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Article ; Online: Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

Timm, Emily C / Purcell, Nicollette L / Ouyang, Bichun / Berry-Kravis, Elizabeth / Hall, Deborah A / O'Keefe, Joan Ann

2024 Volume 24, Issue 8

Abstract: FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 ( ...

Abstract	FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (
MeSH term(s)	Humans ; Fragile X Syndrome/genetics ; Fragile X Syndrome/physiopathology ; Tremor/genetics ; Tremor/physiopathology ; Postural Balance/physiology ; Male ; Middle Aged ; Female ; Ataxia/genetics ; Ataxia/physiopathology ; Aged ; Biomarkers ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Adult ; Prodromal Symptoms
Chemical Substances	Biomarkers ; Fragile X Mental Retardation Protein (139135-51-6) ; FMR1 protein, human
Language	English
Publishing date	2024-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s24082586
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Article ; Online: Validity and Reliability of the Insole3 Instrumented Shoe Insole for Ground Reaction Force Measurement during Walking and Running.

Cramer, Leora A / Wimmer, Markus A / Malloy, Philip / O'Keefe, Joan A / Knowlton, Christopher B / Ferrigno, Christopher

Sensors (Basel, Switzerland)

2022 Volume 22, Issue 6

Abstract: Pressure-detecting insoles such as the Insole3 have potential as a portable alternative for assessing vertical ground reaction force (vGRF) outside of specialized laboratories. This study evaluated whether the Insole3 is a valid and reliable alternative ... ...

Abstract	Pressure-detecting insoles such as the Insole3 have potential as a portable alternative for assessing vertical ground reaction force (vGRF) outside of specialized laboratories. This study evaluated whether the Insole3 is a valid and reliable alternative to force plates for measuring vGRF. Eleven healthy participants walked overground at slow and moderately paced speeds and ran at a moderate pace while collecting vGRF simultaneously from a force plate (3000 Hz) and Insole3 (100 Hz). Intraclass correlation coefficients (ICC) demonstrated excellent vGRF agreement between systems during both walking speeds for Peak 1, Peak 2, the valley between peaks, and the vGRF impulse (ICC > 0.941). There was excellent agreement during running for the single vGRF peak (ICC = 0.942) and impulse (ICC = 0.940). The insoles slightly underestimated vGRF peaks (−3.7% to 0.9% bias) and valleys (−2.2% to −1.8% bias), and slightly overestimated impulses (4.2% to 5.6% bias). Reliability between visits for all three activities was excellent (ICC > 0.970). The Insole3 is a valid and reliable alternative to traditional force plates for assessing vGRF during walking and running in healthy adults. The excellent ICC values during slow walking suggests that the Insole3 may be particularly suitable for older adults in clinical and home settings.
MeSH term(s)	Aged ; Biomechanical Phenomena ; Humans ; Mechanical Phenomena ; Reproducibility of Results ; Shoes ; Walking
Language	English
Publishing date	2022-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s22062203
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Article ; Online: Peripheral blood morphologic findings in patients with COVID-19.

Sadigh, Sam / Massoth, Lucas R / Christensen, Bianca B / Stefely, Jonathan A / Keefe, Joan / Sohani, Aliyah R

International journal of laboratory hematology

2020 Volume 42, Issue 6, Page(s) e248–e251

MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Betacoronavirus ; Blood Cell Count ; Blood Cells/ultrastructure ; COVID-19 ; Cell Lineage ; Cell Size ; Coronavirus Infections/blood ; Coronavirus Infections/therapy ; Extracorporeal Membrane Oxygenation ; Female ; Hematopoiesis ; Humans ; Male ; Middle Aged ; Neutrophils/ultrastructure ; Pandemics ; Plasma Cells/ultrastructure ; Pneumonia, Viral/blood ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; Sensitivity and Specificity
Keywords	covid19
Language	English
Publishing date	2020-07-30
Publishing country	England
Document type	Letter
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.13300
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Article: Digital gait markers to potentially distinguish fragile X-associated tremor/ataxia syndrome, Parkinson's disease, and essential tremor.

Robertson-Dick, Erin E / Timm, Emily C / Pal, Gian / Ouyang, Bichun / Liu, Yuanqing / Berry-Kravis, Elizabeth / Hall, Deborah A / O'Keefe, Joan A

Frontiers in neurology

2023 Volume 14, Page(s) 1308698

Abstract: Background: Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease that affects carriers of a 55-200 CGG repeat expansion in the : Methods: Participants with FXTAS (: Results: PD participants had reduced stride lengths ... ...

Abstract	Background: Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease that affects carriers of a 55-200 CGG repeat expansion in the Methods: Participants with FXTAS ( Results: PD participants had reduced stride lengths compared to FXTAS and ET participants under SS and DT conditions, longer turn duration than ET participants during the FP task, and less arm symmetry than ET participants in SS gait. They also had greater DTC for stride length and velocity compared to FXTAS participants. On the i-TUG, PD participants had reduced sit-to-stand peak velocity compared to FXTAS and ET participants. Stride length and arm symmetry index during the DT 2MWT was able to distinguish FXTAS and ET from PD, such that participants with shorter stride lengths were more likely to have a diagnosis of PD and those with greater arm asymmetry were more likely to be diagnosed with PD. No gait or i-TUG parameters distinguished FXTAS from ET participants in the regression model. Conclusion: This is the first quantitative study demonstrating distinct gait and functional mobility profiles in FXTAS, PD, and ET which may assist in more accurate and timely diagnosis.
Language	English
Publishing date	2023-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1308698
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Article ; Online: Improving Malignancy Detection Rates in Body Fluids Submitted to the Hematology Laboratory for Nucleated Cell Count and Differential: A Quality Improvement Study.

Zhang, M Lisa / Maglantay, Remegio J / Cunningham, Vickie L / Goodwin, Michele T / Feeney, Margaret W / Keefe, Joan / Tambouret, Rosemary H / Sohani, Aliyah R

Archives of pathology & laboratory medicine

2021 Volume 145, Issue 2, Page(s) 201–207

Abstract: Context.—: Body fluid specimens are regularly submitted to the hematology laboratory for cell count and differential. Unless there is high clinical suspicion for malignancy, most cases lack concurrent cytology review and may not benefit from more ... ...

Abstract	Context.—: Body fluid specimens are regularly submitted to the hematology laboratory for cell count and differential. Unless there is high clinical suspicion for malignancy, most cases lack concurrent cytology review and may not benefit from more focused examination for malignancy. Objective.—: To compare rates of malignancy detection before and after fluid-focused training for hematology technologists as part of a quality improvement initiative. Design.—: During an 8-week pretraining period, body fluids submitted to the cytology laboratory were correlated with concurrent hematology specimens. After slide review and training sessions for the hematology technologists, the same data were collected for a 4-week period. Discrepant cases were reviewed by hematology laboratory supervisors and pathologists. Results.—: We collected 465 pretraining and 249 posttraining body fluids with concurrent cytology and hematology evaluation. In the pretraining cohort, 48 cases (10.3%) were diagnosed as malignant by cytology; of those, 33 were detected by hematology. In the posttraining cohort, 30 cases (12.0%) were diagnosed as malignant by cytology of which 27 were detected by hematology. Of the 18 discrepant cases (all carcinomas), hematology slide review showed definite features of malignancy in 15 and no tumor cells in 3. The malignancy detection rate by the hematology laboratory significantly improved after training (68.8% versus 90.0%, P = .01). Conclusions.—: We demonstrate the comparatively lower malignancy detection rate for body fluid specimens processed in our hematology laboratory, particularly for carcinomas. Hematology technologist education/training improved the malignancy detection rate, an important quality improvement given the large proportion of body fluids undergoing hematology evaluation without concurrent cytology reviews.
MeSH term(s)	Body Fluids/cytology ; Carcinoma/diagnosis ; Cytodiagnosis ; Erythroblasts/cytology ; Hematologic Tests ; Hematology ; Humans ; Laboratories/standards ; Quality Improvement ; Specimen Handling
Language	English
Publishing date	2021-01-26
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2019-0617-OA
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Article ; Online: The Effects of Dual-Task Cognitive Interference and Environmental Challenges on Balance in Huntington's Disease.

Purcell, Nicollette L / Goldman, Jennifer G / Ouyang, Bichun / Bernard, Bryan / O'Keefe, Joan A

Movement disorders clinical practice

2019 Volume 6, Issue 3, Page(s) 202–212

Abstract: Background: Huntington's disease (HD) is characterized by chorea, balance and gait impairments, and cognitive deficits, which increase fall risk. Dual task (DT) and environmentally challenging paradigms reflect balance related to everyday life. ... ...

Abstract	Background: Huntington's disease (HD) is characterized by chorea, balance and gait impairments, and cognitive deficits, which increase fall risk. Dual task (DT) and environmentally challenging paradigms reflect balance related to everyday life. Furthermore, the impact of cognitive deficits on balance dysfunction and falls in HD is unknown. Objective: To determine the impact of DT interference, sensory feedback, and cognitive performance on balance and falls in HD. Methods: Seventeen participants with HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative balance testing with APDM inertial sensors. Postural sway was assessed during conditions of manipulated stance, vision, proprioception, and cognitive demand. The DT was a concurrent verbal fluency task. Neuropsychological assessments testing multiple cognitive domains were also administered. Results: HD participants exhibited significantly greater total sway area, jerk, and variability under single-task (ST) and DT conditions compared to controls ( Conclusions: HD participants have worse postural control under DT, limited proprioception/vision, and greater DT interference with a narrowed base and no visual input. These findings may have implications for designing motor and cognitive strategies to improve balance in HD.
Language	English
Publishing date	2019-01-16
Publishing country	United States
Document type	Journal Article
ISSN	2330-1619
ISSN (online)	2330-1619
DOI	10.1002/mdc3.12720
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Article ; Online: Tremorography in fragile X-associated tremor/ataxia syndrome, Parkinson's disease and essential tremor.

Robertson, Erin E / Hall, Deborah A / Pal, Gian / Ouyang, Bichun / Liu, Yuanqing / Joyce, Jessica M / Berry-Kravis, Elizabeth / O'Keefe, Joan A

Clinical parkinsonism & related disorders

2020 Volume 3, Page(s) 100040

Abstract: Background: Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease affecting carriers of a 55-200 CGG repeat in the : Methods: The inertial sensor based Kinesia : Results: FXTAS participants had reduced finger tap speed ... ...

Abstract	Background: Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease affecting carriers of a 55-200 CGG repeat in the Methods: The inertial sensor based Kinesia Results: FXTAS participants had reduced finger tap speed compared to those with ET, and ET had increased kinetic tremor compared to PD. Higher kinetic tremor distinguished FXTAS from PD ( Conclusions: This is the first quantitative study to compare tremor and bradykinesia in FXTAS, PD and ET. Kinetic tremor and bradykinesia measures using a quantitative inertial sensor system distinguished FXTAS from PD and ET, respectively. Such technologies may be useful for detecting precise tremor and bradykinesia abnormalities and distinguishing the tremor and bradykinesia profiles in each of these disorders.
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article
ISSN	2590-1125
ISSN (online)	2590-1125
DOI	10.1016/j.prdoa.2020.100040
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Article ; Online: Gait asymmetry in glucocerebrosidase mutation carriers with Parkinson's disease.

Gera, Anjali / O'Keefe, Joan A / Ouyang, Bichun / Liu, Yuanqing / Ruehl, Samantha / Buder, Mark / Joyce, Jessica / Purcell, Nicolette / Pal, Gian

PloS one

2020 Volume 15, Issue 1, Page(s) e0226494

Abstract: Background: GBA mutation carriers with PD (PD-GBA) are at higher risk of cognitive decline, but there is limited data regarding whether there are differences in gait dysfunction between GBA mutation and non-mutation carriers with PD.: Objectives/ ... ...

Abstract	Background: GBA mutation carriers with PD (PD-GBA) are at higher risk of cognitive decline, but there is limited data regarding whether there are differences in gait dysfunction between GBA mutation and non-mutation carriers with PD. Objectives/methods: The primary aim of this study was to use quantitative inertial sensor-based gait analysis to compare gait asymmetry in 17 PD-GBA subjects, 17 non-mutation carriers with PD, and 15 healthy control subjects using parameters that had gait laterality and were markers of bradykinesia, in particular arm swing velocity and arm swing range of motion and stride length. Results: Arm swing velocity was more symmetric in PD-GBA subjects vs. non-mutation carriers in the OFF state (12.5 +/- 8.3 vs. 22.9 +/- 11.8%, respectively, p = 0.018). In the ON-medication state, non-mutation carriers with PD, but not PD-GBA subjects, exhibited arm swing velocity (16.8 +/- 8.6 vs. 22.9 +/- 11.8%, p = 0.006) and arm range of motion (26.7 +/- 16.3 vs. 33.4 +/- 18.6%, p = 0.02) that was more asymmetric compared with the OFF-medication state. Conclusions: In the OFF medication state, arm swing velocity asymmetry may be a useful parameter in helping to distinguish GBA mutation carriers with PD from non-mutation carriers.
MeSH term(s)	Arm/physiopathology ; Case-Control Studies ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology ; Female ; Gait/physiology ; Glucosylceramidase/genetics ; Heterozygote ; Humans ; Male ; Middle Aged ; Movement Disorders/diagnosis ; Movement Disorders/etiology ; Mutation ; Parkinson Disease/complications ; Parkinson Disease/genetics ; Range of Motion, Articular
Chemical Substances	GBA protein, human (EC 3.2.1.45) ; Glucosylceramidase (EC 3.2.1.45)
Language	English
Publishing date	2020-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0226494
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Article ; Online: Open-label pilot clinical trial of citicoline for fragile X-associated tremor/ataxia syndrome (FXTAS).

Hall, Deborah A / Robertson, Erin E / Leehey, Maureen / McAsey, Andrew / Ouyang, Bichun / Berry-Kravis, Elizabeth / O'Keefe, Joan A

PloS one

2020 Volume 15, Issue 2, Page(s) e0225191

Abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that is characterized by tremor, cerebellar ataxia, frequent falls, cognitive decline, and progressive loss of motor function. There are currently no approved ... ...

Abstract	Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that is characterized by tremor, cerebellar ataxia, frequent falls, cognitive decline, and progressive loss of motor function. There are currently no approved treatments for this disorder. The purpose of this study was to determine if citicoline was safe for the treatment of tremor and balance abnormalities and to stabilize cognitive decline in patients with FXTAS. Ten participants with diagnosed FXTAS were administered 1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was the FXTAS Rating Scale score. Secondary outcomes included change in a battery of neuropsychological tests, an instrumented Timed up and go test, computerized dynamic posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom questionnaires. Safety was also evaluated. Citicoline treatment resulted in minimal adverse events in all but one subject over the course of the study. There was a significant improvement in the Beck Anxiety Inventory (p = 0.03) and the Stroop Color-Word test (p = 0.03), with all other measures remaining stable over the course of 12 months. This open-label pilot trial of citicoline for individuals with FXTAS showed that it is safe and well tolerated in this population. Registration: This trial was registered at ClinicalTrials.gov. Identifier: NCT0219710.
MeSH term(s)	Aged ; Ataxia/diagnosis ; Ataxia/drug therapy ; Cognition/drug effects ; Cytidine Diphosphate Choline/administration & dosage ; Cytidine Diphosphate Choline/adverse effects ; Female ; Fragile X Syndrome/diagnosis ; Fragile X Syndrome/drug therapy ; Humans ; Male ; Middle Aged ; Motor Activity/drug effects ; Neuropsychological Tests ; Nootropic Agents/administration & dosage ; Nootropic Agents/adverse effects ; Pilot Projects ; Postural Balance/drug effects ; Severity of Illness Index ; Time Factors ; Time and Motion Studies ; Treatment Outcome ; Tremor/diagnosis ; Tremor/drug therapy
Chemical Substances	Nootropic Agents ; Cytidine Diphosphate Choline (536BQ2JVC7)
Language	English
Publishing date	2020-02-13
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0225191
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Article ; Online: The effects of dual-task cognitive interference on gait and turning in Huntington's disease.

Purcell, Nicollette L / Goldman, Jennifer G / Ouyang, Bichun / Liu, Yuanqing / Bernard, Bryan / O'Keefe, Joan A

PloS one

2020 Volume 15, Issue 1, Page(s) e0226827

Abstract: Huntington's disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced ... ...

Abstract	Huntington's disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced gait may stress the locomotor system, revealing deficits not seen under single-task (ST). However, the impact of gait "stress tests" on HD individuals needs further investigation. Therefore, the aims of this study were to investigate whether: 1) fast-paced and dual-task walking uncover deficits in gait and turning not seen under single-task, 2) cognitive and gait outcomes relate to fall incidence, and 3) gait deficits measured with wearable inertial sensors correlate with motor symptom severity in HD as measured by the Unified Huntington's disease Rating Scale-total motor score (UHDRS-TMS). Seventeen HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative gait testing via a 25m, two-minute walk test with APDMTM inertial sensors. Gait was assessed under a 1) ST, self-selected pace, 2) fast-as-possible (FAP) pace, and 3) verbal fluency DT. The UHDRS-TMS and a cognitive test battery were administered, and a retrospective fall history was obtained. During ST, DT, and FAP conditions, HD participants demonstrated slower gait, shorter stride length, and greater lateral step and stride length variability compared to controls (p<0.00001 to 0.034). Significant dual-task costs (DTC) were observed for turns; HD participants took more time (p = 0.013) and steps (p = 0.028) to complete a turn under DT compared to controls. Higher UHDRS-TMS correlated with greater stride length variability, less double-support, and more swing-phase time under all conditions. Decreased processing speed was associated with increased gait variability under ST and FAP conditions. Unexpectedly, participant's self-reported falls did not correlate with any gait or turn parameters. HD participants demonstrated significantly greater DTC for turning, which is less automatic than straight walking, requiring coordination of body segments, anticipatory control, and cortical regulation. Turn complexity likely makes it more susceptible to cognitive interference in HD.
MeSH term(s)	Accidental Falls/statistics & numerical data ; Aged ; Case-Control Studies ; Female ; Gait ; Gait Disorders, Neurologic/etiology ; Gait Disorders, Neurologic/physiopathology ; Gait Disorders, Neurologic/psychology ; Humans ; Huntington Disease/complications ; Huntington Disease/physiopathology ; Huntington Disease/psychology ; Male ; Middle Aged ; Psychomotor Performance ; Retrospective Studies ; Walk Test
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0226827
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