Intra-and peritumoral hemorrhage in the meningioma of a nonagenarian due to administration of direct oral anticoagulants after mechanical thrombectomy.

Background: Spontaneous intratumoral hemorrhage of meningiomas is rare, and their incidence due to anticoagulants is unclear. The incidence of both meningioma and cardioembolic stroke increases with age. We report the very elderly case of intra- and peritumoral hemorrhage in frontal meningioma induced by direct oral anticoagulant (DOAC) following mechanical thrombectomy, in whom, surgical resection was required 10 years after the tumor was first indicated. Case Description: A 94-year-old woman with independence in daily living who suffered sudden consciousness disturbance, total aphasia, and right hemiparesis was admitted to our hospital. Magnetic resonance imaging showed an acute cerebral infarction and left middle cerebral artery occlusion. There was also a left frontal meningioma with peritumoral edema, which was discovered 10 years prior, and the size and edema had remarkably increased. The patient underwent urgent mechanical thrombectomy, and recanalization was achieved. Administration of DOAC was initiated for the atrial fibrillation. Computed tomography (CT) revealed an asymptomatic intratumoral hemorrhage at postoperative day 26. The patient's symptoms gradually improved; however, she suffered sudden disturbance of consciousness and right hemiparesis on postoperative day 48. CT revealed intra- and peritumoral hemorrhages with compression of the surrounding brain. Therefore, we decided to perform tumor resection instead of conservative treatment. The patient underwent surgical resection, and the postoperative course was uneventful. It was diagnosed with transitional meningioma with no malignant features. The patient was transferred to another hospital for rehabilitation. Conclusion: Peritumoral edema representing a pial blood supply might be a significant factor associated with intracranial hemorrhage due to DOAC administration in patients with meningioma. The evaluation of hemorrhagic risk due to DOACs is important not only for meningioma but also for other brain tumor cases.

Patterns of failure in glioblastoma multiforme following Standard (60 Gy) or Short course (40 Gy) radiation and concurrent temozolomide.

PURPOSE: The purpose of this study was to analyze the patterns of failure in patients with glioblastoma multiforme (GBM) treated using chemoradiotherapy in the Standard radiotherapy (60 Gy/30 fractions; Standard) or Short course (40 Gy/15 fractions: Short). MATERIALS AND METHODS: Ninety-three consecutive patients with newly diagnosed glioblastoma treated at our hospital between April 2007 and December 2016, and 68 patients who could be followed up were included. All patients underwent surgical resection followed by radiotherapy with concurrent temozolomide. We retrospectively analyzed treatment outcomes and recurrence patterns. RESULTS: The median follow-up period of the surviving patients was 82.8 months (range: 46.0-158.9 months). Of the 68 patients, 58 patients (85%) had recurrences, 34 underwent the Standard and 24 Short course. The Standard course was seen in younger age groups and had a better Karnofsky performance status (KPS) than the Short course. The median survival time (MST) was 25.8 months for the Standard and 15.4 months with the Short in all cases. Standard course had significantly longer MST than the Short (p = 0.001) course. For recurrent cases only, there was no significant difference between Standard and Short courses in OS (p = 0.06). The recurrences occurred at the radiation fields alone (Standard/Short: 85%/83%), only at distant sites (Standard/Short: 12%/13%), and at both the radiation fields and distant sites (Standard/Short: 3%/4%). There was no significant difference in recurrence pattern and frequency between the two protocols (p = 0.11). CONCLUSIONS: Standard course tended to be significant in younger age groups and have a better KPS than the Short course; therefore, the Standard course has a longer OS, but the recurrence pattern of the Short course is similar to that of the Standard treatment.

Ring enhanced aneurysm due to vasa vasorum of aneurysm wall mimicking a metastatic brain tumor.

BACKGROUND: A spherical intracranial mass can be occasionally misdiagnosed due to the lack of typical radiographic features. Completely thrombosed intracranial aneurysms (CTIA) are uncommon, but a possible differential diagnosis must be considered to guarantee the best surgical approach for these lesions. CASE DESCRIPTION: Here, we report an extremely rare case of a right frontal mass mimicking a brain tumor, in which the surgery unveiled a CTIA of the right middle cerebral artery (MCA). A 56-year-old woman presented with right hemiparesis and mild headache. Magnetic resonance imaging (MRI) revealed a right frontal mass with peripheral edema. The lesion enhanced on initial and follow-up MRI of the brain. Subsequent vascular studies and metastatic workup were negative. A temporal craniotomy with neuronavigation (Brain Lab AG, Germany) was performed and an intraoperative diagnosis of a thrombosed aneurysm along the branch of the MCA was established. The aneurysm was successfully trapped and resected. The patient did not exhibit any postoperative neurological deficits. CONCLUSION: This is the rare report of a ring enhanced completely thrombosed aneurysm due to vasa vasorum which is misdiagnosed as metastatic brain tumor. In case of an intracranial ring enhanced mass with signs of intralesional hemorrhage and peripheral edema, CTIA should be considered as a possible differential diagnosis.

Endodermal Cyst with a Non-enhancing Nodule in the Quadrigeminal Cistern Developed in an Octogenarian.

BACKGROUND: Intracranial endodermal cysts are congenital lesions that generally develop in the cerebellopontine angle and ventral brainstem of the posterior fossa, whereas endodermal cysts in the quadrigeminal cistern are very rare. We report a rare case of an endodermal cyst in the quadrigeminal cistern with a non-enhancing nodule that developed in patient over 80 years of age. CASE DESCRIPTION: An 85-year-old man presented to our hospital with progressing gait disturbance and urinary incontinence. Preoperative images showed a cystic mass lesion with a nodule in the quadrigeminal cistern and hydrocephalus. There was no enhanced portion in the lesion, and the intensity of the cyst on magnetic resonance imaging revealed a high protein concentration. Subtotal resection was performed due to the adhesion of the cyst to the brainstem. It was diagnosed as an endodermal cyst. The postoperative course was uneventful, and hydrocephalus improved. CONCLUSIONS: This is a rare case of an intracranial endodermal cyst in terms of location and age of onset compared with previous reports. This case demonstrates that endodermal cysts should be considered as a differential diagnosis for lesions in the quadrigeminal cistern with high protein concentration in the cyst and nodule representing chronic inflammation, regardless of enhancing effects.

Recurrent Spinal Intramedullary Arachnoid Cyst: Case Report and Literature Review.

BACKGROUND: Symptomatic intramedullary arachnoid cysts are rarely observed lesions, particularly in the pediatric age group. Treatment includes cyst fenestration or resection of the cyst wall, and recurrence after surgery has never been reported. We report a rare case of a spinal intramedullary arachnoid cyst, which recurred after cyst fenestration and required reoperation after a certain period. CASE DESCRIPTION: A 4-year-old boy presented to our hospital with tetraparesis and bladder and rectum disorder. A cystic intramedullary lesion in the cervical spinal cord was detected in preoperative imaging. An emergency fenestration of cyst was performed, and his symptoms were resolved immediately. One month after the operation, the symptoms and cyst recurred. The symptoms improved in the natural course without reoperation. However, the cyst increased in size and the symptoms recurred after 27 months from the first relapse and the cyst was removed urgently. The diagnosis was an arachnoid cyst. After the reoperation, the cyst has disappeared and not recurred. CONCLUSIONS: To the best of our knowledge, this is the first report of recurrence of an intramedullary arachnoid cyst. This case indicates the importance of considering the resection of cyst wall as possible because of the probability of cyst recurrence after fenestration, while careful observation is the option in the short term, especially for children or high-risk cases.

[Stereotactic Biopsy in the Lateral Position Using a Neuronavigation System].

BACKGROUND: Stereotactic brain biopsy using a navigation system is minimally invasive because it can be performed under local anesthesia. However, there are problems due to the localization and accessibility of the tumor and instability of the airway under sedation. This study aimed to examine the differences in safety and surgical time between the supine and lateral position. METHODS: This study included 25 cases which underwent navigation-guided brain biopsies from May 2015 to March 2018 in the Kanazawa University Hospital. We compared tumor localization, operation time, standby time, intraoperative difficulties, and final diagnosis acquisition rates between the supine and lateral positions. Puncture sites were then examined by visualizing all biopsy trajectories simultaneously on a three-dimensional cerebral template. RESULTS: Biopsies of the tumor in all cerebrum lobes were possible in the lateral position. There were no significant differences in operating time or standby time between the supine and lateral positions. One case in the spine position required sedation by an anesthesiologist due to body movement, but there were no difficulties in any cases of lateral positioning. The final diagnosis acquisition rate was 100% in all cases. In the lateral position, stable breathing was maintained because the head and the trunk axes remined in the same line. CONCLUSION: Stereotactic brain biopsy in the lateral position can be safer and more useful than in the supine position under local anesthesia.

Efficacy of cyst-cisternal shunt for refractory cyst regrowth of cystic vestibular schwannomas.

Vestibular schwannomas (VSs) are generally benign and slow-growing tumors, and microsurgical resection is the commonly recommended treatment. Some reports suggested that inserting a cystoperitoneal shunt was effective for treatment of cystic VSs; however, there was no report of a cyst-cisternal shunt which diverts cyst fluid into cistern. We report a case of cystic VS with repeated cyst regrowth within weeks after repeated surgeries. We prevented further recurrence using cyst-cisternal shunt. This technique may be a new treatment option for refractory cyst regrowth of cystic VSs.

Case of metastatic glioblastoma with primitive neuronal component to the lung.

Glioblastoma (GBM) with primitive neuronal component (GBM-PNC) is a rare GBM subtype recently categorized by the World Health Organization in the revised classification system of 2016. Extracranial metastases originating from GBM-PNC are rare and metastasis to solid organs has never been reported. Herein, we present the first case of metastasis of GBM-PNC to the lung. A 49-year-old man presenting with headache was diagnosed with multiple tumors adhering to the dura matter in the right temporal lobe. Despite surgery and chemoradiotherapy, 2 months after the initial therapy, the patient presented with CSF dissemination and lung metastases. The patient succumbed to the disease 12 months after the first surgery. We discuss the possibility that GBM-PNC may constitute a subtype of glioma with particularly poor prognosis, tending to dissemination and metastasis. Our results suggest that a complementary regular inspection of the whole body via CT may be recommended for the follow-up of patients with GBM- PNC.

Bright spot analysis for photodynamic diagnosis of brain tumors using confocal microscopy.

BACKGROUND: In a previous study of photodynamic tumor diagnosis using 5-aminolevulinic acid (5-ALA), the authors proposed using fluorescence intensity and bright spot analyses under confocal microscopy for the precise discrimination of tumorous brain tissue (such as glioblastoma, GBM) from normal tissue. However, it remains unclear if bright spot analysis can discriminate infiltrating tumor in the boundary zone and whether this method is suitable for GBM with no 5-ALA fluorescence or for other tumor types. METHODS: Brain tumor tissue resected from 5-ALA-treated patients was sectioned to evaluate bright spots under confocal microscopy with a 544.5 - 619.5 nm band-pass filter, which eliminated the fluorescence induced by 5-ALA. Border regions and adjacent normal tissues were observed for differences in bright spot distribution. Histopathology was also conducted by hematoxylin and eosin (H&E) staining of serial slices from the same samples to confirm the locations of tumorous, infiltrating, and normal regions. Bright spot areas were then calculated for the same regions evaluated by histopathology. This method was applied for GBM with and without 5-ALA-induced fluorescence as well as for lower-grade gliomas and other brain tumor types. RESULTS: The bright spot area was substantially smaller in the GBM body than in normal brain tissues. Bright spot area was also smaller in infiltrating tumors than in normal tissue at the margin. The same bright spot pattern was observed in tumorous tissues with no 5-ALA-induced fluorescence and in non-GBM tumors. The bright spot fluorescence is suggested to arise from lipofuscin based on emission spectra (mainly within 544.5 - 619.5 nm) and optimum excitation wavelength (about 405 nm). CONCLUSIONS: Bright spot analysis is useful for discriminating infiltrating tumor from bordering normal tissue as an alternative or complement to photodynamic diagnosis with 5-ALA. This method is also potentially useful for tumors with no 5-ALA-derived red fluorescence and other nervous system tumors.

Ligand-dependent EphB4 activation serves as an anchoring signal in glioma cells.

Of the erythropoietin-producing human hepatocellular receptors (Ephs), EphB4 has recently emerged as a potential target in several cancers due to its roles in modified cell migration and invasion. As little is known about the roles of EphB4 in glioma, we sought to investigate its function in glioma by in vitro cell migration and invasion assays, immunoblotting and immunostaining. EphB4 was expressed in glioma cell lines and stem-like cell lines. The stimulation of glioma cells with ephrin-B2, the sole ligand of EphB4, conducted EphB4 phosphorylation and suppressed migration and invasion that downregulation of EphB4 using small interfering RNA abrogated. The stimulation also suppressed the phosphorylation of Akt. We confirmed by immunostaining that EphB4-positive cells existing only in the tumor core, whereas ephrin-B2-positive cells widespread in both the tumor core and the invasive area signifying that EphB4-ephrin-B2 reaction occurred only at the tumor core. Taken together, our data suggest that ephrin-B2-dependent EphB4 phosphorylation acts as an anchoring signal to reduce the malignancy by inhibiting Akt phosphorylation in the glioma core, whereas the scarcity of signaling in the tumor periphery promotes invasion into the surrounding brain.

Intratumoral continuous facial nerve stimulation for surgical resection of cystic vestibular schwannoma: Technical note.

BACKGROUND: Cystic vestibular schwannomas (CVSs) account for about 10% of VS. The efficacy of continuous facial nerve stimulation (CFS) was previously reported; however, it is often difficult to place the electrode at the root exit zone (REZ) in the early stage of surgical resection. We proposed a new method of intratumoral CFS (ICFS) by searching for the facial nerve through the cyst wall and leaving the spherically shaped electrode at this point. METHODS: The cyst wall was opened, and the ventral side of the tumor wall was stimulated to search for the positive point of facial nerve stimulation and place the spherically shaped electrode for continuous stimulation at this point through the cyst cavity (intensity: 0.2-1.5 mA, frequency: 1 Hz). Safe surgical resection could be performed under ICFS in all three cases. RESULTS: Good preservation of the facial nerve and extent of resection that was estimated preoperatively was achieved in all cases. CONCLUSION: ICFS is suitable for the preservation of facial nerve function in surgical resection of CVS in cases in which electrode placement at the REZ is difficult.

Finger-attachment device for the feedback of gripping and pulling force in a manipulating system for brain tumor resection.

PURPOSE: Development and evaluation of an effective attachment device for a bilateral brain tumor resection robotic surgery system based on the sensory performance of the human index finger in order to precisely detect gripping- and pulling-force feedback. METHODS: First, a basic test was conducted to investigate the performance of the human index finger in the gripping- and pulling-force feedback system. Based on the test result, a new finger-attachment device was designed and constructed. Then, discrimination tests were conducted to assess the pulling force and the feedback on the hardness of the gripped material. RESULTS: The results of the basic test show the application of pulling force on the side surface of the finger has an advantage to distinguish the pulling force when the gripping force is applied on the finger-touching surface. Based on this result, a finger-attachment device that applies a gripping force on the finger surface and pulling force on the side surface of the finger was developed. By conducting a discrimination test to assess the hardness of the gripped material, an operator can distinguish whether the gripped material is harder or softer than a normal brain tissue. This will help in confirming whether the gripped material is a tumor. By conducting a discrimination test to assess the pulling force, an operator can distinguish the pulling-force resistance when attempting to pull off the soft material. Pulling-force feedback may help avoid the breaking of blood pipes when they are trapped in the gripper or attached to the gripped tissue. CONCLUSION: The finger-attachment device that was developed for detecting gripping- and pulling-force feedback may play an important role in the development of future neurosurgery robotic systems for precise and safe resection of brain tumors.

Damage of the right dorsal superior longitudinal fascicle by awake surgery for glioma causes persistent visuospatial dysfunction.

Patients with glioma frequently present with neuropsychological deficits preoperatively and/or postoperatively, and these deficits may remain after the chronic phase. However, little is known about postoperative recovery course of right hemispheric function. We therefore studied the characteristics and causes of persistent cognitive dysfunction in right cerebral hemispheric glioma. Eighteen patients who underwent awake surgery participated in this study. All patients who received preoperative neuropsychological examinations were assigned to two groups according to their test results: preoperative deficit and normal. They were reassessed 1 week and 3 months after surgery. The rates of remaining deficits in the deficit group at chronic phase were higher than those of the normal group for all functions. Despite preoperative normal function, the remaining rate for visuospatial cognitive deficits was the highest among all functions. The voxel-based lesion-symptom mapping analysis for visuospatial cognition revealed that a part of the medial superior and middle frontal gyri were resected with high probability in patients with low visuospatial cognitive accuracy. Our study indicates that in patients with preoperative neuropsychological deficits, these deficits tend to remain until the chronic phase. Visuospatial dysfunction frequently persists until the chronic phase, which might reflect damage to the superior longitudinal fasciclus I and II.

Radiation-induced gliomas: a report of four cases and analysis of molecular biomarkers.

Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs. Immunohistochemical (IHC) staining for isocitrate dehydrogenase 1 (IDH1), p53, alpha thalassemia/mental retardation syndrome X-linked (ATRX), and H3K27M, and direct DNA sequencing of IDH1/2, telomerase reverse transcriptase (TERT) promoter, Histone H3.3 (H3F3A) and B-Raf (BRAF) genes was performed. All tumor specimens were IDH1-, p53- and H3K27M-negative. The nuclei of tumor cells in all cases exhibited positive staining for ATRX. In direct DNA sequencing analysis, no IDH1, IDH2, TERT promoter, H3F3A or BRAF mutations were found in any of the cases. Our findings suggest that these characteristic glioma-associated molecular mutations may be rare events in RIGs. More RIGs need to be tested for analysis of molecular biomarkers to clarify the clinical and histopathological spectra of this tumor.

Biological basis and clinical study of glycogen synthase kinase- 3ß-targeted therapy by drug repositioning for glioblastoma.

BACKGROUND: Glycogen synthase kinase (GSK)-3ß has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3ß activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3ß in the primary tumor. GBM cells and a mouse model were examined for the effects of GSK3ß-inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ were tested in the mouse model and in a clinical study for recurrent GBM patients. RESULTS: Activation of GSK3ß in the tumor inversely correlated with patient survival as an independent prognostic factor. CLOVA cocktail significantly inhibited cell invasion and proliferation. The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone. CONCLUSIONS: Repositioning of the GSK3ß-inhibitory drugs improved the prognosis of refractory GBM patients with active GSK3ß in tumors. Combination of CLOVA cocktail and TMZ is a promising approach for recurrent GBM.

Glycogen synthase kinase-3ß is a pivotal mediator of cancer invasion and resistance to therapy.

Tumor cell invasion and resistance to therapy are the most intractable biological characteristics of cancer and, therefore, the most challenging for current cancer research and treatment paradigms. Refractory cancers, including pancreatic cancer and glioblastoma, show an inextricable association between the highly invasive behavior of tumor cells and their resistance to chemotherapy, radiotherapy and targeted therapies. These aggressive properties of cancer share distinct cellular pathways that are connected to each other by several molecular hubs. There is increasing evidence to show that glycogen synthase kinase (GSK)-3ß is aberrantly activated in various cancer types and this has emerged as a potential therapeutic target. In many but not all cancer types, aberrant GSK3ß sustains the survival, immortalization, proliferation and invasion of tumor cells, while also rendering them insensitive or resistant to chemotherapeutic agents and radiation. Here we review studies that describe associations between therapeutic stimuli/resistance and the induction of pro-invasive phenotypes in various cancer types. Such cancers are largely responsive to treatment that targets GSK3ß. This review focuses on the role of GSK3ß as a molecular hub that connects pathways responsible for tumor invasion and resistance to therapy, thus highlighting its potential as a major cancer therapeutic target. We also discuss the putative involvement of GSK3ß in determining tumor cell stemness that underpins both tumor invasion and therapy resistance, leading to intractable and refractory cancer with dismal patient outcomes.

Critical Neural Networks in Awake Surgery for Gliomas.

From the embarrassing character commonly infiltrating eloquent brain regions, the surgical resection of glioma remains challenging. Owing to the recent development of in vivo visualization techniques for the human brain, white matter regions can be delineated using diffusion tensor imaging (DTI) as a routine clinical practice in neurosurgery. In confirmation of the results of DTI tractography, a direct electrical stimulation (DES) substantially influences the investigation of cortico-subcortical networks, which can be identified via specific symptoms elicited in the concerned white matter tracts (eg., the arcuate fascicle, superior longitudinal fascicles, inferior fronto-occipital fascicle, inferior longitudinal fascicle, frontal aslant tract, sensori-motor tracts, optic radiation, and so forth). During awake surgery for glioma using DES, it is important to identify the anatomo-functional structure of white matter tracts to identify the surgical boundaries of brain regions not only to achieve maximal resection of the glioma but also to maximally preserve quality of life. However, the risk exists that neurosurgeons may be misled by the inability of DTI to visualize the actual anatomy of the white matter fibers, resulting in inappropriate decisions regarding surgical boundaries. This review article provides information of the critical neuronal network that is necessary to identify and understand in awake surgery for glioma, with special references to white matter tracts and the author's experiences.

Acute Progression of Recurrent Meningioma during Luteinizing Hormone-Releasing Hormone Agonist Treatment for Prostate Cancer.

BACKGROUND: Meningiomas are the most common type of benign brain tumor, and the incidence of meningioma in women is more than twofold higher than in men. Several studies have demonstrated that hormones are somehow related to the growth of meningiomas. CASE DESCRIPTION: A 72-year-old man with benign meningioma underwent tumor resection and had no recurrence for 18 years. He was found to have prostate cancer, and he received hormonal therapy with a luteinizing hormone-releasing hormone (LHRH) agonist. Two years later, he developed severe cognitive dysfunction and gait disturbance. Gadolinium-enhanced brain magnetic resonance imaging revealed a large recurrent mass and obstructive hydrocephalus. Staged resection was performed and stereotactic radiation therapy was administered against the residual tumor. His symptoms improved after endoscopic third ventriculostomy for obstructive hydrocephalus and his residual tumor remains stable. CONCLUSIONS: This is the first report of a case in which an LHRH agonist promoted the growth of a pre-existing meningioma. We suggest that patients with a history of meningioma who are receiving LHRH agonist treatment should be closely monitored.

Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery.

OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal brain parenchyma. Injury to the dorsal frontoparietal subcortical white matter pathway, i.e., the SLF I or SLF I and II, could play a causal role in this chronic deficit. A persistent spatial WM deficit, without motor and language deficits, could affect the professional life of the patient. In such cases, awake surgery would be useful to detect the spatial WM network with appropriate task during tumor exploration.