Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain.

As an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like (TTLL) proteins, TTLL1 and TTLL7, which have been indicated to be important for neuronal polarity. In this study, we constructed pure lines of Ttll1 and Ttll7 knockout mice. Ttll knockout mice showed several abnormal behaviors. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analyses of these brains showed increases in glutamate, suggesting that tubulin polyglutamylation by these TTLLs acts as a pool of glutamate in neurons and modulates some other amino acids related to glutamate.

Optic Nerve Injury Enhanced Mitochondrial Fission and Increased Mitochondrial Density without Altering the Uniform Mitochondrial Distribution in the Unmyelinated Axons of Retinal Ganglion Cells in a Mouse Model.

Glaucomatous optic neuropathy (GON), a major cause of blindness, is characterized by the loss of retinal ganglion cells (RGCs) and the degeneration of their axons. Mitochondria are deeply involved in maintaining the health of RGCs and their axons. Therefore, lots of attempts have been made to develop diagnostic tools and therapies targeting mitochondria. Recently, we reported that mitochondria are uniformly distributed in the unmyelinated axons of RGCs, possibly owing to the ATP gradient. Thus, using transgenic mice expressing yellow fluorescent protein targeting mitochondria exclusively in RGCs within the retina, we assessed the alteration of mitochondrial distributions induced by optic nerve crush (ONC) via in vitro flat-mount retinal sections and in vivo fundus images captured with a confocal scanning ophthalmoscope. We observed that the mitochondrial distribution in the unmyelinated axons of survived RGCs after ONC remained uniform, although their density increased. Furthermore, via in vitro analysis, we discovered that the mitochondrial size is attenuated following ONC. These results suggest that ONC induces mitochondrial fission without disrupting the uniform mitochondrial distribution, possibly preventing axonal degeneration and apoptosis. The in vivo visualization system of axonal mitochondria in RGCs may be applicable in the detection of the progression of GON in animal studies and potentially in humans.

A model for generating differences in microtubules between axonal branches depending on the distance from terminals.

In the remodeling of axonal arbor, the growth and retraction of branches are differentially regulated within a single axon. Although cell-autonomously generated differences in microtubule (MT) turnover are thought to be involved in selective branch regulation, the cellular system whereby neurons generate differences of MTs between axonal branches has not been clarified. Because MT turnover tends to be slower in longer branches compared with neighboring shorter branches, feedback regulation depending on branch length is thought to be involved. In the present study, we generated a model of MT lifetime in axonal terminal branches by adapting a length-dependent model in which parameters for MT dynamics were constant in the arbor. The model predicted that differences in MT lifetime between neighboring branches could be generated depending on the distance from terminals. In addition, the following points were predicted. Firstly, destabilization of MTs throughout the arbor decreased the differences in MT lifetime between branches. Secondly, differences of MT lifetime existed even before MTs entered the branch point. In axonal MTs in primary neurons, treatment with a low concentration of nocodazole significantly decreased the differences of detyrosination (deTyr) and tyrosination (Tyr) of tubulins, indicators of MT turnover. Expansion microscopy of the axonal shaft before the branch point revealed differences in deTyr/Tyr modification on MTs. Our model recapitulates the differences in MT turnover between branches and provides a feedback mechanism for MT regulation that depends on the axonal arbor geometry.

Intermitochondrial signaling regulates the uniform distribution of stationary mitochondria in axons.

In the central nervous system (CNS), many neurons develop axonal arbors that are crucial for information processing. Previous studies have demonstrated that premature axons contain motile and stationary mitochondria, and their balance is important for axonal arborization. However, the mechanisms by which neurons determine the positions of stationary mitochondria as well as their turnover remain to be elucidated. We observed that the distribution of stationary mitochondrial spots along the unmyelinated and nonsynaptic axons is not random but rather relatively uniform both in primary cultured neurons and in tissues. Intriguingly, whereas the positions of each mitochondrial spot changed over time, the overall distribution remained uniform. In addition, local inactivation of mitochondria by KillerRed mediated chromophore-assisted light inactivation (CALI) inhibited the translocation of mitochondrial spots in adjacent axonal regions, suggesting that functional mitochondria enhance the motility of other mitochondria in the vicinity. Signals of ATP:ADP sensor, PercevalHR indicated that the ATP:ADP ratio was relatively high around mitochondria, and treating axons with phosphocreatine (PCr), which supplies ATP, reduced the immobile mitochondria induced by the local mitochondrial inactivation. In a mathematical model, we found that the ATP gradient generated by mitochondria, and ATP dependent regulation of mitochondrial motility could establish uniform mitochondrial distribution. These observations suggest that axons in the CNS possess the system that distributes mitochondria uniformly, and intermitochondrial signaling contribute to the regulation. In addition, our results suggest the possibility that ATP might be one of the molecules mediating the signaling.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Focal Hand Dystonia: A Pilot Study.

BACKGROUND: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for the treatment of focal hand dystonia (FHD) is not well known. OBJECTIVE: We aimed to prospectively investigate the efficacy of MRgFUS thalamotomy for the treatment of FHD. METHODS: We performed MRgFUS thalamotomy of the ventro-oral (Vo) nucleus in 10 patients with FHD. We evaluated the scores of the Writer's Cramp Rating Scale (WCRS, 0-30; higher scores indicating greater severity), Tubiana Musician's Dystonia Scale (TMDS, 0-5; lower scores indicating greater severity), and Arm Dystonia Disability Scale (ADDS, 0%-100%; lower scores indicating greater disability) at baseline and 3 and 12 months post-treatment. RESULTS: WCRS, TMDS, and ADDS scores significantly improved from 6.3 ± 2.7, 1.4 ± 0.5, and 58.7% ± 14.3% at baseline to 1.6 ± 3.1 (P = 0.011), 5.0 ± 0 (P = 0.0001), and 81.6% ± 22.9% (P = 0.0229) at 12 months, respectively. There was one prolonged case of dysarthria at 12 months. CONCLUSION: We show that MRgFUS Vo-thalamotomy significantly improved FHD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neuroprotective effects of aromatic turmerone on activity deprivation-induced apoptosis in cerebellar granule neurons.

Ar-turmerone, which is a major bioactive component found in the essential oil derived from Curcuma longa, has been reported to inhibit proliferation and induce apoptosis in cancer cell lines. Recently, ar-turmerone has been reported to increase the proliferation of neuronal stem cells, in contrast to its actions in cancer cells. These observations raise the possibility that ar-turmerone serves specific functions in neuronal cell lineages. However, the effects of ar-turmerone on postmitotic neurons remain elusive. In the present study, we investigated the neuroprotective functions of ar-turmerone in primary cerebellar granule neuronal cultures. We found that ar-turmerone increased the survival of neurons following activity deprivation. Consistently, the induction of cleaved caspase-3, a hallmark of apoptosis, was prevented by ar-turmerone, although neither the level of reactive oxygen species nor the mitochondrial membrane potential was affected. This study reports a neuroprotective function for ar-turmerone, providing new insights into the potential therapeutic applications of ar-turmerone for neurological disorders.

Reliability of Residual Tumor Estimation Based on Navigation Log.

The mass of residual tumors has previously been estimated using time-series records of the position of surgical instruments acquired from neurosurgical navigation systems (navigation log). This method has been shown to be useful for rapid evaluation of residual tumors during resection. However, quantitative analysis of the method's reliability has not been sufficiently reported. The effect of poor log coverage is dominant in previous studies, in that it did not highlight other disturbance factors, such as intraoperative brain shift. We analyzed 25 patients with a high log-acquisition rate that was calculated by dividing the log-available time by the instrument-use time. We estimated the region of resection using the trajectory of surgical instrument that was extracted from the navigation log. We then calculated the residual tumor region and measured its volume as log-estimation residual tumor volume (RTV). We evaluated the correlation between the log-estimation RTV and the RTV in the post-resection magnetic resonance (MR) image. We also evaluated the accuracy of detecting the residual tumor mass using the estimated residual tumor region. The log-estimation RTV and the RTV in the post-resection MR image were significantly correlated (correlation coefficient = 0.960; P <0.001). The presence of patient-wise residual tumor mass was detected with a sensitivity of 81.8% and a specificity of 92.9%. The individual residual tumor mass was detected with a positive predictive value of 72%. Estimation of residual tumor with adequate log coverage appears to be a suitable method with a high reliability. This method can support rapid decision-making during resection.

Sonodynamic Therapy With Anticancer Micelles and High-Intensity Focused Ultrasound in Treatment of Canine Cancer.

Sonodynamic therapy (SDT) is a minimally invasive anticancer therapy involving a chemical sonosensitizer and high-intensity focused ultrasound (HIFU). SDT enables the reduction of drug dose and HIFU irradiation power compared to those of conventional monotherapies. In our previous study, mouse models of colon and pancreatic cancer were used to confirm the effectiveness of SDT vs. drug-only or HIFU-only therapy. To validate its usefulness, we performed a clinical trial of SDT using an anticancer micelle (NC-6300) and our HIFU system in four pet dogs with spontaneous tumors, including chondrosarcoma, osteosarcoma, hepatocellular cancer, and prostate cancer. The fact that no adverse events were observed, suggests the usefulness of SDT.

Correlation between fractional anisotropy changes in the targeted ventral intermediate nucleus and clinical outcome after transcranial MR-guided focused ultrasound thalamotomy for essential tremor: results of a pilot study.

OBJECTIVE: This study evaluated changes of fractional anisotropy (FA) in the ventral intermediate nucleus (VIM) of the thalamus after transcranial MR-guided focused ultrasound (TcMRgFUS) thalamotomy and their associations with clinical outcome. METHODS: Clinical and radiological data of 12 patients with medically refractory essential tremor (mean age 76.5 years) who underwent TcMRgFUS thalamotomy with VIM targeting were analyzed retrospectively. The Clinical Rating Scale for Tremor (CRST) score was calculated before and at 1 year after treatment. Measurements of the relative FA (rFA) values, defined as ratio of the FA value in the targeted VIM to the FA value in the contralateral VIM, were performed before thalamotomy, and 1 day and 1 year thereafter. RESULTS: TcMRgFUS thalamotomy was well tolerated and no long-term complications were noted. At 1-year follow-up, 8 patients demonstrated relief of tremor (improvement group), whereas in 4 others persistent tremor was noted (recurrence group). In the entire cohort, mean rFA values in the targeted VIM before treatment, and at 1 day and 1 year after treatment, were 1.12 ± 0.15, 0.44 ± 0.13, and 0.82 ± 0.22, respectively (p < 0.001). rFA values were consistently higher in the recurrence group compared with the improvement group, and the difference reached statistical significance at 1 day (p < 0.05) and 1 year (p < 0.01) after treatment. There was a statistically significant (p < 0.01) positive correlation between rFA values in the targeted VIM at 1 day after thalamotomy and CRST score at 1 year after treatment. Receiver operating characteristic curve analysis revealed that the optimal cutoff value of rFA at 1 day after thalamotomy for prediction of symptomatic improvement at 1-year follow-up is 0.54. CONCLUSIONS: TcMRgFUS thalamotomy results in significant decrease of rFA in the targeted VIM, at both 1 day and 1 year after treatment. Relative FA values at 1 day after treatment showed significant correlation with CRST score at 1-year follow-up. Therefore, FA may be considered a possible imaging biomarker for early prediction of clinical outcome after TcMRgFUS thalamotomy for essential tremor.

A single case of MRI-guided focused ultrasound ventro-oral thalamotomy for musician's dystonia.

Musician's dystonia (MD) is a type of focal hand dystonia that develops only while playing musical instruments and interferes with skilled and fine movements. Lesioning of the ventro-oral (Vo) nucleus of the thalamus (Vo-thalamotomy) using radiofrequency can cause dramatic improvement in MD symptoms. Focused ultrasound (FUS) can make intracranial focal lesions without an incision. The authors used MRI-guided FUS (MRgFUS) to create a lesion on the Vo nucleus to treat a patient with MD. Tubiana's MD scale (TMDS) was used to evaluate the condition of musical play ranging from 1 to 5 (1: worst, 5: best). The patient was a 35-year-old right-handed man with involuntary flexion of the right second, third, and fourth fingers, which occurred while playing a classical guitar. Immediately after therapeutic sonications of FUS Vo-thalamotomy, there was dramatic improvement in the MD symptoms. The TMDS scores before; at 0 and 1 week after; and at 1, 3, 6, and 12 months after MRgFUS Vo-thalamotomy were 1, 4, 4, 5, 5, 5, and 5, respectively. No complications were observed. Focused ultrasound Vo-thalamotomy can be an effective treatment for MD.

Inhibition of glycogen synthase kinase-3 reduces extension of the axonal leading process by destabilizing microtubules in cerebellar granule neurons.

Recent studies have uncovered various molecules that play key roles in neuronal morphogenesis. Nevertheless, the mechanisms underlying the neuron-type-dependent regulation of morphogenesis remain unknown. We have previously reported that inhibition of glycogen synthase kinase-3 (GSK3) markedly reduced axonal length of cerebellar granule neurons (CGNs) in a neuron-type-dependent manner. In the present study, we investigated the mechanisms by which the growth of CGN axons was severely suppressed upon GSK3 inhibition. Using time-lapse imaging of cultured CGNs at early morphogenesis, we found that extension of the leading process was severely inhibited by the pharmacological inhibition of GSK3. The rate of somal migration was also reduced with a GSK3 inhibitor in dissociated culture as well as in microexplant culture. In addition, CGNs ectopically expressed with a catalytically inactive mutant of GSK3 exhibited a migration defect in vivo. In axonal leading processes of CGNs, detyrosination and acetylation of α-tubulin, which are known to correlate with microtubule stability, were decreased by GSK3 inhibition. A photoconversion analysis found that inhibition of GSK3 increases the turnover of microtubules. Furthermore, in the presence of paclitaxel, a microtubule-stabilizing reagent, inhibition of GSK3 recovered the axonal leading process extension that was reduced by paclitaxel. Our results suggest that GSK3 supports the extension of axonal processes by stabilizing microtubules, contrary to its function in other neuron-types, lending mechanical insight into neuron-type-dependent morphological regulation.

Study of local intracellular signals regulating axonal morphogenesis using a microfluidic device.

The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca2+ signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs). Local application of nifedipine using a polydimethylsiloxane (PDMS)-based microfluidic device demonstrated that Ca2+ entry from the axonal region via L-type voltage-dependent calcium channels (L-VDCC) is required for branch extension. Furthermore, we developed a method for locally controlling protein levels by combining genetic techniques and use of a microfluidic culture system. A vector for enhanced green fluorescent protein (EGFP) fused to a destabilizing domain derived from E. coli dihydrofolate reductase (ecDHFR) is introduced in neurons by electroporation. By local application of the DHFR ligand, trimethoprim (TMP) using a microfluidic device, we were able to manipulate differentially the level of fusion protein between axons and somatodendrites. The present study revealed the effectiveness of microfluidic devices to address fundamental biological issues at subcellular levels, and the possibility of their development in combination with molecular techniques.

Kinesin-1 sorting in axons controls the differential retraction of arbor terminals.

The ability of neurons to generate multiple arbor terminals from a single axon is crucial for establishing proper neuronal wiring. Although growth and retraction of arbor terminals are differentially regulated within the axon, the mechanisms by which neurons locally control their structure remain largely unknown. In the present study, we found that the kinesin-1 (Kif5 proteins) head domain (K5H) preferentially marks a subset of arbor terminals. Time-lapse imaging clarified that these arbor terminals were more stable than others, because of a low retraction rate. Local inhibition of kinesin-1 in the arbor terminal by chromophore-assisted light inactivation (CALI) enhanced the retraction rate. The microtubule turnover was locally regulated depending on the length from the branching point to the terminal end, but did not directly correlate with the presence of K5H. By contrast, F-actin signal values in arbor terminals correlated spatiotemporally with K5H, and inhibition of actin turnover prevented retraction. Results from the present study reveal a new system mediated by kinesin-1 sorting in axons that differentially controls stability of arbor terminals.

Ttll9-/- mice sperm flagella show shortening of doublet 7, reduction of doublet 5 polyglutamylation and a stall in beating.

Nine outer doublet microtubules in axonemes of flagella and cilia are heterogeneous in structure and biochemical properties. In mammalian sperm flagella, one of the factors to generate the heterogeneity is tubulin polyglutamylation, although the importance of the heterogeneous modification is unclear. Here, we show that a tubulin polyglutamylase Ttll9 deficiency (Ttll9(-/-)) causes a unique set of phenotypes related to doublet heterogeneity. Ttll9(-/-) sperm axonemes had frequent loss of a doublet and reduced polyglutamylation. Intriguingly, the doublet loss selectively occurred at the distal region of doublet 7, and reduced polyglutamylation was observed preferentially on doublet 5. Ttll9(-/-) spermatozoa showed aberrant flagellar beating, characterized by frequent stalls after anti-hook bending. This abnormal motility could be attributed to the reduction of polyglutamylation on doublet 5, which probably occurred at a position involved in the switching of bending. These results indicate that mammalian Ttll9 plays essential roles in maintaining the normal structure and beating pattern of sperm flagella by establishing normal heterogeneous polyglutamylation patterns.

Difficulty in identification of the frontal language area in patients with dominant frontal gliomas that involve the pars triangularis.

OBJECTIVE Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping. METHODS Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women's Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined. RESULTS The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%. Conclusions Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation.

Cell positioning and neuronal network formation are crucial for proper brain function. Disrupted-in-Schizophrenia 1 (DISC1) is anterogradely transported to the neurite tips, together with Lis1, and functions in neurite extension via suppression of GSK3ß activity. Then, transported Lis1 is retrogradely transported and functions in cell migration. Here, we show that DISC1-binding zinc finger protein (DBZ), together with DISC1, regulates mouse cortical cell positioning and neurite development in vivo. DBZ hindered Ndel1 phosphorylation at threonine 219 and serine 251. DBZ depletion or expression of a double-phosphorylated mimetic form of Ndel1 impaired the transport of Lis1 and DISC1 to the neurite tips and hampered microtubule elongation. Moreover, application of DISC1 or a GSK3ß inhibitor rescued the impairments caused by DBZ insufficiency or double-phosphorylated Ndel1 expression. We concluded that DBZ controls cell positioning and neurite development by interfering with Ndel1 from disproportionate phosphorylation, which is critical for appropriate anterograde transport of the DISC1-complex.

Advanced Image Coregistration within the Leksell Workstation for the Planning of Glioma Surgery: Initial Experience.

Background Leksell GammaPlan (LGP) and SurgiPlan (ELEKTA Instruments AB, Stockholm, Sweden) may be used effectively for the detailed evaluation of regional neuroanatomy before open neurosurgical procedures. We report our initial experience in the cases of cerebral gliomas. Methods LGP v.8.3 was used before the surgical resection of cerebral gliomas for (1) the delineation of subdural grid electrodes and a detailed evaluation of their position relatively to cortical structures, and (2) for the fusion of structural magnetic resonance imaging and diffusion tensor imaging (DTI) for a detailed visualization of the corticospinal tract (CST) and optic radiation. Results Delineation of the subdural grid within LGP in a patient with seizures caused by left parietal glioma permitted a detailed assessment of the location of electrodes relative to the cortical gyri and sulci and significantly facilitated interpretation of brain mapping before tumor resection. In another patient with parieto-occipital glioma, simultaneous three-dimensional visualization of the tumor, CST, and optic radiation with the use of LGP permitted us to perform tumor resection without postoperative neurologic complications. Finally, incorporation of DTI into SurgiPlan resulted in precise planning of stereotactic biopsy for bilateral thalamic glioma. Conclusion The possibility for detailed evaluation of regional neuroanatomy based on various images within LGP and SurgiPlan may facilitate effective and safe surgical management of intracranial gliomas.

A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis.

Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

Usefulness of Leksell GammaPlan for preoperative planning of brain tumor resection: delineation of the cranial nerves and fusion of the neuroimaging data, including diffusion tensor imaging.

Leksell GammaPlan (LGP) software was initially designed for Gamma Knife radiosurgery, but it can be successfully applied to planning of the open neurosurgical procedures as well. We present our initial experience of delineating the cranial nerves in the vicinity of skull base tumors, combined visualization of the implanted subdural electrodes and cortical anatomy to facilitate brain mapping, and fusion of structural magnetic resonance imaging and diffusion tensor imaging performed with the use of LGP before removal of intracranial neoplasms. Such preoperative information facilitated choosing the optimal approach and general surgical strategy, and corresponded well to the intraoperative findings. Therefore, LGP may be helpful for planning open neurosurgical procedures in cases of both extraaxial and intraaxial intracranial tumors.