Mutant IDH1 and seizures in patients with glioma

Chen, Hao; Judkins, Jonathon; Thomas, Cheddhi; Wu, Meijing; Khoury, Laith; Benjamin, Carolina; Pacione, Donato; Golfinos, John G.; Kumthekar, Priya; Ghamsari, Farhad; Chen, Li; Lein, Pamela J.; Chetkovich, Dane M.; Snuderl, Matija; Horbinski, Craig

doi:10.1212/wnl.0000000000003911

Cited by 176 publications

(158 citation statements)

References 40 publications

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“…Finally, the lack of molecular information in our cohort of patients with GBM (e.g. isocitrate dehydrogenase 1 mutation status ) might explain our failure to achieve predictive values around 100%.…”

Section: Discussionmentioning

confidence: 92%

Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

Cayuela

Simó

Majós

et al. 2017

Euro J of Neurology

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Section: Discussionmentioning

confidence: 92%

Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

Cayuela

Simó

Majós

et al. 2017

Euro J of Neurology

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“…Tumors involving the cerebral cortex, particularly the motor cortex, are more likely to produce seizures than tumors in the deep gray matter, although the latter can also lead to seizures because of surrounding edema and mass effect . Seizures can be a significant source of quality‐of‐life impairment for patients with brain tumors …”

Section: Seizures In Patients Who Have Cancer With Brain Lesionsmentioning

confidence: 99%

“…In low‐grade, diffuse gliomas (diffuse astrocytoma and oligodendroglioma), the higher incidence of seizures is thought to be related to isocitrate dehydrogenase (IDH) gene mutations, which are present in approximately 80% of these tumors . Mutant IDH converts α‐ketoglutarate into D‐2‐hydroxyglutarate (D2‐HG), an oncometabolite that, in addition to playing a role in oncogenesis through the alteration of epigenetic states, has a chemical structure similar to that of glutamate and, when secreted extracellularly, is thought to produce a proepileptic state by activating neuronal NMDA receptors, creating excitatory postsynaptic potentials and increasing the likelihood of action potentials …”

Section: Seizures In Patients Who Have Cancer With Brain Lesionsmentioning

confidence: 99%

“…11 Seizures can be a significant source of quality-of-life impairment for patients with brain tumors. [12][13][14][15] In addition to the brain lesions themselves, seizures can also be a byproduct of the treatment provided, including surgery, radiation, and systemic therapies. On the basis of retrospective analyses of neurosurgical records, the estimated incidence of seizures after craniotomy is between 15% and 20%.…”

Section: Seizures In Patients Who Have Cancer With Brain Lesionsmentioning

confidence: 99%

“…34 Mutant IDH converts α-ketoglutarate into D-2-hydroxyglutarate (D2-HG), an oncometabolite that, in addition to playing a role in oncogenesis through the alteration of epigenetic states, 35 has a chemical structure similar to that of glutamate and, when secreted extracellularly, is thought to produce a proepileptic state by activating neuronal NMDA receptors, creating excitatory postsynaptic potentials and increasing the likelihood of action potentials. 14 In high-grade gliomas, glutamate also plays an important role in epileptogenicity. SLC7A11/xCT, the catalytic subunit of system x − c (SXC) and a membrane antiporter that couples the efflux of glutamate with the influx of cystine, is upregulated in >50% of high-grade gliomas.…”

Section: Seizures In Patients Who Have Cancer With Brain Lesionsmentioning

confidence: 99%

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Seizures in patients with cancer

Castro

Milligan

2020

Cancer

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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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Glioblastoma and Other Primary Brain Malignancies in Adults

Schaff

Mellinghoff

2023

JAMA

136

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ImportanceMalignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%.ObservationsApproximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P &lt; .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation.Conclusions and RelevanceThe incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals, and approximately 49% of primary malignant brain tumors are glioblastomas. Most patients die from progressive disease. First-line therapy for glioblastoma is surgery followed by radiation and the alkylating chemotherapeutic agent temozolomide.

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Mutant IDH1 and seizures in patients with glioma

Cited by 176 publications

References 40 publications

Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

Seizures in patients with cancer

Glioblastoma and Other Primary Brain Malignancies in Adults

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