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Patients with various neurologic disorders exhibit exaggerated or
inappropriate episodes of laughter, crying, or both without an
apparent motivating stimulus or in response to stimuli that would
not have elicited such an emotional response before the onset of
the underlying disease. During these episodes, patients have
difficulty controlling their emotional expression according to the
contextual information. In contrast, patients with mood disorders
have a pervasive and sustained change in their emotional experience
and thus exhibit spells of laughter or crying because of an
underlying mania or depression. This article focuses on the clinical
presentation, diagnosis, prevalence, and proposed pathophysiological
mechanisms of and available treatment options for this
clinical phenomenon.
Mayo Clin Proc. 2006;81(11):1482-1486
MSA = multiple system atrophy; PLC = pathological laughter and crying
Many patients with neurologic disorders exhibit uncontrollable
episodes of laughing, crying, or both
that are either exaggerated or contradictory to the context in
which they occur. Patients report that their episodes are at
best only partially amenable to voluntary control, and unless
they experience a severe change of mental status, they
often have insight into their problem and judge their emotional
display as inappropriate and out of character.
The cardinal feature of the disorder is a pathologically
lowered threshold for exhibiting the behavioral response of
laughter, crying, or both. An affected individual exhibits
episodes of laughter and/or crying without an apparent
motivating stimulus or in response to stimuli that would not
have elicited such an emotional response before the onset
of their underlying neurologic disorder. In some patients,
the emotional response is exaggerated in intensity but is
provoked by a stimulus with an emotional valence congruent
with the character of the emotional display. For example,
a sad stimulus provokes a pathologically exaggerated
weeping response instead of a sigh, which the patient
normally would have exhibited in that particular situation.
However, in some other patients, the character of the emotional
display can be incongruent with, and even contradictory
to, the emotional valence of the provoking stimulus or
may be incited by a stimulus with no clear valence. For
example, a patient may laugh in response to sad news or cry
in response to stimuli with no emotional undertone, or,
once provoked, the episodes may switch from laughing to
crying or vice versa.
Various terms have been used interchangeably to describe
the problem of laughing and crying in these patients. The
most widely used terms are pseudobulbar affect, pathological
laughter and crying, emotional lability, emotionalism,
and emotional dysregulation. Terms such as forced crying,
involuntary crying, pathological emotionality, and emotional
incontinence have also been used, although less
frequently. In some instances, authors have used the same
term for clinically different conditions, and in other instances,
different terms have been used synonymously to
describe the same clinical presentation. Because the disorder
is primarily a problem with laughing and crying
rather than exhibiting all kinds of emotional displays, the
displays are out of character and disproportionate to the
context in which they occur, and the condition can lead to
social and personal distress and functional impairment,
we use the term pathological laughter and crying (PLC)
in this article, which we believe is a clear and concise
descriptor of the condition and has historical roots in classical
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc. • November 2006;81(11):1482-1486 • 1483
Accurate estimates of the incidence and prevalence of PLC
in the setting of each specific neurologic disorder are lacking.
This may be in part due to confusion in the literature
about the nosology and terminology of this clinical condition,
as described previously. This confusion notwithstanding,
there appears to be considerable potential for errors in
estimating the incidence and prevalence of impaired emotional
regulation. Patients and their family members may
be unaware that such episodes develop in the context of
neurologic disorders.1 If clinical researchers do not ask
specifically about symptoms of impaired emotional regulation
and if the nosological distinctions described previously
are not considered, these symptoms may be either
unrecognized or misinterpreted as a symptom of a mood
disorder. Conversely, some studies have attempted to estimate
the prevalence of the problem generally in clinical
referral samples, which may lead to overestimates of the
incidence and prevalence of this disorder.
With these caveats in mind, it is informative to review
the reported scope of the problem in some neurologic disorders.
Among patients with traumatic brain injury,2,3 the
prevalence of this condition during the first year after injury
is estimated at 5% to 11%. The disorder occurs in 10%
of patients with multiple sclerosis,4-6 49% of patients with
amyotrophic lateral sclerosis,7 11% to 34% of patients with
stroke,8-10 5% of patients with Parkinson disease and the
noncerebellar type of multiple system atrophy (MSA),11
and 37% of patients with the cerebellar type of MSA.12
The scope of the problem in patients with dementia is
controversial. In one report,13 the authors defined the problem
as simply “observable sudden changes in emotional
expressions,” which they observed in about 74% of mildly
to moderately impaired patients with Alzheimer disease.
Starkstein et al14 used the Pathological Laughter and Crying
Scale15 in their study of 103 patients with Alzheimer
disease. Of these 103 patients, 40 had PLC. Of note, however,
21 of these 40 patients also had an underlying congruent
mood disorder. The authors labeled these patients
as having “emotional lability,” which they defined as
“pathological laughing and crying with an underlying
mood disorder.”
Despite the problems associated with accurately estimating
the incidence and prevalence of PLC, the limited
data available suggest that this problem occurs with a frequency
considerably higher than is generally recognized by
physicians. In light of the frequency of the neurologic
conditions in which impaired regulation of emotional expression
develops, numerous patients may be expected to
have PLC and might benefit from its identification and
Several scales are available to identify and characterize
PLC.15-17 Among these, the 2 most commonly used in clinical
research studies are the Pathological Laughter and Crying
Scale15 and the Center for Neurologic Study-Lability
Scale.15-17 The items included in these scales cover the
triggering factors, frequency, duration, and involuntariness
of PLC events, issues that overlap minimally with items
included in scales for the assessment of mood disorders
(for example, the Hamilton Depression Rating Scale and
the Beck Depression Inventory), supporting the differences
in these diagnostic constructs.
Assessment scales developed specifically for characterizing
the problem of laughing and crying may be useful in
clinical trials. Using such scales to screen patients at risk
for PLC and to follow their progress may also be practical.
However, we strongly believe that the diagnosis of the
condition remains a bedside issue. As suggested by the
content of assessment scales for this disorder, a single
screening question regarding the presence of frequent
laughing or crying spells may be sufficient to identify
patients with impaired regulation of emotional expression.
Once the patient’s answer is confirmatory, other routine
questions are warranted to discern whether the patient’s
uncontrollable episodes of laughing or crying are related to
an underlying mood disorder.
In the clinical setting, PLC is often unrecognized. In cases
in which the physician notices spells of uncontrollable
laughing or crying, the condition can often be misdiagnosed
as a mood disorder. However, a thorough evaluation
can lead to proper differentiation of these 2 conditions.
Mood is an emotional state sustained over relatively long
periods, days to weeks or more. Patients with depression
feel depressed most of the time, and thus their emotional
display of crying is primarily a reflection of their underlying
depressed mood. By contrast, patients with pathological
crying exhibit the emotional display in the absence of a
pervasive and sustained depressed mood. The crying occurs
only paroxysmally and is uncontrollable and involuntary.
Such episodes may even occur in the absence of any
congruent changes in the mood of the patient. Crying due to
depression is associated with signs such as anhedonia,
decreased energy, psychomotor slowing, feelings of hopelessness
and helplessness, and suicidal ideation as well as
poor concentration and anxiety. Likewise, patients with
bipolar disease may exhibit laughter or crying during their
cycles of cheerfulness, irritability, and depression. In addition,
these patients have associated problems of grandios-
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1484 Mayo Clin Proc. • November 2006;81(11):1482-1486 •
ity, poor judgment, hyperactivity, pressured speech, poor
sleep, and increased energy. Patients with PLC report none
of these symptoms and, in fact, are often embarrassed by
their episodes of laughing or crying.
Importantly, although PLC and mood disorders appear
to be different clinical entities, they may coexist in the
same patient.12,15,18 Robinson et al15 reported that almost
half of their patients with PLC had coexisting depression.
However, resolution of pathological laughing or pathological
crying seems to be independent of the resolution of
depression in these patients and has no relationship with
the changes in anxiety or aggression scores.15 A recent
study found that all patients with the cerebellar type of
MSA who exhibited pathological laughter and/or crying
also had depression.12
The coexistence of pathological emotional expression
(eg, PLC) and pathological emotional experience (eg,
mood disorders) is an important observation because it
poses limitations in diagnosis and research and will certainly
influence the physician’s choice of treatment.
Pathological laughter and crying often responds to the
same treatments used for mood disorders. However, in
patients with PLC, the beneficial effects of these medications
are evident within days of treatment initiation and
occur in response to much lower dosages than those usually
prescribed for the treatment of mood disorders.12,15,18,19
Schiffer et al18 studied the effect of amitriptyline, a
tricyclic antidepressant, in 12 multiple sclerosis patients
with PLC using a mean dosage of 58 mg/d and compared
its effect to that of placebo in a 30-day, double-blind,
crossover study. They reported a significant improvement
in PLC symptoms in 8 patients taking amitriptyline with no
effect on their coexisting depression. Robinson et al15 administered
nortriptyline in dosages as high as 100 mg/d in
14 stroke patients with PLC and compared its effectiveness
to placebo in 14 other patients with stroke. They
reported significantly greater improvement of PLC in patients
given nortriptyline than in those receiving placebo
and no significant change in the depression status of these
Selective serotonin reuptake inhibitors have also been
used for treatment of PLC. In an open-label study by
Seliger et al,20 all 13 patients (8 with stroke and 5 with
multiple sclerosis) who received 20 mg/d of fluoxetine
reported a decrease in the number of laughing or crying
episodes within 3 to 14 days. Andersen et al21 compared
citalopram, 10 to 20 mg/d, to placebo in 16 consecutive
patients with stroke in a crossover study. They found that
daily crying episodes decreased by 50% in all 13 patients
receiving citalopram compared to only 2 patients who received
placebo. In a double-blind, placebo-controlled
study, Burns et al22 determined that sertraline in dosages up
to 50 mg/d was effective in 13 of 14 patients with PLC and
stroke, whereas placebo produced a beneficial response in
9 of 14 patients (P=.041). Muller et al23 conducted an openlabel
study of 26 patients with PLC after traumatic brain
injury. Thirteen patients were treated with citalopram, and
13 others received paroxetine in a single daily dose of 10 to
40 mg. Significant improvement was seen in 92% of patients,
with rapid onset of effect within 1 to 3 days.
AVP-923 is a new compound that consists of 30 mg of
dextromethorphan and 30 mg of quinidine, which inhibits
the metabolism of dextromethorphan by cytochrome P-450
2D6 enzyme. In a recent randomized, double-blind study
by Brooks et al,24 140 patients with amyotrophic lateral
sclerosis and PLC were randomized to receive dextromethorphan
plus quinidine (n=70) vs dextromethorphan
(n=33) or quinidine (n=37) alone in twice-daily doses. The
authors reported approximately 2-fold lower scores on the
Center for Neurologic Study-Lability Scale in the group
that received dextromethorphan plus quinidine compared
to the groups receiving only dextromethorphan or quinidine.
Moreover, 52% of the patients receiving dextromethorphan
plus quinidine were symptom free during the
last 2 weeks of the study compared to 23% of patients
taking dextromethorphan alone and 12% of patients taking
quinidine alone. Statistically significant improvement in
quality-of-life and quality-of-relationship scores were seen
in the patients receiving the combination treatment compared
to those receiving either drug alone. Adverse effects
reported in the group receiving dextromethorphan plus quinidine
included nausea (33%), dizziness (20%), and somnolence
(13%), resulting in a 24% discontinuation rate in the
group receiving the combination regimen compared to 6%
and 5% in the dextromethorphan and quinidine groups,
respectively. In a study by Panitch et al,25 150 patients with
multiple sclerosis and PLC were randomized to receive
dextromethorphan plus quinidine (n=76) or placebo (n=74).
Patients receiving the active compound experienced significant
improvement of their PLC symptoms as well as
their quality-of-life and relationship scores. Laughing and
crying episodes occurred 4.7 times per week in the group
receiving dextromethorphan plus quinidine compared to
11.5 episodes per week in the placebo group. Headaches
were the most commonly reported adverse effect in both
groups, but the only statistically significant adverse event
was dizziness (26.3% in the dextromethorphan plus quinidine
group vs 9.5% in the placebo group). Discontinuation
of the study medication because of adverse events occurred
in 16% of the dextromethorphan plus quinidine group compared
to 11% in the placebo group.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc. • November 2006;81(11):1482-1486 • 1485
In summary, although several agents have been shown
to be effective in the treatment of PLC, head-to-head
comparative clinical trials are needed to determine whether
any of the aforementioned treatment options are superior in
efficacy or adverse-effect profile.
Given the therapeutic effect of serotonergic agents in patients
with PLC, it has been suggested that a serotonergic
dysfunction is responsible for the impaired emotional regulation
in these patients.21 The fact that a chemical agent,
such as serotonin, is helpful in treating a condition does not
necessarily imply a causal relationship between the agent
and the condition. However, understanding how serotonergic
substitution can improve emotional experience in patients
with mood disorders while also being effective in
patients who have pathological regulation of emotional
expression is important.
The hypothesis proposed by Oppenheim and
Siemerling26 in 1886 and subsequently by Kinnier Wilson27
in 1924 was that impaired emotional regulation results
from disinhibition of a presumed brainstem center for
laughter and crying due to lesions of the voluntary motor
pathways in the descending corticobulbar tracts. As previously
published,28 this explanation has several limitations.
For example, if the inhibitory pathways are damaged in
these patients, why do they not laugh or cry constantly, or
why do they sometimes exhibit a response contradictory to
the emotional valence of the triggering stimulus? Moreover,
why do many patients with this condition lack the
typical features of pseudobulbar palsy? The hypothesis of
disinhibition assumes that a proper operation of emotional
expression is based on a balance between inhibitory and
excitatory inputs to a presumed brainstem center for laughing
and crying. On the basis of the current knowledge of
brain anatomy and function, there is no single brainstem
center for laughter and crying. Rather, a network of
brainstem nuclei is involved in the generation of movements
associated with the acts of laughter or crying, and it
remains to be determined how this network is regulated by
the cerebral cortex. Which cortical structures are involved,
and how do they exert their control over the brainstem
network? Feinstein et al6,29 have shown that the involuntary
and uncontrollable emotional behavior in patients with
multiple sclerosis correlates directly with poor performance
in tests of prefrontal function. This suggests that the
prefrontal cortices, rather than the primary motor cortices
as Oppenheim and Siemerling26 and Kinnier Wilson27 had
suggested, are important for the control of emotional behavior.
30 However, questions remain. For instance, to what
extent and through which pathways do the prefrontal cortices
regulate the operation of the brainstem network? Is this
regulation made possible through direct corticobulbar pathways
or indirectly through additional structures such as the
cerebellum, as suggested recently?12,28,31
A thorough understanding of the etiology and pathophysiology
of PLC awaits further elucidation of the neural
basis of human emotion and of the neurotransmitters and
networks involved in its regulation and coordination.
Meanwhile, the recognition, diagnosis, and treatment of
this clinical entity is important to help patients and their
caretakers enhance their quality of life and relationships.
1. Arciniegas DB, Topkoff J. The neuropsychiatry of pathologic affect: an
approach to evaluation and treatment. Semin Clin Neuropsychiatry. 2000;5:
2. Zeilig G, Drubach DA, Katz-Zeilig M, Karatinos J. Pathological laughter
and crying in patients with closed traumatic brain injury. Brain Inj. 1996;10:
3. Tateno A, Jorge RE, Robinson RG. Pathological laughing and crying
following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2004;16:
4. Minden SL, Schiffer RB. Affective disorders in multiple sclerosis: review
and recommendations for clinical research. Arch Neurol. 1990;47:98-
5. Feinstein A, Feinstein K, Gray T, O’Connor P. Prevalence and
neurobehavioral correlates of pathological laughing and crying in multiple
sclerosis. Arch Neurol. 1997;54:1116-1121.
6. Feinstein A, O’Connor P, Gray T, Feinstein K. Pathological laughing
and crying in multiple sclerosis: a preliminary report suggesting a role for the
prefrontal cortex. Mult Scler. 1999;5:69-73.
7. Gallagher JP. Pathologic laughter and crying in ALS: a search for their
origin. Acta Neurol Scand. 1989;80:114-117.
8. House A, Dennis M, Molyneux A, Warlow C, Hawton K. Emotionalism
after stroke. BMJ. 1989;298:991-994.
9. Morris PL, Robinson RG, Raphael B. Emotional lability after stroke.
Aust N Z J Psychiatry. 1993;27:601-605.
10. Kim JS, Choi-Kwon S. Poststroke depression and emotional incontinence:
correlation with lesion location. Neurology. 2000;54:1805-1810.
11. Siddiqui MS, Kirsch-Darrow L, Fernandez HH, Jacobson CE IV, Okun
MS. Prevalence of pseudobulbar affect in movement disorders and its mood
correlates: a prospective study of 754 consecutive patients [abstract]. Neurology.
2006;66(suppl 2):A369. Abstract P06.156.
12. Parvizi J, Joseph J, Press D, Schmahmann JD. Pathological laughter and
crying in multiple system atrophy—cerebellar type. Mov Disord. In press.
13. Haupt M. Emotional lability, intrusiveness, and catastrophic reactions.
Int Psychogeriatr. 1996;8(suppl 3):409-414.
14. Starkstein SE, Migliorelli R, Teson A, et al. Prevalence and clinical
correlates of pathological affective display in Alzheimer’s disease. J Neurol
Neurosurg Psychiatry. 1995;59:55-60.
15. 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. 1993;150:286-
16. Newsom-Davis IC, Abrahams S, Goldstein LH, Leigh PN. The emotional
lability questionnaire: a new measure of emotional lability in amyotrophic
lateral sclerosis. J Neurol Sci. 1999;169:22-25.
17. Smith RA, Berg JE, Pope LE, Callahan JD, Wynn D, Thisted RA.
Validation of the CNS emotional lability scale for pseudobulbar affect (pathological
laughing and crying) in multiple sclerosis patients. Mult Scler. 2004;
18. Schiffer RB, Herndon RM, Rudick RA. Treatment of pathologic laughing
and weeping with amitriptyline. N Engl J Med. 1985;312:1480-1482.
19. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel
and potential therapy. J Neuropsychiatry Clin Neurosci. 2005;17:447-454.
20. Seliger GM, Hornstein A, Flax J, Herbert J, Schroeder K. Fluoxetine
improves emotional incontinence. Brain Inj. 1992;6:267-270.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1486 Mayo Clin Proc. • November 2006;81(11):1482-1486 •

Questions About PLC
1. Which one of the following statements describes the
condition of PLC, as defined in this article?
a. Patients have congruent mood but exaggerated
episodes of laughter and/or crying
b. Patients have incongruent mood and inappropriate
episodes of laughter and/or crying
c. Patients have exaggerated and inappropriate
episodes of laughter and/or crying due to an
underlying mood disorder
d. Patients have exaggerated and inappropriate
episodes of laughter and/or crying but no comorbid
mood disorder
e. Patients have exaggerated and inappropriate
episodes of laughter and/or crying independent of
any comorbid mood disorder
2. Which one of the following is currently prescribed for
the treatment of PLC?
a. Neuroleptics
b. Antiepileptics
c. Selective serotonin reuptake inhibitors and tricyclic
d. Dextromethorphan
e. Quinidine
3. Which one of the following statements defines the
relationship between PLC and mood disorders?
a. It is not possible to differentiate PLC from any mood
b. By definition, patients with PLC cannot have
comorbid depression or mania
c. Higher dosages and longer durations of
antidepressant therapy are needed for the treatment
of PLC
d. Laughing and crying in patients with PLC are
caused by a pathological mood
e. Mood disorders are a sustained problem of
emotional experience, whereas PLC is a
paroxysmal problem of exaggerated and/or
inappropriate emotional expression
4. Which one of the following neurologic conditions is
most frequently associated with PLC?
a. Amyotrophic lateral sclerosis
b. Multiple sclerosis
c. Stroke
d. Epilepsy
e. Alzheimer disease
5. According to recent clinical trials, which one of the
following treatment options is effective for the
treatment of PLC?
a. 30 mg of dextromethorphan once a day
b. 30 mg of quinidine once a day
c. 30 mg of dextromethorphan plus 30 mg of quinidine
once a day
d. 30 mg of dextromethorphan plus 30 mg of quinidine
twice a day
e. 30 mg of dextromethorphan plus 300 mg of
quinidine twice a day
Correct answers:
1. e, 2. c, 3. e, 4. a, 5. d
21. Andersen G, Vestergaard K, Riis JO. Citalopram for post-stroke pathological
crying. Lancet. 1993;342:837-839.
22. Burns A, Russell E, Stratton-Powell H, Tyrell P, O’Neill P, Baldwin R.
Sertraline in stroke-associated lability of mood. Int J Geriatr Psychiatry.
23. Muller U, Murai T, Bauer-Wittmund T, von Cramon DY. Paroxetine
versus citalopram treatment of pathological crying after brain injury. Brain Inj.
24. Brooks BR, Thisted RA, Appel SH, et al, AVP-923 ALS Study Group.
Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a
randomized trial. Neurology. 2004;63:1364-1370.
25. Panitch HS, Thisted RA, Smith RA, et al, Pseudobulbar Affect in Multiple
Sclerosis Study Group. Randomized, controlled trial of dextromethorphan/
quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol.
26. Oppenheim H, Siemerling E. Mitteilungen uber Pseudobulbarparalyse
und akute Bulbarparalyse. Berl Klin Wochenschr. 1886;46.
27. Wilson SAK. Some problems in neurology, II: pathological laughing and
crying. J Neurol Psychopathol. 1924;4:299-333.
28. Parvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR. Pathological
laughter and crying: a link to the cerebellum. Brain. 2001;124:1708-
29. McCullagh S, Moore M, Gawel M, Feinstein A. Pathological laughing
and crying in amyotrophic lateral sclerosis: an association with prefrontal
cognitive dysfunction. J Neurol Sci. 1999;169:43-48.
30. Wild B, Rodden FA, Grodd W, Ruch W. Neural correlates of laughter
and humour. Brain. 2003;126(pt 10):2121-2138.
31. Parvizi J, Schiffer R. Pathological crying in a patient with a cerebellar
cyst. J Neuropsychiatry Clin Neurosci. In press.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.


Tagged with: Behavioral ResponseCardinal FeatureClinical PresentationEmotional ExperienceEmotional ExpressionEmotional ResponseIntensityLaughterMayo Clin ProcMood DisordersMultiple System AtrophyNeurologic DisorderNeurologic DisordersPathophysiological MechanismsPrevalenceResponse To StimuliStimulusThresholdTreatment OptionsVoluntary Control

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