Chapter 13: Primary Generalized Tonic-Clonic Seizures

Introduction

Generalized tonic-clonic (GTC) seizures may be either primary or secondary in onset.¹ Although the older terms grand mal, convulsion, and fit are still widely used by patients, the preferred terminology of tonic-clonic seizure derives from intensive correlative analysis of GTC clinical seizure semiology with simultaneous ictal electroencephalography (EEG), and implies a usual prototypical progressive sequence of clinical movements that often help distinguish this seizure type from other predominantly motor, primarily generalized, or partial-onset seizure types (i.e., myoclonic, tonic, and extratemporal partial seizures) and from psychogenic or physiologic nonepileptic spells.¹

Primary generalized tonic-clonic (PGTC) seizures arise from bisynchronous ictal behavioral and EEG onset simultaneously from both cerebral hemispheres. They are a chief seizure type within the rubric of generalized seizure types occurring in primary (idiopathic) generalized epilepsy syndromes,² but they could occur as isolated single spontaneous seizures or as acute provoked symptomatic seizures unassociated with the development of epilepsy.³ In contrast, secondarily generalized tonic-clonic (SGTC) seizures are the final common pathway of seizure propagation from focal seizures. An SGTC may be the sole or predominant seizure phenotype and presenting clinical expression of a partial-onset seizure and focal epilepsy syndrome. Diagnostic confusion between PGTC and SGTC seizures occurs frequently, given their overall similar clinical appearance, especially in new-onset epilepsy, when patients have had relatively few seizures, limiting opportunities for direct observation and accurate description.^3,4

Because PGTC and SGTC seizures often have very similar clinical manifestations, careful consideration must be given prior to assigning a diagnosis of a PGTC seizure type when a patient initially presents with a clinical history of a GTC. In practice, differentiating PGTCs from SGTCs may be quite difficult. The distinction between PGTCs and SGTCs in clinical outpatient practice most often relies on indirect evidence, such as neuroimaging and interictal EEG data, or clinical history features, such as described ictal behavior, patient age, family history, seizure periodicity, known aggravating factors, and the presence of other known partial or primary generalized seizure types, including auras. Confident determination of the seizure type and underlying epilepsy syndrome is enabled in children with newly diagnosed epilepsy, given higher seizure burden and more frequently diagnostic interictal EEGs in that patient population, whereas in adults, corroborative investigations are frequently frustratingly negative in new-onset epilepsy, leading to uncertainty regarding the appropriate seizure type and syndromic epilepsy diagnosis in many patients.^5,6 Uncertain epilepsy syndrome diagnosis can hamper appropriate tailoring of antiepileptic drug (AED) treatment in refractory epilepsy.

When diagnostic uncertainty persists, and accurate seizure type diagnosis is necessary to direct further empiric AED therapies and consideration of a surgical approach in refractory patients, ictal video-EEG monitoring (VEM) is necessary to distinguish PGTCs from SGTCs.^7–9 VEM has been found to significantly increase accurate diagnosis of idiopathic generalized epilepsy (IGE).¹⁰ It has a particularly high yield (88%) in identifying diagnostic interictal or ictal EEG manifestations consistent with ...