Myoclonus epilepsy with ragged-red fibers
Nov. 06, 2023
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Laughter is a behavior that occurs in both emotional and nonemotional contexts. Emotional laughter occurs in the context of mirth (amusement), whereas nonemotional laughter is voluntary and used for social communication, usually in conversation. These two types of laughter are produced by two distinct brain networks. International classifications of epilepsy, seizures, and epilepsy syndromes have been updated in recent years. When laughter is the first feature in a focal seizure, the seizure is termed a “focal emotional seizure with laughing.” This seizure type provides unique insight into the neurobiology of laughter. In this article, the authors review the updated classification of this seizure type, associated etiologies (particularly hypothalamic hamartoma), clinical presentations, differential diagnoses, and current treatments. Newer, noninvasive surgical treatments for seizures due to hypothalamic hamartomas are also reviewed.
• Focal emotional seizures with laughing are characterized by unprovoked and stereotyped laughing or giggling that is present from seizure onset, with or without the accompanying emotion of mirth (amusement).
• The differential diagnosis for focal emotional seizures with laughing includes focal seizures in which laughing occurs during the evolution of the seizure (rather than at onset), focal motor seizures causing facial expression change or asymmetry, pseudobulbar affect laughter, gelastic cataplexy, gelastic syncope, and functional neurologic symptom disorder.
• Focal emotional seizures with laughing are classically associated with hypothalamic hamartomas but may also be secondary to structural pathology in the temporal or frontal lobes.
• When associated with hypothalamic hamartomas, focal emotional seizures with laughing are typically intractable to medical therapy and may be one of the early symptoms of the condition.
• The most effective treatment for focal emotional seizures with laughing associated with hypothalamic hamartoma involves removal, ablation, or disconnection of the hamartoma.
The possibility of sudden emotion as a manifestation of an epileptic seizure has been recognized since the end of the 19th century (70). These emotions were usually negative, and the emotion of fear was most often described. Seizures with laughing were first described by Trousseau (77). Gowers observed emotions "with a cheerful character" as part of a seizure (27). Daly and Mulder coined the term “gelastic epilepsy” from the Greek word gelos, meaning “laughter,” to emphasize the main feature of these seizures (14). Gascon and Lombroso subsequently suggested the following criteria for the diagnosis of "gelastic epilepsy": stereotyped recurrence; absence of external precipitants; concomitance of other manifestations generally accepted as epileptic; presence of interictal or ictal epileptiform discharges on EEG; and absence of conditions in which pathologic laughter might occur (24).
In the updated classification of the epilepsies in 2017 (64), the International League Against Epilepsy (ILAE) limited epilepsy types to four: focal, generalized, combined generalized, and focal and unknown. This rendered the term “gelastic epilepsy” obsolete. In a subsequent operational definition of seizure types in 2017, the ILAE subsequently classified seizures with laughing as the first seizure feature as one type of focal (nonmotor) seizure, a focal emotional seizure—specifically a “focal emotional seizure with laughing” (allowing the synonym of “focal emotional gelastic seizure”) (18; 19). Depending on whether awareness is preserved, the seizure might be a focal aware emotional seizure with laughing or a focal impaired awareness emotional seizure with laughing. The application of the term “emotional” only requires the appearance of having an emotion (“affective manifestation”), not that the subjective emotion is present.
When used as a seizure term, “laughing (gelastic)” is defined as “bursts of laughter or giggling, usually without an appropriate affective tone.” Laughing can occur in a seizure but not as the initial feature. When it appears after another initial seizure feature, it is not used to diagnose the seizure type but is instead a “descriptive” seizure term—a term applied to describe features seen in the seizure evolution. A patient with a seizure commencing with a fast heart rate, and laughing later, would now be considered to have a focal autonomic seizure.
The distinction of whether a symptom or sign is the first feature of a seizure (and used to define the seizure type) or a later feature is important. The first feature can more precisely reflect the location of the seizure onset in the brain, whereas later features reflect seizure spread. Past literature on “gelastic seizures” did not make this distinction, and the term was previously used to encompass seizures with laughing at any time during the seizure. Therefore, the term “focal seizure with laughing” is used when referring to data from past literature on “gelastic seizures” prior to 2017, as the literature did not define whether laughing was present from seizure onset (a focal emotional seizure with laughing) or at any time in the seizure evolution. In the future, new literature may provide more precise information on the entities that result in laughing from clinical seizure onset.
It has previously been debated whether entities with focal seizures with laughing compose an epilepsy syndrome. Arguments against this were raised because the syndrome would largely be defined based on a single seizure symptom (41). In 2022, the ILAE published a classification and definition of epilepsy syndromes, confirming that a syndrome requires a cluster of clinical and EEG features that are often supported by specific etiological findings (80). The etiology-specific epilepsy syndrome “gelastic seizures with hypothalamic hamartoma” was officially recognized (83).
The clinical entities associated with focal seizures with laughing have primarily been described in historical case series and case reports. These reports may have ascertainment bias as they primarily arise from tertiary or epilepsy surgery centers. They do not distinguish whether laughing is at seizure onset or during seizure evolution. Data from the older studies can reflect limited detection of certain types of hypothalamic hamartomas or other structural brain abnormalities due to lower resolution MRI. Some studies can reflect findings from patients who developed a secondary epileptic encephalopathy and who have wider cortical and subcortical abnormalities and epilepsy comorbidities, rather than the primary epilepsy etiology. Older studies can reflect perspectives on the localization values of certain investigations or surgical techniques that have been superseded as imaging and surgical techniques have advanced. This article presents a review of the past literature, bearing in mind these limitations.
Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.