Running head: INTEGRATIVE LITERATURE REVIEW 1

Integrative Literature Review

Donald A. Leon
Bon Secours Memorial College of Nursing
Arlene Holowaychuk, EdD
NUR4322
April 26, 2020

I pledge.
INTEGRATIVE LITERATURE REVIEW 2

Abstract
Purpose: The aim of this integrative literature review is to compare the outcomes of treating

breakthrough seizures in patients with epilepsy when the use of antiepileptic drugs alone is used

vs. when adjunctive therapy is used in addition to drug monotherapy.

Background: The mainstay of epilepsy treatment is the use of antiepileptic drugs. Yet, roughly

one-third of epilepsy patients continue to have seizures after one, two, and up to 5 AEDs.

Adjunctive treatment is considered any treatment for seizures that occur after a patient has taken

at least 1 AED, including polypharmacy, oral supplementation, and behavioral interventions.

Method: an online database accessed via Bon Secours Memorial College of Nursing library

portal was used to search and collect the articles. The information contained in those articles

form the basis for this literature review.

Limitations: Limitations to this review come in two main forms: the researcher’s inexperience

and lack of professional credentialing, and various limitations encountered by the authors of the

highlighted articles themselves.

Results and Findings: evidence in the articles indicates that adjunctive treatment for epilepsy

whether polypharmacy, oral zinc supplementation, and stress-reduction techniques, all contribute

to therapeutic epilepsy outcomes (reduction in number of seizures) vs. AED monotherapy alone.

Implications and Recommendations: many of the adjunctive treatments highlighted in this

review come with little or minimal adverse effects. Considering that they have been found to

reduce the number of seizures in patients with drug-resistant epilepsy, they are worth clinical

consideration and further study.

INTEGRATIVE LITERATURE REVIEW 3

Integrative Literature Review

The aim of this integrative literature review is to compare the outcomes of treating

breakthrough seizures in patients with epilepsy. Specifically, this review compares outcomes

with antiepileptic drugs (AEDs) alone (monotherapy), vs. treatment with AED and adjunctive

therapy. Current best-practice is to initiate epilepsy treatment with an AED. However, even with

advances in pharmacology and the introduction of over 15 new AEDs, approximately 1/3 of

patients still experience breakthrough seizures (Haut et al., 2018; Maurousset et al 2016).

Patients who continue to have seizures after monotherapy are often started on a second

and as many as 5 AEDs (polytherapy). The success rates for eliminating seizures when

introducing a third AED is about 3% in those patients who do not have seizure freedom after 2

AEDs (Saad et al, 2015). In general, and for this review seizure occurrences after treatment are

referred to as breakthrough seizures, refractory seizures, refractory epilepsy, or medication-

resistant epilepsy. The researcher seeks to explore and discuss published information on the

PICO question: for patients with epilepsy does the use of adjunctive therapy reduce the future

risk and incidence of breakthrough seizures compared to the use of AEDs (monotherapy) alone?

Design and Methods

The focus of this review is on 5 research articles address adjunctive treatment to AED

monotherapy. In three of the articles, the authors address one AED, perampanel, as an adjunct

treatment to other AEDs. Another article has adjunctive oral zinc supplementation as its subject

of inquiry, and in the remaining article behavioral interventions are studied.

The OVID Discovery database was used to search for relevant articles. Initial search

yielded more than 18,000 articles. Those results were narrowed down using database filters

including year of publication, English language, peer review, and relevance to the PICO
INTEGRATIVE LITERATURE REVIEW 4

question. The results were narrowed down further by the following search terms: drug resistant

epilepsy, epilepsy management, epilepsy AND adjunct, antiepileptic drugs, intractable epilepsy,

refractory epilepsy, animal therapy AND epilepsy, and cannabinoids and epilepsy.

The remaining articles were narrowed again based on their relevance to the PICO

question, the authors credentials, and a breadth of geography and age within the focus. The

researcher’s initial intent was to look at multiple different adjunctive therapies, however, the

proportion of literature that the researcher perceived lended itself to the focus on perampanel

with 3 articles, 1 on a supplement, and 1 on a non-pharmacological approach. The resulting

articles that are the basis of this review are 4 quantitative studies of randomized control trials

from geographically diverse areas (French et al., 2015; Haut et al, 2018; Nishida et al., 2018;

Saad et al., 2015) and one quantitative analysis of epidemiological and clinical data (Maurousset

et al, 2016).

Findings
The authors of each of the 5 articles all found that there is a positive correlation between

their respective adjunctive treatment for epilepsy and seizure outcomes for the cohort in the

studies (French et al., 2015; Haut et al, 2018; Maurousset et al., 2016; Nishida et al., 2018; Saad

et al., 2015). Below follows a brief overview of each of the research articles. Table-1 Article

Evaluation summarizes each.

In 2016, a study with 101 adult patients with epilepsy took place. All 101 in the setting of

a tertiary care center in Tours, France were prescribed and compliant with adjunctive

perampanel. The authors used Kaplan-Meier survival curve statistical analysis. Outcomes were

broken down into four categories from one visit to the next: seizure free, greater than 50%
INTEGRATIVE LITERATURE REVIEW 5

reduction in seizures, less than 50% reduction and seizures, and no reduction or worsening of

seizures.

Maurousset et al performed epidemiological and clinical data collection retrospectively

from the facility in France for the period May 2014 through June 2015. Descriptive data was

analyzed using Kaplan-Meier graphs, which compared the mean and percentile ranks of patients

in several variable categories and their achievement of seizure reduction. The study found that

adjunctive perampanel was effective in over one-third (41.6%) of patient’s in reducing seizures

at least 50% (Maurousset et al., 2016).

Another study involving the use of perampanel as adjunctive treatment for epilepsy was

conducted by French et al (2015). This quantitative study did not identify use of any theoretical

framework and was a double-blind, multicenter, interventional, placebo-controlled study that

took place at 78 sites in 16 countries. The sample size for this study consisted of 162 child and

adult patients 12 years of age and older diagnosed with Idiopathic Generalized Epilepsy (IGE)

who had recently experienced Primary Generalized Tonic Clonic (PGCT) seizures, and been

taking stable doses of 1 to 3 approved AEDs (French et al, 2015).

Patient diaries in both treatment group and placebo (control) group were used to collect

data on patient seizure frequency. In addition, interactive voice response system (IVRS) was

used to register patient data. For frequency of PGCT seizures data were rank-performed,

separately for baseline and for percent-change. Data for treatment differences was analyzed

using Hodges-Lehmann estimator and associated 95% confidence intervals. The authors found a

median change in seizure frequency of -76.5% and a seizure freedom rate in the maintenance

period of 30.9% in the treatment group vs. 12.3% in the placebo group (French et al, 2015).

Adjunctive perampanel is effective at reducing PGCT seizure frequency in patients with IGE.
INTEGRATIVE LITERATURE REVIEW 6

In another quantitative study Nishida et al (2018) examine the outcomes of adjunctive

perampanel use in 3 different doses vs. a placebo control group on the occurrence of partial-onset

seizures (POS). The authors do not specify a theoretical framework used to guide the project.

Study design is randomized, double-blind, multicenter, interventional, parallel-group, and

placebo-controlled. Sample size consists of 707 children and adults age 12 and older in the

setting of 119 sites in the Asia-Pacific (Australia, China, Japan, Malaysia, Republic of Korea,

Taiwan, and Thailand). Further inclusion criteria included that patients had to be diagnosed with

POS, had uncontrolled POS within last two years despite use of at least 2 AEDs, had occurrences

of 5 or more POS during baselines, and were taking stable does of 1-3 AEDs (Nishida et al,

2018).

Data collection was performed by two primary methods. At registration patient data was

registered via interactive voice response system (IVRS). Seizure counts were collected by patient

diaries. Gathered data was analyzed using descriptive statistical analysis mean percent increase

in POS over baseline in a 28-day period. Frequency of seizure changes was analyzed by rank

analysis of covariance and intent to treat (ITT) analysis set was used do delineate who was being

treated. Findings show a -10.8% increase in POS in placebo group and -17.3% for patients

receiving 4mg does, -29% for the 8mg dose, and -38% for perampanel 12mg (Nishida et al,

2018). The study shows a strong positive dose-dependent correlation between adjunctive

perampanel use and reduced numbers of POS.

In a study performed by Saad et al (2015) the authors examine the efficacy of oral zinc

supplementation on children with drug-resistant epilepsy. The authors do not identify any

specific conceptual or theoretical framework that informs their findings. The design of the study

is quantitative, randomized, double-blind, placebo-controlled trial. Inclusion criteria for the

INTEGRATIVE LITERATURE REVIEW 7

sample stipulates that participants were between ages 3 and 12, presented with idiopathic

generalized epilepsy (1 or more seizures per month), and failed two realize seizure freedom in a

6 month period of compliance with taking at least approved AEDs (Saad et al, 2015). Based on

inclusion and exclusion criteria 45 patients were chosen from Assuit University and 3 private

clinical sites in Assiut, Egypt.

Data was gathered by detailed questionnaires developed by the researchers and

completed by the patient’s parents or caregiver. Data analysis involved use of Statistical Package

for Social Sciences (SPSS), version 22, two-way analysis of variance, and Mantel-Haenszsel chi-

square tests, all appropriate methods for the study design. The authors reported findings in terms

of mean percentage of reduction in seizures in the intervention group vs. the placebo group and

found that 31% of patients in treatment group were good responders (decrease in seizures of 50%

or greater) vs. 4.5% in the placebo group (Saad et al, 2015). The authors conclude that oral zinc

supplementation as adjunct treatment has mildly beneficial effects for children treated, holds

promise as a potential for future treatment, and should be further evaluated (Saad et al, 2015).

Haut et al (2018), in a quantitative study, explored the efficacy of stress-reducing

(behavioral) therapy on seizure outcomes in patients with epilepsy. In the article, the authors did

not identify relying on any conceptual or theoretical framework. The study was a double-blind,

multicenter, randomized controlled trial. The sample consisted of 66 adult patients in the setting

of 3 epilepsy centers in disparate geographic regions of the United States (Haut et al. 2018). All

participants were English-speaking, had medication-resistant focal epilepsy, regularly took

AEDs for a minimum of the 30 days prior to the trial, and were capable of keeping an E-diary.

Data collection took place by a combination of E-diaries on an app on study-provided

smartphones. Additionally, due to the nature of the interventions being behavioral-based,

INTEGRATIVE LITERATURE REVIEW 8

multiple standardized assessment questionnaires for mental health, neurological disorders, and

epilepsy were given for baseline data collection and then post-interventions. These assessments

included The Beck Depression Inventory-II, Generalized Anxiety Disorder-7, State-Trait

Anxiety Inventory, Self-Efficacy Scale, MINI, and Neurological Disorders Depression Inventory

for Epilepsy (Haut et al, 2018). Statistical analysis of the primary outcome, seizure frequency

was conducted by mean, median, and standard deviation. Categories were summarized with

frequency and proportion. The authors found that both behavioral interventions employed,

progressive muscle relaxation (PMR) with diaphragmatic breathing and focused attention with

extremity movements were statistically as efficacious in reducing the percent of seizure

occurrence (29% and 25% respectively) over baseline rates. Both behavioral intervention

methods reduced occurrence of seizures over baseline and could be an effective treatment tool as

an adjunct to AEDs (Haut et al, 2018).

Discussion/Implications
The five articles referenced in this study take place in diverse geographical settings. One

article is based in the U.S., another in Tours, France, another in Egypt, and another. The

countries of the Asia-Pacific. One of the studies’ sample includes only adults, another only

children, and 3 of them include adults and children aged 12 and up. Some of the studies focus on

partial onset seizures (POS) while others on primary generalized tonic clonic (PGTC) seizures.

Despite this great diversity of the study participants and the many individual differences between

the articles, there are two common themes that the researcher has identified that run through all

of the articles: all participants are diagnosed with epilepsy, have regularly taken at least 1 AEDs,

have continued to have seizures despite the AEDs, and have even if only as a result of their

participation in the studies have been treated with at least adjunctive treatment. The second
INTEGRATIVE LITERATURE REVIEW 9

theme present in the articles is that of addressing the patient outcome, of reducing the number of

seizures.

Patient Attributes
According the World Health Organization there are 50 million people worldwide who

have epilepsy (WHO, 2020). The researcher did not find statistics indicating the number of

patients worldwide who are treated, however, there is data that approximately one-third of

patients treated for epilepsy continue to have seizures after treatment with an AED Haut et al.,

2018; Maurousset et al., 2016). All the patients comprising the studies in these 5 articles belong

to that roughly 1/3 subset of epileptic patients, who continue to have seizures after treatment.

Patient Outcomes
A second common theme running through the 5 articles is the focus on patient outcomes.

Not only was the focus on patient outcomes, but specifically one primary outcome, the reduction

of seizure occurrences. One of the authors framed the outcome in terms of increase of patient

seizures post interventions, resulting in a negative percent increase (French et al, 2015). The

other 4 articles were framed in terms of percent of seizure reduction (Haut et al, 2018;

Maurousset et al., 2016; Nishida et al., 2018; Saad et al., 2015). All 5 articles pointed to a

conclusion that adjunctive treatment can be effective in some patients and warrants further study.

Limitations
The primary limitation in the progress of this integrative review involves the researcher’s

inexperience and limited qualifications. The researcher is a first-semester Senior in a Bachelor of

Science in Nursing program and has limited experience in practice and academic study of the

topic. In addition, time poses another limitation as this review constitutes a portion of a full-time
INTEGRATIVE LITERATURE REVIEW 10

class load. Therefore, the researcher is limited to a review of the articles as they relate to the

PICO question.

Other limitations are presented by the article themselves. The narrowing criteria

discussed at the beginning of this review were instrumental to finding relevant, quality articles

focused on the topic. At the same time those same criteria limited the number of articles to

review to only 5, within a narrow 5-year period of publication. Most of the authors in the subject

articles acknowledge limitations that they encountered in their own studies. These factors should

be kept in mind when further research is conducted.

Conclusions
The researcher of this review has found that the evidence presented in these articles lends

credence to the idea that adjunctive treatment for refractory epilepsy can be effective in

significantly reducing the number of breakthrough seizures. The two common themes of patient

attributes and patient outcomes further support that position and directly address the PICO

question: for patients with epilepsy does the use of adjunctive therapy reduce the future risk and

incidence of breakthrough seizures compared to the use of AEDs (monotherapy) alone? The

succinct answer to that question is yes. However, it is important to keep in mind that these

studies point to correlation and not causality. The researcher’s recommendation is for further

studies on the above referenced adjunctive treatment methods as well as additional adjunctive

treatment methods that have not been explored here. At the very least the evidence points

towards hope for sufferers of medicine-resistant epilepsy obtaining improved quality of life.
INTEGRATIVE LITERATURE REVIEW 11

References
French, J.A., Krauss, G.L., Wechsler, R.T., Wang, X.F., DiVentura, B., Brandt, C… Bibbiani, F.

(2015). Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy.

Neurology, 85, 950-957.

Haut, S.R., Lipton R.B., Cornes, S., Dwivedi, A.K., Wasson, R., Cotton, S., Strawn, J.R.,

Privatera, M. (2018). Behavioral Interventions as a treatment for epilepsy. Neurology, 90

(11), e963-e970. doi: 10.1212/WNL.0000000000005109

Maurousset, A., Limousin, N., Praline, J., Biberon, J., Corcia, P, De Toffol, B. (2016).

Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center

in Tours. Epilepsy & Behavior, 61, 237-241. doi: 10.1016/j.yebeh.2016.06.005

Nishida, T., Lee, S.K., Inoue, Y., Saeki, K., Ishikawa, K., Kaneko, S. (2018). Adjunctive

perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study. Acta

Neurologica Scandinavica, 137, 392-399. . doi: 10.1111/ane.1288

Saad, K., El-Houfey, A.A., El-Hamed, M.A., El-Asheer, O.M., Al-Atram, A.A., Tawfeek,

(2015). A randomized, double-blind, placebo-controlled clinical trial of the efficacy of

treatment with zinc in children with intractable epilepsy. Functional Neurology, 30(3),

181-185.

World Health Organization (2019). Epilepsy. Retrieved from https://www.who.int/en/news-

room/fact-sheets/detail/epilepsy
Running head: INTEGRATIVE LITERATURE REVIEW 1

APA Citation Author French, J.A., Krauss, G.L., Wechsler, R.T., Wang, X.F., DiVentura, B.,
Qualifications Brandt, C… Bibbiani, F. (2015). Perampanel for tonic-clonic seizures
in idiopathic generalized epilepsy. Neurology, 85, 950-957.
French – MD / Krauss – MD / Wechsler – MD / Wang – MD / DiVentura –
MBA / Brandt – MD / Trinka – MD, MSc / O’Brien MD, BS / Laurenza – MD
/ Patten – PhD / Bibbiani – MD
Background/Problem Few antiepileptic drugs (AEDs) are licensed to treat Primary Generalized
Statement Tonic Clonic (PGCT) seizures. Examined in this study are outcomes of
adjunctive perampanel on patients diagnosed with Idiopathic Generalized
Epilepsy who suffer from PGCT
Conceptual/theoretical
Framework
Design/Method/Philosophica Double-blind, multicenter, interventional, placebo-controlled, randomized
l controlled trial
Underpinnings
Sample/ Setting/Ethical Sample = 162 children and adults > 12 years old with drug-resistant Primary
Considerations Generalized Tonic Clonic (PGCT) seizures diagnosed with Idiopathic
Generalized Epilepsy (IGE).
Setting: 78 sites, 16 countries
Ethical: approval obtained from all participating countries’ regulatory
government bodies, Institutional Review Boards, and independent ethics
commissions. Informed consents signed by all participants
Major Variables Studied Seizure outcomes in patients receiving adjunctive perampanel vs. placebo
(and their definition) (control) group
Measurement Tool/Data Interventional study. Patients were administered perampanel and a placebo
Collection Method group at 1:1 ratio. Patient diaries recorded seizure outcomes
Data Analysis -baseline and percent change rank-transformed separately, with covariance
-treatment difference: Hodges-Lehmann estimator and associated 95%
confidence intervals
-CGI-C scores analyzed using Cochran-Mantel-Haenszel test stratified by
pooled country
Findings/Discussion -adjunctive perampanel PGCT seizure freedom rate=30.9% vs. placebo 12.3%
Appraisal/Worth to practice -adjunctive perampanel is an effective option for reducing seizures in patients
INTEGRATIVE LITERATURE REVIEW 13

with drug-resistant epilepsy

APA Citation Author Haut, S.R., Lipton R.B., Cornes, S., Dwivedi, A.K., Wasson, R., Cotton, S.,
Qualifications Strawn, J.R., Privatera, M. (2018). Behavioral Interventions as a
treatment for epilepsy. Neurology, 90 (11), e963-e970. doi:
10.1212/WNL.0000000000005109
Haut – MD / Lipton – MD / Cornes – MD / Dwivedi – PhD / Cotton – PhD /
Strawn – MD / Privitera – MD
Background/Problem 1/3 of epilepsy patients on medicine continue to have seizures. Behavioral
Statement treatments are garnering increasing interest for treatment of medication
resistant epilepsy.
Conceptual/theoretical
Framework
Design/Method/Philosophica Double-blind, multicenter, randomized controlled trial
l
Underpinnings
Sample/ Setting/Ethical Sample = 66 adults with medication-resistant focal epilepsy recruited from 3
Considerations medical centers in the U.S.A. Institutional Review Board approval. Written
informed consent obtained from all participants
Major Variables Studied Two behavioral interventions compared against each other in improvement
(and their definition), if over baseline of seizure outcomes. Progressive muscle relaxation (PMR) vs.
appropriate focused attention intervention (control)
Measurement Tool/Data 6 assessment scales administered to participants at baseline and for follow-up.
Collection Method Participants kept e-diary on provided smartphones, reporting seizure activity
Data Analysis -Quantitative data - mean (standard deviation) and median
-Categorical data – summarized using frequency and proportion
-Pre-intervention to post-intervention comparison – Wilcoxon signed rank test
and parametric paired t test
Findings/Discussion -Both behavioral interventions PMR and focused attention were found to
reduce seizure frequency at similar rates. Authors conclude that no evidence
was found for PMR as adjunctive treatment, however, both PMR and focused
attention were found to reduce stress, the number 1 reported precipitant of
seizure onset.
Appraisal/Worth to practice -study falls short of providing evidence that PMR is effective as adjunctive
INTEGRATIVE LITERATURE REVIEW 14

therapy, it does demonstrate that PMR and focused attention reduce stress and
also reduce the frequency of seizures in a 28 day and 3-month reporting period
APA Citation Author Maurousset, A., Limousin, N., Praline, J., Biberon, J., Corcia, P, De Toffol, B.
Qualifications (2016). Adjunctive perampanel in refractory epilepsy: Experience at tertiary
epilepsy care center in Tours. Epilepsy & Behavior, 61, 237-241. doi:
10.1016/j.yebeh.2016.06.005

Background/Problem Despite the introduction of 15 new anti epileptic drugs, 1/3 of patients do not
Statement achieve seizure freedom.
Conceptual/theoretical
Framework

Design/Method/Philosophica Quantitative postimplementation

l
Underpinnings
Sample/ Setting/Ethical -101 adult patients in a tertiary center in -France, prescribed adjunct
Considerations perampanel
-Acknowledgement of understanding journal’s
position on ethical standards for studies and compliance therewith
Major Variables Studied -reduction in seizures for those taking adjunctive perampanel
(and their definition), if -results for adults with intellectual disability (ID) or psychologic co-morbidity
appropriate vs. those without ID or comorbidity
Measurement Tool/Data Retrospective collection of epidemiological and clinical data
Collection Method
Data Analysis Descriptive data analysis, Kaplan-Meier

Findings/Discussion -41.6% of patients studied had a 50% or greater reduction in breakthrough

seizures with use of adjunctive perampanel
Appraisal/Worth to practice Perampanel is effective in some patients as an adjunct to other AEDs
INTEGRATIVE LITERATURE REVIEW 15

APA Citation Author Nishida, T., Lee, S.K., Inoue, Y., Saeki, K., Ishikawa, K., Kaneko, S. (2018).
Qualifications Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized
phase III study. Acta Neurologica Scandinavica, 137, 392-399. . doi:
10.1111/ane.1288
Nishida – National Epilepsy Center, Shizuoka Institute of Epilepsy
Lee – Department of Neurology, Seoul National University Hospital
Inoue – Eisai Co Ltd., Tokyo, Japan
Saeki – North Tohoku Epilepsy Center, Minato Hospital, Aomori, Japan
Background/Problem In previous studies perampanel 12mg failed to show additional efficacy over
Statement 8mg. The authors in this study examine treatment over a broad dosing range
Conceptual/theoretical None identified.
Framework
Design/Method/Philosophica Quantitative. Double-blind, multicenter, interventional, placebo-controlled,
l parallel group, randomized controlled trial
Underpinnings

Sample/ Setting/Ethical Sample = 707 children and adults > 12 years old with drug-resistant partial-
Considerations onset seizures (POS).
Setting: 119 sites, Australia, China, Japan, Malaysia, Republic of Korea,
Taiwan, Thailand
Ethical: in accordance with Declaration of Helsinki guidelines
. Approval obtained from all participating countries’ regulatory government
bodies. Written, informed consents signed by all participants
Major Variables Studied Seizure outcomes in patients receiving adjunctive placebo (control) group and
(and their definition) 3 different dosage of adjunctive perampanel (1:1:1:1 ratio).
Measurement Tool/Data Interventional study. Patients were administered perampanel and a placebo
Collection Method group at 1:1:1:1 ratio. Patient diaries recorded seizure outcomes
Data Analysis -median percent change in seizure frequency over baseline (per 28 days)
-50% responder rates
-ITT analysis set
Findings/Discussion -adjunctive perampanel at 8mg and 12mg daily doses is safe and efficacious in
treating partial-onset seizures in Asia-Pacific population
Appraisal/Worth to practice -adjunctive perampanel is an effective option for reducing seizures in patients
INTEGRATIVE LITERATURE REVIEW 16

with partial-onset seizures resulting from epilepsy

APA Citation Author Saad, K., El-Houfey, A.A., El-Hamed, M.A., El-Asheer, O.M., Al-Atram,
Qualifications A.A., Tawfeek, (2015). A randomized, double-blind, placebo-controlled
clinical trial of the efficacy of treatment with zinc in children with intractable
epilepsy. Functional Neurology, 30(3), 181-185.
Saad – MD, Department of Pediatrics, Faculty of Medicine Assiut University.
Assiut, Egypt El-Houfey – PhD, Department of Community Health Nursing,
Assiut University, Assiut Egypt
El-Ahmed – MD, Department of Neurology, Faculty of Medicine, Assiut
University Assiut Egypt
El Asheer – MD, Department of Pediatrics, Faculty of Medicine Assiut
University. Assiut, Egypt
Al-Atram – MD, Department of Psychiatry, College of Medicine, Almajmaah
University KSA
Tawfeek – MD, of Pediatrics, Faculty of Medicine Assiut University. Assiut,
Egypt
Background/Problem Trace elements may play a role in the production and control of seizures in
Statement humans. Zinc, the second most abundant trace element in the human body
regulates the CNS.
Conceptual/theoretical
Framework
Design/Method/Philosophica Randomized, double-blind, placebo-controlled trial
l
Underpinnings

Sample/ Setting/Ethical Sample = 45 children between 3 and 12 years old with Idiopathic Generalized
Considerations Epilepsy (IGE), intractable.
Setting: 4 sites (Assiut University and 3 private centers in the city of Assiut,
Egypt
Ethical: approval obtained from Ethics Committee and IRB of Assiut
University. Informed consent obtained from participants in accordance with
Assiut University IRB. Children gave their assent, their parents’ consent
Major Variables Studied Seizure outcomes in patients receiving adjunctive zinc supplementation vs.
INTEGRATIVE LITERATURE REVIEW 17

(and their definition), if placebo (control) group

appropriate
Measurement Tool/Data Interventional study. Patients were administered zinc supplements and a
Collection Method placebo group at 1:1 ratio. Detailed patient questionnaires completed by
patient’s parents or caregivers
Data Analysis -Statistical Package for Social Sciences (SPSS), version 22
-two-way analysis of variance
-Mantel-Haenszsel chi-square tests
Findings/Discussion -zinc supplementation has positive effect reducing seizures. 31% of
intervention group achieved a reduction in seizure occurrence of 50% or better
Appraisal/Worth to practice -adjunctive zinc supplementation shows promising signs of treating children
with drug-resistant epilepsy