Introduction
Pseudobulbar affect (PBA) can arise in connection with various amyotrophic lateral sclerosis, extrapyramidal and cerebral disorders, multiple sclerosis, and traumatic brain tumors. This condition can have significant psychological and social repercussions. Although it is often mistaken for mood disorders like depression or bipolar disorder, distinct clinical features and validated scales enable accurate identification of PBA, allowing for appropriate management and treatment. Mechanistically, PBA is a disinhibition syndrome involving serotonin and glutamate pathway disruptions.
What Is the Pseudobulbar Effect (PBA)?
Pseudobulbar affect (PBA) is characterized by uncontrolled episodes of crying, laughter, or other emotional expressions in inappropriate social contexts. PBA arises as a secondary condition to various neurological disorders, and its impact can be significant. It often leads to embarrassment for individuals with PBA and their families and caregivers. It may limit their ability to engage in social interactions, resulting in a lower quality of life.
PBA is a term used to describe conditions that are known by other names such as reflex crying, emotional lability, and involuntary emotional expression disorder. PBA can manifest in individuals with stroke, amyotrophic lateral sclerosis, Parkinson’s disease, traumatic brain injury, dementia, Wilson’s disease, multiple sclerosis, and brain tumors.
The underlying mechanisms of PBA involve a disconnect between the frontal lobe, responsible for controlling emotions, and the cerebellum and brain stem, where reflexes are regulated. This disconnection leads to uncontrollable emotional outbursts that can occur without any specific emotional trigger. People with PBA experience involuntary episodes of crying, laughter, or anger, which can sometimes be disproportionate to the situation, such as intense weeping in response to a mildly sad event or sudden bouts of laughter during somber occasions. The condition can also involve rapid switching between laughter and crying.
How Does PBA Occur?
The underlying mechanism behind Pseudobulbar affects seems to involve a lack of voluntary control referred to as disinhibition. However, the specific pathways involved are complex and not yet fully understood. Recent research has highlighted the significant role of the cerebellum in PBA, which was not previously emphasized. There are pathways connecting the cortex to the pons and then to the cerebellum, influencing both motor function and cognitive and emotional aspects. Observations of emotional abnormalities in individuals with cerebellar lesions and a high prevalence of PBA in patients with multiple system atrophy cerebellar types support this.
One hypothesis suggests that the cerebellum modulates emotional responses to maintain appropriateness in social situations and align with the patient’s mood based on input from the cerebral cortex. Disruption of these corticopontine-cerebellar circuits impairs this modulation, leading to PBA. Both sensory and motor inputs appear to be involved.
A theory proposes that the cerebellum acts as a ‘gate control’ for the motor control of emotions. It receives input from the motor cortex, frontal, and temporal cornices through the brainstem, which modulates. Inhibitory input from the somatosensory cortex plays a role, and a reduction in this inhibitory input results in cerebellar disinhibition, leading to socially inappropriate or situationally disproportionate emotional expressions seen in PBA.
Ongoing investigations are exploring the specific cerebellar circuitry involved in this process. The primary neurotransmitters implicated in PBA are serotonin and glutamate. Serotonin’s role in corticolimbic and cerebellar pathways likely contributes to its impact on PBA. At the same time, glutamate, as an excitatory neurotransmitter with widespread distribution in the brain, can have far-reaching effects when its transmission is modulated.
How Is PBA Diagnosed?
The diagnosis of PBA involves:
Informal Diagnosis:
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Clinicians often informally assess the presence of PBA as part of their neurological evaluations.
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Attempts have been made to establish objective criteria for diagnosing PBA.
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In 1969, Poeck defined four criteria for PBA, including:
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Emotional responses are situationally inappropriate.
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The patient’s feelings and emotional responses are not closely related.
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The patient cannot control the episodes’ duration and severity.
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Expressing the emotion does not result in relief.
Later criteria emphasize a disproportionate emotional response as a key feature and consider changes from the patient’s previous emotional responses.
Objective Measurement:
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PBA can be assessed objectively using published scales.
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The Center for Neurologic Study-Lability Scale (CNS-LS) is a self-administered questionnaire with seven items, validated in ALS and MS patients.
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The pathological laughter and crying scale (PLACS) is an interviewer-administered tool with 18 questions validated in acute stroke patients.
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Specific cutoff scores on their scales indicate the presence and severity of PBA.
Cumming’s necessary key elements of episodes for PBA diagnosis include:
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There is a change from the patient’s previous emotional responses.
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Emotional responses are inconsistent with or disproportionate to the patient’s mood.
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Episodes are not dependent on a specific stimulus or are excessive relative to the stimulus.
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These episodes cause significant distress or impairment in social or occupational functioning.
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Another psychiatric or neurological disorder does not explain the symptoms.
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The symptoms are not a result of medication.
What Is the Treatment of PBA?
The treatment of PBA includes:
In General:
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The primary objective in treating PBA is reducing episodes' frequency and severity.
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The primary targets are norepinephrine, serotonin, or glutamate. Medications used include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and Dextromethorphan.
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Historically, medications like Levodopa and Amantadine were used but showed lower response rates.
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SSRIs and TCAs primarily work through serotonergic action, enhancing serotonin availability in corticolimbic and cerebellar pathways. TCAs have a broader range of neurotransmitter effects.
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Dextromethorphan, a cough suppressant, inhibits glutamatergic neurotransmission. When used as monotherapy, it is rapidly converted to an inactive form in the liver. Quinidine sulfate is used alongside it to block this conversion, resulting in higher and sustained plasma concentrations.
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Neudexta was the first FDA-approved drug for PBA, containing Dextromethorphan and Quinidine. Approval was based on a trial showing a significant reduction in laughing and crying episodes in treated patients with MS or ALS.
Specific Treatment:
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Clinicians should consider tolerance and potential adverse effects when selecting treatment. TCAs have a broader range of side effects, including dry mouth, constipation, and cardiotoxicity, making them less tolerable, especially in the elderly.
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TCAs can be useful for controlling sialorrhea (excessive salivation_, as seen in patients with bulbar ALS.
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SSRIs generally have a more limited side effect profile and are better tolerated with a lower discontinuation rate. They are also effective for treating PBA without causing significant sedation.
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Dosing ranges vary depending on the drug and individual.
Common side effects include dizziness, falls, diarrhea, and nausea.
Conclusion
Pseudobulbar affect (PBA) can significantly affect the quality of life and overall disease burden in patients with various neurological disorders, regardless of their mood disturbances. While we may not fully understand the exact mechanism at play, it is evident that serotonergic and glutamatergic transmission are major contributors. Medications like SSRIs, TCAs, Dextromethorphan, or Quinidine have therapeutic advantages in managing PBA. By taking a pharmacological approach to address PBA, clinicians can make a meaningful difference in alleviating socially distressing and functionally constraining symptoms in patients.
