Special considerations for a first seizure in childhood and adolescence

SUPPLEMENT - MANAGEMENT OF A FIRST SEIZURE Special considerations for a first seizure in childhood and adolescence Peter Camfield and Carol Camfield Department of Pediatrics, Dalhousie University and the IWK Health Centre, Halifax, Nova Scotia, Canada SUMMARY Children with a first unprovoked seizure almost always present with a convulsive seizure. The differential diagnosis includes many paroxysmal events, especially convulsive syncope but even with a good history; there is often uncertainty that cannot be eliminated by investigations. In general, an EEG and MRI are indicated with other investigations determined on a case-by-case basis. Epilepsy syndrome identification may be very valuable. Current literature allows at least partial answers to parents six most common questions: Will it happen again? How long do I have to wait for a recurrence? Could my child die during a recurrence? Could there be brain damage with a recurrence? If medication treatment is delayed will there be any long-term change in the chance of a permanent remission? Now that my child has had a seizure, how should his/her activities be restricted? KEY WORDS: First seizure, Child, Adolescent. This paper focuses on children who present to the health care system with a first, unprovoked seizure and no previous seizures. Almost all of these first seizures are dramatic convulsive attacks children who experience only simple partial, complex partial, absence, myoclonus, and other short seizure types usually come to medical attention only after multiple attacks. By convulsion we mean a seizure with generalized or focal clonic activity. Based on the Nova Scotia population-based childhood epilepsy study, we estimate that fewer than 50% of children who will go on to develop epilepsy will present with their first seizure (Camfield et al., 1985). Of 127 children presenting with a first seizure to an expert pediatric clinic in Calgary, Alberta, of the 94 who were diagnosed as having an epilepsy seizure, nearly one-quarter were discovered to have a history of previous less dramatic seizures (Hamiwka et al., 2007 in press). These events were either unrecognized by the family, unclear to the treating physician or the family did not seek medical attention. DEFINITION A controversial issue in pediatric epilepsy is how to categorize one versus two unprovoked first seizures occurring Address correspondence to Dr. Peter Camfield, M.D., F.R.C.P.(C), IWK Health Centre, 5850 University Ave, PO Box 9700, Halifax, Nova Scotia B3K 6R8, Canada. E-mail: camfield@dal.ca Blackwell Publishing, Inc. C International League Against Epilepsy within a 24-h period. Investigators from Albert Einstein in New York have argued that these two events should be considered as a single seizure (Shinnar et al., 2000). In their experience with 407 children with a first seizure, the recurrence risk was the same after one unprovoked seizure as after 2 provoked seizures within 24 h, as judged by a 10-year follow-up. By contrast, we studied 490 children with epilepsy characterized by generalized tonic clonic or partial seizures with an average follow-up of 7 years (Camfield & Camfield, 2000). Seventy children had their first two unprovoked seizures on the same day with complete recovery between the seizures, while 420 had their first two seizures on different days. The recurrence risk (80% and 81%), long-term remission (59% and 56%), and risk of intractable epilepsy (7% and 8%) were so similar that we argued that when two first unprovoked seizures occur on the same day with recovery between the seizures, then these two seizures should mandate the diagnosis of epilepsy. The clinical course will be identical to children with the first two seizures on separate days. The differences between the New York and Nova Scotia data have not been explained. DIFFERENTIAL DIAGNOSIS The diagnosis of a first seizure is usually straightforward but the differential diagnosis in children includes a number of special pediatric disorders most prominent are pallid syncope and breath holding (Stephenson, 1990). As in 40

Special Considerations: Childhood and Adolescence 41 adulthood, a frequent first seizure mimic is syncope with a reflex anoxic seizure. This is particularly common in adolescent girls. The history does not always allow a confident diagnosis. The Dutch group submitted 207 case summaries prepared by a neurologist of first seizures to a panel of three child epilepsy experts (van Donsellar et al., 1989). All patients were then followed for a year. Of 156 considered to have a definite seizure, 46% had a recurrence, which confirmed the seizure diagnosis. Of the 54 with a disputable first attack, 14 recurred and the recurrences were convincingly seizures in 5. The interictal EEG did not assist in the disputable group. This group of investigators has advocated a watch and wait approach when the diagnosis is questionable. We endorse this approach. INVESTIGATIONS A practice parameter of the American Academy of Neurology has examined the value of investigations for children with a first afebrile, unprovoked seizure (Hirtz et al., 2000). This review was based on the available peerreviewed literature. The only investigation that reached the status of a recommendation was an EEG, a test that is of value for syndrome identification and prediction of recurrence. The risk of recurrence is increased by interictal spike discharge, especially focal spikes. Routine blood work has no proven benefit. Since publication of the practice parameter, several studies have suggested that the yield on MRI for causative abnormalities in children with a first seizure is about 20 30% (Sharma et al., 2003; Shinnar et al., 2001). Abnormalities that require intervention are considerably fewer, approximately 1%. Therefore, one can make a reasonable case for MRI, since occasionally there may be a treatable cause detected or the etiology may have prognostic value or point to other health concerns. For selected patients it seems obvious that some blood tests are indicated for example, a serum glucose in a child with diabetes and a seizure. SYNDROME IDENTIFICATION When a child presents with a first seizure it is often possible to diagnose an epilepsy syndrome, a concept that leads to considerable confusion. Epilepsy is usually defined as two or more unprovoked seizures. After a first unprovoked seizure in children, the recurrence risk is about 50%; however, after 2 unprovoked seizures, the recurrence rate is roughly 80% (Camfield et al., 1985; Berg et al., 1991). So, how can a child with only one seizure be said to have an epilepsy syndrome? A recent suggestion has been to change the definition of epilepsy to a single seizure plus a tendency for more seizures (Fisher et al., 2005). This definition is very difficult to use in practice. We prefer to accept the ambiguity and suggest that not everyone with a defined epilepsy syndrome has or will have two or more seizures. It is possible to have an epilepsy syndrome but not have epilepsy (King et al., 1998; Pohlmann- Eden et al., 2006). There may be a tremendous advantage for many children with a first seizure to have an epilepsy syndrome diagnosis. Normal children with a first nocturnal secondarily generalized seizure often turn out to have benign rolandic epilepsy, a diagnosis that can be made by a typical seizure history, normal neurological and developmental examination and centrotemporal spikes on EEG with special morphology plus an anterior-posterior dipole (Wirrell et al., 2005). When this epilepsy syndrome is diagnosed after a first seizure, it is possible to counsel parents that recurrences are likely to be during sleep and that the longrange prognosis is virtually always favorable. This disorder vanishes in adolescence and AED treatment is often not needed. Likewise, a normal child presenting with a nocturnal prolonged focal seizure without convulsive features but with eye deviation and vomiting can be confidently diagnosed as having Panayotopoulos syndrome, if the EEG shows occipital spike waves (Panayotopoulus, 1999). Again, the prognosis is excellent, even if there are recurrent seizures. We are somewhat less sure of the value of a diagnosis of primary generalized epilepsy, when a normal child presents with a first generalized tonic-clonic seizure and generalized spike-wave on EEG. If the EEG shows photosensitivity and the seizure seemed to be provoked by flashing lights then a syndrome diagnosis of idiopathic generalized epilepsy (IGE) with photosensitivity has considerable value in avoiding possible seizure triggers. The diagnosis of the syndromes of cryptogenic partial epilepsy or symptomatic partial epilepsy are of less use after a first unprovoked seizure, except to focus the clinician on a specific area of the MRI scan. Although there are frequent MRI abnormalities in such children, most do not lead to direct intervention. It is still unclear how imaging findings impact on the recurrence risk, although it is tempting to assume that an MRI lesion increases the risk of recurrence. QUESTIONS POSED BY PARENTS AFTER A FIRST SEIZURE Following a child s first seizure parents (and often the child) usually have six major questions Will it happen again? How long do I have to wait for a recurrence? Could my child die during a recurrence? Could there be brain damage with a recurrence? If I choose to delay medication treatment will there be any long-term change in the chance of a permanent remission? Now that my child has had a seizure, how should his/her activities be restricted?

42 P. Camfield and C. Camfield 1. Will it happen again? The recurrence risk after a first unprovoked seizure in childhood is essentially the same as in adulthood and factors that increase the likelihood of recurrence are very similar (Camfield et al., 1985; Berg & Shinnar, 1991). Risk is increased by focal versus generalized seizures, by presence of spike discharge on EEG and by the presence of concomitant neurological deficits. Children with none of these factors have approximately a 20% chance of recurrence and children with all of these factors have about an 80% risk of recurrence (Camfield et al., 1985). While these differences are statistically robust, it is not possible to answer this question with a definitive yes or no. In any case, parents should understand appropriate first aid and have a plan in place for medical attention should there be a recurrence. 2. How long might it be before we can be sure that our child will not have a recurrence? Again, the data for children are similar to adults. In the Nova Scotia series of 168 children with a first seizure, 70% of recurrences were within 6 months of the first seizure, 77% by 1 year, and 90% by 2 years (Camfield et al., 1985). In the series of 407 children from the Bronx with a first unprovoked seizure, 53% of recurrences were by 6 months and 88% by 2 years (Shinnar et al., 2000). The answer to this question is that recurrences may be delayed for 2 years or more, but most recurrences are within 6 months of the first seizure. 3. Could my child die during a recurrence? Perceptions of parents witnessing a first unprovoked seizure have not been directly reported, although it is likely that they are similar to the reactions of parents witnessing a first febrile seizure. During a first febrile seizure almost all parents indicate that they thought their child was dying (Rutter & Metcalfe, 1978). After a first afebrile seizure the fear of death during a seizure may be further increased by information about SUDEP. The risk of death during a first recurrent seizure has not been reported; however, children with established epilepsy have a tiny risk of SUDEP. Three large studies have addressed this issue. In Nova Scotia, 692 children with epilepsy were followed for about 20 years (Camfield et al., 2002a). There were 26 deaths, 1 from status and only 1 from SUDEP when she was 22 years of age. In the Dutch study of childhood epilepsy, 472 children with epilepsy were followed for 5 years with 9 deaths (Callenbach et al., 2001). None of the deaths were related to seizures and there were no cases of SUDEP. In the Connecticut study, 613 children were followed for a median of 7.8 years (Berg et al., 2004). Of the 13 deaths, two were related to seizures one from status and one SUDEP. Therefore, this question can be confidently answered the risk of a child dying during a recurrent seizure is miniscule. 4. Could there be brain damage with a recurrence? There are little data about brain damage in studies of first seizures and recurrences; however, a larger literature addresses this issue for children with established epilepsy. It is clear that children with epilepsy have high rates of cognitive deficits before the first seizure ever occurs. The critical question is whether they show worsening deficits with additional seizures. Austin compared 98 children with epilepsy to 96 children with asthma over a 4-year period (Austin et al., 2000). As expected, the children with epilepsy had less satisfactory performance on school achievement tests at each point in the study compared with those with asthma but there was no suggestion of deterioration over time, even in those with uncontrolled epilepsy. Bourgeois and coworkers noted no consistent decline in IQ in 72 children with newly diagnosed epilepsy (Bourgeois et al., 1983). Psychology testing within 2 weeks of diagnosis and then yearly for 4 years showed no change or improvement in most children. Eleven percent showed some declined in IQ, but the decline was not related to seizure number but rather to drug intoxication. The National Collaborative Perinatal Project (NCPP) ascertained 55,000 children prenatally and followed them to 7 years of age. There were 98 sibling pairs where one sibling had one or more afebrile seizures and the other did not (Ellenberg & Nelson, 1978). It is unclear how many of these children only had a single seizure. Intelligence and academic testing at 7 years of age showed no difference between the siblings with seizures and those without. Furthermore, 62 children had not experienced any seizure(s) by age 4 years when they underwent cognitive testing. Then between age 4 and 7 years, these same 62 children had one or more afebrile seizures. Comparisons of the cognitive testing at age 4 with testing at age 7 showed no change. The answer to this question is that a robust literature shows that clinically significant brain injury does not result from a few recurrent unprovoked seizures. 5. If medication treatment is delayed will there be any long-term change in the chance of a permanent remission? Most authorities (Hirtz et al., 2003) recommend no AED treatment after a first seizure in children, in part because about half of these children will never have another seizure and in part because there seem to be few consequences from a second seizure. Few studies directly address the question of benefit from AED treatment after a first seizure. In the Nova Scotia study of children with established epilepsy, children were prescribed AED treatment after a variable number of seizures (Camfield et al., 1996). This was not a randomized study the decision to start AEDs depended on the number of seizures before diagnosis and a clinical decision on the part of the family and physician. There were between 20 and 71 children in each group who were treated

Special Considerations: Childhood and Adolescence 43 after 1, 2, and up to 10 seizures. Eighty-nine started treatment only after >20 seizures. For a pretreatment number of seizures <10, the long-term remission rates were identical. For children with 10 seizures before AED treatment, there was a statistically decreased chance of longterm remission; however, children with 10 pretreatment seizures were much more likely to have complex partial seizures a seizure type that we reasoned was intrinsically less likely to remit. We concluded that waiting for up to 10 seizures before starting AED treatment was not hazardous from the perspective on long-term remission. There certainly was no penalty for waiting for a second seizure before starting AED treatment. The two main randomized studies of treatment after a first seizure are outlined elsewhere in this monograph. Neither the MESS study (Marsden et al., 2005) nor the FIRST study (Musicco et al., 1997) included large numbers of children but both studies indicated that early AED treatment reduced early recurrences but over several years the remission rates were identical in the early and late treatment groups. We carried out a modest randomized trial of no AED treatment (n = 14) versus daily carbamazepine (n = 14) after a first afebrile seizure (Camfield et al., 1989). Over the next year, statistically fewer children in the carbamazepine arm had afebrile recurrences but when the children were followed up about 20 years later, there was no difference in the long-term remission rate between the two groups (Camfield et al., 2002b). There are rare patients for whom treatment after a first seizures may be reasonable for example, in association with cyanotic heart disease; however, for the vast majority, the answer to this question is a clear no. The chance of remission is not altered by delaying daily AED treatment after a first seizure. 6. Are there any activities that should be restricted after a single seizure? After a first seizure, parents naturally consider restricting their child s activities because of concern for body injury during a recurrent seizure. There is virtually no literature that allows a rational/evidence-based approach to restrictions after a first seizure for children and adolescence (ILAE Commission report, 1997). If there are to be restrictions, they should not be imposed for more than 6 12 months after the first seizure since nearly all recurrences will have happened by then. It is also relevant to consider that most seizure-related injuries occur during normal daily activities and not during sports or other special activities. Here are our suggestions for restrictions after first seizure, although we freely admit that they are not evidence-based. For bathing, we recommend that the child/adolescent take a shower rather than a bath (no pirouetting taps) (Unglaub et al., 2005), have an adult aware of when they are in the shower, and be sure not to lock the bathroom door. For athletic activities, we do not recommend any changes. Helmet use for bicycling makes sense for all children and adults. Swimming should not only be in a supervised area but the child should swim with a responsible buddy. We suggest that the child continue to sleep in his/her own bed. For those who are found to be photosensitive on an initial EEG, we recommend moving back as far as possible when using a video display terminal (VDT) and having ambient lighting. Tree climbing and other high climbing activity might be restricted for 3 months. We usually do not recommend disclosing the first seizure to school authorities because of the risk of stigma and possible further restrictions from normal school activities. 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