DOCSLIB.ORG

Laughter, Crying and Sadness in ALS Nimish J Thakore,1 Erik P Pioro1,2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Laughter, Crying and Sadness in ALS Nimish J Thakore,1 Erik P Pioro1,2 JNNP Online First, published on June 1, 2017 as 10.1136/jnnp-2017-315622 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2017-315622 on 1 June 2017. Downloaded from Neurodegeneration RESEARCH PAPER Laughter, crying and sadness in ALS Nimish J Thakore,1 Erik P Pioro1,2 ► Additional material is ABSTRact are prevalent in amyotrophic lateral sclerosis (ALS), published online only. To view Background Pseudobulbar affect (PBA) is prevalent in where estimates range from 15% to >50%,1 8 and please visit the journal online both negatively affect quality of life (QoL).1 9 There (http:// dx. doi. org/ 10. 1136/ amyotrophic lateral sclerosis (ALS), but there is limited jnnp- 2017- 315622) information on its associations and course. is little information on the interplay or overlap of Objectives Explore prevalence, associations, course and these phenomena. 1Department of Neurology, manifestations of PBA in outpatient cohort of patients The aim of this study of a large cohort of patients Neuromuscular Center, with ALS and examine its relationship to depression. with ALS using self-report measures of PBA and Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA Methods Self-reported measures of PBA and depression is threefold: (1) examine the prevalence, 2Department of Neurosciences, depression (Center for Neurologic Study-Lability Scale associations and course of PBA in ALS; (2) explore Lerner Research Institute, (CNS-LS) and Patient Health Questionnaire (PHQ-9), associations, if any, that differentiate laughter from Cleveland Clinic, Cleveland, respectively) were obtained from consecutive patients crying in PBA; and (3) examine the relationship of Ohio, USA with ALS using tablet devices in waiting rooms PBA and depression, and if self-report instruments (Knowledge Program). effectively distinguish these two phenomena. A Correspondence to Nimish J Thakore, Department Results PBA (CNS-LS ≥13) was seen in 209/735 previous report describes the prevalence and associ- 9 of Neurology, Neuromuscular patients (28.4%). PBA was associated with bulbar ations of depression in this cohort. Center Neurological Institute, onset and dysfunction, upper motor neuron dysfunction, Cleveland Clinic, Cleveland, cognitive impairment, depression and lower quality of Ohio 44195, USA; thakorn@ METHODS ccf. org life. A multivariable model that included lower bulbar This was an exploratory observational study of PBA and gross motor subscores, female gender, younger age and depression in ALS, specifically addressing ques- Received 10 January 2017 and shorter duration of disease predicted PBA with 74% tions listed above. The cohort consisted of consec- Revised 16 March 2017 accuracy. CNS-LS scores increased only slowly with time. utive patients with ALS seen at a neuromuscular Accepted 12 April 2017 Women with PBA reported more crying than men. Crying centre between August 2006 and January 2015. (but not laughter) correlated with depression, and crying was associated with poorer quality of life. Exploratory Data source, participants and measures factor analysis of pooled questions of CNS-LS and PHQ-9 Under a quality initiative called Knowledge Program identified three underlying factors (laughter, crying and (KP),10 all neurology patients at our institution are depression) loaded on appropriate questions of the requested to provide patient-reported outcomes respective instruments. (PROs) during routine clinic visits using wireless Conclusion This study identifies associations of tablet devices in waiting rooms. Live data thus PBA and additionally findsP BA (especially crying- obtained inform clinical care. The practice of predominant PBA) more prevalent in women with ALS. collecting PROs is standard of care in neurology at http://jnnp.bmj.com/ Although the two self-report instruments (CNS-LS and our institution, and no additional consent is sought. PHQ-9) discriminate well between PBA and depression, These data accumulate in the KP Data Registry there is significant overlap between depression and that also includes some discrete elements of the crying in PBA. Studies of PBA should stratify for gender, patient’s electronic health record. Disease-spe- examine crying and laughter as separate outcomes and cific instruments used for ALS include a self-ad- adjust for depression. ministered version of the Revised ALS Functional Rating Scale (ALSFRS-R)11 and Center for Neuro- on September 26, 2021 by guest. Protected copyright. logic Study-Lability Scale (CNS-LS). ALSFRS-R is a widely used 12-question five-level instrument that INTRODUCTION measures function in ALS in the domains of bulbar, Pseudobulbar affect (PBA) is a treatable but fine motor, gross motor and respiratory function under-recognised neuropsychiatric phenomenon (three questions each),12 with a score of 48 repre- observed in a wide range of neurological disor- senting normal function. CNS-LS is a seven-ques- ders.1 PBA manifests with uncontrollable episodes tion five-level measure of PBA that includes four of laughter or crying that are excessive for or questions about laughter and three questions about incongruent with the underlying emotion and situ- crying.5 Total CNS-LS score can range from 7 to ation. Depression, on the other hand, is a pervasive 35, with a score of ≥13 implying clinically identi- disorder of mood characterised by sadness, anhe- fiable PBA (sensitivity 0.84 and specificity 0.81 in donia, worthlessness, suicidal thoughts and cogni- ALS).5 Generic outcomes measured in all neurolog- tive and somatic symptoms. Depression as well as ical disorders include Patient Health Questionnaire To cite: Thakore NJ, Pioro EP. PBA is typically diagnosed by a formal or structured (PHQ-9) andEuroQol five dimensions question- J Neurol Neurosurg Psychiatry Published Online First: [please interview and/or direct observation, and guidelines naire (EQ-5D). PHQ-9 is a nine-question four-level 2 include Day Month Year]. assist clinicians to differentiate the two conditions. instrument that incorporates Diagnostic and Statis- doi:10.1136/jnnp-2017- Additionally, various self-report instruments may be tical Manual for Mental Disorders, Fourth Edition 315622 used to screen for these conditions.3–7 Both states criteria for major depressive disorder.4 Total PHQ-9 Thakore NJ, Pioro EP. J Neurol Neurosurg Psychiatry 2017;0:1–7. doi:10.1136/jnnp-2017-315622 1 Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd under licence. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2017-315622 on 1 June 2017. Downloaded from Neurodegeneration score can range from 0 to 27, with a score of ≥10 implying at (sum of answers 1, 3 and 5) are presented in figure 1. Mean least moderate depression. EQ-5D is a brief five-question three- (SD) CNS-LS score was 10.86 (4.49), whereas median score level generic QoL index that includes a visual analogue scale was 9, and first and third quartiles were 7 and 13, respectively. (VAS) component.13 For this study, the KP Data Registry was The reported threshold for diagnosing PBA in ALS (13 points) queried by dates (2006–2015), diagnosis (International Clas- that we used for further analyses was reached or exceeded by sification of Diseases, ninth version, code 335.20) and depart- 209 of 735 patients (28.4%). In total, 293 (39.9%) reached a ment/centre evaluated (Neuromuscular) to obtain the dataset for liberal threshold of 11 points, but only 95 (12.9%) and 37 (5%) analysis. Corresponding patient charts were manually reviewed reached stringent thresholds of 17 and 21 points, respectively. for additional information including date of onset of weakness, The prevalence of PBA remained similar if we excluded patients site of onset (bulbar or extremity/other), clinical impression of with longer duration from onset (>2 years). cognitive dysfunction and clinical syndrome, namely typical ALS, upper motor neuron (UMN)-predominant disease or Associations of PBA lower motor neuron (LMN)-predominant disease. ALSFRS-R 14 Univariate associations of PBA are reported in columns 3–5 of ‘pre-slope’ was computed by dividing (initial ALSFRS-R minus table 1. PBA (CNS-LS ≥13) was significantly associated with 48) by months from weakness onset. female gender (37.8% vs 21.4% in males), bulbar onset (42.6% vs 23.2% in non-bulbar onset), lower ALSFRS-R score (espe- Statistical methods cially bulbar subscore) and more rapidly progressive disease. Distribution of CNS-LS scores and prevalence of PBA Prevalence of PBA increased with increasing UMN dysfunction (CNS-LS ≥13) were described. Univariate associations of PBA (10%, 29% and 39% for LMN-predominant disease, typical with categorical and continuous variables were examined using ALS and UMN-predominant disease, respectively). Only 1 of 12 Pearson’s χ2 test and Wilcoxon rank-sum test, respectively. (8%) patients with PMA had PBA compared with 10 of 25 (40%) Logistic regression with bootstrap validation was used for multi- patients with PLS. PBA was more prevalent in patients with cogni- variable prediction of PBA. In patients with repeated measures, tive dysfunction (37.9%) than those without (26.1%). Significant change in CNS-LS over time was estimated using a mixed model dysarthria/dysphagia (bulbar subscore ≤9) was observed in 69% that included a time term. The relative prevalence of laughter of patients with PBA compared with only 31% of those without. and crying was explored by centring and scaling corresponding Additionally, PBA was significantly associated with poorer objec- subscores by population means and SD, respectively (z-scores).15 tive (EQ-5D) and subjective (VAS) QoL, and with more prev- Patients with PBA were empirically classified into those who alent use of dextromethorphan-quinidine, antidepressants and cried more (crying-z-score > laughter-z-score), and those who baclofen. For a higher threshold of PBA (CNS-LS ≥17), several laughed more (laughter-z-score > crying-z-score), and asso- univariate associations were similar. An optimal multivariable ciations of these subgroups were examined. The association logistic regression model for PBA (CNS-LS ≥13) is presented between CNS-LS/PBA and PHQ-9/Depression/major depressive in figure 2 and online supplementary table S1 .
Load more

Recommended publications
  • Create a Healing Environment for Patients with Pseudobulbar Affect by Maude Mcgill, Phd, RN-BC, and Marzell Mcgill, BA, LPN
    Strictly Clinical Create a healing environment for patients with pseudobulbar affect By Maude McGill, PhD, RN-BC, and Marzell McGill, BA, LPN tact their provider for prompt appropriate treatment. • Signs and symptoms include: Teach patients how to manage PBA • emotional responses (such as crying or laughing) for optimal quality of life. that don’t fit the situation • emotional episodes lasting longer than expected • sudden emotional outbursts (these outbursts can I just don’t understand why Mom is crying. When I include frustration, anger, laughter, or crying) walked in the room, she was happy and calm. Then, • moments of intense emotions that are out of the when I asked her about her day, her smile turned into patient’s control a frown and she started crying uncontrollably. I’ve nev - • facial expressions that don’t match the emotional er seen her cry like that. I’m concerned. response. EMOTIONS ARE NATURAL . We’ve all heard the cliché, “Emotions make us human.” People cry when they’re hurt and laugh when things are funny. However, mil - lions of people find that controlling their emotions is hard because of pseudobul - bar affect (PBA). PBA refers to inappropriate, involun - tary, or uncontrollable laughing or crying caused by the residual effects of a nervous system disorder. Al - though PBA is closely asso - ciated with post-stroke pa - tients, it can occur with any nervous system condition, including Alzheimer’s dis - ease, traumatic brain injury, and multiple sclerosis. Sci - entists have labeled PBA a disorder of emotional incon - tinence (patients can’t control their emotional respons - Navigating the new normal of PBA es).
    [Show full text]
  • IHH Notification Form Guide
    Integrated Health Home Health Home Notification Form Guide Introduction This is to assist in providing the Health Home with information on criteria and how to enroll the member into an Integrated Health Home (IHH). Enrollment Criteria Member needs to 1. Be eligible for Medicaid. 2. Have 1 or more Serious Mental Illness (SMI) or Serious Emotional Disturbance (SED). 3. Meet the Functional Impairment (FI) as determined by a Licensed Mental Health Professional. SMI & SED Definitions Diagnosis must be determined by use the Diagnostic and Statistical Manual (DSM) of Mental Disorders published by the American Psychiatric Association or its most recent International Classification of Diseases (ICD). SMI is defined as an Adult that has a persistent or chronic mental illness, a behavioral, or emotional disorder that causes serious functional impairment and substantially interferes with or limits one or more major life activities including functioning in the family, school, employment or community. SMI may co-occur with substance use disorder, developmental, neurodevelopmental or intellectual disabilities but those diagnoses may not be the clinical focus for health home services. SED is defined by a Child having a diagnosable mental, behavioral or emotional disorder which results in a functional impairment that substantially interferes with or limits the child’s role or functioning in family, school, or community activities. SED may co-occur with substance use disorder, developmental, neurodevelopmental or intellectual disabilities but those diagnoses may not be the clinical focus for health home services. Mental Health Professional Definition Mental health professional meets all of the following conditions: 1. Holds at least a master’s degree in a mental health field including, but not limited to, psychology, counseling and guidance, psychiatric nursing and social work; or is a doctor of medicine or osteopathic medicine; and 2.
    [Show full text]
  • Nuedexta, INN-Dextromethorphan/Quinidine
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT NUEDEXTA 15 mg/9 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains dextromethorphan hydrobromide monohydrate, equivalent to 15.41 mg dextromethorphan and quinidine sulfate dihydrate, equivalent to 8.69 mg quinidine. Excipient with known effect: Each hard capsule contains 119.1 mg of lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule Brick red gelatin capsule, size 1, with “DMQ / 20-10” printed in white ink on the capsule. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications NUEDEXTA is indicated for the symptomatic treatment of pseudobulbar affect (PBA) in adults (see section 4.4). Efficacy has only been studied in patients with underlying Amyotrophic Lateral Sclerosis or Multiple Sclerosis (see section 5.1). 4.2 Posology and method of administration Posology The recommended starting dose is NUEDEXTA 15 mg/9 mg once daily. The recommended dose titration schedule is outlined below: Week 1 (day 1-7): The patient should take one NUEDEXTA 15 mg/9 mg capsule once daily, in the morning, for the initial 7 days. Weeks 2-4 (day 8-28): The patient should take one NUEDEXTA 15 mg/9 mg capsule, two times per day, one in the morning and one in the evening, 12-hours apart, for 21 days. From Week 4 on: If the clinical response with NUEDEXTA 15 mg/9 mg is adequate, the dose taken in weeks 2-4 should be continued. 2 If the clinical response with NUEDEXTA 15 mg/9 mg is inadequate, NUEDEXTA 23 mg/9 mg should be prescribed, taken two times per day, one in the morning and one in the evening, 12 hours apart.
    [Show full text]
  • What's New in Psychopharmacology
    Wednesday, 3:00 – 4:30, F2 What's New in Psychopharmacology Joel M. Sanchez, MD [email protected] Objectives: Identify advances in clinical assessment and management of selected healthcare issues related to persons with developmental disabilities Notes: 4/7/2016 What’s New in Nuedexta Psychopharmacology • A new medication for pseudobulbar affect (PBA) • Pseudobulbar Affect: Joel M. Sanchez, M.D. • Frequent, uncontrollable outbursts of crying or laughing in people with certain neurologic conditions or brain injuries Diplomate of the American Board of Psychiatry and Neurology, Psychiatry • Episodes may occur several times per day and can last seconds to minutes Diplomate of the American Board of Psychiatry and Neurology, Child/Adolescent Psychiatry • “emotional incontinence” • “pathological laughing and crying” The Right Door for Hope, Recovery and Wellness Wedgwood Christian Services Turning Leaf Behavioral Health Services Community Mental Health Authority - CEI ADHD Medications Antidepressants • Stimulants • SSRIs • Adzenys XR-ODT (amphetamine extended release oral dissolving tablet) • Brintellix (vortioxetine) • Quillivant XR (methylphenidate extended release liquid) • Viibryd (vilazodone) • Daytrana (methylphenidate transdermal) • SNRIs • Non-Stimulants • Fetzima (levomilnacipran) • Clonidine (Catapres / Kapvay) • Pristiq (desvenlafaxine) • Guanfacine (Tenex / Intuniv) • Strattera (atomoxetine) Antipsychotics Blood Pressure Medications • Abilify Maintena & Aristada (aripiprazole) • What’s Old is New • Every 4 weeks or Every 4-6
    [Show full text]
  • Pathological Laughter and Crying in Patients with Multiple System Atrophy-Cerebellar Type
    Movement Disorders Vol. 22, No. 6, 2007, pp. 798–803 © 2007 Movement Disorder Society Pathological Laughter and Crying in Patients with Multiple System Atrophy-Cerebellar Type Josef Parvizi, MD, PhD,1* Jeffrey Joseph, MD, PhD,1 Daniel Z. Press, MD,1 and Jeremy D. Schmahmann, MD2 1Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA Abstract: In the cerebellar type of multiple system atrophy or crying, or both in 9 more patients. Our finding of about (MSA-C), the burden of pathological changes involves the 36% occurrence suggests that the problem of dysregulation cerebellum and its associated brainstem structures in the of emotional expression is more prevalent in MSA-C basis pontis and the inferior olivary nucleus, and as a result, than the paucity of reports in the literature suggests. Our the clinical phenotype is dominated early on by the cerebel- findings are consistent with the view that the cerebellum and lar dysfunction. We report our clinical and post mor- its interconnected structures may be involved in the regula- tem findings in a patient with MSA-C who exhibited patho- tion of emotional expression. © 2007 Movement Disorder logical laughter in the absence of any congruent changes of Society mood. A review of the clinical notes of 27 other patients Key words: olivopontocerebellar atrophy; disinhibition; with MSA-C revealed a problem with pathological laughter, emotion; behavior; pseudobulbar affect Pathological laughter and crying (PLC) is a condition Numerous terms have been introduced to describe the in which a patient with an underlying neurological dis- problem of inappropriate or exaggerated laughing and order exhibits episodes of laughter or crying or both, crying.
    [Show full text]
  • Nuedexta, INN-Dextromethorphan/Quinidine
    authorised longer no product Medicinal SUMMARY OF PRODUCT CHARACTERISTICS ANNEX I 1 1. NAME OF THE MEDICINAL PRODUCT NUEDEXTA 15 mg/9 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains dextromethorphan hydrobromide monohydrate, equivalent to 15.41 mg dextromethorphan and quinidine sulfate dihydrate, equivalent to 8.69 mg quinidine. Excipient with known effect: Each hard capsule contains 119.1 mg of lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule Brick red gelatin capsule, size 1, with “DMQ / 20-10” printed in white inkauthorised on the capsule. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications longer NUEDEXTA is indicated for the symptomatic treatmentno of pseudobulbar affect (PBA) in adults (see section 4.4). Efficacy has only been studied in patients with underlying Amyotrophic Lateral Sclerosis or Multiple Sclerosis (see section 5.1). 4.2 Posology and method of administration product Posology The recommended starting dose is NUEDEXTA 15 mg/9 mg once daily. The recommended dose titration schedule is outlined below: Week 1 (day 1-7): The patientMedicinal should take one NUEDEXTA 15 mg/9 mg capsule once daily, in the morning, for the initial 7 days. Weeks 2-4 (day 8-28): The patient should take one NUEDEXTA 15 mg/9 mg capsule, two times per day, one in the morning and one in the evening, 12-hours apart, for 21 days. From Week 4 on: If the clinical response with NUEDEXTA 15 mg/9 mg is adequate, the dose taken in weeks 2-4 should be continued.
    [Show full text]
  • Clinical Guidelines/Recommendations
    Volume 1, Issue Number 12; July 8, 2005 News Highlights from June 20 – July 1, 2005 Coming in August … TrendsRx® Drug Pipeline and News will be getting a new look! Look for the same up-to-date information with a fresh new format! PIPELINE Generic Medicines for the Treatment of HIV Tentatively Approved Under the Government’s Emergency Plan for AIDS Relief On June 20, 2005, the United States Food and Drug Administration (FDA) announced tentative approval of two applications for nevirapine tablets, manufactured by Ranbaxy Laboratories Limited (Guragon, India) and Aurobindo Pharma Limited (Hyderabad, India).1 These products will be the first generic versions of Viramune® tablets, manufactured by Boehringer Ingelheim. Generic nevirapine will be available for purchase under the President’s Emergency Plan for AIDS Relief (PEPFAR).1 This plan allows for the availability of safe and effective AIDS treatments quicker and at a lower cost as part of worldwide HIV/AIDS relief.1-3 It is designed to prevent new HIV infections, treat HIV-infected people, and care for HIV-affected individuals.1-3 Tentative approval under PEPFAR means that although existing patents and/or exclusivity prevent marketing of these products in the United States, they meet the FDA standards for quality, safety and efficacy.1-3 On June 24 and July 1, 2005, respectively, the FDA also announced tentative approval of efavirenz tablets and stavudine capsules manufactured by Aurbindo Pharma LTD. (Hyderabad, India).2 These are the first generic versions of Sustiva® and Zerit®, respectively, manufactured by Bristol-Myers Squibb. Both generic products will also be considered for purchase under the PEPFAR.2 Nevirapine and efavirenz are non-nucleoside reverse transcriptase inhibitors (NNRTIs) used in combination with other medicines for the treatment of HIV-1 infection.1-2 Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) also used in combination with other medicines for the treatment of HIV-1 infection.3 © Copyright 2005 Caremark.
    [Show full text]
  • Pseudobulbar Affect: When Patients Laugh Or Cry, but Don’T Know Why
    Pseudobulbar affect: When patients laugh or cry, but don’t know why Disruption of neural circuitry undermines voluntary control of affect seudobulbar affect (PBA) is a disorder of affective expression that manifests as stereotyped and frequent Poutbursts of crying (not limited to lacrimation) or laugh- ter. Symptoms are involuntary, uncontrolled, and exaggerated or incongruent with current mood. Episodes, lasting a few seconds to several minutes, may be unprovoked or occur in response to a mild stimulus, and patients typically display a normal affect between episodes.1 PBA is estimated to affect 1 to 2 million people in the United States, although some studies suggest as many as 7 million,1,2 depending on the evaluation method and threshold criteria used.3 Many terms have been used to describe aspects of PBA (Table 14 and Box, page 585-10). This abundance of often con- flicting terminology is thought to have impeded efforts to © SIMONE GOLOB/CORBIS categorize emotional expression disorders, determine their Benjamin Frock, MD prevalence, and evaluate clinical evidence of potential ther- PGY-1 Resident apeutic options.11 Vanderbilt University School of Medicine Nashville, Tennessee Andrew Williams, MD Where to look for pseudobulbar affect PGY-1 Resident Oregon Health & Science University PBA has been most commonly described in 6 major neuro- Portland, Oregon logic disorders: Jason P. Caplan, MD • Alzheimer’s disease Professor and Chair of Psychiatry • amyotrophic lateral sclerosis (ALS) Creighton University School of Medicine • multiple sclerosis (MS) Phoenix Regional Campus Phoenix, Arizona • Parkinson’s disease • stroke • traumatic brain injury (TBI). Disclosures Dr. Caplan has served as a consultant to Avanir Pharmaceuticals, an independent subsidiary of Otsuka America, Inc., manufacturer of the formulation of dextromethorphan/quinidine discussed Current Psychiatry in this article.
    [Show full text]
  • Your Guide to Understanding PBA
    I cry (or sometimes “laugh) out of nowhere, all the time. I can’t seem to control it, and it’s not the way I feel.” Your Guide to Understanding PBA If this sounds like you, and you have a neurologic condition or brain injury, you might have PseudoBulbar Affect (PBA). Learning about PBA is your first step in discovering how to manage the condition. Take a look through this guide to find out more about PBA and what to ask your doctor. Learn more about PBA You’ve taken a great first step in finding out more about PBA This kit is full of information to help you learn about the symptoms of PBA, assess your own symptoms more closely, and have a productive and honest discussion with your doctor. Be sure to fill out your information, and then print or email it to yourself so you can show it to your doctor. Contents of the kit: Your Guide to Understanding PseudoBulbar Affect (PBA) • What does PBA feel like? • What exactly is PBA? • Sometimes PBA can be mistaken for other conditions • What’s the difference between PBA and Depression? • Living with the symptoms of PBA • Reminders for my next doctor’s appointment Your short PBA quiz • Instructions • Take the quiz—print and take to your doctor Preparing for Your Doctor’s Visit • Tips for your visit • Track your episodes • Describe your episodes • 5 questions for you and your doctor What does PBA feel like? These are real quotes from people who have PBA, and they’re not alone. While there are almost 2 million people in the US with neurologic conditions or traumatic brain injury who have PBA, over 7 million people in the US have symptoms that suggest PBA.* PBA episodes can be confusing, frustrating, and draw unwanted attention.
    [Show full text]
  • Wo 2008/097924 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 14 August 2008 (14.08.2008) PCT WO 2008/097924 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/473 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, (21) International Application Number: CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, PCT/US2008/052949 EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, (22) International Filing Date: 4 February 2008 (04.02.2008) LK, LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, (25) Filing Language: English PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (26) Publication Language: English ZA, ZM, ZW (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 60/899,472 5 February 2007 (05.02.2007) US kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): AVANIR GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, PHARMACEUTICALS [US/US]; 101 Enterprise, Suite ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), 300, Aliso Viejo, CA 92656 (US).
    [Show full text]
  • Pseudobulbar Affect
    Pseudobulbar Affect Identifying Pseudobulbar Affect in Alzheimer’s Disease and Dementia David W Crumpacker, MD1 and William A Engelman, MD2 1. Psychiatrist and Neurologist, Private Practice, Plano, Texas, US; 2. Clinical Scientist and Senior Research Associate, Evidera, Lexington, Massachusetts, US Abstract Pseudobulbar affect (PBA) can be challenging to differentiate from the symptoms of various neurological diseases with which it is associated. In patients with Alzheimer’s disease (AD) and dementia such a diagnosis can be particularly difficult as illustrated by a case of an elderly male with sudden tearful outbursts, which is reported and discussed here. PBA attacks are often incorrectly attributed to emotion or distress in response to memory loss or a result of depression or dementia. PBA is common, affecting between 10–40 % of people with AD but is frequently not detected or is misdiagnosed. Multiple authors have published clinical criteria for identifying PBA; in sum, it is described as a condition affecting the brain with episodes of laughing or crying that are sudden and unpredictable, occur without warning and are excessive, exaggerated, or not appropriate to the stimuli and are involuntary and difficult to control. Differentiating PBA from depression and other behavioral disturbances in AD and dementia is helpful to patients by identifying a specific cause of their symptoms and enabling appropriate management. Various different approaches have been taken in the treatment of PBA. A combination of dextromethorphan and quinidine has been shown in well-controlled trials and in clinical use to control the symptoms of PBA associated with several neurological diseases including AD and to reduce the burden on patients and their caregivers.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,973,049 B2 Tung (45) Date of Patent: Jul
    US007973 049B2 (12) United States Patent (10) Patent No.: US 7,973,049 B2 Tung (45) Date of Patent: Jul. 5, 2011 (54) MORPHINAN COMPOUNDS 2005/0129783 A1 6/2005 McCleary et al. 2005/0203125 A1 9, 2005 Yakatan et al. 2006, OO795O2 A1 4/2006 Lang (75) Inventor: Roger Tung, Lexington, MA (US) 2006/0094744 A1 5/2006 Maryanoff et al. 2007/0O82929 A1 4/2007 Gant et al. (73) Assignee: Concert Pharmaceuticals Inc., 2007,0191411 A1 8, 2007 Smith Lexington, MA (US) 2007/O197695 A1 8/2007 Potyen et al. 2008. O103122 A1 5, 2008 Veltri (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS WO WO95/26325 10, 1995 U.S.C. 154(b) by 712 days. WO WO 2007.118651 10/2007 (21) Appl. No.: 12/112,936 OTHER PUBLICATIONS (22) Filed: Apr. 30, 2008 Authorized officer Lee W. Young, International Search Report/Writ ten Opinion in PCT/US 10/27990 mailed Mar. 19, 2010, 11 pages. (65) Prior Publication Data “Combination of dextromethorphan and quinidine Sulphate” online). Prous Science Integrity, retrieved on Apr. 23, 2007). US 2008/O280936A1 Nov. 13, 2008 Retrieved from the Internet: <URL: http://integrity prous.com/integ rity servlet/xmlx.sl/pk prodlist.xml . D. Related U.S. Application Data Anastasia et al., “Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethyla (60) Provisional application No. 60/915,130, filed on May tion with sodium sulfide or potassium thioacetate: an application to 1, 2007, provisional application No.
    [Show full text]