Pseudobulbar Affect: When Patients Laugh Or Cry, but Don’T Know Why
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Pseudobulbar affect: When patients laugh or cry, but don’t know why Disruption of neural circuitry undermines voluntary control of affect seudobulbar affect (PBA) is a disorder of affective expression that manifests as stereotyped and frequent Poutbursts of crying (not limited to lacrimation) or laugh- ter. Symptoms are involuntary, uncontrolled, and exaggerated or incongruent with current mood. Episodes, lasting a few seconds to several minutes, may be unprovoked or occur in response to a mild stimulus, and patients typically display a normal affect between episodes.1 PBA is estimated to affect 1 to 2 million people in the United States, although some studies suggest as many as 7 million,1,2 depending on the evaluation method and threshold criteria used.3 Many terms have been used to describe aspects of PBA (Table 14 and Box, page 585-10). This abundance of often con- flicting terminology is thought to have impeded efforts to © SIMONE GOLOB/CORBIS categorize emotional expression disorders, determine their Benjamin Frock, MD prevalence, and evaluate clinical evidence of potential ther- PGY-1 Resident apeutic options.11 Vanderbilt University School of Medicine Nashville, Tennessee Andrew Williams, MD Where to look for pseudobulbar affect PGY-1 Resident Oregon Health & Science University PBA has been most commonly described in 6 major neuro- Portland, Oregon logic disorders: Jason P. Caplan, MD • Alzheimer’s disease Professor and Chair of Psychiatry • amyotrophic lateral sclerosis (ALS) Creighton University School of Medicine • multiple sclerosis (MS) Phoenix Regional Campus Phoenix, Arizona • Parkinson’s disease • stroke • traumatic brain injury (TBI). Disclosures Dr. Caplan has served as a consultant to Avanir Pharmaceuticals, an independent subsidiary of Otsuka America, Inc., manufacturer of the formulation of dextromethorphan/quinidine discussed Current Psychiatry in this article. Drs. Frock and Williams report no financial relationships with any company whose 56 September 2016 products are mentioned in this article or with manufacturers of competing products. Of these disorders, most studies have Table 1 found the highest PBA prevalence in patients The study of PBA has yielded with ALS and TBI, with lesser (although sig- a long list of descriptive terms nificant) prevalence in Parkinson’s disease (Table 2, page 59).1,12 These “big 6” diagnoses Affective lability are not a comprehensive list, as many other Emotional dyscontrol disease states are associated with PBA (Table Emotional dysregulation 3, page 59).12-14 Emotional incontinence As PBA has become better defined and Emotional lability more widely recognized, additional sequelae Emotionalism have been described. PBA’s sporadic and Excessive emotionality unpredictable nature and the potential Forced laughter or crying embarrassment and distress of public out- Inappropriate hilarity bursts may lead to an agoraphobia-like Involuntary emotional expression disorder response.15 People with PBA report a signifi- Labile affect cantly worse subjective assessment of gen- Pathological affect eral health, quality of life, relationships, and Pathological laughter and crying Clinical Point Pathological weeping work productivity compared with people PBA’s unpredictable with similar primary underlying diagnoses Pseudobulbar crying without PBA.16 PBA: pseudobulbar affect nature and potential Source: Reference 4 embarrassment of public outbursts 2 Pathways: ‘Generator’ and may lead to an ‘governor’ basis pedunculi, and continues on to the agoraphobia-like Despite the many and varied injuries and anteroventral basis pontis. The basis pontis illnesses associated with PBA, Lauterbach then serves as an afferent relay center for response et al10 noted patterns that suggest dysregu- cerebellar activity. Projections from the pons lation of 2 distinct but interconnected brain then regulate the emotional circuitry primar- pathways: an emotional pathway controlled ily at the level of the PAG.10 by a separate volitional pathway. Lesions Lesions of the volitional pathway have to the volitional pathway (or its associated been correlated with conditions of PBA, feedback or processing circuits) are thought whereas direct activation of the emotional to cause PBA symptoms. pathway tended to lead to emotional labil- To borrow an analogy from engineering, ity or the crying and laughing behaviors the emotional pathway is the “generator” observed in dacrystic or gelastic epilepsy.10 of affect, whereas the volitional pathway is The pivotal nature of the regulation the “governor” of affect. Thus, injury to the occurring at the PAG has guided treat- “governor” results in overspill, or overflow, ment options. Neurotransmitter recep- of affect that usually would be suppressed. tors most closely associated with this region include glutamatergic N-methyl-d- The emotional pathway, which coordinates aspartate (NMDA), muscarinic M1 to M3, the motor aspect of reflex laughing or cry- γ-aminobutyric acid (GABA)-A, dopamine ing, originates at the frontotemporal cortex, D2, norepinephrine α-1 and α-2, sero- relaying to the amygdala and hypothala- tonin 5-HT1B/D, and sigma-1 receptors. mus, then projecting to the dorsal brainstem, Volitional inhibition of the PAG is medi- which includes the midbrain-pontine peri- ated by acetylcholine and GABA balance Discuss this article at aqueductal gray (PAG), dorsal tegmentum, at this location.10 www.facebook.com/ CurrentPsychiatry and related brainstem. The volitional pathway, which regulates the When to screen for PBA emotional pathway, originates in the dorsal Ask the right question. PBA as a disease and lateral frontoparietal cortex, projects state likely has been widely under-reported, Current Psychiatry through the internal capsule and midbrain under-recognized, and misdiagnosed (typi- Vol. 15, No. 9 57 Box From Darwin to IEED, nomenclature has evolved over time harles Darwin5 was among the first to was related to motor disinhibition resulting Cacknowledge the correlation between from bilateral corticobulbar lesions that neurologic insult and dysregulated emotional disengaged a brainstem “faciorespiratory expression, writing in 1872 that “certain brain center” from cortical levels of control. In disease, such as hemiplegia, brain-wasting, 1963, Poeck et al8 proposed diagnostic Pseudobulbar and senile decay, have a special tendency to criteria for PLC. induce weeping.” More recently, Cummings et al9 proposed affect In 1886, Oppenheim and Siemerling6 “involuntary emotional expression disorder” proposed the terms “pseudobulbar affect” (IEED) in 2006 as an umbrella term for (PBA) and “pseudobulbar palsy” (a separate disorders having “involuntary outbursts or and distinct state that includes dyscontrol crying and/or laughing” as a primary feature. of facial muscles, resulting in dysarthria, To distinguish more sufficiently between dysphagia, and dysphonia) in their descriptions purely affective etiologies of these features of patients with bilateral forebrain injury that (PBA) and disorders that include dysfunction appeared to mimic brainstem dysfunction. of both mood and affect, Lauterbach et Wilson7 in 1924 proposed that al10 divided IEED into 2 subtypes: PLC and pathological laughing and crying (PLC) emotional lability. Clinical Point A single question might best refine cally, as a primary mood disorder).9 Three presence and severity of PBA symptoms.1 A the likelihood that factors underscore this problem: 7-question, patient self-administered tool, a patient has PBA: • Patients do not specifically report the CNS-LS is graded on a 5-point Likert ‘Do you ever cry symptoms of affective disturbance (perhaps scale. A score ≥13 has high sensitivity and because they lack a vocabulary to separate specificity for diagnosis of PBA, compared for no reason?’ concepts of mood and affect) with physician diagnosis. • Physicians do not ask patients about Another option, the 16-question separations of mood and affect Pathological Laughing and Crying Scale, • Perhaps most importantly, PBA lacks a is a clinician-administered screening tool. general awareness and understanding. Again, a score ≥13 is consistent with symp- Co-occurring mood disorders also may toms required for a PBA diagnosis. thwart PBA detection. One study of PBA in Alzheimer’s dementia found that 53% of patients with symptoms consistent with Treating PBA symptoms PBA also had a distinct mood disorder.17 This Until recently, most pharmacotherapeutic suggests that a PBA-specific screening test is interventions for PBA were based on off- needed for accurate diagnosis. label use of tricyclic antidepressants (TCAs) A single question might best refine the or selective serotonin reuptake inhibitors likelihood that a patient has PBA: “Do you (SSRIs). From 1980 to 2010, only 7 of 22 case ever cry for no reason?” In primary psy- reports or trials of TCAs or SSRIs for PBA chiatric illness, crying typically is associ- were randomized, double-blind, and pla- ated with a specific trigger (eg, depressed cebo-controlled. Five had 12 to 28 patients, mood, despair, anxiety). A patient’s inabil- and 2 had 106 and 128 patients, respectively. ity to identify a trigger for crying suggests Only 1 controlled trial included a validated the pathological separation of mood and symptom severity scale, and none included affect—the core of PBA, and worthy of fur- a scale validated for PBA.18 ther investigation. In particular, imipramine and nortrip- tyline were studied for managing PBA Clinical rating scales that correlate to dis- in patients with stroke;