Download Free Medical When does Huntingtons Disease Begin PowerPoint Presentation

When does Huntingtons Disease Begin PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Neurology, which is titled "When does Huntington’s Disease Begin?", to know about Huntington’s Disease.

Tags : Neurology, Huntington’s Disease

Published on : Aug 18, 2021 | Views : 764 | Downloads : 0

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

When does Huntington’s Disease Begin? Richard Dubinsky, MD, MPH University of Kansas 11/16/12
Slide 2-

Disclosures Current NIH/NCAM and FDA OPD 2CARE CRESTE CHDI ENROLL-HD Facilitator, redefining HD across the life span Completed: NIH: CARE-HD, PHAROS, PREDICT-HD FDA: RID-HD HSG: Longitudinal database CHDI: COHORT
Slide 3-

HD Gene Cloned 1993,from the Venezuela project Trinucleotide repeat, one of the first three described CAG expansion Gene product huntingtin htt
Slide 4-

Ross C, Lancet Neurology 2011;10:83-98
Slide 5-

CAGn Ranges <26 normal, 17 most common 26-29 rarely expand 30-36 expand, mostly 35 and 36 35-38 unstable expansion HD in future generations 39 and above: HD 80% of people with 39 repeats will develop HD
Slide 6-

What happened? Founder effect, maternal germ cell mosaicism Maternal transmission rarely changes CAGn Paternal transmission usually expands Mean expansion 6.2 Mean contraction 1.3
Slide 7-

Lee JM. Neurology 2012;78:690-5
Slide 8-

Onset of HD Traditionally defined as onset of chorea Always gradual, never sudden Cognitive, behavioral and motor changes can precede chorea
Slide 9-

Determining Clinical Onset Historical data Chorea Other domains: Behavior Cognition
Slide 10-

UHDRS-99 Copyright © HSG Ltd.
Slide 11-

HD: Juvenile Form Predominance of dystonic rigidity Early cognitive problems Prolonged survival
Slide 12-

http://promotingexcellence.org/huntingtons/
Slide 13-

Is the initial symptom disease onset? Frequent phenoconversion after predictive testing 4 x > normal population suicide rate around phenoconversion HD is not protective against other disorders
Slide 14-

HD: Progression Total Functional Capacity Five domains Occupation (3) Fiscal (3) Activities of daily living (3) Household chores (2) Residence (2) T Slope ~ 0.9/y
Slide 15-

HD Disease Models Weir Lancet Neurology 2011;10:573-9
Slide 16-

Ross C, Lancet Neurology 2011;10:83-98
Slide 17-

Ross C, Lancet Neurology 2011;10:83-98
Slide 18-

Ross C, Lancet Neurology 2011;10:83-98
Slide 19-

Lee JM. Neurology 2012;78:690-5
Slide 20-

Brinkman R Am J Hum Genet, 1997;60:1202-10
Slide 21-

Brinkman R Am J Hum Genet, 1997;60:1202-10
Slide 22-

Langbehn D, Am J Med Genet B Neuropscyh 2010;153B:397-408
Slide 23-

PREDICT-HD Prospective cohort study of gene +, asymptomatic subjects and gene – controls Near (onset < 9 years) Mid (onset 9-15 years) Far (onset > 15 years) Yearly neuroimaging, cognitive and psychomotor testing
Slide 24-

ppt slide no 24 content not found
Slide 25-

ppt slide no 25 content not found
Slide 26-

Paulsen J, JNNSP 2008;79:874-80
Slide 27-

Paulsen J, JNNSP 2008;79:874-80
Slide 28-

Paulsen J, Brain Res Bull 2010;82:201-7
Slide 29-

Aylward E, JNNSP, 2011;82:405
Slide 30-

COHORT Multi-site, international natural history of HD People with HD, those at risk, family members, some children 2006-2011 Funded by CHDI Dorsey, PLoS 2012
Slide 31-

Dorsey, PLoS 2012
Slide 32-

Dorsey, PLoS 2012
Slide 33-

Dorsey, PLoS 2012
Slide 34-

Dorsey, PLoS 2012
Slide 35-

Symbol Digit Modality / Stroop red green blue blue green red red green blue blue green red
Slide 36-

ppt slide no 36 content not found
Slide 37-

COHORT: Medication Use Dorsey, PLoS 2012
Slide 38-

Dorsey, PLoS 2012
Slide 39-

TRACK-HD Prospective, longitudinal cohort study Manifest HD Gene + (pre-manifest HD) Burden of pathology score Age x (CAG-35.5) > 250 Gene -, non-matched controls
Slide 40-

HD Cohorts PreHD-A and PreHD-B Dichotomized at median predicted years to diagnosis (Langbehn score) HD1 and HD2 Stage 1 TFC 11-13 Stage 2 TFC 7-10
Slide 41-

TRACK-HD Baseline Characteristics Tabrizi S, Lancet Neurology 2009
Slide 42-

Tabrizi S, Lancet Neurology 2009
Slide 43-

Tabrizi S, Lancet Neurology 2009
Slide 44-

Tabrizi, S Lancet Neurology. 2012,11:42-35 ∆ in Brain Volume
Slide 45-

Tabrizi, S Lancet Neurology. 2012,11:42-35 Striatal volumes
Slide 46-

Tabrizi, S Lancet Neurology. 2012,11:42-35
Slide 47-

Tabrizi, S Lancet Neurology. 2012,11:42-35
Slide 48-

Tabrizi, S Lancet Neurology. 2012,11:42-35 Neuropsychological Tests
Slide 49-

Tabrizi, S Lancet Neurology. 2012,11:42-35
Slide 50-

Tabrizi, S Lancet Neurology. 2012,11:42-35
Slide 51-

HD Clinical Trials Completed CARE-HD RID-HD TETRA-HD TREND-HD MINOS CYTE I PHEND-HD DIMEBOND 1 & 2 HSG Database PHAROS COHORT Ongoing 2CARE CRESTE-HD PRE-CREST REACH-HD PREDICT-HD
Slide 52-

Potential Treatments RNA Silencing Anti-sense oligonucleotides RNA interference
Slide 53-

Delivery Mechanisms RNAi injected into CSF Virus injected into: CSF Putamen Virus inserted into bone marrow Inserted via nanotube and heavy metal through the olfactory bulbs
Slide 54-

Bone Marrow Transplantation? Mutant htt expressed in many cells Inflammatory markers before and at phenoconversion Bone marrow derived cells get into the brain
Slide 55-

Lancet 2004;363:1432-7
Slide 56-

ppt slide no 56 content not found
Slide 57-

ppt slide no 57 content not found
Slide 58-

Aronin N NEJM 2012;367-1753
Slide 59-

Conclusion Changes that lead to HD start > 10 years before ‘phenoconversion’ Redefining the onset Research Clinical diagnosis Implications
Slide 60-

Huntington Study Group
Slide 61-

Sleep and HD Insomnia is very common Sun downing Delusions of not sleeping
Slide 62-

ppt slide no 62 content not found
Slide 63-

ppt slide no 63 content not found