Dose-dependent seizure control with MEK inhibitor therapy for progressive glioma in a child with neurofibromatosis type 1

Cantor, Evan; Meyer, Ashley; Morris, Stephanie; Weisenberg, Judith; Brossier, Nicole

doi:10.1007/s00381-022-05571-y

Cited by 8 publications

(6 citation statements)

References 23 publications

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Section: Discussionmentioning

confidence: 89%

“…In terms of clinical findings, a recent case report described use of a MEK inhibitor (i.e., selumetinib) to treat a progressive optic pathway glioma in child with neurofibromatosis type 1 who also had medically refractory epilepsy. This patient showed resolution of seizures upon initiation of therapy with re‐emergence of seizures after dose reduction and subsequent cessation of seizures upon return to full dose (Cantor et al, 2022). Similarly, another study reported reductions in seizures in response to the MEK inhibitor trametinib in two RASopathy patients with treatment‐resistant epilepsy, including one patient carrying a p.F595L germline variant in BRAF (D'Onofrio et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication

Kenney‐Jung,

Collazo‐Lopez,

Rogers

et al. 2023

American J of Med Genetics Pt A

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Treatment‐resistant epilepsy is among the most serious complications of cardiofaciocutaneous syndrome (CFCS), a rare disorder caused by germline variants in the RAS‐MAPK signaling pathway. This study analyzed the clinical characteristics of epilepsy and response to anti‐seizure medications (ASMs) in a multinational CFCS cohort. A caregiver survey provided data regarding seizure history, use of ASMs and other treatment approaches, adverse effects, caregiver perception of treatment response, and neurological disease burden impact among individuals with CFCS. Results from 138 survey responses were quantitatively analyzed in conjunction with molecular genetic results and neurological records. The disease burden impact of CFCS was higher among individuals with epilepsy (n = 74/138), especially those with more severe seizure presentation. Oxcarbazepine, a sodium‐channel blocker, had the best seizure control profile with relatively infrequent adverse effects. The most commonly prescribed ASM, levetiracetam, demonstrated comparatively poor seizure control. ASM efficacy was generally similar for individuals with BRAF and MAP2K1 gene variants. The high proportion of patients with CFCS who experienced poor seizure control despite use of multiple ASMs highlights a substantial unmet treatment need. Prospective study of ASM efficacy and clinical trials of therapies to attenuate RAS‐MAPK signaling may improve avenues for clinical management.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication

Kenney‐Jung,

Collazo‐Lopez,

Rogers

et al. 2023

American J of Med Genetics Pt A

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“…This patient had a bilateral OPG with extension into the hypothalamus, basal ganglia, and subcortical white matter, as well as a mass effect on the right insular cortex and focal symptomatic epilepsy lateralized to the right hemisphere. Repeat brain MRIs after treatment by MEKi revealed a stable mass size but interval reduction in enhancement of the right frontal lesion suggestive of a treatment response 30 …”

Section: Discussionmentioning

confidence: 96%

“…In regard to NF1, a recent case report described effective treatment of the associated epilepsy with selumetinib in a patient who appeared to have dose‐dependent seizure control while receiving MEK inhibition for their glioma 30 . This patient had a bilateral OPG with extension into the hypothalamus, basal ganglia, and subcortical white matter, as well as a mass effect on the right insular cortex and focal symptomatic epilepsy lateralized to the right hemisphere.…”

Section: Discussionmentioning

confidence: 99%

Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1—Developmental and epileptic encephalopathy and optic pathway glioma

Barrière,

Faure‐Conter,

Leblond

et al. 2023

Epileptic Disorders

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BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%. Several case reports and early phase clinical trials have demonstrated that the mitogen‐activated protein kinase inhibitors (MEKi) are effective in NF1‐low‐grade gliomas (LGGs), but their influence on seizure activity in humans has not been established.Case studyHere, we report a patient with NF1 and developmental and epileptic encephalopathy (DEE) harboring pharmacoresistant tonic seizures, and progressive optic pathway glioma (OPG). By using a MEKi therapy for her OPG, we observed an end to epileptic seizures as well as a significant improvement of interictal EEG abnormalities, despite a lack of tumor reduction.ConclusionMEK inhibitor therapy should be considered for patients with NF1 and refractory epilepsy.

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“…Other targeted agents may also hold promise in this regard, including MEK inhibitors. 8 Further study of neurologic symptom control with targeted therapy versus traditional chemotherapeutic agents is needed to understand this effect.…”

mentioning

confidence: 99%

Rapid symptomatic improvement in two patients with ganglioglioma after restarting BRAF inhibitor therapy

Cantor

Berkovich

Navalkele

et al. 2023

Pediatric Blood & Cancer

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Gangliogliomas (GG) are composed of mixed neuronal and glial components and are commonly associated with neurologic symptoms that vary by tumor location. Biologically targeted agents such as the BRAF inhibitors dabrafenib and vemurafenib are now used to treat progressive low-grade gliomas (LGG), including GG, 1,2 but the effect of these agents on the neurologic symptoms that may accompany LGGs is poorly understood. 3 Here, we describe clinical and radiographic response from single-therapy BRAF inhibition in two patients with F I G U R E 1 Case 1: (A) Coronal FLAIR sequence showing medullary ganglioglioma at diagnosis. (B) Coronal FLAIR sequence, prior to discontinuing initial therapy. (C) Coronal FLAIR sequence following discontinuation of initial therapy demonstrating progression of disease. (D) Coronal FLAIR following resumption of therapy demonstrating response to therapy with decreased disease burden after re-challenge.

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Dose-dependent seizure control with MEK inhibitor therapy for progressive glioma in a child with neurofibromatosis type 1

Cited by 8 publications

References 23 publications

Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication

Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication

Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1—Developmental and epileptic encephalopathy and optic pathway glioma

Rapid symptomatic improvement in two patients with ganglioglioma after restarting BRAF inhibitor therapy

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