Center For Neurologic Study-Lability Scale Research Articles

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.

Abstract 107: Dextromethorphan/Quinidine for Treatment of Pseudobulbar Affect Secondary to Stroke: Results from the PRISM-II Study

Introduction: Pseudobulbar affect (PBA) is characterized by sudden, frequent, uncontrollable laughing/crying episodes that are out of proportion or disconnected from mood or social context. PRISM-II evaluated dextromethorphan/quinidine (DM/Q) effectiveness for PBA secondary to stroke (reported here), dementia, or traumatic brain injury. Hypothesis: DM/Q is effective and well tolerated for PBA secondary to neurologic disease such as stroke. Methods: Open-label, 12-week, US multicenter trial of DM/Q 20/10 mg twice/day (starting once/day in week 1). Eligible patients had PBA with Center for Neurologic Study-Lability Scale (CNS-LS) ≥13 (range 7-35), were ≥3 months post-stroke (ischemic or hemorrhagic) and neurologically stable. Primary endpoint: CNS-LS change at Day 90/early withdrawal; secondary endpoints: PBA episode count, CGI-C, PGI-C, PHQ-9, QOL-VAS, patient satisfaction, MMSE, Stroke Impact Scale, and adverse events. Results: 113 enrolled; 91 (80.5%) completed. CNS-LS improved by mean [95% CI] -7.6 [-9.0, -6.2] points at Day 90/endpoint from baseline mean (SD) of 20.8 (4.7), P<.001 vs baseline. PBA baseline mean (SD) weekly episode count of 19.6 (29.6) was reduced by 75.5% at Day 90/endpoint (P<.001 vs baseline). Patients or clinicians reported “much” or “very much” improvement with respect to PBA in 67.7% (PGI-C) and 75.0% (CGI-C) of patients. Improvements were also seen for PHQ-9, QOL-VAS and MMSE. All Stroke Impact Scale domain scores improved vs baseline (P=.02 to P<.001); Adverse events were reported by 40 (35.4%), assessed as treatment-related in 16 (14.2%), and led to discontinuation in 6 (5.3%). Conclusion: Consistent with the approved indication, DM/Q improved PBA symptoms, reduced frequency of PBA episodes and was well tolerated in patients with PBA secondary to stroke. CNS-LS change from baseline was similar to that seen with DM/Q in a Phase 3 trial in ALS or MS (mean change [95% CI] -8.2 [-9.4, -7.0]) and greater than improvement with placebo in that trial (mean change -5.7[-6.8,-4.7]). DM/Q was associated with global clinical improvements (PGI-C, CGI-C), along with improvements in cognition, depressive symptoms, stroke-related function and quality of life. Supported by: Avanir Pharmaceuticals, Inc.

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.

An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results.

Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study-Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C "much"/"very much" improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%). DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.

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.

Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect.

Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients with underlying risk factors for torsade de pointes and in those receiving medications that may interact with DM/Q.

Chemotherapy-Induced Pseudobulbar Affect: A Novel Case

Chemotherapy-Induced Pseudobulbar Affect: A Novel Case

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.

Pseudobulbar affect: an under-recognized and under-treated neurological disorder

Pseudobulbar affect (PBA) is a neurologic syndrome of emotional affect disinhibition, characterized by uncontrollable, exaggerated, and often inappropriate emotional outbursts, which may cause severe distress, embarrassment, and social dysfunction. However, the US prevalence of PBA remains unknown. An online survey was conducted primarily to estimate the US prevalence of PBA in patients with the six most commonly associated conditions: Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, stroke, and traumatic brain injury. Invitations to participate were randomly sent online to adults (aged ≥ 18 years) registered in the Harris Poll Online Panel who were patients or belonged to a household with a patient diagnosed with one of the six conditions (identified through previous screening by Harris Interactive). Participants were screened for PBA using the Pathological Laughing and Crying Scale (PLACS) and the Center for Neurologic Study-Lability Scale (CNS-LS). PBA estimates were made using a cut-off score of ≥ 13 on the PLACS and two different cut-off thresholds on the CNS-LS, a lower one of ≥ 13 and a more rigorous one of ≥ 21. Existing US prevalence data for the six underlying conditions were used to estimate US prevalence of PBA. Of 38,000 individuals invited to participate, 8876 responded (23%) and 2318 (26%) completed the questionnaire. Mean prevalence of PBA across all six conditions was 10.1%, 9.4%, and 37.5% with the PLACS ≥ 13, CNS-LS ≥ 21, and CNS-LS ≥ 13 thresholds, respectively. Using disease population estimates from government agencies and professional organizations, the estimated US population with PBA ranged from 1.8 to 7.1 million. Among patients who discussed their laughing and/or crying episodes with a physician, 41% were diagnosed, and about half received a medication for their episodes. The overall prevalence of PBA was estimated to be about 10% across these commonly associated underlying neurological conditions and appears to be under-recognized.

Pseudobulbar affect: prevalence and quality of life impact in movement disorders

Pseudobulbar affect (PBA) is an affective disinhibition syndrome characterized by sudden, involuntary outbursts of inappropriate crying or laughing. We have previously reported the prevalence of PBA in movement disorders using an interviewer-administered questionnaire that had not been validated. In the current study, a validated self-administered screening instrument, the Center for Neurologic Study-Lability Scale (CNS-LS), was used to study the prevalence of PBA, its association with mood symptoms, and the quality of life impact. Two hundred sixty-nine patients met inclusion criteria (consent, age > 18 years, formal diagnosis, and completion of the CNS-LS). The CNS-LS was used to assess PBA at a cutoff score of 17 (utilized from multiple sclerosis studies). The Beck Depression Inventory (BDI) scale and Parkinson's disease questionnaire (PDQ-39) were used to assess depressive symptoms and quality of life. Logistic regression analysis was used to predict associations with PBA. PBA was prevalent in 7.1% (n = 19) of movement disorder patients. No significant difference in prevalence was observed by patient diagnosis: 7.1% (12/168) in Parkinson's disease (PD), 11.4% (4/35) in essential tremor, 0% (0/13) in dystonia, 0% (0/16) in psychogenic movement disorders, and 10.7% (3/28) in patients with other movement disorders. Patients with PBA had higher BDI depression scores (p < 0.0001) and lower PDQ-39 emotional well-being subscores (p < 0.0001). Patients taking antidepressant medications had significantly higher rates of PBA (p = 0.0008). The prevalence of PBA symptoms was 7.1% in PD and all movement disorders patients. Patients with PBA tend to have more depressive symptoms and poorer quality of life.

Duloxetine for pathological laughing and crying

Pathological laughing and crying (PLC) is a condition characterized by frequent, sudden outbursts of uncontrollable crying and/or laughing that are disproportionate or incongruent to underlying feelings or external triggers (Wortzel et al. 2008). Alternative terms often used to describe this syndrome are pseudobulbar affect, emotional incontinence, emotional or affective lability, organic or pathological emotionalism and involuntary emotional expression disorder. The condition is associated with various neurological disorders, such as stroke, multiple sclerosis, Parkinson's disease, traumatic brain injury, dementia and amyotrophic lateral sclerosis (ALS). PLC can be socially and occupationally disabling and is a source of distress for affected patients and their families. However, it is largely under-recognized or misdiagnosed in clinical settings. An important first step in the recognition and accurate measurement of PLC has been accomplished with the introduction of specific rating scales, such as the interviewer administered Pathological Laughter and Crying Scale validated for use with stroke victims (Robinson et al. 1993) and the self-report Center for Neurologic Study – Lability Scale (CNS-LS) validated for use with ALS and multiple sclerosis patients (Moore et al. …

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.

Exaggerated Crying and Tremor With a Cerebellar Cyst

Exaggerated Crying and Tremor With a Cerebellar Cyst

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis

To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p <or= 0.0077), quality of life (p < 0.0001), quality of relationships (p = 0.0001), and pain intensity score (p = 0.0271). DM/Q was well tolerated; only dizziness occurred with greater frequency than with placebo. Results in multiple sclerosis patients were similar to those of a previous study in amyotrophic lateral sclerosis, demonstrating that DM/Q may be beneficial in treating potentially disabling pseudobulbar affect in a variety of neurological disorders.

Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine

Patients with ALS commonly exhibit pseudobulbar affect. The authors conducted a multicenter, randomized, double-blind, controlled, parallel, three-arm study to test a defined combination of dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) (AVP-923) for the treatment of pseudobulbar affect in ALS. Q inhibits the rapid first-pass metabolism of DM. The effects of AVP-923 (30 mg of DM plus 30 mg of Q) given twice daily for 28 days were compared with those of its components. Patients were evaluated on days 1, 15, and 29. The primary efficacy variable was the change from baseline in the Center for Neurologic Study Lability Scale (CNS-LS) score. Secondary efficacy variables were laughing/crying episode rates and changes in Visual Analog Scales for Quality of Life (QOL) and Relationships (QOR). Efficacy was evaluated in intention-to-treat subjects who were not poor metabolizers of DM (n = 65 for AVP-923, n = 30 for DM, and n = 34 for Q). Safety was assessed in all randomized subjects (n = 140). AVP-923 patients experienced 3.3-point greater improvements in CNS-LS than DM patients (p = 0.001) and 3.7-point greater improvements than Q patients (p < 0.001). AVP-923 patients exhibited lower overall episode rates, improved QOL scores, and improved QOR scores (p < 0.01 for all endpoints). Adverse effects were mostly mild or moderate; treatment-related discontinuation was 24% for AVP-923, 6% for DM, and 8% for Q. AVP-923 palliates pseudobulbar affect in ALS. Overall benefits of treatment are reflected in fewer episodes of crying and laughing and improvements in overall quality of life and quality of relationships.

Measuring pseudobulbar affect in ALS

to neurologists to further characterize the disorder. When it became apparent that pseudobulbar affect could be moderated with treatment, the need for a quantitative test instrument became apparent. About 10 years ago Robinson and his colleagues developed the Pathological Laughing and Crying Scale (PLACS), an interviewer-administered rating scale that was validated for use in patients with cerebral vascular disease.2 This has been utilized as a trial endpoint in several studies of the effect of serotonin uptake inhibitors. 3,4 A modified version of PLACS has been developed for use with ALS patients but it has not been used as an endpoint in a clinical trial. 5 In contrast to PLACS, the Center for Neurologic Study-Lability Scale (CNS-LS) is a self- administered scale that has been validated in a large population of ALS patients. 6 It is short – seven items in the simplest iteration that chronicles labile tearfulness and laughter, and about twice that size when subscales measuring labile anger and frustration are included. (see Appendix 1 for the CNS-LS.) Since its publication in 1997, the CNS-LS has proven to be a useful diagnostic instrument and a robust clinical trial endpoint in ALS.7 While pseudobulbar affect commonly occurs in the setting of ALS, particularly in patients with bulbar involvement, it also occurs in a variety of other disorders including multiple sclerosis, Alzheimer’s disease, and stroke. The lack of disease specificity suggests a common anatomical substrate which in our opinion is best conceptualized as a disconnection syndrome. Several lines of evidence implicate brainstem and/or cerebellar connections to the cortex that are probably disrupted as a result of pathological processes. In the traditional view, advanced by Wilson in the 1920s, lesions in descending cortical pathways disrupt a brainstem control center that is hypothesized to reside in the upper pons or midbrain. This paradigm has been challenged by recent evidence suggesting that the cerebellum moderates emotional responses. Using advanced imaging techniques Parvizi et al. have reconstructed three-dimensional images of the brain of a patient with florid emotionality resulting from a cerebral vascular accident. 8 The only lesions seen in this patient were

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...