Materiały źródłowe

• #1 The epidemiology and pathophysiology of pseudobulbar affect and its association with neurodegeneration

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6065587/

  Pseudobulbar affect is a disorder resulting from neurologic damage manifesting as sudden, stereotyped affective outbursts that are not reflective of internal emotion. […] The disorder appears to result from a disruption of the cortico-limbic-subcortical-thalamic-pontocerebellar network involved in emotional expression and regulation with resulting disruptions of neurotransmitter systems. […] The pathophysiology of PBA is likely varied and best conceptualized as a focal or diffuse disruption in the complex neurocircuitry or neurochemistry involved in the inhibition of emotional expression. […] One of the original hypotheses about PBA came from Wilson, who proposed that there was disruption of the cortical inhibition to an upper brainstem center followed by release of lower bulbar nuclei that coordinate the motor responses associated with laughing and crying.

• #1 Pseudobulbar affect: prevalence and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3849173/

  Pseudobulbar affect (PBA) may occur in association with a variety of neurological diseases, and so may be encountered in the setting of amyotrophic lateral sclerosis, extrapyramidal and cerebellar disorders, multiple sclerosis, traumatic brain injury, Alzheimers disease, stroke, and brain tumors. […] Mechanistically, PBA is a disinhibition syndrome in which pathways involving serotonin and glutamate are disrupted. […] The underlying mechanism in PBA appears to be a lack of voluntary control, also termed disinhibition, but the pathways are complex and are as yet incompletely understood. […] One hypothesis is that the cerebellum plays a key role in modulating emotional responses so as to keep them appropriate to the social situation and to the patients mood based on input from the cerebral cortex. Disruption of corticopontinecerebellar circuits results in impairment of this cerebellar modulation, causing PBA.

• #2 Pseudobulbar affect: prevalence and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3849173/

  Pseudobulbar affect (PBA) may occur in association with a variety of neurological diseases, and so may be encountered in the setting of amyotrophic lateral sclerosis, extrapyramidal and cerebellar disorders, multiple sclerosis, traumatic brain injury, Alzheimers disease, stroke, and brain tumors. […] Mechanistically, PBA is a disinhibition syndrome in which pathways involving serotonin and glutamate are disrupted. […] The underlying mechanism in PBA appears to be a lack of voluntary control, also termed disinhibition, but the pathways are complex and are as yet incompletely understood. […] One hypothesis is that the cerebellum plays a key role in modulating emotional responses so as to keep them appropriate to the social situation and to the patients mood based on input from the cerebral cortex. Disruption of corticopontinecerebellar circuits results in impairment of this cerebellar modulation, causing PBA.

• #2 The epidemiology and pathophysiology of pseudobulbar affect and its association with neurodegeneration

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6065587/

  Postmortem and imaging studies in patients with PBA seem to support this theory. […] At the neurotransmitter level, there is also likely to be dysfunction involved in PBA as evidenced by neuroimaging and based on pharmacologic therapies that will be discussed further, later in this review. […] Serotonin deficiency, dopamine deficiency, glutamate excess, and sigma type one (-1) receptor abnormalities have all been implicated. […] In summary, as Rabins and Arciniegas have proposed, PBA is theorized to come from a disruption in a complex cortico-limbic-subcortico-thalamic-pontocerebellar network, which is often related to lesions in descending corticobulbar fibers that inhibit emotional motor networks, lesions in brainstem and cerebellum white matter pathways that modulate emotion expression, and multiple abnormalities in neurotransmitter function.

• #3 Pseudobulbar Affect in Parkinsonian Disorders: A Review

  https://www.e-jmd.org/journal/view.php?number=234

  Pseudobulbar affect (PBA) is a neurological symptom of inappropriate and uncontrollable laughter or crying that occurs secondary to a variety of neurological conditions, including parkinsonian disorders. […] The pathophysiology of PBA is complex and incompletely understood. It is believed that PBA occurs as a result of injury to the cortico-ponto-cerebellar circuitry involved in regulating the motor aspects of emotional expression. […] Given that PBA commonly occurs in a diverse range of neurological conditions, it appears that the location of the pathology is in fact more important than the underlying pathophysiology of the primary disease process. […] The original hypothesis for the pathophysiology underlying PBA as theorized by Wilson in 1923 was based on postmortem studies, and purported that PBA stems from lesions to the motor cortex resulting in loss of voluntary inhibition to the brainstem.

• #4 Pseudobulbar affect – Wikipedia

  https://en.wikipedia.org/wiki/Pseudobulbar_affect

  PBA is a consequence of another neurologic disorder or brain injury. […] The specific pathophysiology involved in this frequently debilitating condition is still under investigation; the primary pathogenic mechanisms of PBA remain controversial. […] One hypothesis, established by early researchers such as Wilson and Oppenheim, placed emphasis on the role of the corticobulbar pathways in modulating emotional expression in a top-down model, and theorized that PBA occurs when bilateral lesions in the descending corticobulbar tract cause failure of voluntary control of emotion, which leads to the disinhibition, or release, of laughing/crying centers in the brainstem. […] It is hypothesized that these primary neurologic injuries and diseases affect chemical signaling in the brain, which in turn disrupts the neurologic pathways that control emotional expression.

• #5 Pseudobulbar Affect in Parkinsonian Disorders: A Review

  https://www.e-jmd.org/journal/view.php?number=234

  More recently, it has been proposed that PBA occurs secondary to dysfunction of a broader cortico-ponto-cerebellar circuitry, including motor, limbic, and association cortices with descending pathways to the brainstem, basis pontis, and cerebellum. […] Disruption of the cortico-ponto-cerebellar circuitry results in emotional expression that is exaggerated or inconsistent with a given context. […] A number of lines of evidence, including neuroimaging and lesion studies, support the involvement of this circuitry in the pathophysiology of PBA. […] The suggested pathophysiology is also in accordance with the increased prevalence of PBA reported in atypical parkinsonian disorders, such as progressive supranuclear palsy (PSP) and the cerebellar type of multiple system atrophy (MSA-C). […] While numerous neurotransmitters are known to regulate signaling of this cortico-ponto-cerebellar circuitry, the exact role of these neurotransmitters and how they are disrupted in PBA has not been thoroughly elucidated to date.

• #6 Introduction to Pseudobulbar Affect: Setting the Stage for Recognition and Familiarity With This Challenging Disorder

  https://www.ajmc.com/view/introduction-to-pseudobulbar-affect-setting-the-stage-for-recognition-and-familiarity-with-this-challenging-disorder

  Pseudobulbar affect (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 causes of PBA are complex, but it is believed to result from the alteration of neuronal pathways, primarily in the frontal lobe of the brain, which control emotions. […] The pathways related to PBA are multifaceted and thought to result from disruptions of neural networks that control the generation and regulation of motor output of emotions. […] PBA is associated with brain injury or a neurological disease or disorder that alters normal neuronal control and affect likely linked to frontal lobe function and other areas of the brain, such as the brainstem and cerebellum.

• #7 Introduction to Pseudobulbar Affect: Setting the Stage for Recognition and Familiarity With This Challenging Disorder

  https://www.ajmc.com/view/introduction-to-pseudobulbar-affect-setting-the-stage-for-recognition-and-familiarity-with-this-challenging-disorder

  Brain lesions located mostly in the frontal lobes and descending pathways to the brainstem, basis pontis, and cerebellum, which encompass systems thought to be involved in motor control of emotional expression, are linked to PBA. […] One of the original hypotheses regarding the pathophysiology of PBA proposed that there was a disruption of the cortical inhibition to an upper brainstem center followed by release of lower bulbar nuclei that coordinate the motor response connected with laughing and crying. […] An additional hypothesis is that a dysfunction in the connection between the cerebellum and cerebral cortex leads to a disruption in emotional regulation.

• #8 Pseudobulbar Affect (PBA): Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17928-pseudobulbar-affect-pba

  Pseudobulbar affect (PBA) is a neurological condition that causes outbursts of uncontrolled or inappropriate laughing or crying. PBA develops as the result of a brain injury or underlying neurological condition, such as amyotrophic lateral sclerosis (ALS). […] Researchers don’t know the exact cause of pseudobulbar affect. They think it happens as the result of disruption to the neurological pathways in your brain that regulate emotional expression. […] PBA likely affects various brain regions along a cerebro-ponto-cerebellar pathway. Part of this pathway includes your cerebellum, which plays a key role in monitoring emotional responses and ensuring they’re appropriate to the social situation. Disruption of the neural (nerve) pathways from certain areas of your brain to your cerebellum may lead to a loss or lack of control over emotional expression.

• #9 Review of the Diagnosis and Management of Pseudobulbar Affect

  https://www.uspharmacist.com/article/review-of-the-diagnosis-and-management-of-pseudobulbar-affect

  PBA occurs secondary to many neurological disease states. The most common diseases associated with PBA are Alzheimers disease (AD), ALS, multiple sclerosis (MS), Parkinsons disease (PD), stroke, and traumatic brain injury (TBI). The exact cause of PBA is unknown, but it is thought to be related to nerve impulse disruption from the cerebellum to the limbic and paralimbic systems. Dysregulation and disinhibition in the frontal cortex are also thought to be part of the process underlying PBA. The release hypothesis, gate control theory, and dysfunction of neurotransmitters theory are among the proposed mechanisms of PBA. […] The release hypothesis explains the disruption of cortical inhibition in the upper brainstem center, leading to a release of lower bulbar nuclei affecting responses to laughing and crying. A revised theory behind the release hypothesis suggests that cerebellar structures involved in laughing and crying are operating on incomplete information because of the lesions affecting this part of the brain.

• #10 When Tears Keep Falling: A Case Report of Pseudobulbar Affect

  https://www.psychiatrist.com/pcc/when-tears-keep-falling-case-report-pseudobulbar-affect/

  Pseudobulbar affect (PBA) is a disorder of affect regulation or of emotional expression. The phenomenon was described as early as 1872 by Charles Darwin. Clinically, PBA is characterized by paroxistic sudden episodes of exaggerated and uncontrolled emotional expression, usually of laughter or weeping, not necessarily congruent with the patients mood, feelings, or situational context. […] The likely pathophysiologic mechanism of PBA is the disruption of the cortico-ponto-cerebellar pathway. Creating proper affect depends on the involvement of multiple interconnected regions: executive functions in the prefrontal cortex, movement control in the motor cortex, cerebellar coordination, and brain pons (integration, conduction, and emergence of most of the cranial nerves). This mechanism postulates that affect expression is modulated by multiple cortical areas, with afferent connections between the motor cortex, the prefrontal cortex, and the cerebellum, through the ventral portion of the pons. Thus, any disorder, either degenerative or traumatic, that interrupts these connections might result in affect dysregulation. Cerebellar cortex also has an important role in cognition, empathy, and affect modulation.

• #11 Pseudobulbar Affect in Patients with Multiple Sclerosis: A Systematic Review

  https://www.mdpi.com/2813-3064/2/3/13

  Specifically, these lesions disrupt cortico–ponto–cerebellar networks responsible for regulating emotional expression. […] According to a logistic regression model explaining 70% of the variance, brainstem hypointense, left inferior parietal hyperintense and left and right medial inferior frontal hyperintense lesion volumes predicted the development of PBA. […] Moreover, there is evidence that the presence of PBA results in abnormal and excessive activation of certain brain areas in response to neutral stimuli, particularly areas of the somatosensory cortex and regions involved in emotion processing and visual stimuli, which may explain the incongruous emotional reactions (uncontrollable laughter or crying) typical of PBA.

• #12 Pseudobulbar affect: When patients laugh or cry, but don’t know why | MDedge

  https://blogs.the-hospitalist.org/content/pseudobulbar-affect-when-patients-laugh-or-cry-dont-know-why

  Pseudobulbar affect (PBA) is a disorder of affective expression that manifests as stereotyped and frequent outbursts of crying (not limited to lacrimation) or laughter. 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. […] Despite the many and varied injuries and illnesses associated with PBA, Lauterbach et al noted patterns that suggest dysregulation of 2 distinct but interconnected brain pathways: an emotional pathway controlled by a separate volitional pathway. Lesions to the volitional pathway (or its associated feedback or processing circuits) are thought to cause PBA symptoms.

• #13 Pseudobulbar affect: When patients laugh or cry, but don’t know why | MDedge

  https://blogs.the-hospitalist.org/content/pseudobulbar-affect-when-patients-laugh-or-cry-dont-know-why

  The emotional pathway, which coordinates the motor aspect of reflex laughing or crying, originates at the frontotemporal cortex, relaying to the amygdala and hypothalamus, then projecting to the dorsal brainstem, which includes the midbrain-pontine periaqueductal gray (PAG), dorsal tegmentum, and related brainstem. The volitional pathway, which regulates the emotional pathway, originates in the dorsal and lateral frontoparietal cortex, projects through the internal capsule and midbrain basis pedunculi, and continues on to the anteroventral basis pontis. […] Lesions of the volitional pathway have been correlated with conditions of PBA, whereas direct activation of the emotional pathway tended to lead to emotional lability or the crying and laughing behaviors observed in dacrystic or gelastic epilepsy.

• #14 Pseudobulbar affect: when patients laugh or cry, but don’t know why – Document – Gale Academic OneFile

  https://go.gale.com/ps/i.do?id=GALE%7CA465112008&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=15378276&p=AONE&sw=w

  Disruption of neural circuitry undermines voluntary control of affect. Pseudobulbar affect (PBA) is a disorder of affective expression that manifests as stereotyped and frequent outbursts of crying (not limited to lacrimation) or laughter. Symptoms are involuntary, uncontrolled, and exaggerated or incongruent with current mood. […] Despite the many and varied injuries and illnesses associated with PBA, Lauterbach et al (10) noted patterns that suggest dysregulation of 2 distinct but interconnected brain pathways: an emotional pathway controlled by a separate volitional pathway. Lesions to the volitional pathway (or its associated feedback or processing circuits) are thought to cause PBA symptoms. […] To borrow an analogy from engineering, the emotional pathway is the „generator” of affect, whereas the volitional pathway is the „governor” of affect. Thus, injury to the „governor” results in overspill, or overflow, of affect that usually would be suppressed.

• #15 Pseudobulbar affect | MedLink Neurology

  https://www.medlink.com/articles/pseudobulbar-affect

  In cases of unilateral lesions, the left-sided lesions are more often associated with crying and the right-sided lesions with laughter. […] The cause of this dichotomy is not clear, but one explanation is that the left hemisphere’s frontal lobes mediate emotions with a positive valence, and the right hemisphere mediates emotions with a negative valence. […] In the circuitry involved in pathologic laughter and crying, ventral pons appears to be a crucial location, but further investigations are needed to determine how lesions in the basis pontis affect the activity of the cerebellum and the brainstem.

• #16 Pseudobulbar affect: prevalence and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3849173/

  The primary neurotransmitters believed to be involved in PBA are serotonin and glutamate. The role of serotonin in corticolimbic or cerebellar pathways may account for its impact on PBA. Glutamate is an excitatory neurotransmitter whose receptors are widely distributed within the brain. Thus, modulation of glutamatergic transmission can have widespread effects.

• #17 Pseudobulbar Affect in Parkinsonian Disorders: A Review

  https://www.e-jmd.org/journal/view.php?number=234

  The role of serotonin as an important emotional modulator and the presence of serotonergic projections throughout the cortico-limbic areas, including the cerebellum, is also consistent with the importance of serotonergic neurotransmission in PBA. […] The efficacy of DMQ is speculated to stem from anti-glutamatergic effects that serve to restore inhibitory neurotransmission from the cortex to the brainstem, thereby compensating for the gate-control disinhibition of emotional expression thought to underlie PBA.

• #18 Pseudobulbar Affect Versus Depression: Issues in Diagnosis and Treatment

  https://www.psychiatrictimes.com/view/pseudobulbar-affect-versus-depression-issues-diagnosis-and-treatment

  Research also suggests that abnormal glutaminergic and serotonergic neurotransmission may contribute to PBA. However, numerous other neurotransmitters may also be involved given their impact on emotion, such as dopamine, norepinephrine, and acetylcholine. We know that serotonin has many projections throughout the brain, and cell bodies originate in the brainstem raphe nuclei. Glutamate is the main excitatory neurotransmitter in the CNS. The exact etiology of PBA is unknown, but research supports a dysfunction of neural circuits and neurotransmitters that modulate the motor expression of emotion.

• #19 Review of the Diagnosis and Management of Pseudobulbar Affect

  https://www.uspharmacist.com/article/review-of-the-diagnosis-and-management-of-pseudobulbar-affect

  The gate control theory proposes inhibition of the mechanism regulating emotional expression. MS and related neurological damage are thought to be involved in disrupting activity in the cortical structures related to sensory, motor, and emotional processes, along with overactive motor cortical areas. […] In the dysfunctional neurotransmitters theory, serotonin, dopamine, glutamate, and sigma-1 are disrupted in various brain pathways, leading to alterations in emotional expression. Therefore, medications that modulate these neurotransmitters may play a role in providing therapeutic benefit.

• #20

  https://www.iomcworld.org/open-access/neuronal-dysregulation-in-strokeassociated-pseudobulbar-affect-pbadiagnostic-scales-and-current-treatment-options-46381.html

  Ahmed and Simmons have proposed that PBA is a disinhibition syndrome in which specific pathways involving serotonin and glutamate are disrupted. […] If there is reduced cortical inhibition of a brain stem situated emotional center related to laughing and crying, stroke-induced disruption of the pathway may disinhibit voluntary laughing and crying, making the process involuntary. […] Brain mapping studies using diffusion-tensor magnetic resonance imaging (MRI/DTI) and electroencephalography (EEG) suggests that reduced serotonin and dopamine transmission and enhanced glutamate transmission are key components in the emotional dysregulation. […] PBA is due to the dysregulation of 3 main neurotransmitter pathways, dopamine, serotonin and glutamate, from the frontal cortical lobes through the cerebellum and brain stem, the corticolimbic- subcorticothalamic-ponto-cerebellar network. […] Stroke or infarct-mediated interruption of circuits projecting to the cerebellum and brainstem may result in disinhibition of well-controlled voluntary emotions, making them involuntary.

• #21 Pharmacotherapeutic Management of Pseudobulbar Affect

  https://www.ajmc.com/view/pharmacotherapeutic-management-of-pseudobulbar-affect

  The pathophysiology of PBA has helped guide therapeutic treatments. Current prevailing theories suggest that PBA occurs when neural pathways that modulate emotional responses in the brain are interrupted, particularly descending pathways from the brain (such as the frontal lobes) to the cerebellum through the basis pontis. Medical disorders or conditions, such as Parkinson disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), TBI, and stroke, which result in a disruption of those pathways, can produce the hallmark symptoms of PBA – involuntary and uncontrollable laughter and/or crying. The primary neurotransmitters involved in PBA are serotonin and glutamate, and pharmacologic treatments have focused on drugs that modulate these neurotransmitters.

• #22 Pharmacotherapeutic Management of Pseudobulbar Affect

  https://www.ajmc.com/view/pharmacotherapeutic-management-of-pseudobulbar-affect

  Dextromethorphan, which is most commonly used as an antitussive in cough and cold remedies, has CNS activity both as an uncompetitive antagonist of the NMDA-sensitive ionotropic glutamate receptor and as a sigma-1 receptor agonist. These actions align with the prevailing theories on the pathophysiology of PBA. Preliminary reports that suggested the efficacy of dextromethorphan for PBA prompted additional research on its use for treating the condition. […] For dextromethorphan to exert its intended effect, the drug must reach the neural targets in the CNS. The physiochemical properties of dextromethorphan, however, limit its uptake. When administered orally, dextromethorphan is rapidly metabolized by the cytochrome P450 2D6 isoform (CYP2D6) to dextrorphan, which is subsequently glucuronidated, resulting in very low bioavailability of dextromethorphan. Dextrorphan has antitussive effects, and it is believed to be the compound responsible for psychoactive properties based on higher affinity for the NMDA receptor. To increase the oral bioavailability of dextromethorphan, one successful approach is to inhibit CYP2D6 metabolism via the coadministration of the CYP2D6 inhibitor, quinidine. Clinical studies focusing on modulating the metabolism of dextromethorphan by coadministration of quinidine supported the rationale for this approach, and the relatively low-dose combination of dextromethorphan and quinidine became the basis for the commercial product approved for PBA.

• #23 Nuedexta for the Treatment of Pseudobulbar Affect (PBA)

  https://www.clinicaltrialsarena.com/projects/nuedexta-treatment-pseudobulbar-affect-pba/

  Pseudobulbar affect (PBA) is a neurologic disorder that occurs due to neurological conditions or brain injury. […] Nuedexta is presumed to work by regulating excitatory neurotransmissions in the brain through sigma-1 receptor agonist activity and NMDA receptor antagonist activity. […] The exact mechanism of action of the drug is not completely known but it is believed to work by regulating excitatory neurotransmissions through the sigma-1 receptor agonist activity and NMDA receptor antagonist activity.

• #24 Pseudobulbar Affect: Signs, Symptoms, and Treatment for Uncontrollable Laughing or Crying – Neurology Advisor

  https://www.neurologyadvisor.com/features/pseudobulbar-affect-signs-symptoms-and-treatment-for-uncontrollable-laughing-or-crying/

  Pseudobulbar affect (PBA) is a relatively common disorder of emotional expression that occurs in many neurologic disorders including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, dementia, parkinsonian disorders, brain tumor, and traumatic brain injury. […] The pathophysiology of PBA is incompletely understood, but symptoms are thought to result from damage to neural pathways associated with motor functioning and emotional processing. […] Although the mechanism by which the drug exerts therapeutic effects in patients with PBA is unknown, it acts on sigma-1 N-methyl-D-aspartate receptors in the brain and spinal cord. […] Although the mechanisms are not fully understood, serotonergic and glutamatergic transmission appear to play major roles, and there are clear therapeutic benefits in treatment for PBA with SSRIs, TCAs, or dextromethorphan/quinidine.

• #25 Raising Awareness of Pseudobulbar Affect: Knowing the Signs, Symptoms, and Treatment for Patients With Uncontrollable Laughing or Crying – Clinical Advisor

  https://www.clinicaladvisor.com/features/raising-awareness-of-pseudobulbar-affect-knowing-the-signs-symptoms-and-treatment-for-patients-with-uncontrollable-laughing-or-crying/2/

  The goal of treatment of PBA is to diminish the severity and frequency of episodes. […] Although the mechanism by which the drug exerts therapeutic effects in patients with PBA is unknown, it acts on sigma-1 N-methyl-D-aspartate receptors in the brain and spinal cord. […] Although the mechanisms are not fully understood, serotonergic and glutamatergic transmission appear to play major roles, and there are clear therapeutic benefits in treatment for PBA with SSRIs, TCAs, or dextromethorphan/quinidine.

• #26 Pseudobulbar Affect – A Disabling but Under-recognised Consequence of Neurological Disease and Brain Injury – touchNEUROLOGY

  https://touchneurology.com/brain-trauma/journal-articles/pseudobulbar-affect-a-disabling-but-under-recognised-consequence-of-neurological-disease-and-brain-injury/

  The release hypothesis for PBA suggests that lesions or injury causes disruption of cortical inhibition in the upper brainstem and release of motor programmes of the bulbar nuclei that control motor responses associated with laughter and crying. […] Neuroimaging studies have shown that PBA involves changes in circuits that are known to involve a variety of neurotransmitter functions. […] Recently, increasing evidence has suggested that PBA may be associated with damage to the cerebellum. […] Golgi cells may have a gating function that sets a threshold preventing low-level stimuli from eliciting a response such as laughter or crying. […] The anatomical pathways involved in PBA differ from those associated with depression supporting a distinction between these disorders. […] The pathophysiology of PBA is not clearly understood and further work in this area may elucidate its origins and mechanisms.

• #27 Treatment of pseudobulbar affect (PBA) in a patient with a history of traumatic brain injury, partial brain resection, and brainstem stroke: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-020-02525-3

  the pathophysiological gate control model of PBA, which posits the cerebellum as the apparatus responsible for unconscious modulation of emotional expression, scaling it appropriately and producing an emotionally congruent response according to the contextual information transmitted via descending pathways from the sensory cortex through the frontal and temporal cortices. […] the current gate control model cannot adequately explain the discrepancy in resultant symptoms between the patients two neurological traumas. Further research is required in order to provide a more complete pathological picture of this complex neurological disease.

• #28

  https://link.springer.com/article/10.1007/s00415-025-12971-y

  Pseudobulbar affect (PBA) is a well-recognised and troublesome clinical phenomenon in a range of neuroinflammatory, neoplastic, neurovascular and neurodegenerative conditions. […] The severity of pseudobulbar affect correlates with motor manifestations of pseudobulbar palsy, a link supporting emerging imaging studies regarding bilateral corticobulbar tract degeneration as in important aetiological factor. […] Despite sporadic reports, the clinical, social, caregiver burden and quality of life implications of pseudobulbar affect remain poorly characterised. The comprehensive evaluation of the clinical correlates of PBA helps to elucidate the underlying pathophysiology. […] Our study demonstrates that the severity of pseudobulbar affect is closely linked to the motor manifestations of pseudobulbar palsy.

• #29

  https://link.springer.com/article/10.1007/s00415-025-12971-y

  In contrast, PBA was strongly associated with the presence of pseudobulbar symptoms and signs; most significantly with the presence of dysphagia, dysarthria and jaw-jerk hyper-reflexia. […] These findings, taken together are supportive of Oppenheims classic hypothesis of disinhibited brainstem motor centres as underlying PBA and re-emphasise the central role of pseudobulbar motor dysfunction in this frequently distressing symptom. […] The results of this study do not directly address the hypothesised role of the cerebellum in modulating the expression of PBA. […] This study supports the central role of pseudobulbar dysfunction in PBA.

• #30 When Tears Keep Falling: A Case Report of Pseudobulbar Affect

  https://www.psychiatrist.com/pcc/when-tears-keep-falling-case-report-pseudobulbar-affect/

  PBA is sometimes misinterpreted as a psychiatric disorder (depressive disorder, bipolar disorder, or posttraumatic stress disorder). Even though mood disorders may share some common symptoms with PBA, presentation and evolution are often different, and their diagnosis requires the exclusion of a medical condition.

• #31 Raising Awareness of Pseudobulbar Affect: Knowing the Signs, Symptoms, and Treatment for Patients With Uncontrollable Laughing or Crying – Clinical Advisor

  https://www.clinicaladvisor.com/features/raising-awareness-of-pseudobulbar-affect-knowing-the-signs-symptoms-and-treatment-for-patients-with-uncontrollable-laughing-or-crying/

  Pseudobulbar affect (PBA) is a relatively common disorder of emotional expression that occurs in many neurologic disorders including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, dementia, parkinsonian disorders, brain tumor, and traumatic brain injury. […] The pathophysiology of PBA is incompletely understood, but symptoms are thought to result from damage to neural pathways associated with motor functioning and emotional processing. […] Data suggest that PBA is underrecognized by neurologists and psychiatrists; therefore, many cases are believed to go unrecognized or misdiagnosed. […] When misdiagnosed as depression or another personality disorder, such as bipolar disorder, inappropriate management of PBA ensues. […] To differentiate between PBA and depression, it is valuable to determine the duration of the crying episodes in order to distinguish PBA from depression. Episodes of crying with depression are often longer in duration than the episodes of pathologic crying characteristic of PBA. […] Both the exaggerated emotional response and the discordance between mood and emotional display are additional characteristics of PBA that are not expected with depression.

• #32 Pseudobulbar Affect | Dr. Sharon Himmanen

  https://shimmanen.wordpress.com/2012/11/26/pseudobulbar-affect/

  So, here we are, at the last blog entry of the semester. What a long, strange trip its been. […] While researching the brain mechanisms that contribute to laughter, and discovering that there was no single area of the brain that controls laughter, I came across a paragraph in Meyer et al (2007) discussing the source of pathological laughter. This is involuntary, mood-independent laughter that often occurs without any external or internal trigger. Poeck (1985) and Hartje (2006) (as cited by Meyers et al, 2007) suggest that this behavior is not caused by any true affect or emotional state, but is, instead, the result of disinhibition of the motor pathways that control laughter. Its seen in a number of neurological disorders, particularly those that are degenerative. […] So, its somewhat common to see pathological laughter, sometimes termed pseudobulbar affect in Alzheimers Disease, and as I correctly surmised before doing any research on the matter, it was likely due to some disinhibition. The frontal lobes are the main sources of this inhibition. Its the area of the brain that keeps the expression of inappropriate behaviors at bay in social situations, even though we may be thinking about it. For people suffering from a neurologically degenerative disease, such as Alzheimers Disease, the destruction of neural tissue in the frontal lobe removes that inhibition and produces this behavior. […] Its importance in the brain is, I think, highlighted, ironically, by disorders such as those that cause pseudobulbar affect.

• #33 What Is Pseudobulbar Affect?

  https://www.brainandlife.org/articles/what-is-pseudobulbar-affect

  Pseudobulbar affect (PBA) a condition that causes excessive and uncontrollable crying or laughing unrelated to either sadness or happiness can occur with many neurologic conditions, including Alzheimer’s disease and dementia, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, stroke, and traumatic brain injury. […] People may develop PBA when parts of the brain and brain stem that control movement have been damaged on both sides of their brains. The underlying mechanism isn’t completely understood, but it may be that circuits that involve the cerebellum disrupt the coordination of emotion. […] Researchers continue to explore causes and treatment. […] A hallmark of the disorder is a disconnect between how the person is feeling and how the person responds to that feeling (for example, feeling happy but crying or feeling sad but laughing). Other signs include an inability to control the duration or severity of crying/laughing and a lack of relief after an outburst. The condition is not related to medication or other psychiatric or neurologic disorders. PBA outbursts are not constant, and in some people they happen only occasionally.

• #34 Dextromethorphan-quinidine–responsive pseudobulbar affect (PBA): psychopharmacological model for wide-ranging disorders of emotional expression? | CNS Spectrums | Cambridge Core

  https://www.cambridge.org/core/journals/cns-spectrums/article/dextromethorphanquinidineresponsive-pseudobulbar-affect-pba-psychopharmacological-model-for-wideranging-disorders-of-emotional-expression/405FE13AB680859DDBCF3E15E00E29B0

  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. […] Hypothetically, functional disruption of these same brain cortical/cerebellar brain circuits may underlie not only pathological laughing and crying but also several other labile, unstable, and dysfunctional symptoms of emotional dysregulation in psychiatric disorders, such as behavioral symptoms of dementia, traumatic brain injury, post-traumatic stress disorder, borderline personality disorder, treatment refractory mood disorders, multiple impulsive-compulsive disorders, and beyond.

• #35 Dextromethorphan-quinidine–responsive pseudobulbar affect (PBA): psychopharmacological model for wide-ranging disorders of emotional expression? | CNS Spectrums | Cambridge Core

  https://www.cambridge.org/core/journals/cns-spectrums/article/dextromethorphanquinidineresponsive-pseudobulbar-affect-pba-psychopharmacological-model-for-wideranging-disorders-of-emotional-expression/405FE13AB680859DDBCF3E15E00E29B0

  Specifically, the pathophysiology of PBA is thought to involve injury to the brain circuits that regulate the expression of affect. That is, PBA is theoretically the result of brain lesions caused principally by 6 neurological disorders known to damage pathways in the frontal lobes and descending (top-down) to the brain stem, basis pontis, and cerebellum, together comprising systems thought to be involved in motor control of emotional expression. […] The dimensional approach to symptoms thus generates the hypothesis that the additional symptoms of emotional dysregulation beyond pathological laughing and crying seen in the disorders known to cause PBA also may be linked to the same top-down brain circuits thought to be compromised in PBA and therefore also potentially treatable by the same psychopharmacological approach proven effective for the narrowly defined classic neurologic symptoms of PBA. […] Dextromethorphan-quinidineresponsive PBA theoretically can serve as both a pathophysiologic and a treatment model for diverse conditions and symptoms of disordered emotional expression.

• #36 New Pseudobulbar Affect (PBA) treatments 2025 | Everyone.org

  https://everyone.org/explore/treatment/?id=58

  This combination has shown efficacy in reducing the frequency and severity of emotional outbursts associated with PBA, though it does not reverse or cure the underlying neurological condition. […] Existing treatments, including FDA-approved and off-label medications, focus exclusively on symptom management rather than addressing or reversing the underlying neurological dysfunction. […] While these treatments can significantly improve patient quality of life, ongoing research is necessary to identify potential curative therapies.

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