Pseudobulbar affect 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

Brain injury

A brain injury is any injury occurring in the brain of a living organism. Brain injuries can be classified along several dimensions. Primary and secondary brain injury are ways to classify the injury processes that occur in brain injury, while focal and diffuse brain injury are ways to classify...

. 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.

Terminology

Historically there have been a variety of terms used including pseudobulbar affect, pathological laughter and crying, emotional lability, emotionalism, emotional dysregulation, or, more recently, involuntary emotional expression disorder (IEED).
Terms such as forced crying, involuntary crying, pathological emotionality, and emotional incontinence have also been used, although less frequently. Following FDA approval of a treatment indicated for pseudobulbar affect or PBA, this term is likely to become the preferred name in clinical and research use.

Clinical presentation

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.

Characteristics

The symptoms of PBA can be severe, with persistent and unremitting episodes. Characteristics include:

• the onset can be sudden and unpredictable, and has been described by some patients as coming on like a seizure;
• the outburst have a typical duration of a few seconds to several minutes;
• outbursts may happen several times a day

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

PBA was first described in the medical literature more than 130 years ago. Charles Darwin described elements of the condition in his seminal text The Expression of the Emotions in Man and Animals. Although the symptoms of PBA have been recognized for more than a century, 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

Prefrontal cortex

The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

 is involved.

Pseudobulbar affect is 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

Neural Networks

Neural Networks is the official journal of the three oldest societies dedicated to research in neural networks: International Neural Network Society, European Neural Network Society and Japanese Neural Network Society, published by Elsevier...

 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

Traumatic brain injury

Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

 (TBI) and stroke

Stroke

A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, and neurologic diseases such as dementias including Alzheimer's disease

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

, multiple sclerosis

Multiple sclerosis

Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

 (MS), amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

 (ALS), and Parkinson's disease

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

 (PD).

PBA has also been observed in association with a variety of other brain disorders, including brain tumors, Wilson’s disease, syphilitic pseudobulbar palsy

Pseudobulbar palsy

Pseudobulbar palsy results from an upper motor neuron lesion to the corticobulbar pathways in the pyramidal tract. Patients have difficulty chewing, swallowing and demonstrate slurred speech...

, and various encephalitides

Encephalitis

Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

. Rarer conditions associated with PBA include gelastic epilepsy

Epilepsy

Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

, dacrystic epilepsy, central pontine myelinolysis

Central pontine myelinolysis

Central pontine myelinolysis is neurological disease caused by severe damage of the myelin sheath of nerve cells in the brainstem, more precisely in the area termed the pons, predominately of iatrogenic etiology...

, olivopontinocerebellar atrophy, lipid storage diseases, chemical exposure

Toxicity

Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

 (e.g., nitrous oxide

Nitrous oxide

Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...

 and insecticides), fou rire prodromique, and the puppetlike syndrome of Angelman

Angelman syndrome

Angelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....

.

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.

Impact on social life

While not as profoundly disabling as the physical symptoms of these diseases, PBA can have a significant impact on individuals' social functioning and their relationships with others. Such sudden, frequent, extreme, uncontrollable emotional outbursts may lead to social withdrawal and interfere with activities of daily living, social and professional pursuits, and have a negative impact on overal healthcare. For example, patients with ALS and MS are often cognitively normal; however, the appearance of uncontrollable emotions is commonly associated with learning disabilities

Learning disability

Learning disability is a classification including several disorders in which a person has difficulty learning in a typical manner, usually caused by an unknown factor or factors...

; this may lead to severe embarrassment and avoidance of social interactions for the patient, which in turn has an impact on their coping mechanisms and their careers.

Depression: distinct or coexisting

PBA may often be misdiagnosed as depression, however many clear distinctions exist.

In depression and grief syndromes, crying is typically a sign of sadness, whereas the pathological displays of crying which occur in PBA are often in contrast to the underlying mood, or greatly in excess of the mood or eliciting stimulus. In addition, a key to differentiating depression from PBA is duration: PBA episodes are sudden, occurring in a brief episodic manner, while crying in depression is a more sustained presentation and closely relates to the underlying mood state. The level of control that one has over the crying episodes in PBA is minimal or nonexistent, whereas for those suffering from depression, the emotional expression (typically crying) can be modulated by the situation. Similarly, the trigger for episodes of crying in patients with PBA may be nonspecific, minimal or inappropriate to the situation, but in depression the stimulus is specific to the mood-related condition. These differences are outlined in the adjacent Table.

In some cases, depression and PBA may co-exist. In fact, depression is one of the most common emotional changes in patients with neurodegenerative disease or post-stroke sequelae. As a result, it is often comorbid with PBA. Comorbidity implies that depression is distinct from PBA and is not necessary for, nor does it exclude, a diagnosis of PBA.

Prevalence of PBA symptoms

PBA is surprisingly prevalent, affecting both patients and those that care for them. Prevalence estimates place the number of people with PBA between 1.5 and 2 million in the United States alone. However, given the fact that PBA is a relatively common disorder among patients with various neurologic conditions, its actual prevalence may be higher. Furthermore, PBA is generally thought to be under-recognized and undertreated because clinicans are unfamiliar with the disorder. http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=378

Prevalence in patients with stroke

PBA is one of the most frequently reported poststroke 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 poststroke depression and PBA is complicated, because the depressive syndrome also occurs with high frequency in stroke survivors. Poststroke 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 MS

Recent studies suggest a lifetime prevalence of PBA of approximately 10% in patients with MS. 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 ALS

A study designed specifically to survey for prevalence found that 49% of patients with ALS also had PBA. PBA does not appear to be associated with duration of amyotrophic lateral sclerosis. Despite it being a widely-known symptom in ALS, many clinicians choose not to tell their patients about it, despite patients and their caregivers wanting to know more.

Prevalence in patients with TBI

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.

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

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, antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

s such as fluoxetine

Fluoxetine

Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...

, citalopram

Citalopram

Citalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S...

, or amitriptyline

Amitriptyline

Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...

 have been prescribed with moderate efficacy. In 2010, a combination of dextromethorphan

Dextromethorphan

Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

 and quinidine

Quinidine

Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...

 was approved by the U.S. Food and Drug Administration (FDA) for to treat PBA. The drug, Nuedexta, was developed and created by Avanir Pharmaceuticals and became available on January 31, 2011.