Surgery for Drug-Resistant Epilepsy in Children

Shanterra Grable, Mercer University College of Pharmacy

Epilepsy affects 65 million people worldwide. Of those, 3.4 million are in the United States. One third of the people with epilepsy are thought to be resistant to available treatments and live with uncontrolled seizures. [1]

If seizures persist after two trials of the appropriate medication at the proper dose, they are considered to be “drug resistant”. [2] Surgery is an option if patients do not respond to medication therapy alone. These surgeries have been performed for over a century, and their use has seen a significant increase in the 1980s and 1990s. However, evidence suggests that success cannot be guaranteed; therefore, risk versus benefits of these procedures should be carefully weighed. [3]

It has been suggested that the earlier surgery is performed, the better patient outcomes are.  Despite the evidence, the Epilepsy Foundation recommends to consider surgery as a last resort. [3] Previously, a retrospective analysis of 142 children showed that 79.3% were free from seizures post surgery with an average follow up of four years. This study was performed as a follow up on to the aforementioned trial in order to compare outcomes of surgery to medical therapy alone. [4]

Surgery for drug-resistant epilepsy in children
Design Randomized control trial; N=116
Objective To compare seizure outcomes after epilepsy surgery compared to standard medical therapy
Study Groups Brain surgery with appropriate medical therapy (n=57) vs. medical therapy alone (n=59)
Methods Based on seizure type, patients in the surgery group received hemispherotomy or corpus callosotomy. All surgeries were performed one month after the start of the trial with patients also continuing antiepileptics. Patients in the medical therapy group continued antiepileptic medications, but were also placed on a one year wait list for surgery.  If surgery patients went one year without an episode, their antiepileptic medications were tapered off.
Exclusion criteria: no consensus on the location of epileptic focus, metabolic abnormalities either genetic or acquired, cardiac, renal, or any systemic illness, history of status epilepticus
Duration November 2010 to March 2015
Primary Outcome Measure Freedom from seizures at 12 months measured by scores on the Hague Seizure Severity scale and seizure diaries
Baseline Characteristics Surgery (n=57) Medical therapy (n=59)
Median age-years 9.0 10.0
Female –no. (%) 23 (40) 19 (32)
Family history of epilepsy-no. (%) 3 (5) 6 (10)
Median age at onset of seizures-years 1.5 3.0
Median duration of epilepsy-years 4.9 5.0
Type of seizure
Focal 43 43
Secondary generalized 14 16
Frequency of seizures six months before randomization
≥ one per day 48 40
≥ one per week 5 10
≥ one per month 4 6
≥ one per three months 0 3
Median number of previous antiepileptic medications 3 3
Score on Hague Seizure Severity scale 37.9 ± 4.2 37.4 ± 4.3
Intelligence quotient on Binet-Kamat test 63.9 ± 19.3 62.8 ± 21.4
Social quotient on Vineland Social maturity Scale 38.6 ± 24.2 41.8 ± 20.9
Total score on Child Behavior Checklist 69.5 ± 6.3 67.8 ± 5.1
Total score on Pediatric Quality of Life Inventory 53.4 ± 15.4 53.2 ± 16.4
Results
Primary and secondary outcomes at year one
Outcome Surgery group Medical therapy group Absolute difference Difference in change from baseline
Value (95% CI) p value Value (95% CI) p value
Primary outcome: freedom from seizures-no. (%) 44 (77) 4 (7) 70.4 (57.8 to 83.1) <0.001 N/A N/A
Secondary outcomes
Score on Hague Seizure Severity scale 15.4 ± 5.5 34.3± 11.8 18.9 (15.5 to 22.3) <0.001 19.4 (15.8 to 23.1) <0.001
Intelligence quotient on Binet-Kamat test 62.7 ± 18.5 58.9 ± 22.1 3.7 (-6.6 to 14.0) 0.47 2.5 (-0.1 to 5.1) 0.06
Social quotient on Vineland Social Maturity scale 41.5 ± 23.1 39.9 ± 19.7 1.6 (-10.3 to 13.4) 0.79 4.7 (0.4 to 9.1) 0.03
Total score on Child Behavior Checklist 57.2 ± 6.7 68.6 ± 7.6 11.4 (8.8 to 14.0) <0.001 13.1 (10.7 to 15.6) <0.001
Total score on Pediatric Quality of Life Inventory 76.1 ± 13.1 53.9 ± 18.5 22.1 (16.2 to 28.1) <0.001 21.9 (16.4 to 27.6) <0.001
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: 33% overall in the surgery group: monoparesis (n=2), hemiparesis (n=15), generalized hypotonia and language deficits (n=1)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Children with drug resistant epilepsy that received surgery had higher rates of seizure cessation one year post surgery than those with antiepileptic medications alone.

 

This study was performed in India; thus, replicating the study to see if similar outcomes would be observed in the United States may be of an interest.  Most of the study subjects were children with an average age of nine to ten years old; therefore, the results may not be applicable to other age groups. Although the study suggest positive outcomes of surgery, the question remains if the same results would be seen in older patients that continue to have uncontrolled epilepsy despite several years of medications. In conclusion, the study provides further evidence that surgery may be an option for epilepsy control in pediatric patients; however, these results should not be extrapolated to adult patients.

 

 

References

[1] Shafer, Patricia O., RN, MN. Epilepsy Foundation website. Facts about seizures and epilepsy. https://www.epilepsy.com/learn/about-epilepsy-basics/facts-about-seizures-and-epilepsy. Updated March 2014. Accessed December 13, 2017.

[2] Sirven, Joseph I., MD. Epilepsy Foundation website. Refractory epilepsy (difficult to treat seizures). https://www.epilepsy.com/learn/refractory-epilepsy-difficult-treat-seizures. Updated March 2014. Accessed December 13, 2017.

[3] Weiner, Howard L. MD. Epilepsy Foundation website. Treating seizures and epilepsy: surgery. https://www.epilepsy.com/learn/treating-seizures-and-epilepsy/surgery. Updated August 2013. Accessed December 13, 2017.

[4] Dwivedi R, Ramanujam B, Chandra PS, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med. 2017;377(17):1639-1647.

 

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