Pseudobulbar affect (PBA)

Pseudobulbar affect (PBA), emotional lability, labile affect, or emotional incontinence refers to a neurologic disorder characterized by involuntary crying or uncontrollable episodes of crying and/or laughing, or other emotional displays.PBA occurs secondary to neurologic disease or brain injury. Patients may find themselves crying uncontrollably at something that is only moderately sad, being unable to stop themselves for several minutes. Episodes may also be mood-incongruent: a patient might laugh uncontrollably when angry or frustrated, for example.

Background and current understanding

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. Where patients have significant cognitive deficits (e.g., Alzheimer's) it can be unclear whether it is true PBA as opposed to a grosser form of emotional dysregulation, but patients with intact cognition often report the symptom as disturbing. 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 clinical impact of PBA can be severe, with unremitting and persistent symptoms that can be disabling to patients, and may significantly impact quality of life for caregivers.

Causes

The specific pathophysiology involved in this frequently debilitating condition is still under investigation; the primary pathogenic mechanisms of PBA remain controversial.One hypothesis, established by early researchers such as Wilson and Oppenheim, placed emphasis on the role of the corticobulbar pathways in modulating emotional expression in a top-down model, and theorized that PBA occurs when bilateral lesions in the descending corticobulbar tract cause failure of voluntary control of emotion, which leads to the disinhibition, or release, of laughing/crying centers in the brainstem.Other theories implicate the prefrontal cortex.

A secondary condition

Pseudobulbar affect is a condition that occurs secondary to neurological disease or brain injury, and is thought to result from disruptions of neural networks that control the generation and regulation of motor output of emotions. PBA is most commonly observed in people with neurologic injuries such as traumatic brain injury (TBI) and stroke, and neurologic diseases such as dementias including Alzheimer's disease, attention deficit/hyperactivity disorder (ADHD),multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Lyme disease, PANDAS in children and adults, and Parkinson's disease (PD).

PBA has also been observed in association with a variety of other brain disorders, including brain tumors, Wilson's disease, syphilitic pseudobulbar palsy, and various encephalitides. Rarer conditions associated with PBA include gelastic epilepsy, dacrystic epilepsy, central pontine myelinolysis, olivopontinocerebellar atrophy, lipid storage diseases, chemical exposure (e.g., nitrous oxide and insecticides), fou rire prodromique, and Angelman syndrome.

It is hypothesized that these primary neurologic injuries and diseases impact chemical signaling in the brain, which in turn disrupts the neurologic pathways that control emotional expression.

Prevalence of PBA symptoms

Prevalence estimates place the number of people with PBA between 1.5 and 2 million in the United States alone. Some argue that the number is probably higher and that clinicians underdiagnose PBA.However, the prevalence estimate of 2 million is based on an online survey. Self-selected computer savvy patients in at-risk groups evaluated their own symptoms and submitted their self-diagnoses. No doctor or clinic confirmed the data. Motivation to participate could have been influenced by the presence of symptoms, which would have skewed the results. The actual prevalence could very well be quite a bit lower than estimated.

Prevalence in patients with stroke

PBA is one of the most frequently reported post-stroke behavioral syndromes, with a range of reported prevalence rates from 28% to 52%.The higher prevalence rates tend to be reported in stroke patients who are older and/or who have a history of prior stroke.The relationship between post-stroke depression and PBA is complicated, because the depressive syndrome also occurs with high frequency in stroke survivors. Post-stroke patients with PBA are more depressed than poststroke patients without PBA, and the presence of a depressive syndrome may exacerbate the weeping side of PBA symptoms.

Prevalence in patients with multiple sclerosis

Recent studies suggest that approximately 10% of patients with multiple sclerosis (MS) will experience at least one episode of emotional lability.PBA is generally associated with later stages of the disease (chronic progressive phase).PBA in MS patients is associated with more severe intellectual deterioration, physical disability, and neurological disability.

Prevalence in patients with amyotrophic lateral sclerosis

A study designed specifically to survey for prevalence found that 49% of patients with amyotrophic lateral sclerosis (ALS) also had PBA.[18] PBA does not appear to be associated with duration of amyotrophic lateral sclerosis. It is a symptom of ALS that many patients are unaware of and do not get information about by their physician.

Prevalence in patients with traumatic brain injury

One study of 301 consecutive cases in a clinic setting reported a 5% prevalence. PBA occurred in patients with more severe head injury, and coincided with other neurological features suggestive of pseudobulbar palsy.

The Brain Injury Association of America (BIAA) indicates that approximately 80% of survey respondents experience symptoms of an additional neurologic condition called pseudobulbar affect (PBA).

Results from a recent investigation estimates the prevalence of pseudobulbar affect associated with traumatic brain injury to exceed more than 55% of survivors.

Treatment

Recognition is crucial for the treatment of PBA. Education of patients, families, and caregivers is an important component of the appropriate treatment of PBA. Crying associated with PBA may be incorrectly interpreted as depression; laughter may be embarrassing. It is therefore critical for families and caregivers to recognize the pathological nature of PBA and the reassurance that this is an involuntary syndrome that is manageable. Traditionally, antidepressants such as sertraline,fluoxetine,citalopram,nortriptyline and amitriptyline have been prescribed with some efficacy.

Dextromethorphan/quinidine

Dextromethorphan/quinidine (trade name: Nuedexta) is the first FDA-approved drug for the treatment of PBA. Treatment with dextromethorphan/quinidine significantly decreased laughing and crying episodes in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) as compared with placebo in a 12-week, randomized, double-blind study (n=326).