Pseudobulbar Affect and Brain Injury - PowerPoint Presentation

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

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