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Xiao Y, Nie Z, Huang J, Zhao J, Dong C, Zou Y, Li Z, Yan B, Hu Y, Yang F, Lee JW, Lin AP, Tobochnik S, Zhou M, Lei Z. Risk Factors and Prognostic Implications of Tumor-Related Epilepsy in Diffuse Glioma Patients: A Real-World Multicenter Study. Brain Behav 2025; 15:e70510. [PMID: 40320911 PMCID: PMC12050638 DOI: 10.1002/brb3.70510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 04/02/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025] Open
Abstract
PURPOSE The relevance of tumor-related epilepsy (TRE) to glioma survival is controversial. This study aimed to assess the risk factors and prognostic impact of TRE in adult patients with diffuse gliomas by integrating clinical, radiological, and molecular data. METHODS This multicenter retrospective study included 1036 adult patients with diffuse gliomas from local hospitals and the POLA Network. Patients were categorized into three prognostic groups: lower-grade oligodendroglioma/astrocytoma (OD/AC, II-III, IDH-MT), not otherwise specified or not elsewhere classified (NOS/NEC, II-III, IDH-WT), and high-grade gliomas (HGG, IV). Clinico-radiological, molecular, and therapeutic factors were analyzed using univariate and multivariate logistic regression, with the Cox proportional hazards model applied to identify independent prognostic factors for progression-free survival (PFS) and overall survival (OS). RESULTS TRE occurred in 44.4% of OD/AC patients, 25.8% of NOS/NEC patients, and 16.5% of HGG patients. Multivariate analysis identified age as the only significant independent correlate of TRE in the OD/AC group (OR = 0.961; p = 0.004), while the absence of deep structure involvement was independently associated with TRE in the NOS/NEC and HGG groups. In univariate analysis, the presence of TRE was associated with longer PFS and OS across all groups, particularly in the NOS/NEC group, where patients with TRE had a median PFS of 35.2 months compared to 13.6 months in those without TRE (p = 0.02), but was not a significant predictor in multivariate analyses. TRE was the only factor significantly associated with maintaining histological grade at recurrence (HR = 0.094; p = 0.005). CONCLUSION TRE was not a strong independent prognostic factor after controlling for clinical and molecular tumor features, suggesting that the prognostic relevance of TRE is likely driven by underlying glioma biology and other associated clinical factors.
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Affiliation(s)
- Yao Xiao
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Zhuang Nie
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Jinsha Huang
- Department of Neurology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
| | - Jie Zhao
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Chengjun Dong
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Yan Zou
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Zikai Li
- General Hospital of Yangtze River ShippingWuhan Brain HospitalWuhanChina
| | - Bingqing Yan
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Yue Hu
- Cancer Center, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
| | - Fan Yang
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Jong Woo Lee
- Department of NeurologyBrigham and Women's HospitalBostonMassachusettsUSA
| | - Alexander P. Lin
- Department of RadiologyBrigham and Women's HospitalBostonMassachusettsUSA
| | - Steven Tobochnik
- Department of NeurologyBrigham and Women's HospitalBostonMassachusettsUSA
| | - Min Zhou
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
| | - Ziqiao Lei
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Key Laboratory of Molecular ImagingWuhanHubeiChina
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Zhang Y, Li H, Zhang B, Zhang J, Li C. Efficacy and safety of levetiracetam in preventing postoperative seizures in adult patients with brain tumors: a meta-analysis. Front Neurol 2025; 16:1543905. [PMID: 40125402 PMCID: PMC11925779 DOI: 10.3389/fneur.2025.1543905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/14/2025] [Indexed: 03/25/2025] Open
Abstract
Objective Seizures are one of the most common symptoms in patients with brain tumor. The efficacy of prophylactic antiepileptic agents in reducing postoperative seizures in patients with brain tumor remains disputed. We conducted this meta-analysis to evaluate the efficacy and safety of levetiracetam in preventing seizures in adult patients with brain tumor. Review methods We gathered studies comparing the effectiveness of levetiracetam with other antiepileptic drugs in preventing postoperative seizures in individuals with brain tumor from 2008 to 2023. We used the search terms levetiracetam, brain tumor, prevention, and seizures to retrieve relevant studies from the Pubmed, Medline, EMBASE, China National Knowledge Infrastructure, and Wanfang databases. The meta-analysis was conducted using RevMav 5.3 software. Results After the literature search and screening, nine English-language studies involving a total of 2,433 patients were analyzed. The meta-analysis revealed that levetiracetam had higher efficacy for preventing overall seizures than the control intervention (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.44-0.71, p < 0.00001). Subgroup analyses revealed that the efficacy of levetiracetam was superior to that of sodium valproate (OR 0.53, 95% CI 0.39-0.72, p < 0.0001) and phenytoin sodium (OR 0.35, 95% CI 0.19-0.62, p = 0.0004). No statistically significant difference in the efficacy of early seizure prophylaxis (OR 0.55, 95% CI 0.15-2.04, p = 0.37) was observed. The subgroup analysis revealed that the efficacy of levetiracetam for preventing early seizures was better than that of phenytion sodium (OR 0.13, 95% CI 0.03-0.56, p = 0.006). No statistically significant difference was noted in the preventive efficacy against late seizures (OR 0.75, 95% CI 0.27-2.03, p = 0.57). The incidence of adverse drug reactions was lower in the levetiracetam group than in the control group (OR 0.18, 95% CI 0.05-0.64, p = 0.008). Further subgroup analyses revealed that the incidence of adverse drug reactions in the levetiracetam group was lower than that in the phenytion sodium group (OR 0.06, 95% CI 0.02-0.21, p < 0.001). Conclusion Prophylactic levetiracetam decreases the frequency of postoperative seizures, particularly early postoperative seizures, in individuals with brain tumor, with superior effectiveness to phenytion sodium and sodium valproate. In addition, levetiracetam induced only minor adverse effects, with a lower occurrence rate of adverse reactions than phenytion sodium and valproate. Nevertheless, a potential for bias exists. Due to the limited number of high-quality randomized controlled trials included in this meta-analysis, prospective, multicenter, ethnically diverse, high-quality studies on levetiracetam are essential to determine the efficacy of preventive levetiracetam in managing postoperative seizures. Systematic review registration https://inplasy.com/inplasy-2023-6-0091/.
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Affiliation(s)
- Yongyi Zhang
- School of Pharmacy, Shandong Second Medical University, Weifang, China
| | - Haoming Li
- Clinical Medicine School, Shandong Second Medical University, Weifang, China
| | - Bin Zhang
- Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, China
| | - Junchen Zhang
- Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, China
| | - Chengde Li
- School of Pharmacy, Shandong Second Medical University, Weifang, China
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Stritzelberger J, Gesmann A, Fuhrmann I, Balk S, Reindl C, Madžar D, Uhl M, Welte TM, Brandner S, Eisenhut F, Dörfler A, Coras R, Adler W, Schwab S, Putz F, Fietkau R, Distel L, Hamer HM. Status epilepticus in patients with glioblastoma: Clinical characteristics, risk factors, and epileptological outcome. Seizure 2023; 112:48-53. [PMID: 37748366 DOI: 10.1016/j.seizure.2023.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 09/13/2023] [Accepted: 09/14/2023] [Indexed: 09/27/2023] Open
Abstract
PURPOSE Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients. METHODS We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics. RESULTS In the final cohort, 292/520 (56.2 %) patients developed seizures, with 48 (9.4 % of the entire cohort and 16.4 % of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2 %) and the first manifestation of epilepsy in 18 PWE (6.2 %). Most SE episodes occurred postoperatively (n = 37, 77.1 %). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8 %), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7 %) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5 %) cases. CONCLUSION Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2 % of the cases. Higher STESS and CCI were associated with adverse SE outcomes.
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Affiliation(s)
- Jenny Stritzelberger
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE.
| | - Anna Gesmann
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Imke Fuhrmann
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Stefanie Balk
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Caroline Reindl
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Dominik Madžar
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Martin Uhl
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Tamara M Welte
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Sebastian Brandner
- Department of Neurosurgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Felix Eisenhut
- Department of Neuroradiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Arnd Dörfler
- Department of Neuroradiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Roland Coras
- Department of Neuropathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Werner Adler
- Department of Biometry and Epidemiology and Department of Psychosomatic Medicine and Psychotherapy, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany
| | - Stefan Schwab
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
| | - Florian Putz
- Department of Radiooncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Rainer Fietkau
- Department of Radiooncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Luitpold Distel
- Department of Radiooncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Hajo M Hamer
- Epilepsy Center, Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Full member of ERN EpiCARE
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Nåhls NS, Leskelä RL, Saarto T, Hirvonen O, Anttonen A. Effect of palliative care decisions making on hospital service use at end-of-life in patients with malignant brain tumors: a retrospective study. BMC Palliat Care 2023; 22:39. [PMID: 37032344 PMCID: PMC10084612 DOI: 10.1186/s12904-023-01154-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 03/24/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND Palliative care (PC) improves Quality of life and reduces the symptom burden. Aggressive treatments at end of life (EOL) postpone PC. The aim of this single-center retrospective study was to evaluate the timing of the PC decision i.e., termination of cancer-specific treatments and focusing on symptom-centered PC, and its impact on the use of tertiary hospital services at the EOL. METHODS A retrospective cohort study on brain tumor patients, who were treated at the Comprehensive Cancer Center of the Helsinki University Hospital from November 1993 to December 2014 and died between January 2013 and December 2014, were retrospectively reviewed. The analysis comprised 121 patients (76 glioblastoma multiforme, 74 males; mean age 62 years; range 26-89). The decision for PC, emergency department (ED) visits and hospitalizations were collected from hospital records. RESULTS The PC decision was made for 78% of the patients. The median survival after diagnosis was 16 months (13 months patients with glioblastoma), and after the PC decision, it was 44 days (range 1-293). 31% of the patients received anticancer treatments within 30 days and 17% within the last 14 day before death. 22% of the patients visited an ED, and 17% were hospitalized during the last 30 days of life. Of the patients who had a PC decision made more than 30 days prior to death, only 4% visited an ED or were hospitalized in a tertiary hospital in the last 30 days of life compared to patients with a late (< 30 days prior to death) or no PC decision (25 patients, 36%). CONCLUSIONS Every third patient with malignant brain tumors had anticancer treatments during the last month of life with a significant number of ED visits and hospitalizations. Postponing the PC decision to the last month of life increases the risk of tertiary hospital resource use at EOL.
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Affiliation(s)
- Nelli-Sofia Nåhls
- Department of Oncology, Vaasa Central Hospital, Vaasa, Finland.
- Department of Radiotherapy, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
- Department of Oncology, Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
| | | | - Tiina Saarto
- Department of Palliative Care, Comprehensive Cancer Center, Faculty of Medicine, Helsinki University Hospital, Helsinki University, Helsinki, Finland
| | - Outi Hirvonen
- Palliative Center, Turku University Hospital, Turku, Finland
- Department of Clinical Oncology, University of Turku, Turku, Finland
| | - Anu Anttonen
- Department of Radiotherapy, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
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Park J, Park YG. Brain Tumor Rehabilitation: Symptoms, Complications, and Treatment Strategy. BRAIN & NEUROREHABILITATION 2022; 15:e25. [PMID: 36742081 PMCID: PMC9833490 DOI: 10.12786/bn.2022.15.e25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/15/2022] [Indexed: 12/02/2022] Open
Abstract
Brain tumors are receiving increasing attention in cancer rehabilitation due to their high rate of neurological deterioration. Motor dysfunction, cognitive deterioration, and emotional problems are commonly present in patients with brain tumors. Other medical complications, such as seizures, headache, and dysphagia are also common. An individualized multidisciplinary rehabilitation intervention is necessary to treat functional impairment due to the tumor itself and/or treatment-related dysfunction. Herein, we discuss rehabilitation treatment strategies in relation to the neurological and functional complications that commonly occur in patients with brain tumors.
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Affiliation(s)
- Jinyoung Park
- Department of Rehabilitation Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Ghil Park
- Department of Rehabilitation Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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The effect of levetiracetam treatment on survival in patients with glioblastoma: a systematic review and meta-analysis. J Neurooncol 2022; 156:257-267. [PMID: 34982371 DOI: 10.1007/s11060-021-03940-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/28/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND Levetiracetam (LEV) is an anti-epileptic drug (AED) that sensitizes glioblastoma (GBM) to temozolomide (TMZ) chemotherapy by inhibiting O6-methylguanine-DNA methyltransferase (MGMT) expression. Adding LEV to the standard of care (SOC) for GBM may improve TMZ efficacy. This study aimed to pool the existing evidence in the literature to quantify LEV's effect on GBM survival and characterize its safety profile to determine whether incorporating LEV into the SOC is warranted. METHOD A search of CINAHL, Embase, PubMed, and Web of Science from inception to May 2021 was performed to identify relevant articles. Hazard ratios (HR), median overall survival, and adverse events were pooled using random-effect models. Meta-regression, funnel plots, and the Newcastle-Ottawa Scale were utilized to identify sources of heterogeneity, bias, and statistical influence. RESULTS From 20 included studies, 5804 GBM patients underwent meta-analysis, of which 1923 (33%) were treated with LEV. Administration of LEV did not significantly improve survival in the entire patient population (HR 0.89, p = 0.094). Significant heterogeneity was observed during pooling of HRs (I2 = 75%, p < 0.01). Meta-regression determined that LEV treatment effect decreased with greater rates of MGMT methylation (RC = 0.03, p = 0.02) and increased with greater proportions of female patients (RC = - 0.05, p = 0.002). Concurrent LEV with the SOC for GBM did not increase odds of adverse events relative to other AEDs. CONCLUSIONS Levetiracetam treatment may not be effective for all GBM patients. Instead, LEV may be better suited for treating specific molecular profiles of GBM. Further studies are necessary to identify optimal GBM candidates for LEV.
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Ricklefs FL, Drexler R, Wollmann K, Eckhardt A, Heiland DH, Sauvigny T, Maire C, Lamszus K, Westphal M, Schüller U, Dührsen L. OUP accepted manuscript. Neuro Oncol 2022; 24:1886-1897. [PMID: 35511473 PMCID: PMC9629427 DOI: 10.1093/neuonc/noac108] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25%-30% of glioblastoma (GBM) patients initially present with seizures, and an additional 30% develop seizures during the course of the disease. Early studies failed to show an effect of general administration of antiepileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups. METHODS 111 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n = 68). RESULTS Receptor tyrosine Kinase (RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal (MES) GBM (P < .01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (P = .02, OR 5.69) and RTK II (P = .03, OR 5.01) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (P < .01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (P < .01). CONCLUSION Our study shows a strong correlation of RTK II glioblastomas with preoperative and long-term seizures. These results underline the benefit of molecular glioblastoma profiling with important implications for postoperative seizure control.
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Affiliation(s)
| | | | - Kathrin Wollmann
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alicia Eckhardt
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Research Institute Children’s Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Radiation Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dieter H Heiland
- Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany (D.H.H.)
| | - Thomas Sauvigny
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Cecile Maire
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katrin Lamszus
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Manfred Westphal
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ulrich Schüller
- Ulrich Schüller, MD, Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany ()
| | - Lasse Dührsen
- Corresponding Authors: Lasse Dührsen, MD, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany ()
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de Bruin ME, van der Meer PB, Dirven L, Taphoorn MJB, Koekkoek JAF. Efficacy of antiepileptic drugs in glioma patients with epilepsy: a systematic review. Neurooncol Pract 2021; 8:501-517. [PMID: 34589231 PMCID: PMC8475226 DOI: 10.1093/nop/npab030] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma. Methods Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months. Results A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid. Conclusion Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
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Affiliation(s)
| | - Pim B van der Meer
- Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
| | - Linda Dirven
- Department of Neurology, Haaglanden Medical Center, The Hague, the Netherlands.,Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
| | - Martin J B Taphoorn
- Department of Neurology, Haaglanden Medical Center, The Hague, the Netherlands.,Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
| | - Johan A F Koekkoek
- Department of Neurology, Haaglanden Medical Center, The Hague, the Netherlands.,Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
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Walbert T, Harrison RA, Schiff D, Avila EK, Chen M, Kandula P, Lee JW, Le Rhun E, Stevens GHJ, Vogelbaum MA, Wick W, Weller M, Wen PY, Gerstner ER. SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neuro Oncol 2021; 23:1835-1844. [PMID: 34174071 DOI: 10.1093/neuonc/noab152] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. METHODS Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (Class I-IV). RESULTS Thirty-seven articles were selected for final analysis. There were limited high level, Class I studies and mostly Class II and III studies. The AAN affirmed the value of these guidelines. RECOMMENDATIONS In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe anti-epileptic drugs (AEDs) to reduce the risk of seizures (Level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (Level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (Level C). Physicians may consider use of levetiracetam over older AEDs to reduce side effects (Level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features, when deciding whether or not to prescribe prophylactic AEDs (Level U).
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Affiliation(s)
- Tobias Walbert
- Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA
| | | | - David Schiff
- University of Virginia Health System, Charlottesville, VA, USA
| | - Edward K Avila
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Merry Chen
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Padmaja Kandula
- Division of Clinical Neurophysiology and Epilepsy, New York Presbyterian Hospital-Weill Cornell Medicine, New York, New York USA
| | | | - Emilie Le Rhun
- Departments of Neurology and Neurosurgery, Brain Tumor Center & Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Glen H J Stevens
- Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Wolfgang Wick
- Neurology Clinic and Neurooncology Program, Heidelberg University and German Cancer Research Center, Heidelberg, Germany
| | - Michael Weller
- Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Patrick Y Wen
- Center For Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Elizabeth R Gerstner
- Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA and Harvard Medical School, Boston, MA, USA
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10
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Stocksdale B, Nagpal S, Hixson JD, Johnson DR, Rai P, Shivaprasad A, Tremont-Lukats IW. Neuro-Oncology Practice Clinical Debate: long-term antiepileptic drug prophylaxis in patients with glioma. Neurooncol Pract 2020; 7:583-588. [PMID: 33312673 DOI: 10.1093/nop/npaa026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Patients with primary brain tumors often experience seizures, which can be the presenting symptom or occur for the first time at any point along the illness trajectory. In addition to causing morbidity, seizures negatively affect independence and quality of life in other ways, for example, by leading to loss of driving privileges. Long-term therapy with antiepileptic drugs (AEDs) is the standard of care in brain tumor patients with seizures, but the role of prophylactic AEDs in seizure-naive patients remains controversial. In this article, experts in the field discuss the issues of AED efficacy and toxicity, and explain their differing recommendations for routine use of prophylactic AEDs.
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Affiliation(s)
- Brian Stocksdale
- Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Seema Nagpal
- Department of Neurology, Stanford University, California
| | - John D Hixson
- Department of Neurology, University of California San Francisco
| | | | - Prashant Rai
- Department of Neurology, The University of Texas Medical Branch at Galveston
| | - Akhil Shivaprasad
- Stanley H. Appel Department of Neurology, Houston Methodist Hospital, Texas
| | - Ivo W Tremont-Lukats
- Kenneth R. Peak Brain and Pituitary Tumor Center, Houston Methodist Hospital, Texas.,Department of Neurosurgery, Houston Methodist Hospital, Texas
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11
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O'Neal CM, Stephens TM, Briggs RG, Sughrue ME, Conner AK. Navigated transcranial magnetic stimulation following awake craniotomy for resection of glioma: Description of two cases. Surg Neurol Int 2020; 11:433. [PMID: 33365195 PMCID: PMC7749929 DOI: 10.25259/sni_628_2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 11/19/2020] [Indexed: 01/23/2023] Open
Abstract
Background Although transcranial magnetic stimulation (TMS) has been indicated as a potential therapy for several neurologic conditions, there is little known regarding its use during the postoperative rehabilitation period in patients with brain tumors. Furthermore, seizures, a common presentation in these patients, are regarded as a major contraindication for TMS therapy. Case Description We demonstrate that postoperative continuous theta burst stimulation (cTBS), a patterned form of repetitive TMS, was safely tolerated in addition to current neurorehabilitation techniques in two brain tumor patients, including one patient with a history of tumor-related epilepsy. We administered navigated 5 Hz cTBS to two patients within 48 h following awake craniotomy for tumor resection. Active motor thresholds were measured in both patients before TBS administration to determine stimulus intensity. We used resting-state fMRI to identify likely damaged networks based on postoperative deficits. This aided in TMS planning and allowed deficit targeted therapy contralateral to the lesioned network node. Both patients tolerated TBS therapy well and had no adverse effects, including posttreatment seizures, despite one patient having a history of tumor-related epilepsy. Conclusion TBS may be safe in the immediate postoperative period for patients following brain tumor resection. Additional studies are needed to quantify the efficacy of TMS in improving neurologic deficits following tumor resection.
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Affiliation(s)
- Christen M O'Neal
- Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma, United States
| | - Tressie M Stephens
- Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma, United States
| | - Robert G Briggs
- Department of Neurosurgery, University of Southern California, Los Angeles, California, United States
| | - Michael E Sughrue
- Center for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital, Randwick, New South Wales, Australia
| | - Andrew K Conner
- Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma, United States
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12
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Martos-Benítez FD, Soler-Morejón CDD, Lara-Ponce KX, Orama-Requejo V, Burgos-Aragüez D, Larrondo-Muguercia H, Lespoir RW. Critically ill patients with cancer: A clinical perspective. World J Clin Oncol 2020; 11:809-835. [PMID: 33200075 PMCID: PMC7643188 DOI: 10.5306/wjco.v11.i10.809] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 08/09/2020] [Accepted: 09/14/2020] [Indexed: 02/06/2023] Open
Abstract
Cancer patients account for 15% of all admissions to intensive care unit (ICU) and 5% will experience a critical illness resulting in ICU admission. Mortality rates have decreased during the last decades because of new anticancer therapies and advanced organ support methods. Since early critical care and organ support is associated with improved survival, timely identification of the onset of clinical signs indicating critical illness is crucial to avoid delaying. This article focused on relevant and current information on epidemiology, diagnosis, and treatment of the main clinical disorders experienced by critically ill cancer patients.
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Affiliation(s)
| | | | | | | | | | | | - Rahim W Lespoir
- Intensive Care Unit 8B, Hermanos Ameijeiras Hospital, Havana 10300, Cuba
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13
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Delgado-López PD, Martín-Alonso J. Prophylactic anticonvulsant therapy in high-grade glioma: A systematic review and meta-analysis of longitudinal studies. Neurocirugia (Astur) 2020; 31:268-278. [PMID: 32265156 DOI: 10.1016/j.neucir.2020.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 02/12/2020] [Accepted: 02/14/2020] [Indexed: 01/11/2023]
Abstract
INTRODUCTION It is common practice to prescribe prophylactic antiepileptic drugs (AED) to high-grade glioma (HGG) patients without a history of seizures, yet with limited evidence supporting its use. Ideally, the effectiveness of prophylactic anticonvulsants must outweigh the occurrence of adverse effects and interactions related to AED. The authors conducted a systematic review and metanalysis of longitudinal studies regarding the effectiveness of prophylactic AED in seizure-naïve HGG patients. MATERIALS AND METHODS PubMed/MEDLINE, Cochrane Central Register of Controlled trials, Embase and clinicaltrials.gov databases were systematically searched. Of the initial 1773 studies identified, 15 were finally selected for data extraction and analysis. Heterogeneity among studies, pooled hazard ratios, publication bias and sensitivity analyses were performed separately for a 15-study group (HGG patients within larger series of brain tumors) and a 6-study group (exclusively HGG patients). RESULTS AED prophylaxis did not significantly reduce the incidence of postoperative seizures compared with controls, both in the 15-study group (Mantel-Haenszel random-effects pooled OR 1.08, 95% CI 0.82-1.43, 2123 patients) and in the 6-study group (pooled OR 1.22, 95% CI 0.77-1.92, 540 patients). However, some issues (paucity of prospective trials, overall moderate-risk of bias, and few studies addressing HGG patients exclusively) preclude firm conclusions against routine prophylactic AED prescription. Reported adverse effects attributable to AED were acceptable in the majority of studies. CONCLUSIONS Within the limitations of this review, the results of this metanalysis do not support the routine administration of prophylactic AED to HGG patients without a history of seizures.
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14
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Gonzalez Castro LN, Milligan TA. Seizures in patients with cancer. Cancer 2020; 126:1379-1389. [PMID: 31967671 DOI: 10.1002/cncr.32708] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 11/21/2019] [Accepted: 12/18/2019] [Indexed: 12/12/2022]
Abstract
Seizures are common in patients with cancer and either result from brain lesions, paraneoplastic syndromes, and complications of cancer treatment or are provoked by systemic illness (metabolic derangements, infections). Evaluation should include a tailored history, neurologic examination, laboratory studies, neuroimaging, and electroencephalogram. In unprovoked seizures, antiepileptic drug (AED) treatment is required, and a nonenzyme-inducing AED is preferred. Treatment of the underlying cancer with surgery, chemotherapy, and radiation therapy also can help reduce seizures. Benzodiazepines are useful in the treatment of both provoked seizures and breakthrough epileptic seizures and as first-line treatment for status epilepticus. Counseling for safety is an important component in the care of a patient with cancer who has seizures. Good seizure management can be challenging but significantly improves the quality of life during all phases of care, including end-of-life care.
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Affiliation(s)
- L Nicolas Gonzalez Castro
- Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.,Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Tracey A Milligan
- Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
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15
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Kluger BM, Ney DE, Bagley SJ, Mohile N, Taylor LP, Walbert T, Jones CA. Top Ten Tips Palliative Care Clinicians Should Know When Caring for Patients with Brain Cancer. J Palliat Med 2019; 23:415-421. [PMID: 31613698 DOI: 10.1089/jpm.2019.0507] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
The diagnosis of an aggressive, primary brain tumor is life altering for those affected and too often portends a poor prognosis. Despite decades of research, neither a cure nor even a therapy that reliably and dramatically prolongs survival has been found. Fortunately, there are a number of treatments that may prolong the life of select brain tumor patients although the symptom burden can sometimes be high. This article brings together neuro-oncologists, neurologists, and palliative care (PC) physicians to help shine a light on these diseases, their genetics, treatment options, and the symptoms likely to be encountered both from the underlying illness and its treatment. We hope to increase the understanding that PC teams have around these illnesses to improve care for patients and families.
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Affiliation(s)
- Benzi M Kluger
- Department of Neurology, University of Colorado Denver, Denver, Colorado
| | - Douglas E Ney
- Department of Neurology, University of Colorado Denver, Denver, Colorado
| | - Stephen J Bagley
- Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Nimish Mohile
- Department of Neurology, University of Rochester Medical Center, Rochester, New York
| | - Lynne P Taylor
- Department of Neurology, University of Washington, Seattle, Washington.,Department of Neurosurgery, University of Washington, Seattle, Washington.,Seattle Cancer Care Alliance, University of Washington, Seattle, Washington
| | - Tobias Walbert
- Department of Neurology and Neurosurgery, Henry Ford Health System, Detroit, Michigan
| | - Christopher A Jones
- Department of Medicine and the Palliative and Advanced Illness Research Center, University of Pennsylvania, Philadelphia, Pennsylvania
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16
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Wang X, Zheng X, Hu S, Xing A, Wang Z, Song Y, Chen J, Tian S, Mao Y, Chi X. Efficacy of perioperative anticonvulsant prophylaxis in seizure-naïve glioma patients: A meta-analysis. Clin Neurol Neurosurg 2019; 186:105529. [PMID: 31574360 DOI: 10.1016/j.clineuro.2019.105529] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 09/20/2019] [Accepted: 09/21/2019] [Indexed: 01/29/2023]
Abstract
The efficacy of perioperative seizure prophylaxis in seizure-naïve glioma patients is still controversial. Thus we conducted this meta-analysis to assess the effectiveness of perioperative prophylactic antiepileptic drugs (AEDs) on postoperative seizures in seizure-naïve glioma for the first time. We systematically searched PubMed, Embase, Weipu (VIP) and Chinese National Knowledge Infrastructure (CNKI) until July 5, 2019 for eligible studies. Fixed or random model was used to calculate the odds ratios in STATA 12.0 software. Subgroup analyses of early postoperative seizure, late postoperative seizure, high-grade glioma (WHOIII-IV) and phenytoin (PHT) or phenobarbital (PB) prophylaxis were conducted. Altogether 1143 seizure-naïve glioma patients from 9 studies were included in this meta-analysis, containing 643 prophylaxed and 503 non-prophylaxed patients. No significant association was detected between perioperative seizure prophylaxis and postoperative seizure occurrence in glioma patients without preoperative seizure history (OR = 0.91, 95% CI = 0.65-1.26, P = 0.56). Perioperative AED prophylaxis showed no significant benefit to postoperative seizures when stratified by early postoperative seizure(within the first postoperative week), late postoperative seizure (after the first postoperative week), high-grade glioma and PHT or PB prophylaxis (all P > 0.05). Current evidence indicated that perioperative seizure prophylaxis did not reduce the occurrence of postoperative seizure in seizure-naïve glioma patients. The pros and cons of perioperative seizure prophylaxis should be considered before the start of perioperative AEDs treatment.
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Affiliation(s)
- Xiaomeng Wang
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xueping Zheng
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Song Hu
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ang Xing
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Zixuan Wang
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yan Song
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Jingjiao Chen
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Sijia Tian
- Department of Geriatrics, The Second Affiliated Hospital Of Chongqing Medical Universty, Chongqin, China
| | - Yongjun Mao
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xiaosa Chi
- Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
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17
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Maschio M, Aguglia U, Avanzini G, Banfi P, Buttinelli C, Capovilla G, Casazza MML, Colicchio G, Coppola A, Costa C, Dainese F, Daniele O, De Simone R, Eoli M, Gasparini S, Giallonardo AT, La Neve A, Maialetti A, Mecarelli O, Melis M, Michelucci R, Paladin F, Pauletto G, Piccioli M, Quadri S, Ranzato F, Rossi R, Salmaggi A, Terenzi R, Tisei P, Villani F, Vitali P, Vivalda LC, Zaccara G, Zarabla A, Beghi E. Management of epilepsy in brain tumors. Neurol Sci 2019; 40:2217-2234. [PMID: 31392641 DOI: 10.1007/s10072-019-04025-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 07/20/2019] [Indexed: 12/15/2022]
Abstract
Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.
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Affiliation(s)
- Marta Maschio
- Center for Brain Tumor-Related Epilepsy, UOSD Neuro-Oncology, I.R.C.C.S. Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
| | - Umberto Aguglia
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Giuliano Avanzini
- Department of Neurophysiology and Experimental Epileptology, Carlo Besta Neurological Institute, Milan, Italy
| | - Paola Banfi
- Neurology Unit, Department of Emergency, Medicine Epilepsy Center, Circolo Hospital, Varese, Italy
| | - Carla Buttinelli
- Department of Neuroscience, Mental Health and Sensory Organs, University of Rome "La Sapienza", Rome, Italy
| | - Giuseppe Capovilla
- Department of Mental Health, Epilepsy Center, C. Poma Hospital, Mantua, Italy
| | | | - Gabriella Colicchio
- Institute of Neurosurgery, Catholic University of the Sacred Heart, Rome, Italy
| | - Antonietta Coppola
- Department of Neuroscience, Reproductive and Odontostomatological Sciences, Epilepsy Centre, University of Naples Federico II, Naples, Italy
| | - Cinzia Costa
- Neurological Clinic, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Filippo Dainese
- Epilepsy Centre, UOC Neurology, SS. Giovanni e Paolo Hospital, Venice, Italy
| | - Ornella Daniele
- Epilepsy Center-U.O.C. Neurology, Policlinico Paolo Giaccone, Experimental Biomedicine and Clinical Neuroscience Department (BioNeC), University of Palermo, Palermo, Italy
| | - Roberto De Simone
- Neurology and Stroke Unit, Epilepsy and Sleep Disorders Center, St. Eugenio Hospital, Rome, Italy
| | - Marica Eoli
- Molecular Neuro-Oncology Unit, IRCCS-Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
| | - Sara Gasparini
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | | | - Angela La Neve
- Department of Neurological and Psychiatric Sciences, Centre for Epilepsy, University of Bari, Bari, Italy
| | - Andrea Maialetti
- Center for Brain Tumor-Related Epilepsy, UOSD Neuro-Oncology, I.R.C.C.S. Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Oriano Mecarelli
- Neurology Unit, Human Neurosciences Department, Sapienza University, Umberto 1 Hospital, Rome, Italy
| | - Marta Melis
- Department of Medical Sciences and Public Health, Institute of Neurology, University of Cagliari, Monserrato, Cagliari, Italy
| | - Roberto Michelucci
- Unit of Neurology, Bellaria Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
| | - Francesco Paladin
- Epilepsy Center, UOC Neurology, Ospedale Santi Giovanni e Paolo, Venice, Italy
| | - Giada Pauletto
- Department of Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy
| | - Marta Piccioli
- UOC Neurology, PO San Filippo Neri, ASL Roma 1, Rome, Italy
| | - Stefano Quadri
- USC Neurology, Epilepsy Center, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Federica Ranzato
- Epilepsy Centre, Neuroscience Department, S. Bortolo Hospital, Vicenza, Italy
| | - Rosario Rossi
- Neurology and Stroke Unit, San Francesco Hospital, 08100, Nuoro, Italy
| | | | - Riccardo Terenzi
- Epilepsy Consultation Room, Neurology Unit, S. Pietro Fatebenefratelli Hospital, Rome, Italy
| | - Paolo Tisei
- Neurophysiology Unit, Department of Neurology-University "La Sapienza", S. Andrea Hospital, Rome, Italy
| | - Flavio Villani
- Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione IRCCS, Istituto Neurologico C. Besta, Milan, Italy
| | - Paolo Vitali
- Neuroradiology and Brain MRI 3T Mondino Research Center, IRCCS Mondino Foundation, Pavia, Italy
| | | | - Gaetano Zaccara
- Regional Health Agency of Tuscany, Via P Dazzi 1, 50141, Florence, Italy
| | - Alessia Zarabla
- Center for Brain Tumor-Related Epilepsy, UOSD Neuro-Oncology, I.R.C.C.S. Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Ettore Beghi
- Department of Neurosciences, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
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18
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Wasilewski A, Serventi J, Ibegbu C, Wychowski T, Burke J, Mohile N. Epilepsy education in gliomas: engaging patients and caregivers to improve care. Support Care Cancer 2019; 28:1405-1409. [DOI: 10.1007/s00520-019-04968-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 06/26/2019] [Indexed: 11/24/2022]
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19
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Mirian C, Møller Pedersen M, Sabers A, Mathiesen T. Antiepileptic drugs as prophylaxis for de novo brain tumour-related epilepsy after craniotomy: a systematic review and meta-analysis of harm and benefits. J Neurol Neurosurg Psychiatry 2019; 90:599-607. [PMID: 30674543 DOI: 10.1136/jnnp-2018-319609] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 12/10/2018] [Accepted: 12/14/2018] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To investigate potential harm and benefits of antiepileptic drugs (AED) given prophylactically to prevent de novo brain tumour-related epilepsy after craniotomy. METHODS Randomised controlled trials (RCT) and retrospective studies published before 27 November 2018 were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied. Eligible patients were diagnosed with a brain tumour, were seizure naïve and underwent craniotomy. The random effects model was used for quantitative synthesis. The analysis was adjusted for the confounding effect of including patients with a history of seizure prior to study inclusion. RESULTS A total of 454 patients received prophylactic AED whereas 333 were allocated to placebo or no treatment. Two RCTs and four retrospective studies were identified. The OR was 1.09 (95% CI 0.7 to 1.8, p=0.7, I2=5.6%, χ2 p=0.5), indicating study consistency and no significant differences. An additional two RCTs and one retrospective study combined craniotomy and diagnostic biopsy, and were subgroup analysed-which supported no difference in odds for epilepsy. CONCLUSIONS A prophylactic effect of AED could not be demonstrated (nor rejected statistically). Levetiracetam was associated with less adverse effects than phenytoin. The potential harm of AED was not balanced by the potential prophylactic benefit. This study suggests that prophylactic AED should not be administered to prevent brain tumour-related epilepsy after craniotomy.
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Affiliation(s)
- Christian Mirian
- Department of Neurosurgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Maria Møller Pedersen
- Department of Neurosurgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Anne Sabers
- Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Tiit Mathiesen
- Department of Neurosurgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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20
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Akeret K, Serra C, Rafi O, Staartjes VE, Fierstra J, Bellut D, Maldaner N, Imbach LL, Wolpert F, Poryazova R, Regli L, Krayenbühl N. Anatomical features of primary brain tumors affect seizure risk and semiology. NEUROIMAGE-CLINICAL 2019; 22:101688. [PMID: 30710869 PMCID: PMC6354289 DOI: 10.1016/j.nicl.2019.101688] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/19/2019] [Accepted: 01/22/2019] [Indexed: 11/23/2022]
Abstract
Objective An epileptic seizure is the most common clinical manifestation of a primary brain tumor. Due to modern neuroimaging, detailed anatomical information on a brain tumor is available early in the diagnostic process and therefore carries considerable potential in clinical decision making. The goal of this study was to gain a better understanding of the relevance of anatomical tumor characteristics on seizure prevalence and semiology. Methods We reviewed prospectively collected clinical and imaging data of all patients operated on a supratentorial intraparenchymal primary brain tumor at our department between January 2009 and December 2016. The effect of tumor histology, anatomical location and white matter infiltration on seizure prevalence and semiology were assessed using uni- and multivariate analyses. Results Of 678 included patients, 311 (45.9%) presented with epileptic seizures. Tumor location within the central lobe was associated with higher seizure prevalence (OR 4.67, 95% CI: 1.90–13.3, p = .002), especially within the precentral gyrus or paracentral lobule (100%). Bilateral extension, location within subcortical structures and invasion of deeper white matter sectors were associated with a lower risk (OR 0.45, 95% CI: 0.25–0.78; OR 0.10, 95% CI: 0.04–0.21 and OR 0.39, 95% CI: 0.14–0.96, respectively). Multivariate analysis revealed the impact of a location within the central lobe on seizure risk to be highly significant and more relevant than histopathology (OR: 4.79, 95% CI: 1.82–14.52, p = .003). Seizures due to tumors within the central lobe differed from those of other locations by lower risk of secondary generalization (p < .001). Conclusions Topographical lobar and gyral location, as well as extent of white matter infiltration impact seizure risk and semiology. This finding may have a high therapeutic potential, for example regarding the use of prophylactic antiepileptic therapy.
Brain tumor location affects seizure prevalence and semiology. Central lobe location is the strongest independent pro-epileptogenic factor. The precentral gyrus and paracentral lobule are most epileptogenic. Central lobe tumors rarely cause bilateral tonic-clonic seizures. Tumor location and white matter infiltration may guide antiepileptic therapy.
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Affiliation(s)
- Kevin Akeret
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
| | - Carlo Serra
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Omar Rafi
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Victor E Staartjes
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Jorn Fierstra
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - David Bellut
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolai Maldaner
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Lukas L Imbach
- Division of Epileptology, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Fabian Wolpert
- Division of Epileptology, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Rositsa Poryazova
- Division of Epileptology, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Luca Regli
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Niklaus Krayenbühl
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Division of Pediatric Neurosurgery, University Children's Hospital, Zurich, Switzerland
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Abstract
OBJECTIVE To describe the currently accepted standard-of-care practice for surgical and medical management of newly diagnosed high-grade glioma. DATA SOURCES Peer-reviewed journals, nationally accepted guidelines, and personal experience of the authors. CONCLUSION There is a widely accepted standard-of-care treatment protocol for patients with newly diagnosed high-grade glioma that includes maximal safe resection followed by radiation therapy with concurrent and adjuvant temozolomide. The regimen is well-tolerated and side effects are manageable. IMPLICATIONS FOR NURSING PRACTICE Nurses who are involved in the care of patients with newly diagnosed high-grade glioma should be familiar with the regimen and its side effects to provide crucial patient and caregiver education in an accurate and beneficial manner.
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Abstract
PURPOSE OF REVIEW This article discusses common and emergent medical complications encountered in patients with primary brain tumors. RECENT FINDINGS Clinical studies and systematic reviews published in recent years have improved knowledge regarding the incidence of neurologic and medical complications occurring in patients with primary brain tumors. Studies in tumor-related epilepsy and venous thromboembolism provide data for the clinician to make evidence-based decisions about perioperative management, prophylaxis, and therapy. Patients with brain tumors experience unique toxicities related to novel drugs and chemotherapeutics that result in hematologic, infectious, and endocrine disorders. Recent work that has focused on quality of life in patients with brain tumors highlights the importance of good supportive care and optimal medical management of neurobehavioral symptoms and late complications of treatment. SUMMARY A thorough understanding of the variety of medical and neurologic complications in patients with primary brain tumors improves the clinician's ability to quickly recognize and manage common and urgent conditions.
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Nguyen HS, Shabani S, Awad AJ, Kaushal M, Doan N. Molecular Markers of Therapy-Resistant Glioblastoma and Potential Strategy to Combat Resistance. Int J Mol Sci 2018; 19:ijms19061765. [PMID: 29899215 PMCID: PMC6032212 DOI: 10.3390/ijms19061765] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 06/11/2018] [Accepted: 06/13/2018] [Indexed: 12/22/2022] Open
Abstract
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. With its overall dismal prognosis (the median survival is 14 months), GBMs demonstrate a resounding resilience against all current treatment modalities. The absence of a major progress in the treatment of GBM maybe a result of our poor understanding of both GBM tumor biology and the mechanisms underlying the acquirement of treatment resistance in recurrent GBMs. A comprehensive understanding of these markers is mandatory for the development of treatments against therapy-resistant GBMs. This review also provides an overview of a novel marker called acid ceramidase and its implication in the development of radioresistant GBMs. Multiple signaling pathways were found altered in radioresistant GBMs. Given these global alterations of multiple signaling pathways found in radioresistant GBMs, an effective treatment for radioresistant GBMs may require a cocktail containing multiple agents targeting multiple cancer-inducing pathways in order to have a chance to make a substantial impact on improving the overall GBM survival.
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Affiliation(s)
- Ha S Nguyen
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- Faculty of Neurosurgery, California Institute of Neuroscience, Thousand Oaks, CA 91360, USA.
| | - Saman Shabani
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
| | - Ahmed J Awad
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 11941, Palestine.
| | - Mayank Kaushal
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
| | - Ninh Doan
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- Department of Neurosurgery, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36688, USA.
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Farrokh S, Tahsili-Fahadan P, Ritzl EK, Lewin JJ, Mirski MA. Antiepileptic drugs in critically ill patients. Crit Care 2018; 22:153. [PMID: 29880020 PMCID: PMC5992651 DOI: 10.1186/s13054-018-2066-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 05/14/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited. MAIN BODY This article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included. CONCLUSION Optimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.
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Affiliation(s)
- Salia Farrokh
- Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD 21287 USA
| | - Pouya Tahsili-Fahadan
- Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD USA
- Department of Medicine, Virginia Commonwealth University School of Medicine, INOVA Campus, Falls Church, VA USA
| | - Eva K. Ritzl
- Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD USA
- Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Hospital, Baltimore, MD USA
| | - John J. Lewin
- Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD 21287 USA
| | - Marek A. Mirski
- Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD 21287 USA
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Molecular Targeting of Acid Ceramidase in Glioblastoma: A Review of Its Role, Potential Treatment, and Challenges. Pharmaceutics 2018; 10:pharmaceutics10020045. [PMID: 29642535 PMCID: PMC6027516 DOI: 10.3390/pharmaceutics10020045] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 04/03/2018] [Accepted: 04/04/2018] [Indexed: 01/04/2023] Open
Abstract
Glioblastoma is the most common, malignant primary tumor of the central nervous system. The average prognosis for life expectancy after diagnosis, with the triad of surgery, chemotherapy, and radiation therapy, is less than 1.5 years. Chemotherapy treatment is mostly limited to temozolomide. In this paper, the authors review an emerging, novel drug called acid ceramidase, which targets glioblastoma. Its role in cancer treatment in general, and more specifically, in the treatment of glioblastoma, are discussed. In addition, the authors provide insights on acid ceramidase as a potential druggable target for glioblastoma.
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26
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Lu VM, Jue TR, Phan K, McDonald KL. Quantifying the prognostic significance in glioblastoma of seizure history at initial presentation: A systematic review and meta-analysis. Clin Neurol Neurosurg 2017; 164:75-80. [PMID: 29202377 DOI: 10.1016/j.clineuro.2017.11.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 11/15/2017] [Accepted: 11/28/2017] [Indexed: 12/24/2022]
Abstract
The role of prognostic factors in the management of glioblastoma (GBM) is very important given the stasis in improving its clinical outcomes. Patients who initially present with a positive seizure history at diagnosis have anecdotally experienced superior survival outcomes. The aim of this review was to perform a systematic review and meta-analysis to quantify the potential prognostic significance of positive seizure history in GBM patients. A search strategy was performed using the PRISMA guidelines for article identification, screening, eligibility and inclusion. Relevant articles were identified from six electronic databases from their inception to August 2017. These articles were screened against established criteria for inclusion into this study. Meta-analysis was conducted by pooling results with multivariate-adjusted hazard ratios (HRs). After screening, 6 relevant studies were included for analysis. There was a total cohort of 1836 GBM patients, of which 488 (27%) had a positive seizure history at initial presentation. There was a significant association found between positive seizure history in GBM patients and less mortality events, with an overall HR of 0.71 (95%CI=0.63-0.81, p<0.00001, I2=4%). Positive seizure history at initial presentation of GBM can be associated with improved prognosis. However, there are a number of variables that need to be considered further, including genetic profiling, lead time bias, and anti-epileptic drug (AED) therapy. This review represents the highest level of evidence to date, and its result will be validated by future, prospective study of larger cohorts.
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Affiliation(s)
- Victor M Lu
- Cure Brain Cancer Foundation Biomarkers and Translational Research Group, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
| | - Toni R Jue
- Cure Brain Cancer Foundation Biomarkers and Translational Research Group, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia
| | - Kevin Phan
- NeuroSpine Surgery Research Group (NSURG), Prince of Wales Private Hospital, Randwick, Sydney, Australia
| | - Kerrie L McDonald
- Cure Brain Cancer Foundation Biomarkers and Translational Research Group, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia
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Wasilewski A, Serventi J, Kamalyan L, Wychowski T, Mohile N. Acute care in glioblastoma: the burden and the consequences. Neurooncol Pract 2017; 4:248-254. [PMID: 31385967 DOI: 10.1093/nop/npw032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background The utilization of inpatient medical services by patients with glioblastoma (GBM) is not well studied. We sought to describe causes, frequency, and outcomes of acute care visits in GBM. Methods We conducted a retrospective study of 158 GBM patients at the University of Rochester over 5 years. Electronic medical records were reviewed to identify all local and outside acute care visits. Acute care visits were defined as any encounter resulting in an emergency department visit or inpatient admission. Results Seventy-one percent (112/158) of GBM patients had 235 acute care visits corresponding to 163 hospitalizations (69%) and 72 emergency department visits (31%). Sixty-three percent of patients had multiple visits. Admission diagnoses were seizure (33%), neurosurgical procedure (15%), infection (12%), focal neurologic symptoms (9%), and venous thromboembolism (VTE, 9%). Forty-six patients had 1 or more visits for seizures. Median time to first acute care visit was 65.6 days and 22% of patients had an acute care visit within 30 days of diagnosis. Median length of stay was 5 days. Thirty-five percent of admitted patients were discharged home; 62% required a higher level of care than prior to admission (23% were discharged home with services, 17% to a nursing facility, 16% to hospice, 6% to acute rehab) and 3% died. Thirty-eight percent of patients had ACV within 30 days of death. Median survival was 14 months for patients who had acute care visits and 22.2 months for patients who did not. Conclusion The majority of GBM patients utilize acute care, most commonly for seizures. The high number of emergency department visits, short length of stay, and many patients discharged home suggest that some acute care visits may be avoidable.
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Affiliation(s)
- Andrea Wasilewski
- University of Rochester, Department of Neurology (A.W., J.S., L.K., T.W., N.M.)
| | - Jennifer Serventi
- University of Rochester, Department of Neurology (A.W., J.S., L.K., T.W., N.M.)
| | - Lily Kamalyan
- University of Rochester, Department of Neurology (A.W., J.S., L.K., T.W., N.M.)
| | - Thomas Wychowski
- University of Rochester, Department of Neurology (A.W., J.S., L.K., T.W., N.M.)
| | - Nimish Mohile
- University of Rochester, Department of Neurology (A.W., J.S., L.K., T.W., N.M.)
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Ertürk Çetin Ö, İşler C, Uzan M, Özkara Ç. Epilepsy-related brain tumors. Seizure 2016; 44:93-97. [PMID: 28041673 DOI: 10.1016/j.seizure.2016.12.012] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 12/16/2016] [Accepted: 12/16/2016] [Indexed: 02/02/2023] Open
Abstract
Seizures are among the most common presentations of brain tumors. Several tumor types can cause seizures in varying rates; neuroglial tumors and the gliomas are the most common ones. Brain tumors are the second most common cause of focal intractable epilepsy in epilepsy surgery series, with the highest frequency being dysembryoplastic neuroepithelial tumors and gangliogliomas. Seizure management is an important part of the treatment of patients with brain tumors. This review discusses clinical features and management of seizures in patients with brain tumors, including, neuroglial tumors, gliomas, meningioma and metastases; with the help of recent literature data. Tumor-related seizures are focal seizures with or without secondary generalization. Seizures may occur either as initial symptom or during the course of the disease. Brain tumors related epilepsy tends to be resistant to antiepileptic drugs and treatment of tumor is main step also for the seizure treatment. Early surgery and extent of the tumor removal are important factors for achieving seizure freedom particularly in neuroglial tumors and low grade gliomas. During selection of the appropriate antiepileptic drug, the general approach to partial epilepsies can be followed. There are several factors influencing epileptogenesis in brain tumor-related epilepsy which also explains clinical heterogeneity of epilepsy among tumor types. Identification of molecular markers may guide future therapeutic approaches and further studies are needed to prove antitumor effects of different antiepileptic drugs.
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Affiliation(s)
- Özdem Ertürk Çetin
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurology, 34098, Fatih, Istanbul, Turkey
| | - Cihan İşler
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurosurgery, Istanbul, Turkey
| | - Mustafa Uzan
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurosurgery, Istanbul, Turkey
| | - Çiğdem Özkara
- Istanbul University, Cerrahpasa Faculty of Medicine, Department of Neurology, 34098, Fatih, Istanbul, Turkey.
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Mohile NA. How I treat glioblastoma in older patients. J Geriatr Oncol 2015; 7:1-6. [PMID: 26725536 DOI: 10.1016/j.jgo.2015.12.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Revised: 11/02/2015] [Accepted: 12/04/2015] [Indexed: 11/26/2022]
Abstract
Glioblastoma, a WHO grade IV astrocytoma, is the most common primary malignant brain tumor in adults. It is characterized by molecular heterogeneity and aggressive behavior. Glioblastoma is almost always incurable and most older patients survive less than 6 months. Supportive care with steroids and anti-epileptic drugs is critical to improving and maintain quality of life. Young age, good performance status and methylation of the methyl guanyl methyl transferase promoter are important positive prognostic factors. Several recent clinical trials suggest that there is a subset of the elderly with prolonged survival that is comparable to younger patients. Treatment of glioblastoma in older patients includes maximal safe resection followed by either radiation, chemotherapy or combined modality therapy. Recent advances suggest that some patients can avoid radiation entirely and be treated with chemotherapy alone. Decisions about therapy are individual and based on a patient's performance status, family support and molecular features. Future work needs to better determine the role for comprehensive geriatric assessments in this patient population to better identify patients who may most benefit from aggressive therapies.
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Affiliation(s)
- Nimish A Mohile
- Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA.
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Armstrong TS, Grant R, Gilbert MR, Lee JW, Norden AD. Epilepsy in glioma patients: mechanisms, management, and impact of anticonvulsant therapy. Neuro Oncol 2015; 18:779-89. [PMID: 26527735 DOI: 10.1093/neuonc/nov269] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 10/01/2015] [Indexed: 12/16/2022] Open
Abstract
Seizures are a well-recognized symptom of primary brain tumors, and anticonvulsant use is common. This paper provides an overview of epilepsy and the use of anticonvulsants in glioma patients. Overall incidence and mechanisms of epileptogenesis are reviewed. Factors to consider with the use of antiepileptic drugs (AEDs) including incidence during the disease trajectory and prophylaxis along with considerations in the selection of anticonvulsant use (ie, potential side effects, drug interactions, adverse effects, and impact on survival) are also reviewed. Finally, areas for future research and exploring the pathophysiology and use of AEDs in this population are also discussed.
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Affiliation(s)
- Terri S Armstrong
- Department of Family Health, University of Texas Health Science Center at Houston, Houston, Texas (T.S.A.); Edinburgh Centre for Neuro-Oncology, Edinburgh, UK (R.G.); Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.R.G.); Division of EEG and Epilepsy, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (J.W.L.); Center for Neuro-Oncology, Dana-Farber Cancer Institute; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital; and Harvard Medical School, Boston, Massachusetts (A.D.N.)
| | - Robin Grant
- Department of Family Health, University of Texas Health Science Center at Houston, Houston, Texas (T.S.A.); Edinburgh Centre for Neuro-Oncology, Edinburgh, UK (R.G.); Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.R.G.); Division of EEG and Epilepsy, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (J.W.L.); Center for Neuro-Oncology, Dana-Farber Cancer Institute; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital; and Harvard Medical School, Boston, Massachusetts (A.D.N.)
| | - Mark R Gilbert
- Department of Family Health, University of Texas Health Science Center at Houston, Houston, Texas (T.S.A.); Edinburgh Centre for Neuro-Oncology, Edinburgh, UK (R.G.); Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.R.G.); Division of EEG and Epilepsy, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (J.W.L.); Center for Neuro-Oncology, Dana-Farber Cancer Institute; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital; and Harvard Medical School, Boston, Massachusetts (A.D.N.)
| | - Jong Woo Lee
- Department of Family Health, University of Texas Health Science Center at Houston, Houston, Texas (T.S.A.); Edinburgh Centre for Neuro-Oncology, Edinburgh, UK (R.G.); Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.R.G.); Division of EEG and Epilepsy, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (J.W.L.); Center for Neuro-Oncology, Dana-Farber Cancer Institute; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital; and Harvard Medical School, Boston, Massachusetts (A.D.N.)
| | - Andrew D Norden
- Department of Family Health, University of Texas Health Science Center at Houston, Houston, Texas (T.S.A.); Edinburgh Centre for Neuro-Oncology, Edinburgh, UK (R.G.); Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.R.G.); Division of EEG and Epilepsy, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (J.W.L.); Center for Neuro-Oncology, Dana-Farber Cancer Institute; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital; and Harvard Medical School, Boston, Massachusetts (A.D.N.)
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