THE COMPLEXITIES of EPILEPSY an Estimated 50 Million People Worldwide Have Epilepsy

OUTLOOK EPILEPSY THE COMPLEXITIES OF EPILEPSY An estimated 50 million people worldwide have epilepsy. But research funding is low, treatment can fail and the mechanisms of the disease are a mystery. By Neil Savage.

ACHITECTUE OF EPILEPSY Epilepsy is one of the most common neurological disorders and is characterized by uncontrolled ring of the FONTAL LOBE EPILEPSY brain’s neurons. There are more than a dozen types of epilepsy but the main ones are described below; a person A ects a specic brain region can have more than one type. Precisely what happens in the brain during an epileptic seizure and the combination Seizures originating in the frontal of brain areas involved have experts disagreeing on how to categorize the many forms of the disease. See page S4. lobe may develop into partial or generalized epilepsy. The frontal lobe brain tissues are associated with motor function and cognition. Epilepsy arising here may induce temporary alterations in personality. GENEALIZED EPILEPSY 2 A ects most or all of the brain 3 Typically congenital and occurs simultaneously in both sides of the brain. The most widely recognized form is tonic–clonic, which involves a fall to the oor, jerky convulsions and unconsciousness. Absence seizures are another form 60% of generalized epilepsy — 5 these involve transient loss 6 of consciousness, which 1 may last for only a of cases of epilepsy arise few seconds. from unknown causes1.

4 PATIAL EPILEPSY TEMPOAL-LOBE EPILEPSY A ects one part of the brain A ects a specic brain region Usually limited to a speci c region The temporal lobes are associated with 1 in one area of the brain. This form of Occipital lobe the brain’s language and auditory epilepsy is often the result of an accident 2 Parietal lobe centres, as well as memory and emotion. or neurological disease. Manifestations — 3 Frontal lobe This form of epilepsy varies in intensity such as hallucinations, twitching, smelling 4 Temporal lobe and often arises within the hippocampus things or uncontrolled limb movements — 5 Hypothalamus and amygdala — two structures that are can dier considerably. 6 Amygdala deep in the brain’s centre.

YOUNG AND OLD DANGES GEOGAPHICAL VAIATION Developed countries In developed countries, epilepsy is more common in children and the elderly2. Worldwide prevalence of lifetime epilepsy Developing countries (urban) and active epilepsy3. Developing countries (rural)

In children, 300 epilepsy is 20 primarily Epilepsy becomes more The higher gures for epilepsy congenital. common in over-65s as in developing countries 250 people have strokes or are thought to be due to develop chronic conditions 15 factors that include poor 200 such as tumours or management of parasitic Alzheimer’s disease. infections, untreated childhood epilepsy and 150 10 problems during childbirth.

100 Lifetime epilepsy: A person has had at least one seizure Rate per 100,000

(per 1,000 people) 5

Estimated prevalence during his or her life. 50 Active epilepsy: A person has had more than one 0 0 seizure in the past ve years or is currently using epilepsy 0 10 20 30 40 50 60 70 80 90 100 Lifetime Active medication. Age epilepsy epilepsy

SUGICAL GAINS DUGS AT WOK Temporal lobe epilepsy is the kind most likely to Epilepsy becomes more common as people grow older (see ‘Young and old dangers’) but be resistant to drug treatment. Fortunately, this eective antiepilepsy drugs are available for patients over the age of 55 (ref. 5). See page S12. form of epilepsy responds well to surgery. In most people suitable for surgical treatment, surgery to one side of the brain is sucient to control seizures but sometimes the surgeon will need to Phenytoin 1939 Lamotrigine has few side eects and is operate on both sides of the brain. Carbamazepine 1974 eective at alleviating Sodium valproate 1978 seizures in dierent types of epilepsy. Gabapentin 1994 How e ective is surgery? Lamotrigine 1994 A study published in 2012 involving 38 patients reported Topiramate 1997 that 11 of the 15 patients with Levetiracetam 1999 drug-resistant mesial temporal Oxcarbazepine 2000 lobe epilepsy who received surgery to alleviate seizures Zonisamide 2000 had two seizure-free years. None of the 23 patients who US Food and Drug 0 10 20 30 40 50 60 hadn’t been recommended Administration Percentage of epilepsy patients age 55+ for surgery and continued approval who experience a reduction in seizures with drug-only treatment had a seizure-free year4.

PSYCHIATIC CONDITIONS In general, people with epilepsy have more chance of developing psychiatric disorders, particularly depression, but having a psychiatric condition also raises the likelihood of developing epilepsy6.

People without epilepsy People with epilepsy

Depression

Attention de cit When studies were analysed to hyperactivity disorder investigate possible links between epilepsy and psychiatric conditions, the gures varied.* For Anxiety disorders example, one study found that 11% of people with epilepsy had Anterior depression, yet another study temporal lobe Panic disorder found that 80% of people with epilepsy had depression.*

Preparation for an epilepsy operation Psychosis Data from neuroimaging techniques are used to map the brain to precisely identify regions that give rise to epileptic activity. During surgery, the aim is to remove 0 10 20 30 40 50 60 70 80 90 aected tissue without damaging functionally Percentage of people diagnosed with a psychiatric condition important regions. See page S7. *The data used to compile the bars was extracted from studies that looked diagnosed psychiatric conditions in the general population and in people with epilepsy. The studies analysed were published between 1970 and 2002.

UNBALANCED Amyotrophic lateral sclerosis Epilepsy is six times more prevalent than ATTENTION Parkinson’s disease yet US National Institutes Multiple sclerosis receives almost the same of Health spending on amount of funding. epilepsy in 2010 Epilepsy lagged behind less common neurological conditions. A variety of Parkinson’s disease factors, from historical issues at health Stroke agencies to social stigma, may explain this discrepancy7. Alzheimer’s disease See page S10. 600 500 400 300 200 100 0 2 4 6 8 10 Research funding (US$ millions) Prevalence (per 100,000 population)

References: 1. The WHO Epilepsy Fact Sheet No. 999.; 2. Thurman, D. J. See, go.nature.com/2spiwk; 3. Ngugi, A. K. et al; Epilepsia 51, 883–890 (2010).; 4. Engel, J. Jr. et al. J. Am. Med. Assoc. 307, 922–930 (2012).; 5. Arif, H. et al. Arch. Neurol. 67, 408–415 (2010).; 6. LaFrance, W. C. Jr., Kanner, A. M. & Hermann, B. Int. Rev. Neurobiol. 83, 347–383 (2008).; 7. Meador, K. J. et al. Neurology 77, 1305–1307 (2011).