Eugenio Rocksmith MD Assistant Professor Dept of Neurology University of Maryland Medical School CoDirector Brain Injury Unit University of Maryland Rehabilitation and Orthopedic Institute ID: 591573
Download Presentation The PPT/PDF document "Pseudobulbar Affect and Brain Injury" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Pseudobulbar Affect and Brain Injury
Eugenio Rocksmith, MD
Assistant Professor, Dept. of Neurology
University of Maryland Medical School
Co-Director, Brain Injury Unit
University of Maryland Rehabilitation and Orthopedic InstituteSlide2
Objectives
Clinical features of Pseudobulbar Affect (PBA)
Pathophysiology
Association with Acquired Brain Injury (ABI)
Differentiation from mood disorders
TreatmentSlide3
Case Scenario
KT is a 31
yo
man who sustained a TBI as the result of a car accident
Brain imaging revealed evidence of microhemorrhages in bilateral frontal lobes, corpus callosum and midbrain
He was admitted to STC and did not require any neurosurgical intervention
His hospital course was complicated by recurrent fever of unknown origin, persistent tachycardia, hyperhidrosis and frequent hypertensive episodes
He also had intermittent episodes of agitation manifested by yelling, cursing, combativeness, impulsivity and poor safety awareness
Three weeks after his TBI he was transferred to UMROI for acute inpatient rehabilitationSlide4
Public Service Announcement – Typical PBASlide5
Public Service Announcement –Atypical PBASlide6
Clinical Features of PBA
uncontrollable outbursts of crying or laughing
exaggerated or not connected to your emotional state
laughter often turns to tears
mood can appear normal between episodes which can occur at any time
crying or laughing lasting up to several minutes
you might laugh uncontrollably in response to a mildly amusing comment
you might laugh or cry in situations that others don't see as funny or sadSlide7
Differential Diagnoses
Depression
*
Bipolar disorder (with rapid cycling or mixed mood episodes)*
Generalized anxiety disorder
Schizophrenia
personality disorder (e.g. borderline)
Epilepsy
Acute psychosis
Substance-induced mood disorder
Malingering
*
most common D/
DxSlide8
Depression
Depressive symptoms, including depressed mood, typically last weeks to months, but a PBA episode lasts seconds or minutes
crying, as a symptom of PBA, might be unrelated or exaggerated relative to the patient’s mood, but crying is congruent with subjective mood in depression
Other symptoms of depression—fatigue, anorexia, insomnia, anhedonia, and feelings of hopelessness and guilt— are not associated with pseudobulbar affectSlide9
Bipolar disorder (with rapid cycling or mixed mood episodes)
PBA’s relatively brief duration of laughing or crying episodes—with no mood disturbance between episodes—compared with the sustained changes in mood, cognition, and behavior seen in BDSlide10
Previously Known As…..
involuntary emotional expression disorder
emotional lability
emotional dysregulation
pathological laughter and crying
emotional incontinence
emotionalismSlide11
Pathophysiology
Disruption of cortico-pontine-cerebellar circuits, reducing the threshold for motor expression of emotion
Disruption of the
microcircuitry
of the cerebellum itself may likewise impair its ability to act as a gate-control for emotional expression
Current evidence suggests that serotonergic and glutamatergic neurotransmission play key rolesSlide12
Proposed Pathophysiology: the motor control of emotions is modulated by the cerebellum, which acts as a “gate control.” There is direct input from the motor cortex and from the frontal and temporal cortices through the brainstem which is modulated by the cerebellum. The motor input is in turn modulated by inhibitory input from the somatosensory cortex. Reduction of the inhibitory input results in disinhibition of the cerebellum, resulting in socially inappropriate or situationally disproportionate emotional expression, which is manifested as PBA Slide13
CNS-LS for PBA
Seven subjective questions
Answers range from 1 (applies never) to 5 (applies most of the time)
A score of 13 or higher
may suggest
PBASlide14
Neurological Disorders Most Commonly Associated with PBA
Amyotrophic lateral sclerosis
Extrapyramidal and cerebellar disorders
Multiple sclerosis
Traumatic brain injury
Alzheimer’s dementia
Stroke
Brain tumorsSlide15
Affects Quality of Life (QOL) and Quality of Relationships (QOR)
Study of 1,052 respondents (399 PBA group participants and 653 controls
PBA resulted in embarrassment for the patient, family, and caregivers with subsequent restriction of social interactions and a lower quality life
PBA contributed a great deal to or was the main cause of patients becoming housebound for 24% and being moved to supervised living placement for 9% of respondents
PBA is associated with considerable burden incremental to that of the underlying neurological conditions, affecting QOL, QOR, health status, and social and occupational functioning
Adv
Ther
. 2012 Sep;29(9):775-98.
doi
: 10.1007/s12325-012-0043-7.
Epub
2012 Aug 30.
Pseudobulbar affect: burden of illness in the USA.
Colamonico
J1,
Formella
A, Bradley W
.Slide16
Treatment of PBA
The targets of treatment are primarily the neurotransmitters norepinephrine, serotonin, or glutamate
Tricyclic antidepressants (TCAs), selective
serotonin reuptake
inhibitors (SSRIs)
The serotonergic action of SSRIs and TCAs appears to be the most significant therapeutic mechanism in treatment of PBA, via an increase in availability of serotonin at the synapses in corticolimbic and cerebellar pathways
The efficacy of antidepressants appears to be unrelated to the treatment of depression, based upon several pieces of evidence: 1) the onset of action may occur within a few days, which is faster than expected for depression; 2) doses are lower than those usually used to treat depression; and 3) most patients with PBA are not depressedSlide17
Treatment of PBA
Most recently, the cough suppressant dextromethorphan has also shown efficacy
In contrast to SSRIs and TCAs, dextromethorphan inhibits glutamatergic neurotransmission via actions at a variety of locations including N-methyl-D-aspartate receptors and
σ-1
receptors
there is rapid and extensive conversion by the liver; blockade of hepatic metabolism can be accomplished by the concurrent administration of the cardiac antiarrhythmic drug quinidine sulfate leading to higher and sustained plasma concentrations of dextromethorphan at a fraction of the dose required if quinidine sulfate was not used
In October 2010, the US Food and Drug Administration (FDA) approved
Nuedexta
® (
Avanir
Pharmaceuticals, Aliso Viejo, CA, USA) for the treatment of PBA, making this the first FDA-approved drug for this indication.Slide18
Most Common Side Effects of These Medications
TCAs
dry mouth, constipation, orthostatic hypotension, confusion, sedation, and potential cardiotoxicity. The
elderly often tolerate TCAs particularly poorly
. However, TCAs
may facilitate sleep if given as a nighttime dose
. Also, their anticholinergic properties make them
useful for control of
sialorrhea
in patients such as those with bulbar ALS in whom this may be particularly troublesome
commonly used TCAs are nortriptyline and amitriptyline, usually at dosages from 20–100 mg/daySlide19
Most Common Side Effects of These Medications
SSRIs
Much more limited side effect profile, resulting in a much lower rate of discontinuation
Drowsiness, nausea, dry mouth, insomnia, diarrhea, nervousness, agitation or restlessness, dizziness, sexual problems (such as reduced sexual desire or difficulty reaching orgasm or inability to maintain an erection (erectile dysfunction)), headache, blurred vision
Average dose of SSRIs in clinical trials for the treatment of PBA was 20 mg/day for fluoxetine and citalopram and 50 mg/day for sertralineSlide20
Most Common Side Effects of These Medications
Dextromethorphan/Quinidine
most common side effects are dizziness, diarrhea, falls, headache, nausea, fatigue,
nasopharyngitis
, constipation, and dysphagia
May be
contrindicated
in patients with h/o heart disease or patients who have a family history of heart rhythm problems
FDA-approved dosing is one capsule daily for 7 days, followed by an increase to one capsule every 12 hoursSlide21
References
Mayo clinic
Pseudobulbar affect: No laughing matter Current Psychiatry. 2014 April;13(4):66;
Shailesh
Jain, MD, MPH, ABDA
Avanir
Pharmaceuticals
Miller A, Pratt H, Schiffer RB. Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments. Expert Rev
Neurother
. 2011;11(7):1077–1088.
Haiman
G, Pratt H, Miller A. Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect. J
Neurol
Sci. 2008;271(1–2):137–147
YouTube