|Year : 2016 | Volume
| Issue : 5 | Page : 657-660
Epilepsy: Is there hope?
Carlos A. M. Guerreiro
Department of Neurology, Campinas University, Campinas, Brazil
|Date of Submission||30-Jun-2016|
|Date of Web Publication||30-Mar-2017|
Carlos A. M. Guerreiro
Department of Neurology, Campinas University, Campinas, SP
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Epilepsy is a highly prevalent chronic neurologic disorder and leads to social, behavioural, health and economic consequences. 'Treatment gap' varies from 10 per cent in developed countries to 75 per cent in low-income countries. Stigma and discrimination related to epilepsy are prevalent worldwide. Electroencephalography (EEG) is considered the most important tool for evaluating the patient with epilepsy. Video-EEG monitoring is an important tool for confirming the seizure type and estimating the epileptogenic zone in the brain. Neuroimaging evaluation is important to determine the aetiology of the epilepsies. Genetic testing has increased the probability of identifying the causes of some types of epilepsies. Epilepsy can be treated in an affordable way with low-cost medications. Refractory epilepsies occur in approximately one-third of recently diagnosed patients with epilepsy. For this group of patients, there are options of surgical treatment, diets and neurostimulation to improve seizure control and quality of life. In poorly organized societies, there is a lack of prioritization of epilepsy in national health policies, limited resources for trained personnel and a shortage of basic antiepileptic medications. There is evidence of improvement in the understanding of epilepsy and a clear progress in the management of epileptic seizures in recent times.
Keywords: Epilepsy - epileptic seizure - epilepsy treatment
|How to cite this article:|
Guerreiro CA. Epilepsy: Is there hope?. Indian J Med Res 2016;144:657-60
Epilepsy is a chronic neurological disorder characterized by repeated seizures (> 24 h apart); by one seizure with a strong potential for recurrence (at least 60%) or diagnosis of an epilepsy syndrome . It affects people of all ages and results in social, behavioural, health and economic consequences to the patients and their families. It is estimated that more than 50 million people worldwide are affected . Eighty per cent of people with epilepsy live in low- to medium-income countries.
The vast majority of the patients with epilepsy, with adequate treatment, are able to live a normal life. However, some patients have serious comorbidities such as psychiatric disorders and mental retardation. Epilepsy is responsible for 0.3 per cent of all deaths worldwide according to the Global Burden of Disease Study, by the World Health Organization, the World Bank and the Harvard School of Public Health supported by the Bill and Melinda Gates Foundation .
The 'treatment gap' (the proportion of people with epilepsy who require treatment, but either do not receive or receive inadequate treatment) varies from 10 per cent in developed countries to 75 per cent in low-income countries . To illustrate the prevalence of epilepsy, data from Latin America (Brazil) and Asia (India) show a prevalence of 9.2 (lifetime), 5.4 (active) and 4.19 (lifetime) and 3.91 (active) per 1000 population respectively ,. Stigma and discrimination related to epilepsy are extremely prevalent worldwide .
Electroencephalography (EEG) is considered the most important tool for evaluating the patient with epilepsy. When abnormal, it may contribute to the seizure classification, either focal or generalized and it also may characterize the epilepsy syndrome presented by the patient. This possibility allows a prognostic view in most cases in relation to seizure control and also may lead to better treatment choices. Video-EEG monitoring is an important tool for confirming the seizure type and estimating the epileptogenic zone in the brain, particularly when neuroimaging is normal, and surgery is being considered .
Computerized tomography (CT) scans are useful in emergent conditions, but focal lesions are detected in only 30 per cent of patients .
The use of magnetic resonance imaging (MRI) in the investigation of focal epilepsies requires specific protocols based on the region of onset in clinical and EEG findings. The first reason to investigate with MRI is to find the aetiology of epilepsy, and second, to allow a presurgical evaluation when possible. There are MRI epilepsy protocols to be considered as well as post-processing reconstructions. An MRI adds an extraordinary contribution to diagnosis and management of the main focal epilepsies: mesial temporal lobe epilepsy, low-grade tumours such as gangliogliomas, oligodendrogliomas and dysembryoplastic neuroepithelial tumours, malformations of cortical development such as focal cortical dysplasias, tuberous sclerosis, inflammations such as Rasmussen encephalitis and other lesions .
Functional imaging studies such as positron emission tomography (PET) and single photon emission CT (SPECT) can help to identify and confirm the ictal focus to facilitate surgical intervention for refractory focal epilepsies .
Genetic testing has increased the probability of identifying the causes of some types of epilepsies. This is a complex task and requires some expertise in its clinical application. Genetic testing modalities are chromosomal microarray analysis, karyotyping, single-gene testing, gene panel testing, whole exome sequencing and whole genome sequencing. If used with wisdom, it can contribute to the clinical diagnosis and management with practical interventions . Advances in molecular genetics have led to the identification of several genes for childhood epileptic encephalopathies with phenotype-genotype correlations . Limitations of genetic testing are the lack of availability and relatively high cost. Clinicians should always be aware of the ethical, legal and social consequences of genetic testing .
Epilepsy can be treated in an affordable way with low-cost medication such as the traditional antiepileptic drugs: carbamazepine, phenobarbital, phenytoin, valproic acid and benzodiazepines. Most new drugs add more tolerability than efficacy to the medical treatment of these patients. As such, these can sometimes decisively influence the outcome with better compliance, leading to a seizure-free condition . Refractory epilepsies occur in approximately one-third of recently diagnosed patients with epilepsy . The International League Against Epilepsy (ILAE) defines a refractory epilepsy patient as one who does not respond to two adequate medical treatments . For this group of patients, there are options of surgical treatment, diets and neurostimulation to improve seizure control and quality of life . Currently, the best surgical indications are well defined for the treatment of focal epilepsies, with the best outcome for mesial temporal lobe epilepsy, focal lesions such as tumours, arteriovenous malformations and malformation of cortical development, amongst others ,.
The ketogenic diet has been used for refractory epilepsy for many years. Recently, there have been new versions of diets with better compliance and tolerability . These have been used in children with severe epileptic syndromes with relatively good results .
Another palliative procedure that can be used is electrical stimulation for the treatment of refractory epilepsy. There is evidence of the usefulness of vagus nerve stimulation for this population . Recent studies using different technologies suggest that intracerebral stimulation of the anterior thalamic nucleus and the NeuroPace Responsive Neurostimulator can also reduce seizure frequency and improve the quality of life in patients with refractory epilepsies ,.
Despite the advances in the evaluation and treatment of refractory epilepsy in developed societies, basic steps in social, economic and political issues can eventually improve the epilepsy perspective for less privileged societies. We are optimistic as there are many modifiable factors that can be implemented. For example, in low income societies, general preventive measures can help decrease the incidence of epilepsy due to: (i) improvement of sanitary conditions, which may decrease infectious endemic diseases such as neurocysticercosis; (ii) decrease in the occurrence of brain trauma due to motor vehicle accidents; and (iii) improvement in maternal and perinatal assistance. These basic actions may decrease the incidence of epilepsy in the general population.
Political issues also need to be considered. In poorly organized societies, there is a lack of prioritization of epilepsy in national health policies, limited resources for trained personnel and a shortage of basic antiepileptic medications.
In middle-income countries, the creation of comprehensive centres for surgical programmes is increasing, to improve referral for surgical treatment. In 1994, the Brazilian government started an epilepsy programme for surgery, and this is still serving the population. This has had an important impact on the scientific development in epilepsy, training of experts and assistance for patients .
To answer the initial question: is there hope? Yes, taking into account the socio-economic perspective of the considered society, there is evidence of improvement in the understanding of epilepsy and a clear improvement in the management of epileptic seizures.
Conflicts of Interest: Dr Guerreiro has received grants and research support from Abbott, GlaxoSmithKline support from Abbott, GlaxoSmithKline, Jansen-Cilag, Novartis, and Bial; consultation and speaking honoraria and advisory board honorarium from Abbott, GlaxoSmithKline, Jansen-Cilag, Novartis, Merck-Serono, Lundbeck, UCB and Torrent.
| References|| |
Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al.
ILAE official report: a practical clinical definition of epilepsy. Epilepsia
World Health Organization. Atlas: Epilepsy care in the world.
Geneva, Switzerland: World Health Organization; 2005.
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al.
Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet
Meyer AC, Dua T, Ma J, Saxena S, Birbeck G. Global disparities in the epilepsy treatment gap: a systematic review. Bull World Health Organ
Noronha AL, Borges MA, Marques LH, Zanetta DM, Fernandes PT, de Boer H, et al.
Prevalence and pattern of epilepsy treatment in different socioeconomic classes in Brazil. Epilepsia
Mani KS, Rangan G, Srinivas HV, Kalyanasundaram S, Narendran S, Reddy AK. The Yelandur study: a community-based approach to epilepsy in rural South India – Epidemiological aspects. Seizure
Fernandes PT, Snape DA, Beran RG, Jacoby A. Epilepsy stigma: what do we know and where next? Epilepsy Behav
Maganti RK, Rutecki P. EEG and epilepsy monitoring. Continuum (Minneap Minn)
Bronen RA, Fulbright RK, Spencer DD, Spencer SS, Kim JH, Lange RC, et al.
Refractory epilepsy: comparison of MR imaging, CT, and histopathologic findings in 117 patients. Radiology
Cendes F. Neuroimaging in investigation of patients with epilepsy. Continuum (Minneap Minn)
Gaillard WD. Nuclear imaging (PET, SPECT). In: Wyllie E, editor. Wyllie's treatment of epilepsy
: Principles and practice
ed. Philadelphia, PA: Wolters Kluwer; 2015. p. 824-32.
Poduri A, Sheidley BR, Shostak S, Ottman R. Genetic testing in the epilepsies-developments and dilemmas. Nat Rev Neurol
Gonsales MC, Montenegro MA, Soler CV, Coan AC, Guerreiro MM, Lopes-Cendes I. Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice. Arq Neuropsiquiatr
Berkovic SF. Genetics of epilepsy in clinical practice. Epilepsy Curr
Abou-Khalil BW. Antiepileptic Drugs. Continuum (Minneap Minn)
Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology
Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al.
Definition of drug resistant epilepsy: consensus proposal by the ad hoc
Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia
Nair DR. Management of drug-resistant epilepsy. Continuum (Minneap Minn)
Burneo JG, Shariff SZ, Liu K, Leonard S, Saposnik G, Garg A, et al
. Disparities in surgery among patients with intractable epilepsy in a universal health system. Neurolog
y. 2016; 86
Cervenka MC, Henry BJ, Felton EA, Patton K, Kassoff EH. Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges. Epilepsy Behav
Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev
Morris GL 3rd
, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology
Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, et al.
Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology
Bergey GK, Morrell MJ, Mizrahi EM, Goldman A, King-Stephens D, Nair D, et al.
Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology
Guerreiro CAM. Brazil. In: Engel J Jr., Pedley TA, editors. Epilepsy: A comprehensive textbook
ed. Philadelphia: Lippincott William & Wilkins; 2008. p. 2849-57.
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