Guidelines for the Treatment of Adults With WHO Grade II Diffuse Glioma: Update

Neurosurgery 98:984–991, 2026

These updated CNS evidence-based guidelines consolidate current literature on the management of WHO grade II diffuse gliomas, covering imaging, surgical strategies, neuropathology, radiotherapy, chemotherapy, and recurrence. They summarize evidence levels, provide topic-specific recommendations, and identify areas needing higher-quality research to inform clinical decisions.

The document details unchanged, updated, and new recommendations—ranging from MRI protocols and intraoperative mapping to molecular testing and adjuvant therapy—while describing methodology, conflict-of-interest procedures, and plans for periodic revision to ensure clinical relevance.

Scope: Updated evidence-based recommendations for adult WHO grade II diffuse glioma across imaging, surgery, neuropathology/molecular markers, radiotherapy, chemotherapy, and recurrence management.

Methods: Systematic search of MEDLINE/Embase/Cochrane covering Jan 1, 2013–Jan 31, 2020, with recommendations based on evidence rather than consensus.

Imaging (minimum MRI): Minimum evaluation includes T2-weighted and pre- and post-gadolinium T1-weighted MRI; serial imaging is used to detect new enhancement or significant growth suggesting higher-grade transformation.

Imaging (advanced/PET): Diffusion plus perfusion techniques (e.g., DSC/DCE/ASL) are suggested when standard MRI cannot distinguish grade II from higher-grade gliomas; amino-acid PET (FET or FDOPA) may be added when not evident on MRI to help with grading, prognosis (FET), or progression detection (FDOPA).

Surgery: When safe/feasible, resection (gross total or subtotal) is recommended over biopsy alone to reduce progression; extent of resection should be maximized when safely possible (including for IDH-mutant and IDH–wild-type tumors).

Pathology/molecular testing: Diagnosis relies on histopathology from representative tissue; IDH mutation testing is recommended for classification/prognosis, and 1p/19q loss-of-heterozygosity testing is recommended in oligodendroglial cases for prognosis/treatment planning.

Adjuvant therapy (high-risk): For high-risk grade II diffuse glioma (age >40 or <40 without gross total resection), adding chemotherapy to radiotherapy is recommended to improve overall survival (including procarbazine/PCV-based approaches) and is also recommended without decline in neurocognitive function.

Recurrence: At suspected recurrence, advanced imaging (MRS/perfusion/diffusion/PET) is suggested; temozolomide is suggested (often initial choice) and procarbazine may help (strongest evidence in oligodendroglioma); radiation is suggested if not previously given and reirradiation may be considered.

Contemporary cohort of cerebral cavernous malformations: natural history and utility of follow-up MRI

J Neurosurg 141:1159–1167, 2024

This study reports the natural history of cerebral cavernous malformations (CCMs) in a contemporary cohort with prospectively collected data from multiple sources, access to follow-up imaging, integrated electronic medical records, and detailed imaging review by study investigators. The authors aimed to define the first prospective symptomatic hemorrhage (SH) and severe SH rates, determine the risk of a second prospective SH, and identify risk factors for SH.

METHODS From a prospectively maintained database of adult patients with radiologically defined CCM, those with radiation-induced CCM, those who underwent surgery within 3 months postdiagnosis, and those with < 1 year of followup were excluded. The patients’ medical history and radiological features of the CCM were recorded at the time of diagnosis. Follow-up annual written surveys were completed for 5 years after the initial diagnosis and then semiannually thereafter in addition to medical record and follow-up imaging review. Outcomes of interest included SH and severe SH.

RESULTS Of 315 patients, 58.7% were female and 19.7% had familial CCMs. At diagnosis, 37.1% of patients had ruptured CCMs and 28.9% of the CCMs were located in the brainstem. The 5-year cumulative rates of prospective SH and severe SH in those with ruptured CCMs at diagnosis were 41.2% and 12.8%, respectively, compared with 6.1% and 2.5% in patients with unruptured CCMs at diagnosis (p < 0.0001). Risk factors for prospective SH included a ruptured CCM at diagnosis and persistent or new hyperintensity on T1-weighted MRI performed > 3 months after baseline MRI. For those with a ruptured CCM at diagnosis, the risk of developing a second prospective SH was similar to that of developing a first SH.

CONCLUSIONS In a contemporary cohort of adult patients with CCM, the authors report 5-year SH and severe SH rates, rates of second prospective hemorrhage, and predictors of SH. Persistent or new hyperintensity on T1-weighted MRI may be a useful marker of disease activity.

First Experience With Postoperative Transcranial Ultrasound Through Sonolucent Burr Hole Covers in Adult Hydrocephalus Patients

Neurosurgery 92:382–390, 2023

Managing patients with hydrocephalus and cerebrospinal fluid (CSF) disorders requires repeated head imaging. In adults, it is typically computed tomography (CT) or less commonly magnetic resonance imaging (MRI). However, CT poses cumulative radiation risks and MRI is costly. Ultrasound is a radiation-free, relatively inexpensive, and optionally point-of-care alternative, but is prohibited by very limited windows through an intact skull.

OBJECTIVE: To describe our initial experience with transcutaneous transcranial ultrasound through sonolucent burr hole covers in postoperative hydrocephalus and CSF disorder patients.

METHODS: Using cohort study design, infection and revision rates were compared between patients who underwent sonolucent burr hole cover placement during new ventriculoperitoneal shunt placement and endoscopic third ventriculostomy over the 1-year study time period and controls from the period 1 year before. Postoperatively, trans-burr hole ultrasound was performed in the clinic, at bedside inpatient, and in the radiology suite to assess ventricular anatomy.

RESULTS: Thirty-seven patients with sonolucent burr hole cover were compared with 57 historical control patients. There was no statistically significant difference in infection rates between the sonolucent burr hole cover group (1/37, 2.7%) and the control group (0/57, P = .394). Revision rates were 13.5% vs 15.8% (P = 1.000), but no revisions were related to the burr hole or cranial hardware.

CONCLUSION: Trans-burr hole ultrasound is feasible for gross evaluation of ventricular caliber postoperatively in patients with sonolucent burr hole covers. There was no increase in infection rate or revision rate. This imaging technique may serve as an alternative to CT and MRI in the management of select patients with hydrocephalus and CSF disorders.

Blood Biomarkers and Structural Imaging Correlations Post-Traumatic Brain Injury: A Systematic Review

Neurosurgery 90:170–179, 2022

Blood biomarkers are of increasing importance in the diagnosis and assessment of traumatic brain injury (TBI). However, the relationship between them and lesions seen on imaging remains unclear.

OBJECTIVE: To perform a systematic review of the relationship between blood biomarkers and intracranial lesion types, intracranial lesion injury patterns, volume/number of intracranial lesions, and imaging classification systems.

METHODS: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, and Cumulative Index to Nursing and Allied Health Literature from inception to May 2021, and the references of included studies were also screened. Heterogeneity in study design, biomarker types, imaging modalities, and analyses inhibited quantitative analysis, with a qualitative synthesis presented.

RESULTS: Fifty-nine papers were included assessing one or more biomarker to imaging comparisons per paper: 30 assessed imaging classifications or injury patterns, 28 assessed lesion type, and 11 assessed lesion volume or number. Biomarker concentrations were associated with the burden of brain injury, as assessed by increasing intracranial lesion volume, increasing numbers of traumatic intracranial lesions, and positive correlations with imaging classification scores. There were inconsistent findings associating different biomarkers with specific imaging phenotypes including diffuse axonal injury, cerebral edema, and intracranial hemorrhage.

CONCLUSION: Blood-based biomarker concentrations after TBI are consistently demonstrated to correlate burden of intracranial disease. The relation with specific injury types is unclear suggesting a lack of diagnostic specificity and/or is the result of the complex and heterogeneous nature of TBI.

Significance of degree of neurovascular compression in surgery for trigeminal neuralgia

J Neurosurg 133:411–416, 2020

The aim of this study was to identify preoperative imaging predictors of surgical success in patients with classic trigeminal neuralgia (cTN) undergoing microvascular decompression (MVD) via retrospective multivariate regression analysis.

METHODS All included patients met criteria for cTN and underwent preoperative MRI prior to MVD. MR images were blindly graded regarding the presence and severity (i.e., mild or severe) of neurovascular compression (NVC). All patients were contacted by telephone to determine their postoperative pain status.

RESULTS A total of 79 patients were included in this study. Sixty-two patients (78.5%) were pain-free without medication following MVD. The following findings were more commonly observed with the symptomatic nerve when compared to the contralateral asymptomatic nerve: NVC (any form), arterial compression alone, NVC along the proximal trigeminal nerve, and severe NVC (p values < 0.0001). The only imaging variable that was a statistically significant predictor of being pain-free without medication following MVD was severe NVC. Patients with severe NVC were 6.36 times more likely to be pain-free following MVD compared to those without severe NVC (p = 0.007).

CONCLUSIONS In patients with cTN undergoing MVD, severe NVC on preoperative MRI is a strong predictor of an excellent surgical outcome.

 

Predictors of postoperative motor function in rolandic meningiomas

J Neurosurg 130:1283–1288, 2019

Resection of supratentorial meningiomas is generally considered a low-risk procedure, but tumors involving the rolandic cortex present a unique challenge. The rate of motor function deterioration associated with resecting such tumors is not well described in the literature. Thus, the authors sought to report the rates and predictors of postoperative motor deficit following the resection of rolandic meningiomas to assist with patient counseling and surgical decision-making.

METHODS An institution’s pathology database was screened for meningiomas removed between 2000 and 2017, and patients with neuroradiological evidence of rolandic involvement were identified. Parameters screened as potential predictors included patient age, sex, preoperative motor severity, tumor location, tumor origin (falx vs convexity), histological grade, FLAIR signal (T2-weighted MRI), venous involvement (T1-weighted MRI with contrast), intratumoral hemorrhage, embolization, and degree of resection (Simpson grade). Variables of interest included preoperative weakness and postoperative motor decline (novel or worsened permanent deficit). The SPSS univariate and bivariate analysis functions were used, and statistical significance was determined with alpha < 0.05.

RESULTS In 89 patients who had undergone resection of convexity (80.9%) or parasagittal (19.1%) rolandic meningiomas, a postoperative motor decline occurred in 24.7%. Of 53 patients (59.6%) with preoperative motor deficits, 60.3% improved, 13.2% were unchanged, and 26.4% worsened following surgery. Among the 36 patients without preoperative deficits, 22.2% developed new weakness. Predictors of preoperative motor deficit included tumor size (41.6 vs 33.2 cm3, p = 0.040) and presence of FLAIR signal (69.8% vs 50.0%, p = 0.046). Predictors of postoperative motor decline were preoperative motor deficit (47.2% vs 22.2%, p = 0.017), minor (compared with severe) preoperative weakness (25.6% vs 21.4%, p < 0.001), and preoperative embolization (54.5% vs 20.5%, p = 0.014). Factors that trended toward significance included parafalcine tumor origin (41.2% vs 20.8% convexity, p = 0.08), significant venous involvement (44.4% vs 23.5% none, p = 0.09), and Simpson grade II+ (34.2% vs 17.6% grade I, p = 0.07).

CONCLUSIONS Resection of rolandic area meningiomas carries a high rate of postoperative morbidity and deserves special preoperative planning. Large tumor size, peritumoral edema, preoperative embolization, parafalcine origin, and venous involvement may further increase the risk. Alternative surgical strategies, such as aggressive internal debulking, may prevent motor decline in a subset of high-risk patients.

 

The Relationship Between Preoperative Clinical Presentation and Quantitative Magnetic Resonance Imaging Features in Patients With Degenerative Cervical Myelopathy

Neurosurgery 80:121–128, 2017

Degenerative cervical myelopathy encompasses a group of conditions resulting in progressive spinal cord injury through static and dynamic compression. Although a constellation of changes can present on magnetic resonance imaging (MRI), the clinical significance of these findings remains a subject of controversy and discussion.

OBJECTIVE: To investigate the relationship between clinical presentation and quantitative MRI features in patients with degenerative cervical myelopathy.

METHODS: A secondary analysis of MRI and clinical data from 114 patients enrolled in a prospective, multicenter study was conducted. MRIs were assessed for maximum spinal cord compression (MSCC), maximum canal compromise (MCC), signal changes, and a signal change ratio (SCR). MRI features were compared between patients with and those without myelopathy symptoms with the use of t tests. Correlations between MRI features and duration of symptoms were assessed with the Spearman ρ.

RESULTS: Numb hands and Hoffmann sign were associated with greater MSCC (P < .05); broad-based, unstable gait, impairment of gait, and Hoffmann sign were associated with greaterMCC (P<.05); andnumbhands,Hoffmann sign, Babinski sign, lower limb spasticity, hyperreflexia, and T1 hypointensitywere associated with greater SCR (P<.05). Patientswith a T2 signal hyperintensity had greater MSCC and MCC (P < .001).

CONCLUSION: MSCC was associated with upper limb manifestations, and SCR was associated with upper limb, lower limb, and general neurological deficits. Hoffmann sign occurred more commonly in patients with a greater MSCC,MCC and SCR. The Lhermitte phenomenon presented more commonly in patientswith a lower SCR and may be an early indicator of mild spinal cord involvement. Research to validate these findings is required.

Internal and external spheno-orbital meningioma varieties: different outcomes and prognoses

SO Meningiomas

Acta Neurochir (2016) 158:1587–1596

Internal variation among spheno-orbital meningiomas  (SOM) is surgically challenging. Optic canal invasion  management is discussed.

Method This retrospective study includes 70 patients with  SOM who underwent surgery between 1995 and 2012.  Preoperative ophthalmological, neurological and aesthetic  clinical signs were collected. All patients benefitted from repeated  tomography and magnetic resonance imaging (MRI).  The surgical team consisted of a neurosurgeon and a plastic  surgeon. In the majority of cases, resection was followed by  bone reconstruction using an autologous iliac crest graft. The  extent of resection was evaluated on the dural and osseous  sides. Early clinical outcomes, long-term follow-up, recurrence  and adjuvant therapies were reported.

Results The mean age was 52 years old, and 91 % of the  patients were women. Initial symptoms primarily included  proptosis (65 %), decreased visual acuity (39 %) and soft  tissue tumefaction (16 %).We classified 40 cases as the internal  variety when considering the inner third of the greater  wing of the sphenoid, optic canal, anterior clinoid process or  cavernous sinus. The remaining cases were described as the  external variety. The complete resection rates for the internal  and external varieties were 12 % and 61 %, respectively  (P< 0.001). In total, 90% of cases were grade I meningiomas.  For grade I, we reported 30 % recurrence, and 50 % of these  cases recurred in the first 2 years. Grade II cases without early  adjuvant radiotherapy increased at 2 years.We did not observe  any difference in recurrence rate among grade I tumours with  or without tumour remnants. At the end of follow-up, visual  acuity was stabilised or increased in 88 % of patients. In addition,  14 % of patients experienced persistent pain at the  location of the iliac harvesting site.

Conclusions The internal SOM variety exhibited a reduced  total resection rate and a shorter progression-free survival  (PFS). Unroofing of the optic canal extended PFS. Among  grade I cases, the persistence of a negligible tumour remnant  did not alter the probability of recurrence. For superior grades,  radiotherapy must be administered in addition to surgery as  soon as possible. SOMs require prolonged follow-up.  Autologous iliac reconstruction is related to substantial morbidity  and could be replaced by prosthetic bone threedimensional  reconstruction.

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage

J Neurosurg 125:128–136, 2016

This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI).

Methods: Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)–measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated.

Results: Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD–measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI.

Conclusions: Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD–measured BFV increase or persisting coma, do not contribute to information gain.

Prognostic factors of craniopharyngioma with special reference to autocrine/paracrine signaling: underestimated implication of growth hormone receptor

Prognostic factors of craniopharyngioma with special reference to autocrine-paracrine signaling

Acta Neurochir (2015) 157:1731–1740

Craniopharyngioma is a slow-growing tumor classified as benign, but tight adhesion and significant local infiltration to the vital structures are common. In spite of improvement of modern microsurgery techniques and precise anatomical understanding not few cases of this tumor recur, and long-termtumor control and maintenance of quality of life are sometimes difficult. However, very little is known about the effects of the molecular characters of craniopharyngioma on the prognosis.

Methods Ninety eight cases of craniopharyngioma surgically treated at the Department of Neurosurgery, Tohoku University Hospital and Kohnan Hospital from April 1996 to May 2014, 45 males and 53 females aged from 2 to 80 years (mean, 40.84 years) were retrospectively reviewed, and postoperative outcomes and the possible involvement of the autocrine/ paracrine mechanism were investigated. The patients were followed up at intervals of 6 months to assess tumor recurrence, and clinical outcomes were correlated with the findings of immunohistochemical examinations used growth hormone receptor (GHR) and downstream hormones. The follow-up period ranged from 3 to 209 months.

Results Hormone expression was examined in 88 patients, of which 46 specimens (52.3 %) showed high expression of GHR. The GHR high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p=0.007). Simultaneous high expression of growth hormone (GH) and GHR was found in 33 specimens (37.5 %), and the high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p=0.011). No other hormones showed statistically significant differences in outcomes.

Conclusions High expression of GHR is associated with shorter duration of postoperative stable disease in patients with craniopharyngioma. If the surgical specimens were craniopharyngiomas with high GHR expression, GH supplementation would be introduced quite prudently.

Can Preoperative Imaging Predict Tumor Involvement of the Anterior Clinoid in Clinoid Region Meningiomas?

Can Preoperative Imaging Predict Tumor Involvement of the Anterior Clinoid in Clinoid Region Meningiomas?

Neurosurgery 77:525–530, 2015

Anterior clinoid region meningiomas may infiltrate the bone over which they arise, therefore requiring an anterior clinoidectomy to achieve a Simpson grade 1 resection. A clinoidectomy, however, is not without risks.

OBJECTIVE: We performed a study of diagnostic accuracy investigating whether preoperative imaging could predict tumor involvement of the clinoid, and thereby tailor the degree of bony removal.

METHODS: Patients having undergone resection of a clinoid region meningioma between 2001 and 2011 were identified. Included in further analysis were those patients in whom a clinoidectomy was performed with subsequent pathologically confirmed presence or absence of tumor in the clinoid process on decalcified specimens. Two neuroradiologists, blinded to pathology results, independently reviewed available preoperative imaging and stated whether or not they anticipated the clinoid to be involved by tumor. Interobserver agreement and the ability to accurately predict tumor involvement of the clinoid were then analyzed.

RESULTS: Sixty-two patients were included in the final analysis. Interobserver agreement was 100%. Sensitivity and specificity of preoperative imaging to predict tumor involvement was 89% and 52%, respectively, with positive and negative likelihood ratios of 1.85 and 0.20. Positive and negative predictive values were 73% and 76%, respectively.

CONCLUSION: Preoperative imaging of clinoid region meningiomas can accurately predict the presence or absence of tumor involvement of the clinoid in only approximately 75% of cases. In light of the fact that a quarter of patients with radiographically negative clinoids will have tumor present on pathological analysis, we recommend a clinoidectomy for all clinoid region meningiomas.

Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors

Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors

Neurosurg Focus 36 (2):E1, 2014

The intraoperative clear delineation between brain tumor and normal tissue in real time is required to ensure near-complete resection without damaging the nearby eloquent brain. Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems in use, but they are not optimized to the low concentration and amount of ICG. The authors present a novel proof-of-concept near-infrared (NIR) imaging system using a standard charge-coupled device (CCD) camera for visualizing low levels of ICG attached to the tumors. This system is small, inexpensive, and sensitive. The imaging system uses a narrow-band laser at 785 nm and a notch filter in front of the sensor at the band. The camera is a 2-CCD camera, which uses identical CCDs for both visible and NIR light.

Methods. The NIR system is tested with serial dilution of BLZ-100 from 1 μM to 50 pM in 5% Intralipid solution while the excitation energy is varied from 5 to 40 mW/cm2. The analog gain of the CCD was changed from 0, 6, and 12 dB to determine the signal-to-noise ratio. In addition to the Intralipid solution, BLZ-100 was injected 48 hours before euthanizing the mice that were implanted with the human glioma cell line. The brain was removed and imaged using the NIR imaging system.

Results. The authors’ results show that the NIR imaging system using a standard CCD is able to visualize the ICG down to 50 nM of concentration with a high signal-to-noise ratio. The preliminary experiment on human glioma implanted in mouse brains demonstrated that BLZ-100 has a high affinity for glioma compared with normal brain tissue. Additionally, the results show that NIR excitation is able to penetrate deeply and has a potential to visualize metastatic lesions that are separate from the main tumor.

Conclusions. The authors have seen that BLZ-100 has a very high affinity toward human gliomas. They also describe a small, cost-effective, and sensitive NIR system for visualizing brain tumors tagged using BLZ-100. The authors hope that the use of BLZ-100 along with NIR imaging will be useful to delineate the brain tumors in real time and assist surgeons in near-complete tumor removal to increase survival and reduce neurological deficits.

Distribution of cerebellar tonsil position: implications for understanding Chiari malformation

Cerebellar tonsil position

J Neurosurg 119:812–819, 2013

Prior attempts to define normal cerebellar tonsil position have been limited by small numbers of patients precluding analysis of normal distribution by age group. The authors’ objective in the present study was to analyze cerebellar tonsil location in every age range.

Methods. Two thousand four hundred patients were randomly selected from a database of 62,533 consecutive patients undergoing MRI and were organized into 8 age groups. Magnetic resonance images were directly examined for tonsil location, morphology, and other features. Patients with a history or imaging findings of posterior fossa abnormalities unrelated to Chiari malformation (CM) were excluded from analysis. The caudal extent of the cerebellar tonsils was measured at the midsagittal and lowest parasagittal positions.

Results. The mean tonsil height decreased slightly with advancing age into young adulthood and increased with advancing age in the adult age range. An increasing age in the adult age range was associated with a decreased likelihood of a tonsil position 5 mm or more below the foramen magnum (p = 0.0004). In general, the lowest tonsil position in each age group was normally distributed. Patients with pegged morphology were more likely to have a tonsil location at least 5 mm below the foramen magnum (85%), as compared with those having intermediate (38%) or rounded (2%) morphology (p < 0.0001). Female sex was associated with a lower mean tonsil position (p < 0.0001). Patients with a lower tonsil position also tended to have an asymmetrical tonsil position, usually lower on the right (p < 0.0001).

Conclusions. Cerebellar tonsil position follows an essentially normal distribution and varies significantly by age. This finding has implications for advancing our understanding of CM.