Skip to main content
Top
Published in: NeuroMolecular Medicine 2/2021

01-06-2021 | Glioblastoma | Original Paper

Molecular Classification of Gliomas is Associated with Seizure Control: A Retrospective Analysis

Authors: Teresa P. Easwaran, Nicola Lancki, Mario Henriquez, Alexander O. Vortmeyer, Nicholas M. Barbaro, Denise M. Scholtens, Atique U. Ahmed, Mahua Dey

Published in: NeuroMolecular Medicine | Issue 2/2021

Login to get access

Abstract

Classically, histologic grading of gliomas has been used to predict seizure association, with low-grade gliomas associated with an increased incidence of seizures compared to high-grade gliomas. In 2016, WHO reclassified gliomas based on histology and molecular characteristics. We sought to determine whether molecular classification of gliomas is associated with preoperative seizure presentation and/or post-operative seizure control across multiple glioma subtypes. All gliomas operated at our institution from 2007 to 2017 were identified based on ICD 9 and 10 billing codes and were retrospectively assessed for molecular classification of the IDH1 mutation, and 1p/19q codeletion. Logistic regression models were performed to assess associations of seizures at presentation as well as post-operative seizures with IDH status and the new WHO integrated classification. Our study included 376 patients: 82 IDH mutant and 294 IDH wildtype. The presence of IDH mutation was associated with seizures at presentation [OR 3.135 (1.818–5.404), p < 0.001]. IDH-mutant glioblastomas presented with seizures less often than other IDH-mutant glioma subtypes grade II and III [OR 0.104 (0.032–0.340), p < 0.001]. IDH-mutant tumors were associated with worse post-operative seizure outcomes, demonstrated by Engel Class [OR 2.666 (1.592–4.464), p < 0.001]. IDH mutation in gliomas is associated with an increased risk of seizure development and worse post-operative seizure control, in all grades except for GBM.
Literature
go back to reference Avila, E. K., Chamberlain, M., Schiff, D., et al. (2016). Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro-Oncology, 19(1), 12–21.PubMedPubMedCentral Avila, E. K., Chamberlain, M., Schiff, D., et al. (2016). Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro-Oncology, 19(1), 12–21.PubMedPubMedCentral
go back to reference Bridges, R. J., Natale, N. R., & Patel, S. A. (2012). System xc- cystine/glutamate antiporter: An update on molecular pharmacology and roles within the CNS. British Journal of Pharmacology, 165(1), 20–34.PubMedPubMedCentral Bridges, R. J., Natale, N. R., & Patel, S. A. (2012). System xc- cystine/glutamate antiporter: An update on molecular pharmacology and roles within the CNS. British Journal of Pharmacology, 165(1), 20–34.PubMedPubMedCentral
go back to reference Brogna, C., Gil Robles, S., & Duffau, H. (2008). Brain tumors and epilepsy. Expert Review of Neurotherapeutics, 8(6), 941–955.PubMed Brogna, C., Gil Robles, S., & Duffau, H. (2008). Brain tumors and epilepsy. Expert Review of Neurotherapeutics, 8(6), 941–955.PubMed
go back to reference Chang, E. F., Potts, M. B., Keles, G. E., et al. (2008). Seizure characteristics and control following resection in 332 patients with low-grade gliomas. Journal of Neurosurgery, 108(2), 227–235.PubMed Chang, E. F., Potts, M. B., Keles, G. E., et al. (2008). Seizure characteristics and control following resection in 332 patients with low-grade gliomas. Journal of Neurosurgery, 108(2), 227–235.PubMed
go back to reference Chen, H., Judkins, J., Thomas, C., et al. (2017). Mutant IDH1 and seizures in patients with glioma. Neurology, 88(19), 1805.PubMedPubMedCentral Chen, H., Judkins, J., Thomas, C., et al. (2017). Mutant IDH1 and seizures in patients with glioma. Neurology, 88(19), 1805.PubMedPubMedCentral
go back to reference Cohen, A. L., Holmen, S. L., & Colman, H. (2013). IDH1 and IDH2 mutations in gliomas. Current Neurology and Neuroscience Reports, 13(5), 345.PubMedPubMedCentral Cohen, A. L., Holmen, S. L., & Colman, H. (2013). IDH1 and IDH2 mutations in gliomas. Current Neurology and Neuroscience Reports, 13(5), 345.PubMedPubMedCentral
go back to reference Dario, J. E., Mitchel, S. B., Nicholas, M. B., & Edward, F. C. (2011). Predictors of seizure freedom after resection of supratentorial low-grade gliomas. Journal of Neurosurgery JNS, 115(2), 240–244. Dario, J. E., Mitchel, S. B., Nicholas, M. B., & Edward, F. C. (2011). Predictors of seizure freedom after resection of supratentorial low-grade gliomas. Journal of Neurosurgery JNS, 115(2), 240–244.
go back to reference Edward, F. C., Matthew, B. P., Keles, G. E., et al. (2008). Seizure characteristics and control following resection in 332 patients with low-grade gliomas. Journal of Neurosurgery JNS, 108(2), 227–235. Edward, F. C., Matthew, B. P., Keles, G. E., et al. (2008). Seizure characteristics and control following resection in 332 patients with low-grade gliomas. Journal of Neurosurgery JNS, 108(2), 227–235.
go back to reference Engel, J. (1993). Surgical treatment of the epilepsies. New York: Lippincott Williams & Wilkins. Engel, J. (1993). Surgical treatment of the epilepsies. New York: Lippincott Williams & Wilkins.
go back to reference Englot, D. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2011a). Predictors of seizure freedom after resection of supratentorial low-grade gliomas. A review. Journal of Neurosurgery, 115(2), 240–244.PubMed Englot, D. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2011a). Predictors of seizure freedom after resection of supratentorial low-grade gliomas. A review. Journal of Neurosurgery, 115(2), 240–244.PubMed
go back to reference Englot, D. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2012a). Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia, 53(1), 51–57.PubMed Englot, D. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2012a). Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia, 53(1), 51–57.PubMed
go back to reference Englot, D. J., Han, S. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2011b). Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery, 70(4), 921–928. Englot, D. J., Han, S. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2011b). Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery, 70(4), 921–928.
go back to reference Englot, D. J., Han, S. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2012b). Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery, 70(4), 921–928. discussion 928.PubMed Englot, D. J., Han, S. J., Berger, M. S., Barbaro, N. M., & Chang, E. F. (2012b). Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery, 70(4), 921–928. discussion 928.PubMed
go back to reference Gonen, T., Grossman, R., Sitt, R., et al. (2014). Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy. Journal of Neurosurgery, 121(5), 1133–1138.PubMed Gonen, T., Grossman, R., Sitt, R., et al. (2014). Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy. Journal of Neurosurgery, 121(5), 1133–1138.PubMed
go back to reference Huberfeld, G., & Vecht, C. J. (2016). Seizures and gliomas–towards a single therapeutic approach. Nature Reviews Neurology, 12(4), 204–216.PubMed Huberfeld, G., & Vecht, C. J. (2016). Seizures and gliomas–towards a single therapeutic approach. Nature Reviews Neurology, 12(4), 204–216.PubMed
go back to reference Ius, T., Pauletto, G., Tomasino, B., et al. (2020). Predictors of postoperative seizure outcome in low grade glioma: From volumetric analysis to molecular stratification. Cancers (Basel), 12(2), 397. Ius, T., Pauletto, G., Tomasino, B., et al. (2020). Predictors of postoperative seizure outcome in low grade glioma: From volumetric analysis to molecular stratification. Cancers (Basel), 12(2), 397.
go back to reference Koekkoek, J. A., Kerkhof, M., Dirven, L., Heimans, J. J., Reijneveld, J. C., & Taphoorn, M. J. (2015). Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: A systematic review. Neuro Oncology, 17(7), 924–934.PubMedPubMedCentral Koekkoek, J. A., Kerkhof, M., Dirven, L., Heimans, J. J., Reijneveld, J. C., & Taphoorn, M. J. (2015). Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: A systematic review. Neuro Oncology, 17(7), 924–934.PubMedPubMedCentral
go back to reference Louis, D. N., Perry, A., Reifenberger, G., et al. (2016). The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathologica, 131(6), 803–820.PubMed Louis, D. N., Perry, A., Reifenberger, G., et al. (2016). The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathologica, 131(6), 803–820.PubMed
go back to reference Manaka, S., Ishijima, B., & Mayanagi, Y. (2003a). Postoperative seizures: Epidemiology, pathology, and prophylaxis. Neurologia medico-chirurgica (Tokyo), 43(12), 589–600. discussion 600. Manaka, S., Ishijima, B., & Mayanagi, Y. (2003a). Postoperative seizures: Epidemiology, pathology, and prophylaxis. Neurologia medico-chirurgica (Tokyo), 43(12), 589–600. discussion 600.
go back to reference Manaka, S., Ishijima, B., & Mayanagi, Y. (2003b). Postoperative seizures: Epidemiology, pathology, and prophylaxis. Neurologia Medico-Chirurgica, 43(12), 589–600.PubMed Manaka, S., Ishijima, B., & Mayanagi, Y. (2003b). Postoperative seizures: Epidemiology, pathology, and prophylaxis. Neurologia Medico-Chirurgica, 43(12), 589–600.PubMed
go back to reference Maschio, M., & Dinapoli, L. (2012). Patients with brain tumor-related epilepsy. Journal of Neuro-oncology, 109(1), 1–6.PubMed Maschio, M., & Dinapoli, L. (2012). Patients with brain tumor-related epilepsy. Journal of Neuro-oncology, 109(1), 1–6.PubMed
go back to reference Maschio, M., Dinapoli, L., Mingoia, M., et al. (2011). Lacosamide as add-on in brain tumor-related epilepsy: Preliminary report on efficacy and tolerability. Journal of Neurology, 258(11), 2100–2104.PubMed Maschio, M., Dinapoli, L., Mingoia, M., et al. (2011). Lacosamide as add-on in brain tumor-related epilepsy: Preliminary report on efficacy and tolerability. Journal of Neurology, 258(11), 2100–2104.PubMed
go back to reference Maschio, M., Dinapoli, L., Sperati, F., et al. (2010). Oxcarbazepine in brain tumor-related epilepsy: Efficacy, side effects and impact on quality of life. Epilepsia, 51, 76–77. Maschio, M., Dinapoli, L., Sperati, F., et al. (2010). Oxcarbazepine in brain tumor-related epilepsy: Efficacy, side effects and impact on quality of life. Epilepsia, 51, 76–77.
go back to reference Maschio, M., Dinapoli, L., Sperati, F., et al. (2012). Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: Open-label pilot study for assessing the efficacy, tolerability and impact on quality of life. Journal of Neuro-oncology, 106(3), 651–656.PubMed Maschio, M., Dinapoli, L., Sperati, F., et al. (2012). Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: Open-label pilot study for assessing the efficacy, tolerability and impact on quality of life. Journal of Neuro-oncology, 106(3), 651–656.PubMed
go back to reference Mitchel, S. B., Saadi, G., Michael, M. H., Jill, D., & George, A. O. (1993). Low-grade gliomas associated with intractable epilepsy: Seizure outcome utilizing electrocorticography during tumor resection. Journal of Neurosurgery, 79(1), 62–69. Mitchel, S. B., Saadi, G., Michael, M. H., Jill, D., & George, A. O. (1993). Low-grade gliomas associated with intractable epilepsy: Seizure outcome utilizing electrocorticography during tumor resection. Journal of Neurosurgery, 79(1), 62–69.
go back to reference Neal, A., Yuen, T., Bjorksten, A. R., Kwan, P., O’Brien, T. J., & Morokoff, A. (2016). Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas. Journal of Neuro-oncology, 129(2), 259–267.PubMed Neal, A., Yuen, T., Bjorksten, A. R., Kwan, P., O’Brien, T. J., & Morokoff, A. (2016). Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas. Journal of Neuro-oncology, 129(2), 259–267.PubMed
go back to reference North, J. B., Penhall, R. K., Hanieh, A., Frewin, D. B., & Taylor, W. B. (1983). Phenytoin and postoperative epilepsy: A double-blind study. Journal of Neurosurgery, 58(5), 672–677.PubMed North, J. B., Penhall, R. K., Hanieh, A., Frewin, D. B., & Taylor, W. B. (1983). Phenytoin and postoperative epilepsy: A double-blind study. Journal of Neurosurgery, 58(5), 672–677.PubMed
go back to reference Oppenlander, M. E., Wolf, A. B., Snyder, L. A., et al. (2014). An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. Journal of Neurosurgery, 120(4), 846–853.PubMed Oppenlander, M. E., Wolf, A. B., Snyder, L. A., et al. (2014). An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. Journal of Neurosurgery, 120(4), 846–853.PubMed
go back to reference Pallud, J., Audureau, E., Blonski, M., et al. (2014). Epileptic seizures in diffuse low-grade gliomas in adults. Brain, 137(Pt 2), 449–462.PubMed Pallud, J., Audureau, E., Blonski, M., et al. (2014). Epileptic seizures in diffuse low-grade gliomas in adults. Brain, 137(Pt 2), 449–462.PubMed
go back to reference Perry, J., Zinman, L., Chambers, A., et al. (2006). The use of prophylactic anticonvulsants in patients with brain tumours—A systematic review. Current Oncology, 13(6), 222.PubMedPubMedCentral Perry, J., Zinman, L., Chambers, A., et al. (2006). The use of prophylactic anticonvulsants in patients with brain tumours—A systematic review. Current Oncology, 13(6), 222.PubMedPubMedCentral
go back to reference Perucca, E. (2013). Optimizing antiepileptic drug treatment in tumoral epilepsy. Epilepsia, 54, 97–104.PubMed Perucca, E. (2013). Optimizing antiepileptic drug treatment in tumoral epilepsy. Epilepsia, 54, 97–104.PubMed
go back to reference Perucca, E., Gram, L., Avanzini, G., & Dulac, O. (1998). Antiepileptic drugs as a cause of worsening seizures. Epilepsia, 39(1), 5–17.PubMed Perucca, E., Gram, L., Avanzini, G., & Dulac, O. (1998). Antiepileptic drugs as a cause of worsening seizures. Epilepsia, 39(1), 5–17.PubMed
go back to reference Roberts, M., Northmore, T., Shires, J., Taylor, P., & Hayhurst, C. (2018). Diffuse low grade glioma after the 2016 WHO update, seizure characteristics, imaging correlates and outcomes. Clinical Neurology and Neurosurgery, 175, 9–15.PubMed Roberts, M., Northmore, T., Shires, J., Taylor, P., & Hayhurst, C. (2018). Diffuse low grade glioma after the 2016 WHO update, seizure characteristics, imaging correlates and outcomes. Clinical Neurology and Neurosurgery, 175, 9–15.PubMed
go back to reference Rossetti, A. O., & Stupp, R. (2010). Epilepsy in brain tumor patients. Current Opinion in Neurology, 23(6), 603–609.PubMed Rossetti, A. O., & Stupp, R. (2010). Epilepsy in brain tumor patients. Current Opinion in Neurology, 23(6), 603–609.PubMed
go back to reference Rowe, A. S., Goodwin, H., Brophy, G. M., et al. (2014). Seizure prophylaxis in neurocritical care: A review of evidence-based support. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 34(4), 396–409. Rowe, A. S., Goodwin, H., Brophy, G. M., et al. (2014). Seizure prophylaxis in neurocritical care: A review of evidence-based support. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 34(4), 396–409.
go back to reference Ruda, R., Magliola, U., Bertero, L., et al. (2013). Seizure control following radiotherapy in patients with diffuse gliomas: A retrospective study. Neuro Oncology, 15(12), 1739–1749.PubMedPubMedCentral Ruda, R., Magliola, U., Bertero, L., et al. (2013). Seizure control following radiotherapy in patients with diffuse gliomas: A retrospective study. Neuro Oncology, 15(12), 1739–1749.PubMedPubMedCentral
go back to reference Sayegh, E. T., Fakurnejad, S., Oh, T., Bloch, O., & Parsa, A. T. (2014). Anticonvulsant prophylaxis for brain tumor surgery: Determining the current best available evidence: A review. Journal of Neurosurgery, 121(5), 1139–1147.PubMed Sayegh, E. T., Fakurnejad, S., Oh, T., Bloch, O., & Parsa, A. T. (2014). Anticonvulsant prophylaxis for brain tumor surgery: Determining the current best available evidence: A review. Journal of Neurosurgery, 121(5), 1139–1147.PubMed
go back to reference Sirven, J. I., Wingerchuk, D. M., Drazkowski, J. F., Lyons, M. K., & Zimmerman, R. S. (2004). Seizure prophylaxis in patients with brain tumors: A meta-analysis. Mayo Clinic Proceedings, 79, 1489–1494.PubMed Sirven, J. I., Wingerchuk, D. M., Drazkowski, J. F., Lyons, M. K., & Zimmerman, R. S. (2004). Seizure prophylaxis in patients with brain tumors: A meta-analysis. Mayo Clinic Proceedings, 79, 1489–1494.PubMed
go back to reference Taphoorn, M. J. B. (2003). Neurocognitive sequelae in the treatment of low-grade gliomas. Seminars in Oncology, 30, 45–48.PubMed Taphoorn, M. J. B. (2003). Neurocognitive sequelae in the treatment of low-grade gliomas. Seminars in Oncology, 30, 45–48.PubMed
go back to reference Temkin, N. R. (2001). Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: Meta-analysis of controlled trials. Epilepsia, 42(4), 515–524.PubMed Temkin, N. R. (2001). Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: Meta-analysis of controlled trials. Epilepsia, 42(4), 515–524.PubMed
go back to reference Temkin, N. R., Dikmen, S. S., Wilensky, A. J., Keihm, J., Chabal, S., & Winn, H. R. (1990). A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. New England Journal of Medicine, 323(8), 497–502. Temkin, N. R., Dikmen, S. S., Wilensky, A. J., Keihm, J., Chabal, S., & Winn, H. R. (1990). A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. New England Journal of Medicine, 323(8), 497–502.
go back to reference Tremont-Lukats, I. W., Ratilal, B. O., Armstrong, T., & Gilbert, M. R. (2008a). Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database of Systematic Reviews, 2, CD004424. Tremont-Lukats, I. W., Ratilal, B. O., Armstrong, T., & Gilbert, M. R. (2008a). Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database of Systematic Reviews, 2, CD004424.
go back to reference van Breemen, M. S. M., Wilms, E. B., & Vecht, C. J. (2007). Epilepsy in patients with brain tumours: Epidemiology, mechanisms, and management. The Lancet Neurology, 6(5), 421–430.PubMed van Breemen, M. S. M., Wilms, E. B., & Vecht, C. J. (2007). Epilepsy in patients with brain tumours: Epidemiology, mechanisms, and management. The Lancet Neurology, 6(5), 421–430.PubMed
go back to reference Vecht, C. J., Kerkhof, M., & Duran-Pena, A. (2014). Seizure prognosis in brain tumors: New insights and evidence-based management. The Oncologist, 19(7), 751.PubMedPubMedCentral Vecht, C. J., Kerkhof, M., & Duran-Pena, A. (2014). Seizure prognosis in brain tumors: New insights and evidence-based management. The Oncologist, 19(7), 751.PubMedPubMedCentral
go back to reference Vecht, C. J., & Van Breemen, M. (2006). Optimizing therapy of seizures in patients with brain tumors. Neurology, 67(12 suppl 4), S10–S13.PubMed Vecht, C. J., & Van Breemen, M. (2006). Optimizing therapy of seizures in patients with brain tumors. Neurology, 67(12 suppl 4), S10–S13.PubMed
go back to reference Wen, P. Y., Schiff, D., Kesari, S., Drappatz, J., Gigas, D. C., & Doherty, L. (2006). Medical management of patients with brain tumors. Journal of Neuro-oncology, 80(3), 313–332.PubMed Wen, P. Y., Schiff, D., Kesari, S., Drappatz, J., Gigas, D. C., & Doherty, L. (2006). Medical management of patients with brain tumors. Journal of Neuro-oncology, 80(3), 313–332.PubMed
go back to reference Xiao-Ya, L. I. U., & Xue-Feng, W. (2011). Brain-tumor related epilepsy: Review of the literature. Cancer Therapy, 8, 130–138. Xiao-Ya, L. I. U., & Xue-Feng, W. (2011). Brain-tumor related epilepsy: Review of the literature. Cancer Therapy, 8, 130–138.
go back to reference Xu, D. S., Awad, A. W., Mehalechko, C., et al. (2018). An extent of resection threshold for seizure freedom in patients with low-grade gliomas. Journal of Neurosurgery, 128(4), 1084–1090.PubMed Xu, D. S., Awad, A. W., Mehalechko, C., et al. (2018). An extent of resection threshold for seizure freedom in patients with low-grade gliomas. Journal of Neurosurgery, 128(4), 1084–1090.PubMed
go back to reference Yan, H., Parsons, D. W., Jin, G., et al. (2009). IDH1 and IDH2 mutations in gliomas. New England Journal of Medicine, 360(8), 765–773. Yan, H., Parsons, D. W., Jin, G., et al. (2009). IDH1 and IDH2 mutations in gliomas. New England Journal of Medicine, 360(8), 765–773.
go back to reference Ye, Z. C., Rothstein, J. D., & Sontheimer, H. (1999). Compromised glutamate transport in human glioma cells: Reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange. Journal of Neuroscience, 19(24), 10767–10777.PubMed Ye, Z. C., Rothstein, J. D., & Sontheimer, H. (1999). Compromised glutamate transport in human glioma cells: Reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange. Journal of Neuroscience, 19(24), 10767–10777.PubMed
go back to reference Ye, Z. C., & Sontheimer, H. (1999). Glioma cells release excitotoxic concentrations of glutamate. Cancer Research, 59(17), 4383–4391.PubMed Ye, Z. C., & Sontheimer, H. (1999). Glioma cells release excitotoxic concentrations of glutamate. Cancer Research, 59(17), 4383–4391.PubMed
Metadata
Title
Molecular Classification of Gliomas is Associated with Seizure Control: A Retrospective Analysis
Authors
Teresa P. Easwaran
Nicola Lancki
Mario Henriquez
Alexander O. Vortmeyer
Nicholas M. Barbaro
Denise M. Scholtens
Atique U. Ahmed
Mahua Dey
Publication date
01-06-2021
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 2/2021
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-020-08624-0

Other articles of this Issue 2/2021

NeuroMolecular Medicine 2/2021 Go to the issue