The recommendations that follow are those from the guideline's executive summary; detailed recommendations can be found in the original guideline document. Each recommendation is rated based on the level of the evidence and the classes of the recommendation. Definitions of the levels of the evidence (A, B, C, D, and Good Practice Point [GPP]) and classes of the recommendations (Level 1++ through Level 4) are presented at the end of the "Major Recommendations" field.
Diagnosis
GPP The following paroxysmal events may be mistaken for seizures and a primary physician should be aware of them so that he could consult the appropriate specialist, if necessary.
Patient presents with loss of awareness:
- Transient cardiac arrhythmia
- Transient ischaemic attacks
- Hypoglycemia
- Panic attacks
Patient presents with abnormal movement:
- Movement disorders in sleep and wake
- Tremor or paroxysmal choreoathetosis or dystonia
- Drop attacks and cataplexy. (GPP)
D Individuals requiring an electroencephalogram (EEG) should have the test performed soon after the attack. The earlier the EEG is performed, the more likely a helpful result will emerge from the EEG (Fowle & Binnie, 2000). (Grade D, Level 3)
D EEG should be performed to support a diagnosis of epilepsy in adults in whom the clinical history suggests that the seizure is likely to be epileptic in origin (Fowle & Binnie, 2000). (Grade D, Level 3)
D An EEG should not be performed in the case of probable syncope because of the possibility of a false positive result (Fowle & Binnie, 2000). (Grade D, Level 3)
D EEG should not be used in isolation to make a diagnosis of epilepsy because it can be falsely positive (Fowle & Binnie, 2000; Smith, Defall, & Chadwick, 1999). (Grade D, Level 3)
D Repeated EEG may be helpful when the diagnosis of epilepsy is unclear ("Proposal for revised clinical", 1981; King et al., 1998). When a standard EEG has not contributed to diagnosis or classification, a sleep EEG should be performed (Fowle & Binnie, 2000). (Grade D, Level 3)
C Long-term video or ambulatory EEG may be used in the assessment of individuals who present diagnostic difficulties after clinical assessment and standard EEG (Thompson & Ebersole, 1999). (Grade C, Level 2+)
D Photic stimulation and hyperventilation should be a part of standard EEG assessment (Fowle & Binnie, 2000). (Grade D, Level 3)
D Electrocardiogram (ECG) should be performed in the assessment of all patients with altered consciousness, particularly in the older age group when cardiac arrhythmias can simulate epilepsy (Zaidi et al., 2000). (Grade D, Level 3)
GPP Routine blood studies are indicated to identify common metabolic causes of seizure such as abnormalities in electrolytes, glucose, calcium, magnesium, hepatic and renal diseases. Screening for toxins is sometimes done. Lumbar puncture is necessary when meningitis or encephalitis is suspected. (GPP)
D Magnetic resonance imaging (MRI) is the imaging of choice in patients with epilepsy ("Recommendations for neuroimaging," 1997; "Guidelines for neuroimaging," 1998) and is particularly useful in those:
- Who have suggestions of a focal seizure onset from history, examination or EEG.
- In whom seizures continue in spite of first line medication. (Grade D, Level 4)
D Computed tomography (CT) scan has a role in the urgent assessment of seizures or when MRI is contraindicated ("Scottish Intercollegiate Guidelines Network [SIGN]," 2003). (Grade D, Level 4)
D Brain imaging is not routinely required when there is a confident diagnosis of idiopathic generalised epilepsy and if there is rapid and complete response to the first line antiepileptic drugs ("Recommendations for neuroimaging," 1997). (Grade D, Level 4)
Initial Treatment
D Before making the decision to start antiepileptic drugs after a first unprovoked seizure, it is important to verify that the patient has had only one unprovoked seizure, and to confirm that there is no prior history of absence or myoclonic seizures, or partial seizures (SIGN, 2003). (Grade D, Level 4)
D The decision to start antiepileptic drugs after a first unprovoked seizure is based on the risk of seizure recurrence. Early treatment with antiepileptic drugs after a first seizure approximately halves the recurrence risk but does not alter the long-term prognosis of the epilepsy. The decision to treat is made on individually tailored basis (SIGN, 2003; O'Dell & Shinnar, 2001). (Grade D, Level 4)
D The overall risk of a second seizure occurring after a first unprovoked seizure ranges between 27-52% (O'Dell & Shinnar, 2001). However, this is an overall estimate and the recurrence risk of another seizure after a first unprovoked seizure increases to over 80% in the presence of (1) epileptiform abnormalities on the EEG, (2) a neurological deficit, and (3) a structural abnormality in the brain. Antiepileptic drugs therefore should be offered to the patient in these 3 circumstances (SIGN, 2003; O'Dell & Shinnar, 2001). (Grade D, Level 4)
D Antiepileptic drugs should also be considered if the patient or his/her carers consider the risk of a recurrent seizure unacceptable (SIGN, 2003; National Institute of Clinical Excellence [NICE], 2004). (Grade D, Level 4)
D Starting antiepileptic drug treatment is often not a straightforward decision, and the decision should be made jointly with the patient (or his/her caregiver) after explaining the risks and benefits and after assessing his/her preferences. In other words, the decision should be individualized (SIGN, 2003). (Grade D, Level 4)
B The risk of seizure recurrence after 2 unprovoked seizures is 73%. Antiepileptic drugs therefore should be offered to the patient after explaining the risks and benefits and after assessing his/her preferences (NICE, 2004; Hauser et al., 1998). (Grade B, Level 2++)
A Antiepileptic drug treatment strategy should be individualised according to the seizure type, epilepsy syndrome, co-medication, co-morbidity and the individual's lifestyle and preferences (and/or those of their family and/or carers as appropriate) (Beghi et al., 2003; Kwan & Brodie, "Epilepsy after the first drug fails," 2000; Fakhoury et al., 2004; Wheless et al., 2004; Privitera et al., 2003; Kaminow et al., 2003). (Grade A, Level 1++)
A Patients should be commenced on monotherapy initially. Should the patient develop an adverse reaction to the initial drug or if the initial monotherapy is unsuccessful, monotherapy using another drug should be tried (Beghi et al., 2003; Kwan & Brodie, "Epilepsy after the first drug fails," 2000; Fakhoury et al., 2004; Wheless et al., 2004; Privitera et al., 2003; Kaminow et al., 2003). (Grade A, Level 1++)
A All antiepileptic drugs licensed for monotherapy have similar efficacy in newly diagnosed epilepsy. For this reason, the medicine the prescribing physicians are most familiar with can be used (Kwan & Brodie, 2001; Perucca et al., 2000; Browne & Holmes, 2001). (Grade A, Level 1++)
A Carbamazepine, phenytoin and sodium valproate can be considered first line treatments for newly diagnosed partial and generalized tonic-clonic seizures (Tudur, Marson, & Williamson, 2003; Tudur et al., 2002; Marson et al., 2003; Marson et al., 2002). (Grade A, Level 1+)
A Sodium valproate, lamotrigine and clonazepam may be prescribed for absence and myoclonic seizures (Panayiotopoulos, Obeid, & Tahan, 1994; Gazda et al., 2000; Delgado-Escueta & Enrile-Bacsal, 1984; Penry, Dean, & Riela, 1989; Loiseau, Duche, & Pedespan, 1995; Posner, Mohamed, & Marson, 2005). (Grade A, Level 1++)
A Newer antiepileptic medications (gabapentin, lamotrigine, topiramate, levetiracetam, tiagabine, zonisamide, oxcarbazepine) are recommended as add-on medications for the treatment of individuals who have suboptimal treatment response to the older medications (phenytoin, carbamazepine, sodium valproate, phenobarbitone, clonazepam, clobazam) or as monotherapy (lamotrigine, topiramate) in individuals whom the older medications are unsuitable (adverse drug reactions, intolerable side effects, multiple drug interactions to concomitant medications) (Beghi et al., 2003; Kwan & Brodie, "Epilepsy after the first drug fails," 2000; Fakhoury et al., 2004; Wheless et al., 2004; Privitera et al., 2003; Kaminow et al., 2003; "Review: 6 newer drugs," 1997; Sackellares et al., 2002; Chadwick & Marson, 2005; Jette, Marson, & Hutton, 2005; Pereira, Marson, & Hutton, 2005; Chaisewikul et al., 2005; Marson et al., 2005; Castillo, Schmidt, & White, 2005). (Grade A, Level 1++)
C For women of childbearing age or who are pregnant, the appropriate antiepileptic monotherapy at the lowest dose to control seizures is recommended (Adab et al., 2005). (Grade C, Level 2++)
A Folate supplementation is recommended for women of childbearing age on antiepileptic treatment to prevent neural tube defects. Folic acid, 5 mg per day, should be given in these women from pre-conception till the first trimester of pregnancy (Lumley et al., 2005; "Prevention of neural tube defects," 1991; Lewis et al., 1998; Hernandez-Diaz et al., 2000; Dansky et al., 1987). (Grade A, Level 1++)
GPP Seizure precautions - people with epilepsy and their carers should be educated that the following are associated with increased risk for breakthrough seizures:
- Non-compliance to antiepileptic medication or drug interactions with antiepileptic medications lowering blood levels of antiepileptic drugs
- Alcohol abuse
- Sleep deprivation
- Concurrent illness (GPP)
GPP Seizure first-aid:
- Place the seizing individual in recovery position or on his/her side.
- Remove surrounding objects that may harm the individual.
- Do not place any object in the individual's mouth.
- Call for an ambulance in the event of injury during seizure, prolonged seizure (>5 minutes), or seizure clustering without return to individual's baseline state. (GPP)
D Home and workplace safety (SIGN, 2003):
- Minimise exposure to open fires and sharp instruments. Microwave ovens, blenders are options to consider.
- Refrain from soaking in baths over extended periods of time or locking toilet doors; showers should be preferred over baths.
- Operation of heavy machinery is discouraged. (Grade D, Level 4)
D Antiepileptic drugs are not a contraindication for women to breastfeed. All breastfeeding mothers on antiepileptic drugs should be encouraged to breastfeed and receive support from relevant healthcare personnel (SIGN, 2003). (Grade D, Level 4)
GPP Women with epilepsy should be referred to specialist care for preconception counseling as indicated. (GPP)
D Immediate management of seizure (Henry, 2003)
- Remove hazards from the immediate surroundings.
- Protect the patient from falling unsupported to the ground or striking objects.
- Position the patient on their side, with the head supported in a neutral in-line position.
- Protect the head and other parts of the body from striking objects but do not restrain the patient.
- Establish Airway, Breathing and Circulation (ABC) and administer high concentration oxygen.
- Observe and record the pattern of the seizure(s).
- Note and record the duration of the seizure(s).
- Do not force anything, including your fingers, into the person's mouth. This may cause injuries such as chipped teeth or a fractured jaw. You could also get bitten. (Grade D, Level 4)
GPP If the clinical scenario is suggestive of hypoglycaemia, capillary blood glucose level should be checked. With confirmed hypoglycaemia, the patient should be treated with 50 mL of Dextrose 50%. In the setting of malnutrition or suspected ethanol abuse, 100 mg thiamine may also be given as an intravenous push. (GPP)
D When convulsive seizures continue beyond 5 minutes, pharmacotherapy to abort the seizure is recommended (Wyllie, 2006). (Grade D, Level 4)
A Intravenous diazepam and lorazepam are effective first line treatments for prolonged seizures in the community. (Grade A, Level 1+)
D Initially a dose of 5-10 mg diazepam is given either intravenously or rectally. If there is no response, the same dose can be repeated after 10 minutes. Respiratory or circulatory effects should be monitored for and usually come into effect with doses greater than 20 mg (Wyllie, 2006). (Grade D, Level 4)
GPP Emergency medical services (EMS) should be activated if:
- Seizures continue beyond 5 minutes.
- Cardio-respiratory complications from treatment develop and there are no adequate conditions for monitoring the patient's condition.
- There is suspected fracture or central nervous system injury from the seizure. (GPP)
Follow-on Treatment and Management
D Antiepileptic drug levels may help clinical management under the following clinical indications: (1) assessment of compliance to drug treatment for patients with refractory epilepsy (2) assessment of symptoms due to possible antiepileptic drug toxicity (3) titration of phenytoin dose (SIGN, 2003; NICE). Routine checking of antiepileptic drug levels without a clear clinical indication is not required, and is not cost-effective (SIGN, 2003; NICE, 2004). (Grade D, Level 4)
GPP Depending on clinical suspicion of other differential diagnoses, blood tests such as blood glucose, urea, electrolytes, liver function tests and serum calcium may be indicated. (GPP)
B Before commencing multiple antiepileptic drug therapy, monotherapy involving two of the standard drugs (phenytoin, carbamazepine, sodium valproate) should have been tried. When two of these antiepileptic drugs have failed as monotherapy, the chance of seizure-freedom with further monotherapy is very low (Kwan & Brodie, "Early identification," 2000). (Grade B, Level 1+)
B If acceptable seizure control is not achieved with monotherapy using phenytoin, sodium valproate or carbamazepine: add sodium valproate to carbamazepine or phenytoin, add carbamazepine or phenytoin to sodium valproate (Heller et al., 1995; Richens et al, 1994; Turnbull et al., 1985; Mattson et al., 1985; Mattson, Cramer, & Collins, 1992). (Grade B, Level 1++)
A Systematic review has confirmed the efficacy and tolerability of the newer antiepileptics vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine and levetiracetam. All may be used as adjunctive therapy for patients with drug-resistant, focal epilepsy (SIGN, 2003; Wilby et al., 2005). (Grade A, Level 1++)
A Although newer antiepileptic drugs (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate) have been shown to be effective, there is little good quality evidence from clinical trials supporting their superiority as adjunctive therapy over older drugs (Wilby et al., 2005). (Grade A, Level I+)
D If trials of combination therapy do not confer benefit, treatment should revert to the regimen (monotherapy or combination therapy) that has proven most acceptable to the individual, in terms of providing the best balance between effectiveness in reducing seizure frequency and tolerability of side effects (Guberman & Corman, 2000). (Grade D, Level 3)
D Changing the formulation or brand of antiepileptic drugs is not recommended because different preparations may vary in bioavailability or have different pharmacokinetic profiles and, thus, increased potential for reduced effect or excessive side effects (Guberman & Corman, 2000). (Grade D, Level 3)
D Lamotrigine, topiramate, levetiracetam and sodium valproate have a wide spectrum of activity for most types of generalised seizures. Although there is no published evidence of an " add-on" effect of these drugs in generalised epilepsies, this is supported by circumstantial evidence. Any one of these drugs can be added to a standard antiepileptic drug (phenytoin, carbamazepine, sodium valproate) (SIGN, 2003). (Grade D, Level 4)
D Addition of a third antiepileptic may be worth trying if an encouraging but sub-optimal effect is obtained with a particular combination of two drugs (SIGN, 2003). (Grade D, Level 4)
GPP All individuals with a first-onset suspected seizure should be evaluated by a specialist who has experience in epilepsy. This is to ensure accurate and early diagnosis, and initiation of appropriate therapy. Subsequent follow-up can be carried out by a general practitioner. (GPP)
A Withdrawal of antiepileptic drugs can be explored at the end of at least a two-year seizure-free period, after a discussion on the potential risks and benefits (Sirven, Sperling, & Wingerchuk, 2001). (Grade A, Level 1+)
A The decision to withdraw treatment should be individualised, taking into account lifestyle issues and a clear plan agreed upon should the seizures recur (Sirven, Sperling, & Wingerchuk, 2001). (Grade A, Level 1+)
D A repeat EEG prior to initiation of drug withdrawal is not routinely required (O'Dell & Shinnar, 2001). (Grade D, Level 4)
D Withdrawal of treatment should be a gradual process. There is no clear evidence for the length of the withdrawal period although most specialists would advocate a period of few months. Patients on polytherapy should have only one drug withdrawn at a time (O'Dell & Shinnar, 2001). (Grade D, Level 4)
D Patients on benzodiazepines or barbiturates should have these medications reduced over a longer time-course (up to 6 months or longer) (O'Dell & Shinnar, 2001). (Grade D, Level 4)
A Vagus nerve stimulation is indicated for adjunctive therapy and has been shown to reduce frequency of seizures in adults refractory to antiepileptic medication who are not suitable for epilepsy surgery. This includes adults whose epileptic disorder is dominated by partial seizures (with or without secondary generalisation) or generalised seizures (Privitera et al., 2002). (Grade A, Level 1+)
A Complementary treatment such as acupuncture, chiropractic, herbal medicine, homeopathy, osteopathy and yoga should not be advised to the epileptic patient (Stavem et al., 2000; Cott, 2001). (Grade A, Level 1+)
D Patients should be asked if they are using any complementary medicines and warned about the possibility of adverse effects. Problems may arise with the use of some herbal medicines because of interaction with prescribed medication. The potential reduction of the plasma concentrations of carbamazepine and phenytoin should be noted if St John's Wort is used concomitantly. Caution is also advised in the use of evening primrose oil but the evidence for this is less robust (Spinella, 2001). (Grade D, Level 4)
D Some aromatherapy preparations (e.g. hyssop, rosemary, sweet fennel, sage and wormwood) may have an alerting effect on the brain and so may exacerbate seizures (SIGN, 2003). (Grade D, Level 4)
D The ketogenic diet is not recommended for adults with epilepsy. There is no evidence of a worthwhile therapeutic effect. In addition, compared to children, in adults, it is difficult for dietary measures to result in great enough ketogenicity (NICE, 2004). (Grade D, Level 4)
C There is evidence that control of precipitating factors (emotional stress, sleep deprivation) may help better control seizures. This can only be recommended in addition to pharmacological treatments (Nakken et al., 2005). (Grade C, Level 2+)
Definitions:
Levels of Evidence:
Level 1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias.
Level 1+: Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias.
Level 1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
Level 2++: High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
Level 2+: Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
Level 2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
Level 3: Non-analytic studies (e.g. case reports, case series)
Level 4: Expert opinion
Grades of Recommendation:
Grade A: At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++ and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
Grade B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
Grade C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
Grade D: Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
GPP (good practice points): Recommended best practice based on the clinical experience of the guideline development group.
