Preventing cognitive impairment in children with epilepsy

Purpose of review Cognitive impairments are common in children with epilepsy. They may already be present before the onset of epilepsy or occur – and even progress – during its course. Many variables contribute to cognitive dysfunction. Those that can be targeted to prevent (further) cognitive impairment will be highlighted in this review. Recent findings Ideally, but not yet realistically, epileptogenesis is prevented to avert seizures and cognitive impairments in high-risk patients. New and targeted treatments of progressive epileptogenic disorders and precision medicine approaches in genetic epilepsies are increasingly applied. Cognitive outcome benefits from early diagnosis and treatment of epileptic encephalopathy. Ongoing seizures may cause permanent and progressive changes in brain structure and connectivity, suggesting that early seizure control optimizes eventual cognitive functioning. Frequent interictal epileptiform discharges justify treatment in children with cognitive impairments that are otherwise unexplained. Cognitive adverse effects of antiepileptic drugs should be closely monitored and balanced against potential benefits. Finally, early surgical treatment in selected candidates will improve their cognitive outcome. Summary Although important determinants of intellectual functioning – including the child's genetic and environmental background and the epileptogenic pathology – may not be modifiable, several variables that contribute to cognitive impairment can be targeted to improve outcome. Early etiological diagnosis, personalized therapies, presurgical evaluation, and strict control of seizures – or in some patients interictal discharges – can prevent (further) cognitive impairments.

[1]  W. Liao,et al.  Decreased Network Efficiency in Benign Epilepsy with Centrotemporal Spikes. , 2017, Radiology.

[2]  M. Smith,et al.  The Impact of Family Factors on IQ in Pediatric Medically Refractory Epilepsy , 2017, Neuropsychology.

[3]  J. French,et al.  Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study , 2016, The Lancet.

[4]  M. Sillanpää,et al.  Prevention of Epilepsy: Issues and Innovations , 2016, Current Neurology and Neuroscience Reports.

[5]  D. Rizopoulos,et al.  Sirolimus for epilepsy in children with tuberous sclerosis complex , 2016, Neurology.

[6]  Udaya Seneviratne,et al.  Epilepsy beyond seizures: Predicting enduring cognitive dysfunction in genetic generalized epilepsies , 2016, Epilepsy & Behavior.

[7]  C. Stoltenberg,et al.  Comorbidity and Childhood Epilepsy: A Nationwide Registry Study , 2016, Pediatrics.

[8]  Torsten Baldeweg,et al.  Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy , 2016, Epilepsia.

[9]  A. Vezzani,et al.  Preventing epileptogenesis: A realistic goal? , 2016, Pharmacological research.

[10]  E. Wirrell,et al.  Cognitive and neurodevelopmental comorbidities in paediatric epilepsy , 2016, Nature Reviews Neurology.

[11]  Mark S. Seidenberg,et al.  Cognitive phenotypes in childhood idiopathic epilepsies , 2016, Epilepsy & Behavior.

[12]  S. Schubert-Bast,et al.  Attention and executive functions in the early course of pediatric epilepsy , 2016, Epilepsy & Behavior.

[13]  A. Parmeggiani,et al.  Long-term follow-up of cognitive functions in patients with continuous spike–waves during sleep (CSWS) , 2016, Epilepsy & Behavior.

[14]  Cornelis J. Stam,et al.  Electroencephalography based functional networks in newly diagnosed childhood epilepsies , 2016, Clinical Neurophysiology.

[15]  A. Aldenkamp,et al.  Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Subtle behavioural and cognitive manifestations of epilepsy in children. , 2016, Epileptic disorders : international epilepsy journal with videotape.

[16]  A. Aldenkamp,et al.  Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Adverse cognitive and behavioural effects of antiepileptic drugs in children. , 2016, Epileptic disorders : international epilepsy journal with videotape.

[17]  G. Holmes Effect of Seizures on the Developing Brain and Cognition. , 2016, Seminars in pediatric neurology.

[18]  J. Wheless,et al.  Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies. , 2016, Seminars in pediatric neurology.

[19]  A. Vincent,et al.  Progress in autoimmune epileptic encephalitis. , 2016, Current opinion in neurology.

[20]  A. Venkatesan,et al.  A clinical approach to diagnosis of autoimmune encephalitis , 2016, The Lancet Neurology.

[21]  J. Archer,et al.  Epileptic encephalopathy: Use and misuse of a clinically and conceptually important concept , 2016, Epilepsia.

[22]  J. Ojemann,et al.  Interictal epileptiform discharge effects on neuropsychological assessment and epilepsy surgical planning , 2016, Epilepsy & Behavior.

[23]  A. Verrotti,et al.  Neuropsychological profiles and outcomes in children with new onset frontal lobe epilepsy , 2016, Epilepsy & Behavior.

[24]  W. Otte,et al.  White matter abnormalities at a regional and voxel level in focal and generalized epilepsy: A systematic review and meta-analysis , 2016, NeuroImage: Clinical.

[25]  B. Kavanaugh,et al.  Use of a Cumulative Risk Scale to Predict Poor Intellectual and Academic Outcomes in Childhood Epilepsy , 2016, Journal of child neurology.

[26]  A. Verrotti,et al.  Neuropsychological impairment in childhood absence epilepsy: Review of the literature , 2015, Journal of the Neurological Sciences.

[27]  Rebecca C. Spillmann,et al.  Quinidine in the treatment of KCNT1‐positive epilepsies , 2015, Annals of neurology.

[28]  T. Loddenkemper,et al.  Treatment of electrical status epilepticus in sleep: A pooled analysis of 575 cases , 2015, Epilepsia.

[29]  C. Newton,et al.  Cognition and behavior in a prevalent cohort of children with epilepsy in rural northern Tanzania: A three-year follow-up study , 2015, Epilepsy & Behavior.

[30]  Jack J. Lin,et al.  Cognition and brain development in children with benign epilepsy with centrotemporal spikes , 2015, Epilepsia.

[31]  Orrin Devinsky,et al.  Epileptic encephalopathies: Optimizing seizure control and developmental outcome , 2015, Epilepsia.

[32]  G. Holmes,et al.  Seizing control of epileptic activity can improve outcome , 2015, Epilepsia.

[33]  C. Korff,et al.  Epileptic activity is a surrogate for an underlying etiology and stopping the activity has a limited impact on developmental outcome , 2015, Epilepsia.

[34]  Tobias Loddenkemper,et al.  Should epileptiform discharges be treated? , 2015, Epilepsia.

[35]  E. P. Knight Increasing utilization of Pediatric epilepsy surgery in the United States between 1997 and 2009 , 2015 .

[36]  G. Carvill,et al.  SCN2A encephalopathy , 2015, Neurology.

[37]  Boris C. Bernhardt,et al.  Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy , 2015, Epilepsy & Behavior.

[38]  Chang-hyun Park,et al.  Gray and White Matter Volumes and Cognitive Dysfunction in Drug-Naïve Newly Diagnosed Pediatric Epilepsy , 2015, BioMed research international.

[39]  D. Lindhout,et al.  Erratum to: Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related Epilepsy: A Molecular Neuropharmacological Approach , 2015, Neurotherapeutics.

[40]  P. Kahane,et al.  Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery , 2015, Annals of neurology.

[41]  P. Gosselaar,et al.  Changing profiles of pediatric epilepsy surgery candidates over time: A nationwide single‐center experience from 1990 to 2011 , 2015, Epilepsia.

[42]  C. Gillberg,et al.  Cognition in school-aged children with “active” epilepsy: A population-based study , 2015, Journal of clinical and experimental neuropsychology.

[43]  A. Jennekens‐Schinkel,et al.  Parental education predicts change in intelligence quotient after childhood epilepsy surgery , 2015, Epilepsia.

[44]  Xiaoqi Huang,et al.  Altered attention networks in benign childhood epilepsy with centrotemporal spikes (BECTS): A resting-state fMRI study , 2015, Epilepsy & Behavior.

[45]  O. Snead,et al.  Neurodevelopmental outcome of infantile spasms: A systematic review and meta-analysis , 2015, Epilepsy Research.

[46]  P. Hofman,et al.  Aetiology of cognitive impairment in children with frontal lobe epilepsy , 2015, Acta neurologica Scandinavica.

[47]  G. Holmes,et al.  What is more harmful, seizures or epileptic EEG abnormalities? Is there any clinical data? , 2014, Epileptic disorders : international epilepsy journal with videotape.

[48]  O. Dulac,et al.  Occasional seizures, epilepsy, and inborn errors of metabolism , 2014, The Lancet Neurology.

[49]  W. D’Souza,et al.  Cognitive functioning in idiopathic generalised epilepsies: A systematic review and meta-analysis , 2014, Neuroscience & Biobehavioral Reviews.

[50]  K. Braun,et al.  Stopping antiepileptic drugs in seizure-free patients. , 2014, Current opinion in neurology.

[51]  A. van der Leij,et al.  Duration of epilepsy and cognitive development in children: a longitudinal study. , 2014, Neuropsychology.

[52]  Stephen F Traynelis,et al.  GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine , 2014, Annals of clinical and translational neurology.

[53]  M. de Curtis,et al.  Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function? , 2013, Epilepsia.

[54]  C. Stam,et al.  Functional and structural brain networks in epilepsy: What have we learned? , 2013, Epilepsia.

[55]  K. Braun,et al.  Cognitive outcome after epilepsy surgery in children , 2013, Brain and Development.

[56]  O. Snead,et al.  Abnormal white matter correlates with neuropsychological impairment in children with localization‐related epilepsy , 2013, Epilepsia.

[57]  G. Zaccara,et al.  Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy , 2012, Drug Safety.

[58]  A. Berg,et al.  Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes , 2012, Neurology.

[59]  C. Uiterwaal,et al.  Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study , 2012, The Lancet Neurology.

[60]  Walter H Backes,et al.  White matter network abnormalities are associated with cognitive decline in chronic epilepsy. , 2012, Cerebral cortex.

[61]  Max A. Viergever,et al.  Characterization of Functional and Structural Integrity in Experimental Focal Epilepsy: Reduced Network Efficiency Coincides with White Matter Changes , 2012, PloS one.

[62]  L. Lagae,et al.  Successful use of fenfluramine as an add‐on treatment for Dravet syndrome , 2012, Epilepsia.

[63]  N. Halfon,et al.  A National Profile of Childhood Epilepsy and Seizure Disorder , 2012, Pediatrics.

[64]  P. Hofman,et al.  Loss of network efficiency associated with cognitive decline in chronic epilepsy , 2011, Neurology.

[65]  K. Kotulska,et al.  Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. , 2011, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[66]  A. Jennekens‐Schinkel,et al.  Hemispherectomy: a basis for mental development in children with epilepsy , 2011, Epileptic disorders : international epilepsy journal with videotape.

[67]  B. Bourgeois,et al.  The safety and tolerability of newer antiepileptic drugs in children and adolescents , 2010, CNS drugs.

[68]  J. H. Cross,et al.  Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009 , 2010, Epilepsia.

[69]  C. Ikonomidou,et al.  Antiepileptic drugs and brain development , 2010, Epilepsy Research.

[70]  Michael Westerveld,et al.  Global cognitive function in children with epilepsy: A community‐based study , 2008, Epilepsia.

[71]  Bruce Hermann,et al.  Cognitive Progression in Epilepsy , 2007, Neuropsychology Review.

[72]  I. Tuxhorn,et al.  Cognitive Function in Preschool Children after Epilepsy Surgery: Rationale for Early Intervention , 2005, Epilepsia.

[73]  R. Asarnow,et al.  Cerebral hemispherectomy , 2004, Neurology.

[74]  C. Dodrill,et al.  Neuropsychological effects of seizures , 2004, Epilepsy & Behavior.

[75]  A. Jennekens‐Schinkel,et al.  Not only a matter of epilepsy: early problems of cognition and behavior in children with "epilepsy only"--a prospective, longitudinal, controlled study starting at diagnosis. , 2003, Pediatrics.

[76]  A. Jennekens‐Schinkel,et al.  ‘School career of children is at risk before diagnosis of epilepsy only’ , 2001, Developmental medicine and child neurology.

[77]  A. Jennekens‐Schinkel,et al.  School career of children is at risk before diagnosis of epilepsy only. , 2001 .

[78]  I. Awad,et al.  Epilepsy surgery in children and adults. , 1993, Annals of the Academy of Medicine, Singapore.

[79]  M. Trimble,et al.  Antiepileptic Drug-Induced Cognitive Adverse Effects , 2009, CNS drugs.