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Article ; Online: [(3)H]4-(Dimethylamino)-N-[4-(4-(2-methoxyphenyl)piperazin- 1-yl)butyl]benzamide, a selective radioligand for dopamine D(3) receptors. I. In vitro characterization.

Xu, Jinbin / Chu, Wenhua / Tu, Zhude / Jones, Lynne A / Luedtke, Robert R / Perlmutter, Joel S / Mintun, Mark A / Mach, Robert H

Synapse (New York, N.Y.)

2009 Volume 63, Issue 9, Page(s) 717–728

Abstract: ... with tritium (specific activity = 80 Ci/mmol) and [(3)H]WC-10 binding to genetically cloned dopamine D(2L) and ... D(3) receptors was evaluated in vitro. [(3)H]WC-10 binds with a 66-fold higher affinity to human HEK ... However, [(3)H]WC-10 binds to rat Sf9 rD(3) receptors with a K(d) of 3.9 nM, a value that is 3-fold lower ...

Abstract	4-(Dimethylamino)-N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzamide (WC-10), a N-phenyl piperazine analog, has been shown to have high affinity and selectivity for dopamine D(3) receptors versus dopamine D(2) receptors (Chu et al. [2005] Bioorg Med Chem 13:77-87). In this study, WC-10 was radiolabeled with tritium (specific activity = 80 Ci/mmol) and [(3)H]WC-10 binding to genetically cloned dopamine D(2L) and D(3) receptors was evaluated in vitro. [(3)H]WC-10 binds with a 66-fold higher affinity to human HEK D(3) than HEK D(2L) receptors, with a dissociation constant (K(d)) of 1.2 nM at HEK D(3) receptors. However, [(3)H]WC-10 binds to rat Sf9 rD(3) receptors with a K(d) of 3.9 nM, a value that is 3-fold lower than binding to human HEK D(3) receptors and 40-fold value higher than binding to rat Sf9 rD(2L) receptors. The K(d) values obtained from saturation binding experiments were consistent with the results determined from kinetic (k(on) and k(off)) studies. The pharmacologic profiles of a series of dopaminergic drugs for inhibiting the binding of [(3)H]WC-10 to D(3) receptors was in agreement with previously reported data. In vitro autoradiography studies of rat and monkey brains show that [(3)H]WC-10 labeled D(3) sites in the striatal region.
MeSH term(s)	Animals ; Binding, Competitive ; Brain Chemistry/drug effects ; Brain Chemistry/physiology ; Cells, Cultured ; Dopamine/metabolism ; Dopamine Agents/metabolism ; Drug Interactions/physiology ; Humans ; Molecular Structure ; Pharmacokinetics ; Piperazines/chemistry ; Piperazines/metabolism ; Radioligand Assay ; Rats ; Receptors, Dopamine D3/drug effects ; Receptors, Dopamine D3/metabolism ; Synaptic Transmission/drug effects ; Synaptic Transmission/physiology ; Tritium/metabolism
Chemical Substances	Dopamine Agents ; Piperazines ; Receptors, Dopamine D3 ; WC10 compound ; Tritium (10028-17-8) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2009-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639061-4
ISSN	1098-2396 ; 0885-8276 ; 0887-4476
ISSN (online)	1098-2396
ISSN	0885-8276 ; 0887-4476
DOI	10.1002/syn.20652
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Article ; Online: Intramucosal Extent as a Marker for Advanced Disease and Survival in Gallbladder Adenocarcinoma.

Naples, Robert / Perlmutter, Breanna C / Lu, Haiyan / Allende, Daniela / Tu, Chao / Hitawala, Asif / Chadalavada, Pravallika / Padbidri, Vinay / Haddad, Abdo / Simon, Robert / Walsh, R Matthew / Augustin, Toms

The American surgeon

2024 , Page(s) 31348231220581

Abstract: Background: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. The clinical significance of focal vs diffuse GBC remains unclear.: Methods: A retrospective review was conducted on all patients with non- ... ...

Abstract	Background: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. The clinical significance of focal vs diffuse GBC remains unclear. Methods: A retrospective review was conducted on all patients with non-metastatic GBC at a quaternary care center. Pathology was reviewed, and gallbladder cancer pattern was defined based on the extent of mucosal involvement; "diffuse" if the tumor was multicentric or "focal" if the tumor was only in a single location. Patients undergoing liver resection and portal lymphadenectomy were considered to have definitive surgery. The primary outcome was overall survival and assessed by Kaplan-Meier curves. Results: 63 patients met study criteria with 32 (50.7%) having diffuse cancer. No difference was observed in utilization of definitive surgery between the groups (14 [43.8%] with focal and 12 [38.7%] with diffuse, Discussion: Patients with diffuse involvement of the gallbladder mucosa likely represent a subset with aggressive biology and worse overall survival compared to focal disease. These findings may aid surgeons in subsequent surgical and medical decision-making for patients with GBC.
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	202465-2
ISSN	1555-9823 ; 0003-1348
ISSN (online)	1555-9823
ISSN	0003-1348
DOI	10.1177/00031348231220581
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Article ; Online: Natural history and growth prediction model of pancreatic serous cystic neoplasms.

Chang, Jenny H / Perlmutter, Breanna C / Wehrle, Chase / Naples, Robert / Stackhouse, Kathryn / McMichael, John / Chao, Tu / Naffouje, Samer / Augustin, Toms / Joyce, Daniel / Simon, Robert / Walsh, R Matthew

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.

2024 Volume 24, Issue 3, Page(s) 489–492

Abstract: Objective: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical ... ...

Abstract	Objective: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection. Methods: Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package. Results: Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5-160 mm), with a mean follow-up of 72 months (range 3-266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals. Conclusion: SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.
MeSH term(s)	Humans ; Pancreatic Neoplasms/pathology ; Pancreatic Cyst/surgery ; Neoplasms, Cystic, Mucinous, and Serous ; Cystadenoma, Serous/surgery
Language	English
Publishing date	2024-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2056680-3
ISSN	1424-3911 ; 1424-3903
ISSN (online)	1424-3911
ISSN	1424-3903
DOI	10.1016/j.pan.2024.02.016
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Article ; Online: Autophagic disposal of the aggregation-prone protein that causes liver inflammation and carcinogenesis in alpha-1-antitrypsin deficiency.

Perlmutter, D H

Cell death and differentiation

2009 Volume 16, Issue 1, Page(s) 39–45

Abstract: Alpha-1-antitrypsin (AT) deficiency is a relatively common autosomal co-dominant disorder, which causes chronic lung and liver disease. A point mutation renders aggregation-prone properties on a hepatic secretory protein in such a way that the mutant ... ...

Abstract	Alpha-1-antitrypsin (AT) deficiency is a relatively common autosomal co-dominant disorder, which causes chronic lung and liver disease. A point mutation renders aggregation-prone properties on a hepatic secretory protein in such a way that the mutant protein is retained in the endoplasmic reticulum of hepatocytes rather than secreted into the blood and body fluids where it ordinarily functions as an inhibitor of neutrophil proteases. A loss-of-function mechanism allows neutrophil proteases to degrade the connective tissue matrix of the lung causing chronic emphysema. Accumulation of aggregated mutant AT in the endoplasmic reticulum of hepatocytes causes liver inflammation and carcinogenesis by a gain-of-toxic function mechanism. However, genetic epidemiology studies indicate that many, if not the majority of, affected homozygotes are protected from liver disease by unlinked genetic and/or environmental modifiers. Studies performed over the last several years have demonstrated the importance of autophagy in disposal of mutant, aggregated AT and raise the possibility that predisposition to, or protection from, liver injury and carcinogenesis is determined by the balance of de novo biogenesis of the mutant AT molecule and its autophagic disposal.
MeSH term(s)	Animals ; Autophagy/genetics ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Endoplasmic Reticulum/genetics ; Endoplasmic Reticulum/pathology ; Endoplasmic Reticulum/secretion ; Genetic Predisposition to Disease ; Hepatitis/genetics ; Hepatitis/metabolism ; Hepatitis/pathology ; Hepatocytes/pathology ; Hepatocytes/secretion ; Humans ; Metabolism, Inborn Errors/epidemiology ; Metabolism, Inborn Errors/genetics ; Metabolism, Inborn Errors/metabolism ; Metabolism, Inborn Errors/pathology ; Mutation ; Neutrophils/pathology ; Neutrophils/secretion ; Peptide Hydrolases/genetics ; Peptide Hydrolases/metabolism ; alpha 1-Antitrypsin/genetics ; alpha 1-Antitrypsin/secretion ; alpha 1-Antitrypsin Deficiency/epidemiology ; alpha 1-Antitrypsin Deficiency/genetics ; alpha 1-Antitrypsin Deficiency/metabolism ; alpha 1-Antitrypsin Deficiency/pathology
Chemical Substances	alpha 1-Antitrypsin ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2009-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/cdd.2008.103
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Article ; Online: Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.

Nature communications

2024 Volume 15, Issue 1, Page(s) 2750

Abstract: The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD ... ...

Abstract	The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.
MeSH term(s)	Humans ; alpha-Synuclein/chemistry ; Cryoelectron Microscopy ; Lewy Bodies/pathology ; Lewy Body Disease/pathology ; Parkinson Disease/pathology
Chemical Substances	alpha-Synuclein ; SNCA protein, human
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46832-5
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Article ; Online: Interrater reliability of motor severity scales for hemifacial spasm.

Lee, Ha Yeon / Park, Ingyun / Luu, Minnie P / Zhao, Jerry / Vu, Jeanne P / Cisneros, Elizabeth / Berman, Brian D / Jinnah, H A / Kim, Han-Joon / Liu, Catherine Y / Perlmutter, Joel S / Richardson, Sarah Pirio / Weissbach, Anne / Stebbins, Glenn T / Peterson, David A

Journal of neural transmission (Vienna, Austria : 1996)

2023 Volume 130, Issue 10, Page(s) 1269–1279

Abstract: To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, ...

Abstract	To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants' motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee's scale), clinical grading of spasm intensity (Chen's scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc's scale). In Round 2, clinicians rated the same cohort with simplified scale wording after consensus training. For each round, we evaluated the IRR using the intraclass correlation coefficient [ICC (2,1) single-rater, absolute-agreement, 2-way random model]. The scales exhibited IRR that ranged from "poor" to "moderate"; the mean ICCs were 0.41, 0.43, 0.47, 0.43, and 0.65 for the JRS, HSGS, Lee's, Chen's, and Tunc's scales, respectively, for Round 1. In Round 2, the corresponding IRRs increased to 0.63, 0.60, 0.59, 0.53, and 0.71. In both rounds, Tunc's scale exhibited the highest IRR. For clinical assessments of HFS motor severity based on video observations, we recommend using Tunc's scale because of its comparative reliability and because clinicians interpret the scale easily without modifications or the need for consensus training.
MeSH term(s)	Humans ; Hemifacial Spasm/diagnosis ; Reproducibility of Results ; Dystonia
Language	English
Publishing date	2023-07-19
Publishing country	Austria
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	184163-4
ISSN	1435-1463 ; 0300-9564
ISSN (online)	1435-1463
ISSN	0300-9564
DOI	10.1007/s00702-023-02667-w
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Article ; Online: Longitudinal predictors of health-related quality of life in isolated dystonia.

Junker, Johanna / Hall, James / Berman, Brian D / Vidailhet, Marie / Roze, Emmanuel / Bäumer, Tobias / Malaty, Irene A / Shukla, Aparna Wagle / Jankovic, Joseph / Reich, Stephen G / Espay, Alberto J / Duque, Kevin R / Patel, Neepa / Perlmutter, Joel S / Jinnah, H A / Brandt, Valerie / Brüggemann, Norbert

Journal of neurology

2023 Volume 271, Issue 2, Page(s) 852–863

Abstract: Objective: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia.: Methods: Out of 603 dystonia patients prospectively enrolled in the Natural History ...

Abstract	Objective: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia. Methods: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year. Results: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). Higher GAD scores at baseline predicted lower HR-QoL related to general health, pain and emotional well-being, whereas higher SAD scores predicted higher pain-related QoL after 2 years (all p ≤ 0.006). Dystonia severity at baseline predicted social functioning (p = 0.002). Neither dystonic tremor, age, or sex predicted HR-QoL at 2 years. Two latent categories were revealed across the three-time points: Category 1 with higher total HR-QoL scores (mean HR-QoL = 74.4% ± 16.1), susceptible to symptoms of depression and SAD, and Category 2 with lower total HR-QoL scores (mean HR-QoL = 45.5% ± 17.6), susceptible to symptoms of GAD. HR-QoL improved over the course of 1 year irrespective of the use of BoNT. Conclusion: The longitudinal impact of psychiatric symptoms on HR-QoL emphasizes the importance of incorporating mental health treatment, in particular also the therapy of anxiety disorders, into treatment regimens for dystonia.
MeSH term(s)	Humans ; Child, Preschool ; Dystonia ; Quality of Life/psychology ; Tremor/diagnosis ; Dystonic Disorders/drug therapy ; Pain
Language	English
Publishing date	2023-10-15
Publishing country	Germany
Document type	Multicenter Study ; Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-023-12022-4
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Article ; Online: "Another tool in the toolkit"-Perceptions, suggestions, and concerns of emergency service providers about the implementation of a supervised consumption site.

Perlmutter, David / Wettemann, Courteney / Fockele, Callan Elswick / Frohe, Tessa / Williams, Will / Holland, Nathan / Oliphant-Wells, Thea / Meischke, Hendrika / van Draanen, Jenna

The International journal on drug policy

2023 Volume 115, Page(s) 104005

Abstract: Background: As Supervised Consumption Sites (SCS) are implemented in the United States, it is important to consider the needs and perceptions of impacted stakeholders. Emergency service providers (ESP) have a central role in responding to the overdose ... ...

Abstract	Background: As Supervised Consumption Sites (SCS) are implemented in the United States, it is important to consider the needs and perceptions of impacted stakeholders. Emergency service providers (ESP) have a central role in responding to the overdose epidemic. This study intended to assess the how ESP perceive the potential implementation of an SCS in their community, as well as solicit program design and implementation-related concerns and suggestions. Methods: In-depth interviews were conducted by videoconference with 22 ESP, including firefighters, paramedics, police, and social workers in King County, Washington, USA. Data were analyzed using a thematic analysis approach. Results: Participants expressed the importance of feeling safe while responding to calls where drug use is involved and highlighted how this perception would be linked to ESP response times to calls from an SCS. Suggestions for improving the perceived safety of an SCS included training program staff in de-escalation as well as planning the layout of the SCS to accommodate ESP. The inadequacy of the emergency department as a point of care for PWUD was also identified as a theme, and some participants expressed enthusiasm regarding the prospect of the SCS as an alternative destination for transport. Finally, support for the SCS model was conditional on the appropriate utilization of emergency services and a reduction in call volume. Participants listed clarifying roles and pursuing opportunities for collaboration as ways to ensure appropriate utilization and maintain positive working relationships. Conclusion: This study builds on literature regarding stakeholder perceptions of SCS by focusing on the perceptions of a critically important stakeholder group. Results enhance understanding of what motivates ESP to support SCS implementation in their community. Other novel insights pertain to ESP thoughts about alternative care delivery models and strategies for emergency department visit diversion.
MeSH term(s)	Humans ; Substance-Related Disorders ; Drug Overdose/epidemiology ; Emergency Medical Services ; Police ; Delivery of Health Care
Language	English
Publishing date	2023-03-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010000-0
ISSN	1873-4758 ; 0955-3959
ISSN (online)	1873-4758
ISSN	0955-3959
DOI	10.1016/j.drugpo.2023.104005
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Article ; Online: Assessing civility at an academic health science center: Implications for employee satisfaction and well-being.

Campbell, Lisa A / LaFreniere, Jenna R / Almekdash, Mhd Hasan / Perlmutter, David D / Song, Huaxin / Kelly, Patricia J / Keesari, Rohali / Shannon, Kay Leigh

PloS one

2021 Volume 16, Issue 2, Page(s) e0247715

Abstract: Incivilities are pervasive among workers in healthcare institutions. Previously identified effects include deterioration of employee physical and mental health, absenteeism, burnout, and turnover, as well as reduced patient safety and quality of care. ... ...

Abstract	Incivilities are pervasive among workers in healthcare institutions. Previously identified effects include deterioration of employee physical and mental health, absenteeism, burnout, and turnover, as well as reduced patient safety and quality of care. This study documented factors related to organizational civility at an academic health sciences center (AHSC) as the basis for future intervention work. We used a cross-sectional research design to conduct an online survey at four of five campuses of an AHSC. Using the Organizational Civility Scale (OCS), we assessed differences across gender, race (White and non-White) and job type (faculty or staff) in the eleven subscales (frequency of incivility, perceptions of organizational climate, existence of civility resources, importance of civility resources, feelings about current employment, employee satisfaction, sources of stress, coping strategies, overall levels of stress/coping ability, and overall civility rating). Significant gender differences were found in six of the eleven subscales: perception of organizational climate (p < .001), existence of civility resources (p = .001), importance of civility resources (p < .001), frequency of incivilities (p < .001), employee satisfaction (p = .002), and overall civility rating (p = .007). Significant differences between respondents by self-identified race were found only in one subscale: existence of civility resources (p = .048). Significant differences were found between faculty and staff in four subscales: perception of organizational climate (p = .001), importance of civility resources (p = .02), employee satisfaction (p = .01), and overall levels of stress (p = .03). Results suggest that gender and employment type differences exist in the perception of organizational climate at the academic health center, while significant racial differences only occurred in reference to reported existence of civility resources. Attention to these differences should be incorporated into the development of programs to address the problem.
MeSH term(s)	Absenteeism ; Academic Medical Centers/organization & administration ; Adaptation, Psychological ; Adolescent ; Adult ; Burnout, Professional/psychology ; Cross-Sectional Studies ; Faculty/psychology ; Female ; Humans ; Incivility ; Job Satisfaction ; Male ; Middle Aged ; Occupational Health ; Personal Satisfaction ; Personnel Turnover ; Surveys and Questionnaires ; Workplace/psychology ; Young Adult
Language	English
Publishing date	2021-02-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0247715
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Article ; Online: Neuropathology of blepharospasm.

Fagan, Maggie / Scorr, Laura / Bernhardt, Doug / Hess, Ellen J / Perlmutter, Joel S / Pardo, Carlos A / Jinnah, H A

Experimental neurology

2021 Volume 346, Page(s) 113855

Abstract: Background: The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal repetitive movements or postures. In blepharospasm, the face is affected, leading to excessive eye blinking and spasms of muscles ... ...

Abstract	Background: The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal repetitive movements or postures. In blepharospasm, the face is affected, leading to excessive eye blinking and spasms of muscles around the eyes. The pathogenesis of blepharospasm is not well understood, but several imaging studies have implied subtle structural defects in several brain regions, including the cerebellum. Objective: To delineate cerebellar pathology in brains collected at autopsy from 7 human subjects with blepharospasm and 9 matched controls. Methods: Sections from 3 cerebellar regions were sampled and processed using Nissl and silver impregnation stains. Purkinje neurons were the focus of the evaluation, along with as several other subtle pathological features of cerebellar dysfunction such as Purkinje neuron axonal swellings (torpedo bodies), proliferation of basket cell processes around Purkinje neurons (hairy baskets), empty baskets (missing Purkinje neurons), and displacement of cell soma from their usual location (ectopic Purkinje neurons). Results: The results revealed a significant reduction in Purkinje neuron and torpedo body density, but no changes in any of the other measures. Conclusions: These findings demonstrate subtle neuropathological changes similar to those reported for subjects with cervical dystonia. These findings may underly some of the subtle imaging changes reported for blepharospasm.
MeSH term(s)	Aged ; Aged, 80 and over ; Blepharospasm/pathology ; Cerebellum/pathology ; Female ; Humans ; Male ; Middle Aged ; Purkinje Cells/pathology
Language	English
Publishing date	2021-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2021.113855
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