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Assessment of Associations and Interventions in Movement Disorders: NSAID Use and Risk of Parkinsonian Markers in Genetic At-Risk Populations, and Examining Deep Brain Stimulation Surgery in Isolated and Acquired Dystonia
Assessment of Associations and Interventions in Movement Disorders: NSAID Use and Risk of ...
Assessment of Associations and Interventions in Movement Disorders: NSAID Use and Risk of Parkinsonian Markers in Genetic At-Risk Populations, and Examining Deep Brain Stimulation Surgery in Isolated and Acquired Dystonia

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202103151
ISBN  
9798280752047
DDC  
614.4
저자명  
San Luciano Palenzuela, Marta.
서명/저자  
Assessment of Associations and Interventions in Movement Disorders: NSAID Use and Risk of Parkinsonian Markers in Genetic At-Risk Populations, and Examining Deep Brain Stimulation Surgery in Isolated and Acquired Dystonia
발행사항  
[Sl] : University of California, San Francisco, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
123 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
주기사항  
Advisor: Tanner, Caroline.
학위논문주기  
Thesis (Ph.D.)--University of California, San Francisco, 2025.
초록/해제  
요약Parkinson's disease (PD) and dystonia are neurologic conditions with complex etiologies, significant disability, and limited treatment options. This dissertation explores the role of anti-inflammatory medication use in genetically mediated PD risk, outcomes of deep brain stimulation surgery in isolated dystonia, and a novel neuromodulation therapy for acquired dystonia in cerebral palsy (CP).The first study analyzed non-steroidal anti-inflammatory drug (NSAID) exposure in asymptomatic pathogenic variant carriers of LRRK2 and GBA1 variants -the most common genetic risk factors for PD- using longitudinal data from the Parkinson's Progression Marker Initiative (PPMI). NSAID use was not significantly associated with progression of parkinsonian markers, though wide confidence intervals and measurement challenges underscored the need for larger, detailed studies. The second study characterized short- and long-term DBS outcomes in isolated dystonia using a large, two-decade, single-center cohort. DBS consistently improved symptoms, disability, and quality of life in over 80% of patients. Favorable predictors of one-year outcomes included shorter disease duration, lower baseline severity, and having a TOR1A variant. While outcomes were generally similar between GPi and STN targets, STN stimulation was associated with greater improvement in cervical symptoms, and to a more rapid improvement. The third study explored safety and preliminary efficacy of cerebellar DBS in young patients with dyskinetic CP. Given limited success with traditional DBS targets in this condition, the cerebellum represents a promising alternative due to its role in dystonia networks and relative sparing in CP pathology. The study presents the protocol for an ongoing, single-center series of N-of-1 clinical trials with intracranial recordings and neuroimaging. Together, these studies address critical gaps in the understanding and management of neurodegenerative and neurodevelopmental disorders, paving the way for more effective, targeted interventions and improved patient outcomes.
일반주제명  
Epidemiology
일반주제명  
Neurosciences
일반주제명  
Genetics
키워드  
Cerebellum
키워드  
Cerebral palsy
키워드  
Deep brain stimulation
키워드  
Dystonia
키워드  
Genetic risk factors
키워드  
Parkinson's disease
기타저자  
University of California, San Francisco Epidemiology and Translational Science
기본자료저록  
Dissertations Abstracts International. 86-12B.
전자적 위치 및 접속  
로그인 후 원문을 볼 수 있습니다.

MARC

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■00520260202103151
■006m          o    d                
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■020    ▼a9798280752047
■035    ▼a(MiAaPQ)AAI31996971
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a614.4
■1001  ▼aSan  Luciano  Palenzuela,  Marta.▼0(orcid)0000-0002-9885-704X
■24510▼aAssessment  of  Associations  and  Interventions  in  Movement  Disorders:  NSAID  Use  and  Risk  of  Parkinsonian  Markers  in  Genetic  At-Risk  Populations,  and  Examining  Deep  Brain  Stimulation  Surgery  in  Isolated  and  Acquired  Dystonia
■260    ▼a[Sl]▼bUniversity  of  California,  San  Francisco▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a123  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-12,  Section:  B.
■500    ▼aAdvisor:  Tanner,  Caroline.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  San  Francisco,  2025.
■520    ▼aParkinson's  disease  (PD)  and  dystonia  are  neurologic  conditions  with  complex  etiologies,  significant  disability,  and  limited  treatment  options.  This  dissertation  explores  the  role  of  anti-inflammatory  medication  use  in  genetically  mediated  PD  risk,  outcomes  of  deep  brain  stimulation  surgery  in  isolated  dystonia,  and  a  novel  neuromodulation  therapy  for  acquired  dystonia  in  cerebral  palsy  (CP).The  first  study  analyzed  non-steroidal  anti-inflammatory  drug  (NSAID)  exposure  in  asymptomatic  pathogenic  variant  carriers  of  LRRK2  and  GBA1  variants  -the  most  common  genetic  risk  factors  for  PD-  using  longitudinal  data  from  the  Parkinson's  Progression  Marker  Initiative  (PPMI).  NSAID  use  was  not  significantly  associated  with  progression  of  parkinsonian  markers,  though  wide  confidence  intervals  and  measurement  challenges  underscored  the  need  for  larger,  detailed  studies.  The  second  study  characterized  short-  and  long-term  DBS  outcomes  in  isolated  dystonia  using  a  large,  two-decade,  single-center  cohort.  DBS  consistently  improved  symptoms,  disability,  and  quality  of  life  in  over  80%  of  patients.  Favorable  predictors  of  one-year  outcomes  included  shorter  disease  duration,  lower  baseline  severity,  and  having  a  TOR1A  variant.  While  outcomes  were  generally  similar  between  GPi  and  STN  targets,  STN  stimulation  was  associated  with  greater  improvement  in  cervical  symptoms,  and  to  a  more  rapid  improvement.  The  third  study  explored  safety  and  preliminary  efficacy  of  cerebellar  DBS  in  young  patients  with  dyskinetic  CP.  Given  limited  success  with  traditional  DBS  targets  in  this  condition,  the  cerebellum  represents  a  promising  alternative  due  to  its  role  in  dystonia  networks  and  relative  sparing  in  CP  pathology.  The  study  presents  the  protocol  for  an  ongoing,  single-center  series  of  N-of-1  clinical  trials  with  intracranial  recordings  and  neuroimaging.  Together,  these  studies  address  critical  gaps  in  the  understanding  and  management  of  neurodegenerative  and  neurodevelopmental  disorders,  paving  the  way  for  more  effective,  targeted  interventions  and  improved  patient  outcomes.
■590    ▼aSchool  code:  0034.
■650  4▼aEpidemiology
■650  4▼aNeurosciences
■650  4▼aGenetics
■653    ▼aCerebellum
■653    ▼aCerebral  palsy
■653    ▼aDeep  brain  stimulation
■653    ▼aDystonia
■653    ▼aGenetic  risk  factors
■653    ▼aParkinson's  disease
■690    ▼a0766
■690    ▼a0317
■690    ▼a0369
■71020▼aUniversity  of  California,  San  Francisco▼bEpidemiology  and  Translational  Science.
■7730  ▼tDissertations  Abstracts  International▼g86-12B.
■790    ▼a0034
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357226▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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