1. Articulating the Unmet Need in the Diagnosis and Treatment of Pseudobulbar Affect: Prevalence of the Condition and Limitations of Existing Therapies Ursula Hess, PhD Torre Lazur McCann West

2. Estimated US Patients With PBA: 1.7 Million 1 o Disorder PBA Prevalence Total US Cases With 1 o Disorder MS10%300,000 ALS49%30,000 AD39%4,000,000 Stroke18%590,000 Severe TBI5%230,000

3. PBA Impact on Quality of Life (QOL) No QOL studies PBA can be severe, persistent, and deteriorate Widely recognized that PBA can be profoundly disabling socially and occupationally –Embarrassing and distressing –Can impair ability to communicate –May be dangerous during eating or drinking –Related to decreased sexual activity poststroke –Fear of attacks, secondary phobias and social withdrawal often make symptoms worse –Interferes with rehabilitation

4. Poorly Clinically Defined Condition With Unknown Disease Mechanism Evidenced by plethora of names for condition Lack of agreement on defining features –Episodes are sudden, involuntary, difficult to control, excessive, disproportionate, and labile –Mood congruent or incongruent? –Limited to laughing and crying? Etiology unknown –Caused by structural brain damage, but seen after bilateral, diffuse as well as single, focal lesions –Possible that lesions within different neural systems result in different manifestations of the syndrome

5. PBA Is Underrecognized and Sometimes Misdiagnosed Validated scales exist to measure PBA but are infrequently and inconsistently used –PLACS, interviewer-rated instrument (Robinson et al, 1993) –CNS-LS, self-report measure (Moore et al, 1997) PBA is distinct from, but can coexist with, affective disorders such as depression Crying spells in depression and laughing episodes in schizophrenia, hysteria, and mania may mimic PBA symptoms Neurological disease as a cause of crying is vastly underestimated by referring physicians (Green et al, 1987)

6. No Approved Pharmacotherapy With Indication for PBA Antidepressants (TCAs, SSRIs) and dopaminergic agents used with varying success –Complete resolution of symptoms or no response –DA agents only ~40%-50% successful Available agents do NOT have proven efficacy in large, well-controlled clinical trials using standardized scales –5 comparative antidepressant trials with N≤28 –2/5 trials did not use objective scales TCAs have an unfavorable side effect profile, and their use may be limited in PBA patients Even severe cases often remain untreated

7. Neurodex TM Specific indication for PBA Proven effective and safe in large (N=140), well-controlled trial using the CNS-LS Significantly improved QOL and QOR; not shown for existing therapies Offers a potentially more targeted approach to the treatment of PBA than existing agents

8. Physician and Patient Education Needed Raise awareness of PBA Facilitate seeking of counseling and treatment –Neurodex TM Implement the use of standardized scales for diagnosis and assessment of therapy –CNS-LS