Seizure

Background and Classification

Seizures are excessive excitatory neuronal activity associated with hypersynchrony of neighboring cells, resulting in sensory, motor, autonomic, or cognitive function alterations. Convulsion refers specifically to the motor manifestations of a seizure. The ictal period is the time during which a seizure or seizure-like activity occurs. A postictal period is an interval of transient neurologic dysfunction (commonly altered mental status or weakness) immediately following a seizure, generally lasting less than 1 hour. Longer ictal activity is associated with more prominent and prolonged postictal symptoms. When precipitating factors can be identified, provoked seizures are termed acute symptomatic seizures. Conversely, primary seizures are unprovoked and have no acute inciting pathology. Epilepsy refers to a condition of recurrent unprovoked seizures.

The International League Against Epilepsy defines epilepsy as a disease in which the threshold for seizures is lower than the normal population reflected by meeting at least one of the following: (A) diagnosis of epilepsy syndrome (e.g., juvenile myoclonic epilepsy, Lennox-Gastault syndrome, benign rolandic epilepsy, infantile spasms); (B) two or more seizures occurring more than 24 hours apart without an identified trigger; (C) one unprovoked seizure coupled with a higher likelihood of recurrent seizures over the subsequent decade (similar to the recurrence risk for fulfilling criterion B, or ≥60% recurrence risk). For example, a patient who suffers head trauma might have a seizure in close proximity to the acute brain injury but would not be considered to have epilepsy unless unprovoked seizures recur remotely from the initial brain injury. Epilepsies are classified further according to seizure onset and semiology (focal with or without impairment of awareness, generalized or unknown onset; see Figure 14.1 in Chapter 14 ), epilepsy syndrome (e.g., idiopathic generalized and self-limited focal epilepsies), and etiology (e.g., structural, genetic, infectious, metabolic, immune, or unknown).

The majority of epilepsy syndromes have onset during childhood or adolescence. However, there have been reports of onset in early adulthood ; a thorough evaluation with a specialist is indicated in these cases. Breakthrough seizures in patients with epilepsy are commonly triggered by sleep deprivation, emotional or physical stress, and menses. Additionally, even slight adjustments in the antiseizure regimen or missing doses of medications may precipitate a recurrent seizure. A specific sensory stimulus, such as flashing lights or a specific smell, may also trigger seizures in epilepsies; these are still considered “unprovoked” when triggered by a process that would not cause a seizure in the patient that does not have epilepsy.

Medically refractory epilepsy (also known as “uncontrolled” or “drug-resistant”) refers to patients who are unable to achieve or maintain seizure freedom despite 2 trials of adequately dosed antiseizure regimens. These patients continue to have seizures with a variable baseline frequency of occurrence. There are several definitions for seizure clusters reported in the literature: 3 or more seizures in 24 hours, 2 or more seizures in 24 hours, or 2 or more seizures in 6 hours. The timely recognition of seizure clusters allows for prompt administration of seizure abortive measures (at home as instructed by the neurologist or epileptologist, in the pre-hospital, or in the hospital settings). Patients with medically refractory epilepsy presenting with seizure clusters are at a higher risk for status epilepticus.

Uncontrollable seizures, or status epilepticus, are seizures that have reached a prespecified duration according to specific seizure types (see Table 14.1 in Chapter 14 ) or recur with a frequency that does not allow a patient to return to the baseline neurologic status in between seizures.

Seizures may be provoked by a multitude of insults, such as acute brain injury (e.g., ischemic and hemorrhagic strokes, trauma, meningoencephalitis), toxins, and metabolic derangements. The main cause of status epilepticus and epilepsy in the elderly remains cerebrovascular disease. Patients with diabetes, higher stroke severity, cortical location of infarcts, and thromboembolic mechanisms are at the highest risk for experiencing seizures in the acute phase, with an incidence of up to 5% of all ischemic strokes in some series. ^, Nevertheless, the true incidence of seizures in the setting of stroke is difficult to ascertain because studies had variable methods of detection, use of primary seizure prophylaxis, and follow-up duration. Box 88.1 summarizes etiologies of seizures and status epilepticus according to the type of insult or neurologic process. Being familiar with common seizure triggers allows for identifying patients at higher risk for seizures and status epilepticus who may benefit from further diagnostic workup such as neuroimaging, EEG, or neurologic consultation.

When seizures are prolonged and the duration exceeds the respective threshold according to type (convulsive, nonconvulsive, or absence; see Table 14.1 in Chapter 14 ), they are termed status epilepticus . Overall, status epilepticus is associated with significant morbidity and mortality, particularly convulsive generalized status epilepticus. In the United States, reported status epilepticus incidence ranges from 10 to 40 persons per 100,000 annually. In a meta-analysis, the leading cause of status epilepticus globally was acute symptomatic (in close temporal relationship with a brain insult). Overall case fatality rates were 15%; the highest case fatality rates were seen in low- and middle-income countries, refractory status epilepticus, and in the elderly population.

Several different scores exist to predict outcomes in status epilepticus. The Epidemiology based Mortality Score in Status Epilepticus (EMSE; Table 88.1 ) accounts for etiology of seizures, age, comorbidities, and EEG findings and performs well in predicting mortality and morbidity, but fails to predict responses to therapy satisfactorily.

Anatomy, Physiology, and Pathophysiology

Neuronal cell membranes are stabilized by transmembrane electrochemical gradients and equilibrium among inhibitory neurotransmitters (e.g., GABA) and excitatory neurotransmitters (e.g., glutamate and acetylcholine). Seizures start when the equilibrium across the cell membrane is disrupted by an imbalance between these factors, leading to abnormal electrical discharge of cortical and subcortical neurons. The recruitment of neighboring neurons leads to spreading of this abnormal excitation. It may manifest clinically by propagating clonic activity in adjacent areas in the body following their corresponding topography in the brain (i.e., Jacksonian March , when focal motor seizure symptoms spread in a step-wise fashion). If there is involvement of large areas in both hemispheres, thalami, or deeper structures, and of the reticular activating system in the brainstem, impairment in consciousness ensues.

Physiologic mechanisms implicated in seizure termination involve reflex inhibition, hyperpolarization of neurons preventing their depolarization, and neuronal exhaustion, among others. Most drugs used to interrupt seizures act on GABA _A subtype receptors, therefore enhancing inhibitory activity. However, with prolonged seizure activity, GABA _A receptors are sequestered inside the cells and become unresponsive to GABA (and GABA-ergic medications), whereas excitatory N -methyl-D-aspartate (NMDA) receptors may be upregulated. This perpetuates an excitatory state and leads to sustained seizure activity, explaining why timely treatment of seizures is of utmost importance.