Download ROCKSMITH - Pseudobulbar Affect and Brain Injury

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 Institute
Objectives
 Clinical features of Pseudobulbar Affect (PBA)
 Pathophysiology
 Association with Acquired Brain Injury (ABI)
 Differentiation from mood disorders
 Treatment
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
rehabilitation
Public Service Announcement – Typical PBA
Public Service Announcement –Atypical PBA
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 sad
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/Dx
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 affect
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 BD
Previously Known As…..
 involuntary emotional expression disorder
 emotional lability
 emotional dysregulation
 pathological laughter and crying
 emotional incontinence
 emotionalism
Pathophysiology
 Disruption of cortico-pontinecerebellar 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 gatecontrol for emotional expression
 Current evidence suggests that
serotonergic and glutamatergic
neurotransmission play key roles
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
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 PBA
Neurological Disorders Most Commonly
Associated with PBA
 Amyotrophic lateral sclerosis
 Extrapyramidal and cerebellar disorders
 Multiple sclerosis
 Traumatic brain injury
 Alzheimer’s dementia
 Stroke
 Brain tumors
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
.
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 depressed
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-Daspartate 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.
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/day
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 sertraline
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 hours
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