parkinson’s syge - update · james parkinson, 1817 jean-martin charcot, 1867 clinical...
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Parkinson’s Syge- Update
Kristian WingeNeurologisk AfdelingSjællands UniversitetshospitalRoskilde
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Parkinson’s sygdom
Ca 1500 f.Kr.: Indien:
Ayurvedic tekster: Kampavata (Kampa: tremor;
Vata: den væske som styrer bevægelse).
Charaka Samhita: 'Tremors of hands and feet;
difficulty with body movements'.
Behandling: Fava bønner
1500-tallet: Leonardo da Vinci beskrev en
“paralytisk” tilstand med rysten.
1700-tallet: John Hunter, beskrev patienter med
‘severe tremor on awakening who do not complain
from tiredness in the muscles.’
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“The Shaking Palsy” by James Parkinson 1817
James Parkinson, 1817
Jean-Martin Charcot, 1867
Clinical classification and differential diagnosis
Suggests the eponyme “Maladie de Parkinson”
First treatment: belladonna
Friedrich Heinrich Lewy, 1912
Intracytoplamatic inclusions
Constantin Trétiakoff, 1919
Cell loss in the substantia Nigra
Herbert Ehringer og Oleh Hornykiewicz, 1960
Loss of dopamine in the striatum
Donald Calne et al, 1992
British Brain Bank Criteria
Postuma et al. 2015
Evidence based diagnostic criteria
Parkinson J. An Essay on the Shaking Palsy; 1817.
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Hvordan udvikler sygdommen sig?
Molekylerne bag sygdommen…….
Patienternes ”Ugens” hotte emne: Cannabis!
Lægens ”Ugens” hotte emne: impuls kontrol forstyrrelser!
Hvad tænker I?
Disposition
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Parkinsons sygdomDiagnose
Cellertab i Substantia Nigra
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Grundig klinisk undersøgelse
Monitorering af sygdomsforløb
Dopa-challenge/ apomorfin test
Diagnostiske hjælpemidler
Neuro-imaging
MR/CT
SPECT 123I-FP-CIT (Datscan)
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Parkinsons sygdom
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Terminale del af dopaminergt axon
Dopamin frigivesReceptorer på
modtagercellen
123I-FP-CIT“DAT-skan”
Radioaktivt mærket cocain-derivat med høj affinitet for de præ-synaptiskemono-aminergere-uptake sites.
Præ-synaptiskDopaminTransporterDAT-receptor
Diagnostiske hjælpemidler
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123I-FP-CIT SPECT
KONTROL PARKINSONS SYGDOM
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Patient
Rigiditet
Tremor
Bradykinesi
Postural
instabilitet
Parkinsonisme
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Terminale del af
dopaminergt axon
Dopamin frigives
Receptorer på
modtagercellen
IBZM & Racloprid
123I-FP-CIT
“DAT-skan”
Diagnostiske hjælpemidler
18F-dopa
11C/18F-DTBZ
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DAT SPECT har en
Specificitet på 88%Sensitivitet på 97%
Diagnostiske hjælpemidler
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Patient
Rigidity
Tremor
Bradykinesia
Postural
instability
Parkinsonism
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Alpha-synuclein
Amyloid-beta
Tau
Proteiner i Parkinson’s syge
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Lewy bodies
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Mere end 76 komponenter er hidtil beskrevet i Lewy bodies.
De tilhører ti forskellige protein klasser, herunder
strukturelle proteiner,
alfa-synuclein-bindende proteiner,
synphilin-1-bindende proteiner,
dele af ubiquitin-proteasom systemet,
proteiner involveret i cellulært respons,
proteiner associeret med phosphorylering og signal transduktion,
cytoskeletale proteiner,
cellecyklusproteiner,
cytosoliske proteiner og andre
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Det helt dominerede protein i Lewy bodies er α-synuclein.
Består af 140 aminosyrer, <40kDaα –synuclein er et protein som er forbundet med synaptiske vesikler (Maroteaux et al., 1988).
I modsætning til mange andre proteiner involveret i neurodegeneration, er α -synuclein lokaliseret specifikt i nerveterminalen (George et al. 1995; Iwai et al., 1995).
Flere non-neurale væv, herunder erytrocytter (røde blodlegemer) udtrykker også α -synuclein (Barbour et al., 2008), men proteinet er relativt specifikt for nervesystemet (Iwai et al., 1995).
Lewy bodies
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Alpha-synuclein i Parkinsonisme
AP
D
CB
D
DL
B
MS
A
PD
PS
P
Co
ntr
ol
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
CS
F
-sy
nu
cle
in (
pg
/mL
)
* ** *
* *
Heegaard et al., Future Medicine, 2015
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Levels of total α-synuclein were significantly reduced (P < 0.05) in PD, in contrast to increased levels of α-synuclein oligomers, with a higher oligomeric/total α-synuclein ratio in PD patients when compared with controls (P< 0.001).
A combination of β-glucocerebrosidase activity, oligomeric/total α-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve = 0.87).
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Neurologisk Afdeling Roskilde
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Parasympaticus:
Tager over når der er ro og fredog især når sympaticus-tonusaftager:
Øger:TarmbevægelserSpytproduktionBlærekontraktionKontraherer pupiller
Nedsætter:PulsRespirationsfrekvens
Neurotransmitter:Acetylkolin
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Parkinsons sygdom
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Neuroner
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Usmarte nerveceller
Uchihara & Giasson. 2016
Braak et al. 2003b
Vaguskernen
Hukommelsekroppen / fordøjelse
BevægeforstyrrelserLangsomhed, stivhed, rysten
ARVMILJØ
TILFÆLDIGHEDER
Slides venligst udlånt af Per Borghammer,
Aarhus Universitet
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Neurologisk Afdeling Roskilde
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Usmarte nerveceller
Hjernen selv1% risikoLugtenerven
1% risiko
Vagus5% risiko
Sympatikus2% risiko
VAGUS50% risiko
SYMPATIKUS20% risiko
LUGTENERVEN10% risiko
GIFTSTOF 10 x RISIKO
kontrol (n=66.700)
vagotomi (n=5.300)
-47%
KOMPLET VAGOTOMI
Slides venligst udlånt af Per Borghammer,
Aarhus Universitet
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Neurologisk Afdeling Roskilde
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Despite the low sample size and quality of these studies, the data suggest cannabinoid agonists and antagonists are probably ineffective for both LID and motor symptoms although further study using different doses, formulations or target symptoms (e.g. dystonia, psychosis, sleep) may be justified. While there were no serious adverse events reported, side effects included hypotension, vertigo, visual hallucinations, dizziness and somnolence.
Neurologisk Afdeling Roskilde
Cannabis
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Neurologisk Afdeling Roskilde
Gør det selv…… ;-)
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Neurologisk Afdeling Roskilde
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Patient Miljø
MCI
Emotioner
Medicin
ICD
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MCI
Emotioner
Medicin
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Medicin
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Overordnet er impulskontrol problemer associeret til brugen af dopamin-agonisterne.
Ses også med brug af levo-dopa-præparater.
Hyppighed < 10%, få har betydelige problemer.
Amantadin kan hjælpe.
Mest effektiv er at lægge behandling om, evt. med brug af andre stoffer.
Bispebjerg Hospital – en del af Københavns Universitetshospital
Medicin
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Betegnelsen mild cognitive impairment ('let kognitiv svækkelse') angiver, at de mentale funktioner er mere svækkede end normalt for alderen, men personen er ikke dement og den basale praktiske funktionsevne i hverdagen er ikke påvirket.
MCI er ikke en specifik sygdom, men et begreb, der beskriver en tilstand præget af let svækkelse af kognitive funktioner som for eksempel hukommelse, forarbejdningstempo eller mentale styringsfunktioner.
MCI
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Definitioner
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Coping forstås som de mentale og/eller adfærds-mæssige strategier en person bruger til at håndtere nye, svære eller truende situationer.
Det er et komplekst begreb som kan dække over forskellige reaktionsmåder, hvor faktorer som fysiske ressourcer og støtte fra andre kan have indflydelse på valg af strategier i personens håndtering af dagliglivet.
Forskning tyder på, at patienter med PD har forskellige typer af strategier til håndtering af symptomerne på sygdommen, afhængig af personlighed, symptombillede og den uforudsigelighed der følger med PD i det avancerede stadie.
Coping og Parkinsons sygdom
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Groft sagt kan vi møde vores verden med brug af to strategier:
• Emotionsfokuseret
• Problemfokuseret
Hos personer med Parkinson er en problemfokuseret strategi var signifikant associeret med bedre QoL i relation til kognitive deficits, kommunikation og kropslig utilpashed (bodily discomfort).
Bucks RS, et al. Int J Geriatr Psychiatry 2011; 26:247-255.
Coping og Parkinsons sygdom
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Gruppen i Newcastle undersøgte kognitive funktioner og valg af coping strategier og fandt, at dårligt outcomevar associeret med kognitive deficits og brugen af emotionsfokuseret strategier.
Ydermere fandt man, at graden af kognitive deficits muligvis kan påvirke, hvorledes PD patienter håndterer dagligdagens dilemmaer. Hurt CS et al.,Int Psychogeriatr 2012:1656-1663
Et andet studie af pegede modsat på, at den kognitive status ikke influerede på coping strategierne, men derimod at PD patienter med eksekutive dysfunktioner benyttede forskellige coping strategier i en håndtering af deres kognitive deficits. Montel S, et al. European Journal of Neurology 2008:
1131–1134.
Coping og Parkinsons sygdom
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Patient Miljø
MCI
Emotioner
Medicin
ICD
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I er velkomne med spørgsmål….
Neurologisk Afdeling Roskilde
Klarede vi det?