This study was performed to elucidate quality of life (QOL) and its determinants in adult drug refractory epilepsy (DRE) patients who were not candidates for epilepsy surgery.
A correlational study was performed at the center of excellence, epilepsy between July 2014 to June 2016. All consecutive DRE patients who were not candidates for epilepsy surgery were enrolled. The outcomes were QOL, assessed using the quality of life inventory in epilepsy-31 items (QOLIE-31) inventory and the correlation of QOL with epilepsy-related variables like seizure severity and frequency. We also compared current QOL with QOL during the pre-surgical evaluation to strengthen our study outcome.
A total of 129 adult patients were enrolled over two years. The mean age was 26.5 ± 6.7 years and male: female ratio was 3: 1. The mean age at epilepsy onset was 9.6 ± 6.6 years and mean duration of epilepsy was 14.9 ± 7.5 years. There was lower seizure frequency than during pre-surgical evaluation in 37.2% of patients, while in 62.8% the seizure frequency remained the same or was higher. Nine (6.98%) patients became seizure free. In comparison to QOL status during the pre-surgical evaluation, there was statistically significant worsening of QOL in all domains (
The QOL of DRE patients who were not candidates for epilepsy surgery worsened relative to the QOL during the pre-surgical evaluation period. Seizure severity significantly correlated with QOL, but seizure frequency did not.
Drug refractory epilepsy (DRE) is defined
After pre-surgical evaluation, some patients were found to be ineligible for epilepsy surgery. Very few studies
Therefore, we planned this study with the aim of studying QOL of these non-surgical DRE patients during follow-up to elucidate which epilepsy-related variables correlated with their QOL.
After approval from the institutional ethics committee, we designed a 2-year correlational study from July 2014 to June 2016 at an apex tertiary care hospital and epilepsy surgery center. During their scheduled outpatient department visits, we enrolled consecutive DRE patients who were not candidates for epilepsy surgery. We included all patients who were aged 18 years or more, had undergone pre-surgical evaluations at our institute more than 2 year back. Patients were excluded if they had significant comorbidity, intellectual decline, or did not provide consent. Those patients who did not undergo surgery due to a lack of consent for invasive pre-surgical evaluation, lack of consent for epilepsy surgery even though cleared for surgery, or unable to afford of epilepsy surgery/complete pre-surgical evaluation were also excluded from the analysis. We recorded data related to socio-demographic details including age, sex, occupation, and marital status. Epilepsy-related variables including age at onset (age when first seizure noticed) and duration of epilepsy in years (defined as current age minus age at onset) were recorded. Seizure frequency per month during the pre-surgical evaluation (when patient was admitted to an epilepsy monitoring unit) was extracted from the epilepsy surgery database. Data related to risk factors of epilepsy including history of perinatal hypoxia, febrile seizure, head trauma, and nervous system infection were also extracted from epilepsy surgery database and reconfirmed during out patient department visits. Current seizure frequency per month was recorded from a seizure diary (if available) using the average number of seizures per month in the last 6 months. In those patients who were not maintaining a diary, approximate seizure frequency per month was calculated from the daily frequency to frequency per week for the last 6 months. For perceived change in seizure frequency, patients were simply asked one question regarding change in current seizure frequency in comparison to frequency during the pre-surgical evaluation. There were two potential responses, decreased frequency or not decreased (i.e., the same or increased frequency). Seizure severity was assessed using the national hospital seizure severity scale (NHS3). Seizure freedom was defined as no clinical seizures in the last year with antiepileptic drug treatment. Data related to the results of various pre-surgical investigations including video electroencephalography in the epilepsy monitoring unit, magnetic resonance imaging of brain, single-photon emission computed tomography, positron emission tomography scan of the brain, magneto-encephalography, and reasons of non-clearance for epilepsy surgery were extracted from the epilepsy surgery database. After obtaining informed consent, patients were asked to fill out a disease-specific QOL proforma. The quality of life inventory in epilepsy 31-items (QOLIE 31) was used to record current quality of life.
The NHS3
The QOLIE-31
The QOLIE 31 scale has no cut-off value distinguishing good and poor QOL. At our center, all patients who underwent pre-surgical evaluation also underwent QOL evaluation during pre-surgical evaluation using the same QOLIE 31 scale. Data related to QOL during the pre-surgical evaluation were stored in the epilepsy database. Therefore, we planned to compare current QOL with QOL during the pre-surgical evaluation of same patients as a historical control to strengthen our study. QOL during the pre-surgical evaluation was extracted from epilepsy database.
Statistical analysis was performed using STATA 12.0 (Stata Corp. LP, College Station, TX, USA). The outcomes were current quality of life and the comparison of current QOL with QOL during pre-surgical evaluation. The other outcome was the correlation between epilepsy-related variables, including seizure severity, seizure frequency, age at onset of epilepsy, duration of epilepsy, and perceived change in seizure frequency with the status of various current QOL domains. For correlational analyses, the non-parametric Spearman correlation test was used for continuous variables, and the non-parametric Wilcoxon rank-sum test and parametric
A total of 129 adult patients were enrolled over a 2-year period from 2014 to 2016. Socio-demographic and epilepsy-related baseline characteristics are shown in
Regarding epileptic risk factors, a history of perinatal hypoxia was present in 11.6%, febrile seizure in 16.3%, and other risk factors including head trauma, nervous system infections, and family history in 11.6%. Mean age at epilepsy onset was 9.6 ± 6.6 years and mean duration of epilepsy was 14.9 ± 7.5 years. Mean NHS3 score was 9.2 ± 6.5 (range, 0–21) and median (interquartile range) seizure frequency was 12 (2–60) per month. Only 14 patients (10.8%) had maintained a proper seizure diary. There was decreased seizure frequency relative to that in the pre-surgical evaluation period in 37.2%, including seizure-free patients, while in 62.8% seizure frequency remained the same or increased. Only nine patients (6.98%) reported seizure freedom. The median number of anti epileptic drugs (AED) being taken by them was four (3–4) (
We recruited drug refractory patients who were not candidates for epilepsy surgery after pre-surgical evaluation. Various causes of non-clearance for epilepsy surgery were extracted from the pre-surgical database. These were multifocal epileptic zones in 20.6%, epileptic zone in eloquent cortex in 10.5%, diffuse abnormality in 16.8%, lack of consent for invasive pre-surgical evaluation in 15.5%, lack of consent due to inability to afford treatment in 23.4%, lack of consent for surgery 4.2%, and other causes like discordant imaging and electro-encephalographic locus in 5.0% or normal imaging/no focus in 3.2%.
QOL in adult epilepsy patients was measured using the QOLIE-31 scale and reported as the mean score of seven QOL domains and overall score (
Epilepsy-related independent variables including age at onset, duration of epilepsy, seizure severity (NHS3 total score), current seizure frequency, and change in seizure frequency (decreased and not decreased) were evaluated for their correlation with individual QOL domains and total QOL score (
This study was performed with the aim of evaluating the QOL of DRE patients who were not candidates for epilepsy surgery. The results suggest that the QOL of these patients worsened with time in all domains, relative to QOL during pre-surgical evaluation. This is the main strength of this study where we not only measured the current QOL but also compared it with QOL during pre-surgical evaluation.
Like other studies,
We also studied various epilepsy-related variables that determine QOL in these patients. In adult DRE patients, seizure severity was the most important modifiable factor to improve QOL, as with increasing seizure severity, patients’ worry about their epilepsy also increased. Patients with severe seizures were more likely to have poor cognition and lack energy. They felt emotionally disturbed and more socially restricted. Therefore, we speculate that to improve the QOL of these patients, seizure severity should be controlled. An early age of onset of epilepsy correlated with poor social function and poor overall QOL, while a long duration of epilepsy correlated with poor social function, worsening of cognition, and more medication-related adverse effects. Only a single QOL domain correlated with absolute seizure frequency, overall QOL, but two domains including overall QOL and social function, along with overall score correlated with perceived change in seizure frequency. Like previous studies,
Therefore, the QOL of DRE patients was not only worsened, but at the same time was very difficult to determine based on only epilepsy-related variables except seizure severity. It is not over-speculative to state that there is not only an urgent need for new AEDs as well as interventions for these patients, but also outcome assessments in trials should be holistic and account for improvements in QOL and not mere reduction in seizure frequency. Therapeutic interventions should target the determinants of QOL including those that are directly epilepsy related, as well as indirectly related, such as psychological factors.
Meanwhile these patients require social, occupational, and psychological support as well as legal help regarding disability benefits from health policy makers and recommendations from the national epilepsy governing body.
Our study has limitations. The study subjects were enrolled at a tertiary care hospital and therefore may have more severe disease; thus, the determinants may vary from a typical community population of DRE patients. This was a correlational study and involved the assessment of the association of the analyzed variables with a single point in time across the cohort of patients. A longitudinal study might allow for examination of the variables that were associated with change in QOL over time and/or as the effects of a specific intervention. We did not evaluate depression or other psychiatric co-morbidities as a co-determinant of QOL domains with epilepsy-related variables. Regardless, this study still has the power to highlight the current knowledge gap and suggest directions for future research.
The QOL of DRE patients who were not candidates of epilepsy surgery worsened during follow-up relative to QOL during pre-surgical evaluation. Seizure severity has significant correlation with most QOL factors but seizure frequency did not.
Baseline characteristics of adult drug refractory epilepsy patients who were not candidates for epileptic surgery
Baseline variable | Value (n = 129) |
---|---|
Age (years) | 26.5 ± 6.7 |
Gender | |
Male | 96 (74.4) |
Female | 33 (25.6) |
Occupation | |
Student | 57 (44.3) |
Employed | 39 (30.3) |
Unemployed | 33 (25.4) |
Marital status | |
Married | 21 (16.3) |
Unmarried | 108 (83.7) |
Perinatal hypoxia | 15 (11.6) |
Febrile seizure | 21 (16.3) |
Others | 15 (11.6) |
Localization | |
Temporal | 54 (41.9) |
Extra-temporal | 75 (58.1) |
Age at onset (years) | 9.6 ± 6.6 |
Duration of epilepsy (years) | 14.9 ± 7.5 |
Duration after pre-surgical evaluation (years) | 3.8 ± 1.4 |
Seizure severity score | 9.2 ± 6.5 |
Seizure frequency per month | 12 (2–60) |
Change in seizure frequency | |
Decreased | 48 (37.21) |
Not decreased (same or increased) | 81 (62.79) |
Seizure free patients | 9 (6.98) |
Number of antiepileptic drugs | 4 (3–4) |
Values are presented as mean ± standard deviation, number (%), or median (interquartile range).
Quality of life among adult epilepsy patients currently, during pre-surgical evaluation, and in comparison
QOLIE-31 QOL domains | Pre-surgical evaluation QOL status | Current QOL status | Difference between two means | |
---|---|---|---|---|
Seizure worry | 57.1 ± 26.3 | 41.2 ± 20.1 | 15.9 | < 0.01 |
Overall QOL | 50.8 ± 20.6 | 38.0 ± 9.3 | 12.8 | < 0.01 |
Emotional wellbeing | 55.7 ± 13.2 | 41.4 ± 12.4 | 14.3 | < 0.01 |
Energy/fatigue | 51.6 ± 13.4 | 46.9 ± 11.7 | 4.7 | < 0.03 |
Cognition | 51.4 ± 25.4 | 45.1 ± 16.7 | 6.3 | < 0.02 |
Medication side effects | 57.2 ± 21.0 | 46.0 ± 14.2 | 11.2 | < 0.01 |
Social function | 53.9 ± 30.0 | 40.6 ± 19.4 | 13.3 | < 0.01 |
Overall score | 54.1 ± 19.3 | 42.7 ± 15.7 | 11.4 | < 0.01 |
QOLIE-31, quality of life inventory in epilepsy-31 items; QOL, quality of life.
Correlation between QOL domains and epilepsy-related variables
QOLIE-31 domain | Age at onset of epilepsy | Duration of epilepsy | Seizure severity | Seizure frequency | Perceived change in seizure frequency |
---|---|---|---|---|---|
Seizure worry | 0.15 (0.35) | −0.28 (0.06) | −0.65 |
−0.10 (0.54) | 0.21 |
Overall QOL | 0.31 |
−0.24 (0.12) | −0.67 |
−0.33 |
< 0.01 |
Emotional wellbeing | 0.02 (0.92) | −0.25 (0.10) | −0.40 |
−0.15 (0.34) | 0.02 |
Energy/fatigue | 0.32 |
−0.16 (0.32) | −0.41 |
−0.24 (0.13) | 0.20 |
Cognition | 0.27 (0.09) | −0.37 |
−0.55 |
−0.15 (0.34) | 0.13 |
Medication side effects | −0.09 (0.58) | −0.30 |
−0.15 (0.34) | 0.11 (0.47) | 0.89 |
Social function | 0.36 |
−0.39 |
−0.68 |
−0.18 (0.26) | < 0.01 |
Overall score | 0.33 |
−0.42 |
−0.69 |
−0.24 (0.13) | 0.03 |
QOL, quality of life; QOLIE-31, quality of life inventory in epilepsy-31 items.
Spearman correlation coefficient, rho (