Pathological laugher and crying in motor neuron diseases: a matter of bulbar and neurobehavioral involvement with sex imbalance.

Background: Emotional lability (EL), also known as pathological laughter and crying, is a common but understudied symptom in motor neuron diseases (MND): amyotrophic lateral sclerosis and primary lateral sclerosis. This study aimed to investigate the prevalence of EL in MND and to explore the independent frequency components of laughter and crying in relation to motor, cognitive, neuropsychiatric, and neuroimaging factors.

Methods: A total of 198 incident MND patients were enrolled. The Centre of Neurological Study-Lability Scale was used to measure EL. Associations between EL and motor function, mood, neuropsychological variables, and structural MRI were examined, with cortical thinning measured on a subset of 48 patients.

Results: EL was identified in 36% of patients showing more severe motor functional disabilities, heightened depressive and anxiety symptoms and behavioral changes than those without EL. Women exhibited more severe EL and altered mood with frequent crying episodes than men. EL was strongly correlated with bulbar involvement. Crying episodes were associated with mood disorders, while laughter correlated with disinhibition and emotional regulation difficulties. EL had a specific association with the thinning of frontal regions, including the right pars orbitalis, which was also linked to altered emotional and behavioral regulation.

Conclusion: These findings underscore the role of corticobulbar and frontal pathways in EL pathophysiology. The study highlights the distinct mechanisms underlying pathological crying and laughter and their independency from general cognitive decline. It emphasizes the need for clinicians to recognize EL as an independent symptom, necessitating targeted management strategies to improve patient outcomes and support caregivers.