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PM & R : the Journal of Injury,... Oct 2018Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic...
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.
Topics: Adult; Brain Injuries, Traumatic; Dextromethorphan; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injury Severity Score; Male; Maximum Tolerated Dose; Middle Aged; Neuropsychological Tests; Patient Safety; Patient Selection; Prognosis; Prospective Studies; Pseudobulbar Palsy; Quinidine; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 29477412
DOI: 10.1016/j.pmrj.2018.02.010 -
Korean Journal of Neurotrauma Apr 2022Central pontine myelinolysis (CPM) is a disorder wherein variable symptoms are associated with pontine dysfunction. It has been known to occur inconstantly, particularly...
Central pontine myelinolysis (CPM) is a disorder wherein variable symptoms are associated with pontine dysfunction. It has been known to occur inconstantly, particularly when serum sodium in patients with prolonged hyponatremia is rapidly corrected. Further, it is known that patients with liver diseases, malnutrition, malignancy, adrenal insufficiency, and metabolic derangements are more vulnerable to this disorder. However, there is limited literature about the occurrence of CPM in patients with traumatic brain injury, especially in those with normal serum sodium levels. A 36-year-old man having no medical history was bought to our hospital due to an open skull fracture and underwent surgery. During the hospitalization period, he showed a sudden pseudobulbar palsy and rigidity. Imaging study of the brain was characteristic for CPM. He had no fluctuation of serum sodium levels during the hospitalization period. We speculate that the brain trauma itself might cause a CPM, and its pathophysiology may not be related to rapid serum sodium correction.
PubMed: 35557639
DOI: 10.13004/kjnt.2022.18.e3 -
BMJ Case Reports Nov 2020Carotid artery dissection is one of the most common causes of ischaemic stroke in young and middle-aged population. We report a case of bilateral carotid artery...
Carotid artery dissection is one of the most common causes of ischaemic stroke in young and middle-aged population. We report a case of bilateral carotid artery dissection presenting with opercular syndrome or Foix-Chavany-Marie syndrome. This 46-year-old obese and hypertensive man with a history of fall from bike 1 week prior, presented with sudden onset of anarthria, dysphagia and deviation of angle of mouth. His speech and dysphagia gradually improved over 10 days to normal, but he developed pseudobulbar affect and difficulty in calculations 4 weeks later. MRI showed acute infarcts in bilateral operculum. CT angiography showed dissection in bilateral cervical ICAs. He was managed conservatively with oral anticoagulation, given for 6 months. Probability of dissection must be considered in patients with a history of trauma or falls developing focal neurological deficits. To our knowledge, this is the first case report of bilateral ICA dissection presenting with Foix-Chavany-Marie syndrome.
Topics: Aortic Dissection; Brain; Carotid Arteries; Carotid Artery Diseases; Computed Tomography Angiography; Deglutition Disorders; Dysarthria; Facial Paralysis; Humans; Ischemic Stroke; Magnetic Resonance Imaging; Male; Middle Aged; Obesity
PubMed: 33257395
DOI: 10.1136/bcr-2020-239080 -
Proceedings (Baylor University. Medical... Feb 2021Foix-Chavany-Marie syndrome (FCMS) is a cortical-subcortical pseudobulbar palsy characterized by automatic voluntary dissociation of...
Foix-Chavany-Marie syndrome (FCMS) is a cortical-subcortical pseudobulbar palsy characterized by automatic voluntary dissociation of facio-masticatory-pharyngo-glosso-laryngeal movements. FCMS is typically caused by vascular insults on the bilateral anterior opercular or adjacent subcortical areas. Acute onset of FCMS secondary to a unilateral lesion is extremely rare. Herein we present a case of FCMS caused by acute unilateral anterior opercular infarction with preexisting bilateral leukoaraiosis. Our case shows that an acute unilateral anterior opercular lesion can decompensate preexisting corticobulbar-subcortical lesions and cause the typical features of FCMS.
PubMed: 33953472
DOI: 10.1080/08998280.2021.1878976 -
Prion Dec 2021Swallowing function in long-term survivors of Creutzfeldt-Jakob disease (CJD) has not been elucidated. Herein, we report a patient with MM2-cortical-type sporadic CJD...
Swallowing function in long-term survivors of Creutzfeldt-Jakob disease (CJD) has not been elucidated. Herein, we report a patient with MM2-cortical-type sporadic CJD (MM2C-type sCJD) with long-term preservation of pharyngeal swallowing function using videofluoroscopic (VF) examination of swallowing. A 55-year-old woman was admitted to hospital because of dyscalculia and memory disturbance 3 years after the onset of these symptoms. Neurological examination revealed dementia, extrapyramidal signs, and delusion. Diffusion-weighted MRI revealed bilateral hyperintensity in the basal ganglia and frontal, temporal, and parietal cortices. No mutation with the methionine homozygote at codon 129 was found on PRNP gene analysis. VF was performed 68 months after the onset. Although bolus transport from the oral cavity to the pharynx worsened, the pharyngeal swallowing function was preserved even 68 months after onset. Serial MRI examinations revealed no apparent atrophy of the brainstem. Single photon emission computed tomography revealed that the regional cerebral blood flow in the brainstem was preserved. These findings suggest that pseudobulbar palsy is the pathophysiology underlying dysphagia in long-term survivors of MM2C-type sCJD, probably owing to preserved brainstem function even in a state of akinetic mutism.
Topics: Creutzfeldt-Jakob Syndrome; Deglutition; Diffusion Magnetic Resonance Imaging; Female; Humans; Middle Aged; Pharynx; Tomography, Emission-Computed, Single-Photon
PubMed: 34078217
DOI: 10.1080/19336896.2021.1930851 -
PloS One 2019Congenital Zika Syndrome (CZS) is a unique pattern of congenital abnormalities found in fetuses and neonates infected with the Zika virus (ZIKV). Here, we clinically...
Congenital Zika Syndrome (CZS) is a unique pattern of congenital abnormalities found in fetuses and neonates infected with the Zika virus (ZIKV). Here, we clinically identify and characterize infants with CZS between 2015 and 2018 in Mato Grosso do Sul, Brazil-a border area with Paraguay and Bolivia. This cross-sectional study, based on primary and secondary data, tracks the cases registered in the Brazilian Public Health Reporting System through the following stages: (1) preliminary data analysis, (2) identification of the congenital syndrome cases, (3) etiologic classification of the cases, (4) active search, and (5) clinical assessment. Of the 72 investigated cases, 16 were probable cases of CZS. Of these, it was only possible to clinically assess 11 infants. Considering the 16 probable cases of CZS, nine were classified as confirmed cases, and five as potential cases of the syndrome. Regarding clinical features, brain palsy was identified in all analyzed infants. Moreover, microcephaly and pseudobulbar syndrome were found in eight infants, and hydrocephalus was found in three individuals. In addition to these conditions, seven children were malnourished. Our study may provide significant insights for other researches that aim to elucidate CZS and its clinical and populational consequences.
PubMed: 31584972
DOI: 10.1371/journal.pone.0223408 -
Acta Neurochirurgica Dec 2018This report describes a case of a 62-year-old man who developed Foix-Chavany-Marie syndrome subsequent to traumatic brain injury. The initial presentation of the...
This report describes a case of a 62-year-old man who developed Foix-Chavany-Marie syndrome subsequent to traumatic brain injury. The initial presentation of the syndrome was profound loss of voluntary control of orofacial muscles, causing a loss of speech and impairment of swallow. Over subsequent months, a remarkable recovery of these functions was observed. The natural history of FCMS in this case was favourable, with good improvement in function over months. Furthermore, the pattern of bilateral opercular injury was more readily recognised on MRI than on CT, supporting the role of MRI in cases of traumatic brain injury.
Topics: Brain Injuries, Traumatic; Deglutition Disorders; Dysarthria; Facial Paralysis; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Temporal Lobe
PubMed: 30328523
DOI: 10.1007/s00701-018-3702-x -
Annals of Indian Academy of Neurology 2016Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the...
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL.
PubMed: 27293347
DOI: 10.4103/0972-2327.173403 -
Case Reports in Neurological Medicine 2017Central pontine myelinolysis (CPM) is an acute demyelinating neurological disorder affecting primarily the central pons and is frequently associated with rapid...
Central pontine myelinolysis (CPM) is an acute demyelinating neurological disorder affecting primarily the central pons and is frequently associated with rapid correction of hyponatremia. Common clinical manifestations of CPM include spastic quadriparesis, dysarthria, pseudobulbar palsy, and encephalopathy of various degrees; however, coma, "locked-in" syndrome, or death can occur in most severe cases. Rarely, CPM presents with neuropsychiatric manifestations, such as personality changes, acute psychosis, paranoia, hallucinations, or catatonia, typically associated with additional injury to the brain, described as extrapontine myelinolysis (EPM). We present a patient with primarily neuropsychiatric manifestations of CPM, in the absence of focal neurologic deficits or radiographic extrapontine involvement. A 51-year-old female without significant medical history presented with dizziness, frequent falls, diarrhea, generalized weakness, and weight loss. Physical examination showed no focal neurological deficits. Laboratory data showed severe hyponatremia, which was corrected rather rapidly. Subsequently, the patient developed symptoms of an acute psychotic illness. Initial brain magnetic resonance imaging (MRI) was unremarkable, although a repeat MRI two weeks later revealed changes compatible with CPM. This case demonstrates that acute psychosis might represent the main manifestation of CPM, especially in early stages of the disease, which should be taken into consideration when assessing patients with acute abnormalities of sodium metabolism.
PubMed: 28392953
DOI: 10.1155/2017/1471096 -
Case Reports in Neurology 2019Foix-Chavany-Marie syndrome (FCMS) is a rare type of pseudobulbar palsy characterized by automatic-voluntary dissociation of movements of the face, tongue, pharynx, and...
Foix-Chavany-Marie syndrome (FCMS) is a rare type of pseudobulbar palsy characterized by automatic-voluntary dissociation of movements of the face, tongue, pharynx, and masticatory muscles. Most cases are due to bilateral ischemic lesions of the anterior operculum, but the syndrome has also been described after unilateral opercular damage, either isolated or associated with contralateral cortico-nuclear tract involvement. We report a patient with FCMS due to right anterior opercular lesion with contralateral infarction of the corona radiata. The patient presented with paralysis of the face and tongue with automatic and voluntary dissociation. To our knowledge, FCMS with this peculiar lesion topography has rarely been reported. We discuss the underlying mechanism with reference to MRI and diffusion tensor imaging.
PubMed: 31824287
DOI: 10.1159/000503856