Use of Escitalopram for pseudobulbar affect following severe traumatic.

Those who have suffered from traumatic brain injury (TBI) often develop behavioural, affective, and cognitive complications. Some might experience episodes of involuntary and/or exaggerated laughter and crying. This condition is commonly known as 'pseudobulbar affect'(PBA) and leads to anger, frustration, and social disability. This case report presents the use of low-dose Escitalopram in an individual suffering from agitation and PBA following severe TBI (sTBI). It emphasises the importance of adopting a holistic approach in the treatment of such individuals with appropriate attention paid to factors such as cognitive and behavioural impairment, and caregiver distress.

Pathological laughter and crying: insights from lesion network-symptom-mapping.

The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied 'lesion network-symptom-mapping' to 70 focal lesions identified in a systematic literature search for case reports of PLC. In lesion network-symptom-mapping normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions that are likely affected by diaschisis based on the lesion locations. With lesion network-symptom-mapping we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons, and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a centre for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed, which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus; and a volitional system descending from the lateral premotor cortices that can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the 'positive PLC subnetwork' is part of the emotional system and the 'negative PLC subnetwork' overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.

Pharmacotherapy for the Pseudobulbar Affect in Individuals Who Have Sustained a Traumatic Brain Injury: a Systematic Review.

Pseudobulbar affect is a debilitating condition that significantly reduces quality of life for many individuals following traumatic brain injury (TBI). It is characterized by embarrassing and often uncontrollable episodes of crying or laughter. The aim of this systematic review was to evaluate the effectiveness of pharmacotherapy as compared to all other comparators for the management of pseudobulbar affect in adults who have sustained TBI. Six databases were searched, with additional hand searching of journals, clinical trials registries and international drug regulators to identify published and unpublished studies in English up to June 2018. Studies were eligible for this review if they included adults who had sustained a medically confirmed TBI and presented with pseudobulbar affect. All pharmacotherapy and comparator interventions were considered for inclusion, and study design was not limited to randomised controlled trials. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Two quasi-experimental studies examining the effectiveness of dextrometamorphan/quinidine (DM/Q) were identified. These studies reported that DM/Q was effective in reducing symptoms of pseudobulbar affect and had a positive safety profile, over follow-up periods of 3 months (n = 87) and 12 months (n = 23). However, both studies were limited by lack of a control group and a high dropout rate. The findings of twelve case reports examining the effectiveness of DM/Q (n = 6) and anti-depressants (n = 6) are also discussed. Further research is required to determine which pharmacological interventions provide the best outcomes for individuals with pseudobulbar affect following TBI, with consideration given to side effect profiles and financial costs.

[Pseudobulbar affect in stroke patients in Argentina]. / Síndrome pseudobulbar en pacientes con accidente cerebrovascular en Argentina.

BACKGROUND: Pseudobulbar affect is defined by involuntary or exaggerated episodes of laughter or crying, subsequent to a specific disease. After-stroke pseudobulbar affect is reported in 11%-34% of patients. In our population is underdiagnosed. Our objective was to determine its frequency in a group of stroke patients. PATIENTS AND METHODS: Prospective observational study from June/2017 to June/2018. Two populations were evaluated: chronic stroke (Group A) and acute stroke (Group B). Patients with severe psychiatric illness, cognitive impairment and/or aphasia were excluded. PLACS ("pathological laughing and crying scale") and CNS-LS ("lability scale for pseudobulbar affect") scales were performed. Pseudobulbar affect was defined with diagnostic criteria plus both positive scales. RESULTS: Fifty patients were evaluated. Sixty-eight percent were men. Mean age: 65±12 years. Group A: 19 cases and group B: 31 cases. Positive PLACS: 21% group A and 29% group B. Positive CNS-LS: 58% group A and 26% group B. Both positive scales in 8 patients (2 in group A and 6 in group B). Three of them had associated depression. CONCLUSIONS: Pseudobulbar affect should be screened after stroke. Post-stroke depression is frequent and differential diagnose with emotional lability attributable to pseudobulbar affect must be ruled out. The administration of a single scale would not be sufficient for diagnostic guidance.

Pseudobulbar Affect Correlates With Mood Symptoms in Parkinsonian Disorders but Not Amyotrophic Lateral Sclerosis.

Pseudobulbar affect (PBA) is a syndrome of affective disturbance associated with inappropriate laughter and crying, independent of mood. PBA is common in amyotrophic lateral sclerosis (ALS) and increasingly recognized in Parkinson's disease (PD) and atypical parkinsonism (aP). Correlates of PBA have not been systematically studied. The purpose of this study was to determine whether cognitive and psychiatric comorbidities correlated with patient-reported symptoms of PBA by using the Center for Neurological Study-Lability Scale among patients with ALS, PD, and aP. A total of 108 patients (PD, N=53; aP, N=29; ALS, N=26) completed a cognitive screener and self-reported measures of lability, depression, anxiety, apathy, and quality of life. Statistical analyses included one- and two-way analyses of covariance to evaluate group differences, Pearson's correlations to determine relationships between PBA symptoms and comorbidities, multiple regression for predicting PBA symptom severity in clinical correlates, and chi-square t tests for predicting demographic variables. PBA symptom severity did not vary between the three groups. Younger age and worse anxiety correlated with PBA symptom severity in all three groups, whereas depression and poor mental health/quality of life only correlated with PBA symptom severity in the PD and aP groups. PD and aP patients may be more likely to benefit from treatment with antidepressants. Increased PBA symptoms were associated with declines in cognitive functioning in the aP group, but sufficient numbers of PD and ALS patients with cognitive dysfunction may not have been recruited. The results suggest the possibility of an alternate pathophysiologic mechanism for PBA, which may vary between neurological disorders and disease progression. Mood and cognition are of particular relevance and should be evaluated when symptoms of PBA are suspected.

Pseudobulbar affect as a negative prognostic indicator in amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate whether the presence of pseudobulbar affect (PBA) in an early stage of the disease influences survival in a population-based incident cohort of amyotrophic lateral sclerosis (ALS). METHODS: Incident ALS cases, diagnosed according to El Escorial criteria, were enrolled from a prospective population-based registry in Puglia, Southern Italy. The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate PBA. Total scores range from 7 to 35. A score ≥13 was used to identify PBA. Cox proportional hazard models were used for survival analysis. The modified C-statistic for censored survival data was used for models' discrimination. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify subgroups of patients with different patterns of risk, depending on baseline characteristics. RESULTS: We enrolled 94 sporadic ALS, median age of 64 years (range: 26-80). At the censoring date, 65 of 94 (69.2%), 39 of 60 (65.0%), and 26 of 34 (76.5%) patients reached the outcome (tracheotomy/death), in the whole, non-PBA and in the PBA groups, respectively. Kaplan-Meier survival curves for the two subgroups were not significantly different (log-rank test: 1.3, P = .25). The discrimination ability of a multivariable model with demographic and clinical variables of interest was not improved by adding PBA. In the RECPAM analysis, ALSFRSr and the total score of CNS-LS scale (

Identification of pseudobulbar affect symptoms in the nursing home setting: Development and assessment of a screening tool.

Pseudobulbar Affect (PBA) is a neurologic condition characterized by involuntary outbursts of crying and/or laughing disproportionate to patient mood or social context. Although an estimated 9% of nursing home residents have symptoms suggestive of PBA, they are not routinely screened. Our goal was to develop an electronic screening tool based upon characteristics common to nursing home residents with PBA identified through medical record data. Nursing home residents with PBA treated with dextromethorphan hydrobromide/quinidine sulfate (n = 140) were compared to age-, gender-, and dementia-diagnosis-matched controls without PBA or treatment (n = 140). Comparative categories included diagnoses, medication use and symptom documentation. Using a multivariable regression and best decision rule analysis, we found PBA in nursing home residents was associated with chart documentation of uncontrollable crying, presence of a neurologic disorder (e.g., Parkinson's disease), or by the documented presence of at least 2 of the following: stroke, severe cognitive impairment, and schizophrenia. Based on these risk factors, an electronic screening tool was created.

Laughter, crying and sadness in ALS.

BACKGROUND: Pseudobulbar affect (PBA) is prevalent in amyotrophic lateral sclerosis (ALS), but there is limited information on its associations and course. OBJECTIVES: Explore prevalence, associations, course and manifestations of PBA in outpatient cohort of patients with ALS and examine its relationship to depression. METHODS: Self-reported measures of PBA and depression (Center for Neurologic Study-Lability Scale (CNS-LS) and Patient Health Questionnaire (PHQ-9), respectively) were obtained from consecutive patients with ALS using tablet devices in waiting rooms (Knowledge Program). RESULTS: PBA (CNS-LS ≥13) was seen in 209/735 patients (28.4%). PBA was associated with bulbar onset and dysfunction, upper motor neuron dysfunction, cognitive impairment, depression and lower quality of life. A multivariable model that included lower bulbar and gross motor subscores, female gender, younger age and shorter duration of disease predicted PBA with 74% accuracy. CNS-LS scores increased only slowly with time. Women with PBA reported more crying than men. Crying (but not laughter) correlated with depression, and crying was associated with poorer quality of life. Exploratory factor analysis of pooled questions of CNS-LS and PHQ-9 identified three underlying factors (laughter, crying and depression) loaded on appropriate questions of the respective instruments. CONCLUSION: This study identifies associations of PBA and additionally finds PBA (especially crying-predominant PBA) more prevalent in women with ALS. Although the two self-report instruments (CNS-LS and PHQ-9) discriminate well between PBA and depression, there is significant overlap between depression and crying in PBA. Studies of PBA should stratify for gender, examine crying and laughter as separate outcomes and adjust for depression.

PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.

BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013.

Prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents.

OBJECTIVE: Pseudobulbar affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications. METHODS: A retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic-care residents were included in the "predisposed population" if they had a neurological disorder affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study-Lability Scale (CNS-LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment. RESULTS: Of 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the "predisposed population." PBA symptom prevalence, based on having a CNS-LS score ≥13, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms. CONCLUSIONS: Pseudobulbar affect symptoms were present in 17.5% of nursing home residents with neurological conditions, and 9.0% of residents overall. Increasing awareness and improving diagnostic accuracy of PBA may help optimize treatment. Copyright © 2015 John Wiley & Sons, Ltd.

An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results.

BACKGROUND: Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. METHODS: This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study-Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). RESULTS: 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C "much"/"very much" improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%). CONCLUSIONS: DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.

Prevalence of Pseudobulbar Affect following Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have reported that emotional lability is a common consequence of stroke. However, there is uncertainty about the "true" prevalence of the condition because, across these studies, patients have been recruited at different stages of recovery, from different settings, and using different diagnostic methods. There have been no systematic reviews of the published evidence to ascertain how the prevalence of poststroke pseudobulbar affect (PBA) might vary according to these factors. METHODS: A systematic review and meta-analysis of the published literature were undertaken. RESULTS: A total of 15 studies (n = 3391 participants) met inclusion criteria for the review. Meta-analysis estimated that the prevalence of PBA was 17% (95% confidence interval 12%-24%) acutely (<1 month post stroke), 20% (14%-29%) post acutely (1-6 months post stroke), and 12% (8%-17%) in the medium to longer term (>6 months post stroke). The evidence from the published literature, although limited, is that crying is a more common PBA presentation following stroke than laughter. CONCLUSIONS: PBA is a common condition that affects approximately 1 in 5 stroke survivors at the acute and postacute phases, and 1 in 8 survivors beyond 6 months post stroke. These prevalence data are very important for clinicians and the commissioners of services.

Crying and suicidal, but not depressed. Pseudobulbar affect in multiple sclerosis successfully treated with valproic acid: Case report and literature review.

OBJECTIVE: Pseudobulbar affect/emotional incontinence is a potentially disabling condition characterized by expressions of affect or emotions out of context from the normal emotional basis for those expressions. This condition can result in diagnostic confusion and unrelieved suffering when clinicians interpret the emotional expressions at face value. In addition, the nomenclature, etiology, and treatment for this condition remain unclear in the medical literature. METHOD: We report the case of a 60-year-old woman with multiple sclerosis who was referred to an inpatient psychiatry unit with complaints of worsening depression along with hopelessness, characterized by unrelenting crying. Our investigation showed that her symptoms were caused by pseudobulbar affect/emotional incontinence stemming from multiple sclerosis. RESULTS: The patient's history of multiple sclerosis and the fact that she identified herself as depressed only because of her incessant crying suggested that her symptoms might be due to the multiple sclerosis rather than to a depressive disorder. Magnetic resonance imaging demonstrated a new plaque consistent with multiple sclerosis lateral to her corpus callosum. Her symptoms resolved completely within three days on valproic acid but returned after she was cross-tapered to dextromethorphan plus quinidine, which is the FDA-approved treatment for this condition. SIGNIFICANCE OF RESULTS: This case provides important additional information to the current literature on pseudobulbar affect/emotional incontinence. The existing literature suggests a selective serotonin reuptake inhibitor (SSRI) and dextromethorphan/quinidine (Nuedexta) as first-line treatments; however, our patient was taking an SSRI at the time of presentation without appreciable benefit, and her symptoms responded to valproic acid but not to the dextromethorphan/quinidine. In addition, the case and the literature review suggest that the current nomenclature for this constellation of symptoms can be misleading.

Exploring the Impact of Amyotrophic Lateral Sclerosis on Otolaryngological Functions.

IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons at the spinal or bulbar level. OBJECTIVE: We aim to describe the most frequent otolaryngology (ORL) complaints and voice disturbances in patients with bulbar onset ALS. DESIGN: Retrospective cohort study. SETTING: Single-center study with combined ORL and ALS clinic evaluation. PARTICIPANTS: Patients with a confirmed diagnosis of ALS following an ORL visit and who underwent comprehensive voice assessments between January 2021 and January 2023. EXPOSURE: Objective voice assessments. MAIN OUTCOMES AND MEASURES: Glottal functional index (GFI), voice handicap index (VHI), reflux system index (RSI), and voice quality characteristics such as shimmer, jitter, maximum phonation time (MPT), and other essential parameters were assessed. RESULTS: One hundred and thirty-three patients (age 62.17 ± 10.79, 54.48% female) were included. Three patients were referred from the ORL department to the ALS clinic. The most frequent symptoms were; dysphagia, dysarthria, facial weakness, pseudobulbar affect, and sialorrhea. The mean of forced vital capacity was 59.85%, EAT-10 15.91 ± 11.66, RSI 25.84 ± 9.03, GFI 14.12 ± 5.58, VHI-10 42.81 ± 34.94, MPT 15.22 s ± 8.06. Many patients reported voice impairments mainly related to spastic dysarthria and the combination of lower and upper motor neuron dysarthria, hypernasality, reduced verbal expression, and articulatory accuracy. Shimmer was increased to 8.46% ± 7.20, and jitter to 2.26% ± 1.39. CONCLUSIONS AND RELEVANCE: Based on our cohort, this population with bulbar onset ALS has a higher frequency of voice disturbance characterized by hypernasality, spastic dysarthria, and reduced verbal expression. LEVEL OF EVIDENCE: Level 3.

Chinese Translation and Validation of the Center for Neurologic Study Lability Scale.

INTRODUCTION: Pseudobulbar palsy is a common symptom in patients with amyotrophic lateral sclerosis (ALS), but it is often underdiagnosed or misdiagnosed as other diseases. The Center for Neurologic Study Lability Scale (CNS-LS) is a self-report scale consisting of seven questions designed for evaluating pseudobulbar affect (PBA). The current study aimed to validate a Chinese version of the CNS-LS. METHODS: The Chinese version of the CNS-LS was obtained through a standardized forward-backward translation and cultural adaptation. A total of 105 patients with ALS were recruited from the ALS database of Peking University Third Hospital in Beijing, China, to complete the CNS-LS. The reliability of the Chinese version was determined by the test-retest method, and receiver operating characteristic (ROC) analysis was performed for criterion validity. RESULTS: Of 105 patients with ALS, 37 had symptoms of PBA and were diagnosed with that condition by neurologists. Forty-two patients completed the CNS-LS twice, and there was no statistically significant difference between the scores (Z = -0.896, p = 0.37). The Spearman correlation coefficient between the test and retest scores was 0.940 (p < 0.0005), and the Cronbach alpha coefficient was high (α = 0.905, n = 105). Scores of 12 or higher on the CNS-LS identified PBA with sensitivity of 0.919 and specificity of 0.882. The area under the ROC curve was 0.924. CONCLUSION: The Chinese version of the CNS-LS demonstrated good sensitivity and specificity in the group of patients with ALS enrolled in this study. The CNS-LS should be a useful instrument for clinical and research purposes for patients in this language group.

Pseudobulbar Affect in an Elderly Female With Small Vessel Ischemic Disease and Alcohol Abuse Disorder: A Case Report.

Pseudobulbar affect (PBA) is a neurological condition characterized by recurrent, inappropriate, and involuntary outbursts of emotion, primarily crying and laughter, which are dissociated from the individual's emotional experience. The precise underlying cause of PBA remains unknown; however, existing evidence suggests the involvement of dopaminergic, serotonergic, and glutamatergic neurotransmission within the corticopontine-cerebellar pathways responsible for regulating the motor expression of emotions. Additionally, PBA has been observed to co-occur with other neurocognitive and psychiatric disorders. Therefore, it is crucial to consider the possibility of a PBA diagnosis in patients with underlying neurological damage and disorders.

Classics in Chemical Neuroscience: Dextromethorphan (DXM).

Dextromethorphan (DXM) was introduced in 1958 as the first non-opioid cough suppressant and is indicated for multiple psychiatric disorders. It has been the most used over-the-counter cough suppressant since its emergence. However, individuals quickly noticed an intoxicating and psychedelic effect if they ingested large doses. DXM's antagonism at N-methyl-d-aspartate receptors (NMDAr) is thought to underly its efficacy in treating acute cough, but supratherapeutic doses mimic the activity of dissociative hallucinogens, such as phencyclidine and ketamine. In this Review we will discuss DXM's synthesis, manufacturing information, drug metabolism, pharmacology, adverse effects, recreational use, abuse potential, and its history and importance in therapy to present DXM as a true classic in chemical neuroscience.

Radiological correlates of pseudobulbar affect: Corticobulbar and cerebellar components in primary lateral sclerosis.

INTRODUCTION: Pseudobulbar affect (PBA) is a distressing symptom of a multitude of neurological conditions affecting patients with a rage of neuroinflammatory, neurovascular and neurodegenerative conditions. It manifests in disproportionate emotional responses to minimal or no contextual stimulus. It has considerable quality of life implications and treatment can be challenging. METHODS: A prospective multimodal neuroimaging study was conducted to explore the neuroanatomical underpinnings of PBA in patients with primary lateral sclerosis (PLS). All participants underwent whole genome sequencing and screening for C9orf72 hexanucleotide repeat expansions, a comprehensive neurological assessment, neuropsychological screening (ECAS, HADS, FrSBe) and PBA was evaluated by the emotional lability questionnaire. Structural, diffusivity and functional MRI data were systematically evaluated in whole-brain (WB) data-driven and region of interest (ROI) hypothesis-driven analyses. In ROI analyses, functional and structural corticobulbar connectivity and cerebello-medullary connectivity alterations were evaluated separately. RESULTS: Our data-driven whole-brain analyses revealed associations between PBA and white matter degeneration in descending corticobulbar as well as in commissural tracts. In our hypothesis-driven analyses, PBA was associated with increased right corticobulbar tract RD (p = 0.006) and decreased FA (p = 0.026). The left-hemispheric corticobulbar tract, as well as functional connectivity, showed similar tendencies. While uncorrected p-maps revealed both voxelwise and ROI trends for associations between PBA and cerebellar measures, these did not reach significance to unequivocally support the "cerebellar hypothesis". CONCLUSIONS: Our data confirm associations between cortex-brainstem disconnection and the clinical severity of PBA. While our findings may be disease-specific, they are consistent with the classical cortico-medullary model of pseudobulbar affect.

Emotional dysmetria after cerebellar-pontine stroke: a case report.

INTRODUCTION: Pseudobulbar affect, or emotional dysregulation, commonly occurs following stroke. However, it is frequently missed in cases involving the cerebellum, resulting in a lack of treatment, which can directly impact stroke rehabilitation. CASE PRESENTATION: A 63-year-old Caucasian female with no history of mood disorders presented with gait instability, dysarthria, and right sided hemiplegia, secondary to cerebellar and pontine ischemic stroke from a basilar occlusion. She underwent endovascular therapy and her deficits gradually improved. However during recovery she began to develop uncontrollable tearfulness while retaining insight that her emotional expression was contextually inappropriate. She was treated with a selective serotonin reuptake inhibitor with reported improvements in her emotional regulation at one year follow up. CONCLUSION: This case highlights cerebellar injury as a potential cause of poorly regulated emotions, or an emotional dysmetria. The recognition of this disorder in patients with cerebellar or pontine strokes is critical, as untreated pseudobulbar affect can impact future stroke rehabilitation.