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

OBJECTIVE: Depression, 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 METHODS: A 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). RESULTS: A 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. CONCLUSION: MoCA 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.

The psychopharmacology of pseudobulbar affect.

Pseudobulbar affect (PBA) is characterized by uncontrollable emotional episodes disconnected or disproportionate with mood, in association with an array of neurologic conditions. PBA is associated with disruption of descending control of brainstem motor circuitry and dysregulation of serotonergic and glutamatergic function. PBA has been historically under recognized, though advances resulting in more specific diagnostic criteria, validated rating scales, and an approved pharmacotherapy offer opportunities for improved treatment outcomes.

Introduction to pseudobulbar affect: setting the stage for recognition and familiarity with this challenging disorder.

Pseudobulbar affect (PBA), despite its prevalence and distinctive symptoms, is widely underrecognized and undertreated. It is characterized by uncontrollable laughing or crying that can occur in an exaggerated manner or inappropriately to a given situation or stimuli. PBA is thought to center around preexisting neurological conditions, which include Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, traumatic brain injury, and stroke. The PBA Registry Series trial was created to measure the prevalence of PBA among patients with these underlying neurological conditions. Through greater awareness, recognition, and diagnosis, treatment for patients with PBA can be improved.

Dextromethorphan-quinidine-responsive pseudobulbar affect (PBA): psychopharmacological model for wide-ranging disorders of emotional expression?

The symptoms of emotional dysregulation associated with the syndrome known as pseudobulbar affect (PBA) can be effectively treated by the sigma, glutamate, and serotonergic agent dextromethorphan combined with quinidine. If the same brain circuits affected in PBA are also compromised in related disorders of emotional expression, dextromethorphan-quinidine and other novel sigma-glutamate-serotonin agents could prove to be novel psychopharmacologic treatments for these conditions as well.

Recognizing and treating pseudobulbar affect.

Pseudobulbar affect, thought by many to be a relatively newly described condition, is in fact a very old one, described as early as the 19th century. It refers to those who experience inappropriate affect, disconnected from internal state, or mood, generally thought to be the result of an upper motor neuron injury or illness. One possible explanation for this condition's relative obscurity is the dearth of treatment options; clinical medicine is not typically in the habit of identifying conditions that cannot be modified. Now, however, there is good evidence for the treatment of pseudobulbar affect, and even a therapy approved for use by the U.S. Food and Drug Administration (FDA). As a result, appropriate identification and subsequent management of pseudobulbar affect is more important than ever. This article purports to summarize the origins of pseudobulbar affect, most current hypotheses as to its physiopathology, clinical identification, and evidence for management.

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions.

BACKGROUND: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. OBJECTIVE: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. METHODS: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. CLINICAL TRIAL REGISTRATION: #NCT00056524. RESULTS: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. CONCLUSIONS: DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions.

Dextromethorphan/quinidine for the treatment of pseudobulbar affect.

OBJECTIVE: To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA). DATA SOURCES: A literature search of MEDLINE/PubMed (January 1966-June 2013) was conducted using search terms pseudobulbar affect, pathological laughing and/or crying, emotional lability, dextromethorphan, and quinidine. STUDY SELECTION AND DATA EXTRACTION: English language clinical trials and case reports evaluating the safety and efficacy of DM/Q in PBA were included for review. Bibliographies of all relevant articles were reviewed for additional citations. DATA SYNTHESIS: PBA, a poorly understood disorder, is characterized by involuntary crying and/or laughing. In the past, antidepressants and antiepileptics have been used off-label with mixed results. Four clinical trials have evaluated the use of DM/Q for the treatment of PBA. Although the therapeutic outcomes with DM/Q have been positive, interpretation of the published evidence is limited by small sample size and short treatment duration. CONCLUSIONS: Based on the data available, DM/Q may be a viable, short-term treatment alternative for PBA. Long-term safety and efficacy data are lacking.

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.

[Spasmodic laughter syncope. An unusual complication of pseudobulbar palsy]. / Syncope du rire spasmodique. Une complication inhabituelle du syndrome pseudobulbaire.

INTRODUCTION: Spasmodic laughter is a classical sign of pseudobulbar palsy, but it has never been reported, to our knowledge, to provoke syncope. CASE REPORT: A 63-year-old hypertensive and diabetic man with peripheral neuropathy and lacunar pseudobulbar palsy presented with three episodes of spasmodic laughter which had induced syncope. No new episode was observed after the beginning of low dose bisoprolol. DISCUSSION: Sustained or spasmodic laughter is accompanied by repetitive bursts of forced expiration, corresponding to short repetitive Valsalva maneuvers. Laughter-induced syncope is considered as one of the many Valsalva-type/vagally mediated syncopal attacks leading to rapid fall in blood pressure without compensatory tachycardia. The presence of autonomic diabetic neuropathy may also contribute to these attacks.

The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content ad incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.