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Table of Contents
Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 115-116

Drug-resistant epilepsy: A challenge, but ought to be overcome!

1 Department of Neurology, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India
2 Department of Neurology, HMC Advanced Neuro Spine Institute, Ludhiana, Punjab, India

Date of Submission28-Aug-2020
Date of Acceptance28-Aug-2020
Date of Web Publication12-Sep-2020

Correspondence Address:
Dr. Jasmine Parihar
Department of Neurology, Lady Hardinge Medical College and Associated Hospitals, New Delhi - 110 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-2884.294951

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How to cite this article:
Parihar J, Grewal K. Drug-resistant epilepsy: A challenge, but ought to be overcome!. Indian J Med Spec 2020;11:115-6

How to cite this URL:
Parihar J, Grewal K. Drug-resistant epilepsy: A challenge, but ought to be overcome!. Indian J Med Spec [serial online] 2020 [cited 2023 Jun 9];11:115-6. Available from: http://www.ijms.in/text.asp?2020/11/3/115/294951

Epilepsy is one of the most common chronic neurologic disorders. Although most cases can be easily controlled with appropriate antiepileptic drugs (AEDs), many patients continue to have seizures despite medical management. The International League Against Epilepsy defines drug-resistant epilepsy (DRE) as a failure of adequate trials of two (or more) tolerated, appropriately chosen, and appropriately used AED regimens (whether administered as monotherapies or in combination) to achieve seizure freedom. DRE is a challenge for the clinician, patient, caregiver, and society.

Epidemiological studies from the west have shown that the overall DRE burden among epilepsy patients is 30%–40%.[1] The exact incidence and prevalence of medically intractable epilepsy in India are unknown. An Indian study of 2153 epilepsy patients reports a lower proportion of DRE (11.3%).[2]

Various factors that have been reported to be associated with an increased risk of developing DRE include epilepsy onset at <1 year of age, symptomatic etiology, presence of neuropsychiatric disorder, history of febrile seizure, status epilepticus, multiple seizure types, abnormal EEG, and neuroimaging.[3] At the same time, gender, family history of epilepsy, idiopathic epilepsy, and seizure type were not associated with the risk of developing DRE.[3]

This issue carries an article titled “Etiological Spectrum of DRE – A Glimpse from North East India,”xs; which is a welcome addition to the data on DRE cases in India.[4] Different studies have shown variable distribution pattern of etiologies. Medial temporal lobe epilepsy has been reported as the most common etiology in this article from Northeast India,[4] but Chatterjee et al. reported gliotic lesions secondary to perinatal insult as the most common etiology in their patients with DRE whereas most patients in the study by Mukherjee et al. had idiopathic DRE.[2],[5] Focal epilepsy is the most common seizure type in patients with DRE in most studies.[4],[5]

Patients with DRE have increased risks of seizure-related injuries, premature death, unemployment, poor long-term intellectual outcome, psychiatric comorbidities, social stigmata, and reduced quality of life. The mortality rate in DRE patients has been estimated to be 1.37/100 person-years.[6] According to Chatterjee et al., epilepsy affected education in 60% of patients, employment in 40%, and marital prospects in 90%.[5] In addition, DRE imposes a significant financial burden on the patient and family. It accounts for 80% of the cost of epilepsy in the United States.[1] In an Indian study, the direct cost of DRE epilepsy care was nearly one-fourth of GDP/capita, of which average monthly expenditure for AEDs was over ₹2000 (USD 28.5), which amounted annually to 19% of gross national product (GNP)/capita whereas medical consultations and investigations cost 9% of the GNP/capita annually.[5]

Apart from a holistic approach to management and care, patients with DRE should undergo a trial of combinations of conventional AEDs. The clinician should also consider adding the newer antiepileptics available such as vigabatrin, brivaracetam, perampanel, stiripentol, and cannabinoids depending on the epilepsy profile. The unmet need for appropriate, adequately dosed antiepileptics, which though is included in the definition of DRE, is hardly implemented at the primary care level.

It has been reported that nearly one-third of DRE patients may have prolonged seizure-free periods (12 months or more), but they have higher relapse rates of more than 70%.[7] The ketogenic diet, which is a high-fat, low-protein, low-carbohydrate diet, and modified Atkins diet, has shown effectiveness in all seizure types and should be considered in addition to AEDs.

Surgery has shown promising results in selected patients. According to a recent Cochrane review, surgically treated DRE patients are 15 times more likely to be seizure free at 1 year compared to medical management alone.[8] Recent data from a randomized controlled trial shows that surgery for pharmacoresistant epilepsy in the subgroup of 18 years or younger population resulted in a significantly higher rate of freedom from seizures and better scores of quality of life than those who continued medical therapy alone at 12 months.[9] All patients who had undergone temporal lobectomy and hypothalamic hamartoma surgery were seizure free, highlighting the essential role of etiology in guiding us in prognosis and outcome. It is hence imperative to elucidate the etiology of epilepsy so that further management can be planned.

In patients in whom the definitive surgery is not possible, palliative surgical procedures can be considered. These procedures, including corpus callosotomy and multiple subpial resections, disrupt the pathways responsible for propagating epileptiform discharges. The vagus nerve stimulation has also been used as adjunctive therapy for DRE. However, the surgical facility is available at selected centers in India with a long waiting list. A review of data from multiple countries reports that average delay between DRE diagnosis and epilepsy surgery has remained approximately 20 years in adults and 5 years in children.[10]

Hence, it is essential to identify DRE patients at the earliest possible, and a thorough evaluation should be conducted to find the etiology. It is also crucial that physicians and health-care teams be guided and adapted to the challenges of managing DRE, focusing on semiology and etiology-based management with adequate and appropriate dosed AED regimens. Early identification and referral to comprehensive care centers of DRE patients can avoid premature death and reduce the seizure burden.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Berg AT, Langfitt J, Shinnar S, Vickrey BG, Sperling MR, Walczak T, et al. How long does it take for partial epilepsy to become intractable? Neurology 2003;60:186-90.  Back to cited text no. 1
Mukherjee J, Chakraborty DP, Guha G, Bose B, Saha SP. Recent drug resistant epilepsy spectrum in eastern India. J Epilepsy Res 2017;7:39-44.  Back to cited text no. 2
Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis. Epilepsia 2018;59:2179-93.  Back to cited text no. 3
Synmon B, Sharma SR, Hussain M, Hyniewta Y. Etiological spectrum of drug-resistant epilepsy – A glimpse from North East India. Indian J Med Spec 2020;11:127-31.  Back to cited text no. 4
  [Full text]  
Chatterjee A, Nair R, Gandeti R, Puppala GK, Chandran V, Gorthi SP, et al. Socioeconomic consequences of drug-resistant epilepsy in an adult cohort from southern India. Epilepsy Behav 2020;110:107173.  Back to cited text no. 5
Sperling MR, Feldman H, Kinman J, Liporace JD, O'Connor MJ. Seizure control and mortality in epilepsy. Ann Neurol 1999;46:45-50.  Back to cited text no. 6
Callaghan B, Schlesinger M, Rodemer W, Pollard J, Hesdorffer D, Hauser WA, et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia 2011;52:619-26.  Back to cited text no. 7
West S, Nolan SJ, Cotton J, Gandhi S, Weston J, Sudan A, et al. Surgery for epilepsy. Cochrane Database Syst Rev 2015;7:CD010541.  Back to cited text no. 8
Dwivedi R, Ramanujam B, Chandra PS, Sapra S, Gulati S, Kalaivani M, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med 2017;377:1639-47.  Back to cited text no. 9
Solli E, Colwell NA, Say I, Houston R, Johal AS, Pak J, et al. Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): A literature review. Epilepsia 2020;61:1352-64.  Back to cited text no. 10


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