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Pathological laughter heralding a neurological deficit was first described by Ferré in 1903 as Fou rire prodromique. 1 2 We present a patient with prodromal pathological laughter and a right pontine infarction in the territory of the paramedian branch of the basilar artery. These are the first clinicoanatomical correlates integrating MRI lesion mapping with immunohistochemical studies for a serotoninergic specific enzyme of human brain stems.
A right handed 61 year old woman was admitted to hospital for a left hemiplegia. She presented with a history of diabetes, high blood pressure, and an old myocardial infarct. She had experienced spells of uncontrolled and inappropriate laughter during the night and the subsequent morning. At noon, her left side became paralysed. On admission, she was alert, attentive, and had a right sixth nerve palsy and a left hemiparesis that included the face. There was a left Babinski's sign. Neuropsychological testing disclosed a mild attentional deficit and a decreased phonological fluency. There was no lability of affect and no inappropriate crying. She recognised the laughter as abnormal. The spells were usually totally inappropriate and without any associated mirth. Sometimes they could be triggered by an unfamiliar situation, such as talking to the physical therapist. To measure pathological laughter with a validated scale, we used the pathological laughter and crying scale3 (PLCS) and her score was 15/27. A psychiatric evaluation was negative for manic disorder. Brain MRI disclosed an infarction in the right ventral pons without other focal lesion (figure, A). An EEG was normal. Spells of pathological laughter continued for a week then gradually resolved. After 2 weeks, the PLCS score was 2/27.
The limits of the lesion in the right ventral pons were overlayed on a section of a corresponding level taken from a series of immunohistochemical preparations used to map the entire human serotoninergic system.4 The main tracts and structures involved are shown in the figure (B, C).
Pathological laughter is an exaggerated, uncontrollable, and inappropriate laughter usually unrelated to a true emotion or a congruent mood. It is found in gelastic epilepsy (ictal pathological laughter), associated with lesions in the hypothalamus, anterior cingulate, or basal temporal lobe. Non-ictal pathological laughter is often associated with pathological crying and usually seen with bilateral, multiple cerebral lesions as a component of pseudobulbar palsy. However, non-ictal pathological laughter can occur in patients with unilateral lesion, and without pseudobulbar palsy. In these cases, imaging studies show lesions in the lenticulocapsular, thalamocapsular, and pontine base areas. Recognised causes include strokes or tumours. Non-ictal pathological laughter may also occur in the cortical and subcortical territory of large arteries, usually the middle cerebral artery, and, in these cases, it may be very difficult to distinguish from a gelastic seizure. In prodromal pathological laughter, the locations of the lesions and the pathologies are similar, and include mainly strokes and tumours. The pathophysiology of pathological laughter was discussed by Wilson5 in 1924, who suggested a motor release phenomenon. He pointed to an imbalance between voluntary motor pathways in the corticobulbar tract and involuntary pathways from limbic circuits to the facial nerve nucleus, the nucleus ambiguous, and anterior horn cells that subserve the phrenic nerve (faciorespiratory coordination of laughter). Another hypothesis involves serotoninergic neurotransmission, originating in the pontine serotoninergic raphe nuclei. Pharmacological evidence also shows that serotonin reuptake inhibitors may improve a patient's laughter.3
The raphe nuclei are divided in a rostral and a caudal group.4 Nuclei of the rostral group, in the midbrain and rostral pons, project rostrally to the forebrain. They are separated by a gap from the nuclei of the caudal group extending from the caudal pons to the end of the medulla. These nuclei project to the entire brainstem and spinal cord. Serotoninergic neurons of the caudal pons lying in the ventral tegmentum belong to the raphe nucleus magnus (RMg), and are at the origin of a widespread innervation of brainstem structures.
Our patient presented with prodromal pathological laughter heralding an infarction in the right ventral pons, in the territory of the paramedian branch of the basilar artery. She had no other signs of pseudobulbar palsy. It is unlikely that pathological laughter in our case was due to seizures (gelastic epilepsy) because of the long duration of the episodes, the absence of altered sensorium, automatisms, or EEG abnormalities, and the location of the stroke. The unique and circumscribed lesion of the corticospinal and corticobulbar tracts at the level of the ventral pons, saving the medial lemniscus, may seem to favour Wilson's hypothesis; however, the posterior angle of the lesion along the midline also involves the serotoninergic RMg (figure, A-C). An involvement of this serotoninergic nucleus is further supported by the temporal characteristics of pathological laughter, occuring in transient bursts before the development of motor signs in the limbs. We therefore conjecture that pathological laughter was prodromal because ischaemia began at the distal end of the vascular territory of the paramedian branch of basilar artery involving the RMg first. Both hypotheses could be reconciled if we assume that emotional motor pathways can be modulated by serotononergic neurotransmission from the raphe nuclei. A small lesion involving convergence of both emotional motor pathways and raphe nuclei would also explain the location of prodromal pathological laughter in the pons.