Abdominal epilepsy in chronic recurrent abdominal pain.

BACKGROUND: Abdominal epilepsy (AE) is an uncommon cause for chronic recurrent abdominal pain in children and adults. It is characterized by paroxysmal episode of abdominal pain, diverse abdominal complaints, definite electroencephalogram (EEG) abnormalities and favorable response to the introduction of anti-epileptic drugs (AED). We studied 150 children with chronic recurrent abdominal pain and after exclusion of more common etiologies for the presenting complaints; workup proceeded with an EEG. We found 111 (74%) children with an abnormal EEG and 39 (26%) children with normal EEG. All children were subjected to AED (Oxcarbazepine) and 139 (92%) children responded to AED out of which 111 (74%) children had an abnormal EEG and 27 (18%) had a normal EEG. On further follow-up the patients were symptom free, which helped us to confirm the clinical diagnosis. CONTEXT: Recurrent chronic abdominal pain is a common problem encountered by pediatricians. Variety of investigations are done to come to a diagnosis but a cause is rarely found. In such children diagnosis of AE should be considered and an EEG will confirm the diagnosis and treated with AED. AIMS: To find the incidence of AE in children presenting with chronic recurrent abdominal pain and to correlate EEG findings and their clinical response to empirical AEDs in both cases and control. SETTINGS AND
DESIGN: Krishna Institute of Medical Sciences University, Karad, Maharashtra, India. Prospective analytical study.
MATERIALS AND METHODS: A total of 150 children with chronic recurrent abdominal pain were studied by investigations to rule out common causes of abdominal pain and an EEG. All children were then started with AED oxycarbamezepine and their response to the treatment was noted.
RESULTS: 111 (74%) of the total 150 children showed a positive EEG change suggestive of epileptogenic activity and of which 75 (67.56%) were females and 36 (32.43%) were male, majority of children were in the age of group of 9-12 years. Temporal wave discharges were 39 (35.13%) of the total abnormal EEG's. All the children were started on AEDs and those with abnormal EEG showed 100% response to treatment while 27 (18%) children with normal EEG also responded to treatment. Twelve (8%) children did not have any improvement in symptoms.
CONCLUSIONS: A diagnosis of AE must be considered in children with chronic recurrent abdominal pain, especially in those with suggestive history, and an EEG can save a child from lot of unnecessary investigations and suffering.

Introduction

Abdominal pain is a common complaint of children. Chronic recurrent abdominal pain is a perplexing problem for pediatricians. Among the various causes of pain, abdominal epilepsy (AE) is a relatively uncommon cause and hence, is frequently ignored. It is said that Trousseau first described AE in 1868.[1] Later, Stille in 1912 suggested that periumbilical pain might be a form of “masked epilepsy” and Wilson in 1940 suggested that some visceral discomfort might be epileptic.[1] During the past 30 years, scattered reports have appeared in the literature describing a condition that has been variously designated “the periodic syndrome,” abdominal migraine, AE and abdominal equivalents.[2] Apley accepted that abdominal pain as an “epileptic equivalent” occurred very occasionally and that it was nearly always associated with a history of transient impairment of consciousness or with typical convulsions.[3] The fact that abdominal sensations like nausea, vomiting, bloating and diarrhea can occur prior to epileptic attacks is widely accepted, and the sequence of events occur frequently in temporal lobe epilepsy.[4] A particular and consistently reproducible electroencephalogram (EEG) pattern has lately been found to occur in children having paroxysmal attacks of headache, abdominal pain and associated autonomic disturbances such as pallor, sweating, temperature changes, etc.[2] In this study, an attempt will be made to determine the incidence of AE in children suffering from chronic recurrent abdominal pain, with the help of clinical symptoms and EEG, and to study the response to empirical anti-epileptic drug (AED).

Materials and Methods

The study was carried out in the Department of Pediatrics, Krishna Institute of Medical Sciences University, Karad, India. This prospective study involved 150 children, in the age group of 6-15 years, suffering from chronic recurrent abdominal pain (i.e., pain severe enough to affect child's activity or three episodes of abdominal pain within 3 months and abdominal pain associated with nausea, vomiting, bloating, headache and diarrhea) from May 2007 to March 2010.

Children included in this study were having chronic recurrent abdominal pain, which means pain that fits in the above-mentioned criteria. Children below 6 years and above 15 years of age and those who were unable to give a proper history and those having acute abdominal pain of duration less than 3 months, having visceral disease, were excluded from the study.

A detailed present, past and family history was obtained from the patients or their parents. Clinical and systemic examination was performed with a special focus on abdominal and central nervous system (CNS) examination. Informed consent was taken from the parents for inclusion in the study and consent regarding treatment with AED (oxcarbazepine). Consent for use of oxcarbazepine was also taken from the institutional review board.

All children were investigated for stool and urine examination to rule out worm infestation, acute gastrointestinal infection and urinary tract infection. Urine porphobilinogen was performed before starting AED and to rule out intermittent porphyria. Complete blood count was performed to rule out anemia and systemic infections. Abdomen and pelvis ultrasonography was done to rule out organic intra-abdominal cause for chronic recurrent abdominal pain. EEG was done in every child to correlate the findings of EEG with clinical diagnosis of AE.

If any other investigation done showed a positive finding then the child was treated accordingly and excluded from the study.

An EEG was performed on all children with a Recorders and Medicare systems (RMS) EEG 24 BRAINVIEW PLUS (24 channel EEG machine) from RMS Chandigarh. The EEG system used was digital, and the amplified signal was digitized via an analog-to-digital converter after being passed through an anti-aliasing filter. The representation of the EEG channels is referred to as a montage; the representation used in our case was bipolar montage. All EEGs were reported by experts.

Results

Of the 150 cases, EEG changes were seen in 111 (74%) patients between the ages of 6 and 15 years with chronic recurrent abdominal pain. Of the 111 patients with an abnormal EEG suggestive of AE, 75 (67.56%) were girls and 36 (32.43%) were boys [Table 1]. Of the 111 abnormal EEG cases, 39 (35.13%) cases had temporal type of EEG changes, 36 (32.43%) cases had fronto-temporal type of EEG changes, 33 (29.72%) cases had generalized type of EEG changes and 3 (2.70%) cases had parieto-temporal type of EEG changes [Table 2]; the most common pattern was sharp wave in 99 (89.18%) cases and 12 (10.81%) cases had spike and wave pattern [Table 3]. The age and sex distribution were as follows [Table 4], with females being the most affected, between the age group of 9 and 12 years. All 150 patients, along with chronic recurrent abdominal pain, had other neurological symptoms [Table 5].

Table 1

Pattern of electroencephalogram according to sex

Table 2

Types of electroencephalogram

Table 3

Type of waves

Table 4

Age and sex wise distribution

Table 5

Symptoms

Of the 111 (74%) patients with abnormal EEG, all the patients had symptomatic improvement after treatment with the AED oxcarbazepine. Of the 39 (24%) patients with a normal EEG record, 27 (18%) patients had asymptomatic improvement after treatment and 12 (8%) patients had normal EEG; however, they did not have any significant improvement in the symptoms after treatment with oxcarbazepine [Table 6].

Table 6

Response to treatment

Discussion

AE is now considered a definite clinical entity.[5] It is characterized by: (1) otherwise unexplained, paroxysmal gastrointestinal complaints, (2) symptoms of a CNS disturbance, (3) an abnormal EEG with findings specific for a seizure disorder and (4) improvement with anti-convulsant drugs.[6] Although its symptoms may be similar to those of functional gastrointestinal abnormalities, detailed history taking and a high index of suspicion enable it to be distinguished from the latter condition.[7] Among the diagnostic possibilities are migraine and AE.[89] In our study, all the 150 children had chronic recurrent abdominal pain. The other commonly associated symptoms were headache, giddiness, nausea, vomiting and loose stools. History of aura or prodrome, as suggested by Gowers in 1907, or post-ictal phenomenom like exhaustion or sleep, as reported by Livingstone et al. in 1971,[10] were not seen in any of our cases.

Past history of febrile seizures, CNS infections and trauma are considered important events in history in case of epilepsy, as postulated by many authors in the past.[11011] No such history was reported in any of our cases.

The pathophysiology of AE remains unclear. Temporal lobe seizure activity usually arises in or involves the amygdala. Thus, patients who have seizures involving the temporal lobe usually have gastrointestinal symptoms as discharges arising in the amygdala can be transmitted to the gut via dense projections to the dorsal motor nucleus of the vagus.[12] Patients with AE usually have specific EEG abnormalities, particularly a temporal lobe seizure disorder, although some studies had reported an extratemporal origin (parietal or even frontal).[1314]

The diagnosis of AE is essentially a clinical one; however, EEG forms an important supportive evidence for the diagnosis of epilepsy. EEG was done in all of our 150 patients with chronic recurrent abdominal pain, of which 111 (74%) children had an abnormal EEG record. EEG analysis revealed that temporal lobe (35.15%) EEG changes was the most common, fronto-temporal (32.45%) was the second most common, followed by generalized (29.75%), whereas parieto-frontal (2.7%) EEG changes had the least incidence. Peppercorn[7] and Babb, Eckman[15] observed that AE was the most commonly associated EEG abnormality in one or both temporal lobes, and could include paroxysmal positive spikes at 14 and/or 6/s or generalized slow wave dysrhythmias. Schade et al.[11] reported that a temporal focus was seen in 22 patients among the 46 patients reviewed. Livingstone[10] reported in his study on 14 children that majority of the patients had a temporal focus on EEG records. Another study by Peppercorn and Herzogin in 1989 reported 10 patients, all of who had specific EEG abnormalities consisting of bursts of sharp waves and/or spikes over one or both temporal regions. In our study, we found that sharp waves were seen in 99 (89.1%) of the 111 patients and the spike and wave pattern was seen in 12 (10.9%) patients. The diagnostic yield of EEG is increased by activation procedures like photic stimulation and hyperventilation; thus, we used activation procedures in all our patients during EEG recording and found no change in the EEG recording[Table 7].

Table 7

Studies showing the incidence of AE

In various previous studies, the incidences of AE were as follows:

In our study, of the 111 children with AE (based on EEG and symptoms), it was found that the incidence was higher in girls (67.56%) than in boys (32.43%). In studies by Schade and Hoffman,[11] the incidence in boys was 56.5% and in girls was 43.5%. In other studies by Douglas and White,[1] the incidence in boys was 40% and that in girls was 60%. Peppercorn and Herzog[16] reported 10 cases of AE, and all 10 cases were females. Neuroendocrine dysfunction has been described in women with temporal lobe epilepsy, but the relationship of such abnormalities to the occurrence of GI symptoms has not been studied in such patients.

Historically, patients of AE were being treated using various drugs. Schade et al.[11] used diphenylhydantoin, mephobarbital, phenobarbital and primidone. The best results obtained from their study were with the use of diphenylhydantoin combined with one of the barbiturates. Livingstone et al. used diphenylhydantoin in all 14 of these patients of AE. Three patients did not respond to diphenylhydantoin and hence the drug was discontinued and these patients were later started on 3-methylhydantoin and mesantoin. Douglas et al.[1] used phenobarbital and diphenylhydantoin in the treatment of their patients with AE. Peppercorn and Herzog[16] used phenobarbital, phenytoin, valproic acid and carbamazepine for the treatment of their patients with AE. A sustained response to anti-convulsants has been accepted as one of the criteria for the diagnosis of patients with AE.[717] In our study, all the 150 children were treated with oxcarbazepine, irrespective of abnormal or normal EEG. On follow-up, all the 111 (74%) patients had an abnormal EEG and 27 (18%) patients with a normal EEG had significant decrease in all the symptoms. Twelve (8%) patients did not respond to treatment. None of the other studies conducted have started AED in patients with a normal EEG.

All the patients were advised to continue AED and follow-up till they were symptom free or a normal EEG was recorded or, maximum, up to a period of 2 years. AED was started in another group of children with normal EEGs suffering from chronic abdominal pain as abnormal brain waves are not always present in children suffering from epilepsy, and the presence of a normal EEG need not necessarily eliminate the diagnosis of AE in any given case if history and therapeutic test validate such a diagnosis, as was stated by Livingstone et al.[10]

Patients with epilepsies may have normal inter-ictal records of EEG, and treatment should not be based on EEG alone; correlation with the clinical condition is important.[18]

Conclusion

To conclude, therefore, a diagnosis of AE must be considered in children with chronic recurrent abdominal pain, especially in those with suggestive history, and an EEG can save a child from a lot of unnecessary investigations and suffering.