Pseudobulbar Affect and Brain Injury Eugenio Rocksmith MD

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 ex aggerated relative to the patient’s mood, but crying is congruent with subjective mood in depression Other symptoms of depres sion—fatigue, anorexia, insomnia, anhedo nia, 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 cry ing 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 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 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/s 12325 012 0043 7. Epub 2012 Aug 30. . Pseudobulbar affect: burden of illness in the USA. Colamonico J 1, 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 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.

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 You. Tube