Rare case of pseudobulbar palsy: subopercular syndrome.

We present a case of a 73-year-old man who developed sudden onset dysarthria, dysphagia and bilateral facial weakness with automato-voluntary dissociation, which deteriorated rapidly to anarthria and aphonia within a few days. MRI scan of the head showed acute infarct in right internal capsule and an old infarct in the left corona radiata while the rest of the investigations were normal. Based on these findings, diagnosis was thought to be subopercular syndrome. He recovered significantly in a few weeks' time.

[Fire needling on dysphagia due to pseudobulbar palsy after stroke: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of fire needling on dysphagia due to pseudobulbar paralysis after stroke and to compare the difference in clinical effect between fire needling and swallowing function rehabilitation training. METHODS: A total of 76 patients with dysphagia due to pseudobulbar paralysis after stroke were randomly divided into an observation group and a control group, 38 cases in each group (1 case dropped out in the control group). The both groups were based on conventional western medication treatment. Fire needle pricking was exerted at Lianquan (CV 23), Fengchi (GB 20), Wangu (GB 12), Shuigou (GV 26), Neiguan (PC 6) and Zusanli (ST 36) without needle retaining every other day in the observation group. The control group was treated with the swallowing function rehabilitation training. In both groups, treatment for 2 weeks was as one course and 2 courses of treatment with 2-day interval were required. After treatment, swallowing scores of Fujishima Ichiro and swallow quality of life questionnaire (SWAL-QOL) scores were observed in both groups, and the clinical effect was compared. Follow-up of swallowing scores of Fujishima Ichiro in 4 weeks after treatment was completed to evaluate the clinical effect. RESULTS: The clinical effective rates after treatment and follow-up were 92.1% (35/38) and 94.7% (36/38) in the observation group, higher than 75.7% (28/37) and 83.8% (31/37) in the control group (P<0.05). After treatment, the swallowing scores of Fujishima Ichiro and SWAL-QOL scores were increased in the two groups (P<0.05), and those in the observation group were higher than the control group (P<0.05). The swallowing scores of Fujishima Ichiro were increased during follow-up in the two groups (P<0.05). CONCLUSION: Fire needling has a better effect than conventional rehabilitation training in the treatment of dysphagia due to pseudobulbar paralysis after stroke, which can obviously improve the swallowing function and quality of life in patients with dysphagia.

Assessment of Use of Combined Dextromethorphan and Quinidine in Patients With Dementia or Parkinson Disease After US Food and Drug Administration Approval for Pseudobulbar Affect.

Importance: In 2010, the US Food and Drug Administration (FDA) approved a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect after studies in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This medication, however, may be commonly prescribed in patients with dementia and/or Parkinson disease (PD). Objective: To investigate the prescribing patterns of dextromethorphan-quinidine, including trends in associated costs. Design, Setting, and Participants: This population-based cohort study of patients prescribed dextromethorphan-quinidine used data from 2 commercial insurance databases, Optum Clinformatics Data Mart and Truven Health MarketScan. The Medicare Part D Prescription Drug Program data set was used to evaluate numbers of prescriptions and total reported spending by the Centers for Medicare & Medicaid Services. Patients were included if they were prescribed dextromethorphan-quinidine from October 29, 2010, when the drug was approved, through March 1, 2017, for Optum and December 31, 2015, for Truven. Data were analyzed from December 1, 2017, through August 1, 2018. Main Outcomes and Measures: The proportion of patients prescribed dextromethorphan-quinidine with a diagnosis of MS, ALS, or dementia and/or PD, as well as the number of patients with a history of heart failure (a contraindication for the drug). Results: In the commercial health care databases, 12 858 patients filled a prescription for dextromethorphan-quinidine during the study period. Mean (SD) age was 66.0 (18.5) years, 66.7% were women, and 13.3% had a history of heart failure. Combining results from both databases, few patients had a diagnosis of MS (8.4%) or ALS (6.8%); most (57.0%) had a diagnosis of dementia and/or PD. In the Medicare Part D database, the number of patients prescribed dextromethorphan-quinidine increased 15.3-fold, from 3296 in 2011 to 50 402 in 2016. Reported spending by Centers for Medicare & Medicaid Services on this medication increased from $3.9 million in 2011 to $200.4 million in 2016. Conclusions and Relevance: Despite approval by the FDA for pseudobulbar affect based on studies of patients with ALS or MS, dextromethorphan-quinidine appears to be primarily prescribed for patients with dementia and/or PD.

Pseudobulbar Affect in Survivors of Extreme Prematurity With Cerebellar Injury: Support for the Cerebellar Link in Pathologic Laughter and Crying.

Pseudobulbar affect, that is, pathologic laughter and crying is being increasingly recognized in adults and is seen in association with a number of diseases like Parkinson disease, dementia, traumatic encephalopathy, and others, but has not previously been described in children with cerebral palsy. The condition pseudobulbar affect may be due to lesions in (or degeneration of) the cerebro-ponto-cerebellar pathways. Here we report 2 children with cerebral palsy who have structural cerebellar injury because of their being born extremely premature who have pathologic crying and probably laughter.

[Therapeutic effects of acupuncture combined with rehabilitation training on dysphagia in post-stroke pseudobulbar palsy].

OBJECTIVE: To compare the therapeutic effects on dysphagia in post-stroke pseudobulbar palsy between the combined treatment with acupuncture and rehabilitation training and the combined treatment with low-frequency electrical therapy and rehabilitation training and to explore its more effective therapy, using the ultrasonographic examination. METHODS: A total of 60 patients of dysphagia in post-stroke pseudobulbar palsy were randomly assigned into an observation group and a control group, 30 cases in each one. The rehabilitation treatment was provided in the two groups. Additionally, in the observation group, acupuncture was used at the three-tongue points [Shanglianquan (Extra), located in the depression between the lingual bone and the border of lower jaw, 1 cun inferior to the midline of the jaw; and the other two points, located at 0.8 cun bilateral to Shanglianquan (Extra)], bilateral Fengchi (GB 20) and Fengfu (GV 16). After arrival of qi, the last two tongue-points were stimulated with electricity, with disperse-dense wave, periodically at 2 Hz, 10 Hz and 100 Hz, at the interval of 3 s, lasting for 30 min. Bilateral Fengchi (GB 20) was stimulated with electricity, with disperse-dense wave and the same frequency as above, lasting for 30 min. In the control group, the low-frequency electrical stimulation was adopted. The electrodes were placed on the bilateral sides of the midline of the throat, 30 min each time. The treatment was for 1 month in the two groups, once a day. The scores of the standardized swallowing assessment (SSA) and the videofluoroscopy swallowing study (VFSS) were observed and the reducing rate of the hyoid-thyroid cartilage distance was determined with ultrasound quantitative measure. RESULTS: After treatment, SSA scores of the two groups were all lower than those before treatment and VFSS scores were higher than those before treatment (all P<0.05). The above scores in the observation group were better than those in the control group (both P<0.05). The reducing rates of the hyoid-thyroid cartilage distance were higher than those before treatment in the two groups (both P<0.05). The result in the observation group was higher than that in the control group (P<0.05). CONCLUSION: The treatments with acupuncture and rehabilitation training or with the low-frequency electrical therapy and rehabilitation obtain the effects on dysphagia in post-stroke pseudobulbar palsy in the patients. The effects of the combined treatment with acupuncture and rehabilitation training are better. The ultrasonographic technology effectively and quantitatively analyzes the changes in the glossopharyngeal complex in the patients of dysphagia.

Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect Among Study Participants With Traumatic Brain Injury: Results From the PRISM-II Open Label Study.

BACKGROUND: Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). OBJECTIVE: To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary endpoint was change in Center for Neurologic Study-Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). RESULTS: DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, -5.6 [5.2]; day 90, -8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had "much improved" or "very much improved" on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (-3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (-3.2 [5.3], P<.001) and 90 (-5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). CONCLUSIONS: DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials. LEVEL OF EVIDENCE: II.

Hashimoto's encephalopathy presenting as pseudobulbar palsy.

INTRODUCTION: Hashimoto's encephalopathy (HE) is an autoimmune condition with varied neurological and psychiatric features. HE is very unusual as a cause of pseudobulbar palsy (PSP). CASE PRESENTATION: A 14-year-old male was admitted with right-sided weakness, dysphagia, speech disorder, and aggressiveness. Brain magnetic resonance imaging showed increased intensity in bilateral temporal, insular cortex, amygdala, and parahippocampal area on T2-weighted and fluid-attenuated inversion recovery images. Autoimmune encephalitis was considered as the patient had subacute onset of psychiatric and motor disturbances with normal findings for cerebrospinal fluid. N-methyl-D-aspartate receptor, anti-glutamate-type α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2, anti-contactin-associated protein-like 2, anti-gamma-aminobutyric acid receptor, anti-Leucine-rich, and glioma-inactivated 1 antibodies were negative but the anti-thyroperoxidase (antiTPO) level was greater than 998 IU/ML (n:0-9). Steroid therapy was initiated as pulse therapy and maintained with 2-mg/kg/day dose with the diagnosis of HE. He was symptom free for 6 months. In the follow-up period, he had two recurrences which responded to steroid therapy. CONCLUSION: The common causes of PSP are demyelinating, vascular, and motor neuron diseases and congenital malformations of the opercular or insular cortex. However, there are no cases of PSP developing after any autoimmune encephalitis. This case highlights the importance of early detection of antiTPO antibodies with the findings of PSP due to autoimmune encephalitis.

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.

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.

Pseudobulbar affect (PBA) in an incident ALS cohort: results from the Apulia registry (SLAP).

The aim of this study is to investigate the frequency and the clinical correlations of pseudobulbar affect (PBA) in a population-based incident cohort of ALS patients. Incident ALS cases, diagnosed in 2011 and 2012, according to El Escorial criteria were enrolled from a prospective population-based registry in Apulia, Southern Italy. Neurological status was assessed using a standard neurological examination and the revised ALS Functional Rating Scale (ALSFRSr). The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate the presence and severity of PBA. Total scores range from 7 to 35. A score ≥13 was used to identify the presence of PBA. One-hundred thirty-two sporadic incident ALS cases were enrolled. Median disease duration was 20 months (range 2-143), median onset-diagnosis interval (ODI) 12 months (range 2-131), median ALSFRSr at baseline 36/48 (range 2-47) and median ALSFRSr bulbar sub-score 10/12 (range 0-12). Neurological examination revealed presence of PBA in 34/132 patients (26%). Pathological CNS-LS score was found in 45/132 patients (34%). Median total CNS-LS score was 9/35 (range 7-29). The subgroup with pathological CNS-LS was characterized by a short disease duration from symptom onset, ODI, time to diffusion to a second region, time to generalization and ALSFRSr bulbar sub-score, bulbar onset, "definite" diagnostic category, bulbar upper motor-neuron involvement and presence of PBA at neurological examination. In population-based setting, one-third of ALS patients present PBA at diagnosis. The presence of PBA is associated with bulbar UMN involvement and markers of a more severe phenotype.

[TRANSIENT PSEUDOBULBAR SYNDROME IN UNILATERAL FRONTAL OPERCULAR INFARCTS]. / ÁTMENETI PSEUDOBULBARIS TÜNETCSOPORT EGYOLDALI FRONTÁLIS OPERCULARIS INFARKTUSOKNÁL.

The classic anterior (frontal) opercular syndrome (Foix-Chavany-Marie sy.) is a cortical pseudobulbar palsy mainly due to bilateral lesions of anterior brain operculum. In 2000 the authors had a 70-year old female patient with acute onset of swallowing and speaking difficulty. Neurological examination established a left facial central palsy, the palsy of the tongue and the soft palate, dysarthry, difficulty in chewing with left side hemiparesis. The CT scan showed a right side (one-sided) frontal opercular ischemic lesion. This event switched their attention especially to this group of cases and subsequently the authors collected 12 patients with these symptoms. Authors discuss the patomechanism of transient pseudobulbar palsy that occurs due to unilateral opercular lesion that the diaschisis effect might explain.

PSEUDOBULBAR AFFECT IN MULTIPLE SCLEROSIS PATIENTS.

The aim of the study was to determine the prevalence of pseudobulbar affect (PBA) in patients with multiple sclerosis (MS) and to analyze the link between PBA and patient age, sex, clinical course of MS, disease duration and degree of disability. The study was conducted on 79 MS patients that underwent inpatient rehabilitation at the Lipik Special Hospital for Medical Rehabilitation in the period from August 15, 2014 to February 15, 2015. PBA is a term used for an emotional disinhibition syndrome characterized by sudden and involuntary episodes of crying or laughing which are not in proportion to the stimulus applied or occur without stimulus. The condition can be present in patients with various neurological disorders, such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, patients having recovered from stroke, or following traumatic brain injury. The estimated prevalence in patients with MS ranges from 10% to 46.2%. As a measuring instrument in the study, we used the Center for Neurologic Study-Lability Scale (CNS-LS), where a sum 17 denoted positive finding. The total number of respondents was 79, of which 33 (41.8%) met the CNS-LS criteria for the diagnosis of PBA. There was no statistically significant correlation between PBA, age and degree of disability, although PBA was more common in women and in patients with a secondary progressive form of the disease. We found that 42.4% of respondents with positive CNS-LS criteria for PBA did not inform their neurologist on the presence of sudden mood changes. The high frequency of PBA and the fact that a significant proportion of patients did not inform the neurologist on their affective disturbances call for an active approach to diagnosis and treatment.

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.

Pseudobulbar paralysis in the Renaissance: Cosimo I de' Medici case.

Cosimo I de' Medici (1519-1574) was the first Grand Duke of Tuscany. He was one of the most important members of the Medici family. He was an excellent conqueror and a good politician. Moreover, he was able to attract and encourage artists, scientists and architects to promote Florence as the cultural capital of the Italian Renaissance. Historical chronicles report that he suffered from a stroke when he was 49 years old. Together with the acute manifestation of stroke, he displayed peculiar symptoms. He had gait disturbances and sphincter dysfunctions. His language became poor and hard to understand. His mood was very fluctuating and in the last years of his life he was a short-tempered man. In addition, he had a characteristic symptom, so-called pathological laughing and crying. The course of his disease was slow and stuttering. Taken together, these data seem to be one of the first reports of pseudobulbar paralysis. The disease of Cosimo I was probably due to a chronic cerebral vasculopathy, known as small vessels disease. We discuss this hypothesis regarding an ancient clinical case, with the support of current studies.

Behind the screen: pseudobulbar symptoms after deep brain stimulation.

BACKGROUND: Thalamotomy was formerly used to treat different tremor syndromes. Nowadays, deep brain stimulation has become an established technique to treat -different movement disorders. The combination of these two stereotactic interventions is rare. CLINICAL PRESENTATION: We present a patient in which a right-sided tremor -syndrome with an underlying pathology of combined essential tremor and Parkinsonian tremor was successfully treated initially with a left-sided thalamotomy and subsequently with -bilateral deep brain stimulation in the subthalamic nucleus. RESULTS: Deep brain stimulation in the subthalamic nucleus resulted in hemidystonia, pathological laughing and crying, dysarthria and dysphagia, all due to dislocation of the stimulation electrodes contacting the internal capsule. After discontinuation of the high-frequency stimulation these side-effects disappeared, but were then reactivated by an LCD television in stand-by mode. CONCLUSION: In this report we discuss the pathophysiology of pseudobulbar symptoms and pathological laughing and crying in context of thalamotomy and dislocated DBS electrodes. Furthermore, we report on the occurrence that magnetic fields in the household have an impact on deep brain stimulation, even if they are in stand-by mode.