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KEY POINTS * Working memory and processing speed are often impaired in children with epilepsy, even in those with intact general cognitive abilities, and can adversely affect learning and

problem-solving * Attention deficit–hyperactivity disorder, primarily of the inattentive type, is seen in 28–70% of people with epilepsy and is common among children with epilepsy; the

diagnosis is often delayed in individuals with epilepsy * Despite favourable seizure outcomes, people with genetic generalized epilepsy have cognitive and behavioural comorbidities

suggestive of frontal lobe dysfunction, which have an adverse effect on long-term psychosocial outcome * In individuals with focal epilepsy arising from a single focus, the spectrum of

neurocognitive disability is broad, owing to dysfunction of the epileptogenic zone as well as the more-extensive networks connecting with this zone * The underlying aetiology of seizures has

a substantial causative role in the development of comorbidities, and frequent seizures and/or interictal epileptiform discharges may further exacerbate neurocognitive dysfunction *

Neuropsychological testing is the gold standard for evaluation of cognitive comorbidities; in addition, formal screening questionnaires completed by parents and/or children are feasible and

well received, and enable widespread screening ABSTRACT Cognitive and behavioural comorbidities are often seen in children with epilepsy, and are more common and severe in refractory

epilepsy. These comorbidities are associated with worse quality of life, increased behavioural and language problems and worse social skills, all of which adversely affect long-term

psychosocial functioning. To enable early intervention and therapy, children and teens with epilepsy should be periodically screened for cognitive comorbidities. The location of the

epileptic focus can, to a certain degree, predict the type(s) of comorbidity; however, the spectrum of disability is often broad, presumably because focal perturbations can cause network

dysfunction. Comorbidities often result from underlying structural or functional pathology that has led to seizures. In selected cases, therapy targeting the underlying cause, such as the

ketogenic diet for GLUT1 deficiency syndromes, may be remarkably effective in ameliorating both seizures and cognitive concerns. In many cases, however, cognitive impairment persists despite

seizure control. In epileptic encephalopathies, frequent seizures and/or interictal epileptiform abnormalities exacerbate neurocognitive dysfunction, owing to synaptic reorganization or

impaired neurogenesis, or to other effects on developing neural circuits, and prompt initiation of effective antiepileptic therapy is essential to limit cognitive comorbidities. Access

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SIMILAR CONTENT BEING VIEWED BY OTHERS NEUROBEHAVIOURAL COMORBIDITIES OF EPILEPSY: TOWARDS A NETWORK-BASED PRECISION TAXONOMY Article 22 September 2021 DEVELOPMENTAL AND EPILEPTIC

ENCEPHALOPATHIES Article 05 September 2024 ENHANCING DAILY LIFE FOR CHILDREN WITH COGNITIVE DEVELOPMENTAL DELAY THROUGH INSIGHTS INTO BRAIN DEVELOPMENT Article 18 October 2024 REFERENCES *

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Cognitive Changes in Children with Epilepsy_ (abstract 1.293) (American Epilepsy Society, 2015). Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Child and

Adolescent Neurology and Epilepsy, Mayo Clinic, 200 First Street SW, Rochester, 55905, Minnesota, USA Katherine C. Nickels, Michael J. Zaccariello & Elaine C. Wirrell * Seattle

Children's Hospital, MB.7.420 — Neurology, 4800 Sand Point Way NE, Seattle, 98105, Washington, USA Lorie D. Hamiwka Authors * Katherine C. Nickels View author publications You can also

search for this author inPubMed Google Scholar * Michael J. Zaccariello View author publications You can also search for this author inPubMed Google Scholar * Lorie D. Hamiwka View author

publications You can also search for this author inPubMed Google Scholar * Elaine C. Wirrell View author publications You can also search for this author inPubMed Google Scholar

CONTRIBUTIONS K.C.N., L.D.H. and E.C.W. contributed to discussion of content. All authors contributed to searching data for the article, and writing, reviewing and editing the manuscript

before submission. CORRESPONDING AUTHOR Correspondence to Elaine C. Wirrell. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. POWERPOINT SLIDES

POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR TABLE 1 POWERPOINT SLIDE FOR TABLE 2 POWERPOINT SLIDE FOR TABLE 3 GLOSSARY * Full Scale Intelligence Quotient (FSIQ) A theoretical construct

used to describe one's complete cognitive capacity as measured by standardized tests, such as the Wechsler Intelligence Scale for Children, which is the most commonly used measure in

paediatrics. * Symptomatic epilepsy Epilepsy is called 'symptomatic' when it has a known or implied cause, such as a traumatic brain injury, tumour, infection or developmental

delay. * West syndrome West syndrome, also referred to as epileptic spasms or infantile spasms, is an epilepsy syndrome characterized by the triad of infantile spasms, hypsarrhythmia and

developmental delay, with an onset typically at about 3–24 months of age. * Behavioural problems Continued problems with behaviour that are unusually severe and can themselves be problematic

for development; severe behavioural problems can warrant a diagnosis of oppositional defiant disorder (typically seen in children) or conduct disorder (teenagers and adolescents). *

Internalizing behaviours Negative behaviours and attitudes directed towards the self, such as anxiety, depression, social withdrawal, self-harm and suicidal behaviour. * Periventricular

leukomalacia A disorder that is particularly common in premature infants, and is caused by injury to the white matter adjacent to the lateral ventricles owing to lack of oxygen or blood

flow, or by infection _in utero_ or early infancy. * Dravet syndrome Dravet syndrome is almost always attributed to _SCN1A_ mutations and begins before 18 months of age with hemiclonic

seizures that are often prolonged and triggered by fever. Around 2–5 years of age, myoclonic seizures, atypical absence seizures and focal dyscognitive seizures develop. * Epileptic

encephalopathy with continuous spike-and-wave during slow-wave sleep (CSWS). A syndrome characterized by continuous spike-and-wave EEG pattern during slow-wave sleep, progressive decline in

cognitive and behavioural functioning, and psychiatric symptoms. * Landau–Kleffner syndrome ((LKS) A syndrome characterized by subacute onset of acquired aphasia in a child with normal prior

development and cognition; in this disorder, EEG shows marked activation of epileptiform activity in sleep. * Eloquent cortex The brain areas that have essential roles in, for example,

speech and linguistic ability, motor control, or sensory processing. Lesioning or dysfunction of these brain areas manifests as deficits in these functions. * Benign epilepsy with

centrotemporal spikes (BECTS) A self-limiting, pharmacoresponsive epilepsy seen in children of early school age that is characterized by brief hemifacial seizures, which can secondarily

generalize during sleep. * Panayiotopoulos syndrome A self-limited epilepsy characterized by autonomic, sometimes prolonged, seizures that typically begin in the preschool years. * Childhood

absence epilepsy (CAE) Presents in mid childhood (4–10 years) with very frequent (20–50 per day) typical absence seizures and an EEG showing 3Hz generalized spike-and-wave discharges. *

Juvenile absence epilepsy (JAE) Presents in late childhood or adolescence (10–16 years) with less frequent (one or two per day) typical absence seizures, generalized tonic–clonic seizures

that typically begin months to years after absences, and an EEG showing 3–4 Hz generalized spike-and-wave discharges. * Juvenile myoclonic epilepsy (JME) A condition that presents in

adolescence or early adulthood with myoclonic jerks, which typically occur in the early morning and are triggered by sleep deprivation, generalized tonic–clonic seizures, and an EEG showing

generalized spike-and-wave discharges, often with a photoparoxysmal response. * Seizure kindling studies Rats can be divided into two groups on the basis of how quickly seizures can be

kindled: animals who are more epilepsy-prone can be kindled more quickly ('fast-kindling' rats) than those who are more epilepsy-resistant ('slow-kindling' rats). RIGHTS

AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nickels, K., Zaccariello, M., Hamiwka, L. _et al._ Cognitive and neurodevelopmental comorbidities in paediatric

epilepsy. _Nat Rev Neurol_ 12, 465–476 (2016). https://doi.org/10.1038/nrneurol.2016.98 Download citation * Published: 22 July 2016 * Issue Date: August 2016 * DOI:

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