Gelastic Seizures: No Laughing Matter

We encounter seizures commonly in the Emergency Department.  While they can be dramatic and devastating, we have learned to become comfortable with the wide variety that may present in children.  From the simple febrile seizure to the complex seizure, we know how to stabilize and how to evaluate.  While fortunately most seizure activity is short lived, we also know that status epilepticus can be difficult to manage, and persistent seizures should make us consider specific etiologies (ex. Vitamin B6 Deficiency).  Being comfortable evaluating and managing pediatric seizures also requires a lot of humility.  The vast spectrum of seizure presentations, especially subtle or focal seizures, makes it challenging to know all there is to know about seizures.  Let’s take a moment to consider one unique and concerning seizure that might seem silly, but is really not a laughing matter – Gelastic Seizures:

Gelastic Seizures: Basics

• Gelastic Seizures = epileptic manifestations characterized by stereotypical laughing. [Nicotera, 2024;  Bacus, 2023]
  • The laughing often described as being unmotivated or disproportionate to the emotional context.
  • Pathologic uncontrollable laughing without mirth (lacking joy). 
    • Although… some gelastic seizures may be associated with appropriate mirth. [Nicotera, 2024]
    • Emotional laughter can occur if seizure is in Temporal lobe. 
    • Mirthless laughter occurs if origin of seizure is the Frontal area.
  • Can even become status gelasticus. [Nicotera, 2024]

• Can have associated autonomic features also: [Bacus, 2023; Striano, 2017]
  • Flushing
  • Pupillary dilation
  • Tachycardia
  • Altered respirations

• Rare seizure type
  • ~1% of all epilepsies
  • Likely under-reported

• Ages:
  • Typically seen in children ages 4 to 10 years. [Bacus, 2023]
  • Cases as young as 4 months have been described. [Nicotera, 2024]

• Often associated with other conditions:
  • Other seizure types 
    • Seen in ~75% with hypothalamic hamartomas [Striano, 2017]
    • Evolution of seizures toward generalized Lennox-Gastaut-like epilepsy, atypical absences, atonic, tonic-clonic. [Striano, 2017]
  • Precocious puberty
  • Psychiatric disorders
  • Cognitive difficulties (ex, autism spectrum disorders)

• May seem simple but become complicated.
  • Are difficult to control with medications
  • Can evolve toward generalized epileptic encephalopathy with congnitive regression. [Striano, 2017]
  • Early treatment is critical to help reduce risk for worsening seizures and neuropsychological and behavioral problems. [Striano, 2017]

Gelastic Seizures: Etiologies 

• Heterogenous etiologies have been related to gelastic seizures:
  • Brain abnormalities (ex. Hypothalamic Hamartomas)
  • Genetic conditions

• Hypothalamic Hamartomas are the primary cause of gelastic seizures.
  • Hypothalamic Hamartomas (HH):
    • Rare, congenital, tumor-like mass
    • Malformations composed of heterotopic neurons and glia surrounding the hypothalamus. [Guo, 2023]
    • Associated with seizures and/or precocious puberty
    • The relationship is such that gelastic seizures are thought of as a marker for hypothalamic hamartomas, although not pathognomonic. [Striano, 2017]
  • Some use the term = Gelastic Epilepsy-HH Syndrome

• Other etiologies include: [Nicotera, 2024]
  • Tubers from tuberous sclerosis
  • Pituitary tumors, gliomas, meningiomas
  • Cortical malformations
  • Atrophy of the thalamus, leukomalacia
  • Aneurysms of the basilar artery (extremely rare)
  • Genetic Disorders (ex, Niemann Pick C Disease)

Gelastic Seizure: Treatment

• Treatment is difficult. [Nicotera, 2024]
• Carbamazepine is most often used, but patients often develop drug-resistant epilepsy. [Nicotera, 2024]
  • New anti-seizure medications have been promising.
  • Cannabidiol and/or Perampanel have been used in drug-resistant epilepsies.
  • Interestingly, Levetiracetam may exacerbate the condition. [Nicotera, 2024]
• Medication is more efficacious for those patients without structural abnormalities.
  • ~25% without brain lesions will have a more benign clinical course and won’t develop epileptic encephalopathy.
• Early Surgical resection or Gamma-knife ablation of Hypothalamic Hamartomas is the most effective treatment for gelastic epilepsy-HH syndrome. [Nicotera, 2024]

Moral of the Morsel

• Seizures can be subtle! While many will be obvious, remain vigilant for the repetitive behavior that may be a subtle seizure.
• Laughter is not always healing. While it may be true that “Laughter is the best Medicine,” laughter may also be a seizure.
• Act now to prevent worsening problems. If you are concerned for a Gelastic Seizure, expedite actions to evaluate for Hypothalamic Hamartomas and know that the “simple laughter” can evolve into encephalopathy (which is no laughing matter.).

References:

Nicotera AG, Spoto G, Amore G, Butera A, Di Rosa G. Comprehensive review of status gelasticus: Diagnostic challenges and therapeutic insights. Epilepsy Behav. 2024 Feb 29;153:109719. doi: 10.1016/j.yebeh.2024.109719. Epub ahead of print. PMID: 38428176.

Patricia Bacus I, Haghighat Z, Raslau F. Laughter isn’t always the best medicine, sometimes it’s one of the symptoms. Epilepsy Behav Rep. 2023 Jun 6;23:100609. doi: 10.1016/j.ebr.2023.100609. PMID: 37359085; PMCID: PMC10285542.

Guo ZH, Zhang JG, Shao XQ, Hu WH, Sang L, Zheng Z, Zhang C, Wang X, Li CD, Mo JJ, Zhang K. Neural network mapping of gelastic behavior in children with hypothalamus hamartoma. World J Pediatr. 2023 Nov 8. doi: 10.1007/s12519-023-00763-1. Epub ahead of print. PMID: 37938453.

Striano S, Striano P. Clinical features and evolution of the gelastic seizures-hypothalamic hamartoma syndrome. Epilepsia. 2017 Jun;58 Suppl 2:12-15. doi: 10.1111/epi.13753. PMID: 28591476.