) in the thalamus of rat. A sharp wave was recorded in the VPM nucleus, in which the latency was shorter than that of N1. This suggests that all 5 peaks were generated by neural activities in the suprathalamic pathway. Conclusion：In terms of recording near-field potentials, our data also suggests that TEP in the rat may be superior to other SSEPs. In overall, these results may afford normative data for the studies of supratentorial lesions such as hydrocephalus or cerebral ischemia which can have an influence on near-field potentials.ope

Long-Term Follow-Up Results of Gamma Knife Radiosurgery for Hypothalamic Hamartoma : How can we Improve the Results?

Objective: Hypothalamic hamartomas (HH) constitute rare developmental lesions associated with gelastic seizure, precocious puberty, and abnormal behavior. Treatment for this lesion is very complicated due to its location. Gamma Knife radiosurgery (GKS) may be an efficient and safe treatment option, which produces little morbidity. The authors evaluated the long-term results of GKS for the HH. Methods: Eights patients with HH-related intractable gelastic seizure and/or precocious puberty underwent GKS between 1992 and 1996, with a mean age of 8.3 years at the time of GKS (range, 3.5-17.7 years). Three patients were presented with intractable gelastic seizure, and 4 patients with precocious puberty. One patient had both intractable seizure and precocious puberty. The mean follow-up duration was 76.6 (28.9-141) months. Results: The mean marginal dose for the large sessile type HH with intractable gelastic seizure was 11.5Gy (range, 9-13Gy) and that for the small pedunculated type with precocious puberty was 27Gy (range, 20-34Gy). There was no lesion volume change on follow-up MRI. Intractable seizure disappeared in only 1 patient and was not improved in the other 3 patients. Precocious puberty was not resolved by GKS in all cases. Conclusion: The long-term results of GKS for HH were not satisfactory. As for the control of epilepsy, the radiation dose in our cases was not enough to suppress and block the epileptogenic focus of HH and its propagation to surrounding tissue. Precocious puberty caused by HH is not indicated for GKS. If we could get better treatment outcome with higher radiation dose and/ or new dose planning technique, GKS might be primary treatment option for HH.ope

The Results of Gamma Knife Radiosurgery for Brain Metastases from Renal Cell Carcinoma

Objective: Renal cell carcinoma (RCC) is a rare tumor which tends to metastasize to the brain in about 4-11% of patients. Metastases from RCC raise specific therapeutic problems because they are relatively unresponsive to whole brain radiation therapy and tend to bleed. The aim of this study was to analyze the therapeutic effects after Gamma Knife radiosurgery (GKS) as a primary treatment for patients harboring brain metastases of RCC. Methods: Between May 1992 and September 2005, 26 patients with 102 brain metastases from RCC underwent 31 GKS procedures. Overall median survival, main cause of death, local control rate, and morbidity related to GKS were evaluated. Age, sex, performance status, number of metastases, volume of metastases, presenting symptom, prior history of craniotomy, prior history of fractionated radiation therapy, prior history of chemotherapy or immunotherapy, maximal dose, tumor marginal dose, number of treatment isocenters, recursive partitioning analysis (RPA) class, and latency period from diagnosis of RCC to that of brain metastases were statistically analyzed to identify significant factors related to prolonged survival. Results: The mean tumor volume was 3.3 (0.02-35.1)cc. Mean maximal and tumor margin dose were 28.0 (15-43)Gy and 17.7 (9-26.6)Gy, respectively. The period of median survival was 10.5 months after GKS and RPA class was only significant factor related to survival. Local tumor control rate was 92.0% and tumor volume was related to local control. Radiation-related edema occurred in 8.9% of cases. Additional whole brain radiation therapy could not affect survival time, local tumor control, but could increase the risk of radiation-related complication. Local and distant tumor recurrences were treated by additional GKS. There was no permanent morbidity after GKS. Conclusion: Despite of the radioresistant nature of RCC, GKS alone could effectively control brain metastases from RCC not only as a primary treatment, but also as a secondary salvage for recurrence. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including repeated radiosurgery without a combination of whole brain radiation therapy can offer patients an extended survival.ope

Optical Imaging of the Motor Cortex Following Antidromic Activation of the Corticospinal Tract after Spinal Cord Injury

Spinal cord injury (SCI) disrupts neuronal networks of ascending and descending tracts at the site of injury, leading to a loss of motor function. Restoration and new circuit formation are important components of the recovery process, which involves collateral sprouting of injured and uninjured fibers. The present study was conducted to determine cortical responses to antidromic stimulation of the corticospinal tracts, to compare changes in the reorganization of neural pathways within normal and spinal cord-injured rats, and to elucidate differences in spatiotemporal activity patterns of the natural progression and reorganization of neural pathways in normal and SCI animals using optical imaging. Optical signals were recorded from the motor cortex in response to electrical stimulation of the ventral horn of the L1 spinal cord. Motor evoked potentials (MEPs) were evaluated to demonstrate endogenous recovery of physiological functions after SCI. A significantly shorter N1 peak latency and broader activation in the MEP optical recordings were observed at 4 weeks after SCI, compared to 1 week after SCI. Spatiotemporal patterns in the cerebral cortex differed depending on functional recovery. In the present study, optical imaging was found to be useful in revealing functional changes and may reflect conditions of reorganization and/or changes in surviving neurons after SCI.ope

Characteristics and Pathways of the Somatosensory Evoked Field Potentials in the Rat

Objective：Somatosensory evoked potentials(SSEPs) have been used widely both experimentally and clinically to monitor the function of central nervous system and peripheral nervous system. Studies of SSEPs have reported the various recording techniques and patterns of SSEP. The previous SSEP studies used scalp recording electrodes, showed mean vector potentials which included relatively constant brainstem potentials(far-field potentials) and unstable thalamocortical pathway potentials(near-field potentials). Even in invasive SSEP recording methods, thalamocortical potentials were variable according to the kinds, depths, and distance of two electrodes. So they were regarded improper method for monitoring of upper level of brainstem. The present study was conducted to investigate the characteristics of somatosensory evoked field potentials(SSEFPs) of the cerebral cortex that evoked by hindlimb stimulation using ball electrode and the pathways of SSEFP by recording the potentials simultaneously in the cortex, VPL nucleus of thalamus, and nucleus gracilis. Methods：In the first experiment, a specially designed recording electrode was inserted into the cerebral cortex perpendicular to the cortical surface in order to recording the constant cortical field potentials and SSEFPs mapped from different areas of somatosensory cortex were analyzed. In the second experiment, SSEPs were recorded in the ipsilateral nucleus gracilis, the contralateral ventroposterolateral thalamic nucleus(VPL), and the cerebral cortex along the conduction pathway of somatosensory information. Results：In the first experiment, we could constantly obtain the SSEFPs in cerebral cortex following the transcutaneous electrical stimulation of the hind limb, and it revealed that the first large positive and following negative waves were largest at the 2mm posterior and 2mm lateral to the bregma in the contralateral somatosensory cortex. The second experiment showed that the SSEPs were conducted by way of posterior column somatosensory pathway and thalamocortical pathway and that specific patterns of the SSEPs were recorded from the nucleus gracilis, VPL, and cerebral cortex. Conclusion：The specially designed recording electrode was found to be very useful in recording the localized SSEFPs and the transcutaneous electrical stimulation using ball electrode was effective in evoking SSEPs. The characteristic shapes, latencies, and conduction velocities of each potentials are expected to be used the fundamental data for the future study of brain functions, including the hydrocephalus model, middle cerebral artery ischemia model, and so forth.ope

The Role of Gamma Knife Radiosurgery for Diffuse Astrocytomas

Objective：The management of diffuse astrocytomas is one of the most controversial areas in clinical neurooncology. There are numerous reviews and editorials outlining the difficulties in the management of these lesions. In this study, we assess the role of Gamma Knife radiosurgery(GKS) for diffuse astrocytomas. Methods : Twenty-three patients with a diffuse astrocytoma were treated with GKS as a primary or adjuvant method from February 1995 to October 2003. The mean marginal dose was 13.6 (8.5~17.5)Gy and the mean maximal dose was 27.3 (17.0~ 35.0)Gy. Local control and the pattern of radiologic response were evaluated. The probable factors affecting local control, such as tumor volume, margin dose, previous history of craniotomy or stereotactic biopsy, and the presence or absence of previous radiotherapy were statistically analyzed. The average duration of follow-up was 39.7 (11.3~101.5) months after GKS. Results : Of the 23 lesions treated, 16 lesions (69.6%) were controlled during the follow-up period. The mean progression-free interval was 57.4 months and the 5-year progression-free rate was 68%. Only tumor volume was found to be a statistically significant factor for local control. Smaller tumors were better controlled by GKS; it was significantly effective in tumors with less than a 10cm3 volume. Conclusion : GKS could be a valuable therapeutic modality both as a primary treatment and as a postoperative adjuvant therapy in some selected cases.ope