Use of Valproate for Acute-Onset Prolonged Pathological Laughter

Dear Editor,

Pathological laughter is a condition defined by uncontrollable episodes of laughter, which may or may not be mood and stimulus congruent.[1] Poststroke pathological laughter can occur with lesions of descending corticobulbar pathways most commonly at the level of internal capsule, cerebral peduncles, and the basis pontis.[2] Here, we present a case of pontine stroke, where the patient developed acute-onset persistent pathological laughter, which lasted for more than 4 h and was aborted by intravenous valproate therapy. A 71-year-old male presented with acute-onset uncontrollable laughter, which had been persistent for 3–4 h and occurred in episodes lasting few seconds. Patient was aware of his surroundings and did not have any automatisms, eye blinking, facial twitching, or any other form of seizure-like activity. He reported feeling happy from inside and compared the feeling similar to being tickled, although he did not feel any tickling sensation. He had suffered from left pontine stroke, which caused right ataxic hemiparesis without facial involvement, around 5 days back and was on dual antiplatelet therapy for the same. He was hypertensive, and his magnetic resonance angiography (MRA) revealed poor signal from the cavernous and supraclinoid segments of the left internal carotid artery (ICA) and middle cerebral artery (MCA) and complete loss of signal from anterior cerebral artery (ACA) and its branches [Figure 1]. Rest of his workup for stroke did not reveal any significant abnormality.

Figure 1.

(a) MRI of the brain showing diffusion restriction in the left pontine area. (b) Fluid-attenuated inversion recovery image showing hyperintensity in the left pontine area. (c) MR angiography image showing complete loss of signal from ACA and its branches. (d) MR angiography images showing poor signal from the cavernous and supraclinoid segments of the left ICA and MCA. MR: magnetic resonance, MRI: magnetic resonance imaging, ICA: Internal carotid artery, MCA: Middle cerebral artery

In view of acute onset of uncontrollable laughter, initial diagnosis of gelastic seizures was made and patient was given 1 g of intravenous valproate loading dose, which aborted his laughter attack, and patient did not have further such episodes for the next 24 h. His magnetic resonance imaging was repeated, but did not reveal any findings such as hypothalamic, frontal, or temporal lesion, which could suggest gelastic seizures or any other etiology apart from pathological laughter secondary to pontine stroke. His electroencephalogram did not reveal any interictal epileptiform discharges. He was continued on valproate, but reported intermittent episodes of uncontrolled laughter, which occurred for a few seconds. He was then started on escitalopram, and valproate was gradually tapered off. Patient is currently doing well on escitalopram therapy.

The most widely acknowledged classification of symptomatic laughter by Poeck[3] differentiates symptomatic laughter into i) epileptic seizures (gelastic seizures), ii) fou rire prodromique, and iii) motor neuron disease, vascular pseudobulbar palsy, and extrapyramidal motor disorders.[3] Gelastic seizures are characterized by the presence of sudden laughter attacks out of social context without any particular emotion like joy or happiness. Although hypothalamic hamartomas are the most common cause in children, gelastic seizures in adults are usually associated with temporal or frontal foci.[4] Fou rire prodromique is a rare condition characterized by unmotivated, inappropriate laughter occurring as the first symptom of cerebral ischemia. The laughter is utterly uncontrollable and may be followed by giggling, which is then replaced by typical symptoms of stroke, such as hemiparesis or aphasia.[5] Pathological laughter may occur secondary to vascular pseudobulbar palsy, motor neuron disease, or extrapyramidal motor disorders. Various studies have reported development of pathological laughter following pontine stroke due to the involvement of cortico-ponto-cerebellar pathways, which form the neurophysiological substrate for laughter.[6] Researchers have proposed the existence of pontine “faciorespiratory center,” which is involved in the pathogenesis of pathological laughter. Drugs commonly used in the treatment of poststroke pathological laughter include selective serotonin reuptake inhibitors, tricyclic antidepressants, other antidepressants, levodopa and dextromethorphan/quinidine combination.[2] Lamotrigine has also been found to be effective in poststroke pathological laughter.[7] Our patient presented with acute-onset prolonged episode of laughter, which was treated with valproate in view of initial diagnosis of gelastic seizures. Further clinical course and workup revealed it to be more consistent with poststroke pathological laughter. Literature search did not reveal any previous use of valproate for pathological laughter, although its use in gelastic seizures is common. The efficacy of antiepileptic drugs like lamotrigine and valproate may indicate possible ictal phenomenon in the pathophysiology of pathological laughter. It needs to be noted, however, that intravenous valproate may itself cause pathological laughter in a few cases.[8]

Poststroke pathological laughter is common and multiple treatment options are available for the same. Antiepileptics such as valproate may be useful in acute prolonged attacks and need to be further evaluated.

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Informed written consent was obtained from the patient for writing and publication of the clinical information and image.

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Conflicts of interest

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