Overview

It is said that laughter is the best medicine, but involuntary laughing (or crying) can be socially debilitating and embarrassing. Pseudobulbar affect (PBA) is an uncontrollable response of the central nervous system in which an individual has emotional eruptions such as outbursts of crying or laughing.¹ These expressions may not have precipitating stimuli and are often disruptive, unrelated to mood, and incongruent with or disproportionate to the context. Despite its common occurrence among patients with neurologic disorders, PBA has low recognition among health care professionals (AV 1).¹

PBA has also been known by a variety of other terms, including affective lability, involuntary emotional expression disorder, or simply pathological laughing and crying.^2–4 The 6 neurologic conditions most commonly associated with PBA are Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), MS, Parkinson’s disease, stroke, and traumatic brain injury (TBI).¹ An online survey by Work et al¹ screened 2,318 patients with these conditions for PBA, and, using disease population estimates from government agencies and professional organizations, the investigators reported a US prevalence of PBA ranging from 1.8 million to 7.1 million people, depending on the screening tools and thresholds used.¹ The highest prevalence (a mean rate of 37.5%) was found using the Center for Neurologic Study-Lability Scale (CNS-LS) with a cutoff score of 13.

In a registry study called PRISM,⁵ Brooks and colleagues evaluated the prevalence of PBA by enrolling patients with these 6 neurologic diseases at 173 sites. Data from 5,290 patients showed an overall prevalence rate of 37%, ranging from 26% in Parkinson’s disease to 52% in TBI (AV 2).⁵

Due to the potential for an increasing incidence of neurologic conditions such as Alzheimer’s disease among the aging population,⁶ health care professionals may begin to encounter more patients with PBA.³ In the PRISM study, 58% of participants were aged 65 years and older, and in this subgroup the overall prevalence of PBA was 27% (AV 3).⁷

AV 3. Prevalence of PBA in Patients Aged ≥ 65 Years by Neurologic Condition (N=3,048)

---

Unfortunately, PBA has often been missed by clinicians. The survey¹ by Work and colleagues indicated that, among patients who discussed their crying/laughing symptoms with a physician, 41% received a diagnosis, but none received a diagnosis of PBA. One-third of patients who were diagnosed received a major depressive disorder (MDD) diagnosis, 28% were told the symptoms were just part of the neurologic condition, and others received diagnoses of bipolar disorder, posttraumatic stress disorder, anxiety, or other conditions. About half of those diagnosed received a medication to treat their episodes.

Proposed Pathophysiology of PBA

The exact causes of PBA are unclear, although it is believed to be related to disruption of neural networks involving the limbic and paralimbic systems modulated by the cerebellum.⁴ PBA is believed to be a disorder of frontal dysregulation and disinhibition (AV 4).³ Several hypotheses describe proposed pathophysiologic processes involved.

Release hypothesis. The release hypothesis posited by Wilson⁸ in 1924 holds that PBA is due to disruption of cortical inhibition to an upper brainstem center, followed by release of lower bulbar nuclei that affect the motor responses associated with laughing and crying.⁴ In a revised theory, Parvizi and colleagues suggested that brain lesions affect the cerebro-pontocerebellar pathways, meaning the cerebellar structures that would normally trigger laughing or crying in response to a stimulus are forced to “operate on the basis of incomplete information about that context.”^9[p.1708]

Gate control theory. Studies of the etiology of PBA in patients with MS suggest that the disorder is due to disinhibition of the “gate control” mechanisms that normally hold emotional expressions in check.¹⁰ In this theory, neurologic damage from MS or another neurodegenerative disease disrupts activity in the cortical structures related to sensory-motor and emotional processing, as well as overactive involvement of motor cortical areas.

Dysfunction of neurotransmitters theory. Disruption of cortico-limbic-subcortico-thalamic-pontocerebellar pathways that control human emotion is suggested in each of the previous theories.¹¹ Key neurotransmitters, including serotonin, dopamine, glutamate, and sigma-1, are involved in carrying signals between neurologic structures to convey information about emotional expression.⁴ This suggests that interventions targeting these modulators may offer a possible avenue for treatment.¹¹

Diagnosis of PBA

PBA can be confusing to the patient, family members, and social contacts because the behavior does not necessarily reflect how the affected person is actually feeling. PBA sometimes occurs as an exaggerated response to a predictable (and expected) emotion, but it also can occur as a completely paradoxical response to the circumstances.³ Diagnostic criteria for PBA include the following symptoms and impairment:^2,3

• Involuntary or exaggerated emotional expression, including episodes of laughing, crying, or related emotional displays, resulting from a brain disorder (patients may have only laughing or only crying episodes, or they may have both)
• Episodes represent a change in the patient’s usual emotional reactivity, are exaggerated or incongruent with the patient’s subjective emotional state, and are independent or in excess of an eliciting stimulus
• Symptoms cause clinically significant distress or impairment in social or occupational functioning
• The person may also experience outbreaks of anger
• Symptoms cannot be attributed to another neurologic or psychiatric disorder or to the effects of a substance

In patients with neurologic disorders, clinicians must carefully differentiate PBA from other conditions affecting behavior and cognition, including MDD and psychosis. For example, depression occurs in roughly 20% to 45% of people with Parkinson’s disease and MS and about 10% to 35% of people with stroke.¹² Depending on the criteria used, 35% to 54% of patients with Alzheimer’s disease have MDD.¹³ Psychotic symptoms have been found in 41% of people with Alzheimer’s disease¹⁴ and about 25% of individuals with Parkinson’s disease.^15,16

Family members are frequently the first to notice the onset of PBA symptoms—often before the patient does. However, because of the relatively low awareness and understanding of PBA, friends and family members may assume that the behavior is conscious or voluntary on the part of the patient. PBA can cause embarrassment in social situations, but many family members will not bring up the issue with a health care professional unless they are asked. If PBA is suspected, questioning family members separately may assist in the diagnostic process. The provider should first confirm that the individual is authorized to share the patient’s health care information.

CME Background Information

Supported by an educational grant from Otsuka America Pharmaceutical, Inc.

Brought to you through the joint providership of the CME Institute of Physicians Postgraduate Press, Inc., and CMEology.

Participants may receive credit by reading the activity, correctly answering the posttest questions, and completing the evaluation.

Objective

After completing this educational activity, you should be able to:

• Use appropriate validated instruments to screen for PBA
• Implement strategies for improving the differential diagnosis of PBA
• Provide evidence-based pharmacologic treatment for PBA

Financial Disclosure

The faculty for this CME activity and the CME Institute and CMEology staffs were asked to complete a statement regarding all relevant personal and financial relationships between themselves or their spouse/partner and any commercial interest. The CME Institute has resolved any conflicts of interest that were identified. No member of the CME Institute or CMEology staffs reported any relevant personal financial relationships. Faculty financial disclosure is as follows:

Dr David W. Crumpacker is a member of the speakers/advisory boards for Avanir, Otsuka, Merck, and Forest and is a stock shareholder of Pfizer.

Accreditation Statement

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the CME Institute of Physicians Postgraduate Press, Inc., and CMEology. The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The American Academy of Physician Assistants (AAPA) accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 1 hour of Category I credit for completing this program.

To obtain credit for this activity, study the material and complete the CME Posttest and Evaluation.

Release, Review, and Expiration Dates

This Psychlopedia activity was published in July 2016 and is eligible for AMA PRA Category 1 Credit™ through July 31, 2017. The latest review of this material was June 2016.

Statement of Need and Purpose

Pseudobulbar affect (PBA) is a socially debilitating condition that affects a large portion of patients with neurologic diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and traumatic brain injury. This condition is widely underrecognized and misunderstood among the public and health care providers. With the association between PBA and some neurologic conditions related to aging, the incidence of this syndrome is likely to increase as the population ages. Because PBA is frequently mistaken for depression, psychiatrists need to be familiar with the differential diagnosis. Psychiatrists and other health care professionals who treat patients with neurologic conditions need updated guidance on how to screen patients for PBA, how to differentiate its symptoms from those of mood disorders, and how to implement evidence-based management approaches.

This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc., who have requested information on pseudobulbar affect.

Disclosure of Off-Label Usage

Dr Crumpacker has determined that, to the best of his knowledge, dextromethorphan hydrobromide, fluoxetine, and quinidine sulfate are not approved by the US Food and Drug Administration for the treatment of pseudobulbar affect.

Review Process

The faculty reviewed the activity for accuracy and fair balance, and a member of the External Advisory CME Board who is without conflict of interest peer-reviewed the activity to determine whether the material is evidence-based and objective.

Acknowledgment

The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher or the commercial supporter.