Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma.

BACKGROUND AND OBJECTIVES: Patients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory. METHODS: We retrospectively included patients with IDH1/2-mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence. RESULTS: We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH-mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH-mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037). DISCUSSION: This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.

Prevalence of seizures in brain tumor: A meta-analysis.

OBJECTIVES: Prevalence of seizures in brain tumors vary substantially between studies even with similar histopathological types. We aimed to identify the seizure prevalence of the commonest types of brain tumors. METHODS: Systematic computerized search of PubMed, Embase, and Web of Science were performed. The meta-analysis of pooled prevalence and 95 % confidence interval (CI) for tumor-related seizures were calculated by using a random effect model. Based on the 2014 epilepsy definition, a mean seizure prevalence of 60 % is used to indicate high seizure prevalence in this study. RESULTS: 74 studies that reported seizure prevalence with 23,116 patients were included in this meta-analysis. These tumors has higher seizure incidence rate (at least 60 %) with pooled prevalence of 63 % for adult with low-grade astrocytoma (95 % CI: 57-68 %), 65 % for oligodendroglioma (95% CI: 57-72 %), 72 % for oligoastrocytoma (95 % CI: 67-77 %), 81 % for ganglioglioma (95 % CI: 66-97 %) and 94 % for DNET (94 % CI: 83-100 %). CONCLUSION: This study highlights the type of brain tumors that carry a high seizure prevalence. Screening for subtle seizures and early management of seizures may be beneficial in patients with low-grade astrocytoma (adult), oligodendroglioma, oligoastrocytoma, ganglioglioma or DNET brain tumor.

Seizures in patients with IDH-mutated lower grade gliomas.

PURPOSE: Most patients with Lower Grade Gliomas (LGG) present with epileptic seizures. Since the advent of molecular diagnostics, more homogenous sub-entities have emerged, including the isocitrate dehydrogenase-mutated (IDH-mutated) astrocytomas and 1p19q-codeleted oligodendrogliomas. We aimed to describe the occurrence of seizures in patients with molecularly defined LGG pre- and postoperatively and to analyze factors affecting seizure status postoperatively. METHODS: A population-based cohort of 130 adult patients with IDH-mutated WHO grade 2 or 3 astrocytomas and oligodendrogliomas was assessed pertaining to seizure burden before and after surgery. RESULTS: Fifty-four (79.4%) patients with astrocytoma and 45 (72.6%) patients with oligodendroglioma had a history of seizures before surgery. At 12 months postoperatively, 51/67 (76.1%) patients with astrocytoma and 47/62 (75.8%) patients with oligodendrogliomas were seizure free. In a multivariable logistic regression analysis, lower extent of resection (EOR) (OR 0.98; 95% CI 0.97-1.00, p = 0.01) and insular tumor location (OR 5.02; 95% CI 1.01-24.87, p = 0.048) were associated with presence of seizures within 1 year postoperatively in the entire LGG cohort. In sub-entities, EOR was in a similar manner associated with seizures postoperatively in astrocytomas (OR 0.98; 95% CI 0.96-0.99, p < 0.01) but not in oligodendrogliomas (p = 0.34). CONCLUSION: Our results are well in line with data published for non-molecularly defined LGG with a large proportion of patients being seizure free at 1 year postoperative. Better seizure outcome was observed with increased EOR in astrocytomas, but this association was absent in oligodendrogliomas.

Seizure in Indonesian Glioma Patients: Associated Risk Factors and Impact on Survival.

OBJECTIVE: Seizure is commonly found in patients with glioma. This study aimed to find risk factors for seizures in Indonesian patients with glioma. We also sought to determine the association between seizure and survival in this patient population. METHODS: Patients with glioma were enrolled from the Dr. Sardjito General Hospital and other hospitals in Yogyakarta Province, Indonesia. Detailed demographic and clinical data were collected from medical records. DNA extraction and polymerase chain reaction (PCR) were performed to detect IDH1 mutation. Tumor tissue samples were stained by hematoxylin-eosin and classified according to the 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Expression of Ki-67 was detected by immunohistochemistry staining. Survival data were also collected. RESULTS: In total, 107 patients were included in the analysis. Age, gender, history of smoking, tumor side, tumor grade, Ki-67 expression, and IDH1 mutation were not associated with seizure. Tumors involving the frontal lobe (p=0.037) and oligodendroglioma histology (p=0.031) were associated with the development of seizures in this study. However, multivariate analysis showed that only oligodendrogial histology was associated with seizure [p=0.032, odds ratio (OR) = 4.77, 95% confidence interval (CI) = 1.146-19.822]. Patients with seizures have significantly longer median overall survival than patients without seizures (69.3±25.01 vs. 10.6±6.14 months, respectively, p=0.04). CONCLUSION: This study showed that seizure in patients with glioma in Indonesia is associated with frontal lobe location and oligodendroglioma histology. Patients with seizures also have significantly longer overall survival. 
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Low-grade developmental and epilepsy associated brain tumors: a critical update 2020.

Brain tumors represent the second most frequent etiology in patients with focal seizure onset before 18 years of age and submitted to epilepsy surgery. Hence, this category of brain tumors, herein defined as low-grade, developmental, epilepsy-associated brain tumors (LEAT) is different from those frequently encountered in adults as (A): 77% of LEAT occur in the temporal lobe; (B): the vast majority of LEAT are of low malignancy and classified as WHO I°; (C): LEAT are often composed of mixed glial and neuronal cell components and present with variable growth patterns including small cysts or nodules; (D): LEAT do not share common gene driving mutations, such as IDH1 or 1p/19q co-deletions. Characteristic entities comprise the ganglioglioma (GG), the dysembryoplastic neuroepithelial tumor (DNT), the angiocentric glioma (AG), the isomorphic diffuse glioma (IDG) and the papillary glio-neuronal tumor (PGNT), representing 73.2% of 1680 tumors collected in a large German series of 6747 patients submitted to epilepsy surgery. In the realm of exciting discoveries of genetic drivers of brain tumors new genes have been also reported for LEAT. BRAF V600E mutations were linked to GG with CD34 expression, FGFR1 mutations to DNT, MYB alterations to AG and also IDG and PRKCA fusions to PGNT, suggesting the possibility to also develop a genetically driven tumor classification scheme for LEAT. Rare availability of LEAT in a single center is a challenging obstacle, however, to systematically unravel the neurobiological nature and clinical behavior of LEAT. Other challenges in need of clarification include malignant tumor progression of LEAT entities, seizure relapse in patients following bulk tumor resection and the controversial issue of associated focal cortical dysplasia as additional pathomechanism. In order to advance our understanding and promote reliable diagnostic work-up of LEAT, we recommend, therefore, international collaboration to achieve our goals.

Molecular Aberrations Associated with Seizure Control in Diffuse Astrocytic and Oligodendroglial Tumors.

Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135-218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.

[Difficulties in distinguishing abnormal intensities associated with convulsion from tumor on MRI: a case report].

A 48-year-old man was admitted to our department with generalized convulsive seizures followed by recurrent partial clonic convulsions in the left face and arm. Convulsions stopped temporarily after administration of diazepam, fosphenytoin, and levetiracetam. However, frequent partial seizures occurred repeatedly and general anesthesia was required to control seizures. Diffusion-weighted and T2-weighted images revealed a high-intensity lesion in the right frontal lobe. A tumor-like area in the white matter showed high intensity on T2-weighted images with ring enhancement on gadolinium-enhanced T1-weighted images. An area of frontal cortex near the tumor was also enhanced. Brain surgery was performed for the purposes of diagnosis, seizure control and tumor resection. Histological findings demonstrated oligodendroglioma in the ring-enhancing area, but not in the frontal cortex. This fact indicated that contrast enhancement of the frontal cortex was caused by status epilepticus. It is important to recognize that status epilepticus could cause contrast enhancement on magnetic resonance imaging.

Case Report of Rarely Described Polymorphous Low-Grade Neuroepithelial Tumor of the Young and Comparison with Oligodendroglioma.

BACKGROUND: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a central nervous system tumor that shares many qualities with oligodendroglioma but is rarely and only very recently described as a distinct entity in the literature. CASE DESCRIPTION: A previously healthy, 19-year-old man presented with new onset of seizures. Imaging showed an intracranial mass, which was treated with surgical removal. Preoperative and postoperative magnetic resonance imaging, histopathologic examination, genetic testing, and immunohistochemical staining all supported a diagnosis of PLNTY. CONCLUSIONS: Diagnostic investigation of PLNTY shows many similarities with oligodendroglioma, and thus these entities can be mistaken for one another. Certain studies are needed to distinguish PLNTY and other dysembryoplastic neuroepithelial tumors, such as oligodendroglioma.

Superior Sagittal Sinus Invasion by Malignant Glioma: Case Report and Literature Review

Anaplastic oligodendrogliomas (AOs) correspond to 23% of all oligodendrogliomas. They correspond to a tumor with malignant histological characteristics, focal or diffuse, associated with a worse prognosis. In the present case report, we describe the case of a 30-year-old female submitted to resection of a right parietal lesion whose histology showed to be an AO. She underwent complementary treatment with chemotherapy and radiotherapy according to the Roger Stupp protocol. Four years after the initial diagnosis, there was tumor recurrence within the superior sagittal sinus, with no evidence of recurrence elsewhere. In the literature, we have found no similar published case reinforcing the rarity of this condition.

A case report about oligodendrogliomas of the fourth ventricle.

RATIONALE: Oligodendrogliomas are usually located in the frontal, parietal and the temporal lobe, with the ones in the fourth ventricle quite rare. Hence we want to introduce a case about the rare disease. PATIENT CONCERNS: An eight-year old boy complained of progressive headache, dizziness and vomit for about 2 months. Then the slight ataxia was found by the physical examinations, with no sensory disturbances and other motor disturbances. DIAGNOSES: Abnormal signals on the fourth ventricle were found by the preoperative brain computed tomography (CT) scan and magnetic resonance imaging (MRI) scan. So the patient accepted a gross total resection of the lesion with pathologically confirmed oligodendroglioma. INTERVENTIONS: Radiotherapy was then delivered in 27 fractions at 2Gy per fraction after the operation, with one fraction daily for five days weekly. No other therapies were used for the patient. OUTCOMES: The brain MRI was used for follow-up every three months until now when he has finished all therapies for more than one year. No progressive behaviors (for example, headache, dizziness, vomit and other symptoms about cerebellar tonsillar hernia) or images have been presented. And the follow-up will be continued. LESSONS: Although oligodendrogliomas are usually located in the frontal lobe, with the ones of fourth ventricle extremely rare, they must be kept in mind all times. Treatments applied to our case may be provided as a reference for clinicians. Furthermore, the maximal range of resection, histologically proved oligodendroglioma and the 1p/19q loss of heterozygosity are associated with favorable prognosis.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) mimicking Whipple's disease: a case report and literature review.

INTRODUCTION: Diffuse leptomeningeal glioneuronal tumor is a new entity under the neuronal and mixed neuronal-glial tumors in the WHO 2016 updated classification and commonly found in children and adolescents. The initial diagnosis is challenging because of its non-specific radiologic feature and negative CSF cytology analysis. A 17 years male was presented with intractable headache subsequently followed by back pain and joint pain. MRI showed enhancement of arachnoid membrane at basal cistern, bilateral sylvian fissure and cerebral cistern with slight enlargement of ventricles. There were no evidences of infection in CSF and blood samples. Based on the duodenal biopsy and prodromal symptom of joint pain, the patient was suspected of having Whipple's disease. Eleven months after the onset, a small mass lesion was observed at the anterior horn of right lateral ventricle. The histology was remarkable for anaplastic oligodendroglioma. Immunostainings revealed positivity for GFAP, Olig2, synaptophysin and negativity for IDH1 mutation, H3K27M. MIB1 labeling index was 40% and 1p19q FISH analysis showed only 1p deletion. Therefore, a final diagnosis of DLGNT was made. CONCLUSION: DLGNT should be included as a differential diagnosis of patients with leptomeningeal-enhanced and high CSF protein level with normal white blood cell count.

Pediatric Basal Ganglia Region Tumors: Clinical and Radiologic Features Correlated with Histopathologic Findings.

PURPOSE: To summarize the clinical and radiologic features of pediatric basal ganglia region tumors (PBGRT) in correlation with their histopathologic findings to reduce inappropriate surgery and identify tumors that can benefit from maximal safe resection. METHODS: The records of 35 children with PBGRT treated in our hospital from December 2011 to December 2015 were analyzed retrospectively. The clinical and radiologic features of these tumors were summarized and correlated with their histopathologic diagnosis. RESULTS: Our series included 15 astrocytomas and 11 germ cell tumors (GCTs). Basal ganglia astrocytomas were characterized by various clinical presentations and an ill-circumscribed mass with the involvement of surrounding structures on neuroimaging and mostly occurred in the first decade of life (n = 10; 66.7%). Basal ganglia GCT mostly occurred in the second decade of life (n = 8; 72.7%) with hemiparesis as the most common symptom (n = 9; 81.8%). The tumors were located predominantly in the caput of caudate nucleus (n = 8; 72.7%) with hemiatrophy as the typical sign (n = 8; 72.7%). Occasionally, other tumors also could occur in this region, including primitive neuroectodermal tumor (n = 1), atypical teratoid/rhabdoid tumor (n = 1), anaplastic ependymoma (n = 1), lymphoma (n = 1), extraventricular neurocytoma (n = 1), gangliogliomas (n = 2), oligodendroglioma (n = 1), and dysembryoplastic neuroepithelial tumor (n = 1). CONCLUSIONS: Astrocytoma and GCT are the most common PBGRTs. Low-grade astrocytomas could benefit from maximal surgical resection, whereas GCTs merit neoadjuvant chemoradiation therapy followed by second-look surgery. We advocate routine testing of tumor markers and analysis of their clinical and radiologic features to optimize the therapeutic strategy.

Delusional Disorder Arising From a CNS Neoplasm.

Erotomania arising from a central nervous system (CNS) neoplasm has not been previously described. Here, we present the first known case, to our knowledge, of erotomania with associated persecutory delusions arising following diagnosis and treatment of a left frontal lobe brain tumor.