Papers by jeremy schmahmann
Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3) is the most common autosomal dominant... more Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed.We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI.Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial a...
The Cerebellum
Ataxia rating scales are observer administered clinical outcome assessments (COAs) of the cerebel... more Ataxia rating scales are observer administered clinical outcome assessments (COAs) of the cerebellar motor syndrome. It is not known whether these COAs mirror patient experience of their disease. Here we test the hypothesis that ataxia COAs are related to and reflect patient reported symptoms and impact of illness. A concept library of symptoms and activities impacted by ataxia was created by reviewing (a) concept elicitation data from surveys completed by 147 ataxia patients and 80 family members and (b) cognitive debrief data from focus groups of 17 ataxia patients used to develop the Patient Reported Outcome Measure of Ataxia. These findings were mapped across the items on 4 clinical measures of ataxia (SARA, BARS, ICARS and FARS). Symptoms reported most commonly related to balance, gait or walking, speech, tremor and involuntary movements, and vision impairment. Symptoms reported less frequently related to hand coordination, loss of muscle control, dizziness and vertigo, muscle ...
Journal of the Neurological Sciences
arXiv (Cornell University), Dec 12, 2016
For many movement disorders, such as Parkinson's disease and ataxia, disease progression is visua... more For many movement disorders, such as Parkinson's disease and ataxia, disease progression is visually assessed by a clinician using a numerical disease rating scale. These tests are subjective, time-consuming, and must be administered by a professional. This can be problematic where specialists are not available, or when a patient is not consistently evaluated by the same clinician. We present an automated method for quantifying the severity of motion impairment in patients with ataxia, using only video recordings. We consider videos of the finger-to-nose test, a common movement task used as part of the assessment of ataxia progression during the course of routine clinical checkups. Our method uses neural network-based pose estimation and optical flow techniques to track the motion of the patient's hand in a video recording. We extract features that describe qualities of the motion such as speed and variation in performance. Using labels provided by an expert clinician, we train a supervised learning model that predicts severity according to the Brief Ataxia Rating Scale (BARS). The performance of our system is comparable to that of a group of ataxia specialists in terms of mean error and correlation, and our system's predictions were consistently within the range of inter-rater variability. This work demonstrates the feasibility of using computer vision and machine learning to produce consistent and clinically useful measures of motor impairment.
Tienda online donde Comprar Cerebellar Disorders In Children al precio 150,00 € de Jeremy Schmahm... more Tienda online donde Comprar Cerebellar Disorders In Children al precio 150,00 € de Jeremy Schmahmann | Eugen Boltshauser, tienda de Libros de Medicina, Libros de Neurologia - Neurologia infantil
the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustra... more the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
Parkinsonism & Related Disorders, 2020
Florida; has received travel reimbursement for a Biohaven Pharmaceuticals meeting. Dr. Zesiewicz ... more Florida; has received travel reimbursement for a Biohaven Pharmaceuticals meeting. Dr. Zesiewicz has served on the editorial board for Neurodegenerative Disease Management and Tremor and other Hyperkinetic Movements, and has received research support for her division for approximately 20 clinical trials for Parkinson's disease, Friedreich's ataxia, and spinocerebellar ataxias. Dr. Zesiewicz's division is a site in a multi-site trial of Parkinson's disease patients with the LRRK2 mutation and is sponsored by the National Institutes of Health but funded by Emory University. Dr. Ying is an employee of Wave Life Sciences and conducts research funded by the National Institutes of Health. The remaining authors report no conflicts of interest.
Biological Psychiatry, 2018
Methods: 24 currently depressed patients with co-morbid BPD; 84 age-, gender-, and HAMD17-matched... more Methods: 24 currently depressed patients with co-morbid BPD; 84 age-, gender-, and HAMD17-matched depressed patients without BPD and 31 healthy controls received resting state fMRI on a Siemens Prisma 3T scanner. Scans were parcellated into 264 functional nodes using the system of Power (Neuron, 72, 665-678). Subjects were assigned depression subtypes using the previously defined classifier (Drysdale, et al). Results: Functional connectivity was reduced in Limbic Networks in subjects with MDD, with or without BPD, compared to controls. In contrast, functional connectivity in the Cognitive Control Network was reduced in MDD alone compared to controls and elevated in MDD with Co-Morbid BPD relative to controls. Depression Subtype 1, characterized by anxiety, anergia and middle insomnia, was more prevalent in subjects with MDD with Co-Morbid BPD (46%) compared to in MDD alone (27%). Conclusions: Our results suggest that depression with co-morbid BPD may be characterized by different network abnormalities than depression without this co-morbidity. Further, as Depression Subtype 1 predicts the highest response rate (80%) to TMS targeting the dorsomedial prefrontal cortex (DMPFC), therapeutic TMS for depression with co-morbid BPD should be investigated prospectively.
The Cerebellum, 2019
The cerebellum is relevant for virtually all aspects of behavior in health and disease. Cerebella... more The cerebellum is relevant for virtually all aspects of behavior in health and disease. Cerebellar findings are common across all kinds of neuroimaging studies of brain function and dysfunction. A large and expanding body of literature mapping motor and non-motor functions in the healthy human cerebellar cortex using fMRI has served as a tool for interpreting these findings. For example, results of cerebellar atrophy in Alzheimer's disease in caudal aspects of Crus I/II and medial lobule IX can be interpreted by consulting a large number of task, resting-state, and gradient-based reports that describe the functional characteristics of these specific aspects of the cerebellar cortex. Here, we provide a concise summary that outlines organizational principles observed consistently across these studies of normal cerebellar organization. This basic framework may be useful for investigators performing or reading experiments that require a functional interpretation of human cerebellar topography.
Cell, 2019
Expansion of CAG trinucleotide repeats in ATXN1 causes spinocerebellar ataxia type 1 (SCA1), a ne... more Expansion of CAG trinucleotide repeats in ATXN1 causes spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease that impairs coordination and cognition. While ATXN1 is associated with increased Alzheimer's disease (AD) risk, CAG repeat number in AD patients is not changed. Here, we investigated the consequences of ataxin-1 loss of function and discovered that knockout of Atxn1 reduced CIC-ETV4/5-mediated inhibition of Bace1 transcription, leading to increased BACE1 levels and enhanced amyloidogenic cleavage of APP, selectively in AD-vulnerable brain regions. Elevated BACE1 expression exacerbated Ab deposition and gliosis in AD mouse models and impaired hippocampal neurogenesis and olfactory axonal targeting. In SCA1 mice, polyglutamine-expanded mutant ataxin-1 led to the increase of BACE1 post-transcriptionally, both in cerebrum and cerebellum, and caused axonal-targeting deficit and neurodegeneration in the hippocampal CA2 region. These findings suggest that loss of ataxin-1 elevates BACE1 expression and Ab pathology, rendering it a potential contributor to AD risk and pathogenesis. (F) Densitometry of BACE1 levels. n = 3; n.s., not significant; ***p < 0.001. (G) qRT-PCR analysis of Atxn1 and Bace1 mRNA expression in the whole brain. n = 4; **p < 0.01, ***p < 0.001 versus WT Atxn1 mRNA; ## p < 0.01 versus WT Bace1 mRNA. (H) Bace1 mRNA levels in dissected cortex and cerebellum. n = 4. (I) Representative real-time qPCR amplification graphs for cortical cDNA. RFU, relative fluorescence unit. See also Figure S1.
Movement disorders : official journal of the Movement Disorder Society, Jan 29, 2017
Dr. Zesiewicz has served as a clinical advisor for Steminent Biotherapeutics, and she has receive... more Dr. Zesiewicz has served as a clinical advisor for Steminent Biotherapeutics, and she has received travel reimbursement from the department of neurology at University of Southern Florida; has received travel reimbursement for a Biohaven Pharmaceuticals meeting. Dr. Zesiewicz has served on the editorial board for Neurodegenerative Disease Management and Tremor and other Hyperkinetic Movements, and has received research support for her division for approximately 20 clinical trials for Parkinson's disease, Friedreich's ataxia, and spinocerebellar ataxias. Dr. Zesiewicz's division is a site in a multi-site trial of Parkinson's disease patients with the LRRK2 mutation and is sponsored by the National Institutes of Health but funded by Emory University.
Tremor and other hyperkinetic movements (New York, N.Y.), 2017
Postural tremor can sometimes occur in spinocerebellar ataxias (SCAs). However, the prevalence an... more Postural tremor can sometimes occur in spinocerebellar ataxias (SCAs). However, the prevalence and clinical characteristics of postural tremor in SCAs are poorly understood, and whether SCA patients with postural tremor have different ataxia progression is not known. We studied postural tremor in 315 patients with SCA1, 2, 3, and 6 recruited from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), which consists of 12 participating centers in the United States, and we evaluated ataxia progression in these patients from January 2010 to August 2012. Among 315 SCA patients, postural tremor was most common in SCA2 patients (SCA1, 5.8%; SCA2, 27.5%; SCA3, 12.4%; SCA6, 16.9%; p = 0.007). SCA3 patients with postural tremor had longer CAG repeat expansions than SCA3 patients without postural tremor (73.67 ± 3.12 vs. 70.42 ± 3.96, p = 0.003). Interestingly, SCA1 and SCA6 patients with postural tremor had a slower rate of ataxia progression (SCA1, β = -0.91, p < 0.001; ...
Parkinsonism & Related Disorders, 2016
Background-Depression is a common comorbidity in spinocerebellar ataxias (SCAs) but its associati... more Background-Depression is a common comorbidity in spinocerebellar ataxias (SCAs) but its association with ataxia progression is not well understood. Objectives-To study the prevalence and influence of depressive symptoms in SCAs. Methods-We studied 300 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and repeatedly measured depressive symptoms by the 9-item Patient Health Questionnaire (PHQ-9) along with other clinical features including ataxia, functional status, and quality of life every 6 months for 2 years. We employed regression models to study the effects of depressive symptoms on clinical progression indexed by Scale for Assessment and Rating of Ataxia (SARA), Unified Huntington's Disease Rating Scale Part IV (UHDRS-IV) and EQ5D after adjusting for age, sex and pathological CAG repeats. Results-Comorbid depression is common in SCAs (26%). Although the baseline prevalence of depression was similar among different SCA types, suicidal ideation was more frequently reported in SCA3 (65%). Depressive symptoms were associated with SARA scores but did not significantly progress over time within 2 years or deteriorate by increased numbers of pathological CAG repeats. The effects of depression on ataxia progression varied across different SCA types. Nevertheless, depression had consistently negative and significant impact on functional status and quality of life in all SCAs, even after accounting for ataxia progression. Conclusions-Depressive symptoms are not simply the consequence of motor disability in SCAs. Comorbid depression per se contributes to different health outcomes and deserves more attention when caring patients with SCAs.
NeuroImage: Clinical, 2015
Motor abnormalities, including impaired balance and increased postural sway, are commonly reporte... more Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD. Method: In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board. Results: Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX). Conclusion: These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate.
Tremor and other hyperkinetic movements (New York, N.Y.), 2015
The contributions of vascular risk factors to spinocerebellar ataxia (SCA) are not known. We stud... more The contributions of vascular risk factors to spinocerebellar ataxia (SCA) are not known. We studied 319 participants with SCA 1, 2, 3, and 6 and repeatedly measured clinical severity using the Scale for Assessment and Rating of Ataxia (SARA) for 2 years. Vascular risk factors were summarized by CHA2DS2-VASc scores as the vascular risk factor index. We employed regression models to study the effects of vascular risk factors on ataxia onset and progression after adjusting for age, sex, and pathological CAG repeats. Our secondary analyses took hyperlipidemia into account. Nearly 60% of SCA participants were at low vascular risks with CHA2DS2-VASc = 0, and 31% scored 2 or greater. Higher CHA2DS2-VASc scores were not associated with either earlier onset or faster progression of ataxia. These findings were not altered after accounting for hyperlipidemia. Vascular risks are not common in SCAs and are not associated with earlier onset or faster ataxia progression.
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Papers by jeremy schmahmann