Center For Neurologic Study-Lability Scale Score Research Articles

Prevalence of Pseudobulbar Affect (PBA) in Parkinson's Disease: An Underrecognized Patient Burden.

ObjectivePseudobulbar affect (PBA) is a neurological condition characterized by emotional lability and a discrepancy between the patient’s emotional expression and emotional experience. These uncontrollable episodes cause distress in social situations resulting in embarrassment and social withdrawal. The most comprehensive study to date estimated that 26% of Parkinson’s disease (PD) patients screened positive for PBA symptoms via the validated Center for Neurologic Study-Lability Scale (CNS-LS) screening tool. We hypothesize that the prevalence of this disabling syndrome is higher than reported, often being labeled as depression.MethodsOne hundred patients were enrolled in the study and screened with a CNS-LS tool, all of whom were diagnosed with PD by a fellowship-trained movement disorder specialist. Patients were also asked about previous diagnosis of depression, current antidepressant medication use, and history of PBA diagnosis and treatment.ResultsThe percentage of PD patients (n = 100) with PBA symptoms as defined by a CNS-LS score ≥13 was 41% (n = 41) and by a CNS-LS score ≥17 was 21.0% (n = 21). In our sample, 38.0% of patients (n = 38) had a previous clinical diagnosis of depression and 25.0% (n = 25) were currently undergoing treatment for their depression. There was a significant association between previous depression diagnosis, current antidepressant use, and higher CNS-LS scores (p < 0.001).ConclusionUsing either of the CNS-LS score cutoffs, a significant proportion of the PD population in our sample displayed symptoms of PBA. We also found an association between previous diagnosis of depression and higher CNS-LS scores as well as between antidepressant use and higher CNS-LS scores. This suggests both a higher prevalence than prior studies showed as well as frequent misdiagnosis or co-diagnosis with depression.

Dextromethorphan/Quinidine for Pseudobulbar Affect Following Stroke: Safety and Effectiveness in the PRISM II Trial.

Dextromethorphan (DM) / quinidine (Q) was approved for pseudobulbar affect (PBA) treatment based on efficacy and safety trials in patients with PBA caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic brain injury. To report results from the stroke cohort of PRISM II, including the Stroke Impact Scale (SIS). Open-label trial evaluating twice-daily DM/Q over 90 days. Adults (n = 113) with a clinical diagnosis of PBA secondary to stroke; stable psychiatric medications were allowed. PRISM II was an open-label, 12-week trial enrolling adults with PBA caused by dementia, stroke (reported here), or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at days 30 and90. 150 U.S. centers. Primary efficacy measure was changed from baseline to day 90 in Center for Neurologic Study-Lability Scale (CNS-LS) scores. Secondary outcomes included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver Global Impression of Change (CGI-C and PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State Examination (MMSE). Compared with baseline, CNS-LS scores (SD) improved by -6.2 (6.1, P<.001) at day 30 and -7.6 (6.7, P<.001) at day 90. PBA episodes were reduced by 65% and 75% at day 30 and 90, respectively. Seventy-five percent of clinicians and 67% of patients/caregivers rated PBA as "much" or "very much improved." All SIS items significantly improved from baseline (P < .05, all). Adverse events included diarrhea (4.4%), headache (3.5%), constipation (2.7%), and dizziness (2.7%); 5.3% had adverse events leading to study discontinuation. DM/Q effectively treated PBA and was associated with global and functional improvement; adverse events were consistent with the known safety profile of DM/Q.

Laughter, crying and sadness in ALS

BackgroundPseudobulbar affect (PBA) is prevalent in amyotrophic lateral sclerosis (ALS), but there is limited information on its associations and course.ObjectivesExplore prevalence, associations, course and manifestations of PBA in outpatient cohort...

PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.

BackgroundPhase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI).MethodsParticipants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C).ResultsThe study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, −7.7 [6.1]; P < .001, 95 % CI: −8.4, −7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, −8.2 [−9.4, −7.0]) and numerically exceeds the improvement seen with placebo in that study (−5.7 [−6.8, −4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were “much” or ”very much” improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related.ConclusionsDM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q.Trial registrationClinicaltrials.gov, NCT01799941, registered on 25 February 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0609-0) contains supplementary material, which is available to authorized users.

Pseudobulbar affect (PBA) in an incident ALS cohort: results from the Apulia registry (SLAP).

The aim of this study is to investigate the frequency and the clinical correlations of pseudobulbar affect (PBA) in a population-based incident cohort of ALS patients. Incident ALS cases, diagnosed in 2011 and 2012, according to El Escorial criteria were enrolled from a prospective population-based registry in Apulia, Southern Italy. Neurological status was assessed using a standard neurological examination and the revised ALS Functional Rating Scale (ALSFRSr). The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate the presence and severity of PBA. Total scores range from 7 to 35. A score ≥13 was used to identify the presence of PBA. One-hundred thirty-two sporadic incident ALS cases were enrolled. Median disease duration was 20 months (range 2-143), median onset-diagnosis interval (ODI) 12 months (range 2-131), median ALSFRSr at baseline 36/48 (range 2-47) and median ALSFRSr bulbar sub-score 10/12 (range 0-12). Neurological examination revealed presence of PBA in 34/132 patients (26%). Pathological CNS-LS score was found in 45/132 patients (34%). Median total CNS-LS score was 9/35 (range 7-29). The subgroup with pathological CNS-LS was characterized by a short disease duration from symptom onset, ODI, time to diffusion to a second region, time to generalization and ALSFRSr bulbar sub-score, bulbar onset, "definite" diagnostic category, bulbar upper motor-neuron involvement and presence of PBA at neurological examination. In population-based setting, one-third of ALS patients present PBA at diagnosis. The presence of PBA is associated with bulbar UMN involvement and markers of a more severe phenotype.

Prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents

ObjectivePseudobulbar affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications.MethodsA retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic‐care residents were included in the “predisposed population” if they had a neurological disorder affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study‐Lability Scale (CNS‐LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment.ResultsOf 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the “predisposed population.” PBA symptom prevalence, based on having a CNS‐LS score ≥13, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms.ConclusionsPseudobulbar affect symptoms were present in 17.5% of nursing home residents with neurological conditions, and 9.0% of residents overall. Increasing awareness and improving diagnostic accuracy of PBA may help optimize treatment. © 2015 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Identification of pseudobulbar affect symptoms in Veterans with possible traumatic brain injury.

Pseudobulbar affect (PBA), a neurological syndrome characterized primarily by involuntary episodes of laughing and crying, can develop secondary to neurological conditions including traumatic brain injury (TBI). Veterans of the wars in Afghanistan and Iraq have an unprecedented risk for TBI, primarily from blast-related munitions. In this cross-sectional study with linkage to Department of Veterans Affairs (VA) clinical data, Veterans screening positive for TBI on the VA TBI screen (N = 4,282) were mailed packets containing two PBA symptom assessments: a single PBA symptom screen question and the Center for Neurologic Study-Lability Scale (CNS-LS) questionnaire. Seventy percent (n = 513) of the 728 Veteran respondents screened positive for PBA symptoms with a CNS-LS score of 13 or greater. There was strong concordance between PBA symptom prevalence measured with the single screening question and CNS-LS, with high sensitivity (0.87) and positive predictive value (0.93), and moderate specificity (0.79). Posttraumatic stress disorder (54% vs 32%), major depression (35% vs 22%), and anxiety disorder (20% vs 13%) were more common for Veterans with PBA symptoms than for those without. PBA symptoms were common in this Veteran cohort, were detected using simple screening tools, and often co-occurred with other psychiatric disorders common in Veterans.

Review of Dextromethorphan 20mg/Quinidine 10mg (NUEDEXTA(®)) for Pseudobulbar Affect.

Pseudobulbar affect (PBA) is a dysfunction of emotional expression characterized by involuntary outbursts of crying or laughing disproportionate or unrelated to mood, occurring in patients with various underlying neurologic disorders. This review describes the clinical data supporting dextromethorphan (DM) hydrobromide combined with quinidine sulfate (Q) as treatment of PBA and briefly surveys the ongoing debates concerning the terminology for dysfunction of emotional expression, as well as the ongoing searches for its brain substrates. Until recently, pharmacologic intervention consisted chiefly of off-label antidepressants. In October 2010, however, DM/Q at 20/10 mg twice daily received approval from the United States Food and Drug Administration for PBA in any setting, and in June 2013, dosages of 20/10 and 30/10 mg twice daily (labeled as 15/9 and 23/9 mg, respectively, DM/Q base) received approval from the European Medicines Agency. DM is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, a sigma-1 receptor agonist, and a serotonin and norepinephrine reuptake inhibitor. To block DM hepatic metabolism, thereby increasing DM bioavailability, Quinidine, a cytochrome P450 2D6 inhibitor, is coadministered at a dosage well below those for treating cardiac arrhythmia. Three large-scale DM/Q trials have utilized PBA-episode counts and the Center for Neurologic Study-Lability Scale (CNS-LS), a validated PBA rating scale, to measure efficacy. In a 4-week study of patients with PBA in amyotrophic lateral sclerosis (ALS), DM/Q 30/30 mg was superior to its component drugs. A 12-week, double-blind, placebo-controlled study of DM/Q 30/30 mg showed similar efficacy in patients with PBA in multiple sclerosis (MS). A subsequent 12-week study of patients with PBA and ALS or MS showed superiority to placebo for the 20/10 and 30/10 mg doses. Efficacy was maintained during a 12-week, open-label extension (30/10 mg dose), with further improvement of mean CNS-LS scores. Across these studies, DM/Q was generally safe and well tolerated, with no evidence of clinically relevant cardiac or respiratory effects. DM/Q is being studied (currently unapproved) for conditions including agitation in autism and in dementia.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-014-0018-5) contains supplementary material, which is available to authorized users.

PRISM: A Novel Research Tool to Assess the Prevalence of Pseudobulbar Affect Symptoms across Neurological Conditions

BackgroundPseudobulbar 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.MethodsParticipating 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.ResultsPRISM 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).ConclusionsData 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.

Poster 62 Pseudobulbar Affect in Stroke: A National Stroke Association Survey

To assess the prevalence and burden of pseudobulbar affect (PBA), a disorder of emotional affect disinhibition associated with brain injury, in stroke survivors. This Internet survey was commissioned by the National Stroke Association (NSA) and Avanir Pharmaceuticals, and conducted by infogroup/Opinion Research Corporation. Respondents were located across the United States. Potential respondents were drawn from the NSA database of stroke survivors and caregivers and emailed a link to the survey. Eligible respondents were stroke survivors or main caregivers of stroke survivors, as confirmed by screening questions, with PBA symptoms, defined as a score of ≥ 13 on the Center for Neurologic Study Lability Scale (CNS-LS), administered during the screening portion of the survey. Fifty-four questions were asked for screening and data collection. Primary measures included the frequency, burdensomeness, limitations, interference with activities, and impact on life situation of PBA, and the sufficiency of PBA treatment. Of 30,641 recipients emailed, 578 answered the screening questions, and 304 (53%) screened positive for PBA (≥ 13 CNS-LS score), including 229 (75%) stroke survivors. Among eligible respondents, 27% experienced PBA episodes frequently or often, and 27% described their symptoms as moderate to severe. More than half (52%) of respondents said PBA was extremely, very, or somewhat burdensome, and substantial percentages said PBA interfered extremely, very, or somewhat often with social activities and other leisure (38%), spending time with friends/family (39%), and talking on the phone (33%). PBA also contributed at least somewhat in about a third of respondents to having trouble maintaining friends (31%) and becoming housebound (30%). Only 38% of respondents were treated for PBA, of whom almost half (47%) were dissatisfied with their treatment. PBA occurs in about half of stroke survivors and often imposes a significant burden, but is under treated.

Involuntary emotional expression disorder (IEED) in Parkinson's disease

Objective To estimate the frequency and correlates of involuntary emotional expression disorder (IEED) in Parkinson's disease (PD) using the Center for Neurologic Study-Lability Scale (CNS-LS) and recently-proposed diagnostic criteria for IEED. Background IEED is characterized by uncontrollable emotional episodes, typically unrelated to or in excess of the underlying mood, and occurring with minimal or no stimulus. IEED has been reported to occur in many neurological disorders and neurodegenerative diseases, but its prevalence and correlates in PD have not been well studied. Additionally, there is no published research using recently-proposed IEED diagnostic criteria in any population. Methods 193 patients with idiopathic PD were assessed with a neuropsychiatric battery, including the CNS-LS and the 15-item Geriatric Depression Scale (GDS-15). A subset ( N = 100) was also administered a diagnostic interview by a blinded rater that applied criteria for both IEED and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) depressive disorders. Results Applying formal diagnostic criteria, 7.0% of patients were diagnosed with IEED, and an additional 7.0% had subsyndromal IEED symptoms. Applying recommended CNS-LS cutoff scores from other populations, either 42.5% (cutoff ≥13) or 16.6% (cutoff ≥17) screened positive for IEED. Depressive symptoms were associated with higher CNS-LS scores ( B[SE] = 0.27[.08], P = .001) but not with a diagnosis of IEED (odds ratio = 1.1, [95% CI = 1.0–1.3], P = .16). The CNS-LS had poor discriminant validity for an IEED diagnosis (AUC = .79, no cutoff value with sensitivity and specificity both >60%). Conclusions IEED and depression are overlapping but distinct disorders in PD. IEED symptoms may occur in up to 15% of PD patients, but a disorder occurs in only half of those, suggesting that often IEED symptoms are not clinically significant in this population. The CNS-LS does not appear to be a good screening instrument for IEED in PD, in part due to its high correlation with depressive symptoms.

A self report measure of affective lability

OBJECTIVESThe development and validation of the Center for Neurologic Study- Lability Scale (CNS-LS), the first self report measure of affective lability in patients with amyotrophic lateral sclerosis (ALS).METHODSPotential questionnaire items...