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REVIEW ARTICLE
Year : 2017  |  Volume : 65  |  Issue : 7  |  Page : 6-11

Evidence-based guidelines for the management of epilepsy


1 Department of Neurology, Creighton University School of Medicine, Omaha, Nebraska, USA
2 Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

Date of Web Publication8-Mar-2017

Correspondence Address:
Sanjay P Singh
Department of Neurology, Creighton University School of Medicine, Omaha, Nebraska - 68131
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/neuroindia.NI_1027_16

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 » Abstract 

Approximately 50 million people live with epilepsy worldwide. The aim of this review is to present an overview of the current evidence and management recommendations for evaluation and treatment of patients with epilepsy. Systematic literature reviews were undertaken. A review of contemporary published evidence-based guidelines (American Academy of Neurology, American Epilepsy Society, and the Indian Epilepsy Society) and published peer reviewed scientific publications was done. The guideline is addressed to all clinicians who manage epilepsy patients. Evidence-based recommendations are provided for the evaluation and treatment of the first seizure, use of antiepileptic medications, treatment of status epilepticus, use of epilepsy surgery, and the management of epilepsy in specific populations as well as in unique clinical situations such as neurocysticercosis infestation, brain tumor and human immunodeficiency virus infection. It also addresses the special considerations in women with epilepsy.


Keywords: Antiepileptic medications, epilepsy, epilepsy surgery, evidence-based medicine, guidelines, seizures, status epilepticus
Key Messages: An overview of the current evidence and management recommendations for evaluation and treatment of patients with epilepsy is provided. The specific clinical situations focused upon include a single unprovoked seizure, antiepileptic medications, status epilepticus, epilepsy surgery, special considerations in women; and, the management of epilepsy in unique clinical situations such as neurocysticercosis, brain tumor and human immunodeficiency virus.


How to cite this article:
Singh SP, Sankaraneni R, Antony AR. Evidence-based guidelines for the management of epilepsy. Neurol India 2017;65, Suppl S1:6-11

How to cite this URL:
Singh SP, Sankaraneni R, Antony AR. Evidence-based guidelines for the management of epilepsy. Neurol India [serial online] 2017 [cited 2017 May 29];65, Suppl S1:6-11. Available from: http://www.neurologyindia.com/text.asp?2017/65/7/6/201660


Modern medicine is based on scientific evidence. We practice evidence-based medicine, and it is in this context that reputable professional organizations publish practice guidelines on specific topics to summarize the best available evidence on a medical topic to guide the physicians in their management of patients suffering from that disorder.

This article attempts to summarize the various practice guidelines issued by the American Academy of Neurology, American Epilepsy Society, and the Indian Epilepsy Society that focus on the management of epilepsy. Topics that a neurologist would require for appropriate management of an epilepsy patient have been included in this article.

This article will organize these topic under evaluation, treatment, and special topics.


 » Evaluation of a Seizure Patient Top


Evaluation and management of first unprovoked seizure

An estimated 150,000 adults present annually with an unprovoked first seizure in the United States. Therefore, in India, its incidence would be approximately three or four times of this figure. It is, thus, imperative that clinicians know how to manage this clinical situation.

Adult patient with a seizure

After the patient is stabilized, the physician should confirm with a detailed history and neurological examination that the event was indeed a seizure [Table 1]. Other conditions such as syncope, breath holding spells, gastroesophageal reflux, esophageal reflux, movement disorders, and nonepileptic spells should be excluded. Serum prolactin level and creatine kinase level cannot be used to diagnose a seizure reliably.[1] Further management of a patient presenting with first seizure depends on whether the seizure was provoked (acute symptomatic seizure), as well as the risk of recurrence of the seizure.[2],[3]
Table 1: ILAE Classification of Seizures

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Adults presenting with an unprovoked first seizure should be informed that the chance for a recurrent seizure is greatest within the first 2 years after the first seizure (21–45%). Clinicians should also advise such patients that clinical factors associated with an increased risk for seizure recurrence include a prior brain insult such as stroke or trauma, an electroencephalogram (EEG) with epileptiform abnormalities, a significant brain-imaging abnormality, and a nocturnal seizure.

For evaluation, an EEG should be considered to be a part of the routine neurodiagnostic evaluation of the adult with an apparent unprovoked first seizure because it has value in determining the risk for seizure recurrence. Brain imaging using computed tomography (CT) or magnetic resonance imaging (MRI) should be ordered, preferably an MRI brain.[4],[5] Blood glucose, blood counts, and electrolyte panels (particularly sodium) may be helpful in specific clinical circumstances. A lumbar puncture may be helpful in specific clinical circumstances such as in patients who are otherwise febrile. It is not routinely indicated. A toxicological screening may be helpful in specific clinical circumstances.

Clinicians should advise patients that immediate antiepileptic drug (AED) therapy, compared with delay of treatment pending a second seizure, is likely to reduce the risk for seizure recurrence in the 2 years subsequent to the first seizure. Immediate AED therapy may not improve quality of life (QOL). In the long term (>3 years), immediate AED treatment is unlikely to improve the prognosis for sustained seizure remission. Risk for AED adverse events (AEs) ranges from 7% to 31%, with these AEs being predominantly mild and reversible.

The decision to initiate immediate AED treatment after the first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, considering educated patient preferences [Table 1], [Table 2], [Table 3].
Table 2: Common side effects of common AEDs

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Table 3: Indications and dosing guides for common AEDs

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Pediatric patient with a seizure

Studies on the incidence of first unprovoked seizure suggest that there are between 25000 and 40000 children per year in the United States who experience a first unprovoked seizure. A clinician needs to be aware of the issues specific to the pediatric population in this clinical scenario.

The majority of children who experience the first unprovoked seizure will have few or no recurrences. In one large study, 46% had one or more recurrences during the next 10 years. Over the extended follow-up period, 19% of the children enrolled experienced >4 seizures and only 10% experienced >10 seizure episodes. Patients with remote symptomatic seizures (with a prior identifiable major brain insult such as severe trauma or accompanying a condition such as cerebral palsy or mental retardation) and an abnormal EEG were more likely to have recurrent seizures. The overall recurrence risk following a prolonged first seizure was no different from the recurrence risk following a brief first seizure.

In such pediatric patients, an EEG is recommended as part of the neurodiagnostic evaluation of the child with an apparent first unprovoked seizure. If a neuroimaging study is obtained, MRI is the preferred modality. Emergent neuroimaging should be performed in a child of any age who exhibits a postictal focal deficit (Todd's paresis) not quickly resolving or which has not returned to baseline within several hours after the seizure. Nonurgent imaging studies with MRI should be seriously considered in any child with a significant cognitive or motor impairment of unknown etiology, unexplained abnormalities on neurologic examination, a seizure of partial (focal) onset with or without secondary generalization, an EEG that does not represent a benign partial epilepsy of childhood or primary generalized epilepsy, or a seizure in children under 1 year of age.

There is no evidence of a difference in achieving a 1 or 2-year seizure remission when treatment is started after the first seizure versus after a second seizure. Treatment with AED is not indicated for the prevention of development of epilepsy. Treatment with AED may be considered in circumstances where the benefits of reducing the risk of a second seizure outweigh the risks of pharmacologic and psychosocial side effects.


 » Treatment of a Patient With Seizures Top


Antiepileptic medications

The treatment options for epilepsy have come a long way from the bromides to the current era in which we now have multiple treatment modalities, including medications, implantable devices, and surgery. AEDs are the mainstay for treatment of epilepsy with approximately 70% of the patients achieving good control with medications alone. The goal for treatment should be to enable patients with epilepsy to lead a lifestyle consistent with their capabilities. The past decade has witnessed the emergence of multiple AEDs—with more than 24 AEDs to choose from at present. The newer drugs provide us with novel mechanisms of action and improved safety profile [Table 2].[6],[7] This has expanded the choice of AEDs and has made it possible to offer tailored-treatment plans based on unique patient profiles as displayed in [Table 3]. Based on a large meta-analysis of 11 AEDs, an increased occurrence of suicidal ideation was found in patients taking AEDs. When using AEDs, it is advisable to be vigilant and screen for psychiatric comorbidities and suicidal ideations.

Refractory epilepsy

Refractory or drug-resistant epilepsy is defined as failure of two or more appropriately selected and adequately tried AEDs to achieve seizure freedom. Up to 70% of the patients with epilepsy are well controlled with AEDs. For those who have refractory epilepsy, the likelihood that further AEDs will achieve seizure freedom decreases significantly. When a patient with drug-resistant epilepsy is evaluated, it is important to verify that the diagnoses of epilepsy is correct. Other things to question are the compliance with AEDs, use of appropriate dosing, and use of the appropriate drug for the given diagnosis. The likelihood of seizure freedom does not differ substantially whether a single established (67%) or a new-generation AED (69%) is used.

Combination of AEDs with different mechanisms of action has been thought to have improved efficacy but this fact has not been proven; however, we do know that combining of AEDs with similar action such as sodium channel blockers is more likely to produce side effects such as ataxia and dizziness. Oxcarbazepine (OXC) and carbamazepine (CBZ) share a common mechanism of action. Some patients who are inadequately treated with CBZ improve after switching to OXC. Some evidence suggests benefit in combining valproic acid and lamotrigine in partial (frontal lobe) epilepsy; however, lamotrigine serum levels increase when used along with valproate [Table 1],[Table 2],[Table 3].[8]

Felbamate

In 1993, felbamate was approved by the Food and Drug Administration (FDA). At that time, it represented a significant advance for many patients with inadequately controlled seizures. In September 1994, the FDA issued a letter, warning of a higher than expected incidence of aplastic anemia and hepatic failure among patients receiving felbamate. Patients for whom risk/benefit ratio still supports its use, because there is Class I evidence for benefit, are Lennox–Gastaut patients over age 4 years, unresponsive to primary AEDs; intractable partial seizures in patients over 18 years of age who have failed with standard AEDs at therapeutic levels; and, patients on felbamate for more than 18 months.

Patients should be educated regarding the early signs of potentially serious hepatic and hematopoetic side effects. The manufacturer, in conjunction with the FDA, suggests liver function tests at baseline and every 1 to 2 weeks for the first year of therapy. Patients should be advised of the manufacturer's recommendations. There is no evidence that such monitoring will prevent adverse outcomes. After the first year, the risk of aplastic anemia drops and the need for ongoing laboratory screening becomes even less clear.[9]

Status epilepticus

Status epilepticus (SE) is considered to be the most extreme form of a seizure associated with a high mortality (up to 20% in adults) and morbidity. Most seizures last less than 5 min. SE was defined as more than 30 min of either (1) continuous seizure activity or (2) two or more sequential seizures without full recovery of consciousness between them. The International League Against Epilepsy (ILAE) has since revised the definition to incorporate all types of SE as well as the operational definition of SE, which suggests starting treatment if seizures do not spontaneously stop within 5 min. The new definition of SE states that SE is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures [Table 4].[10]
Table 4: Operational dimensions for t1 (time when treatment should be started) and t2 (time at which long term consequences may be expected)

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Diagnostic assessment and treatment of patients with status epilepticus

EEG and AED levels are indicated in patients who develop status epilepticus. EEG is an important tool to diagnose nonconvulsive SE, ascertain seizure type and etiology of SE, rule out nonepileptic spells, as well as for immediate follow-up of patients treated for SE. Neuroimaging is indicated in patients with SE after stabilizing the patient, especially if the etiology is unknown. Toxicology screen and tests for inborn errors of metabolism (in children) should be considered and investigated in case of clinical suspicion or if the etiology is unclear after the initial evaluation. Blood culture and cerebrospinal fluid (CSF) analysis should be performed if there is clinical suspicion of CNS infection.[11] The guidelines for treatment of a patient presenting with convulsive SE are detailed below in [Table 5].[12]
Table 5: Treatment of convulsive status epilepticus in adults

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Maintenance antiepileptic drug treatment following status epilepticus

AEDs should be maintained in sufficient doses to maintain therapeutic concentrations (therapeutic concentrations may exceed published target concentrations) and should be individualized to achieve seizure control and prevent recurrence of seizures. When patients are exposed to the prolonged use of phenobarbital or pentobarbital, there is increased risk of withdrawal seizures and precipitation of refractory status epileptics, and hence, their levels should be carefully monitored and they should be weaned off very slowly, if necessary.

Epilepsy surgery

Epilepsy surgery is the next treatment option after antiepileptic medications. Patients with disabling complex partial seizures, with or without secondary generalized seizures, who have failed appropriate trials of first-line antiepileptic drugs should be considered for referral to an epilepsy surgery center.

Patients referred to an epilepsy surgery center for the reasons stated above who meet the established criteria for an anteromesial temporal lobe resection and who accept the risks and benefits of this procedure, as opposed to continuing pharmacotherapy, should be offered surgical treatment.[13]

There are other types of resective epilepsy surgeries, which are often performed on patients; however, there is no Class 1 evidence to support their use. This does not mean that it is inappropriate to recommend these extratemporal neocortical resections in the right clinical scenarios; however, patients should be appropriately counseled about the level of evidence available that support the recommendations for performing them. The need to achieve optimal seizure control is particularly important given that uncontrolled seizures are the main risk factor for SUDEP (Sudden Unexpected Death in Epilepsy Patients).

Other surgical procedures such as corpus callosotomy and hemispherectomy also lack any level 1 evidence supporting their use but are appropriate in the right clinical situation with proper counseling.

Vagal nerve stimulation in the treatment of epilepsy

Vagal nerve stimulation (VNS) is an effective therapy for patients with focal or partial epilepsy who have failed multiple medications and are not candidates for epilepsy surgery.[14] VNS therapy is approved as an adjunctive therapy for partial-onset seizures in patients over 12 years of age. Optimal VNS settings are still unknown, and the evidence is insufficient to support a recommendation for the use of standard stimulation versus rapid stimulation to reduce seizure occurrence. Therapy is started at the lowest possible settings and adjusted during each clinical visit depending on the efficacy and side effects. Patients may be counseled that VNS magnet activation may be associated with seizure abortion when used at the time of seizure auras. VNS may be considered to be progressively effective in patients over multiple years of exposure. In adult patients receiving VNS for epilepsy, improvement in mood may be an additional benefit. Diagnosis of epilepsy should be confirmed with EEG or video EEG before implanting the vagal nerve stimulator in any patient.

VNS may be considered in patients with Lennox–Gastaut syndrome. VNS may be considered to be an adjunctive treatment for children with partial or generalized epilepsy.


 » Special Topics in Seizure Care Top


Epilepsy in women

The recent estimates of prevalence [17] of epilepsy indicate that approximately half a million women with epilepsy (WWE) are of childbearing age. It has also been estimated that 3–5 births per thousand will be to WWE.[18] Therefore, it is critically important that we understand the special issues involved in treating WWE.

WWE on antiepileptic medications are at a higher risk of contraceptive failure, menstrual irregularities, and reduced fertility. Folic acid supplementation (1–4 mg per day) should be initiated in all WWE to decrease the risk of neural tube defects. The dose of antiepileptic medications should be adjusted during pregnancy and the immediate postpartum period due to wide fluctuation in the serum levels. Pregnant WWE on enzyme inducing AEDs should be on oral vitamin K (10 mg per day) from the 36th week of gestation until delivery. Breast feeding is not contraindicated in WWE.

WWE who are pregnant or are contemplating pregnancy should reflect that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84–92%) of remaining seizure free during pregnancy. There is substantial evidence that, if possible, valproate (VPA) should be avoided during the first trimester of pregnancy to decrease the risk of major congenital malformations (MCM). The avoidance of AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations. Avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes. In addition, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes.

Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at an increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of 7. WWE who are pregnant or are contemplating pregnancy should reflect that there is possibly a moderately increased risk (up to 1.5 times expected) of cesarean delivery for WWE taking AEDs. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy only for WWE who smoke.

Human immunodeficiency virus and antiepileptic drugs

Seizures are common in individuals infected with HIV (as high as 11% when compared to 1% in the general population). It is important to recognize the interactions between antiretrovirals and antiepileptic drugs because they can influence the metabolism of each other and lead to the failure of treatment or toxic levels of the drugs involved.[9] Certain AEDs induce cytochrome P450 system resulting in decreased efficacy of non-nucleotide reverse transcriptase inhibitors (NNRTI's) and protease inhibitors (PIs). This is especially more likely with the first generation AEDs such as phenytoin, phenobarbital, carbamazepine, and oxcarbamazepine. Phenytoin reduces lopinavir and ritonavir levels by approximately 30% and patients receiving this regimen with phenytoin may need to increase the dose by approximately 50% to maintain unchanged serum concentrations. Carbamazepine, when administered with efavirent, has reduced serum levels by 36%. Ritoanavir/atazanavir possibly reduces lamotrigine exposure by approximately 30% and patients receiving this combination may require a lamotrigine dosage increase of approximately 50% to maintain the expected serum concentration. Valproic acid has no effect when used with efavirenz. Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations.

Treatment of neurocysticercosis

Albendazole plus either dexamethasone or prednisolone should be considered for adults and children with neurocysticercosis, both to decrease the number of active lesions on brain-imaging studies and to reduce long-term seizure frequency. The evidence is insufficient to support or refute the use of steroid treatment alone in patients with intraparenchymal neurocysticercosis. Patients with parenchymal neurocysticercosis should be treated with antiepileptic medications until there are no active cysts. The efficacy of praziquental as first line therapy and corticosteroids without albendazole is unclear.[15]

Seizures with brain tumor

In patients with newly diagnosed brain tumors, anticonvulsant medications are not effective in preventing the first seizure. Because of their lack of efficacy and potential side effects, prophylactic anticonvulsants should not be used routinely in patients with newly diagnosed brain tumors. In patients with cortical brain tumor who have had an epileptic seizure, it is recommended that AED therapy should be initiated.

In patients with brain tumors who have not had a seizure, tapering and discontinuing anticonvulsants, that might have been started after the first postoperative week, is appropriate, particularly in patients who are medically stable and are experiencing anticonvulsant-related side effects.

Infantile spasms

Infantile spasm is a unique age-specific epilepsy syndrome of early infancy, and clinically, has a triad of epileptic spasms, neurodevelopmental regression and hypsarrythmia on EEG.[16],[17],[18]

Adrenocorticotrophic hormone (ACTH) may be offered for short-term treatment of infantile spasms. VGB may also be offered for short-term treatment of infantile spasms, particularly in patients with tuberous sclerosis. Evidence suggests that ACTH may be offered over VGB particularly in cryptogenic infantile spasms. Low-dose ACTH should be considered as an alternative to high-dose ACTH for the treatment of infantile spasms. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB may be considered to improve long-term cognitive outcomes. The evidence is insufficient to recommend other therapies (valproic acid, vitamin B6, nitrazepam, levetiracetam, zonisamide, topiramate, the ketogenic diet, or novel/combination therapies) for treatment of infantile spasms.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest

 
 » References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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