PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions

Abstract

Background: Pseudobulbar affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA.

Methods: Participating clinicians were asked to enroll ≥20 consenting patients with any of 6 conditions: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study-Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient's quality of life (QOL). Presence of PBA symptoms was defined as a CNS-LS score ≥13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded.

Results: PRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score ≥13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS ≥13 vs <13 (6.7 [2.5] vs. 4.7 [3.1], respectively; P<0.0001 two-sample t-test). A greater percentage of patients with CNS-LS ≥13 versus <13 were using antidepressant/antipsychotic medications (53.0% vs 35.4%, respectively; P<0.0001, chi-square test).

Conclusions: Data from PRISM, the largest clinic-based study to assess PBA symptom prevalence, showed that PBA symptoms were common among patients with diverse neurological conditions. Higher CNS-LS scores were associated with impaired QOL and greater use of antipsychotic/antidepressant medications. These data underscore a need for greater awareness, recognition, and diagnosis of PBA.

Conflict of interest statement

Competing Interests: Funding for the PRISM study and editorial support for manuscript preparation were provided by Avanir Pharmaceuticals, Inc. Other potential conflicts of interest are as follows: Dr. Brooks has received funding and/or research grants from Biogen Idec, Avanir Pharmaceuticals, Inc., Acorda, Cytokinetics, GlaxoSmithKline Pharmaceuticals, Neuraltus Pharmaceuticals, NINDS Clinical Research Consortium, Synapse; Dr. Crumpacker has served on a scientific advisory board for and received speaking fees from Avanir Pharmaceuticals, Inc., and has received speaking fees from Accera and Novartis; Dr. Fellus has received a research grant and consulting fees from, has served on the Speakers Bureau for, and is a stockholder of Avanir Pharmaceuticals, Inc.; Dr. Kantor has received consulting fees from Avanir Pharmaceuticals, Inc.; Dr. Kaye is an employee and stockholder of Avanir Pharmaceuticals, Inc. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Published PBA symptom prevalence estimates by primary neurological condition.

Shading indicates multiple estimates. AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CNS-LS, Center for Neurologic Study–Lability Scale; MS, multiple sclerosis; PBA, pseudobulbar affect; PD, Parkinson’s disease; PRISM, PBA Registry Series; TBI, traumatic brain injury. aPatient interview; bCNS-LS ≥13 (higher estimate), CNS-LS ≥21, lower estimate; c Poeck criteria: pathological affect could be mood congruent (emotional lability) or incongruent (pathological laughing and crying); dRetrospective review of hospital or clinic records; eMailed questionnaire; fEmotional lability questionnaire (ELQ); gAscertainment method unknown; hPatient interview, Poeck criteria; iBrief questionnaire (uncontrollable laughing/crying when not happy/sad); jCNS-LS ≥13 (highest estimate), CNS-LS ≥17 (middle estimate), Cummings Involuntary Emotional Expression Disorder criteria (lowest estimate); kCNS-LS ≥17 (lower estimate), CNS-LS ≥13 (higher estimate); lPathological Laughing and Crying Scale (PLACS) ≥10 and score of ≥2 on PLACS items 2 (frequency), 13 (loss of voluntary control), and 18 (distress/embarrassment); mPatient interview House (lower estimate), and Kim (higher estimate) criteria; nPatient interview House criteria; oPatient interview Kim criteria; pPatient interview Kim criteria (lower estimate; n = 516) and modified Kim criteria (patient report only without corroboration from relatives; higher estimate); qPatient interview Kim criteria at hospital admission (lower estimate) and at 3 months (higher estimate) following stroke.

Figure 2. Sample interim PRISM registry report available to activated sites.

CNS-LS, Center for Neurologic Study–Lability Scale; PRISM, PBA Registry Series.

Figure 3. PBA symptom prevalence by CNS-LS threshold.

AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CNS-LS, Center for Neurologic Study–Lability Scale; MS, multiple sclerosis; PBA, pseudobulbar affect; PD, Parkinson’s disease; PRISM, PBA Registry Series; TBI, traumatic brain injury.

Figure 4. Impact of neurological condition on quality of life by CNS-LS threshold.

*P<0.0001 compared with CNS-LS <13; two-sample t-test. CNS-LS, Center for Neurologic Study–Lability Scale. Note: Group with CNS-LS ≥21 is a subset of the group with CNS-LS ≥13.

Figure 5. Psychotropic medication use by CNS-LS threshold.

*P<0.0001 compared with CNS-LS <13; chi-square test. CNS-LS, Center for Neurologic Study–Lability Scale; TCA, tricyclic antidepressant(s). Note: Group with CNS-LS ≥21 is a subset of the group with CNS-LS ≥13.