CNS Spectr. 2007;12:4(Suppl 5):6-10.
An expert review of clinical challenges in psychiatry
This supplement is supported by an educational grant from Avanir Pharmaceuticals.
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Credit Designation Statement
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 4.0 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with their participation in the activity.
First described by Charles Darwin in 1872, Involuntary Emotional Expression Disorder (IEED) continues to be under-recognized and misdiagnosed. It can be extremely debilitating to patients and their caregivers/families, and its symptoms are often mistaken for mood disorders.
This educational program will enable participants to better understand and identify the disorder and the importance of treatment. The course will provide an overview of the condition and additional information on diagnosis, suggested pathophysiology, approaches to treatment, gaps in current therapies, and the promise of future therapies improving patient care.
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.
Johns Hopkins Course Director/Program Co-Chair: Peter V. Rabins, MD, MPH
Program Co-Chair: Jeffrey L. Cummings, MD
This course is intended for neurologists, psychiatrists, geriatricians, physiatrists, medical directors, and primary care physicians. There are no prerequisites for this course.
At the conclusion of this activity, participants should be able to:
• Recognize involuntary emotional expressive disorder (IEED) as a debilitating disorder that is frequently overlooked or misdiagnosed.
• Identify the diseases that are most commonly associated with IEED.
• Describe the clinical expression of IEED and the impact of this condition on patients and caregivers.
• Discuss current theories regarding the pathophysiology of IEED.
• Describe how to differentiate IEED from mood disorders.
• Discuss current and emerging management strategies.
Notice of Unlabeled/Unapproved Uses
The following faculty members have disclosed that their articles will reference unlabeled/unapproved use of drugs or products:
Dr. Brooks: amantadine, citalopram, desipramine, dextromethorphan, fluoxetine, fluvoxamine, memantine, imipramine, paroxetine, and sertraline.
Dr. Rabins: amantadine, amitriptyline, citalopram, dextromethorphan, fluoxetine, guanidine, imipramine, L-dopa, nomifensine, nortriptyline, paroxetine, quinidine, and sertraline.
To Receive Credit for this Activity
This educational activity is expected to require 4.0 hours to complete.
To receive CME credit, participants should visit www.hopkinscme.org/courses/new_course.cgi?tid=396 to compete the program post-test and evaluation. A score of 70% is necessary to successfully pass the post-test. Upon receiving a passing score, participants may print out their certificates immediately.
Release Date: April 1, 2007
Expiration Date: April 30, 2008
Faculty Affiliations and Disclosures
Dr. Duda is co-director of the Parkinson’s Disease Research, Education and Clinical Center (PADRECC) of the Philadelphia VA Medical Center, and assistant professor of neurology at the University of Pennsylvania.
Disclosures: Dr. Duda has received research support from the National Parkinson’s Foundation, the Michael J. Fox Foundation, the Department of Veterans’ Affairs, and the National Institutes of Health; has served as a consultant to Avanir and Boehringer-Ingelheim, and is on the speaker’s bureau for Avanir. No faculty member has received compensation from Avanir for the preparation of this article.
Submitted for publication: January 15, 2007; Accepted: March 16, 2007.
Please direct all correspondence to: John Duda, MD, Parkinson’s Disease Research, Education and Clinical Center, Philadelphia VA Medical Center, Philadelphia, PA 19104. Tel: 215-823-5934; Fax: 215-823-5818; Email: email@example.com.
• Involuntary emotional expression disorder (IEED) has been in existence for a long time, under different terminologies.
• IEED is under-recognized and under-diagnosed.
• The use of the IEED nomenclature may help to clarify and demystify the disease amongst both patients and physicians.
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.
It is only within the last few decades that the studies of neurology and psychology have begun to shed light on the phenomenon of pathological laughing and/or crying. While instances of these uncontrollable and disproportionate emotional outbursts have been documented for more than a century, confusing and conflicting terminology may have hampered the progress of physicians in recognizing the symptoms as part of a more widespread disorder linked to brain injuries, or disease-associated brain abnormalities. This article will review the terminology surrounding this condition and the recent introduction of new, more defined nomenclature, to describe it. In addition, the prevalence of the syndrome will be examined, and the necessity for more accurate recognition and diagnosis of the disorder in order to minimize the psychosocial impact on both sufferers and caregivers will be discussed.
Laughter, weeping, the interrelationship between the two, and how we control them have fascinated philosophers for millennia and neurologists for over a century. More than 2,000 years ago, Hippocrates noted that joy, laughter, sorrow, lamentation, and other emotions and emotional expressions were all entirely regulated by the brain.1
Emotions are essential to rational human behavior, permitting development of optimally adaptive responses to both personal and social events.2
Occasionally, however, control over emotions can be lost or disrupted, leading to reduced psychological well-being and social and occupational dysfunction.3,4
A dissociation between emotional facial expressions and those under voluntary control was suggested decades ago, and the idea that diseases which affect the brain can alter the output of emotion is not a new idea.5
Indeed, as far back as 1837 the first cases of dysregulated emotional affect (involuntary laughter and crying) in the context of abnormal brain pathology were being described in medical literature.6
Such emotional outbursts were quickly recognized to be a result of neurological damage, with Charles Darwin writing that “...certain brain diseases, such as hemiplegia, brain wasting and senile decay, have a special tendency to induce weeping.”7
Some years later, Brissaud8
published several case reports on pathological laughter and crying in patients with hemiplegia. In addition, he postulated the existence of a thalamic center for laughter regulation, and suggested that spasmodic laughter and crying were due to lesions of the anterior internal capsule or irritation of the corticobulbar tract. In 1903, Charles Féré, a French neurologist, introduced the term “fou rire prodromique” to describe pathological laughter heralding an apoplectic event,9
while in 1905, Giannuli10
described a patient forced to walk with his eyes glued to the ground, since meeting the gaze of another person precipitated compulsory laughter, sometimes lasting for several minutes. In 1904, Weisenberg11
described the first case series of pseudobulbar palsy patients in the American literature and stated the following:
Impulsive laughter and crying are......entirely beyond the control of the patient, coming on at any time, and may be brought on by the slightest irritation, or may occur without it. In some cases, impulsive laughter or crying is present alone, though it has seemed to me that crying is more often present alone. Crying may terminate in laughing or vice versa.
However, it was not until 1924 when Wilson12
penned the first comprehensive discussion of the syndrome that all of the core features were described. He defined pathological laughing and crying as “a sequel to and consequence of a recognizable cerebral lesion or lesions in which attacks of involuntary, irresistible laughing or crying, or both, have come to the foreground of the clinical picture.” In the same paper, he described the association of these emotional outbursts with both focal and diffuse brain pathology across widely distributed networks. In addition to distinguishing pathological laughter and crying from other neurological diseases such as depression, Wilson also noted that patients’ emotional displays were often disproportionate to the evoking stimulus, and usually inappropriate to the context in which they occurred. In one case, a patient was reported to have burst into uncontrollable weeping upon reading a report of the death of a complete stranger, while in another often-quoted example, a patient was noted to have laughed heartily at news reported from the Great War—and the more serious and anxious the news, the more he laughed.12
Cause and Affect
The specific pathophysiology involved in this condition is still under investigation. Wilson’s studies into disorders involving pathological laughing and crying led him to propose the “disinhibition” or “release phenomenon” hypothesis.12
This hypothesis postulates an upper brainstem center capable of coordinating the faciorespiratory functions associated with laughing and crying. Loss of voluntary, cortical inhibition (ie, disinhibition) of this center would release lower bulbar nuclei from higher control and result in affective displays dissociated from the underlying emotion. Indeed, until very recently, this hypothesis stood unchallenged as the pathophysiology of uncontrollable laughter and crying. However, Wilson’s hypothesis does not adequately address some of the more puzzling manifestations of the disorder, such as why patients have been noted to both laugh and cry in response to the same stimulus, and why the voluntary control of the faciorespiratory functions remains otherwise intact. Such questions have led to a more recent hypothesis which postulated the involvement of the cerebellum in the emotional dysregulation, and proposed the idea of a “disconnect” between perceived and displayed emotion.13
Whatever the pathophysiological causes of the condition, it is obvious that IEED has been recognized and discussed for at least 170 years, albeit under different names.
Previous Terminology for IEED
Multiple terms have been used to describe conditions that alter affective motor output (Table).14
The use of names such as pathological laughing and crying (PLC), emotional or affective lability, emotional incontinence, and pseudobulbar affect (PBA) has, however, been inconsistent and may have hampered efforts to accurately identify and treat patients. Terms have sometimes been used to denote a specific or distinct condition, and at other times have been used as synonyms.15,16
One researcher working in the field has even described the terminology used to describe these conditions as a “semantic minefield”.16
Recently, in an attempt to alleviate this confusion, the term involuntary emotional expression disorder (IEED) was introduced as an umbrella term which includes all of these terminologies, and the respective subtle differences among the conditions that they traditionally describe.14
In 1924, Wilson was the first to give a specific name (pathological crying and/or laughing) to disorders of emotional affective expression.12
He defined the syndrome as “exaggerated, forced, involuntary, uncontrollable laughing or weeping”. PLC has since been variously described as crying or laughing that is incongruous to the eliciting stimulus,16,17
or as laughing or crying that is out of proportion to any provocation.12,18-20
The term emotional lability entered the literature almost 100 years ago, initially associated with descriptions of mania, and latterly with mental abnormalities due to chemical abuse.21,22
However, it was quickly adopted as a suitable name for the emotional symptoms seen in patients following traumatic brain injury (TBI)23
or in those displaying emotional traits as part of the condition of pseudobulbar palsy.24
A very similar name, affective lability, came in to use at around the same time, and was used interchangeably with emotional lability by many researchers.24-27
Another designation, emotional incontinence, was used briefly around the 1980s, although recently it has not been widely utilized, being deemed derogatory to patients.28-30
The term PBA was introduced because of the prevalence of pathological laughter and crying in pseudobulbar palsy, a condition in which symptoms such as dysathria and dysphagia are caused by interruption of cortical control of brainstem (bulbar) nuclei.31
Unfortunately, PBA quickly became another term with multiple definitions, being alternatively defined as either mood-incongruent, or mood-congruent but proportionally excessive to the circumstances.32-34
Other definitions are more inclusive and have identified PBA with affective and emotional lability.35
Clearly, definitive terminology for this disorder was required, in order to assist physicians in recognition, diagnosis, and management. A consensus has therefore been reached amongst several researchers in the field of neuropsychiatry, that the name IEED could be used as an umbrella term for all the conditions described above.14
Encompassing involuntary episodes of laughing, crying, or related emotional displays, with the primary manifestation as the physical expression of emotions unrelated or incongruent to the underlying mood, the terminology of IEED is easy to understand for patients and caregivers, and removes blame for the condition from the sufferer.
Prevalence of IEED
IEED has been observed in association with a wide range of neurological conditions, including amyotrophic lateral sclerosis (ALS), stroke, dementias such as Alzheimer’s disease, multiple sclerosis, TBI, and Parkinson’s disease.3,14,36
It is notable that despite variations in the underlying pathology between patients, the presentation of IEED is remarkably consistent and similar, and the disorder is always associated with structural brain damage.12,35
However, the number of patients who present with symptoms of IEED is extremely variable between each neurological group, and even sometimes within a group. It is thought that this variability is at least partially due to the different criteria applied to assess patients in different studies, which has varied from single questions regarding the propensity to laugh or cry uncontrollably to a reliance on current rating scales that have not necessarily been validated in the underlying condition in question. Therefore the true prevalence of IEED, as defined by current diagnostic criteria is difficult to ascertain, and only approximate minimum and maximum values can be estimated for most disease conditions (Figure).36-43
IEED may present in as many as 60% of ALS patients, although the use of more stringent diagnostic criteria have led some researchers to postulate a level as low as 2%.37,38
In a study by Gallagher and colleagues,44
the incidence of IEED (defined as unprovoked episodes of emotion) was examined in patients whose motor neuron disease had initially presented prior to the age of 45 years. A total of 73 patients were identified, with an average disease duration of 8.85 years, and ~50% (n=36) demonstrated episodes of IEED. Twenty of these patients displayed mixed laughter and crying, nine had crying alone, and seven had laughter alone.
IEED is also seen in a significant number of patients with dementias, including Alzheimer’s disease, vascular dementia, and frontotemporal dementia. In a case study series, the prevalence and pathophysiologic correlates of IEED in patients with Alzheimer’s disease was examined.36
In this series, IEED was defined as the presence of sudden episodes of laughter or crying in either the absence of a mood disorder, or the presence of a non-congruent mood state, and was distinguished from emotional lability, which was defined as the presence of sudden episodes of laughing or crying in the presence of a congruent mood state. Of the 103 patients evaluated, 40 (39%) showed disorders of pathological affect, which the authors defined as either emotional lability (21 patients) or pathological laughing and crying (19 patients).36
In studies of multiple sclerosis, IEED has been estimated to affect ~10% of patients, although estimates range from 7% to 29%.39 In a study of 152 consecutive patients, 15 (10%) were found to have IEED, which was defined as pathologic laughter and crying, and distinguished from emotional lability on the basis of clearly inappropriate, rather than simply exaggerated, emotional expression. This suggests that by the more current definition of IEED (which includes exaggerated emotional responses) the incidence in multiple sclerosis patients may be rather higher than 10%. IEED was found to occur in patients with long-standing disease and severe physical disability, cognitive dysfunction, and bilateral lesions, and was not observed to be associated with the occurrence of clinical exacerbations.16 Additionally, in contrast to many of the other underlying conditions, some reports suggest that patients with multiple sclerosis have a higher likelihood of displaying pathological laughter rather than pathological crying, although this remains to be statistically confirmed.45
IEED, often (though not exclusively) expressed as episodes of crying, is also frequently observed in patients following stroke or cerebrovascular disease (CVD), although calculations of its prevalence vary widely, with the lowest estimate being 6%,42
and the highest 52%.43
In one study, IEED (defined as frequent episodes of excessive crying or laughter, often without associated feelings of sadness or happiness, difficult to control and occurring in response to minor emotional triggers) was documented in 12 (18%) out of 66 consecutive inpatients with first stroke.46
In a second study, 148 patients with single, unilateral stroke were evaluated for IEED, defined as excessive or inappropriate laughter, crying, or both, compared with the patient’s pre-stroke state, as determined by interviews of patient and relatives. When both the patient and relatives agreed that the emotional outbursts had occurred on two or more occasions, the patients was considered to have IEED. In this patient group, 52% were deemed to have IEED.43
Limited literature is available on the frequency of IEED in patients with TBI, although one study suggested that 5% of patients may be affected.40
The authors of this study also noted that pathological laughter, alone or combined with crying, was more frequent than crying alone in these patients, raising some interesting questions about the precise relationship of the brain injury with emotional control. A more recent study suggests that at least 11% of patients develop IEED within a year after a TBI.41
Finally, a proportion of patients suffering from Parkinson’s disease also display symptoms of IEED, although again, detailed evaluations are lacking.47,48
However, irrespective of whether the highest or lowest estimates within each patient group are considered, it would appear that several million people worldwide suffer from the effects of IEED.
Recognition and Impact of IEED
While some debate remains regarding the name and exact limits of the defining clinical presentation of this disorder, it is clear that the syndrome is both under-recognized and under-treated. There is a need for better understanding by clinicians of the epidemiology of IEED and the best tools for diagnostic evaluation and clinical management. The symptoms of the disorder may prove to be functionally disabling; for example, the fear of developing uncontrollable bouts of laughter or crying may result in occupational or therapeutic difficulties, secondary phobias, or even cause the sufferer to avoid social contacts altogether.3,17,31
It is also important to remember that patient-caregiver education is an essential component of clinical management.3,31
Crying associated with IEED may be interpreted as depression, while both crying and laughter may be embarrassing and mood incongruent affect can be interpreted as bipolar disorder or psychosis.49
However, due to the fundamental differences between them, these conditions can be effectively differentiated by clinicians, enabling family members to recognize both the biologic nature of this condition, and the nature of the affective display and its discordance from mood. Such information lets patients and caregivers know that IEED is a recognizable and manageable condition, and reassures them that the symptoms from which they are suffering should not be a source of embarrassment or stigma.
While physicians have described and discussed the symptoms of IEED for at least 170 years, it remains an under-recognized condition and much is still unknown regarding the cause of these symptoms. The recent delineation of diagnostic criteria14 should engender definitive studies to determine the prevalence of IEED in the various underlying conditions, as well as clarify why some disease processes, such as multiple sclerosis, appear to be generally associated with pathological laughter while others, such as CVD, are associated predominantly with crying and yet others with both laughter and crying.
1. Hipocrates. On the Sacred Disease
. 4th Century BC.
2. Damasio AR. Descartes Error: Emotion, Reason and the Human Brain
. New York, NY: Putnam; 1994.
3. Dark FL, McGrath JJ, Ron MA. Pathological laughing and crying. Aust N Z J Psychiatry
4. Green RL, Bernat JL. Pathologic crying. In: Joseph AB, Young RR, eds. Movement disorders in Neurology and Neuropsychiatry
. Oxford: Blackwell Science; 1999.
5. Wild B, Rodden FA, Rapp A, et al. Humor and smiling: cortical regions selective for cognitive, affective, and volitional components. Neurology
6. Magnus A. Fall von Aufhebung des Willenseinflusses auf einige Hirnnerven. In: Müllers Archiv für Anatomie, Physiologie und wissenschaftliche Medicin., eds
7. Darwin C. The Expression of the Emotions in Man and Animals
. New York & London: D Appleton and Company; 1872.
8. Brissaud E. Lecons sur les Maladies Nerveuses
. Paris: Masson; 1895.
9. Féré C. Le fou rire prodromique. Rev Neurol (Paris)
10. Giannuli A. Ann Istit Psich Univ Roma. iv, 213
11. Weisenberg T. Report of three cases with necropsy and of three cases without necropsy. Univ Penn Medical Bull
12. Wilson SAK. Some problems in neurology. No. II. - Pathological laughing and crying. J Neurol Psychopathol
13. Parvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR. Pathological laughter and crying. A link to the cerebellum. Brain
14. Cummings JL, Arciniegas DB, Brooks BR, et al. Defining and diagnosing involuntary emotional expression disorder. CNS Spectr
15. Arciniegas DB, Lauterbach EC, Anderson KE, et al. The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Roundtable monograph supplement. CNS Spectr
16. Feinstein A, Feinstein K, Gray T, O’Connor P. Prevalence and neurobehavioral correlates of pathological laughing and crying in multiple sclerosis. Arch Neurol
17. Poeck K. Pathophysiology of emotional disorders associated with brain damage. In: Disorders of Emotion, eds
18. House A, Dennis M, Molyneux A, Warlow C, Hawton K. Emotionalism after stroke. BMJ
19. Keller R, Torta R, Lagget M, Crasto S, Bergamasco B. Psychiatric symptoms as late onset of Wilson’s disease: neuroradiological findings, clinical features and treatment. Ital J Neurol Sci
20. Robinson RG, Parikh RM, Lipsey JR, Starkstein SE, Price TR. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry
21. Soueif MI. Chronic cannabis takers: some temperamental characteristics. Drug Alcohol Depend
22. Hobi V, Ladewig D, Dubach UC, Miest P-C, Ehrensberger T. Analgesic abuse and personality characteristics. Int J Clin Pharmacol Biopharm
23. Koufen H, Dichgans J. [Similarities and differences after head injuries in children and adults (author’s transl)]. Med Klin
24. Lieberman A, Benson DF. Control of emotional expression in pseudobulbar palsy. A personal experience. Arch Neurol
25. Sloan RL, Brown KW, Pentland B. Fluoxetine as a treatment for emotional lability after brain injury. Brain Inj.
26. Levinson B, Wright P, Barklem S. Effect of buflomedil on behaviour, memory, and intellectual capacity in patients with dementia. A placebo-controlled study. S Afr Med J
27. Schiffer RB, Cash J, Herndon RM. Treatment of emotional lability with low-dosage tricyclic antidepressants. Psychosomatics
28. Seliger GM, Hornstein A, Flax J, Herbert J, Schroeder K. Fluoxetine improves emotional incontinence. Brain Inj
29. Wolf JK, Santana HB, Thorpy M. Treatment of “emotional incontinence” with levodopa. Neurology.
30. Sandyk R. Nomifensine for “emotional incontinence” of the pseudobulbar type. J Am Geriatr Soc
31. Arciniegas DB, Topkoff J. The neuropsychiatry of pathologic affect: an approach to evaluation and treatment. Semin Clin Neuropsychiatry
32. Brooks BR, Thisted RA, Appel SH, et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology
33. Okun MS, Riestra AR, Nadeau SE. Treatment of ballism and pseudobulbar affect with sertraline. Arch Neurol
34. Okuda DT, Chyung AS, Chin CT, Waubant E. Acute pathological laughter. Mov Disord
35. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci
36. Starkstein SE, Migliorelli R, Tesón A, et al. Prevalence and clinical correlates of pathological affective display in Alzheimer’s disease. J Neurol Neurosurg Psychiatry
37. Gubbay SS, Kahana E, Zilber N, Cooper G, Pintov S, Leibowitz Y. Amyotrophic lateral sclerosis. A study of its presentation and prognosis. J Neurol
38. Caroscio JT, Mulvihill MN, Sterling R, Abrams B. Amyotrophic lateral sclerosis. Its natural history. Neurol Clin
39. Minden SL, Schiffer RB. Affective disorders in multiple sclerosis. Review and recommendations for clinical research. Arch Neurol
40. Zeilig G, Drubach DA, Katz-Zeilig M, Karatinos J. Pathological laughter and crying in patients with closed traumatic brain injury. Brain Inj.
41. Tateno A, Jorge RE, Robinson RG. Pathological laughing and crying following traumatic brain injury. J Neuropsychiatry Clin Neurosci
42. Tang WK, Chan SSM, Chiu HFK, et al. Emotional incontinence in Chinese stroke patients. Diagnosis, frequency, and clinical and radiological correlates. J Neurol.
43. Kim JS, Choi S, Kwon SU, Seo YS. Inability to control anger or aggression after stroke. Neurology
44. Gallagher JP. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand
45. Shaibani AT, Sabbagh MN, Doody R. Laughter and crying in neurologic disorders. Neuropsychiatry Neuropsychol Behav Neurol
46. Morris PL, Robinson RG, Raphael B. Emotional lability after stroke. Aust N Z J Psychiatry
47. Houeto JL, Mesnage V, Mallet L, et al. Behavioural disorders, Parkinson’s disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry
48. Kaschka WP, Meyer A, Schier KR, Froscher W. Treatment of pathological crying with citalopram. Pharmacopsychiatry
49. Lader M, Pétursson H. Psychiatric disorders. In: Girdwood RH, Petrie JC, eds. Textbook of Medical Treatment
. Edinburgh: Churchill Livingstone; 1987:285-301.