Epilepsia, 49(Suppl. 1):45–49, 2008 doi: 10.1111/j.1528-1167.2008.01450.

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SUPPLEMENT - MANAGEMENT OF A FIRST SEIZURE

Special problems: Adults and elderly
Linda J. Stephen and Martin J. Brodie
Epilepsy Unit, Division of Cardiovascular and Medical Sciences, Western Infirmary, Glasgow, Scotland, United Kingdom

SUMMARY
A first seizure out of a clear blue sky can be a major life-changing event. Careful history-taking and appropriate investigation together with a clear explanation provided to patient and family are an essential requirement. Although for most patients, pharmacotherapy can be withheld and events awaited, there are circumstances where introduction of antiepileptic drug (AED) therapy should be considered. Medical causes of seizures should also be sought and treated. In addition, a first seizure

in HIV-positive patients and in those with underlying neurocysticercosis should usually provoke the introduction of AED therapy. Particular problems can occur in patients with a single episode of provoked status epilepticus, a first tonic–clonic seizure during pregnancy and, particularly, an unprovoked event in older and learning disabled people. Treatment following a first seizure should balance risk factors for recurrence with the informed opinion of the patients and their family. KEY WORDS: Elderly, Epilepsy, First seizure, Investigation, Treatment.

A first seizure out of a clear sky can be a terrifying experience, particularly if it is a full-blown tonic–clonic event. An individual’s life may be turned upside down in a matter of minutes. Reduction in control, physical injury, and prolonged postictal symptoms can lead to loss of confidence and impairment of independence. Longer-term sequelae include employment difficulties, rescinding of the driving license, worry about having further events, and changes in attitude among family and friends (Dworetzky et al., 2000). Indeed, Lindsten and colleagues recently reported that adults with a newly diagnosed unprovoked epileptic seizure became significantly less physically active, traveled abroad less frequently, and were generally less energetic during their leisure time than sex- and age-matched referents (Lindsten et al., 2003). There has been much debate about how to best manage a person who has suffered a first seizure, which varies substantially among health-care systems throughout the world (Pohlmann-Eden et al., 2006). Some objective advice can be gleaned from a variety of guidelines (SIGN Guidelines, 2003; American Academy guidelines 2003, 2004; NICE guidelines, 2004; Glauser et al., 2006). Old age is now the commonest time to develop seizures and, as the global elderly population swells, so
Address correspondence to Prof. Martin J. Brodie, Epilepsy Unit, Western Infirmary, Glasgow G11 6NT, Scotland, United Kingdom. E-mail: Martin.J.Brodie@clinmed.gla.ac.uk Blackwell Publishing, Inc. C International League Against Epilepsy

too will the incidence of epilepsy (Forsgren et al., 2005). This paper explores some of the issues that need to be considered in managing adults and senior citizens following their first seizure. Details of the clinical trials exploring the risks and consequences of additional seizures have been discussed earlier in this supplement.

D IAGNOSIS
An adult who is suspected to have had a first seizure should be referred to an epilepsy specialist for rapid assessment (SIGN Guidelines, 2003). Diagnosis is based on the history, ideally from a witness. Difficulties can arise with partial seizures, which can have many varied presentations from a brief sensory, autonomic or motor disturbance to confusion and aggression lasting several minutes. Postictal symptoms and signs such as exhaustion, headache, muscle pain and Todd’s paresis can provide useful clues. A patient presenting with a first convulsive seizure can, on occasion, have undiagnosed epilepsy. It is worth asking about partial events, absence seizures and myoclonic jerks. These may have been occurring for many years without a diagnosis having been made (Kwan & Brodie, 2000). It is essential too to ensure that long QT syndrome, which can present with a seizure, is excluded by obtaining a routine electrocardiogram (ECG) (Dunn et al., 2005). Diagnosis of a first seizure in old age can be particularly challenging and it may take some time before an 45

46 L. J. Stephen and M. J. Brodie Table 1. Differential diagnoses of seizures in elderly people
Neurological • Transient ischemic attack • Transient global amnesia • Migraine • Narcolepsy • Restless legs syndrome Cardiovascular • Vasovagal syncope • Orthostatic hypotension • Cardiac arrhythmias • Structural heart disease • Carotid sinus syndrome Endocrine/metabolic • Hypoglycemia • Hyponatremia • Hypokalemia Sleep disorders • Obstructive sleep apnea • Hypnic jerks • Rapid eye movement sleep disorders Psychological • Psychogenic seizures

accurate clinical picture can be pieced together (Brodie & Kwan, 2005). The patients may remember little or nothing of the episode and, if they live alone, there may be no witness. A history of trauma with physical damage such as bruises, cuts, and burns can be helpful as can the timescale of the episode (Stephen & Brodie, 2000). It is important to consider the many differential diagnoses, which may mimic or coexist with seizure activity in this population (Table 1). Syncope, particularly, can occur without warning in elderly people. Physical examination should concentrate on the neurological and cardiovascular systems. Investigations such as full blood count, serum electrolytes, renal parameters, and random blood glucose are important, as well as an ECG and chest radiograph (Stephen & Brodie, 2000). Prolonged ECG recording, carotid and basilar ultrasonography, orthostatic blood pressure measurement may also be necessary. Tilt table testing can be useful to detect baroreceptor and vasopressor dysfunction or sympathetic failure due to autonomic neuropathy in older people (McKeon et al., 2006).

Other treatable causes of symptomatic seizures, such as malaria, hypertensive encephalopathy, systemic lupus erythematosus, and acute intermittent porphyria, should be considered in the appropriate clinical setting (Delanty et al., 1998). Because seizures are likely to recur in patients infected with HIV and because they are a poor prognostic indicator, it is generally recommended that all HIV seropositive patients experiencing a first seizure without a recognizable and reversible cause be treated with a nonenzyme-inducing antiepileptic drug (AED) (Romanelli & Ryan, 2002). Similarly, a first seizure in a patient with underlying neurocysticercosis should probably be treated, as the prognosis for the epilepsy is usually excellent (Riley & White, 2003). Patients with concomitant treated depression may also benefit from early introduction of AED therapy because of the increasingly recognized overlap between the neurobiological bases of these common disorders (Kanner, 2006).

U NPROVOKED S EIZURE
In some people, seizure type can be determined according to the clinical (ideally witnessed) history. A young adult who presents with an unprovoked tonic–clonic seizure, which occurs without warning or witnessed prodrome, may be developing an idiopathic primary generalized epilepsy syndrome. Other markers of this include seizures on awakening, during sleep deprivation or in the early morning. Juvenile myoclonic epilepsy (JME) is the commonest syndrome in this population and, although amenable to treatment, it is often a life-long condition (Specchio & Beghi, 2004). Photosensitivity will be present in around 5% of epilepsies. Photosensitive epilepsies generally have a good prognosis and there is a 14–37% probability that the seizures will remit spontaneously (Verrotti, 2004). For people with focal-onset seizures, prognosis depends on whether the seizures are idiopathic, cryptogenic, or remote symptomatic in nature. Remote symptomatic seizures carry an increased risk of mortality (Beghi et al., 2005). Patients found to have a progressive neurological disorder are highly likely to reseizure and should, therefore, be considered for early AED treatment. On the other hand, there is no evidence that AED therapy following a provoked seizure, such as after a traumatic head injury, will prevent later unprovoked episodes and the subsequent development of epilepsy (Temkin et al., 2001).

M EDICAL C AUSES
Around 8–10% of seizures are provoked by an acute precipitating stimulus such as a brain insult, metabolic or toxic disturbance, systemic illness, opportunist infection or a cryptic cancer (Annegers et al., 1995). Many drugs carry high epileptogenic potential, particularly meperidine, sevoflurane, clozapine, phenothiazines, and cyclosporin (Ruffmann et al., 2006). Alcoholics can have a seizure as a result of excessive alcohol intake, abstinence complications of their alcoholism, or an underlying seizure disorder (American College of Emerging Physicians, 1997). Recreational drug use, particularly with cocaine, phencyclidine, amphetamines, and heroin, can also produce seizures (Henry et al., 1992; Koppel et al., 1996). Specific enquiry should be made regarding these lifestyle issues following a potentially unprovoked tonic–clonic seizure.
Epilepsia, 49(Suppl. 1):45–49, 2008 doi: 10.1111/j.1528-1167.2008.01450.x

S TATUS E PILEPTICUS
Status epilepticus de novo is a frequent occurrence in adults (56%) and elderly (70%) patients who have not previously suffered from epilepsy (DeLorenzo et al., 1996). In this population, there is a significant risk of

47 Special Considerations: Adults and the Elderly developing epilepsy (Hesdorffer et al., 1998). The underlying etiology is the most important determining factor (Rossetti et al., 2006). This is particularly the case for adults where damaging pathology, such as acute vascular events, trauma, encephalitis, or a rapidly growing neoplastic lesion, can cause serious brain damage as well as status epilepticus. It is therefore important to consider long-term AED therapy in these patients as well as treating the underlying cause. of epilepsy is secure. As the history is crucial, the patient must be accompanied by a carer who knows him or her very well and has witnessed the presenting event. Problems can arise differentiating epileptic seizures from repetitive stereotyped behavior. In this setting, investigations such as EEG or brain imaging are rarely helpful. With specialist supervision, over 40% of this population can become seizurefree with AED treatment (Kelly et al., 2004).

E LDERLY P EOPLE
A first seizure in an older person can have profound physical and psychological consequences. For those who develop epilepsy, morbidity and mortality are high (Luhdorf et al., 1987) as are rates of sudden unexpected death (Jallon et al., 1999). Old age was found to be a significant predictor for seizure recurrence by the FIRST Seizure Trial Group (Musicco et al., 1997). It is usually assumed that underlying cerebral pathology is responsible for ictal generation. Magnetic resonance imaging (MRI) is not always tolerated in this age group and computerized tomography (CT) may be preferred by some patients (Tallis et al., 2002). In our elderly population of 117 patients with newly diagnosed epilepsy, 66% had abnormal neuroimaging. Of the 61% of patients who had an interictal EEG, epileptiform discharges were seen in just 28% (Stephen et al., 2006). As with younger adults, however, there were no differences in outcome for those with normal and abnormal brain imaging. The prognosis in this population, however, is better than for patients under 65 years of age (Mohanraj & Brodie, 2006). This, in itself, may be a good reason for starting AED therapy in the elderly, which is often readily accepted by a patient already taking a number of drugs for other indications.

P REGNANCY
On occasion, a woman will present with a first unprovoked seizure during pregnancy. This is a reasonably rare occurrence. Provoked seizures secondary to eclampsia are the commonest reason for seizure activity during pregnancy (SIGN Guidelines, 2003). The management of the seizure requires balancing the well-being of the fetus with the health of the mother. After a generalized tonicclonic seizure, alterations in fetal heart rate compatible with acidosis have been reported (Crawford, 2001). In general, however, tonic-clonic seizure activity does not appear to adversely affect fetal outcome (Crawford, 2001). Even status epilepticus appears to have a better prognosis for mother and child than previously thought (EURAP, 2006). Routine inter-ictal EEG appears to be safe in pregnancy, although it would seem sensible to avoid provocation procedures, such as photic stimulation and sleep deprivation. Brain MRI is preferable to CT scanning given that it does not involve exposure to radiation. Some practitioners prefer to wait until after the first trimester, although there is no conclusive evidence that MRI can lead to fetal problems. Indeed, brain imaging can have a direct effect on the management of pregnancy. For example, a woman with a highpressure vascular malformation could be at risk of rupture during labor and thus may benefit instead from an elective cesarean section. Given their teratogenic potential, many clinicians prefer to delay AED treatment, where possible, until well into the second trimester (Shorvon, 2002; Tomson et al., 2004). Exceptions may be patients presenting with a first episode of status epilepticus or seizures secondary to a rapidly progressive neurological disorder.

L EARNING D ISABILITIES
Around 1–2.5% of people in the Western world have a learning disability (Gillberg & Soderstrum, 2003). Of these, 14–44% will have epilepsy, with rates highest occurring in those with the most severe disabilities (Jones et al., 2002). There are no specific data regarding management of a first seizure in this population (Bowey & Kerr, 2000). Clinicians therefore have to rely on information pertaining to outcomes in those with established epilepsy. Given that these patients are likely to have underlying cerebral pathology, those with a first remote symptomatic seizure fall into a poor prognostic category (Beghi et al., 2005). Learning disability is associated with seizure clusters, more prolonged seizures, status epilepticus, and sudden unexpected death in epilepsy (SUDEP) (Hannah & Brodie, 1998). Early introduction of treatment may therefore be warranted in these individuals to minimize the risk of complications assuming, of course, that the diagnosis

T HE PATIENT ’ S P ERSPECTIVE
When considering whether or not to treat a first seizure, it is important to take into consideration the patient’s views of the situation and that of their family. To this end, it is vital that everyone concerned is provided with a clear explanation of what has happened and what are the likely consequences. For patients who are anxious not to have another seizure, early introduction of treatment may be the best course of action. These patients may rely on their ability to drive for their work and lifestyle. Those with a family history of epilepsy may be more inclined to accept
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48 L. J. Stephen and M. J. Brodie long-term treatment. Occasionally, a person will have a relative who has succumbed to a seizure-related death and will, therefore, gain peace of mind by starting medication. At the opposite end of the spectrum, some patients will choose not to start treatment even after a number of seizures because they dislike taking medication. Others may have a problem with the stigma of the diagnosis of epilepsy and all that this entails. Treatment may be difficult in people who have problems with drug or alcohol abuse or who are unwilling or unlikely to take medication. These individuals should be counseled appropriately and be made aware of the implications of further seizure activity, including the risk of SUDEP (Mohanraj et al., 2006).
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C ONCLUSIONS
The management of an adult with a first seizure can be complicated and is best undertaken by an epilepsy specialist. Patients at particular risk of seizure recurrence include those presenting with provoked or unprovoked status epilepticus, remote symptomatic seizures, and those with progressive underlying neurological pathology. Elderly patients and those with learning disabilities may be at a higher risk of seizure recurrence. Treatment following a first seizure should balance these risk factors with the informed opinion of the patient and their family.
Disclosure of Conflicts of Interest: MJB has acted as a paid consultant to Pfizer, UCB, Eisai, Johnson & Johnson, Schwarz, Jazz and Shire and has received research funding from Pfizer, UCB and Eisai. LJS declares no conflicts of interest.

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49 Special Considerations: Adults and the Elderly
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