- Email: [email protected]
A clinical overview of pseudobulbar affect
The American Journal of Geriatric Pharmaeotherapy D.B.Arciniegas
A Clinical Overview of Pseudobulbar Affect David B. Arciniegas, M D
Director, Neuropsychiatry Service, Assistant Professor of Psychiatry and Neurology, University of Colorado Health Sciences Center, Denver, Colorado, and Co-Medical Director, Brain Injury Rehabilitation Unit, HealthONE Spalding Rehabilitation Hospital, Aurora, Colorado
INTRODUCTION The ability to regulate the internal experience and outward expression of emotion is among the most complex and recently acquired aspects of our neurobiology. When compromised by disease or injury, emotional dysregulation can have a substantial impact on patients, families, and society. >3 Disorders of emotion are common, and are most usefully divided into those in which m o o d disturbances predominate and those in which dysregulation of affect is the characteristic feature. To understand this division, it may be necessary for some clinicians to revise their understanding of the terms mood and affect.
NOSOLOGY: MOOD A N D AFFECT Most clinicians are taught some version of this statement: "Mood is the emotional feeling stated by a patient, and affect is the emotional appearance of the patient." This division is essentially one that relies on the perspective from which an individual's emotional state is viewed: subjective (patient report) versus objective (examiner observation). An alternative and more useful definition of mood and affect first characterizes these domains of emotion temporally, and then evaluates their subjective and objective features. Temporally, mood denotes an individual's emotional baseline: an emotional state that is pervasive and sustained over a relatively long period of time (ie, days to weeks). Affect refers to an emotional state of relatively short duration (minutes to hours) that varies from moment to moment and that is superimposed on the prevailing mood. By analogy, mood is the emotional climate, whereas affect is the emotional weather. ~ Both m o o d and affect have subjective (experienced) and objective (expressed) components. Subjective components include visceral sensations and emotion-related cognitions that contribute to the conscious "feeling" of emotion. Objective components include visceral/autonomic activity, motor behavior, and vocalizations. 1,S Using this heuristic approach facilitates organization of disorders of emotion into those principally involving mood disturbances and those involving affect dysregulation. Most clinicians are familiar with the essential features of major depressive disorder, dysthymic disorder, bipolar disorder, and cyclothymic disorder. At their core, each of these disorders entails a disturbance of emotion that is present most of the day, nearly every day, over many days (hypomania), weeks (mania, depression), or longer (dysthymia, cyclothymia). Additionally, the disturbance results in changes in cognition, behavior, and physical (neurovegetative) function. 4 Despite the presence of these additional features, the core clinical feature of these disorders is a sustained and pervasive change in emotion--a shift in the emotional climate or mood. Accordingly, these disorders are most accurately described as mood disorders rather than affective disorders. Accepted for publication August 19, 2005. Printed in the USA, Reproduction in whole or part is not permitted,
4
October 2005
Volume 3 • Supplement A
doi:l 0. I 016/j.amjopharm.2005.09.01 I 1543-5946/05
Copyright © 2005 Excerpta Medica, Inc.
D.B. Arciniegas
The disorders of mood are described in considerable detail in the Diagnostic and Statistical Manual of Mental Disorders4 (DSM)-based diagnostic system, and that description has facilitated improved identification and treatment of these disorders in many clinical settings. Unfortunately, the exclusive presentation of mood disorders in that system also has had the unintended effect of nearly eliminating the disorders of affect from the minds of clinicians. Disorders of affect are characterized by impairment of the moment-to-moment regulation of emotion. In these disorders, sustained and pervasive disturbances of mood are not necessary for the diagnosis and are usually absent. The disorders of affect may be divided into those characterized by excesses of affect and those in which there is a deficit of affect. The former category includes pathological laughing and crying (PLC), affective lability, essential crying, and witzelsucht. The prototypical example of the latter category is affective placidity in Kliiver-Bucy-like syndromes. Among these, PLC and affective lability are the most common. 2,s~6
C O M M O N DISORDERS OF AFFECT Pathological Laughing and Crying Episodes of laughing and crying are considered pathological when they occur without voluntary control and modulation, are not meaningfully related to the stimuli that provoke them (ie, contextually inappropriate), neither reflect nor change the prevailing mood, and involve a dissociation between affective expression and experience. 7,8 The classic example of such is a patient with a stroke who appears emotionally normal most of the time, but unpredictably bursts into tears and grimaces, and vocalizes at the slightest provocation. After these excessively intense and uncontrollable episodes run their course over a few minutes, the patient returns to an emotionally "neutral" baseline. When asked how he felt during the episode, the patient replies that he felt nothing at all--no sadness, anxiety, joy, or any other subjective emotional experience occurs during these episodes. This form of affect dysregulation-crying without feeling sad and laughing without feeling mirth or amusement--is the prototype of PLC. Many persons with PLC experience both episodes of crying and of laughing. When only one type of episode occurs in an individual patient, pathological crying alone is the more common presentation. 9-11 Any neurological disorder that interferes with the corticobulbar or cortico-subcortical-thalamo-cerebellar circuits that permit regulation of affect can produce PLC. Common underlying neurological conditions
The American Journal of Geriatric Pharmacotherapy
include stroke, amyotrophic lateral sclerosis, Parldnson's disease, multiple sclerosis, frontotemporal dementia, traumatic brain injury, Alzheimer's disease, epilepsy, normal pressure hydrocephalus, progressive supranuclear palsy, Wilson's disease (hepatolenticular degeneration), and neurosyphilis. 2,s,7,9,12 PLC is often a source of embarrassment for patients and families, and may interfere substantially with rehabilitation, feeding, or other basic care needs entailed by the underlying neurological disorder from which PLC arises.
Affective Lability Episodes of affective lability are similar to those of PLC in that they are brief, excessively intense with respect to the inciting stimulus, not fully amenable to normal voluntary control, and neither reflect nor change the prevailing mood. s However, these episodes are often less severe and more understandably related to sentimental stimuli than are episodes of PLC. Additionally, the subjective and objective dimensions of affect are not dissociated during episodes of affective lability. Persons with affective lability feel sad when they cry and feel amusement when they laugh, but they are unable to control the intensity, duration, or frequency of these episodes. While the stimulus for such episodes may carry some sentimental valence, the quality of the affective response is in excess of that merited by the stimulus that incites it. As a result, episodes of affective lability are more stereotyped than normal affective variability (ie, they are pathological), 13 although they tend to be less stereotyped than episodes of PLC. s,14 Any neurological disorder that interferes with the corticobulbar or cortico-subcortical-thalamo-cerebellar circuits involved in affect regulation can produce affective lability; not surprisingly, the causes of affective lability overlap substantially with those that produce PLC. 5 As with PLC, affective lability may be a source of substantial distress and disability for persons with this condition and for their families/caregivers. Pseudobulbar Affect The differcnces between PLC and affective lability are more a matter of degree than of ldnd. In fact, these conditions are described using a varletT of other terms, including emotional incontinence, emotional instability, emotional lability, emotional dyscontrol, excessive emotionalism, and uncontrollable laughing and crying, among others. The common referent of these terms is a condition characterized by episodic, uncontrollable affects. For the purposes of nosological simplicity, we will use the historical term pseudobulbar affect (PBA) to
The American Journal of Geriatric Pharmacotherapy D.B.Arciniegas
refer to this condition. There are several other disorders of affect not encompassed by PBA, and about which clinicians should be aware before proceeding to diagnose and treat PBA. These include essential crying, witzelsucht, and placidity, each of which is described briefly below.
U N C O M M O N DISORDERS OF AFFECT Essential Crying Essential crying refers to a lifelong, and probably hereditary, tendency to cry easily,is Persons with essential crying experience brief episodes of subjectively and objectively congruent sadness in response to sentimentally meaningful stimuli. While these episodes are noteworthy, they tend to be only modestly more intense than would be expected--based on the sentimental value of the stimulus that incites them--are not fully stereotyped, and tend to be more amenable to voluntary modulation than episodes of PBA. Essential crying may be embarrassing to both the individual and to others around them, but is not severely distressing or functionally impairing. Accordingly, essential crying is best understood as a form of affect regulation that lies midway on the continuum between normal affective variability and PBA. 5,16 Witzelsucht Roughly translated from German as "a peculiar addiction to trivial jolting," witzelsucht describes a condition in which patients find and/or seek humor in things that others do not. The patient has a frequently and inappropriately elevated or giddy affect subjectively, and frequently laughs and makes childish, facetious, or sarcastic remarks. ~,l°,n,16 Rather than reflecting genuine humor, persons with witzelsucht tend to have an irritable, aggressive quality to their affective dysregulation. It is this admixture of irritability and mirth that distinguishes witzelsucht from PBA, and in particular, from pathological laughing. Although quite uncommon, when witzelsucht develops, it does so most often in the context of frontal lobe disease or injury, especially involving the right frontal lobe. s,l°,n,16 Placidity in Kliiver~Bucy-Like Syndromes Placidity in Kltiver-Bucy-like syndromes involves a marked deficit of affective responding. Stimuli that would normally provoke extreme motor responses produce no observable expressions of affect in patients with these syndromes. Originally described in macaque monkeys in whom bilateral amygdala lesions were produced experimentally, humans with lesions in this location may
also develop affective placidity. 17 Causes of such lesions and the Kliiver-Bucy-like syndromes include herpes simplex encephalitis, traumatic brain injury, frontotemporal dementia, ischemia or anoxia, temporal lobectomy, progressive subcortical gliosis, adrenoleukodystrophy, systemic lupus erythematosus, porphyria, and limbic encephalitis. 17 In general, affective placidity rarely develops as an isolated symptom. Instead, it occurs with the other features of the Kdtiver-Bucy-like syndromes, including hyperorality, hypermetamorphosis, altered sexual behavior, associative visual agnosia, aphasia, amnesia, echopraxia, and/or partial complex seizures.
PBA: EPIDEMIOLOGY, DIAGNOSIS, AND EVALUATION Epidemiology Although the overall prevalence of PBA is tmlmown, its prevalence among persons with multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury suggests an annual rate of >1 million persons in the United States. 16 Given that PBA occurs among persons with many other neurological conditions, this estimate may underrepresent the actual frequency of this condition. However, additional research regarding the incidence of PBA and also its persistence (ie, lifetime prevalence) in all ofthesc conditions is needed before firm estimates can be made.
Differential Diagnosis The first step in the differential diagnosis of episodic tmcontrollablc crying and laughing is identifying their occurrence as a manifestation of a mood disorder or as a disorder of affect. Such identification is guided most usefully by an understanding of the temporal differences between mood and affect in the manner described earlier in this article. Alternative (or comorbid) diagnoses could include anxiety disorders or personality disorders producing dramatic and/or erratic behaviors. Other neurobehavioral syndromes should also be considered in the initial differential diagnosis. After identifying such episodes as a dysrcgulation of affect alone, PBA must then be differentiated from other disorders of excessive affect, including essential crying and witzelsucht, as described earlier. After identifying episodic uncontrollable laughing and crying as PBA, the causes of this condition must be identified. In most cases, the underlying neurological disorder producing PBA will be a known element of the paticnt's history. However, in some cases PBA may be the first presentation of this condition; in such cases, clinicians should undertake a thorough neurological
D.B. Arciniegas
history and examination, including magnetic resonance imaging of the brain, to identify that underlying neurological condition. In particular, clinicians should be aware of epilepsy as a cause of episodic affective displays. Dacrystic (or quiritarian) seizures are a form of complex partial epilepsy in which the ictal manifestation is crying) 8,19 In addition, gelastic seizures are a form of complex partial epilepsy in which laughing is the ictal manifestation. 19,20Although the episodes of crying and laughing in these types of seizures may resemble PBA, they are generally followed by at least a brief period of postictal confusion. This postictal disturbance of consciousness should facilitate clinical identification of these episodes as seizures rather than PBA. When the history does not facilitate distinction between seizure and PBA, electroencephalography (EEG) may be of use. Persons with dacrystic and gelastic seizures will often demonstrate interictal epileptiform discharges on sleep-deprived EEG. In cases where the EEG is performed during an affective display, ictal epileptiform activity and postictal slowing may be observed. When there is concern regarding the possibility of an epileptic basis for episodic uncontrollable crying or laughing, consultation with a neurologist specializing in epilepsy is prudent. Clinicians should also be mindful that epilepsy may also be a cause of PBA, and that there is a possibility that, though rare, some patients will present with both ictal and interictal displays of pathological affect. Evaluation
A simple screening question regarding the occurrence of episodic uncontrollable crying and/or laughing will, in many cases, suffice for the identification of persons with possible PBA. Affirmative responses to a screening question should prompt further characterization of such episodes. Clinicians first should seek to obtain information sufficient to ascertain whether PBA is the most correct diagnosis (ie, sort through the differential diagnosis described previously). After determining that the condition experienced by the patient is PBA, information regarding the symptom types, severity, frequency, and functional import should be obtained. This information is needed for diagnostic purposes, but also to establish a baseline against which the effects of treatment for PBA may be measured. Several scales have been developed for this purpose, including the Pathological Laughter and Crying Scale (PLACS), 21 the Emotional Lability Questionnaire (ELQ), 22 the Affective Lability Scale (A]_~),23 and the Center for Neurologic Study-Lability Scale (CNS-LS). 14
The American Journal of Geriatric Pharmacotherapy
The PLACS was developed specifically for the evaluation of post-stroke PBA, and has also been applied to the study of PBA following traumatic brain injury. 24 The PLACS is a valid and reliable measure with which to assess both baseline PBA symptoms and response to treatment. The ELQ is an adaptation of the PLACS specifically for use among persons with amyotrophic lateral sclerosis, and appears to be valid and reliable in that context. The ALS evaluates lability and intensity of affect, and was developed as a measure of such among healthy college students. It has not yet been applied to characterization or treatment studies among persons with PBA, leaving its reliability and validity in this context uncertain. The CNS-LS was developed for the purpose of evaluating PBA among persons with amyotrophic lateral sclerosis, 14 and also has been applied to the study of PBA due to multiple sclerosis) 2 The CNSLS also appears to be a valid and reliable measure with which to assess baseline PBA symptoms and response to treatment. Among these scales, the PLACS and the CNS-LS are used most often in research and clinical practice. Even if clinicians elect not to use the PLACS or the CNS-LS in everyday clinical practice, familiarity with the content of these scales will improve clinicians' abilities to identify PBA and the response of this condition to pharmacologic intervention. CONCLUSIONS Disorders of affect are distinct from disorders of mood, and may be a substantial source of distress and disability for patients and their families. Distinguishing disorders of affect from disorders of mood requires clinicians to first define mood and affect on temporal grounds, and to then characterize the subjective and objective aspects of these domains of emotion. Using a temporallybased nosology for mood and affect facilitates the identification of the primary domain in which emotional disturbances arise: mood versus affect. Among the disorders of affect, affective lability and PLC--grouped here under the term PBA--are the most common. PBA develops in the context of many neurological disorders, and occurs morc frequently than is commonly recognized in general medical, neurological, and psychiatric practices. Generating a differential diagnosis for PBA requires clinicians' familiarity with mood disorders, disorders of affect, and other neurological conditions (ie, dacrystic and gelastic epilepsy) that may present with such symptoms as well. Clinical evaluation of PBA may be guided usefully by assessment scales specifically designed for this purpose.
r
7
The AmericanJournal of Geriatric Pharmacotherapy D.B.Arciniegas
Use of these scales, formally or informally, will assist clinicians' efforts to diagnose PBA and to measure the effects of treatments they prescribe for this condition. REI=ERI~NCES
1. Damasio AR. Descartes~Error: Emotion, Reason, and the Human Brain. New York, NY: Putnam Publishing; 1994. 2. Dark FL, McGrath JJ, Ron MA. Pathological laughing and crying. Aust NZJPsychiatry. 1996;30:472-479. 3. Green RL. Regulation of affect. Semin Clin Neuropsychiatry. 1998;3:195-200. 4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder6 Fourth Edition. Washington, DC: American Psychiatric Press; 1994. 5. Arciniegas DB, TopkoffJ. The neuropsychiatry of pathologic affect: An approach to evaluation and .treatment. Semin Clin Neuropsychiatry. 2000;5:290-306. 6. 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. 7. Poe& K. Pathological laughing and weeping in patients with progressive bulbar palsy. Ger Med Mon. 1969;14: 394-397. 8. Poeck K. Pathological laughter and crying. In: Fredericks JAM, ed. Handbook of Clinical Neurology. Vol 45. Amsterdam, Netherlands: Elsevier Science Publishers; 1985. 9. Green RL, Bernat JL. Pathologic crying. In: Joseph AB, Young RR, eds. Movement Disorders in Neurology and Neuropsychiatry. Oxford, England: Blackwell Science Inc.; 1999. 10. Berkovic SF, Andermann F. Pathological laughing. In: Joseph AB, Young RR, eds. Movement Disorders in Neurology and Neuropsychiatry. Oxford, England: Blackwell Science Inc.; 1999. 11. Duchowny MS. Pathological disorders of laughter. In: McGhee PE, Goldstein JH, eds. Handbook of Human Research. Vol 8. New York, NY: Springer Verlag; 1983. 12. Smith RA, Berg JE, Pope LE, et al. Validation of the CNS emotional lability scale for pseudobulbar affect
8
(pathological laughing and crying) in multiple sclerosis patients. Mult Scler. 2004;10:679-685. 13. Woyshville MJ, Lackamp jM, Eisengart JA, Gilliland JA. On the meaning and measurement of affective instability: Clues from chaos theory [published correction appears in Biol Psychiatry. 1999;45:1081]. Biol Psychiatry. 1999;45: 261-269. 14. Moore SR, Gresham LS, Bromberg MB, et al. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997;63:89-93. 15. Green RL, McAllister TW, Bernat JL. A study of crying in medically and surgically hospitalized patients. A m J Psychiatry. 1987;144:442447, 16. Arciniegas DB, Lauterbach EC, Anderson KE, et al. The differential diagnosis ofpseudobulbar affect (PBA): Distinguishing PBA amor*g disorders of mood and affect. Proceedings of a roundrable meeting. CNS Spectr. 2005;10: 1-14. 17. Trimble MR, Mendez MF, Cummings JL. Neuropsychiatric symptoms from the temporolimbic lobes. J Neuropsychiatry Clin Neurosei. 1997;9:429-438. 18. Luciano D, Devinsky O, Perrine K. Crying seizures. Neurology. 1993;43:2113-2117. 19. Sackeim HA, Greenberg MS, Weiman AL, et al. Hemisphere asymmetry in the expression of positive and negative emotions: Neurologic evidence. Arch Neurol. 1982;39:210-218. 20. Pearce JM. A note on gelastic epilepsy. Eur Neurol. 2004;52:172-174. 21. Robinson RG, Parikh RM, Lipsey JR, et al. Pathological laughing and crying following stroke: Validation of a measurement scale and a double-blind treatment study. Am J Psychiatry. 1993;150:286-293. 22. Newsom-Davis IC, Abrahams S, Goldstein LH, Leigh PN. The emotional lability questionnaire: A new measure of emotional lability in amyotrophic lateral sclerosis. f Neurol Sd. 1999;169:22-25. 23. Harvey PD, Greenberg BR, Serper MR. The affective lability scales: Development, reliability, and validity.J Clin Psychol. 1989;45:786-793. 24. Tateno A, Jorge RE, Robinson RG. Pathological laughing and crying following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2004;16:426-434.
A Clinical Overview of Pseudobulbar Affect David B. Arciniegas, M D
Director, Neuropsychiatry Service, Assistant Professor of Psychiatry and Neurology, University of Colorado Health Sciences Center, Denver, Colorado, and Co-Medical Director, Brain Injury Rehabilitation Unit, HealthONE Spalding Rehabilitation Hospital, Aurora, Colorado
INTRODUCTION The ability to regulate the internal experience and outward expression of emotion is among the most complex and recently acquired aspects of our neurobiology. When compromised by disease or injury, emotional dysregulation can have a substantial impact on patients, families, and society. >3 Disorders of emotion are common, and are most usefully divided into those in which m o o d disturbances predominate and those in which dysregulation of affect is the characteristic feature. To understand this division, it may be necessary for some clinicians to revise their understanding of the terms mood and affect.
NOSOLOGY: MOOD A N D AFFECT Most clinicians are taught some version of this statement: "Mood is the emotional feeling stated by a patient, and affect is the emotional appearance of the patient." This division is essentially one that relies on the perspective from which an individual's emotional state is viewed: subjective (patient report) versus objective (examiner observation). An alternative and more useful definition of mood and affect first characterizes these domains of emotion temporally, and then evaluates their subjective and objective features. Temporally, mood denotes an individual's emotional baseline: an emotional state that is pervasive and sustained over a relatively long period of time (ie, days to weeks). Affect refers to an emotional state of relatively short duration (minutes to hours) that varies from moment to moment and that is superimposed on the prevailing mood. By analogy, mood is the emotional climate, whereas affect is the emotional weather. ~ Both m o o d and affect have subjective (experienced) and objective (expressed) components. Subjective components include visceral sensations and emotion-related cognitions that contribute to the conscious "feeling" of emotion. Objective components include visceral/autonomic activity, motor behavior, and vocalizations. 1,S Using this heuristic approach facilitates organization of disorders of emotion into those principally involving mood disturbances and those involving affect dysregulation. Most clinicians are familiar with the essential features of major depressive disorder, dysthymic disorder, bipolar disorder, and cyclothymic disorder. At their core, each of these disorders entails a disturbance of emotion that is present most of the day, nearly every day, over many days (hypomania), weeks (mania, depression), or longer (dysthymia, cyclothymia). Additionally, the disturbance results in changes in cognition, behavior, and physical (neurovegetative) function. 4 Despite the presence of these additional features, the core clinical feature of these disorders is a sustained and pervasive change in emotion--a shift in the emotional climate or mood. Accordingly, these disorders are most accurately described as mood disorders rather than affective disorders. Accepted for publication August 19, 2005. Printed in the USA, Reproduction in whole or part is not permitted,
4
October 2005
Volume 3 • Supplement A
doi:l 0. I 016/j.amjopharm.2005.09.01 I 1543-5946/05
Copyright © 2005 Excerpta Medica, Inc.
D.B. Arciniegas
The disorders of mood are described in considerable detail in the Diagnostic and Statistical Manual of Mental Disorders4 (DSM)-based diagnostic system, and that description has facilitated improved identification and treatment of these disorders in many clinical settings. Unfortunately, the exclusive presentation of mood disorders in that system also has had the unintended effect of nearly eliminating the disorders of affect from the minds of clinicians. Disorders of affect are characterized by impairment of the moment-to-moment regulation of emotion. In these disorders, sustained and pervasive disturbances of mood are not necessary for the diagnosis and are usually absent. The disorders of affect may be divided into those characterized by excesses of affect and those in which there is a deficit of affect. The former category includes pathological laughing and crying (PLC), affective lability, essential crying, and witzelsucht. The prototypical example of the latter category is affective placidity in Kliiver-Bucy-like syndromes. Among these, PLC and affective lability are the most common. 2,s~6
C O M M O N DISORDERS OF AFFECT Pathological Laughing and Crying Episodes of laughing and crying are considered pathological when they occur without voluntary control and modulation, are not meaningfully related to the stimuli that provoke them (ie, contextually inappropriate), neither reflect nor change the prevailing mood, and involve a dissociation between affective expression and experience. 7,8 The classic example of such is a patient with a stroke who appears emotionally normal most of the time, but unpredictably bursts into tears and grimaces, and vocalizes at the slightest provocation. After these excessively intense and uncontrollable episodes run their course over a few minutes, the patient returns to an emotionally "neutral" baseline. When asked how he felt during the episode, the patient replies that he felt nothing at all--no sadness, anxiety, joy, or any other subjective emotional experience occurs during these episodes. This form of affect dysregulation-crying without feeling sad and laughing without feeling mirth or amusement--is the prototype of PLC. Many persons with PLC experience both episodes of crying and of laughing. When only one type of episode occurs in an individual patient, pathological crying alone is the more common presentation. 9-11 Any neurological disorder that interferes with the corticobulbar or cortico-subcortical-thalamo-cerebellar circuits that permit regulation of affect can produce PLC. Common underlying neurological conditions
The American Journal of Geriatric Pharmacotherapy
include stroke, amyotrophic lateral sclerosis, Parldnson's disease, multiple sclerosis, frontotemporal dementia, traumatic brain injury, Alzheimer's disease, epilepsy, normal pressure hydrocephalus, progressive supranuclear palsy, Wilson's disease (hepatolenticular degeneration), and neurosyphilis. 2,s,7,9,12 PLC is often a source of embarrassment for patients and families, and may interfere substantially with rehabilitation, feeding, or other basic care needs entailed by the underlying neurological disorder from which PLC arises.
Affective Lability Episodes of affective lability are similar to those of PLC in that they are brief, excessively intense with respect to the inciting stimulus, not fully amenable to normal voluntary control, and neither reflect nor change the prevailing mood. s However, these episodes are often less severe and more understandably related to sentimental stimuli than are episodes of PLC. Additionally, the subjective and objective dimensions of affect are not dissociated during episodes of affective lability. Persons with affective lability feel sad when they cry and feel amusement when they laugh, but they are unable to control the intensity, duration, or frequency of these episodes. While the stimulus for such episodes may carry some sentimental valence, the quality of the affective response is in excess of that merited by the stimulus that incites it. As a result, episodes of affective lability are more stereotyped than normal affective variability (ie, they are pathological), 13 although they tend to be less stereotyped than episodes of PLC. s,14 Any neurological disorder that interferes with the corticobulbar or cortico-subcortical-thalamo-cerebellar circuits involved in affect regulation can produce affective lability; not surprisingly, the causes of affective lability overlap substantially with those that produce PLC. 5 As with PLC, affective lability may be a source of substantial distress and disability for persons with this condition and for their families/caregivers. Pseudobulbar Affect The differcnces between PLC and affective lability are more a matter of degree than of ldnd. In fact, these conditions are described using a varletT of other terms, including emotional incontinence, emotional instability, emotional lability, emotional dyscontrol, excessive emotionalism, and uncontrollable laughing and crying, among others. The common referent of these terms is a condition characterized by episodic, uncontrollable affects. For the purposes of nosological simplicity, we will use the historical term pseudobulbar affect (PBA) to
The American Journal of Geriatric Pharmacotherapy D.B.Arciniegas
refer to this condition. There are several other disorders of affect not encompassed by PBA, and about which clinicians should be aware before proceeding to diagnose and treat PBA. These include essential crying, witzelsucht, and placidity, each of which is described briefly below.
U N C O M M O N DISORDERS OF AFFECT Essential Crying Essential crying refers to a lifelong, and probably hereditary, tendency to cry easily,is Persons with essential crying experience brief episodes of subjectively and objectively congruent sadness in response to sentimentally meaningful stimuli. While these episodes are noteworthy, they tend to be only modestly more intense than would be expected--based on the sentimental value of the stimulus that incites them--are not fully stereotyped, and tend to be more amenable to voluntary modulation than episodes of PBA. Essential crying may be embarrassing to both the individual and to others around them, but is not severely distressing or functionally impairing. Accordingly, essential crying is best understood as a form of affect regulation that lies midway on the continuum between normal affective variability and PBA. 5,16 Witzelsucht Roughly translated from German as "a peculiar addiction to trivial jolting," witzelsucht describes a condition in which patients find and/or seek humor in things that others do not. The patient has a frequently and inappropriately elevated or giddy affect subjectively, and frequently laughs and makes childish, facetious, or sarcastic remarks. ~,l°,n,16 Rather than reflecting genuine humor, persons with witzelsucht tend to have an irritable, aggressive quality to their affective dysregulation. It is this admixture of irritability and mirth that distinguishes witzelsucht from PBA, and in particular, from pathological laughing. Although quite uncommon, when witzelsucht develops, it does so most often in the context of frontal lobe disease or injury, especially involving the right frontal lobe. s,l°,n,16 Placidity in Kliiver~Bucy-Like Syndromes Placidity in Kltiver-Bucy-like syndromes involves a marked deficit of affective responding. Stimuli that would normally provoke extreme motor responses produce no observable expressions of affect in patients with these syndromes. Originally described in macaque monkeys in whom bilateral amygdala lesions were produced experimentally, humans with lesions in this location may
also develop affective placidity. 17 Causes of such lesions and the Kliiver-Bucy-like syndromes include herpes simplex encephalitis, traumatic brain injury, frontotemporal dementia, ischemia or anoxia, temporal lobectomy, progressive subcortical gliosis, adrenoleukodystrophy, systemic lupus erythematosus, porphyria, and limbic encephalitis. 17 In general, affective placidity rarely develops as an isolated symptom. Instead, it occurs with the other features of the Kdtiver-Bucy-like syndromes, including hyperorality, hypermetamorphosis, altered sexual behavior, associative visual agnosia, aphasia, amnesia, echopraxia, and/or partial complex seizures.
PBA: EPIDEMIOLOGY, DIAGNOSIS, AND EVALUATION Epidemiology Although the overall prevalence of PBA is tmlmown, its prevalence among persons with multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury suggests an annual rate of >1 million persons in the United States. 16 Given that PBA occurs among persons with many other neurological conditions, this estimate may underrepresent the actual frequency of this condition. However, additional research regarding the incidence of PBA and also its persistence (ie, lifetime prevalence) in all ofthesc conditions is needed before firm estimates can be made.
Differential Diagnosis The first step in the differential diagnosis of episodic tmcontrollablc crying and laughing is identifying their occurrence as a manifestation of a mood disorder or as a disorder of affect. Such identification is guided most usefully by an understanding of the temporal differences between mood and affect in the manner described earlier in this article. Alternative (or comorbid) diagnoses could include anxiety disorders or personality disorders producing dramatic and/or erratic behaviors. Other neurobehavioral syndromes should also be considered in the initial differential diagnosis. After identifying such episodes as a dysrcgulation of affect alone, PBA must then be differentiated from other disorders of excessive affect, including essential crying and witzelsucht, as described earlier. After identifying episodic uncontrollable laughing and crying as PBA, the causes of this condition must be identified. In most cases, the underlying neurological disorder producing PBA will be a known element of the paticnt's history. However, in some cases PBA may be the first presentation of this condition; in such cases, clinicians should undertake a thorough neurological
D.B. Arciniegas
history and examination, including magnetic resonance imaging of the brain, to identify that underlying neurological condition. In particular, clinicians should be aware of epilepsy as a cause of episodic affective displays. Dacrystic (or quiritarian) seizures are a form of complex partial epilepsy in which the ictal manifestation is crying) 8,19 In addition, gelastic seizures are a form of complex partial epilepsy in which laughing is the ictal manifestation. 19,20Although the episodes of crying and laughing in these types of seizures may resemble PBA, they are generally followed by at least a brief period of postictal confusion. This postictal disturbance of consciousness should facilitate clinical identification of these episodes as seizures rather than PBA. When the history does not facilitate distinction between seizure and PBA, electroencephalography (EEG) may be of use. Persons with dacrystic and gelastic seizures will often demonstrate interictal epileptiform discharges on sleep-deprived EEG. In cases where the EEG is performed during an affective display, ictal epileptiform activity and postictal slowing may be observed. When there is concern regarding the possibility of an epileptic basis for episodic uncontrollable crying or laughing, consultation with a neurologist specializing in epilepsy is prudent. Clinicians should also be mindful that epilepsy may also be a cause of PBA, and that there is a possibility that, though rare, some patients will present with both ictal and interictal displays of pathological affect. Evaluation
A simple screening question regarding the occurrence of episodic uncontrollable crying and/or laughing will, in many cases, suffice for the identification of persons with possible PBA. Affirmative responses to a screening question should prompt further characterization of such episodes. Clinicians first should seek to obtain information sufficient to ascertain whether PBA is the most correct diagnosis (ie, sort through the differential diagnosis described previously). After determining that the condition experienced by the patient is PBA, information regarding the symptom types, severity, frequency, and functional import should be obtained. This information is needed for diagnostic purposes, but also to establish a baseline against which the effects of treatment for PBA may be measured. Several scales have been developed for this purpose, including the Pathological Laughter and Crying Scale (PLACS), 21 the Emotional Lability Questionnaire (ELQ), 22 the Affective Lability Scale (A]_~),23 and the Center for Neurologic Study-Lability Scale (CNS-LS). 14
The American Journal of Geriatric Pharmacotherapy
The PLACS was developed specifically for the evaluation of post-stroke PBA, and has also been applied to the study of PBA following traumatic brain injury. 24 The PLACS is a valid and reliable measure with which to assess both baseline PBA symptoms and response to treatment. The ELQ is an adaptation of the PLACS specifically for use among persons with amyotrophic lateral sclerosis, and appears to be valid and reliable in that context. The ALS evaluates lability and intensity of affect, and was developed as a measure of such among healthy college students. It has not yet been applied to characterization or treatment studies among persons with PBA, leaving its reliability and validity in this context uncertain. The CNS-LS was developed for the purpose of evaluating PBA among persons with amyotrophic lateral sclerosis, 14 and also has been applied to the study of PBA due to multiple sclerosis) 2 The CNSLS also appears to be a valid and reliable measure with which to assess baseline PBA symptoms and response to treatment. Among these scales, the PLACS and the CNS-LS are used most often in research and clinical practice. Even if clinicians elect not to use the PLACS or the CNS-LS in everyday clinical practice, familiarity with the content of these scales will improve clinicians' abilities to identify PBA and the response of this condition to pharmacologic intervention. CONCLUSIONS Disorders of affect are distinct from disorders of mood, and may be a substantial source of distress and disability for patients and their families. Distinguishing disorders of affect from disorders of mood requires clinicians to first define mood and affect on temporal grounds, and to then characterize the subjective and objective aspects of these domains of emotion. Using a temporallybased nosology for mood and affect facilitates the identification of the primary domain in which emotional disturbances arise: mood versus affect. Among the disorders of affect, affective lability and PLC--grouped here under the term PBA--are the most common. PBA develops in the context of many neurological disorders, and occurs morc frequently than is commonly recognized in general medical, neurological, and psychiatric practices. Generating a differential diagnosis for PBA requires clinicians' familiarity with mood disorders, disorders of affect, and other neurological conditions (ie, dacrystic and gelastic epilepsy) that may present with such symptoms as well. Clinical evaluation of PBA may be guided usefully by assessment scales specifically designed for this purpose.
r
7
The AmericanJournal of Geriatric Pharmacotherapy D.B.Arciniegas
Use of these scales, formally or informally, will assist clinicians' efforts to diagnose PBA and to measure the effects of treatments they prescribe for this condition. REI=ERI~NCES
1. Damasio AR. Descartes~Error: Emotion, Reason, and the Human Brain. New York, NY: Putnam Publishing; 1994. 2. Dark FL, McGrath JJ, Ron MA. Pathological laughing and crying. Aust NZJPsychiatry. 1996;30:472-479. 3. Green RL. Regulation of affect. Semin Clin Neuropsychiatry. 1998;3:195-200. 4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder6 Fourth Edition. Washington, DC: American Psychiatric Press; 1994. 5. Arciniegas DB, TopkoffJ. The neuropsychiatry of pathologic affect: An approach to evaluation and .treatment. Semin Clin Neuropsychiatry. 2000;5:290-306. 6. 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. 7. Poe& K. Pathological laughing and weeping in patients with progressive bulbar palsy. Ger Med Mon. 1969;14: 394-397. 8. Poeck K. Pathological laughter and crying. In: Fredericks JAM, ed. Handbook of Clinical Neurology. Vol 45. Amsterdam, Netherlands: Elsevier Science Publishers; 1985. 9. Green RL, Bernat JL. Pathologic crying. In: Joseph AB, Young RR, eds. Movement Disorders in Neurology and Neuropsychiatry. Oxford, England: Blackwell Science Inc.; 1999. 10. Berkovic SF, Andermann F. Pathological laughing. In: Joseph AB, Young RR, eds. Movement Disorders in Neurology and Neuropsychiatry. Oxford, England: Blackwell Science Inc.; 1999. 11. Duchowny MS. Pathological disorders of laughter. In: McGhee PE, Goldstein JH, eds. Handbook of Human Research. Vol 8. New York, NY: Springer Verlag; 1983. 12. Smith RA, Berg JE, Pope LE, et al. Validation of the CNS emotional lability scale for pseudobulbar affect
8
(pathological laughing and crying) in multiple sclerosis patients. Mult Scler. 2004;10:679-685. 13. Woyshville MJ, Lackamp jM, Eisengart JA, Gilliland JA. On the meaning and measurement of affective instability: Clues from chaos theory [published correction appears in Biol Psychiatry. 1999;45:1081]. Biol Psychiatry. 1999;45: 261-269. 14. Moore SR, Gresham LS, Bromberg MB, et al. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997;63:89-93. 15. Green RL, McAllister TW, Bernat JL. A study of crying in medically and surgically hospitalized patients. A m J Psychiatry. 1987;144:442447, 16. Arciniegas DB, Lauterbach EC, Anderson KE, et al. The differential diagnosis ofpseudobulbar affect (PBA): Distinguishing PBA amor*g disorders of mood and affect. Proceedings of a roundrable meeting. CNS Spectr. 2005;10: 1-14. 17. Trimble MR, Mendez MF, Cummings JL. Neuropsychiatric symptoms from the temporolimbic lobes. J Neuropsychiatry Clin Neurosei. 1997;9:429-438. 18. Luciano D, Devinsky O, Perrine K. Crying seizures. Neurology. 1993;43:2113-2117. 19. Sackeim HA, Greenberg MS, Weiman AL, et al. Hemisphere asymmetry in the expression of positive and negative emotions: Neurologic evidence. Arch Neurol. 1982;39:210-218. 20. Pearce JM. A note on gelastic epilepsy. Eur Neurol. 2004;52:172-174. 21. Robinson RG, Parikh RM, Lipsey JR, et al. Pathological laughing and crying following stroke: Validation of a measurement scale and a double-blind treatment study. Am J Psychiatry. 1993;150:286-293. 22. Newsom-Davis IC, Abrahams S, Goldstein LH, Leigh PN. The emotional lability questionnaire: A new measure of emotional lability in amyotrophic lateral sclerosis. f Neurol Sd. 1999;169:22-25. 23. Harvey PD, Greenberg BR, Serper MR. The affective lability scales: Development, reliability, and validity.J Clin Psychol. 1989;45:786-793. 24. Tateno A, Jorge RE, Robinson RG. Pathological laughing and crying following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2004;16:426-434.