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Causes of New-Onset Seizures and Their Treatment in Children With Non-CNS Malignancies: A Retrospective Study in a Tertiary Care Center

  • Fatima Jaafar
    Affiliations
    Division of Child Neurology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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  • Miguel R. Abboud
    Affiliations
    Division of Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Children's Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
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  • Makram Obeid
    Correspondence
    Communications should be addressed to: Dr. Obeid; Department of Anatomy; Cell Biology and Physiological Sciences; American University of Beirut; Diana Tamari Sabbagh (DTS) Building, 117b, P.O. Box 11-0236, Riad El-Solh; Beirut 1107 2020, Lebanon.
    Affiliations
    Division of Child Neurology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Department of Anatomy, Cell biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
    Search for articles by this author

      Abstract

      Background

      Seizures occur in up to 13% of children with non-central nervous system (CNS) malignancies, but little is known about their causes and optimal diagnostic and therapeutic approaches. Here we sought to determine etiologies and clinical trajectories of new-onset seizures in this patient population.

      Methods

      A retrospective chart review over a 10-year period was conducted at the American University of Beirut Medical Center to identify children with non-CNS malignancies and at least one new-onset seizure. Data were collected on the underlying malignancy, seizure etiology, clinical course, treatments, electroencephalograms, and brain imaging.

      Results

      New-onset seizures occurred in 56 children (2-year median follow-up), most commonly in the context of acute lymphoblastic leukemia, lymphomas, and sarcomas. In 19 children, the first seizure consisted of status epilepticus. The most common etiologies were cerebrovascular accidents, posterior reversible encephalopathy syndrome, and metastasis. Forty-nine patients received anti-seizure medications (ASMs). Withdrawal of ASMs was successful in 19 children with normal initial or follow-up brain imaging but failed in three patients with persistent brain lesions. The remaining children, all of whom except two had structural brain abnormalities, received chronic ASMs and remained seizure free for a median period of 2 years at the last follow-up in survivors.

      Conclusions

      Not only are seizures in children with non-CNS cancers often indicative of a serious brain insult, but they can also be challenging in the form of status epilepticus. An urgent diagnostic evaluation is therefore needed to expedite treatment, which should be tailored to the chronicity of the underlying cause.

      Keywords

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      References

        • Singh G.
        • Rees J.H.
        • Sander J.W.
        Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment.
        J Neurol Neurosurg Psychiatry. 2007; 78: 342-349
        • Neil E.C.
        • Hanmantgad S.
        • Khakoo Y.
        Neurological complications of pediatric cancer.
        J Child Neurol. 2016; 31: 1412-1420
        • Nassar S.L.
        • Conklin H.M.
        • Zhou Y.
        • et al.
        Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia.
        Pediatr Blood Cancer. 2017; 64: e26436
        • Gonzalez Castro L.N.
        • Milligan T.A.
        Seizures in patients with cancer.
        Cancer. 2020; 126: 1379-1389
        • Antunes N.L.
        Seizures in children with systemic cancer.
        Pediatr Neurol. 2003; 28: 190-193
        • Weller M.
        • Stupp R.
        • Wick W.
        Epilepsy meets cancer: when, why, and what to do about it?.
        Lancet Oncol. 2012; 13: e375-e382
        • Khan R.B.
        • Morris E.B.
        • Pui C.H.
        • et al.
        Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.
        J Child Neurol. 2014; 29: 774-781
        • Trinka E.
        • Cock H.
        • Hesdorffer D.
        • et al.
        A definition and classification of status epilepticus–report of the ILAE task force on classification of status epilepticus.
        Epilepsia. 2015; 56: 1515-1523
        • Shah V.A.
        • Suarez J.I.
        Seizures and status epilepticus in critically ill cancer patients.
        in: Oncologic Critical Care. Springer International Publishing, Cham2020: 335-352
        • Hun M.
        • Xie M.
        • She Z.
        • et al.
        Management and clinical outcome of posterior reversible encephalopathy syndrome in pediatric oncologic/hematologic diseases: a PRES subgroup analysis with a large sample size.
        Front Pediatr. 2021; 9678890
        • Zima L.A.
        • Tulpule S.
        • Samson K.
        • Shonka N.
        Seizure prevalence, contributing factors, and prognostic factors in patients with leptomeningeal disease.
        J Neurol Sci. 2019; 403: 19-23
        • Ajinkya S.
        • Fox J.
        • Houston P.
        • et al.
        Seizures in patients with metastatic brain tumors: prevalence, clinical characteristics, and features on EEG.
        J Clin Neurophysiol. 2021; 38: 143-148
        • Ajithkumar T.
        • Parkinson C.
        • Shamshad F.
        • Murray P.
        Ifosfamide encephalopathy.
        Clin Oncol (R Coll Radiol). 2007; 19: 108-114
        • Gandy K.
        • Scoggins M.A.
        • Jacola L.M.
        • Litten M.
        • Reddick W.E.
        • Krull K.R.
        Structural and functional brain imaging in long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy: a systematic review.
        JNCI Cancer Spectr. 2021; 5pkab069
        • Rijmenams I.
        • Moechars D.
        • Uyttebroeck A.
        • et al.
        Age- and Intravenous methotrexate-associated leukoencephalopathy and its neurological Impact in pediatric patients with lymphoblastic leukemia.
        Cancers (Basel). 2021; 13: 1939
        • Sabin N.D.
        • Cheung Y.T.
        • Reddick W.E.
        • et al.
        The Impact of persistent leukoencephalopathy on brain white matter microstructure in long-term survivors of acute lymphoblastic leukemia treated with chemotherapy only.
        AJNR Am J Neuroradiol. 2018; 39: 1919-1925
        • Obeid M.
        • Frank J.
        • Medina M.
        • et al.
        Neuroprotective effects of leptin following kainic acid-induced status epilepticus.
        Epilepsy Behav. 2010; 19: 278-283
        • Spindler M.
        • Jacks L.M.
        • Chen X.
        • Panageas K.
        • DeAngelis L.M.
        • Avila E.K.
        Spectrum of nonconvulsive status epilepticus in patients with cancer.
        J Clin Neurophysiol. 2013; 30: 339-343
        • Asdikian R.
        • Hajjar H.
        • Alturk S.
        • et al.
        Hippocampal injury and learning deficits following non-convulsive status epilepticus in periadolescent rats.
        Epilepsy Behav. 2021; 125108415
        • Khan R.B.
        • Marshman K.C.
        • Mulhern R.K.
        Atonic seizures in survivors of childhood cancer.
        J Child Neurol. 2003; 18: 397-400
        • Ghali M.G.Z.
        • Davanzo J.
        • Leo M.
        • Rizk E.
        Posterior reversible encephalopathy syndrome in pediatric patients: pathophysiology, diagnosis, and management.
        Leuk Lymphoma. 2019; 60: 2365-2372
        • Gloss D.
        • Pargeon K.
        • Pack A.
        • et al.
        Antiseizure medication withdrawal in seizure-free patients: practice advisory update summary: report of the AAN guideline subcommittee.
        Neurology. 2021; 97: 1072-1081
        • Hnaini M.
        • Darwich M.
        • Koleilat N.
        • et al.
        High-dose levetiracetam for neonatal seizures: a retrospective review.
        Seizure. 2020; 82: 7-11
        • Obeid M.
        • Pong A.W.
        Efficacy and tolerability of high oral doses of levetiracetam in children with epilepsy.
        Epilepsy Res. 2010; 91: 101-105
        • Medlej Y.
        • Salah H.
        • Wadi L.
        • et al.
        Overview on emotional behavioral testing in rodent models of pediatric epilepsy.
        Methods Mol Biol. 2019; 2011: 345-367