Clinical Neurology and Neurosurgery 100 (1998) 196 – 198
‘Respiratory epilepsy’—does it exist? J. Barr *, Y. Katz, B. Barzilay, E. Lahat The Pediatric Di6ision, ‘Assaf Harofeh’ Medical Center (Affiliated to the Sackler Faculty of Medicine, Tel A6i6 Uni6ersity), Zerifin, 70300, Israel Received 12 February 1998; accepted 26 May 1998
Abstract Past literature suggests a possible relationship between two recurrent illnesses: bronchial asthma and epilepsy. Only one preliminary study, performed 30 years ago, demonstrated epileptiform EEG activity in patients with bronchial asthma who were treated successfully for their asthma with antiepileptic drugs. We demonstrated epileptiform activity in six out of 24 (25%) children with bronchial asthma who had no history of neurological illnesses or epilepsy, compared to one out of 24 (4.2%) children in the control group. This relatively high percentage of EEG abnormalities raises the possibility that there is a subgroup of patients with bronchial asthma, in whom the asthma might be considered as an ‘epileptic equivalent’. These patients possibly deserve a different, unique therapeutic approach. © 1998 Published by Elsevier Science B.V. All rights reserved. Keywords: Epilepsy; Asthma; EEG
1. Introduction Infantile asthma and febrile seizures are very common medical disorders during early childhood. In the majority of children the frequency of these disorders gradually decreases within the first years of life. However, in some cases, asthma continues through childhood and sometimes even into adulthood as bronchial asthma, and in others, febrile seizures continue, with the development of one of the epileptic disorders in later childhood and adulthood. Two important mediators, the cyclic nucleotides– cyclic AMP (cAMP) and cyclic GMP (cGMP), which have opposite physiological roles, may be involved in the pathogenesis of both asthma and epilepsy [1–6]. 30 years ago, preliminary work on electroencephalographic (EEG) studies in patients with bronchial asthma was published in the Lancet . The authors performed EEG studies on a group of 16 patients with
* Corresponding author. Fax: +972 8 9779109, + 972 8 9779108; e-mail: [email protected]
bronchial asthma, and found abnormalities in 14 of the 16. Subsequently these patients were treated with antiepileptic drugs, and showed both clinical and electroencephalographic improvement. Since that article appeared, no further studies seeking a relationship between bronchial asthma and epilepsy have been published. The aim of our study is to investigate the EEG patterns of children with bronchial asthma in an attempt to identify a sub-group of asthmatic children who might need a different therapeutic approach.
2. Patients and methods The study group comprised 24 children with bronchial asthma who were being followed up in the Pediatric Pulmonary and Allergy Clinic, and who volunteered to participate in the study. Criteria for inclusion were: 1. Children aged 3–16 years with bronchial asthma, diagnosed at least 3 months prior to the study.
0303-8467/98/$ - see front matter © 1998 Published by Elsevier Science B.V. All rights reserved. PII S0303-8467(98)00040-7
J. Barr et al. / Clinical Neurology and Neurosurgery 100 (1998) 196–198
2. All children had been born by vaginal delivery following an uncomplicated pregnancy, with a normal neonatal course and appropriate developmental milestones. 3. No history of neonatal seizures, febrile seizures or any epileptic disorder in the patients or first degree relatives. 4. No history of any neurological illness either chronic or acute, including head trauma. 5. Normal neurological examination including head circumference, and no evidence of a neurocutaneous syndrome. The control group included 24 children, aged and sex matched to the study group, without history of bronchial asthma, allergies or neurological illnesses, including epilepsy. The study design was approved by the hospital ethical committee. The children in both groups underwent an EEG during a routine visit to the Pediatric Outpatient Clinic, at a time when they had no active asthmatic attack. The EEG’s were recorded with an 11-channel ‘DG compact 32’ machine (Medelec, Division of Vickers, UK). All studies were interpreted in a blind fashion by two pediatric neurologists who were not aware of the study design. Data were collected in dBASE IV®, a computerized database, and Statistix® version 3.1 (Analytical Software, St. Paul, MN) was used for the statistical analysis.
3. Results The study group consisted of 24 children with bronchial asthma— nine girls (37.5%) and 15 boys (62.5%) aged from 3 to 16 years (mean age 9.693.5). All patients underwent routine skin tests and 18 (75%) had evidence of skin atopy. Neurological examination performed prior to the EEG study by the same pediatric neurologist, were normal in all patients. The control group included 24 children, ten girls (41.5%) and 14 (58.5%) boys aged from 3.5 to 16 years (mean age 9.1 93.2). All children in this group were examined by the same physicians before performing the EEG study. Out of 24 EEG studies in the study group, 18 (75%) were interpreted as normal and six (25%) were abnormal, with epileptiform activity manifested by spikes or spike and slow wave complexes. The EEG abnormalities were generalized in two cases and focal in four cases (two in the temporal region, one frontal and one occipital region). Of these six asthmatic children with an abnormal EEG tracing (two girls and four boys), four had positive skin tests for house-dust mite. Only one child (4.2%) from the control group had abnormal EEG demonstrating few discharges of spike, and spike and slow wave complexes.
4. Discussion The possible relationship of epilepsy to allergic disorders in general, and bronchial asthma in particular, has been discussed in the medical literature since the early 1920s. Several clinical observations suggested that in the absence of any other etiological factor, convulsions may be due to an allergic reaction . This issue was abandoned for years and was raised again in the 1960s. Sayar and Polvan  reported their experience with 16 patients (their ages are not mentioned in the article) with bronchial asthma and frequent asthmatic crises, who underwent EEG studies. Two records were considered normal. Of the remaining 14 that were considered to be abnormal, epileptogenic abnormalities were found in the temporal regions in eight patients, in both temporal and other regions in one patient, in the frontal region in one, and in the occipital region in one. All patients were told to discontinue their antiasthmatic drugs and were given only antiepileptic drugs for an average of 45 days. Of ten patients who were followed, seven had no asthmatic crises at all. EEG following the treatment had returned to normal in five of six patients. The author’s conclusion was that certain bronchial asthmas may well be considered as epileptic equivalents. On the other hand, a retrospective study of 342 children with intractable bronchial asthma admitted to hospital for treatment showed that the incidence of abnormal EEGs in asthmatic children without seizures was similar to that among healthy, normal children . That study also showed that the development of abnormal EEGs and asthma-related seizures was best correlated with cyanotic asthmatic episodes to the point of loss of consciousness. Seizure activity and EEG abnormalities may be related to bronchial asthma via several possible mechanisms: 1. Severe asthmatic crises can cause severe and prolonged hypoxia, and subsequently hypoxic encephalopathy, including seizure activity. 2. Treatment with antiasthmatic drugs such as aminophyllines and salbutamol can cause seizures. In our patients, the abnormal EEGs were not related to either of the above mentioned mechanisms since the patients did not have severe asthmatic episodes, and the studies were obtained while they were symptom-free and without medication. The relatively high percentage of epileptiform activity (25%) found, compared to 4.2% in the control and to the incidence of 2% reported in normal children , might suggest that there is indeed a sub-group of patients with bronchial asthma in whom the pathophysiological mechanisms might relate to the epileptiform activity recorded in the EEG studies, and therefore, deserves specific treatment. We considered the option of
J. Barr et al. / Clinical Neurology and Neurosurgery 100 (1998) 196–198
antiepileptic therapy for these patients, but their asthma attacks were infrequent and mild, so no significant observations could have been obtained. In conclusion, our study results, even though based on a relatively small number of patients, support the observation that there are patients with bronchial asthma and epileptiform EEG activity, who might need a distinct therapeutic approach. The relationship of this finding and its clinical application should probably be further investigated in larger series of patients. References  Riekkinen PJ, Pitkanen A, Halonen T, Lehtinen M, Ylin A, Sivenius J. Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy—a CSF study. Prog Neuropsychopharmacol Biol Psychiatr 1988;12:81–91.  Ludvig N, Moshe SL. Different behavioral and electrographic effects of acoustic stimulation and dibutyryl cyclic AMP injection into the inferior colliculus in normal and in genetically epilepsy-prone rats. Epilepsy Res 1989;3:185–90.
 Ahang ZH, Zuo QH. Changes in amino acid neurotransmitters and cAMP in cerebral – spinal fluid from children and rabbits with epilepsy and convulsions. Chin Med J 1985;98:759–64.  Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boulu RG. Nitric oxide: an endogenous anticonvulsant substance. Neuroreport 1993;4:444 – 6.  Sato T, Bewtra AK, Hopp RJ, Nair N, Townley RG. Alphaand beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma. J Allergy Clin Immunol 1990;86:839 – 50.  Angus RM, McCallum MJ, Hulks G, Thompson NC. Bronchodilator, cardiovascular and cyclic guanylyl monophosphate response to high-dose infused atrial natriuretic peptide in asthma. Am Rev Respir Dis 1993;147:1122– 5.  Sayar B, Polvan O. Epilepsy and bronchial asthma. Lancet 1968;1:1038.  Stevens H. Allergy and epilepsy. Epilepsia 1965;6:205–16.  Nelihaus G, Neuman I, Ellis R, Pirnat M. Asthma and seizures in children. Ped Clin North Am 1975;22:89 – 100.  Eeg-Olofsson O, Petersen I, Sellden U. The development of the electroencephalogram in normal children from the age of one through fifteen years. Paroxysmal activity. Neuropaediatrie 1971;2:375 – 404.