Post-operative dexmedetomidine-based sedation after uneventful intracranial surgery for unruptured cerebral aneurysm: comparison with propofol-based sedation.

BACKGROUND: Clinical applications of dexmedetomidine (DEX) for neurosurgical procedures have not been adequately investigated. This study aimed to test the use of DEX infusion, alone or as an adjunct to propofol infusion, as compared to propofol infusion in patients with an unruptured cerebral aneurysm after uneventful intracranial procedures. METHODS: In this retrospective observational study from a single institute, of 184 patients who underwent uneventful intracranial procedures for an unruptured cerebral aneurysm between January 2003 and March 2007, we reviewed 50 managed with DEX-based sedation (DEX alone or as an adjunct to propofol infusion) between April 2005 and March 2007, and 50 managed with propofol-based sedation (propofol alone) between January 2003 and April 2005. With DEX-based sedation, both intubated and extubated patients received DEX infusion at an initial dose of 0.4 µg/kg/h, followed by a maintenance dose of 0.2-0.7 µg/kg/h. Propofol was used in both groups at a dose range of 0.5-5.0 mg/kg/h. Hemodynamic variables, including heart rate (HR) and blood pressure (BP), and adverse events were recorded and compared between the groups. RESULTS: HR during sedation and systolic BP at 2 h after beginning sedation were significantly lower in the DEX group. No serious adverse events were observed. In the DEX group, 66% were sedated in combination with propofol, of whom 94% were intubated. CONCLUSIONS: DEX could be used safely for both intubated and extubated patients following uneventful intracranial procedures for an unruptured cerebral aneurysm, though it significantly reduced HR. Our findings also indicate that it is preferable to add low-dose propofol to DEX for management of intubated patients.

DNA ligase IV is a potential molecular target in ACNU sensitivity.

Nimustine (ACNU) is a chloroethylating agent which was the most active chemotherapy agent used for patients with high-grade gliomas until the introduction of temozolomide, which became the standard of care for patients with newly diagnosed glioblastomas in Japan. Since temozolomide was established as the standard first-line therapy for glioblastoma multiforme (GBM), ACNU has been employed as a salvage chemotherapy agent for recurrent GBM in combination with other drugs. The acting molecular mechanism in ACNU has yet to be elucidated. ACNU is a cross-linking agent which induces DNA double-strand breaks (DSBs). The work described here was intended to clarify details in repair pathways which are active in the repair of DNA DSBs induced by ACNU. DSBs are repaired through the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. Cultured mouse embryonic fibroblasts were used which have deficiencies in DNA DSB repair genes which are involved in HR repair (X-ray repair cross-complementing group 2 [XRCC2] and radiation sensitive mutant 54 [Rad54]), and in NHEJ repair (DNA ligase IV [Lig4]). Cellular sensitivity to ACNU treatment was evaluated with colony forming assays. The most effective molecular target which correlated with ACNU cell sensitivity was Lig4. In addition, it was found that Lig4 small-interference RNA (siRNA) efficiently enhanced cell lethality which was induced by ACNU in human glioblastoma A172 cells. These findings suggest that the down-regulation of Lig4 might provide a useful tool which can be used to increase cell sensitivity in response to ACNU chemotherapy.

DNA ligase IV as a new molecular target for temozolomide.

Temozolomide (TMZ) is a methylating agent used in chemotherapy against glioblastoma. This work was designed to clarify details in repair pathways acting to remove DNA double-strand breaks (DSBs) induced by TMZ. Cultured mouse embryonic fibroblasts were used which were deficient in DSB repair genes such as homologous recombination repair-related genes X-ray repair cross-complementing group 2 (XRCC2)and radiation sensitive mutant54 (Rad54), non-homologous end joining repair-related gene DNAligase IV (Lig4). Cell sensitivity to drug treatments was assessed using colony forming assays. The most effective molecular target which was correlated with TMZ cell sensitivity was Lig4. In addition, it was found that small interference RNAs (siRNA) for Lig4 efficiently enhanced cell lethality induced by TMZ in human glioblastoma A172 cells. These findings suggest that down regulation of Lig4 might provide a useful tool for cell sensitization during TMZ chemotherapy.

Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 x 10(-9) M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.

OBJECTIVE: The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations. MATERIALS AND METHODS: ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with cyclosporine A. RESULTS: Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH(+) cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3. CONCLUSION: Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period.

"Sukeroku sign" and "dent internal-capsule sign"--identification guide for targeting the subthalamic nucleus for placement of deep brain stimulation electrodes.

INTRODUCTION: The purpose of this study was to assess the usefulness of signs ("Sukeroku sign" and "dent internal-capsule sign") for the recognition of subthalamic nucleus (STN). MATERIALS AND METHODS: Five Parkinson's disease cases in which there was a successful placement of deep brain stimulation (DBS) electrodes at the STN were retrospectively reviewed. Five radiologists who were not engaged in localization of STNs in clinical practice were asked to locate the STNs before and after instructions on the signs. We evaluated the deviation between the reader-located points and the location of the DBS electrode for which there had been a successful installation. RESULTS: After instruction, there was a significant reduction in the deviation between the reader-located points and the DBS electrode. The time required for localization was also reduced after the instructions. CONCLUSION: Sukeroku sign and dent internal-capsule sign are feasible indicators of STN and seem to be useful in helping to identify the STN.

Protective effect of C1 esterase inhibitor on acute traumatic spinal cord injury in the rat.

OBJECTIVE: The complement system and activated neutrophils are thought to play a major role in initiating some of the inflammatory events that occur in spinal cord injury. The aim of the present study was to assess the effects of C1 esterase inhibitor (C1-INH) on traumatic spinal cord injury (SCI) in the rat. METHODS: Thirty-eight male Wistar rats were used. Just after SCI by a pneumatic impact device, C1-INH (n=16, C1-INH group) or saline (n=16, saline group) was administered. Sham operated animals (n=6, sham group) received only laminectomy. Eighteen (six from each group) rats were killed and an assessment of leukocyte infiltration by myeloperoxidase (MPO) activity and immunoreactivity of MPO were performed 24 hours after SCI. Twenty (ten from each of C1-INH and saline groups) rats were examined using behavioral function on post-operative days. They were also examined after 7 days by histologic analysis using Luxol fast blue for axons and myelin. Lesion volume was calculated by considering a lesion as being composed of two cones with juxtaposed bases. During the experiment, sequential changes in regional spinal cord blood flow (rSCBF) were measured using the laser Doppler (LD) scanning technique. RESULTS: The recovery of motor function was better in the C1-INH group than in the saline group. In the C1-INH group, immunoreactivity of MPO showed a tendency to be smaller than that of the saline group. Lesion volume was significantly smaller in the C1-INH group than in the control group (p<0.01) and MPO activity was also significantly smaller in the C1-INH group than in the control group (p<0.01). After SCI, the rSCBF value decreased gradually and significantly in both injured groups. Significant differences were observed from 30 to 120 minutes after SCI (p<0.05). DISCUSSION: The results of this study provided the first evidence that C1-INH reduced accumulation of polymorphonuclear leukocytes (PMLs) and neuronal damage in acute stage after SCI. This protection was not related to an improvement in rSCBF.

The effects of the neuromuscular blockade levels on amplitudes of posttetanic motor-evoked potentials and movement in response to transcranial stimulation in patients receiving propofol and fentanyl anesthesia.

BACKGROUND: Patient movement in response to transcranial stimulation during monitoring of myogenic motor-evoked potentials (MEPs) may interfere with surgery. We recently reported a new technique to augment the amplitudes of myogenic MEPs, called "post-tetanic MEPs (p-MEPs)," in which tetanic stimulation of a peripheral nerve was applied prior to transcranial stimulation. We conducted the present study to determine an appropriate level of neuromuscular blockade during the monitoring of p-MEPs with a focus on patient movement. METHODS: In 15 patients under propofol/fentanyl anesthesia, conventional MEPs (c-MEPs) and p-MEPs in response to transcranial electrical stimulation were recorded from the abductor hallucis muscle. For p-MEP recording, tetanic stimulation to the posterior tibial nerve at an intensity of 50 mA for 5 s was started 6 s prior to transcranial stimulation. The level of neuromuscular blockade was assessed by recording the amplitude of compound muscle action potentials (T1) from the abductor hallucis brevis muscle in response to supramaximal electrical stimulation of the median nerve at the wrist. After the baseline recordings of c-MEP and p-MEP at a T1 of 50% of control, 0.1 mg/kg of vecuronium was injected and the amplitudes of c-MEPs and p-MEPs were recorded. Patient movement was also assessed with the movement score ranging from 1 to 4 (1 = no movement, 4 = severe movement). RESULTS: T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score changed in parallel after the administration of vecuronium. The amplitudes of p-MEPs before and 15-45 min after the administration of vecuronium were significantly higher than those of c-MEPs. When T1 and %T1 were less than and equal to 1 mV and 10%, respectively, the movement score was 1 or 2 in all patients, indicating that microscopic surgery was possible without the interruption of surgical procedures. When T1 was around 1 mV (0.8-1.2 mV), the success rates of recording of c-MEPs and p-MEPs were 73% (11 of 15) and 100% (15 of 15), respectively. CONCLUSIONS: Under propofol/fentanyl anesthesia, p-MEP could be recorded at a T1 of 1 mV, in which patient movement in response to transcranial stimulation did not interfere with surgery. This technique may be used in patients without preoperative motor deficits, in which patient movement during surgical procedures is not preferable.

Molecular pathogenesis of pediatric astrocytic tumors.

Astrocytomas are the most common pediatric brain tumors, accounting for 7%-8% of all childhood cancers. Relatively few studies have been performed on their molecular properties; therefore, classification of pediatric astrocytic tumors into genetic subtypes similar to that of adult tumors remains to be defined. Here, we report an extensive characterization of 44 pediatric astrocytomas--16 diffuse astrocytomas (WHO grade II), 10 anaplastic astrocytomas (WHO grade III), and 18 glioblastomas (WHO grade IV)--in terms of genetic alterations frequently observed in adult astrocytomas. Some form of p53 mutation was found in three diffuse astrocytomas, in three anaplastic astrocytomas, and in six glioblastomas examined; PTEN mutations were detected only in two glioblastomas. EGFR amplification was detected in only one anaplastic astrocytoma and two glioblastomas, but no amplification was observed for the PDGFR-alpha gene. Loss of heterozygosity (LOH) on 1p/19q and 10p/10q was less common in pediatric astrocytic tumors than in those seen in adults, but the frequency of LOH on 22q was comparable, occurring in 44% of diffuse astrocytomas, 40% of anaplastic astrocytomas, and 61% of glioblastomas. Interestingly, a higher frequency of p53 mutations and LOH on 19q and 22q in tumors from children six or more years of age at diagnosis was found, compared with those from younger children. Our results suggest some differences in children compared to adults in the genetic pathways leading to the formation of de novo astrocytic tumors. In addition, this study suggests potentially distinct developmental pathways in younger versus older children.

Expression of angiogenic growth factor in the rat DAVF model.

OBJECTIVE: The precise mechanisms responsible for the development and growth of dural arteriovenous fistula (DAVF) remain unclear, but it has been hypothesized that vascular endothelial growth factor (VEGF) might be involved in the pathogenesis. The aim of this study was to examine the expression of VEGF in the rat DAVF model. METHODS: Forty-five Sprague-Dawley rats were used in two experiments. In Experiment 1 (n = 20, including sham-operated controls), VEGF expression was analysed by Western blots in three different rat DAVF models: model I: common carotid artery-external jugular vein (CCA-EJV) anastomosis (n = 5); model II: sagittal sinus thrombosis and bipolar coagulation of the vein draining the transverse sinus (n = 5); model III: CCA-EJV anastomosis and bipolar coagulation of the vein draining the transverse sinus and sagittal sinus thrombosis to induce venous hypertension (n = 5). Based on the results of Experiment 1, Western blots were performed at weekly intervals 1, 2 and 3 weeks in Experiment 2 following induction of venous hypertension in model III (n = 5 at each time point and n = 5 sham controls); in addition, VEGF expression was immunohistochemically examined in the dura and the brain near the occluded sinus in five model III animals after 1 week. RESULTS: In Experiment 1, Western blot analysis showed barely detectable bands with molecular weights of 45 kD, corresponding to VEGF, in the sham group, but the highest level of VEGF was induced in model III, followed by models I and II (model III>model I>model II). In Experiment 2, the expression of VEGF peaked 1 week after induction of venous hypertension in model III, decreasing in a linear fashion over 2 and 3 weeks (week 1>weeks 2 and 3). The expression of immunoreactive VEGF was restricted in the connective tissue and the endothelial layer of the dura matter, cerebral cortical tissue and neurons of the basal ganglia. CONCLUSION: Our results strongly suggest a possible contribution of an angiogenic factor to the growth of DAVF. Venous ischemia by venous hypertension might be a mechanism for inducing up-regulation of angiogenic factor expression.

Long-term follow-up outcome after surgical treatment for lesional temporal lobe epilepsy.

OBJECTIVES: Lateral or neocortical temporal lobe epilepsy (TLE) is regarded as a distinct clinical entity from medial TLE. Surgery for neocortical TLE can be considered as a viable treatment option; however, there is very limited information available on aspects such as long-term seizure outcome. Thus, we retrospectively reviewed our ten surgical cases of lateral TLE with a minimum 2 year follow-up outcome. METHODS: The series comprised four male and six female patients, ranging in age from 3 to 46 years (mean: 28.8 years). Seven cases were found to be drug-resistant. Invasive pre-surgical evaluation for intractable epilepsy was performed in six patients. RESULTS: The pathologic lesions were removed completely in nine cases. Lesionectomy alone was performed in four cases and total epileptogenic focus resection was confirmed in four cases. The epileptogenic regions within eloquent areas were preserved in two cases. The medial temporal structure was intact and preserved in all cases. Neuropathologic diagnoses were cavernoma in three cases, astrocytoma (grade 2) in two cases, arteriovenous malformation in two cases, gliosis in two cases and ganglioglioma in one case. The mean duration of follow-up was 6.5 years (range: 2.2-9.3 years). Outcomes categorized according to Engel classes were class I (E1) in six cases and class II (E2) in four cases. Patients who had post-operative seizures may also achieve long-term seizure decrease or freedom in three cases: case 5 (E4-E2), case 6 (E4-E2) and case 7 (E3-E1). Thus, worthwhile improvement was achieved in 100% of the cases in this series, with 60% of patients being seizure-free during the followed-up period. CONCLUSIONS: The controlled long-term follow-up results suggested that surgery for lesional TLE can be considered as a viable treatment option to control seizure with a low morbidity rate and good outcomes.

[Three cases of de novo aneurysms].

We report 3 cases of de novo aneurysms that developed long after neck clipping of the initial aneurysms (range, 7 to 20 years, mean 12 years). Case 1 was a 58-year-old female who had undergone clipping of a ruptured aneurysm 17 years previously. Ten years later, she suffered another subarachnoid hemorrhage due to rupture of a new aneurysm, for which neck clipping was performed. Another seven years later, she had a third subarachnoid hemorrhage, and angiography revealed a new aneurysm, for which neck clipping was performed. Case 2 and 3 were both 68-year-old females who had suffered subarachnoid hemorrhage with two aneurysms and had undergone neck clipping for them respectively, 20 years and 12 years previously. Each patient was admitted to our hospital with complaints of headache, diplopia, vertigo, etc., and newly formed aneurysms were detected by magnetic resonance angiography. Conventional angiography revealed three and one new aneurysms, respectively. Since case 1 was a special case of multiple aneurysms in which lesions appeared in series rather than in parallel, all three patients harbored multiple aneurysms. It is recommended that patients with multiple aneurysms, especially those after a long period postoperatively, undergo periodic examination on an outpatient basis to detect formation of de novo aneurysms by magnetic resonance angiography or 3D-CT angiography.

Use of multifocal visual evoked potential tests in the objective evaluation of the visual field in pediatric epilepsy surgery.

OBJECT: To evaluate objectively the visual fields of patients with pediatric epilepsy who are uncooperative with perimetry and in whom postoperative visual field deficits are expected, the authors investigated the usefulness of the multifocal visual evoked potential (VEP) method. METHODS: Normal waves in multifocal VEP were determined in 21 healthy children (21 eyes) 6 to 15 years of age (mean 11.4 years). Responses from eight sites in each child were divided into four quadrants (superior and inferior temporal and superior and inferior nasal). In each quadrant, two response waves were grouped and averaged. The peak latency and amplitude at approximately 100 msec were used for assessment. In three cases involving patients with epilepsy, multifocal VEP measurements were also recorded and compared with the peak latency and amplitude in the healthy children. In these children, no significant differences were observed in the peak latency of amplitude among four quadrants using one-way analysis of variance. In each patient, multifocal VEP tests showed abnormal waves in the quadrant corresponding to the lesion demonstrated in neuroradiological images. This result was useful in the treatment of choice and the postoperative evaluation. CONCLUSIONS: Multifocal VEP tests can be useful in evaluating the visual field of children objectively. They can also be valuable in assessing preoperative visual field defects and revealing changes in the visual field after treatment.

Sequential and spatial profiles of apoptosis in ischemic penumbra after two-vein occlusion in rats.

OBJECT: The two-vein occlusion model is known to be useful for ischemic penumbra studies in vivo. It was applied here to examine sequential changes in the expression of Bax and Bcl-2 proteins and in apoptotic cells to assess the relationship between penumbra and apoptosis. METHODS: Two cortical veins were occluded photochemically by using rose bengal dye in 27 Wistar rats. The animals were killed with perfusion fixation at the following intervals: 4, 12, 24, 48, 96, and 168 hours after vein occlusion (four at each interval; three additional rats were sham-treated). Immunohistochemical analysis for the Bcl-2 family of proteins was performed along with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay to examine the relationship to single-cell death. Cells positive for antiapoptotic proteins began to appear in the TUNEL assay for animals killed 24 hours after vein occlusion, with a peak at 48 hours. These cells were localized in the core of infarction. Immunohistochemical staining for Bax protein showed an increased presence around ischemic lesions at 4 hours after vein occlusion, and the amounts continued to rise until 24 hours, when the localization was diffuse around the core of infarction. Negative findings on immunohistochemical studies for Bcl-2 protein were seen at the early phase after two-vein occlusion. CONCLUSIONS: After vein occlusion, apoptosis appeared sequentially and widely in cortical lesions considered to be the penumbra. Therefore, control of apoptosis would be expected to offer a therapeutic window for treatment of venous infarction.

Use of differentiating embryonic stem cells in the Parkinsonian mouse model.

Progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the following reduction in striatal dopamine cause Parkinson's disease (PD). Transplantation of dopamine-producing cells into the striatum is a proposed treatment modality. In this report, we describe a model experiment assessing the effectiveness of mouse embryonic stem (ES) cell-derived dopaminergic neurons using a mouse model of PD. ES cells were shown to be an attractive and promising source for the generation of dopaminergic neurons, and the mouse PD model was useful to assess the efficacy of transplantation therapy with dopamine-producing cells, including ES cell-derived dopaminergic neurons.

Long-term outcome of unruptured giant cerebral aneurysms.

The long-term outcome of 39 patients with unruptured giant aneurysm (>2.5 cm) treated during the last 12 years was retrospectively reviewed. The 7 male and 32 female patients, aged 32 to 81 years, presented with symptoms related to compression of the surrounding structures by the aneurysm in 28 cases, cerebral infarction in one, and asymptomatic in 10. The locations were the internal carotid artery (ICA) in 27 cases, middle cerebral artery in three, anterior cerebral artery in one, and basilar artery in eight. Therapeutic modalities were direct clipping in 11 patients, ICA occlusion combined with extracranial-intracranial bypass in 15, and conservative treatment in 13. The follow-up period ranged from 16 to 128 months (mean 54.0 months). The mortality was 9% (1/11), 0% (0/15), and 31% (4/13), and morbidity was 18% (2/11), 20% (3/15), and 8% (1/13), respectively. Surgery reduced the mortality (from 31% to 4%) but increased the morbidity (from 8% to 19%) as compared with conservatively treated patients (p < 0.05). Giant intracranial aneurysm has a poor prognosis if left untreated, but these lesions are difficult to treat with the present management options.

Surgical removal of a live worm by stereotactic targeting in cerebral sparganosis. Case report.

A 64-year-old man presented with generalized tonic clonic convulsion followed by weakness of the right lower extremity. He had a medical history of hypertension, hyperlipidemia, and right cerebellar infarction. Computed tomography (CT) showed a small high density nodule with an enhanced perifocal low density area in the left occipital lobe. T1-weighted magnetic resonance (MR) imaging showed a ring-shaped and partial string-like nodule with enhancement by gadolinium. T2-weighted MR imaging showed the white matter of the left occipital lobe as high intensity. CT and MR imaging seemed to indicate metastatic brain tumors, although cortical atrophy and ventricular dilation were recognized. Left parietal craniotomy was performed under stereotactic targeting to obtain a definitive diagnosis. During manipulation at the center of the targeted lesion, a white, tape-like body was found and recognized to be a live worm. Serological testing revealed strong immunopositivity against Spirometra mansoni. The infection route in the present case was probably through eating raw chicken meat. Cerebral sparganosis is extremely rare but should be considered in the differential diagnosis of metastatic brain tumors, especially in endemic areas.

Predictors of outcome of surgery for cervical compressive myelopathy: retrospective analysis and prospective study.

The outcomes of surgical treatment in 80 patients with cervical compressive myelopathy were retrospectively reviewed to examined the correlations between surgical outcomes and the following seven predictive factors: age at surgery, duration of symptoms, severity of myelopathy, number of compressed segments, intramedullary high intensity segments on T(2)-weighted magnetic resonance (MR) imaging, surgical method, and the type of disease. The recovery rates were evaluated at 3 months after the surgery. Significant correlations were observed between recovery rate and duration of symptoms, severity of myelopathy, and high intensity segments on T(2)-weighted MR imaging. No statistical correlation was observed with the other factors. Multivariate analysis revealed significant correlations between recovery rate and duration of symptoms and number of high intensity segments on T(2)-weighted MR imaging. The multiple regression equation was expressed as follows: recovery rate = 82.981 + 0.101 x (age) - 0.675 x (duration) - 1.452 x (number of compressed segments) - 1.451 x (preoperative Neurosurgical Cervical Spine Scale) - 13.826 x (number of high intensity segments). Based on this predicted formula, we compared the predicted and actual recovery rates for 17 patients treated recently. The two values were similar except in two patients with long duration of symptoms. We conclude that the surgical outcome can be predicted to a certain extent and this information could be provided to patients considering surgery for cervical compressive myelopathy.

Novel tumor suppressor loci on 6q22-23 in primary central nervous system lymphomas.

Deletions on the long arm of chromosome 6 (6q) are one of the most common chromosomal alterations in systemic high-grade non-Hodgkin's lymphomas. However, the locations of allelic deletions and their roles have not yet been reported in primary central nervous system lymphomas (PCNSLs), most of which are classed as non-Hodgkin's lymphoma. We thus performed fine loss of heterozygosity (LOH) mapping of 6q in 29 samples of surgically resected PCNSLs using 39 microsatellite markers to identify commonly deleted regions. LOH was found at 1 or more loci at 6q22-23 in 19 samples (66%); furthermore, 18 of these samples shared a deletion in the same small ( approximately 140 kb) region flanked by D6S1030 and D6S1690, a region in which the human R-PTP-kappa gene (PTPRK) is reported to be located. Reverse transcription-PCR analysis of the mRNA from 4 cases with 6q deletions confirmed loss of this gene, and loss of PTPRK expression was observed in 76% (22 of 29) of tumors with immunohistochemistry. In addition, LOH on 6q22-q23 significantly correlated to shorter patient survival (12.8 +/- 4.3 versus 23.4 +/- 3.5 months; P < 0.0001). Our results suggest that a 140-kb deletion located at 6q22-23 may contain the putative tumor suppressor, PTPRK, that appears to be relevant to the pathogenesis and prognosis of PCNSLs.

Expression of ciliary neurotrophic factor (CNTF), CNTF receptor alpha (CNTFR-alpha) following experimental intracerebral hemorrhage in rats.

Ciliary neurotrophic factor (CNTF) is known as a neuro-survival factor in the developing and developed CNS, as well as in the CNS following injury. However, little is known about the expression of CNTF or that of its receptor (CNTFR-alpha) in cases of intracerebral hemorrhage (ICH). We investigated the temporal and spatial profiles of CNTF and CNTFR-alpha expression using a collagenase-induced ICH rat model. CNTF expression was up-regulated from the day following ICH induction and reached a peak level at 5 to 14 days, with increased expression observed in brain tissue surrounding the hematoma lesion and white matter structures in association with astroglial proliferation. Further, CNTFR-alpha was transiently expressed in the cerebral cortex surrounding the hematoma, with a peak at 5 days. Administration of exogenous CNTF into the lesion following initiation of ICH resulted in a prolonged expression of CNTFR-alpha on cortical neurons neighboring the hematoma. Our findings suggest differential regulation of CNTF and CNTFR-alpha, and the possibility of a therapeutic strategy using CNTF administration for ICH.