CHAPTER 52 Diagnosis and Classification of Seizures and Epilepsy
Epilepsy is perhaps the most complex neurological disorder from a clinical and pathophysiologic perspective. Many distinct molecular changes in neurons and glia can cause seizures,1 and seizures occurring in specific neuronal networks manifest very different clinical symptoms and signs. In fact, there are many different epilepsy syndromes, each with multiple neurobiologic origins.2 For example, juvenile myoclonic epilepsy is now understood to be associated with mutations on several different chromosomes.3 Complex partial seizures of temporal lobe origin4 may be caused by mesial temporal sclerosis,5,6 developmental malformations,7,8 brain injury, specific genetic mutations, or possibly a combination of these causes.9 One of the major challenges of contemporary neuroscience is to better understand the ways in which the clinical manifestations of the epilepsies represent underlying structural, physiologic, and genetic alterations.
The epilepsies have importance for public health in that they are among the most common disabling neurological disorders occurring across the life span.10–12 The prevalence of epilepsy is estimated to be about 1% of the U.S. population.13 The World Health Organization reports that more than 100 million people are affected by epilepsy worldwide.14 It is noteworthy that the Centers for Disease Control and Prevention emphasizes the lack of research on prevalence and incidence and recently stated that “epidemiological and surveillance data on epilepsy are limited” (www.cdc.gov/Epilepsy/).
Although earlier clinical studies suggested that more than 85% of patients with epilepsy have “adequate” seizure control with antiepileptic drugs,15,16 more recent data indicate that in 35% to 40%, the available medications will not fully control the epilepsy.13,17 In a Scottish study of more than 470 patients with recently diagnosed epilepsy, about 35% had a seizure during the most recent year of follow-up after a mean of 5 years of treatment. Furthermore, in only 11% was the epilepsy ever fully controlled with subsequent medications after the first antiepileptic drug failed.17 A recent population-based study by the Centers for Disease Control and Prevention that included 120,000 people from 19 states found results that supported the Scottish data: 44% of patients with epilepsy who were currently taking medications had at least one seizure during the past 3 months.13 Because the most important initial steps in effective treatment of epilepsy involve accurate diagnosis and subsequent selection of appropriate antiepileptic drugs based on seizure type, classification of the epilepsy based on precise history and supportive clinical testing is critical for optimal outcome.18
Seizure and Epilepsy Classification
The Commission on Classification and Terminology of the International League Against Epilepsy (ILAE) developed a widely used classification system based on review of videotaped seizures at commission workshops.19 This classification system categorizes seizures in a format that facilitates diagnosis, treatment, and communication among medical professionals through standardized nomenclature.
Seizures are divided into two major categories—partial and generalized. Partial seizures are “those in which the first clinical and electrographic changes indicate initial activation of a system of neurons in one hemisphere and are subclassified based on the presence or absence of impairment of consciousness.”19 Simple partial seizures are associated with minimal change in awareness, as indicated clinically by the patient’s complete recollection of the event. Complex partial seizures are characterized by alteration of awareness and amnesia for at least a portion of the seizure. Partial seizures may include signs or symptoms correlating with activation of any brain region—specifically, motor, autonomic, somatosensory, special sensory, or psychic, as elegantly demonstrated by Drs. Penfield and Jasper in their intraoperative stimulation studies of persons with epilepsy.20 Both simple and complex partial seizures can propagate throughout the brain to become secondarily generalized seizures, typically with tonic or clonic motor features (or with both). Generalized seizures are “those in which the first clinical changes indicate initial involvement of both hemispheres.”19 The subclassification of generalized seizures includes absence, myoclonic, clonic, tonic, tonic-clonic, and atonic seizures. The generalized epilepsies, as opposed to generalized seizures, are often divided into primary (idiopathic) and secondary (symptomatic).2 This distinction is useful because the seizures of primary generalized epilepsy are frequently genetic,21,22 are usually limited to childhood or adolescence, and respond readily to certain anticonvulsant medications.23
Knowledge of the frequency of the common causes of epilepsy is necessary when assessing a patient with seizures. Cerebrovascular disease is the most frequently identified cause of epilepsy, followed by developmental disorders, head trauma, brain tumor, infection, and degenerative disorders.24 The proportional incidence of the causes of seizures varies considerably with age, with cerebrovascular disease predominating in senior adults, head trauma and brain tumors more common in adolescents and adults, and developmental and infectious disorders proportionally most frequent in neonates and young children.24
Epilepsy syndromes are disorders associated with specific seizure types, clinical characteristics, and ages at onset. Similar to seizure classifications, the epilepsies are divided into two main categories: localization related and generalized. The ILAE classification system for epileptic syndromes is summarized in Table 52-1.2
TABLE 52-1 International Classification of the Epilepsies and Epileptic Syndromes
|
1 Localization-related (focal, local, partial) epilepsies and syndromes
2 Generalized epilepsies and syndromes
3 Epilepsies and syndromes undetermined regarding whether they are focal or generalized
|
Adapted from Commission on the Classification and Terminology of the International League Against Epilepsy. A revised proposal for the classification of epilepsy and epileptic syndromes. Epilepsia. 1989;30:268-278.
Diagnosis of Epilepsy
Epilepsy is often operationally defined as two unprovoked seizures occurring more than 24 hours apart. However, the ILAE recently proposed that “epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.”25 For the purposes of this chapter, we will consider epilepsy to be two unprovoked seizures or one unprovoked seizure with additional clinical evidence of increased risk for recurrent seizures. Hence, factors that influence the risk for seizure recurrence will be discussed as they relate to the diagnosis and especially to the decision for treatment to prevent subsequent seizures.
Approach to the First Seizure
Acute Evaluation
The urgent evaluation should include serum glucose, sodium, urea nitrogen, creatinine, and calcium and hepatic enzyme concentrations. Arterial blood pH, oxygen, and carbon dioxide are important to measure. A toxicology screen is necessary if no other cause is readily identified, especially for ethyl alcohol, cocaine, amphetamines, benzodiazepines, opioids, phencyclidine, tricyclic antidepressants, and antipsychotic drugs.26 Hypothyroidism with myxedema coma has been associated with seizures in rare cases.27
Brain imaging, preferably computed tomography (CT) in view of its rapid availability at most centers, is necessary to exclude a structural cerebral abnormality such as hemorrhage, tumor, abscess, or contusion.28 If significant temperature elevation, nuchal rigidity, leukocytosis, or other signs of possible central nervous system inflammation are present, a lumbar puncture is required to exclude infection or subarachnoid hemorrhage. If the patient has a possible history of seizures, anticonvulsant medications should be identified and serum concentrations determined.
Decreased responsiveness or unusual behavior may be the only indication of a persistent seizure.29 An urgent EEG is therefore recommended for any patient whose mentation does not begin to normalize within minutes after a witnessed seizure. Furthermore, an EEG should be considered for any patient without a clearly defined cause of the altered mental status. If “subclinical” seizures are a possible cause of the confusion or abnormal behavior and the EEG is not diagnostic, intravenous injection of a short-acting benzodiazepine such as lorazepam may support the diagnosis if clinical improvement is observed soon after administration.29 Change in the EEG pattern after injection does not confirm that a rhythmic or semirhythmic pattern was a seizure; in many cases, this can be determined only by correlative improvement in the mental status examination.30
