[en] Complex febrile seizures (CFS), a subset of paediatric febrile seizures (FS), have been studied for their prognosis, epileptogenic potential and neurocognitive outcome. We evaluated their functional connectivity differences with simple febrile seizures (SFS) in children with recent-onset FS. Resting-state fMRI (rs-fMRI) datasets of 24 children with recently diagnosed FS (SFS-n = 11; CFS-n = 13) were analysed. Functional connectivity (FC) was estimated using time series correlation of seed region-to-whole-brain-voxels and network topology was assessed using graph theory measures. Regional connectivity differences were correlated with clinical characteristics (FDR corrected p < 0.05). CFS patients demonstrated increased FC of the bilateral middle temporal pole (MTP), and bilateral thalami when compared to SFS. Network topology study revealed increased clustering coefficient and decreased participation coefficient in basal ganglia and thalamus suggesting an inefficient-unbalanced network topology in patients with CFS. The number of seizure recurrences negatively correlated with the integration of Left Thalamus (r = - 0.58) and FC of Left MTP to 'Right Supplementary Motor and left Precentral' gyrus (r = - 0.53). The FC of Right MTP to Left Amygdala, Putamen, Parahippocampal, and Orbital Frontal Cortex (r = 0.61) and FC of Left Thalamus to left Putamen, Pallidum, Caudate, Thalamus Hippocampus and Insula (r 0.55) showed a positive correlation to the duration of the longest seizure. The findings of the current study report altered connectivity in children with CFS proportional to the seizure recurrence and duration. Regardless of the causal/consequential nature, such observations demonstrate the imprint of these disease-defining variables of febrile seizures on the developing brain.
Disciplines :
Neurology
Author, co-author :
Acharya, Ullas V ✱; Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Kulanthaivelu, Karthik ✱; Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Panda, Rajanikant ✱; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Saini, Jitender; Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Gupta, Arun K; Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Sankaran, Bindu Parayil; Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Raghavendra, Kenchaiah; Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Mundlamuri, Ravindranath Chowdary; Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Sinha, Sanjib; Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India
Keshavamurthy, M L; Department of Paediatric Medicine, Indira Gandhi Institute of Child Health, Bengaluru, 560029, Karnataka, India
Bharath, Rose Dawn; Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, Karnataka, India. drrosedawnbharath@gmail.com
✱ These authors have contributed equally to this work.
Language :
English
Title :
Functional network connectivity imprint in febrile seizures.
We thank the children with febrile seizures and their parents for being part of the study. We also thank the staff and students of the department of Neuroimaging and Interventional Radiology for their support during data acquisition.
Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile seizures: Clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics 121, 1281–1286 (2008).
Offringa, M. & Moyer, V. A. Evidence based paediatrics: Evidence based management of seizures associated with fever. BMJ 323, 1111–1114 (2001).
Stafstrom, C. E. Chapter 1: The Incidence and Prevalence of Febrile Seizures. In Febrile Seizures (eds Baram, T. Z. & Shinnar, S.) 1–25 (Academic Press, 2002).
Baulac, S. et al. Fever, genes, and epilepsy. Lancet Neurol. 3, 421–430 (2004).
Nakayama, J. Progress in searching for the febrile seizure susceptibility genes. Brain Dev. 31, 359–365 (2009).
Waruiru, C. Febrile seizures: An update. Arch. Dis. Child. 89, 751–756 (2004).
Berg, A. T. & Shinnar, S. Complex febrile seizures. Epilepsia 37, 126–133 (1996).
Jensen, F. E. & Sanchez, R. M. Chapter 11: Why does the developing brain demonstrate heightened susceptibility to febrile and other provoked seizures? In Febrile Seizures (eds Baram, T. Z. & Shinnar, S.) 153–168 (Academic Press, 2002).
Cendes, F. & Andermann, F. Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: An MRI volumetric study. Neurology 43(6), 1083–1083 (1993).
Shinnar, S. & Glauser, T. A. Febrile seizures. J. Child Neurol. 17, S44–S52 (2002).
Theodore, W. H. Do Febrile Seizures cause mesial temporal sclerosis?. Epilepsy Curr. 3, 121–122 (2003).
Pavlidou, E., Hagel, C. & Panteliadis, C. Febrile seizures: recent developments and unanswered questions. Childs Nerv. Syst. 29, 2011–2017 (2013).
French, J. A. et al. Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Ann. Neurol. 34(6), 774–780. 10.1002/ana.410340604 (1993). DOI: 10.1002/ana.410340604
Tsai, M.-L., Hung, K.-L., Tsan, Y.-Y. & Tung, W.T.-H. Long-term neurocognitive outcome and auditory event-related potentials after complex febrile seizures in children. Epilepsy Behav. 47, 55–60 (2015).
Dube, C. et al. Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann. Neurol. 47, 336–344 (2000).
Dubé, C. et al. Temporal lobe epilepsy after experimental prolonged febrile seizures: Prospective analysis. Brain 129, 911–922 (2006).
Theodore, W. H. et al. Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures. Neurology 52, 132–132 (1999).
Bharath, R. D. et al. Seizure frequency can alter brain connectivity: Evidence from resting-state fMRI. AJNR Am. J. Neuroradiol. 36, 1890–1898 (2015).
Bharath, R. D. et al. Reduced small world brain connectivity in probands with a family history of epilepsy. Eur. J. Neurol. 23, 1729–1737 (2016).
Bernhardt, B. C., Bonilha, L. & Gross, D. W. Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy. Epilepsy Behav. 50, 162–170 (2015).
Fisher, R. S. et al. Operational classification of seizure types by the International League Against Epilepsy: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58, 522–530 (2017).
Shinnar, S. et al. MRI abnormalities following febrile status epilepticus in children: The FEBSTAT study. Neurology 79, 871–877 (2012).
Silverstein, A. M. & Alexander, J. A. Acute postictal cerebral imaging. Am. J. Neuroradiol. 19, 1485–1488 (1998).
Szabo, K. et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain 128, 1369–1376 (2005).
Grillo, E., da Ronaldo, J. M. & Silva, F. MRI Peri-ictal Abnormalities in Febrile Status Epilepticus. Cause or Consequence? (AAn Enterprises, 2020).
Berg, M. J. & Abou-Khalil, B. Childhood febrile status epilepticus: Chicken or egg? Does it matter?. Neurology 79, 840–841 (2012).
Bertram, E. The relevance of kindling for human epilepsy. Epilepsia 48(Suppl 2), 65–74 (2007).
Lothman, E. W., Bertram, E. H. & Stringer, J. L. Functional anatomy of hippocampal seizures. Prog. Neurobiol. 37, 1–82 (1991).
McClelland, S., Dubé, C. M., Yang, J. & Baram, T. Z. Epileptogenesis after prolonged febrile seizures: Mechanisms, biomarkers and therapeutic opportunities. Neurosci. Lett. 497, 155–162 (2011).
Hillary, F. G. et al. Hyperconnectivity is a fundamental response to neurological disruption. Neuropsychology 29, 59–75 (2015).
Nakamura, T., Hillary, F. G. & Biswal, B. B. Resting network plasticity following brain injury. PLoS ONE 4, e8220 (2009).
Chawla, D., Lumer, E. D. & Friston, K. J. Relating macroscopic measures of brain activity to fast, dynamic neuronal interactions. Neural Comput. 12, 2805–2821 (2000).
Birca, A. et al. Enhanced EEG connectivity in children with febrile seizures. Epilepsy Res. 110, 32–38 (2015).
Bender, R. A., Dubé, C., Gonzalez-Vega, R., Mina, E. W. & Baram, T. Z. Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures. Hippocampus 13, 399–412 (2003).
Goddard, G. V., McIntyre, D. C. & Leech, C. K. A permanent change in brain function resulting from daily electrical stimulation. Exp. Neurol. 25, 295–330 (1969).
Zhao, D., Xiru, Wu., Pei, Y. & Zuo, Q. Kindling phenomenon of hyperthermic seizures in the epilepsy-prone versus the epilepsy-resistant rat. Brain Res. 358, 390–393 (1985).
Danielson, N. B., Guo, J. N. & Blumenfeld, H. The default mode network and altered consciousness in epilepsy. Behav. Neurol. 24, 55–65 (2011).
Li, Y., Chen, Q. & Huang, W. Disrupted topological properties of functional networks in epileptic children with generalized tonic-clonic seizures. Brain Behav. 10, e01890 (2020).
Ji, G.-J. et al. Decreased network efficiency in benign epilepsy with centrotemporal spikes. Radiology 283, 186–194 (2017).
Huang, W. et al. Gray-matter volume reduction in the thalamus and frontal lobe in epileptic patients with generalized tonic-clonic seizures. J. Neuroradiol. 38, 298–303 (2011).
Wang, Y., Goodfellow, M., Taylor, P. N. & Baier, G. Dynamic mechanisms of neocortical focal seizure onset. PLOS Comput. Biol. 10, e1003787 (2014).
Perani, S. et al. Thalamic volume reduction in drug-naive patients with new-onset genetic generalized epilepsy. Epilepsia 59, 226–234 (2018).
Fair, D. A. et al. The maturing architecture of the brain’s default network. Proc. Natl. Acad. Sci. USA 105, 4028–4032 (2008).
Lv, J., Liu, D., Ma, J., Wang, X. & Zhang, J. Graph theoretical analysis of BOLD functional connectivity during human sleep without EEG monitoring. PLoS ONE 10, e0137297 (2015).
Jenkinson, M., Bannister, P., Brady, M. & Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17, 825–841 (2002).
Beckmann, C. F., DeLuca, M., Devlin, J. T. & Smith, S. M. Investigations into resting-state connectivity using independent component analysis. Philos. Trans. R. Soc. Lond. B 360, 1001–1013 (2005).
Shi, F. et al. Infant brain atlases from neonates to 1- and 2-year-olds. PLoS ONE 6, e18746 (2011).
Whitfield-Gabrieli, S. & Nieto-Castanon, A. Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2, 125–141 (2012).
Behzadi, Y., Restom, K., Liau, J. & Liu, T. T. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37, 90–101 (2007).
Whitfield-Gabrieli, S. & Ford, J. M. Default mode network activity and connectivity in psychopathology. Annu. Rev. Clin. Psychol. 8, 49–76 (2012).
Lindquist, M. A., Loh, J. M., Atlas, L. Y. & Wager, T. D. Modeling the hemodynamic response function in fMRI: Efficiency bias and mis-modeling. Neuroimage 45, S187–S198 (2009).
Rubinov, M. & Sporns, O. Complex network measures of brain connectivity: Uses and interpretations. Neuroimage 52, 1059–1069 (2010).
Zalesky, A., Fornito, A. & Bullmore, E. T. Network-based statistic: Identifying differences in brain networks. Neuroimage 53, 1197–1207 (2010).
Bassett, D. S. & Bullmore, E. D. Small-world brain networks. Neuroscientist 12, 512–523 (2006).
Iturria-Medina, Y., Sotero, R. C., Canales-Rodríguez, E. J., Alemán-Gómez, Y. & Melie-García, L. Studying the human brain anatomical network via diffusion-weighted MRI and Graph Theory. Neuroimage 40, 1064–1076 (2008).
Latora, V. & Marchiori, M. Efficient behavior of small-world networks. Phys. Rev. Lett. 87, 198701 (2001).
Xia, M., Wang, J. & He, Y. BrainNet Viewer: A network visualization tool for human brain connectomics. PLoS ONE 8, e68910 (2013).
