No laughing matter – recognising pseudobulbar affect

Once in a lifetime: As part of our series on rare diagnoses, Dr James Chambers describes the condition pseudobulbar affect which GPs may only encounter once in a career at the most, partly due to its under-recognition

What is it?

Pseudobulbar affect (PBA) is a collection of symptoms, characterised by an uncontrollable sensation of crying or laughing that is disproportionate or inappropriate to the patient’s current social context.

The patient with PBA will therefore experience a discrepancy between the emotion or emotions they feel internally and those they portray externally.

GPs may have come across these clusters of symptoms being described by other terms, such as emotional lability, emotional dysregulation or pathological laughing and crying.¹

These symptoms can have a serious impact on a person’s life. They often cause embarrassment for both the patient and their family, limit the patient’s ability to socialise or take part in everyday activities and can lead to a significantly impaired quality of life. A study of 400 PBA sufferers in the United States found 25% of patients had become housebound as a result of the condition.²Thus, the impact and burden these symptoms have on the individual patients cannot be understated.

How rare is it?

PBA is a relatively rare condition in the population overall, but is seen more frequently in patients with pre-existing brain disorders. Studies have found that among patients with a traumatic brain injury, the prevalence of the condition during the first year post-injury can be as high as 5%-11%.¹

The disorder has been found to occur in almost 10% of patients with multiple sclerosis (MS), 49% of patients with amyotrophic lateral sclerosis (ALS), 11-34% of patients with a stroke and in 5% of patients with Parkinson disease.¹

Despite this equating to an estimated prevalence of approximately 1 in 400, many of us won’t encounter a definite diagnosis of this condition, reinforcing the suggestion that it is probably under-recognised or under-recorded.

The commonest misconception for the patient’s emotional display is that it is part of a mood disorder such as depression or bipolar disorder.

Clues to early detection

Consider the diagnosis in patients with labile emotional expression, especially if it is sudden, brief and uncontrollable.

It is worth using a screening tool in patients with a pre-existing neurological condition as highlighted above. The Centre for Neurologic Study-Liability Scale (CNS-LS) is a 7-item, self-rated quantitative measurement tool for the frequency and severity of PBA symptoms. Studies have found a score of 13 or more is suggestive of a diagnosis of PBA and warrants specialist review. It has been validated in both ALS and MS patient populations.^3,4

When suspected, a referral to a neurologist or the patient’s specialist team for their primary condition is warranted for confirmation of the diagnosis.

Not to be confused with…

While PBA and mood disorders both involve excessive emotional expression, it is important to recognise the key differences.

In mood disorders, the episodes of crying or laughing occur alongside a sustained change in mood (such as persistent low mood in depression) and are accompanied by other symptoms such as anhedonia, hopelessness or low energy.

In contrast, emotional episodes in PBA are sudden, brief, out of character, and – most importantly – uncontrollable. This highlights the importance of good history taking to differentiate these symptoms.

Confusingly, however, many studies have also found patients with PBA have co-existing mood disorders. It remains unclear whether this overlap is due to common pathophysiological pathways or whether the symptoms of PBA impact quality of life so significantly that they lead to the development of a mood disorder.

However, differentiation remains important, as treating the mood disorder does not always resolve symptoms of PBA; as such they remain separate diagnostic and therapeutic entities.⁵

Pathophysiology of PBA

The exact underlying mechanism in PBA remains unclear although new theories have been emerging in recent years. One of the most prominent involves the role of the cerebellum as ‘gatekeeper’ for emotional responses from the motor, frontal and temporal cortex through to the brainstem.

The theory suggests that in PBA the cerebellum’s regulatory function on emotional responses is impaired.⁶ Consequently increasingly inappropriate emotional responses are ‘fired off’ through the brainstem, resulting in symptoms.

This is supported through evidence that conditions that affect the cerebellum predominantly (such as multiple system atrophy cerebellar type) are associated with a higher frequency of PBA symptoms than other neurological conditions. Studies have also shown serotonin and glutamate neurotransmission have significant roles, influencing management.⁶

Usual treatment and prognosis

The main aim is to reduce the frequency and severity of the episodes for the patient. Treatment is with the ‘off-label’ use of antidepressants targeting the relevant neurotransmitters noradrenaline, serotonin and glutamate, to increase their availability in corticolimbic and cerebellar pathways.

Placebo-controlled trials have shown positive results with the use of both tricyclic antidepressants (such as amitriptyline, imipramine and nortriptyline) and SSRIs (such as fluoxetine, citalopram and sertraline).⁷ NICE guidelines support the use of amitriptyline in patients with MS for emotional lability.⁸

In the US, a combination medication of dextromethorphan and quinidine (tradename Nuedexta) is licensed specifically for the management of PBA. The combination medication is a potent N-methyl-D-aspartate (NDMA) receptor antagonist, regulating glutamate and serotonin levels. Despite placebo-controlled trials showing positive improvement in symptoms for ALS and MS patients, the medication is not available in Europe, as it was withdrawn from the market in 2016 on commercial grounds.⁹

While PBA itself is not a life-threatening illness, it is a long-term condition, which can be challenging to manage even with treatment. Treatment primarily aims to control symptoms rather than cure, so patients often continue to experience a significant impact on their quality of life, providing a mixed prognosis.

Key points for GPs

While pseudobulbar affect remains a rare and unusual condition in general practice, it is important to consider in high-risk patients, such as those with neurological conditions like ALS, brain injuries, strokes and MS.
Many patients may normalise their symptoms as part of their condition and not report them, therefore it is necessary to enquire about PBA symptoms specifically in these cohorts.
The use of a screening test, such as the CNS-LS can be helpful.
Avoiding misdiagnosis with mood disorder is vital, as this has significant implications on treatment options, duration and understanding of their symptoms.
Good history taking and involvement of our neurology colleagues may be helpful in managing these cases.

Dr James Chambers is a GP in Staffordshire