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Cognitive and neurodevelopmental comorbidities in paediatric epilepsy

Nature Reviews Neurology volume 12, pages 465–476 (2016)Cite this article

Subjects

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.

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Figure 1: Relationship between seizures and comorbidities.

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Authors and Affiliations

  1. 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

  2. Seattle Children's Hospital, MB.7.420 — Neurology, 4800 Sand Point Way NE, Seattle, 98105, Washington, USA

    Lorie D. Hamiwka

Authors
  1. Katherine C. Nickels
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  2. Michael J. Zaccariello
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  3. Lorie D. Hamiwka
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  4. Elaine C. Wirrell
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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.

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Correspondence to Elaine C. Wirrell.

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PowerPoint slides

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).

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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

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