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Seizure

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Introduction and Etiology

Seizure is defined clinically as a paroxysmal disturbance of electrical function in the brain associated with altered neurologic function. Seizures occur when a large number of neurons discharge abnormally. Ferrell & Coyle (2005) note that this abnormal discharge results in involuntary paroxysmal behavioral changes. Perkin et al (2008) says that definition includes clinical phenomena that are associated temporally with surface recorded EEG seizure activity and, therefore, are clearly epileptic.

A long-term prognosis for patients with a remote symptomatic etiology is relatively less favorable than idiopathic or cryptoigenic etiologies. Consistent with this less favorable long-term prognosis, there is a lower likelihood of remaining seizure-free after discounting treatment in children with a remote symptomatic etiology versus idiopathic etiologies. Volpe (2008) notes that patients with idiopathic or cryptogenic etiologies have seizure free-rates of approximately 70%.

There are two types of seizure, which include primary, also called generalized, and focal, also called partial. Ferrell & Coyle (2010) say that primary seizures involve larger parts of brain and include both grand mal and petit mal types. Focal seizures are isolated to specific regions of the brain, and symptoms reflect the area of disturbance (Ferrell & Coyle, 2010). About 50% of all seizure cases are idiopathic, the possible causes of which include birth trauma, prenatal infection, anoxia, and infectious diseases. Research shows that patients with malignancies known to metastasize to the brain such as breast, lung, hypernephroma, and melanoma should be considered at risk of seizure (Volpe, 2008). Leukemia and lymphomas are also known to produce infiltrates in the brain. Cerabrovascular disease is the leading cause of seizures among the elderly.

Ferrell & Coyle (2010) note that multiple metastases or brain and leptomenigeal disease are commonly associated with seizures. Medications can lead to seizure in palliative care setting through several mechanisms. Medications, such as phenothiazines, butyrophenones, and tricyclic antidepressants, can place patients at risk of lowering seizure threshold (Ferrell & Coyle, 2010). Benzodiazepines, barbiturates, and Baclofen are the most common drugs associated with seizures during abstinence.  

Assessment

The practitioner should obtain a thorough history from the patient and caregiver to ascertain any symptom existing with the onset of the seizure, the specific type of seizure activity, and whether there was any aura immediately before the seizure. Ferrell & Coyle (2010) say that the family may relate staring-type behavior, where the patient does not respond to stimuli for a brief moment. The practitioner should assess past medical history, which might reveal a seizure disorder. Nurses should review all drugs recently added to the plan of care for agents that might lower the seizure threshold or produce metabolites (Ferrell & Coyle, 2010).

A practitioner should assess neurological status and compare to baseline, assess characteristics of seizure such as tonic, progression, and duration. If possible, the practitioner should have a witness who was at the scene to explain the seizure. Perkin et al (2008) note that details about when it started and how long it lasted should be noted. It is important for a practitioner to review medical history of the patient for generalized and focal seizures. The practitioner should obtain drug history, including prescription and over-the-counter drugs and ask the patient about alcohol intake. Physical assessment should include noting patient’s vital signs (Perkin et al, 2008), performing full neurologic assessments, and assessing the patient for possible injuries caused by the seizure.

During the assessment, Paul & Williams (2009) indicate that the practitioner should note the first thing the patient does in a seizure, where the movement or stiffness starts, conjugate gaze position, and the position of head at the beginning of the seizure. This information gives clues to the location of seizure origin in the brain. The nurse should note the presence or absence of automatisms or involuntary motor activity such as lip smacking or repeated swallowing. Duration of each phase of the seizure and any obvious paralysis or weakness of arms or legs after the seizure should be carefully assessed (Paul & Williams, 2009).

Treatment

The most common approach to treatment of seizure is the use of anticonvulsants. This type of treatment consists of drug therapy. Prophylactic anticonvulsant therapy has demonstrated benefit only in the case of brain metastases from melanoma (Ferrell & Coyle, 2010). The most common anticonvulsants used to prevent seizure are Phenytoin, Carbamazepine, Valproate, and Phenobarbital (Press, 2005). The most common agents used during seizure treatment include Diazepam, Lorazepam, Midazolam, and Phenytoin.

According to Paul & Williams (2009), the goals of treatment are to stop seizures as quickly as possible, to ensure adequate cerebral oxygenation, and to maintain the patient in a seizure free state. An airway and adequate oxygenation are established. Paul & Williams (2009) noted that “if the patient remains unconscious and unresponsive, a cuffed endotracheal tube is inserted. Intravenous Diazepam (Valium), Lorazepam (Ativan), or Fosphenytoin (Cerebyx) is given slowly in an attempt to halt seizures immediately” (p. 2088).

Evidence-Based Treatment of Seizure

Evidence-based care has played an important role in treatment and management of seizures. Topiramate has been extensively evaluated as monotherapy. Shorvon (2010) says that in a pivotal regulatory study, a dose of 400mg/day was compared to 50mg/day in an RCT in newly diagnosed partial or primary generalized tonic-clonic seizures. Shorvon (2010) notes that a greater proportion of patients were seizure-free at 6 and 12 months on 400mg/day (p<0.001). Shorvon (2010) notes that in an open trial of topiramate monotherapy in 692 patients with partial or generalized seizure, who were treatment naive or had failed with prior treatment using one anti seizure drugs, 76% of patients were reported to have had more than 50% reduction in seizure frequency, with 44% of patients rendered seizure free. In these monotherapy studies, 40-82% of those with partial seizures and 62-85% of those with generalized seizures were free of seizures (Shorvon, 2010).

In a comparative RCT of 613 patients with newly diagnosed seizure, the time to trial exit, the time to first seizure, and the proportion of seizure-free patients were found to be similar Topiramate (110-200 mg/day), Carbamazepine (600mg/day), and Valproate (1250mg/day). 6-month seizure free rates with 100 and 200 mg/day were 49% and 44%, compared with 44% on Carbamazepine and Valproate. Shorvon (2010) notes that discontinuation rates owing to adverse events for 100mg/day Topiramate, 200mg/day Topiramate, Carbamazephine, and Valproate were 18%, 28%, 25%, and 23%, respectively.

In another study, RCT in children with partial onset seizure, the addition of Topiramate reduced median seizure frequency by 33% compared with 11% in the placebo group, p=0.03. No child discontinued Topiramate treatment because of adverse4 events in the trial period. It was noted that 5% of children receiving Topiramate were free from seizures during 16-week study, and none in the placebo-treated group. In an open label extension study of the RCT (for a mean of 2.5 years), 14% of children became seizure free for at least 6 months, and seizure frequency over the last 3 months of therapy was reduced in 57% of children. According to Shorvon (2010), the study also indicated that 6% of children discontinued treatment because of adverse events and 13% because of inadequate seizure control.

Analysis of Research Studies

Article 1: Simple Febrile Seizures: Are the AAP Guidelines Regarding Lumbar Puncture Being Followed?

Clinical guidelines play an important role in the management of the condition. The American Academy of Neurology (AAN) has produced 14 evidence-based guidelines focused on some aspect of seizure and its evaluation on treatment. AAN uses appropriate methodology to provide evidence-based recommendations to specifically address clinically relevant questions of seizure. Shaked et al (2009) note that the AAN guideline also states that treatment discontinuation may be appropriate for patients who do not meet the guidelines. An important part of this guideline of a patient with seizure is education of family and child about the disease as well as its management.

In AAN guidelines article, the primary outcomes of seizure treatment are clearly defined. Exclusion and inclusion criteria are clearly defined in this article. The article provides adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias in seizure study (Shaked et al, 2009). The article presents relevant baseline characteristics and substantially equivalent among treatment groups or there are appropriate statistical adjustments for differences. The limitation of the article is that it presents inadequate and conflicting data. Therefore, given the current knowledge, the treatment is unproven.  

Article 2: ILAE Treatment Guidelines: Evidence-based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes

Glauser et al (2006) published an evidence-based guideline on the treatment of new on-set epilepsy of all seizures types and all ages. Although the International League against Epilepsy (ILAE) guidelines defines febrile seizures as occurring in childhood, many investigators and clinicians prefer to set an upper limit of 5 years (Glauser et al, 2006).

It is important to note that the article presents a convention, which is not based on scientific evidence that febrile seizures in older children are substantively different from those in younger children (Glauser et al, 2006). The ILAE guideline, therefore, without solid scientific evidence to provide a basis for an absolute age cut-off, one can understand clinicians' reticence to diagnosis. Glauser et al (2006) note that the ILAE guideline presented in this article should go beyond the scope of the guideline to incorporate all considerations relevant to each patient. While the article suffers from the limitation of a retrospective study, it does highlight the fact that there may be subgroups within the broad classification of seizure with slightly different remission outcomes.

Article 3: Early Management of Adults With an Uncomplicated First Generalized Seizure

Dunn et al (2005) in their article note that SIGN seizure management guideline has undertaken comprehensive reviews of seizure care, including recommendations regarding AED therapy. While the scientific value of these documents is remarkable, their format, and in particular, their length and complexity, make the guidelines unlikely to be read and endorsed by a large number of neurologists (Dunn et al, 2005). SIGN seizure management guideline has undertaken comprehensive reviews of seizure care, including recommendations regarding AED therapy (Dunn et al, 2005).

The major limitation associated with SIGN seizure management guideline is that while the scientific value of these documents is remarkable, its format, and specifically its length and complexity makes it unlikely to be read and endorsed by a large number of neurologists. Dunn et al (2005) indicate that the strength associated with this seizure guideline is that it offers intermediate recommendations with a selection of only two old and two new generation AEDs as first line monotherapy.  

Article 4: NICE Epilepsy Guidance “May Be Detrimental to Patient Care”

Pellock et al (2008) in their article note that newer AEDs Gabapentin, Tiagabine, Topiramate, and Lamotrigine are recommended for the management of epilepsy in children who have not benefitted from treatment with older agents. Nice guidelines provide recommendations for the syndrome of childhood and juvenile absence. NICE guidelines recommend certain drugs in certain seizure types. NICE guidelines state that each person should have a comprehensive care plan, including medical and lifestyle issues that are agreed upon by the individual and the primary, secondary, or tertiary services (Pellock et al, 2008).

According to Holmes (2012), NICE seizure management guidelines propose a tiered approach to the use of the newer AEDs in this indication recommending that they be employed only when the patient does not respond adequately to established drugs used in first-line therapy (Holmes, 2012). Limitation of NICE seizure management guidelines is that it does not completely recognize the appropriate choice for anticonvulsant medication for women with seizure, which is different than that for men with seizures. Holmes (2012) notes that NICE seizure management guidelines are long and complex and, therefore, it is unlikely that they are endorsed by a large number of neurologists.  

Article 5: Developmental Medicine & Child Neurology Developmental Medicine & Child Neurology

Limitation of EBM seizure guidelines is that they rely heavily on the power of RCTs. RCTs tends to minimize bias that can affect trial's outcome, they minimize the impact of variability, and they provide better information than anecdotal medicine. EBM guidelines use RCT trial but may not pick a clinically significant treatment effect and do not explain the factors underlying inter-subject variability in response to therapy (Press, 2005). In EBM guidelines, the study population size in most RCTs is selected to answer only one specific question, and all alternative questions and analyses may not show any treatment effect because they are underpowered (Pellock et al, 2008).

Limitation of EBM seizure guideline is impossible to practice because of time demands, financial issues, and patient variability seen outside academic centers. EBM is limited because it relies primarily on randomized trials and meta-analyses (Press, 2005). However, EBM is still a young discipline, and much work still must be done before it becomes the standard approach for medical care for patients with seizures. 

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