Involuntary emotional expression disorder (IEED), a distressing and potentially debilitating condition characterized by uncontrollable episodes of laughing and/or crying, causes extensive social and occupational dysfunction amongst patients. However, despite affecting more than one million people worldwide, IEED is often overlooked or misdiagnosed, and current treatments are compromised by uncertain efficacy. In this supplement we review the epidemiology and pathophysiology of IEED, and discuss new pharmacologic interventions which may afford opportunities for symptom control amongst IEED sufferers.

Although the uncontrollable episodes of emotion which characterize IEED were first described more than a century ago, a bewildering profusion of terminology has since confused and hampered the efforts of physicians to recognize and treat this condition. In the first article, John E. Duda, MD, examines the history of IEED in the medical literature, and evaluates the prevalence of the condition amongst patients in whom emotional or affective motor control has become dysregulated, either as a result of brain damage from neurological disease or as a result of brain injury.

The syndrome now known as involuntary emotional expression disorder (IEED) is a condition characterized by uncontrollable episodes of laughing and/or crying. It has been known for more than a century, but confusing and conflicting terminology may have hampered the progress of physicians in recognizing this condition. IEED is associated with various neurological disorders and neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and neurological injuries such as stroke and traumatic brain injury. It is hoped that better defined terminology for IEED may help in the future diagnosis of this debilitating condition, the establishment of accurate prevalence rates for IEED in the varying underlying conditions, and also in removing blame and stigma from sufferers by providing reassurance about the nature of their condition.

Involuntary emotional expression disorder (IEED) is a syndrome in which emotional or affective motor control becomes dysregulated as a result of brain damage from neurological disease or as a result of brain injury. A debilitating disorder with persistent symptoms, IEED has a significant impact upon the lives of patients and caregivers, but is often overlooked or misdiagnosed. IEED is a clinically well-defined disorder, and specific criteria may be used when making a diagnosis. It must be distinguished from depression or other psychological and neurological conditions. Several assessment scales have been validated for use in IEED, in order to evaluate the baseline severity and to track the course of the disorder and response to treatment.

Extensive clinical experience and research suggest that a cortico-limbic-subcortico-thalamic-ponto-cerebellar network plays a significant role in the expression of human emotions. This network includes specific cerebral, cerebellar, and brainstem areas and their multiple projections/pathways, with activity modulated through serotonergic, dopaminergic, glutamatergic, and possibly sigma receptor neurotransmitter systems. Disruptions of regulatory and inhibitory mechanisms in the structure and function of this network likely constitute a pathophysiological basis for the crying and laughing episodes characteristic of involuntary emotional expression disorder. Pharmacologic interventions targeting the neurochemical modulators of the emotional expression systems may afford opportunities for symptom control among persons affected by this disorder.

Patients with involuntary emotional expression disorder (IEED) have impaired social and occupational functioning and there is currently no Food and Drug Administration-approved treatment. Treatment options include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), dopaminergic agents, and a combination of dextromethorphan and quinidine. Studies of monaminergic agents have typically been small and executed in single-center settings. Assessment measures generally show significant symptomatic improvements, including a reduction in the number of laughing or crying episodes and improvements in patients' clinical condition. The tolerability profiles of these agents are well defined, and include dizziness, tachycardia, and QTc prolongation (TCAs), and sleep and sexual disturbances (SSRIs). The combination of dextromethorphan and quinidine has also been assessed in two large multicenter studies in patients with amyotrophic lateral sclerosis and multiple sclerosis. Compared with placebo and either agent alone, there were significant improvements in symptoms, quality of life, and relationships. The most common side effects were dizziness and nausea, and potential drug interactions with quinidine should also be considered. Choice of treatment should be evidence-based, taking into account both efficacy and tolerability.