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EXPERTOPINION Edited by Randolph W EXPERTOPINION Edited by Randolph W. Evans, MD Is Uncontrollable Crying and Laughter in Dementia a Treatable Disorder? This case suggests important considerations in the diagnosis and treatment of pseudobulbar affect associated with dementia. Case and expert opinion Questions by Ralph Ritcher, MD (1) What is pseudobulbar affect (PBA), and how prevalent is it in demen- Case tia? A 78-year-old woman presents with a (2) How does PBA impact the lives of one-year history of episodes of uncon- patients and their caregivers? trollable crying that sometimes spills into (3) What are the diagnostic criteria explosive laughter. The condition has for PBA? gradually deteriorated from moderate to (4) What treatments are available or severe episodes, with paroxysmal emo- in the pipeline? tional displays of variable duration now (5) What is the patient’s prognosis? occurring multiple times during the day, and occasionally lasting up to 4-5 min- Expert Opinion utes. Outbursts are often unprovoked or The patient’s disinhibited crying/laugh- triggered by small emotional events. ing episodes are hallmark symptoms of a They may escalate from a grimace, and neurological disorder1 variously referred are substantially out of proportion to the to as pseudobulbar affect (PBA), patho- Figure 1. Still-picture of a dementia patient in midst of a mixed crying and laughing situation. Crying/laughing episodes are logical laughing and crying (PLC), and episode, characteristic of pseudobulbar 2 sometimes associated with inappropriate emotional lability. PBA may be caused affect (PBA). communication (facetious, sarcastic by pathophysiological changes affecting jokes or nonsensical remarks), as well as brain pathways involved in motor con- periods of agitation, frustration and trol of emotional expression.3-5 The con- ful to caregivers, who often blame them- anger. The patient’s husband and pri- dition can occur in various neurological selves for their occurrence, as in our case. mary caregiver often feels guilty, as it diseases as well as brain injuries, includ- Indeed, emotional lability was found to appears to him that his presence and ing: amyotrophic lateral sclerosis,6 multi- be the strongest predictor of impaired conversation trigger the episodes. ple sclerosis,7 stroke,8 traumatic brain well being of spouse caregivers to AD The patient has progressive moder- injury,9 Parkinson’s disease10 and various patients.15 Health care provider educa- ate dementia with a Mini-Mental State dementias, including Alzheimer’s dis- tion of the family members and other Exam score of 18, and is being treated ease.11,12 caregivers is of paramount importance. with Aricept and Namenda. Memory The neuroimaging findings in this Despite its seriousness, the condition problems began three years ago and dete- case support a diagnosis of Alzheimer’s remains largely unrecognised and under- rioration has been slow and steady, with disease.13 The reported prevalence of treated.2,14 some acceleration in the last six months. PBA in dementia has varied considerably The patient has also developed a gait in early studies of AD and frontotempo- What are the Diagnostic apraxia. Positron emission tomography ral dementia.11,12 It is my clinical experi- Criteria for PBA? and computer tomography scans show ence that PBA may also occur with sever- Outbursts of crying or laughter or mixed relatively symmetrical, bilateral dimin- al other dementias (Table 1). episodes are generally inappropriate to ished metabolic activity in the posterior PBA can be severe, persistent2 and can context.3 Although sometimes triggered parietal and temporal regions, as well as have a profound impact on patients’ rela- by minor emotional themes/events,2 the decreased activity in the mesial temporal tionships with their family and care- threshold for response is considerably lobes. givers.3,14 Episodes can be deeply distress- diminished, and emotional displays may October 2005 Practical Neurology 73 EXPERTOPINION Edited by Randolph W. Evans, MD What Treatment Table 1. PBA Can Occur in Association Would You Recommend? With the Following Dementias There is no approved therapy with an indication for PBA. Off-label use of anti- Alzheimer’s disease, particularly later, more severe stages depressants has yielded only partial suc- Frontotemporal dementia (FTD) cess, as shown in small comparative trials Multi-infarct or vascular dementia with tricyclics and selective serotonin reuptake inhibitors.3,14,23 However, none Lewy body dementia of these agents have been tested in large, Sequelae of viral encephalitis well-controlled trials, and there is a Progressive supranuclear palsy paucity of information on their use in dementia.24 Huntington’s disease Additionally, the use of tricyclic anti- Creutzfeldt-Jakob disease depressants is limited by a high incidence of adverse events (e.g., memory deficits), Lupus cerebritis particularly problematic in elderly and * For differential diagnosis please refer to Richter RW. Alzheimer's disease: Clinical evaluation and disease man- demented patients . In my clinical expe- agement-Update. J Okla State Med Assoc 2004; 97: 546-56. rience, the use of antidepressants for PBA has not been particularly effective. be exaggerated and stereotyped.3 Crying common in psychiatric disorders, while Some patients may show slight improve- is more common in dementia. The type dissociated crying is more common in ment, but most do not receive significant and severity of episodes may possibly be neurological disorders.17 One should ask therapeutic benefit. New treatment correlated with premorbid personality. if episodes are evoked by feelings of sad- options have been needed and are under PBA may be seen more often when ness or joy. development. dementia patients are entering later It is possible for patients to suffer The investigational drug AVP-923 stages of their illness.16 PBA in dementia from both depression and PBA, but the consists of a fixed combination of dex- is somewhat atypical relative to other two disorders should be clinically differ- tromethorphan hydrobromide (DM, neurological conditions, in that there is entiated.19,20 The Center for Neurologic 30mg) and quinidine sulfate (Q, 30mg). frequently a broader loss of emotional Study Lability Scale (CNS-LS) is a self- AVP-923 is believed to exert its thera- regulation. assessment instrument validated in ALS21 peutic effects in PBA, at least in part, by Outbursts of irritability, frustration and MS22 patients. It includes an auxil- reducing excitatory glutamatergic and anger are often intertwined with iary subscale measuring labile frustra- responses.25 irresistable laughing/crying, as seen here. tion, anger and impatience, although The therapy has been shown to palli- In some cases there is also an association further research is needed to clarify any ate PBA in two large, phase III clinical of “Witzelsucht,” a peculiar tendency to syndromal association between these fac- trials involving ALS25 and MS26 patients, make clever remarks and tell trivial jokes tors. and lasting one and three months respec- and senseless stories, while being extraor- A CNS-LS caregiver score may be tively. AVP-923 significantly improved dinarily amused thereby.3 The inappro- informative, even if dementia procludes PBA symptoms as measured by the priate communication described for this self-evaluation. The Pathological Laugh- CNS-LS in both studies. In addition, patient may partly be so identified. ing and Crying Scale, validated in stroke treatment significantly reduced crying/ Diagnosis can be facilitated by clinical patients,19 may also be used as an inter- laughing episodes by more than 40 per- observation and interviews, and by the viewer-rated tool. These scales quantitate cent, and resulted in marked improve- use of measurement scales. Caregiver aspects of laughter and crying, such as ments in quality of life and quality of input as to history of the disorder is crit- frequency, duration, intensity, lability, relationships, assessed by visual analog ical. Mood disorders, such as depression degree of voluntary control, relation of scales.25,26 Therapeutic effects were and bipolar disease, should be ruled out. episodes to external events and emotions, observed as early as the first week26 and Crying spells in depression17 and emo- and degree of resultant distress.19,21,22 sustained throughout the trials. Fifty-two tional lability in mania18 may at times Ideally, more adequate scales for evaluat- percent of AVP-923 patients were symp- resemble PBA episodes. However, appro- ing dementia patients need to be devel- tom-free over the last two weeks of the priate crying (related to mood) is more oped. ALS study.25 Adverse events (AEs) were 74 Practical Neurology October 2005 mostly mild to moderate and reversible. the clinical trials.25,26 In my experience, An open-label trial is being conducted AEs may clear up after several weeks of to assess the safety of chronic exposure treatment,27 and starting with a lower Advertising Index (at least six months) to AVP-923 in dose may increase tolerability.25 Some PRACTICAL NEUROLOGY, OCTOBER 2005 patients with PBA associated with vari- dementia patients may require long-term ous neurological disorders, including treatment. In others, psuedobulbar affect Astra Zeneca dementia. may gradually resolve as the dementia • Zomig ...............................................47-48 progresses. PN What is the Prognosis? Athena Diagnostics Based on my personal clinical experience Ralph W. Richter, MD is Clinical Professor of • Laboratory
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