Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24282
Durability of effect and safety of open-label ampreloxetine (TD-9855), a norepinephrine reuptake inhibitor, for symptomatic treatment of neurogenic orthostatic hypotension [Meeting Abstract]
Background: Inadequate norepinephrine (NE) release in neurogenic orthostatic hypotension (nOH) causes blood pressure to fall on standing and debilitating symptoms of cerebral hypoperfusion. Ampreloxetine, a novel, long-acting NE reuptake inhibitor, potentiates the effects of endogenous NE, and may improve symptoms of nOH. The objective of the study was to explore the durability of effect and safety of once-daily oral ampreloxetine for the symptomatic treatment of nOH in subjects with synucleinopathies.
Method(s): In an open-label, phase 2, exploratory, multicenter study, subjects received open-label ampreloxetine (3-20 mg) once-daily for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal and restarting alternative pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint), OHSA and Orthostatic Hypotension Daily Activities Scale (OHDAS) composite scores, and Patient Global Impression of Severity (PGI-S).
Result(s): Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). At Week 4, mean (SD) improvement on OHSA#1 was -3.8 (3.1) points; approximately 77% of subjects reported >=1-point improvement (minimal clinically important difference). At Week 20, mean improvement was -3.1 (3.0) points; approximately 86% reported >=1-point improvement. Symptom improvement was observed as early as Week 1 and was sustained throughout the study. Deterioration to baseline symptom severity was after ampreloxetine withdrawal. Similar trends were seen in OHSA and OHDAS composite scores, and PGI-S. Most common adverse events were urinary tract infection (24%), hypertension (19%), and headache (14%), with no study-drug related serious adverse events.
Conclusion(s): Ampreloxetine showed durable symptom improvement in symptomatic subjects with nOH over 20 weeks, with return to baseline symptom severity after ampreloxetine withdrawal. Ampreloxetine was well tolerated with a favorable safety profile. These encouraging open-label findings are being evaluated further in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH and synucleinopathies.
Copyright
Method(s): In an open-label, phase 2, exploratory, multicenter study, subjects received open-label ampreloxetine (3-20 mg) once-daily for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal and restarting alternative pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint), OHSA and Orthostatic Hypotension Daily Activities Scale (OHDAS) composite scores, and Patient Global Impression of Severity (PGI-S).
Result(s): Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). At Week 4, mean (SD) improvement on OHSA#1 was -3.8 (3.1) points; approximately 77% of subjects reported >=1-point improvement (minimal clinically important difference). At Week 20, mean improvement was -3.1 (3.0) points; approximately 86% reported >=1-point improvement. Symptom improvement was observed as early as Week 1 and was sustained throughout the study. Deterioration to baseline symptom severity was after ampreloxetine withdrawal. Similar trends were seen in OHSA and OHDAS composite scores, and PGI-S. Most common adverse events were urinary tract infection (24%), hypertension (19%), and headache (14%), with no study-drug related serious adverse events.
Conclusion(s): Ampreloxetine showed durable symptom improvement in symptomatic subjects with nOH over 20 weeks, with return to baseline symptom severity after ampreloxetine withdrawal. Ampreloxetine was well tolerated with a favorable safety profile. These encouraging open-label findings are being evaluated further in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH and synucleinopathies.
Copyright
EMBASE:2010479747
ISSN: 1873-5126
CID: 5184262
Transpalpebral Incision for Resection of an Ethmoidal Dural Arteriovenous Fistula: 2-Dimensional Operative Video
Ethmoidal dural arteriovenous fistulas are vascular malformations with arterial supply from the anterior ethmoidal artery and ultimate drainage into the sagittal sinus.1-3 They are characterized by a high risk of hemorrhage. Microsurgical disconnection of the fistula represents a safe and robust treatment option. Endovascular treatment requires catheterization of the ophthalmic artery and carries a risk of visual deficits. The supraorbital craniotomy provides an excellent corridor to the anterior skull base and is well suited for the treatment of ethmoidal dural arteriovenous fistulas. The supraorbital craniotomy may be performed through a transpalpebral "eyelid" incision. The transpalpebral incision allows for a well-hidden scar and does not have any associated hair loss, as can be seen with the eyebrow incision. The patient consented to the procedure and being videotaped.
PMID: 32674152
ISSN: 2332-4260
CID: 5177892
FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease
Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.
PMCID:6972869
PMID: 31964863
ISSN: 2041-1723
CID: 5134432
Should we standardize the EEG classification of mild, moderate, and severe cerebral dysfunction?
PMID: 32759028
ISSN: 1525-5069
CID: 5102832
Musical anhedonia: A review
Objectives: Anhedonia, or the inability or the loss of the capacity to experience pleasure, is a core feature of several psychiatric disorders. Different types of anhedonia have been described including social and physical anhedonia, appetitive or motivational anhedonia, consummatory and anticipatory anhedonia. Musical anhedonia is a rare condition where individuals derive no reward responses from musical experience. Methods: We searched the PubMed electronic database for all articles with the search term "musical anhedonia". Results: A final set of 12 articles (six original research articles and six clinical case reports) comprised the set we reviewed. Conclusions: Individuals with specific musical anhedonia show normal responses to other types of reward, suggesting a specific deficit in musical reward pathways. Those individuals are not necessarily affected by psychiatric conditions, have normal musical perception capacities, and normal recognition of emotions depicted in music. Individual differences in the tendency to derive pleasure from music are associated with structural connections from auditory association areas in the superior temporal gyrus to the anterior insula. White matter connectivity may reflect individual differences in the normal variations of reward experiences in music. The moderate amount of heterogeneity between the reviewed studies is a limitation to the generalizability of our conclusions. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
PSYCH:2021-30906-008
ISSN: 2499-6904
CID: 5094682
Editors' note: Miller Fisher syndrome and polyneuritis cranialis in COVID-19 [Comment]
PMID: 32839298
ISSN: 1526-632x
CID: 5092792
Editors' note: COVID-19 presenting with ophthalmoparesis from cranial nerve palsy [Comment]
PMID: 32868478
ISSN: 1526-632x
CID: 5092812
Editors' note: Value of witness observations in the differential diagnosis of transient loss of consciousness [Comment]
PMID: 31988210
ISSN: 1526-632x
CID: 5092752
Editors' note: Neurologic complications of coronavirus infections [Comment]
PMID: 32817352
ISSN: 1526-632x
CID: 5092782
Author response: Disputes, debates, dialogue, and dodgers [Comment]
PMID: 32205393
ISSN: 1526-632x
CID: 5092772
