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Epilepsy and cognition z Research

Beyond seizures: understanding

cognitive deficits in epilepsy
Mark Greener
Cognitive impairment can pose lifelong problems for people with epilepsy. However,
researchers are now beginning to understand the nature of these impairments, which
may ultimately lead to new management approaches. Mark Greener reports.

P eople with epilepsy endure far

more than living with the
stigma, fear and lifestyle limita-
chronic epilepsy, some of whom
were younger than 40 years of
age, showed senile plaques.
ically produces anterograde mem-
or y loss. This amnesic pattern
helps account for the ‘minimal’
tions imposed by recurrent Further more, plaques formed improvements resulting from
seizures. They are especially vul- more rapidly in people with practice effects often shown by
nerable to cardiac and respiratory chronic epilepsy than in the gen- people with TLE compared with
disorders. They may endure phys- eral population, especially in controls. The lack of a practice
ical disabilities following, for exam- those patients expressing the effect suggests that TLE might
ple, burns and fractures. They can epsilon 4 allele.5 (Other studies undermine patients’ ability to
suffer depression (see March April link epsilon 4, which encodes learn from experience.6
issue of Progress1), anxiety and psy- apolipoprotein E4, with an In TLE, the extent and site of
choses.2 What is more, epilepsy is increased risk of Alzheimer’s dis- hippocampal atrophy seems to
intimately intertwined with cogni- ease and cardio vascular condi- predict the severity and form of
tive impairment, which often tions.) the memor y impairment. 4,6 For
emerges from the synergistic inter- Indeed, cognitive impairments instance, in people who are left-
actions of lesions, seizures and often predate the first seizure. For dominant for language, atrophy of
treatment.3 However, increasing example, about a quarter of chil- the left hippocampus typically
insights into the multifaceted dren with new-onset idiopathic translates into impaired verbal
causes of cognitive impairment epilepsies needed support from learning and memory. Atrophy of
may pave the way to new special education services before the right hippocampus is, in gen-
approaches to management. the onset of seizures. Similarly, eral, associated with defective non-
some adults with new-onset verbal learning and memor y. 4
A lifelong problem epilepsy already show cognitive Nevertheless, the cognitive impair-
Cognitive impairments potentially and behavioural disturbances.6 In ment and damage in TLE seems to
pose lifelong problems for people one analysis, only 28 per cent of extend beyond memory and the
with epilepsy. For instance, cogni- 247 treatment-naïve patients with hippocampus. For instance, TLE
tive deficits during childhood can newly diagnosed epilepsy showed patients may also develop abnor-
translate into learning disabilities unaffected attention, executive malities in, among other cognitive
that undermine social skills and functions and memory. Forty-nine domains, executive functions and
educational attainment.4 As such, per cent showed impaired atten- language, 6 while MRI scans link
the consequences of childhood tion and executive functions, while memory impairment with atrophy
cognitive impairment can persist 48 per cent showed memor y of the thalamus, amygdala and
for the rest of the patient’s life. As defects.7 mammillar y bodies (part of the
people with epilepsy age, they are limbic system).4
also exposed to the risk factors – Patterns of impairment A range of cognitive deficits
such as cardiovascular disease, In part, the pattern of cognitive also characterises several other
increased inflammation and social impairment depends on the forms of epilepsy. For example:
isolation – that hasten cognitive pathophysiology underlying the • Changes in the thalamocortical
decline even in the general popu- seizure disorder. For example, network seem to underlie child-
lation.5 temporal lobe epilepsy (TLE) hood absence epilepsy, which is
In one study, for example, seems to arise in the hippocampus characterised by impaired atten-
around 10 per cent of people with and mesial temporal lobe, and typ- tion as well as defective linguistic

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Research z Epilepsy and cognition

abilities, executive functions and ‘substantial’ weight gain. Some Nevertheless, researchers have
social competences.6 other AEDs, including phenytoin only just begun to understand the
• Juvenile myoclonic epilepsy and carbamazepine, increase lev- basis of cognitive deficits charac-
(JME) seems to arise in the fronto- els of homocysteine. Indeed, epi- teristic of epilepsy and their evo-
thalamic network. Patients with demiological studies suggest that lution over the patient’s lifetime.
JME or frontal lobe epilepsy typi- hypertension, ischaemic heart dis- For example, modern MRI scans
cally show impaired executive ease, heart failure, diabetes and visualise the microstructural and
functions. Some JME patients also cerebrovascular conditions are functional abnormalities poten-
exhibit impaired verbal and visual especially common among people tially associated with cognitive
memory, processing speed and lan- with epilepsy.5 impairment in unprecedented
guage.6 detail. However, a recent review
• Dysfunction of the Sylvian and Managing cognitive deficits noted that the use of microstruc-
Rolandic regions of the brain Unlike, for example, Alzheimer’s tural and functional MRI in
seems to produce benign epilepsy disease, pharmacologists have yet epilepsy ‘has been limited and
with centrotemporal spikes, which to devise a treatment that offsets focused mostly on adults’ and
is commonly associated with the cognitive impairment in called for longitudinal studies
impaired linguistic abilities. epilepsy. Nevertheless, proactive, from diagnosis.4 Hopefully, over
However, patients may also show multidisciplinary management can the next few years, a growing
mildly impaired attention and help. As a result, healthcare pro- body of evidence might help
executive functions.6 fessionals could consider screen- researchers develop much-
ing for cognitive adverse events, needed new ways to prevent,
Exacerbating factors especially when patients begin or detect and manage this common
Co-morbidities (including depres- switch an AED or report a possible comorbidity.
sion) and antiepileptic drugs cognitive side-effect. 3 Avoiding
(AEDs) can synergistically exacer- rapid titration, using the lowest Mark Greener is a Freelance Medical
bate the deficits arising from the effective AED dose and limiting Writer
neurological pathophysiology. overall exposure, choosing slow-
For example, bromide, benzo - release drugs to maintain relatively References
diazepines and phenobarbital steady blood levels, and selecting 1. Muzerengi S, Moor CC. What do we know
about depression in people with epilepsy?
impair cognition more frequently AEDs based on their cognitive Progress in Neurology and Psychiatry 2013;
than phenytoin, valproic acid or effects can help reduce the impact 17(2):20-4.
carbamazepine. Never theless, of treatment on cognition.3 2. Cardamone L, Salzberg M, O'Brien T, Jones
N. Antidepressant therapy in epilepsy: can
phenytoin, valproic acid and car- In addition, the multidiscipli- treating the comorbidities affect the underly-
bamazepine may still impair atten- nar y approach could manage ing disorder? Br J Pharmacol 2013;168:
tion and memor y. In general, behavioural problems, intervene in 1531-54.
3. Witt JA, Helmstaedter C. Monitoring the
newer AEDs produce fewer cogni- unsupportive family environments, cognitive effects of antiepileptic pharma-
tive effects, although topiramate and offer memory and cognitive cotherapy – approaching the individual
may impair attention, memor y training. For example, people with patient. Epilepsy Behav 2013;26:450-6.
4. Braakman HM, van der Kruijs SJ, Vaessen
and language. The cognitive epilepsy could benefit from com- MJ, et al. Microstructural and functional MRI
adverse events of AEDs usually puter-assisted working memory pro- studies of cognitive impairment in epilepsy.
abate after dose reduction or ces- grams, diaries and calendars, Epilepsia 2012;53:1690-9.
5. Hermann B, Seidenberg M, Sager M, et al.
sation.3 self-regulation exercises and prob- Growing old with epilepsy: the neglected issue
In addition, some AEDs can lem-solving techniques.6 Further - of cognitive and brain health in aging and
exacerbate vascular risk factors more, certain cardiovascular risk elder persons with chronic epilepsy. Epilepsia
that, potentially, promote vascu- factors – which can also contribute 6. Lin JJ, Mula M, Hermann BP. Uncovering
lar dementia and Alzheimer’s dis- to abnormal cognitive ageing and the neurobehavioural comorbidities of
ease. 8 In turn, dementia can dementia in the general population epilepsy over the lifespan. Lancet 2012;
further undermine cognitive – seem to be especially common in
7. Witt J-A, Helmstaedter C. Should cognition
functions that are already people with epilepsy.5 Therefore, be screened in new-onset epilepsies? A study
impaired by chronic epilepsy. For considering screening for and treat- in 247 untreated patients. J Neurol 2012;
example, valproic acid can lead to ing modifiable cardiovascular risk 259:1727-31.
8. Greener M. Clarifying the link between
hyperinsulinaemia, increase factors in people with epilepsy Alzheimer’s and vascular disease. Progress in
insulin resistance and promote seems prudent. Neurology and Psychiatry 2013;17(2):27-8.

32 Progress in Neurology and Psychiatry May/June 2013 www.progressnp.com