Some people with multiple sclerosis find that they experience sudden episodes of uncontrollable laughing and/or crying at inappropriate times, or which are unrelated, or out of proportion, to their current mood.
This can happen if MS lesions have occurred in the areas of the brain that control your emotions. These excessive emotional symptoms are known by a number of names including:
- pseudobulbar affect
- pathological laughing and crying
- emotional lability
- emotional incontinence
Pseudobulbar affect (PBA) is seen in many other conditions including amyotrophic lateral sclerosis (ALS). motor neurone disease (MND), Parkinson's disease (PD), stroke, traumatic brain injury, Alzheimer's disease (AD) and other dementias.
What is pseudobulbar affect?
Pseudobulbar affect is a physical disorder that results from a disturbance in how you express your emotions, rather than of your actual feelings themselves. Whilst you may be laughing or crying uncontrollably, you may not actually be experiencing any corresponding inner feelings of happiness or sadness. Sometimes the laughing or crying may start in response to something funny or sad you've seen or experienced, but the feelings are usually much more intense, last longer than expected and it may be difficult, or impossible, for you to stop laughing or crying. Some people with PBA find they have episodes where they become excessively angry or frustrated.
You may find it embarrassing if you have these outbursts, particularly if they happen at inappropriate times, or in situations that other people don't find sad or funny. You may worry about it happening again. This can lead to people avoiding social interactions or can affect relationships if you feel you are embarrassing family and friends.
Pseudobulbar affect can be mistaken for depression, because it often involves crying. However, typically depression lasts longer than PBA outbursts, which are usually fairly brief – lasting for several minutes. Also, pseudobulbar affect is not associated with common features of depression such as problems sleeping or losing your appetite. It is possible to have PBA and depression at the same time, but they should be managed separately.
What causes pseudobulbar affect?
The exact cause of PBA is unclear but it is thought to be due to a combination of damage to the central nervous system in the areas of the brain that are involved with controlling your emotions and the effect this has on how signals are carried between nerve cells by neurotransmitters – chemicals which allow the cells to communicate with one another. However, the pathways controlling emotions are complex and not completely understood.
It is thought that the area of the brain known as the cerebellum may have a key role in regulating emotional repsonses and keeping them proportional to the situation. So if you have lesions in the cerebellum you may be more susceptible to pseudobulbar affect.
The neurotransmitters thought to be involved in PBA are serotonin, dopamine, glutamate and noradrenaline (also known as norepinephrine). These neurotransmitters are also involved with depression and manic episodes, and as indicated previously pseudobulbar affect can sometimes be mistaken for depression.
How many people get pseudobulbar affect?
Pseudobulbar affect often goes unrecognised and undiagnosed. Estimates of how many people with MS are affected by PBA vary widely ranging from 7% to 95% depending on the terminology used, the diagnostic criteria and the population of people being studied. However, the majority of studies have estimated the prevalence in MS to be in the narrower range of 10% to 46%.
The first criteria to be used to diagnose PBA was developed by Poeck in 1969 and defined four criteria that must be met:
- the emotional response is situationally inappropriate
- the patient’s feelings and the affective response are not closely related
- the duration and severity of the episodes cannot be controlled by the patient
- expression of the emotion doesn’t lead to a feeling of relief.
A more recent set of criteria were developed in 2006 by Cummings. These criteria put more of an emphasis on the fact that PBA is a change from the individual’s normal emotional responses:
- a change from previous emotional responses
- inconsistent with, or disproportionate to, mood
- not dependent on a stimulus, or are excessive relative to that stimulus
- cause significant distress or social/occupational impairment
- not accounted for by another psychiatric or neurologic disorder
- not due to a drug.
There are also some published scales available which measure pseudobulbar affect more objectively. The Center for Neurologic Study – Lability Scale (CNS-LS) is a self-administered questionnaire with seven questions which are scored by the patient from one to five. It looks at aspects such as the frequency of episodes, their intensity and how inappropriate they were with regards to the context. This scale has been validated for use in people with MS, where a score of 17 or more would indicate PBA.
The Pathological Laughter and Crying Scale (PLACS) consists of 18 questions and is carried out by a health professional. Scores for each question range from zero (normal) to three (excessive emotional lability). It looks at several aspects of PBA including duration of, and the extent of distress following, an episode. This scale has not been validated in people with MS but it has been used in MS studies of PBA. A score of 13 or more would indicate PBA.
A 2015 study in Croatia aimed to determine the prevalence of PBA in a group of 79 people with MS using the CNS-LS. 33 of the 79 participants (41.8%) met the criteria for a diagnosis of pseudobulbar affect. This study also looked at whether there was a link between PBA, patient age, gender, type of MS, time with MS and level of disability. It found no significant correlation between PBA, age and level of disability, but in this population it was more common in women and those with secondary progressive MS (SPMS). This contrasts with a 1997 study which found that it occurred equally amongst men and women and tended to be associated with more progressive disability.
A 2018 study in the United States also looked at the prevalence of PBA in a large group of people with MS using the CNS-LS. The study assessed whether there was an association between PBA and symptom severity and disability. Of the 8,136 responders, 574 (7%) had a score of 17 or higher. However, only 200 (2.5%) had a score of 17 or higher who didn't also experience depression. This highlights why if pseudobulbar affect is suspected, it's important to have a full evaluation of your mood to ensure the correct diagnosis is made. Of the 200 with a score of 17 or more and no depression, only 22 had a diagnosis of PBA, confirming that although the prevalence of PBA is low, it is an underdiagnosed symptom of MS. The study also found that individuals with PBA tended to be younger, non-white, have a lower annual income and were more likely to experience cognitive difficulties.
What can I do if I get pseudobulbar affect?
It is important to try and get a prompt and accurate diagnosis of pseudobulbar affect to enable you to access appropriate treatment, as well as support for you and your family. Counselling may be helpful to reassure you and your family that PBA is not your fault.
How is pseudobulbar affect treated?
The aim of treatment for PBA is to reduce the frequency and severity of episodes. The mainstay of treatment has been the 'off-label' use of antidepressants which target the neurotransmitters noradrenaline, serotonin and glutamate. 'Off-label' use means that the medicine is being used in a way that is different to that described in the licence. For example, here it is being used for a different illness (PBA) to that stated in the licence (depression). Doctors have found that the medicine works very well for this condition, but the drug manufacturer has not extended the licence to include it.
Both tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline, and selective serotonin reuptake inhibitors (SSRIs) including fluoxetine, citalopram and sertraline are used. Efficacy appears to be similar whichever antidepressant is used. The doses used tend to be lower than those used for depression and the effects are seen quite quickly, typically in less than a week.
The NICE MS Guideline suggests that amitriptyline be tried as a treatment for emotional lability in people with MS.
In 2013, the European Medicine Agency (EMA) licensed a new combination drug called Nuedexta for treating pseudobulbar affect in MS and other neurological conditions, including MND. Nuedexta is a combination of dextromethorphan (a cough suppressant) and quinidine. Dextromethorphan is thought to work by attaching to several nerve cell receptors in the brain, including those for the neurotransmitters glutamate and serotonin. It helps normalise the activity of the neurotransmitters and reduces the symptoms in MS. The role of quinidine is to stop dextromethorphan from being broken down as quickly by the body, therefore prolonging its action.
It is thought that Nuedexta takes longer to have an effect on pseudobulbar affect than antidepressants, taking up to four to five weeks to work. Although available in the United States since 2010, Nuedexta was never marketed in the European Union and in February 2016, the manufacturers requested that the marketing authorisation be withdrawn in the EU for commercial reasons.
The withdrawal wasn’t related to any safety issues, or due to lack of efficacy of the drug, simply the manufacturer did not feel that they could market Nuedexta profitably in Europe. This may be because it treats symptoms that can be managed successfully using antidepressants which are relatively cheap in Europe, also doctors are more familiar with antidepressants and they work more quickly than Nuedexta. Although Nuedexta has never been available in the UK it is still used in the United States.
Pseudobulbar affect: an under-recognized and under-treated neurological disorder.
Advances in Therapy 2011; 28(7):586-601.
Summary (link is external)
Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.
Annals of Neurology 2006;59(5):780-787.
Summary (link is external)
A Clinical Bulletin from the Professional Resource Center of the National Multiple Sclerosis Society: Pseudobulbar affect (uncontrollable laughing and/or crying).
New York, NY: National Multiple Sclerosis Society; 2012.
Full text (PDF, 200KB) (link is external)
Enhancing approaches to the identification and management of pseudobulbar affect.
Journal of Clinical Psychiatry 2016;77(9):e115.
Summary (link is external)
Pseudobulbar affect: prevalence and association with symptoms in multiple sclerosis.
Neurology Clinical Practice 2018;8(6):472-481.
Full article (link is external)
Pseudobulbar affect in neurodegenerative disease: a systematic review and meta-analysis.
Journal of Clinical Neuroscience 2022;100:100-107.
Summary (link is external)