Center For Neurologic Study-Lability Scale Research Articles

Chinese Translation and Validation of the Center for Neurologic Study Lability Scale.

Pseudobulbar palsy is a common symptom in patients with amyotrophic lateral sclerosis (ALS), but it is often underdiagnosed or misdiagnosed as other diseases. The Center for Neurologic Study Lability Scale (CNS-LS) is a self-report scale consisting of seven questions designed for evaluating pseudobulbar affect (PBA). The current study aimed to validate a Chinese version of the CNS-LS. The Chinese version of the CNS-LS was obtained through a standardized forward-backward translation and cultural adaptation. A total of 105 patients with ALS were recruited from the ALS database of Peking University Third Hospital in Beijing, China, to complete the CNS-LS. The reliability of the Chinese version was determined by the test-retest method, and receiver operating characteristic (ROC) analysis was performed for criterion validity. Of 105 patients with ALS, 37 had symptoms of PBA and were diagnosed with that condition by neurologists. Forty-two patients completed the CNS-LS twice, and there was no statistically significant difference between the scores (Z = -0.896, p = 0.37). The Spearman correlation coefficient between the test and retest scores was 0.940 (p < 0.0005), and the Cronbach alpha coefficient was high (α = 0.905, n = 105). Scores of 12 or higher on the CNS-LS identified PBA with sensitivity of 0.919 and specificity of 0.882. The area under the ROC curve was 0.924. The Chinese version of the CNS-LS demonstrated good sensitivity and specificity in the group of patients with ALS enrolled in this study. The CNS-LS should be a useful instrument for clinical and research purposes for patients in this language group.

1 Post-stroke Apathy, Pseudobulbar Affect and Memory Loss Hinder Return-to-Work After CVA

Objective:Post-stroke depression (PSD) and anxiety disorders are the most common psychiatric issues that occur after cerebrovascular accident (CVA), with prevalence rates of up to 50%. Less studied, post-stroke apathy and pseudobulbar affect (PBA) also occur in a subset of individuals after CVA leading to reduced quality of life. Cognitive impairments also persist, especially memory, language, and executive difficulties. Residual cognitive and emotional sequelae after CVA limit return-to-work with between 20-60% becoming disabled or retiring early. This study examined the frequency and relative contribution of cognitive, behavioral and emotional factors for not returning-to-work after CVA.Participants and Methods:Participants included 242 stroke survivors (54% women, average age of 59.2 years) who underwent an outpatient neuropsychological evaluation approximately 13 months after unilateral focal CVA. Exclusion criteria were a diagnosis of dementia, comprehension issues identified during assessment, multifocal or bilateral CVA, and inpatients. Predictors of return-to-work included in logistic regression analyses were psychological (depressive and anxiety disorders, apathy, PBA, history of psychiatric treatment before stroke) and neuropsychological (memory, executive functioning) variables. Depression and anxiety were diagnosed using DSM-IV-TR or -5 criteria. Apathy was operationalized as diminished goal-directed behavior, reduced initiation and decreased interest that impacted daily life more than expected from physical issues after stroke (including self- and family-report using the Frontal Systems Behavior Scale [FrSBe]). PBA was defined by the Center for Neurologic Study-Lability Scale and clinical judgment based on chart review.Results:Post-stroke apathy persisted in 27.3% of patients 13 months after stroke, PBA persisted in 28.2% of patients (i.e., uncontrollable crying spellings not simply attributable to depression alone, uncontrollable laughing spells), anxiety disorders persisted in 18.6% of patients (mainly panic attacks), and PSD persisted in 29.8% of patients. Memory loss persisted in 67.4% of patients and executive difficulties persisted in 74.4% of patients. Thirteen months after stroke, 34.7% of individuals had returned-to-work and 47.1% had not returned-to-work. The other 18.2% were not working either at the time of their stroke or after the stroke. Logistic regression indicated that post-stroke apathy, PBA, and memory loss were significant predictors of not returning-to-work (odds ratio p &lt; 0.001). Patients who experienced post-stroke apathy were 7.1 times more likely to not return-to-work after stroke (p=0.008), those who suffered from PBA were 4.8 times more likely to not return-to-work (p=0.028), and those with memory loss were 6.6 times more likely to not return-to-work (p=0.005). PSD, history of treatment for psychiatric issues before the stroke, presence of an anxiety disorder after stroke, and executive difficulties were not significant predictors (p’s&gt;0.05).Conclusions:Results replicate the finding that return-to-work is hindered by residual cognitive deficits after stroke and extends previous research by clarifying the multifactorial emotional and behavioral barriers to not returning-to-work. Results highlight the importance of quantifying post-stroke apathy and pseudobulbar affect in a standard neuropsychological work-up after stroke to identify candidates for services to facilitate efforts in returning to work (e.g., vocational rehabilitation services, psychotherapy, interventions for decreased initiation).

Pharmaceutical interventions for emotionalism after stroke.

Antidepressants may be useful in the treatment of abnormal crying associated with stroke. This is an update of a Cochrane Review first published in 2004 and last updated in 2019. To evaluate the benefits and harms of pharmaceutical treatment in people with emotionalism after stroke. We searched the Cochrane Stroke Group Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registers (May 2022). We included randomised controlled trials (RCTs) and quasi-RCTs comparing psychotropic medication to placebo in people with stroke and emotionalism (also known as emotional lability, pathological crying or laughing, emotional incontinence, involuntary emotional expression disorder, and pseudobulbar affect). Two review authors independently selected trials, assessed risk of bias, extracted data from all included trials, and used GRADE to assess the certainty of the body of evidence. We calculated the mean difference (MD) or standardised mean difference (SMD) for continuous data and the risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic. The primary emotionalism measures were the proportion of participants achieving at least a 50% reduction in abnormal emotional behaviour at the end of treatment, improved score on the Center for Neurologic Study - Lability Scale (CNS-LS) or Clinician Interview-Based Impression of Change (CIBIC), or diminished tearfulness. We did not identify any new trials for this update. We included seven trials with a total of 239 participants. Two trials had a cross-over design, but outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Thus, the results of the review are based on five trials with a total of 213 participants. It is uncertain whether fluoxetine increases the number of people who have a 50% reduction in emotionalism when compared to placebo (risk ratio (RR) 0.26, 95% CI 0.09 to 0.77; P = 0.02; 1 trial, 19 participants) because the certainty of evidence is very low. Sertraline may lead to little to no difference in Center for Neurologic Study - Lability Scale (CNS-LS) scores and Clinician Interview-Based Impression of Change (CIBIC) scores when compared to placebo (RR 0.20, 95% CI 0.03 to 1.50; P = 0.12; 1 trial, 28 participants; low-certainty evidence). Antidepressants probably increase the number of people who experience a reduction in tearfulness (RR 0.32, 95% CI 0.12 to 0.86; P = 0.02; 3 trials, 164 participants; moderate-certainty evidence). No trials were found that evaluated the impact of other pharmaceutical interventions. Only two trial authors systematically recorded and reported adverse events, resulting in limited data on the potential harms of treatment. Six trials reported death as an adverse event and found no difference between the groups (antidepressants versus placebo) in the number of deaths reported (RR 0.59, 95% CI 0.08 to 4.50; P = 0.61; 172 participants; moderate-certainty evidence). This review provides very low- to moderate-certainty evidence that antidepressants may reduce the frequency and severity of emotionalism. The included trials were small and had some degree of bias. Antidepressants may reduce the frequency and severity of crying or laughing episodes when compared to placebo, based on very low-certainty evidence. Our conclusions must be qualified by several methodological deficiencies in the trials and interpreted with caution despite the effect being very large. The effect does not seem specific to one drug or class of drugs. More reliable data are required before appropriate conclusions can be made about the treatment of post-stroke emotionalism. Future trialists investigating the effect of antidepressants in people with emotionalism after stroke should consider developing and using a standardised method to diagnose emotionalism, determine severity, and assess change over time; provide treatment for a sufficient duration and follow-up to better assess rates of relapse or maintenance; and include careful assessment and complete reporting of adverse events.

The relationship between stress, anxiety, and depression levels and pseudobulbar affect in patients with multiple sclerosis

Background Pseudobulbar affect (PBA) has recently been added to the list of mental disorders commonly observed in patients with Multiple Sclerosis (MS). The emotional changes experienced by MS patients may be associated with other mental problems and adversely affect disease prognosis. However, there are limited studies in the international and national literature on this subject. Aim This study aimed to evaluate the relationship between PBA and stress, anxiety, and depression levels in patients with MS. Design This is a descriptive, relational, and cross-sectional study. Methods A total of 442 MS patients followed in the neurology outpatient clinic of a hospital and registered with the MS Society in Turkey participated in this study. Data were collected using a personal information form, the Turkish version of the Center for Neurologic Study–Lability Scale (CNS-LS), and the Depression Anxiety Stress Scale (DASS). Results In this study, 63.3% of the patients had PBA, 21% had extremely severe depression, 41.6% had extremely severe anxiety, and 24.9% had severe stress. Correlation analysis revealed weak positive correlations between CNS-LS total score and DASS subscale and total scores. Depression, anxiety, and stress levels accounted for 22.5% of the variation in CNS-LS total score. Conclusion The results of this study indicate that a majority of MS patients in Turkey experience PBA, depression, anxiety, and stress, and that PBA is positively associated with depression, anxiety, and stress. Impact statement This study, indicates that should be increased consultation-liaison psychiatry services in Turkey, and MS patients should benefit from comprehensive psychiatric services.

Evaluation of neuropsychiatric symptoms in patients with multiple sclerosis

Purpose: The aim of this study was to comprehensively assess the neurophyschiatric symptoms of multiple sclerosis (MS) such as apathy and pseudobulbar affect and their correlation with other concomitant factors.&#x0D; Materials and Methods: Montreal Cognitive Assessment (MoCA), Apathy Evaluation Scale (AES), Fatigue severity scale (FSS), Center for Neurologic Study-Lability Scale (CNS-LS), Beck Depression Inventory (BDI) are applied to 258 MS patients. Correlation and regression analysis are conducted between scales and other possible causers.&#x0D; Results: 53.6% of the patients have psuedobulbar affect, 76.2% of patient population have fatigue. Pseudobulbar affect had positive correlation with fatigue and also depression while apathy negatively correlate with pseudobulbar affect or fatigue. Additionally, apathy and depression correlated negatively. There was no relation between cognition and depression and/or disease duration and/or other scales’ scores. &#x0D; Conclusion: Pseudobulbar affect and apathy are quite common symptoms in MS patients, that are cross-cutting issues. Also, apathy may be an independent neuropyschiatric symptom of MS that need to be approached separately.

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.

Pseudobulbar Affect Symptoms in Nursing Home Patients with Neurocognitive Disorders

Background: Symptoms of pseudobulbar affect (PBA) often are misinterpreted as those of a mood disorder. Symptoms seen in patients with PBA can be influenced by a mood disorder and vice versa. Our aim in this study was to determine the occurrence rate of PBA symptoms and comorbid depressive symptoms in a cohort of nursing home patients with different subtypes of neurocognitive disorders (NCD)/dementia. Methods: Eighty patients were screened and 61 met the inclusion criteria. These individuals were divided into 5 groups according to NCD subtypes: Alzheimer’s disease, vascular, HIV, unspecified, or combined types. The Center for Neurologic Study–Lability Scale (CNS-LS) and the Geriatric Depression Scale–Short Form (GDS-SF) were used to screen for PBA and depressive symptoms, respectively. The Mini-Mental Status Exam (MMSE) was used to determine patients’ baseline functioning. Fifty-nine patients successfully completed the CNS-LS and 42 completed the GDS. Results: Forty-four percent of individuals screened positive for PBA symptoms. Depressive symptoms were found among 23% of these patients. Not only were PBA-symptoms positive patients common among this nursing home residents, the PBA-symptoms positive patients were found to cluster mostly among those with NCD due to HIV (66.0%). PBA symptom-positive patients often received psychotropics. Conclusion: Better awareness, screening tools, and treatment approaches for patients with NCD expressing PBA-symptoms—especially those with NCD due to HIV Infection—are needed.

Non-motor features of amyotrophic lateral sclerosis: A clinic-based study

Introduction:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of motor neurons. Spread of pathology to other brain areas leads to development of non-motor symptoms (NMSs). These usually remain undiagnosed because of overwhelming motor problem and are responsible for significant distress to the patient. Our objective was to explore the burden of various NMSs of patients with ALS, compare between limb-onset and bulbar-onset patients, and to correlate with severity and duration of disease.Methods:Fifty patients with ALS diagnosed according to revised El Escorial Criteria and 50 healthy controls were included in this study. They were assessed with NMS Questionnaire, Beck's Depression Inventory, Center for Neurologic Study-Lability Scale, Drooling Frequency and Severity Scale, Epworth Sleepiness scale, Bengali Mental State Examination, and Frontal Assessment Battery and relevant statistical analyses were carried out.Results:The patients with ALS had significantly increased prevalence of almost all NMSs compared to controls. There was also significant increase in depression, suicidal ideation, pseudobulbar affect, and daytime sleepiness in patients with ALS. The bulbar onset subgroup had significantly increased daytime drooling, dysphagia, nausea and vomiting, whereas the limb onset subgroup reported increased frequency of leg swelling. Executive dysfunction was detected in 24% of patients with ALS and 9.8% had mild cognitive impairment. Weight loss, frequency of falling, insomnia, unpleasant nocturnal leg sensations, difficulty having sex, depression, and cognitive impairment increased significantly with an increase in severity of the disease.Conclusion:NMSs were significantly more prevalent in patients with ALS. Some NMSs worsened with advancement of the disease.

Involuntary emotional expression disorder in postural tachycardia syndrome.

To study the frequency of latent and overt involuntary emotional expression disorder (IEED) in postural tachycardia syndrome (PoTS). We compared 51 PoTS patients with 15 neurally mediated hypotension (NMH) patients and 12 control subjects using the Center for Neurologic Study-Lability Scale (CNS-LS) for latent IEED and the PHQ-9 questionnaire for depression screening before head-up tilt (HUT). Overt IEED occurrence was observed during HUT. HUT precipitated overt IEED in 11 (22%) PoTS patients but not in NMH patients or controls. CNS-LS identified latent IEED in 23 (45%) PoTS patients, 5 (33%) NMH patients, and no control subjects. The CNS-LS tearfulness subscale was elevated in PoTS patients compared with controls (P = 0.0006). The PHQ-9 questionnaire scores were elevated in 69% of PoTS patients and 47% of NMH patients. The PHQ-9 score was higher in PoTS (<0.0001) and NMH (P = 0.0002) patients compared with controls. The study demonstrated frequent occurrence of latent IEED in PoTS and NMH and overt IEED in PoTS without "structural" involvement. HUT was a specific trigger for overt IEED in PoTS. Depression was co-morbid with PoTS. Neurohumoral and cerebral blood flow changes in supine position along with reduced gray matter volume in the insula and cingulate gyrus may underlie susceptibility to IEED. During HUT, cerebral hypoperfusion, rising epinephrine levels, and augmented autonomic arousal provide underpinnings for overt IEED. Clinicians should recognize this entity and counsel PoTS patients and their families. Limiting the duration of orthostatic stress may reduce morbidity.

Neuropsychiatric profile of patients with craniocervical dystonia: A case-control study

ObjectiveDepression, anxiety, and obsessive-compulsive disorder have been widely reported in patients with dystonia. On the other hand, cognitive impairment, frontal lobe function, impulsiveness and pseudobulbar affect are less studied. The objective of the study is to assess these neuropsychiatric symptoms along with the quality of life of subjects with craniocervical dystonia. Patients and methodsA cross-sectional study was carried out in patients with craniocervical dystonia. Sex- and age-matched healthy controls were included. Neuropsychiatric assessment included the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Barrat Impulsiveness Scale (BIS-11), Center for Neurologic Study-Lability Scale (CNS-LS), Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), and the 12-item Short Form Health Survey (SF-12). ResultsA total of 44 patients with craniocervical dystonia and 44 controls were included. The mean age was 57 ± 13.7 years. Depression (56.1 % vs 9.1 %, p < 0.001), anxiety (56.8 % vs 6.8 %, p < 0.001), and pseudobulbar affect (31.8 % vs 9.1 %, p = 0.02) were more common in the dystonia group in comparison to controls. No difference between groups was found in impulsiveness (p = 0.65), MoCA score (p = 0.14) or executive dysfunction (p = 0.42). Quality of life was worst in the dystonia group with 90.9 % (p = 0.03) and 61.4 % (p < 0.001) of the subjects scoring under average in the Physical Composite Score (PCS) and Mental Composite Score (MCS) of the SF-12. ConclusionMoCA scores ≤18, pseudobulbar affect, depression and anxiety are more prevalent in subjects with craniocervical dystonia in comparison to sex- and age-matched healthy controls. Regarding quality of life, MCS is more affected that the PCS in subjects with dystonia.

B-59 Prevalence of Pseudobulbar Affect Symptoms in Professional Fighters

Abstract Objective Pseudobulbar Affect (PBA) is defined as dysregulation of emotional expression and is characterized by sudden, uncontrollable, laughing and/or crying that is discordant with the present mood or social context. This study sought to establish the prevalence of PBA symptoms in individuals with a high incidence of sports-related head injuries and explore the relationship between two rating scales designed to measure PBA symptoms. Methods Sixty-three professional fighters (age: M = 44.7, SD = 10.0; 98% male) underwent neurological and neuropsychological assessment including completion of the Pathological Laughing and Crying Scale (PLCS) and the Center for Neurologic Study – Lability Scale (CNS-LS). Diagnostic criteria for PBA were reviewed during the neurological exam to establish the prevalence of the clinical syndrome. Prevalence statistics for item endorsement on the rating scales and diagnostic status were calculated. To investigate the rate of agreement between rating scales, concordance correlation coefficient (CCC) and root mean square difference (RMSD) were calculated. Results Eleven percent of participants met clinical criteria for PBA diagnosis, 25% of participants endorsed clinically significant PBA symptoms on the CNS-LS (M = 10.9, SD = 4.9), and 8% endorsed significant symptoms on the PLCS (M = 3.1, SD = 6.5). The rating scales were significantly positively correlated (r = .58; p &lt; .01), though overall agreement was low (CCC = 0.55; RMSD = 5.4). Conclusions This study demonstrates that the prevalence of PBA symptoms in a sample of professional fighters is not uncommon. Although both the CNS-LS and PCLS are designed to measure PBA symptoms, they appear to be measuring unique aspects of PBA that may provide complimentary, rather than redundant information.

Pharmaceutical interventions for emotionalism after stroke.

Antidepressants may be useful in the treatment of abnormal crying associated with stroke. This is an update of a Cochrane Review first published in 2004 and last updated in 2010. To determine whether pharmaceutical treatment reduces the frequency of emotional displays in people with emotionalism after stroke. We searched the trial register of Cochrane Stroke (last searched May 2018). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; to May 2018), MEDLINE (1966 to 14 May 2018), Embase (1980 to 14 May 2018), CINAHL (1982 to 14 May 2018), PsycINFO (1967 to 14 May 2018), BIOSIS Previews (2002 to 14 May 2018), Web of Science (2002 to 14 May 2018), WHO ICTRP (to 14 May 2018), ClinicalTrials.gov (to 14 May 2018), and ProQuest Dissertations and Theses Database (to 14 May 2018). Randomised controlled trials (RCTs) and quasi-RCTs comparing psychotropic medication to placebo in people with stroke and emotionalism (also known as emotional lability, pathological crying or laughing, emotional incontinence, involuntary emotional expression disorder, and pseudobulbar affect). Two review authors independently selected studies, assessed risk of bias, extracted data from all included studies, and used GRADE to assess the quality of the body of evidence. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data and risk ratio (RR) for dichotomous data with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. The primary emotionalism measures were the proportion of participants achieving at least a 50% reduction in abnormal emotional behaviour at the end of treatment, improved score on Center for Neurologic Study - Lability Scale (CNS-LS), Clinician Interview-Based Impression of Change (CIBIC) or diminished tearfulness. We included seven trials with a total of 239 participants. Two trials were of cross-over design, and outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Thus, the results of the review are based on five trials with 213 participants. Treatment effects were observed on the following primary endpoints of emotionalism: There is very low quality of evidence from one small RCT that antidepressants increased the number of people who had 50% reduction in emotionalism (RR 16.50, 95% CI 1.07 to 253.40; 19 participants) and low quality evidence from one RCT of improved scores on Center for Neurologic Study - Lability Scale (CNS-LS) and Clinician Interview-Based Impression of Change (CIBIC) with antidepressants (RR 1.44, 95% CI 0.95 to 2.19; 28 participants). There was moderate quality evidence from three RCTS that they increased the number of people who had a reduction in tearfulness (RR 2.18, 95% CI 1.29 to 3.71; 164 participants); and low quality evidence from one RCT of improved scores on the Pathological Laughter and Crying Scale (PLCS) (MD 8.40, 95% CI 11.56 to 5.24; 28 participants).Six trials reported adverse events (death) and found no difference between the groups in death (RR 0.59, 95% CI 0.08 to 4.50; 6 RCTs, 172 participants, moderate-quality evidence). Antidepressants may reduce the frequency and severity of crying or laughing episodes based on very low quality evidence. Our conclusions must be qualified by several methodological deficiencies in the studies and interpreted with caution despite the effect being very large. The effect does not seem specific to one drug or class of drugs. More reliable data are required before appropriate conclusions can be made about the treatment of post-stroke emotionalism. Future trialists investigating the effect of antidepressants in people with emotionalism after stroke should consider developing and using a standardised method to diagnose emotionalism, determine severity and assess change over time; provide treatment for a sufficient duration and follow-up to better assess rates of relapse or maintenance and include careful assessment and complete reporting of adverse events.

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.

Pseudobulbar affect: Prevalence and association with symptoms in multiple sclerosis.

We sought to determine the prevalence of pseudobulbar affect (PBA) in a large MS population and assess its association with disability and symptom severity. North American Research Committee on MS (NARCOMS) registry participants completed the Center for Neurologic Study-Lability Scale (CNS-LS), a validated 7-question self-report measure of PBA. A composite PBA score was derived from the sum of responses to the 7 questions. We categorized individuals as PBA-positive (PBA[+]) if they had a composite score ≥17 without current depression. Participants also reported their demographic characteristics and their clinical characteristics using Patient-Determined Disease Steps and Performance Scales. We compared clinical and disease characteristics for PBA(+) responders with those without PBA using descriptive statistics and multivariable multinomial logistic regression. Of the 8,136 responders, 574 (7%) had scores ≥17 on the CNS-LS; however, only 200 (2.5%) individuals had scores ≥17 without comorbid depression, of whom only 22 (11%) reported a diagnosis of PBA. PBA(+) individuals tended to be younger (mean [SD] 53.4 [11.0] vs 57.2 [10.3] years), non-white (13% vs 9%), and have lower socioeconomic status (≤$30,000 annual income: 28% vs 22%). In multivariable models, PBA(+) was associated with increased odds of more severe cognitive impairment (moderate vs mild disability OR: 1.37; 95% CI: 1.01, 1.84). Our findings suggest that the prevalence of PBA in MS is low, but similar symptoms may co-occur or overlap with depression, highlighting the importance of concomitant assessment of mood when evaluating potential PBA. PBA may be associated with cognitive impairment in people with MS.

Pseudobulbar affect prevalence in Turkish multiple sclerosis patients

Objective:&nbsp;Pseudobulbar affect (PBA) is characterized by uncontrolled crying or laughing attacks which are usually socially inappropriate. The estimated prevalence in patients with multiple sclerosis (MS) ranges from 10% to 46.2%. We conducted a cross-sectional study to evaluate the prevalence of PBA in the Turkish MS population. Also, we aimed to estimate whether there was gender preference or coexistent depression. Material and Methods:&nbsp;We used the Center for Neurologic Study - Lability Scale (CNS-LS) for this study. We included patients who were followed up at our outpatient clinic of Sultan Abdulhamid Han Education and Research Hospital with definitive diagnosis of MS at least for one year. The total number of patients was 328. 60.4% were women (198/328) and 39.6% were men (130/328). Descriptive statistical methods, student t test and chi-square tests were used for the analysis by using SPSS. The prevalence of PBA in the Turkish MS population was 39.6%. 34.6% of the men with MS had PBA; whereas 42.9% of the women with MS had PBA (p=0.132). The incidence of PBA was 48.1% in MS patients with depression and 38% in those without depression (p=0.175). Results:&nbsp;As a result of t-test applied it was understood that depression did not significantly contribute to PBA frequency. The average depression test score was 13.28 in non-depressed, 17.85 in others. Furthermore, there was a difference between pathological laughing and pathological crying (p&lt;0.05). Also, in both gender pathological laughing laughter was more and the difference was significant (p&lt;0.05). Conclusion:&nbsp;Our study revealed the increased frequency of PBA in MS patients. Gender and having depression did not make a significant difference on the PBA prevalence. However, depression significantly increased PBA test scores

Pseudobulbar affect as a negative prognostic indicator in amyotrophic lateral sclerosis.

To evaluate whether the presence of pseudobulbar affect (PBA) in an early stage of the disease influences survival in a population-based incident cohort of amyotrophic lateral sclerosis (ALS). Incident ALS cases, diagnosed according to El Escorial criteria, were enrolled from a prospective population-based registry in Puglia, Southern Italy. The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate PBA. Total scores range from 7 to 35. A score ≥13 was used to identify PBA. Cox proportional hazard models were used for survival analysis. The modified C-statistic for censored survival data was used for models' discrimination. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify subgroups of patients with different patterns of risk, depending on baseline characteristics. We enrolled 94 sporadic ALS, median age of 64years (range: 26-80). At the censoring date, 65 of 94 (69.2%), 39 of 60 (65.0%), and 26 of 34 (76.5%) patients reached the outcome (tracheotomy/death), in the whole, non-PBA and in the PBA groups, respectively. Kaplan-Meier survival curves for the two subgroups were not significantly different (log-rank test: 1.3, P=.25). The discrimination ability of a multivariable model with demographic and clinical variables of interest was not improved by adding PBA. In the RECPAM analysis, ALSFRSr and the total score of CNS-LS scale (</≥10) were the most important variables for differentiating all risk categories. These preliminary results underlie that the presence of PBA at entry negatively influences survival in a specific subgroup of patients with ALS characterized by less functional impairment.

Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect Among Study Participants With Traumatic Brain Injury: Results From the PRISM-II Open Label Study

BackgroundDextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). ObjectiveTo report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. DesignOpen-label trial evaluating twice-daily DM/Q over 90 days. Study ParticipantsAdults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. MethodsPRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. Setting150 U.S. centers. Main Outcome MeasurementsPrimary endpoint was change in Center for Neurologic Study–Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life–Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). ResultsDM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, –5.6 [5.2]; day 90, –8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had “much improved” or “very much improved” on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (–3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (–3.2 [5.3], P<.001) and 90 (–5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). ConclusionsDM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials. Level of EvidenceII

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.

Telephone based cognitive-behavioral screening for frontotemporal changes in patients with amyotrophic lateral sclerosis (ALS)

Our objective was to establish a valid and reliable battery of measures to evaluate frontotemporal dementia (FTD) in patients with ALS over the telephone. Thirty-one subjects were administered either in-person or by telephone-based screening followed by the opposite mode of testing two weeks later, using a modified version of the UCSF Cognitive Screening Battery. Equivalence testing was performed for in-person and telephone based tests. The standard ALS Cognitive Behavioral Screen (ALS-CBS) showed statistical equivalence at the 5% significance level compared to a revised phone version of the ALS-CBS. In addition, the Controlled Oral Word Association Test (COWAT) and Center for Neurologic Study-Lability Scale (CNS-LS) were also found to be equivalent at the 5% and 10% significance level, respectively. Similarly, the Mini-Mental State Examination (MMSE) and the well-established Telephone Interview for Cognitive Status (TICS) were also statistically equivalent. Equivalence could not be claimed for the ALS-Frontal Behavioral Inventory (ALS-FBI) caregiver interview and the Written Verbal Fluency Index (WVFI). In conclusion, our study suggests that telephone-based versions of the ALS-CBS, COWAT, and CNS-LS may offer clinicians valid tools to detect frontotemporal changes in the ALS population. Development of telephone based cognitive testing for ALS could become an integral resource for population based research in the future.