Treatment of ballism and pseudobulbar affect with sertraline

BACKGROUND: The pathogenesis of ballism is uncertain and may involve more than one mechanism; treatment is not always efficacious. OBJECTIVE: To provide evidence of a nondopaminergic mechanism and the potential for a prompt and nearly complete response to a serotonergic agent. METHODS: Report of 2 separate trials of sertraline hydrochloride in a single patient. RESULTS: Complete remission of symptoms within 48 hours of each drug trial. CONCLUSION: Sertraline may offer an alternative with a better adverse effect profile than dopamine receptor blockers in the treatment of patients with ballism.     

A real reason for patients with pseudobulbar affect to smile

Pseudobulbar affect (PBA) is a dramatic disorder of emotional expression and regulation characterized by uncontrollable episodes of laughing and crying that often cause embarrassment, curtailment of social activities, and reduction in quality of life. The disorder occurs in patients with brain injury caused by many types of neurological disease, including stroke, tumors, and neurodegenerative gray and white matter disorders. Although the pathophysiology is unknown, PBA may relate to release of brainstem emotional control centers from regulation by the frontal lobes. Diagnosis of PBA can be difficult and relies on careful characterization of episodes and differentiation from depression. Although there are no US Food and Drug Administration-approved treatments for PBA, several agents have been shown to be effective, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and a new agent containing dextromethorphan and quinidine. The growing number of treatment options, some of great benefit to patients, highlights the importance of accurate diagnosis of this disorder.     

Review of pseudobulbar affect including a novel and potential therapy

Pseudobulbar affect (PBA) is an affective disinhibition syndrome associated with various neuropathologies, which is characterized by involuntary and inappropriate outbursts of laughter and/or crying. The PBA syndrome can be socially and occupationally disabling, and it is largely unrecognized in clinical settings. Validated instruments to distinguish PBA from other disorders of affective regulation exist and could be used to improve recognition of the disorder. There is no pharmacological therapy with a Food and Drug Administration indication for PBA, although antidepressants and dopaminergic agents have been reported to show varying levels of treatment success. Recent evidence suggests that treatment with a fixed combination of dextromethorphan and the cytochrome P450 2D6 enzyme inhibitor, quinidine, can improve PBA. This review describes the clinical and neuropathological features of PBA, and presents an overview of current and future treatment approaches.     

Therapeutic use of dextromethorphan: key learnings from treatment of pseudobulbar affect

A variety of neurological conditions and disease states are accompanied by pseudobulbar affect (PBA), an emotional disorder characterized by uncontrollable outbursts of laughing and crying. The causes of PBA are unclear but may involve lesions in neural circuits regulating the motor output of emotional expression. Several agents used in treating other psychiatric disorders have been applied in the treatment of PBA with some success but data are limited and these agents are associated with unpleasant side effects due to nonspecific activity in diffuse neural networks. Dextromethorphan (DM), a widely used cough suppressant, acts at receptors in the brainstem and cerebellum, brain regions implicated in the regulation of emotional output. The combination of DM and quinidine (Q), an enzyme inhibitor that blocks DM metabolism, has recently been tested in phase III clinical trials in patients with multiple sclerosis and amyotrophic lateral sclerosis and was both safe and effective in palliating PBA symptoms. In addition, clinical studies pertaining to the safety and efficacy of DM/Q in a variety of neurological disease states are ongoing.     

Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect

PURPOSE: To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). METHODS: Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. RESULTS: Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. CONCLUSIONS: PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. SIGNIFICANCE: These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.     

Treatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopthy

Pseudobulbar affect (PBA) manifests in a variety of neurologic illnesses suggesting a heterogeneous pathophysiology with common underpinnings. We report successful treatment of PBA with a selective serotonin reuptake inhibitor (SSRI) in a 54-year-old woman following progressive multifocal leukoencephalopathy (PML). In light of recent focus on dextromethorphan/quinidine (DM/Q) for the treatment of PBA, the clinician is reminded of the effectiveness of SSRIs.     

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 相似文献   

Neuroanatomy of autism

Autism spectrum disorder is a heterogeneous, behaviorally defined, neurodevelopmental disorder that occurs in 1 in 150 children. Individuals with autism have deficits in social interaction and verbal and nonverbal communication and have restricted or stereotyped patterns of behavior. They might also have co-morbid disorders including intellectual impairment, seizures and anxiety. Postmortem and structural magnetic resonance imaging studies have highlighted the frontal lobes, amygdala and cerebellum as pathological in autism. However, there is no clear and consistent pathology that has emerged for autism. Moreover, recent studies emphasize that the time course of brain development rather than the final product is most disturbed in autism. We suggest that the heterogeneity of both the core and co-morbid features predicts a heterogeneous pattern of neuropathology in autism. Defined phenotypes in larger samples of children and well-characterized brain tissue will be necessary for clarification of the neuroanatomy of autism.     

Neuroanatomy of creativity

Creativity has long been a construct of interest to philosophers, psychologists and, more recently, neuroscientists. Recent efforts have focused on cognitive processes likely to be important to the manifestation of novelty and usefulness within a given social context. One such cognitive process – divergent thinking – is the process by which one extrapolates many possible answers to an initial stimulus or target data set. We sought to link well established measures of divergent thinking and creative achievement (Creative Achievement Questionnaire – CAQ) to cortical thickness in a cohort of young (23.7 ± 4.2 years), healthy subjects. Three independent judges ranked the creative products of each subject using the consensual assessment technique (Amabile, 1982) from which a “composite creativity index” (CCI) was derived. Structural magnetic resonance imaging was obtained at 1.5 Tesla Siemens scanner. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer image analysis suite. A region within the lingual gyrus was negatively correlated with CCI; the right posterior cingulate correlated positively with the CCI. For the CAQ, lower left lateral orbitofrontal volume correlated with higher creative achievement; higher cortical thickness was related to higher scores on the CAQ in the right angular gyrus. This is the first study to link cortical thickness measures to psychometric measures of creativity. The distribution of brain regions, associated with both divergent thinking and creative achievement, suggests that cognitive control of information flow among brain areas may be critical to understanding creative cognition. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.