Perceived trigger factors of seizures in persons with epilepsy

Open ArchivePublished:June 26, 2013DOI:https://doi.org/10.1016/j.seizure.2013.05.018

      Abstract

      Purpose

      Little is known about the triggering factors (TFs) of seizures in persons with epilepsy (PWE). This study aimed to document the perception of PWE of factors that precipitated their seizures.

      Materials and methods

      Data was obtained from 405 patients attending the Epilepsy Clinic at the All India Institute of Medical Sciences (AIIMS). This was analyzed using appropriate descriptive and inferential biostatistical methods. A Trigger Assessment Tool (TAT) was designed for this study.

      Results

      89% of the participants reported at least one TF. Between one and ten TFs were endorsed. The most common TFs reported by the patients (in descending order) were found to be: Missing medication (40.9%), emotional stress (31.3%), sleep deprivation (19.7%), fatigue (15.3%), missing meals (9.1%), fever (6.4%), and smoking (6.4%). A significant association was seen among some of the commonly reported TFs (missing medication, sleep deprivation, emotional stress, and fatigue).

      Conclusion

      TFs should be evaluated during the management of PWE. However, self perceived TF should be interpreted with caution and differentiated from actual TF. Future studies may consider empowering patients with avoidance strategies and self-control techniques done.

      Keywords

      1. Introduction

      Epilepsy is a chronic neurological condition characterized by an enduring propensity to generate seizures and requires prolonged regular medication.
      • Berg A.T.
      • Kelly M.M.
      Defining intractability: comparisons among published definitions.
      According to a World Health Organization (WHO) survey, India alone has approximately eight to ten million people suffering from epilepsy. The risk of developing epilepsy over one's life time is 1.4–3.3%.
      • Satishchandra P.
      • Gururaj D.
      • Mohammed D.
      • Senanayake N.
      • Sllpaklt O.
      Global campaign against: epilepsy out of shadows.
      It is generally accepted that even though most seizures appear to occur spontaneously, they may be precipitated by a variety of endogenous or exogenous factors.
      • Burdette D.E.
      • Feldman R.G.
      Factors that can exacerbate seizures.
      According to Aird and Gordon,
      • Aird R.B.
      • Gordon N.S.
      Some excitatory and inhibitory factors involved in the epileptic state.
      precipitating factors are classified into seizure-inducing and seizure-triggering factors. The inducing factors may be environmental or endogenous in origin and cause a transient lowering of the seizure threshold, while the TFs refer to chemical or physiological stimuli that are capable of precipitating a seizure. These triggering factors (TFs), which precede the onset of a seizure, are usually considered by the patient, to precipitate or initiate an episode.
      • Nakken K.O.
      • Solaas M.H.
      • Kjeldsen M.J.
      • Friis M.L.
      • Pellock J.M.
      • Corey L.A.
      Which seizure-precipitating factors do patients with epilepsy most frequently report?.
      • Pinikahana J.
      • Dono J.
      The lived experience of initial symptoms of and factors triggering epileptic seizures.
      There is limited data available on the triggering factors (TF)
      • Aird R.B.
      The importance of seizure-inducing factors in the control of refractory forms of epilepsy.
      and about 1% of the 30,000 epilepsy-related articles refer to this issue. Identification and avoidance of such factors, as an adjuvant to the Antiepileptic Drugs (AED) therapy, may prove beneficial.
      • Trenite D.
      Provoked and reflex seizures: Surprising or common?.
      Recognizing the precipitants may be of interest, as avoidance of stimuli is vital in the management of seizures.
      • Spatt J.
      • Langbauer G.
      • Mamoli B.
      Subjective perception of seizure precipitants: Results of a questionnaire study.
      This study was designed with an objective of identifying the TFs of seizures in PWE, in the North Indian population.

      2. Materials and methods

      This study was conducted in the Outpatient Facility of AIIMS, New Delhi, after obtaining due clearance from the Ethics Committee of the Institution. About 100–150 PWE attend this clinic on any given day. Patients were explained the details of the study at length, those who gave consent and met the following inclusion criteria were included in the study: (a) age ≥ 9 years, (b) unequivocal diagnosis of epilepsy and its type based on the International League Against Epilepsy (ILAE) criteria,
      • Commission on Classification and Terminology of the International League Against Epilepsy
      Proposal for revised classification of epilepsies and epileptic syndromes.
      and was a clinical diagnosis and (c) literate patients (being able to read and write Hindi or English).
      Patients with psychiatric and emotional disturbances were excluded (unreliable responses). A history of other neurological disorders was also taken into consideration, with respect to the common neurological disorders, such as, stroke, dementia, headache disorders, multiple sclerosis, neurological disorders associated with malnutrition, or Parkinson's disease these patients were excluded from the study. To ensure the reliability of the data obtained from children, primary caregivers were actively involved. Data was assembled over a period of seven months, from June to December 2010. Patients with psychogenic nonepileptic events were ruled out of the study there events had to be confirmed by a VEEG recording.

      2.1 Development and description of the tool

      Demographic and clinical data were collected from the patient's medical records. A list of TFs was presented to the patients who were asked to indicate details pertinent to them. In many previous studies, a list of TFs was presented to the patients who were asked to report the factors that precipitated seizures in them. Spatt et al.
      • Spatt J.
      • Langbauer G.
      • Mamoli B.
      Subjective perception of seizure precipitants: Results of a questionnaire study.
      suggested that the above-mentioned method had difficulty in proving a causal relationship between a potential trigger and a seizure. Also, ruling out mere coincidence between the two was not undertaken in many previous studies. To overcome this problem, a Trigger Assessment Tool (TAT) was developed. The TAT was designed to collect data relevant to the triggering factors in two different groups – the first being the most recent episode and the second included all the previous episodes, as a group. This would enable the patient to relate the events preceding the episodes, and correlate appropriately, reducing the scope for errors or coincidences.
      The tool included 38 triggering factors including age and environment and culturally relevant factors which had been previously reported in literature (Table 1). To know the triggers that preceded their last seizure, the same 38 triggers were framed as close-ended questions (yes/no) in a retrospective manner, for example, Did you smoke before your last seizure? Did you consume alcohol before your last episode?
      • Content validity: Content validity of both tools was established by 4 experts in the field of Neurology. Modifications made as per the suggestions of experts led to a content validity index of 0.97.
      • Reliability: Reliability of the tool was established by the researcher using test re-test method. The reliability coefficient was found to be, r = 0.89. The reliability coefficient for the individual items ranged from r = 0.88–0.90.
      • Tool translation: Both tools were translated into Hindi by experts in Hindi department AIIMS and back translation was done to English and needed correction was made in the Hindi Version.
      • Tools try out: Both the tools were tried out on 10 subjects prior to use and they were found to be appropriate for the population under study. Time taken for data collection was 30–40 min.
      Table 1Seizure trigger factors observed in PWE (n = 405).
      S. No.Trigger factorLast seizure, n (%)Previous seizures, n (%)
      1AED dose reduction41 (10.12)19 (4.69)
      2Alcohol intake21 (1.76)9 (2.22)
      3Arithmetic work0 (0)0 (0)
      4Caffeine foods8 (1.97)9 (2.22)
      5Changing AED10 (2.46)12 (2.96)
      6Constipation9 (2.22)7 (1.72)
      7Decision-making12 (1.00)10 (2.46)
      8Deep thinking15 (1.26)36 (8.88)
      9Electronic screen30 (7.40)8 (1.97)
      10Emotional stress181 (44.69)166 (40.9)
      11Excitement or shock28 (2.35)16 (3.95)
      12Fatigue94 (23.20)102 (25.18)
      13Fever39 (9.62)43 (10.61)
      14Flickering lights0 (0)0 (0)
      15Heavy meal9 (2.22)0 (0)
      16Heavy physical activity33 (8.14)29 (7.16)
      17Hot water bath0 (0)0 (0)
      18High Humidity8 (1.97)4 (0.98)
      19Hyperventilation26 (2.18)24 (5.96)
      20Intense reading0 (0)0 (0)
      21Listening to music0 (0)0 (0)
      22Loud Noise6 (1.48)0 (0)
      23Menstruation16 (8.83)24 (13.25)
      24Missing meals81 (20)77 (17.28)
      25Missing medication192 (47.40)185 (45.6)
      26Moon cycle variation8 (1.97)0 (0)
      27Over-the-counter drugs13 (1.09)22 (5.43)
      28Pain32 (7.90)27 (6.66)
      29Prescribed drug apart from AED25 (2.10)0 (0)
      30Quarrel12 (1.00)16 (3.95)
      31Sexual activity13 (1.09)0 (0)
      32Sleep70 (17.28)28 (6.91)
      33Sleep deprivation120 (29.62)133 (32.8)
      34Smoking26 (6.41)26 (6.41)
      35Specific unusual diet0 (0)0 (0)
      36Strobe lights0 (0)0 (0)
      37Vomiting/diarrhea/sweating8 (1.97)18 (4.4)
      38Weather change19 (1.59)185 (45.6)

      2.2 Statistical analysis

      Data from the patient data sheet was analyzed using the SPSS for windows version 13.5 (SPSS Inc., Chicago, IL, USA). The demographic and clinical data were expressed as mean and standard deviation (SD). Wilcoxon signed rank test, the McNemar chi square value was computed to identify the triggering factors reported consistently in the past and last episode. Step-wise forward logistic regression analysis was performed to identify the factors that significantly influenced each trigger. Finally, the Phi coefficient was computed to find out the degree of association between each triggering factor. Level of significance (alpha) was set as <0.05.

      3. Results

      The questionnaire was applied to 405 PWE. The mean age of the patients at the time of interview was 27.56 years (9–60 years) and the mean age of onset of epilepsy was at 23.12 years (5–50 years). Generalized seizures based on clinical history with or without EEG findings of generalized discharges were seen in 61% of PWE (Table 2).
      Table 2Demographic profile of PWE (n = 405).
      Number (%)
      1. Age of onset (mean ± SD) (range)23.12 ± 13.924 (5–50)
      2. Seizure type
       • Focal + Sec gen158 (39)
       • Generalized247 (61)
      3. Frequency of seizure
       • ≤2 (per month)218 (53.8)
       • >2 (per month)187 (46.2)
      4. Duration of illness (years)
       • ≤5314 (77.5)
       • >591 (22.5)
      5. Duration of AED (years) (mean ± SD) (range)4.55 ± 3.600 (1–11)
      6. Family history of epilepsy
       • Yes83 (20.5)
       • No322 (79.5)
      7. History of Neurological illness
       • Yes69 (17)
       • No366 (83)
      8. Type of AED
       • Monotherapy139 (34.3)
       • Polytherapy266 (65.7)
      9. Seizure control
       • Active epilepsy
      Active epilepsy – PWE who had at least one episode in the past two years and still on AEDs.
      252 (62.2)
       • Epilepsy in remission
      Epilepsy in remission PWEs who are seizure-free from the past two years.
      153 (37.8)
      a Active epilepsy – PWE who had at least one episode in the past two years and still on AEDs.
      b Epilepsy in remission PWEs who are seizure-free from the past two years.

      3.1 Frequency and number of TF

      Of the 405 patients who were interviewed, 352 (86.9%) reported at least one identified TF in their past episodes that coincided with the most recent episode. Each patient could identify anywhere between a minimum of one and a maximum of 10 TFs. The TF reported by the patients in the past episodes and the most recent one were not same for all patients. For example, factors like moon cycle variation, heavy meal, and a loud noise, which preceded the most recent episode were not reported by patients as TFs in the past episodes (Table 1). Seven TFs were reported consistently in both (recent and past episodes). These were, missing medication (40.98%), emotional stress (31.35%), sleep deprivation (19.75%), fatigue (15.30%), missing meals (9.13%), fever (6.41%), and smoking (6.41%).

      3.2 Logistic regression

      Each of the above listed triggers was studied using the logistic regression model with regard to the clinical factors, age group, gender, educational status, seizure type, seizure frequency, duration of illness, and seizure control. Variables like duration of illness, seizure control, and family history of epilepsy significantly correlated with the missed medication.

      3.3 TF and duration of epilepsy

      Patients with duration of illness ≤5 years had 10.4 times greater tendency of reporting this TF than people with more than five years of illness (48.1 vs. 16.5%, p < 0.01). Patients who were seizure-free in the past two years had 9.4 times greater chance of reporting missed medication as a TF than people whose seizures were not controlled (70.6 vs. 23%, p < 0.01).

      3.4 TF and family history

      A greater tendency (8.4 times) of reporting this TF was found in patients with a positive family history (47.5 vs. 15.7%, p < 0.01).

      3.5 Stress

      Emotional stress as TF was reported more frequently (16.6 times) by adults (>21 years) than by younger patients (45.4 vs. 6.2%, p < 0.01).
      PWE ≤ 5 years (22.6%, p < 0.01) and adults (27.3%, p < 0.01) had a greater disposition to report sleep deprivation as a TF, compared to a longer duration of epilepsy and to the pediatric age group, respectively.
      Fatigue as a TF was reported more commonly by male patients (21%, p < 0.01) and in younger (<14 years of age) patients (30.3%, p < 0.1) than by females and adults. Patients with generalized seizures were more likely to report fatigue as a TF (21.9%, p < 0.01) than those who were seizure-free in the past two years (35.9%, p < 0.01). Adult patients reported missing meals as a TF, 9.09 times more than children (11.9 vs. 4.1%, p < 0.01). Fever as TF was reported more frequently by patients with focal seizures than by patients with generalized (12.7 vs. 2.4%, p < 0.05).

      3.6 Association between the common triggering factors

      As many patients reported more than one TF for their seizures, we applied the phi coefficient to find the degree of association between the TFs. A statistically significant association was found between the following triggering factors: Missing medication with emotional stress, fatigue, and sleep deprivation (Phi = 0.162, 0.413, and 0.217) (Table 3).
      Table 3Association between the common triggering factors (n = 405).
      Triggering factorsMissing medicationEmotional stressMissing mealsFatigueSleep deprivation
      Missing medication.162
      p-Value<0.01.
      .119
      p-Value<0.05.
      .413
      p-Value<0.01.
      .217
      p-Value<0.01.
      Emotional Stress.162
      p-Value<0.05.
      .007−.273
      p-Value<0.01.
      .453
      p-Value<0.01.
      Missing meals.119
      p-Value<0.05.
      .007−.135
      p-Value<0.05.
      −.114
      p-Value<0.05.
      Fatigue.413
      p-Value<0.01.
      −.273
      p-Value<0.01.
      −.135
      p-Value<0.05.
      −.194
      p-Value<0.01.
      Sleep deprivation.217
      p-Value<0.01.
      .453
      p-Value<0.01.
      −.114
      p-Value<0.05.
      −.194
      p-Value<0.01.
      Phi coefficient used:
      * p-Value < 0.05.
      ** p-Value < 0.01.

      4. Discussion

      The prevalence and nature of the TFs in the seizures was studied in 405 PWE. Several potential causes for epilepsy exist, including genetic predisposition, an underlying central nervous lesion, one or more precipitants, or a combination of these. More than 40 triggering factors have been described in the literature.
      • Aird R.B.
      The importance of seizure-inducing factors in the control of refractory forms of epilepsy.
      It is difficult, and maybe impossible, for a patient to determine which trigger(s) may have facilitated an actual seizure. Sometimes multiple factors can converge resulting in a complex relationship between TFs and seizure occurrence. In such cases it may be difficult to discern the relative importance of the individual factors. In other cases, however, patients may oversimplify the explanations for their seizures. Therefore, self-reported information on seizure precipitants should be interpreted with caution, as close-ended questionnaires have a high probability of false positives. Patients in whom epilepsy is controlled are likely to under report such trigger factors due to difficulty in recalling the events. More accurate methods used in previous studies, such as, prospective long-term monitoring or detailed seizure diaries,
      • Haut S.R.
      • Hall C.B.
      • Masur J.
      • Lipton R.B.
      Seizure occurrence: precipitants and prediction.
      • Spector S.
      • Cull C.
      • Goldstein L.H.
      Seizure precipitants and perceived self-control of seizures in adults with poorly-controlled epilepsy.
      were not feasible, as our study was a one-time interview. The other limitations of our study were that the TAT would have some bias because of self-reporting and its cross-sectional design. But we did try to minimize this by administering the questions under two sections of close ended questions and self administered questions. Another limitation of the study is that we based our diagnosis on clinical history but as many of these patients did not have drug refractory epilepsy it would have not been cost and resource effective to confirm the diagnosis by video EEG in all. However, the findings of this study did sensitize patients to what could be avoided to prevent their future episodes. As based on the response most patients felt the need to sleep more and avoid as far as possible the TF without being obsessed by the same. Improving sleep hygiene and reducing stress are easily modifiable factors which may improve seizure control. Though this was not objectively assessed as a part of the protocol of this study.
      Two important findings of our study were: First, a majority of the patients identified one or more specific triggering factors responsible for their seizures. Second, several triggering factors were clustered together, suggesting either a common mechanism of action or an interplay of these.
      The prevalence rate in our survey was consistent with the previous findings, as 86.9% of the PWE reported at least one TF that was responsible for their seizures.
      • Aird R.B.
      The importance of seizure-inducing factors in the control of refractory forms of epilepsy.
      • Da Silva Sousa P.
      • Lin K.
      • Garzon E.
      • Sakamoto A.C.
      • Yacubian E.M.
      Self-perception of factors that precipitate or inhibit seizures in juvenile myoclonic epilepsy.
      Our study attempted to measure the TFs in both the defined groups, that is, the most recent episode and the previous episodes; hence, we believe the prevalence rate in our study might be more consistent than recording only one episode.
      Every subject was able to report between one to a maximum of 10 TFs that precipitated their seizures. A similar finding was reported in two previous studies.
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      On the other hand, an Australian survey
      • Aird R.B.
      The importance of seizure-inducing factors in the control of refractory forms of epilepsy.
      reported a maximum of 26 TFs in PWE. The reason behind the under-identification in our subjects could be the lower awareness about TFs. Besides, 37.8% of the subjects in our study were seizure-free for the past two years, which could have resulted in a recall bias for the TFs associated with their past episodes.
      Missing medication was the most frequently reported TF (40.98%). This figure is consistent with the findings of Joo-Hui Tan et al. who prospectively evaluated seizure precipitating factors in 40 PWE.
      • Koutsogiannopoulos S.
      • Adelson F.
      • Lee V.
      • Andermann F.
      Stressors at the onset of adult epilepsy: implication for practice.
      Many of the previous studies reported emotional stress as the most common triggering factor.
      • Neugebauer R.
      • Paik M.
      • Hauser W.A.
      • Nadel E.
      • Leppik I.
      • Susser M.
      Stressful life events and seizure frequency in patients with epilepsy.
      • Da Silva Sousa P.
      • Lin K.
      • Garzon E.
      • Sakamoto A.C.
      • Yacubian E.M.
      Self-perception of factors that precipitate or inhibit seizures in juvenile myoclonic epilepsy.
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      • Koutsogiannopoulos S.
      • Adelson F.
      • Lee V.
      • Andermann F.
      Stressors at the onset of adult epilepsy: implication for practice.
      • Sperling M.R.
      • Schilling C.A.
      • Glosser D.
      • Tracy J.I.
      • Asadi-Pooya A.A.
      Self perception of seizure precipitants and their relation to anxiety level, depression, and health locus of control in epilepsy.
      • Lamdhade S.J.
      • Taori G.M.
      Study of Factors Responsible for recurrence of Seizure for controlled Epileptics for more Than one year after withdrawal of Antiepileptic drug.
      • Stanaway L.
      • Lambie D.J.
      • Johnson R.H.
      Non-compliance with anticonvulsant therapy as a cause of seizures.
      This may be due to the cultural differences in the perception of stress and its management/adaptation strategies. As missing medications were the most common TF in our study group, it required immediate attention, more so as these could be prevented by educating the patients about compliance. There may be many reasons for missing medications.
      • Buck D.
      • Jacoby A.
      • Baker G.A.
      • Chadwick D.W.
      Factors influencing compliance with antiepileptic drug regimes.
      • Hart Y.M.
      • Shorvon S.D.
      The nature of epilepsy in the general population: I. Characteristics of patients receiving medication for epilepsy.
      A shorter duration of illness and stress were found to have a positive correlation with missing medication.
      Emotional stress was the second most frequently reported TF (31.5%). This was not surprising, as clinical experience and previous studies revealed a strong correlation between stressful events in life and seizures.
      • Haut S.R.
      • Hall C.B.
      • Masur J.
      • Lipton R.B.
      Seizure occurrence: precipitants and prediction.
      • Temkin N.R.
      • Davis G.R.
      Stress as a risk factor for seizures among adults with epilepsy.
      Temkin and Davis
      • Spector S.
      • Cull C.
      • Goldstein L.H.
      High and low perceived self-control of epileptic seizures.
      also observed that daily difficulties were directly proportional to seizure occurrence, while pleasant life experiences were inversely proportional. The notion that emotional stress lowers seizure threshold was also consistent with the results of the psychopharmacological and behavioral intervention studies, which revealed a reduction in stress and anxiety levels, resulting in decreased seizure frequency.
      • Mattson R.H.
      Emotional effects on seizure occurrence.
      • Dahl J.
      • Melin L.
      • Leissner P.
      Effects of a behavioural intervention on epileptic seizure behaviour and paroxysmal activity: a systematic replication of three cases of children with intractable epilepsy.
      Adults have a greater propensity to report this TF, which is consistent with the findings of previous studies.
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      A TF can increase the seizure frequency on its own; it may also interact with other TFs to provoke further seizures. A positive association between the TFs of stress, fatigue, and sleep deprivation in our study, suggest that they may be related. These precipitating factors may represent different facets of the same pathophysiology, as is the case with sleep disorders.
      • Malow B.
      • Pasaro E.
      • Hall J.
      Sleep deprivation does not increase seizure frequency during long-term monitoring.
      • Waters W.F.
      • Adams Jr., S.G.
      • Binks P.
      • Varnado P.
      Attention, stress and negative emotion in persistent sleep-onset and sleep-maintenance insomnia.
      A similar positive association was reported in Brazilian
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      and American subjects.
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      Sleep deprivation was the third frequently reported TF among our patients (19.75%), although with limited evidence. Sleep deprivation increases the incidence of inter-ictal epileptiform discharges,
      • Gourie D.
      • Vijender S.
      • Bala K.
      Knowledge, attitude and practices among patients of epilepsy attending tertiary hospital in Delhi, India and a review of Indian studies.
      and thus, it has long been used as a precipitating factor in epilepsy patients for ictal studies. As sleep deprivation rarely occurs in a vacuum, but rather in association with physical or emotional stress and substance abuse, it is difficult to tease out the relative contribution of sleep deprivation. This is again a modifiable factor for better seizure control.
      Fatigue was the fourth most common triggering factor reported (15.30%). Fatigue as a TF in our study, was consistent with two previous studies, with similar statistical values.
      • Aird R.B.
      • Gordon N.S.
      Some excitatory and inhibitory factors involved in the epileptic state.
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      Patients with generalized seizures had a greater chance of citing fatigue, than patients with focal seizures. In contrast, two American series reported varying results; one of which documented that patients with focal seizures were more likely to report fatigue than patients with generalized seizures,
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      and the another reported that generalized and focal seizure patients were equally sensitive to fatigue.
      • Aird R.B.
      • Gordon N.S.
      Some excitatory and inhibitory factors involved in the epileptic state.
      Sometimes several factors could converge such that a complex relationship existed between the precipitating factors and seizure occurrence; for example, emotional stress might lead to sleep deprivation, fatigue, noncompliance, and stress. In such cases it might be difficult to discern the relative precedence of the individual factors. This variation in the findings could be attributed to the difference in sample size of the studies and the possible interplay of various other triggering factors.
      Ours is a tertiary referral center for epilepsy in north India, with a high proportion of drug refractory epilepsy patients. The incidence of photosensitive and hot water epilepsy, which could trigger seizures is low in north India, and was not encountered in this cohort.
      Fever was reported as a TF by 6.41% of our subjects, which was consistent with the findings of the previous studies.
      • Aird R.B.
      • Gordon N.S.
      Some excitatory and inhibitory factors involved in the epileptic state.
      Missing meals was noted by 9.13% of our subjects. The prevalence of this TF was relatively higher in our study versus the previous studies, with prevalence rates of 2, 1.9, and 3%,
      • Aird R.B.
      The importance of seizure-inducing factors in the control of refractory forms of epilepsy.
      • Tan J.H.
      • Wilder-Smith E.
      • Lim E.C.
      • Ong B.K.
      Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore.
      • Koutsogiannopoulos S.
      • Adelson F.
      • Lee V.
      • Andermann F.
      Stressors at the onset of adult epilepsy: implication for practice.
      respectively. This could be due to the cultural, economic, and religious constraints prevailing in our study population as fasting is often undertaken as a spiritual activity.
      • Desai P.
      • Padma M.V.
      • Jain S.
      • Maheshwari M.C.
      Knowledge, attitudes and practice of epilepsy: experience at a comprehensive rural health services project.
      Smoking was observed in (6.41%). None of the studies, in the past, have documented smoking as a TF. The relation between smoking and seizures is not clear and it could hypothetically lower the seizure threshold in predisposed individuals. This needs confirmation in prospective studies with a control group.

      5. Conclusion

      Based on our data, we conclude that the PWE believe that some of their seizures may be triggered by more than one factor. There may be interplay of mechanisms to predispose seizures in PWEs. Prospective studies may clarify the relationship between seizure TFs and seizure occurrence. However, until such studies are undertaken, patients could be educated on common triggering factors, which are mostly modifiable behaviour and lifestyle related while managing PWE.

      Conflict of interest statement

      None declared.

      Acknowledgment

      The authors gratefully acknowledge the editorial review by Mr. Narayanan.The study is also supported by the Center of Excellence for Epilepsy, funded by the Department of Biotechnology, India.

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