Abstract
Theodore WH, Porter RJ, Albert P, Kelley K, Bromfield E, Devinsky O, Sato S. Neurology. 1994 Aug;44(8):1403-1407. doi: 10.1212/wnl.44.8.1403. PMID: 8058138. We studied 120 generalized tonic-clonic seizures (GTCSs) in 47 patients with video-EEG telemetry. GTCSs were preceded by antecedent seizures, including 13 simple partial, 70 complex partial, 17 simple partial leading to complex partial, 7 tonic, 7 clonic, and 1 typical absence. We divided GTCSs into the following phases: onset of generalization, pretonic clonic, tonic, tremulousness, and clonic. The mean GTCS duration was 62 s. There was a nonsignificant trend toward longer duration on reduced antiepileptic drug doses. Marked heterogeneity in GTCS phenomenology was present; only 27% of seizures included all 5 phases. Individual phase duration and clinical expression, including tonic and clonic phases, was highly variable. The clinical phenomena suggest that multiple cortical and subcortical routes of spread may exist. When GTCSs last longer than 2 min, intravenous antiepileptic drug treatment should be initiated.
Commentary
The century-old cliché “a picture is worth a thousand words” now has a natural extension: if so, how much is a video worth? The use of photography in neurology predates the advertising industry's coinage of the cliché. As early as 1852, Guillaume Duchenne used it to depict the action of individual muscles. 1 However, it was the father of neurology, Charcot, who brought the technology into clinical neurology. He established a photographic lab at the Salpêtrière to primarily investigate “hystero-epilepsy.” 2 Since the late 19th century, advances in video technology, followed by EEG recordings, have enabled us to understand the evolution of seizure semiology and its electrophysiological correlates (Table 1). Along the way, some seminal articles have left an indelible mark on our fundamental knowledge of semiology and are foundational to its use in patient care. The article by Theodore et al is 1 such article and easily a citation classic. 3
Evolution of Video-EEG (vEEG) Technology and Its Clinical Applications. 2
Generalized tonic-clonic seizures (GTCS) are the earliest known, documented, and most easily recognized seizure type. However, the sequence of its evolution, specifically when the seizures start focally and progress to GTCS [now known as focal to bilateral tonic-clonic seizures (FBTCS) 4 ], was poorly understood until the 1994 article by Theodore et al They analyzed 120 FBTCS recorded in 47 patients (19 female; aged 11-56 years) evaluated in the NINDS Clinical Epilepsy section's epilepsy monitoring unit from 1974 to 1987. Each seizure was characterized into a maximum of 7 different phases. The first 2 phases (“antecedent seizure”) included a simple partial seizure (SPS) with preserved responsiveness (first phase) and a complex partial seizure (CPS), when the patient developed altered consciousness (Phase 2). Almost all (96%) FBTCS had an antecedent seizure. Of all FBTCS, 11% started as SPS, 58% as CPS, and 14% progressed from SPS to CPS. Overall, three-fourths of FBTCS had a preceding CPS, characterized mainly by oral or manual automatisms. The remaining 5 phases were used to describe the GTCS itself. The onset of head or eye version, or vocalization, noted on 84% seizures, marked the generalization (ie, focal to bilateral spread) of FBTCS (Phase 3). It could progress to asymmetric and irregular jerking (Phase 4), followed by a generalized tonic phase (Phase 5), and a tremulousness phase (Phase 6), when irregular, frequent jerking starts to interrupt the tonic phase. This interrupted tonic phase culminates in the generalized clonic phase, where the jerks are typically rhythmic and could be timed (Phase 7). They found that the mean duration of FBTCS was 62.2 s, and none lasted more than 2 min. Only 27% of seizures, with considerable duration variation, had all 5 GTCS phases. In current routine practice, some phases (eg, Phases 4 and 6) may not be precisely appreciable and are not clinically significant.
This study by Theodore et al was 1 of the first systematic, video-based studies to describe the clinical semiology and evolution of FBTCS. It provided a detailed framework for recognizing the transition from focal onset to bilateral motor involvement. These insights have since guided clinical diagnosis, seizure management, and presurgical evaluation. Let's evaluate the most salient contribution of this article in the 3 decades since its publication.
Seizure classification and terminology: The systematic dissection of FBTCS into 7 distinct phases replaced the earlier, less detailed triphasic description (preictal, tonic, clonic) by Gastaut and Broughton. Their taxonomy and findings provided a reproducible framework for future studies. By underscoring the focal onset and later bilateral spread, their work laid the empirical groundwork for the International League Against Epilepsy (ILAE) 2017 and 2025 shift from “secondarily generalized” to FBTCS.
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Additionally, a nearly thorough line from their work to the latest expanded seizure classification is the recommendation that seizures should be described in terms of their temporal semiological evolution rather than the initial single label. Differentiating tonic-clonic seizures in focal and generalized epilepsy: Despite their salience, distinguishing whether the onset of a bilateral tonic-clonic seizure is focal or generalized from history is often challenging. Given its diagnostic importance, this question continues to drive contemporary research.5,6 Theodore et al's methods strongly influenced later studies, and current evidence supports their findings that multiple focal signs, such as asymmetries of automatisms, clonic movements, spread of the tonic phase, and head version, are significantly more suggestive of FBTCS rather than a generalized onset.5–7 Presurgical evaluation in drug-resistant epilepsy (DRE): Semiology remains a critical building block of presurgical assessment. Theodore et al meticulously charted the evolution of seizures from focal signs and symptoms to impaired consciousness and subsequent motor phases. They informed that almost a quarter of seizures had auras, which are a highly localizing feature, before FBTCS. Versive movements and vocalization remain reliable semiological landmarks that herald the bilateral spread of FBTCS. Later studies expanded on their framework, defining additional lateralizing signs, such as the “Figure 4 sign” and asymmetric last clonic jerk, which now guide surgical planning.
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Antecedent phase and patient safety in FBTCS: The bilateral tonic-clonic phase of an FBTCS is a major cause of seizure-related morbidity. Theodore et al showed that almost all FBTCS have an antecedent phase in the form of intact or impaired consciousness, which, as we now know, is a graded rather than absolute phenomenon.
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This period can be a critical time for the patient to alert witnesses or reach safety. This knowledge and other subsequent studies now allow us to make personalized seizure action plans to mitigate seizure-related morbidities. Status epilepticus (SE) definition and management: Coined by Louis Calmeil in 1824, status epilepticus (SE) was long defined as near-continuous seizures “when coma and exhaustion are continuous between seizures.”
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After Meldrum's work in baboons demonstrated excitotoxic neuronal injury, a 30-min duration was first proposed as the operational threshold. However, it was the study by Theodore et al, along with others, that objectively quantified the typical duration of FBTCS. It proved instrumental in helping ILAE define the operational time point (t1) of SE when an FBTCS becomes an “abnormally prolonged seizure.”
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Their findings helped shift SE management paradigms, with AES endorsing t1 as the time point at which abortive seizure treatment should be initiated for FBTCS. Therefore, Theodore et al helped reduce SE treatment delay, standardize care, and lower morbidity and mortality. Management of prolonged seizures: Notably, no FBTCS in the Theodore et al study exceeded 2 min, supporting this as the upper limit of typical duration. Building on their work, experts now define FBTCS lasting beyond 2 min as “prolonged” seizures.
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This definition underpins the rapid and early seizure termination (REST) paradigm that promotes rapid abortive treatment to prevent FBTCS progression to SE, reduce morbidity, improve quality of life, and decrease healthcare utilization.
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The tonic phase and SUDEP risk: Some of Theodore et al's most insightful contributions are only now being appreciated. They qualitatively assessed that peak tonicity lasts approximately 20 s and starts to decrease in Phase 6, persisting for roughly a minute. We now know that the duration and persistence of tonic activity following bilateral spread are mechanistically linked to SUDEP risk through their impact on respiration and postictal recovery.13,14 Therefore, by virtue of being 1 of the first studies in humans to quantify tonic phase dynamics, their work has gained renewed relevance as ongoing research connects these motor patterns to ictal and postictal physiology and SUDEP risk.
It is easy to forget that many canonical facts about seizures and epilepsy were once unknown or uncertain and gradually clarified through painstaking observation and research. The study by Theodore et al exemplifies this evolution. It bridged the descriptive era of neurology with the modern, data-driven understanding of seizure evolution. Their meticulous dissection of FBTCS phases transformed visual observation into quantitative science. It continues to inform seizure and status epilepticus terminology and classification, presurgical evaluation, and safety counseling. Their work serves as a reminder that careful clinical observation, amplified by emerging technology, can transform epilepsy care. Thirty years later, its enduring relevance lies not only in what it revealed but also in how it taught us to look patiently, precisely, and with curiosity. These traits are needed now more than ever, in the age of AI, to continue advancing the field.
Footnotes
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
