Patoligia Extrapiramidala VERSIUNE P STUDENTI

Patologia
extrapiramidal
Boala Parkinson
Probleme de
diagnostic
Principii de
tratament
Istorie
Micri involuntare
tremurtoare, care
micoreaz fora
muscular... cu
tendina nclinrii
corpului anterior [...],
simurile i inteligena
fiind nevtmate.
James Parkinson
(1817)
Istorie
An Essay on the Shaking Palsy

James Parkinson - primul, care
a descris n mod cert maladia,
care i poart numele
Descrierea a 6 cazuri din
practica sa clinic sau observate
n zona cartierului unde locuia
Doar unul din ele a fost examinat
detaliat
Descrierea pacienilor a fost
detaliat i exact
Unul din scopurile crii a fost
apelul i ncurajarea medicilor s
studieze aceast maladie
Istorie
60 de ani mai trziu

Jean-Martin Charcot
a propus ca aceast
entitate s fie numit
Boala Parkinson
Istorie
James Parkinson
11 aprilie 1755 21 decembrie 1824
Studii n London Hospital Medical
College 6 luni (vrsta 20 ani)
6 ani de ucenicie la tatl su (medic
chirurg)
Activitati medico-tiinifice
n afar de The Shaking Palsy', a scris

articole i cri n diverse domenii:
Bolile psihice i reforme n actele normative
i regimul caselor de alienai mintali
Efectul aciunii fulgerului asupra
organismului
Deosebirea dintre tulburrile de memorie,
disfazie i nebunie
A raportat primul caz de apendicit
complicat cu peritonit i deces
Probleme de instruire a studenilor n
medicin
Repere istorice n cercetarea

bolii Parkinson
Istorie
1817:
J. Parkinson Essay on the Shaking Palsy
1873:
Charcot a descris i sistematizat tabloului clinic i
efectuat primele ncercri de tratament
1919:
Trtiakoff Descoperirea degenerescenei
substanei negre substratul anatomic al BP
1957:
Carlsson Descoperirea deficienei dopaminice n
striatum ca substrat biochimic (Premiul Nobel, 2000)
1961:
Birkmayer & Hornykiewicz Utilizarea clinic a L-dopa
1974:
Calne Introducerea agonitilor dopaminergici
Definiie
Boala Parkinson
Simptome Clinice: Sindrom neurodegenerativ
cronic cu evoluie progresiv
Patogeneza: Degenerarea neuronilor
dopaminergici a sistemului
nigrostriatal
Etiologie:
Idiopatic vs. formele

simptomatice
Epidemiologie
Aspecte epidemiologice
Afecteaz pna la 0.3% din populaia general
Circa 1% - 3% din cei afectai 65 ani
n Republica Moldova nu au fost efectuate cercetri
epidemiologice, dar teoretic numrul pacienilor cu MP
poate fi estimat la 10-12.000
Circa 25% de pacieni cu Parkinson rmn nediagnosticai
Expectaia medie de via este uor redus
Lang & Lozano. N Engl J Med. 1998;339:1044-1053.

Olanow & Koller. Neurology. 1998;50(3 suppl 3):S1-S57.
Tuite & Ebbitt. Semin Neurol. 2001;21:9-14.
Epidemiologie
Incidena n funcie de vrst a cazurilor

noi de maladia Parkinson
Incidena
(la 100,000 populaie)
250
USA
200
Islanda
Japonia
150
Estonia
Finlanda
100
50
0
30-39
40-49
50-59
60-69
Vrsta
70-79
80+
Epidemiologie
Factorii de risc
Vrsta
Antecedente familiale
Posibili: intoxicaii cu erbicide,
pesticide, metale grele
Discutabili: Personalitatea
-
Introversie
- Rigiditate
- Inflexibilitate
Viaa n mediu rural

Factori protectivi posibili:
Consum de ceai i cafea
Nicotin
Butterfield PG et al. Neurology. 1993;43:1152. Lang AE et al. N Engl J Med. 1998;339(15):1050.

Olanow CW et al. Neurology. 2001;56(suppl 5):S1-S2.Rybicki BA et al. Movement Disorders.
1993;8:87
Degenerescena celulelor
n substana nigra
Patogeneza
Patogeneza
PARK
PARK 11
Cauzele genetice
Locus:
Locus: Cromosomul
Cromosomul4q21
4q21
Produs
Produsgenetic:
genetic: -Synuclein
-Synuclein
PARK
PARK 22
(Polymeropoulos
(Polymeropoulosetetal.,
al.,1997)
1997)
(Parkinsonismul juvenil
autosomal recisiv)
Locus:
Locus: Cromosomul
Cromosomul6q25
6q25
Produs
Produsgenetic:
genetic: Necunoscut
Necunoscut (Kitada
(Kitadaet
etal.,
al.,1998)
1998)
PARK
PARK 33
Locus:
Locus:Cromosomul
Cromosomul2p13
2p13
Produs
Produsgenetic:
genetic: Necunoscut
Necunoscut
Mutaii parkin de diferite
tipuri
- deleii
- mutaii punctiforme
- duplicarea exonilor etc
(Gasser
(Gasseret
etal.,
al.,1998)
1998)
PARK
4,4,5.....
10
PARK
5.....
10
PARK
4,
5.....
PARKIN 4 10
10
Corpii Lewy
Date microscopice
Patogeneza
Patogeneza
Corpii Lewy. Modelul
anatomo-patologic de cascad
Etapele formrii
corpilor Lewy :
I. Nucleul dorsal al
n. vag/bulbul olfactor
II. Trunchiul cerebral/formaia
reticulat
III. Nucleii bazali/amigdala/
substana nigra
IV. Mesocortex
V. Neocortex ariile asociative
VI. Neocortex ariile senzitive i
motorii
(Braak et al., 2002)

presimptomatic
simptomatic
60%
II
III
40%
IV
VI
Symptome
Semne clinice cardinale

Bradikinezia
Rigiditatea
Tremorul
Instabilitatea postural
Orphan Man with Cap and Walking Stick
by Vincent van Gogh, 1882
Simptomele principale:
Tremorul, postura -
Simptome
Simptome
Simptomele principale: Rigiditatea
Tulburri de vorbire,
tulburri de mers-
Simptome
Bradikinezie,
Instabilitate postural-
Symptome
Instabilitate postural-
Simptome
Simptome
Simptomele asociate non-motorii

Vegetative
Vegetative
Seboree
Seboree
Sialoree
Sialoree
Tulburridigestive
digestive
Tulburri
Tulburride
de miciune
miciunei
i de
de poten
poten
Tulburri
Hipotensiuneortostatic
ortostatic
Hipotensiune
Tulburride
de termoreglare
termoreglare
Tulburri
Psihopatologice
Psihopatologice
Depresie
Depresie
Bradifrenie
Bradifrenie
Demen
Demen
23
Simptome
Simptome frecvente n debutul BP
Dureri cervicale i brahiale

Depresie/reducerea drive-ului
Tulburri senzoriale: ex. tulburri olfactive
Modificarea scrisului
Tip echivalent
Tulburri de vorbire
42%
Tulburri de mers
Redoare/akinezie
34%
Dominarea tremorului
24%
Tratament
Strategii de
tratament
n
Boala Parkinson
Punctele de atac a terapiei

medicamentoase
Dopa
decarboxylase
Tratament
Agonit
Dopaminergic
L-Dopa
Antgonist
Glutamatic
Inhibitorii
MAO-B
Glu
(3,4-Dihydr-oxy-phenyl-acetic acid)
Presynapse
Glial cell
Boala Parkinson:
Tratament de debut
Blocarea selectiv
a inhibitorilor MAO-B
Se utilizeaz n terapia simptomatic

de debut a bolii Parkinson
Selegilina (Selegos, Jumex, Cognitiv,
LEVODOPA
revoluie
n tratamentul
Bolii Parkinson
Levodopa
Madopar
Nacom
Isicom
Simptome
BP Diskinezii
A II revoluie
n tratamentul
Bolii Parkinson
Agonitii
dopaminergici
Agonitii
dopaminergici
REQUIP
(ropinirole)
Tratament
Agonitii Dopaminergici
Agoniti dopaminergici derivai de Ergot
Prima generaiei
Bromocriptine
Pergolide
Agoniti dopaminergici derivai nonergolinici

A doua generaie
REQUIP (ropinirole)
Pramipexole
Olanow CW et al. Neurology. 2001;56(suppl 5):S14.
Tratament
Agonitii dopaminergici (I)

Efecte antiparkinsoniene comparabile cu
L-dopa
Se utilizeaz n stadiile 1 i 2 (Hoehn, Yahr)
Reduce semnificativ riscul complicaiilor
motorii
- LD: stimulare pulsatil, discontinu
(T 1 -3 ore)
- AD: durata de aciune mult mai lung
(T 6 ore)
Tratament
Controlul simptomelor Prevenirea complicaiilor

motorii
Levodopa
Eficien cert
Nu se utilizeaz
Levodopa eliberare lent
Eficien cert
Ineficien cert
Apomorfina
Nu s-a utilizat n faza precoce
Bromocriptina
Eficien probabil
Eficien probabil
Cabergolina
Eficien probabil
Eficien cert
Dihidroergocriptina
Eficien cert
Date insuficiente
Lisuride
Eficien probabil
Eficien posibil
Pergolide
Eficien cert
Eficien probabil
Piribedil
Eficien possibil
Date insuficiente
Pramipexol
Eficien cert
Eficien cert
Ropinirol
Eficien cert
Eficien cert
Selegilina
Eficien cert
Ineficien cert
Rasagilina
Eficien cert
Date insuficiente
Entacapone
Date insuficiente
Date insuficiente
Tolcapone
Date insuficiente
Date insuficiente
Amantadina
Eficien probabil
Date insuficiente
Anticolinergicii
Eficien probabil
Date insuficiente
Reabilitare
Date insuficiente
Eficien probabil
Chirurgie
Nu se utilizeaz in faza precoce
Kineziile
paradoxale n
Boala Parkinson
Kineziile paradoxale n
Boala Parkinson
Un viitor mai putin sumbru pentru

persoanele afectate de BP
Diverse forme de Tremor

non-parkinsonian
Tremorul de aciune
Tremorul de atitudine
Tremorul postural
Coreea-
Spasmul de torsiune
Torticolisul-
Blefarospasm
Crampa scriitorului
Hemispasmul facial
Ticurile
Diskinezii Tardive
Hemibalism-
Bibalism-
Partile cerebelului
Cerebelul
Morfologia externa:
2 lobi laterali
lob median
Filogenetic si functional:
arheocerebelul
paleocerebelul
neocerebelul
Tonus muscular
Maduva spinarii
Motilitatea
voluntara
Paleocerebel
Cortex
Neocerebelul
Nucleii vestibulari
Echilibrul
Arheocerebelul
(lobul floculonodular)
Cerebelul
I Substanta alba
fibre nervoase intrinseci
fibre nervoase extrinseci
II Substanta cenusie
Nuclei nervosi: - n.fastigiali
- n. globos
- n. emboliform - n. dintat
Scorta cerebeloasa:
> stratul molecular
> stratul intermediar
> stratul granular
Functiile cerebelului
Mentine la un nivel constant starea de excitatie a

scoartei cerebrale
Asigura postura, echilibrul corporal si locomotia
Coordoneaza miscarile voluntare
Mentine tonusul muscular
+
Functia cognitiva
Ataxia Cerebeloas
Ataxia Paroxistic Ereditar
Mioclonusul de aciune
(Sndr Lance-Adam)
Simptome
Diagnostic
Boala Parkinson: un diagnostic dificil ?
Diagnosticul iniial al BP stabilit de neurologi generaliti n fazele

iniiale ale bolii a fost incorect n 24% - 35% fiind confruntate cu
rezultatele investigaiilor post-mortem
1/3 din pacienii cu MSA supravegheai de specialiti n micri

anormale (movements disorders) au fost tratai incorect pn la
deces
41-88% pacieni cu PSP au beneficiat de un diagnostic corect n

timpul vieii (supravegheai de specialiti n micri anormale)
United Kingdom Parkinson's Disease Society Brain Bank Diagnostic

Criteria for Parkinsons Disease (20% greeli)
Jankovic, et al.,Joseph MD; Rajput, Ali H. MD; McDermott, Michael P. PhD; Perl, Daniel P. MD; for the Parkinson
Study Group 2000
Diagnostic
Clasificarea Parkinsonismului
Parkinsonism
Primar (degenerativ)
Atipic
PSP
B. Parkinson
Secundar
Iatrogen
Toxic
Metabolic
MSA
Vascular
CBD
Infecios
DLBD
Traumatic
Special Article
Practice Parameter: Diagnosis and

prognosis of new onset Parkinson disease
(an evidence-based review)
Report of the Quality Standards Subcommittee of the
American Academy of Neurology
O. Suchowersky, MD; S. Reich, MD; J. Perlmutter, MD; T.
Zesiewicz, MD; G. Gronseth, MD;
and W.J. Weiner, MD NEUROLOGY 2006;66:968975
Special Article
Practice Parameter: Treatment of

Parkinson disease with motor
fluctuations and dyskinesia
(an evidence-based review)
Report of the Quality Standards Subcommittee of the
American Academy of Neurology
From the University of Kansas Medical Center (R.P., K.E.L., G.G.), Kansas City; Emory University School of Medicine (S.A.F.),
Atlanta, GA; Baylor College of Medicine (W.G.O.), Houston, TX; Stanford University Hospital (H.B.-S.), San Francisco, CA;
National Institutes of Health (M.H.), Bethesda, MD; Toronto Western Hospital (J.M.), Canada; Fort Wayne Neurological Center
(J.S.), Fort Wayne, IN; and University of Maryland School of Medicine (W.J.W.),Baltimore.
NEUROLOGY 2006;66:983995
Diagnostic
United Kingdom Parkinson's Disease Society Brain

Bank Diagnostic Criteria for Parkinsons Disease
Etapa 1: Diagnostic de Boala Parkinson

Bradikinezia plus cel puin unul din
urmtoarele:
Redoare muscular
Tremor de repaus 46 Hz
Instabilitate ce nu este condiionat de o
tulburare primar vizual, vestibular,
cerebeloas sau proprioceptiv
Diagnostic

Rigiditate muscular
Bradikinezie + 1
Tremor de repaus (4 6 Hz)

Instabilitate postural
Watts & Koller. Movement Disorders: Neurologic Principles and Practice. 1997.
Diagnostic

Etapa 2: Trsturi clinice ce ndeprteaz diagnosticul de
Boala Parkinson
AVC repetate cu progresia fenomenelor parkinsoniene

TCC repetate
Encefalit n antecedente
Tumoare cerebral sau hidrocefalie comunicant la CT
Semne cerebeloase
Semnul Babinski
Paralizie supranuclear
Demen precoce sever cu tulburri de memorie, limbaj
i praxis
Diagnostic

Bank Diagnostic Criteria for Parkinsons Disease II
Etapa 2: Trsturi clinice ce ndeprteaz diagnosticul de
Boala Parkinson
Tulburri vegetative precoce severe

Tratament cu neuroleptice anterior de apariia simptomelor
>1 rud afectat
Remisiuni de durat
Simptomatic strict unilateral dup 3 ani
Rspuns negativ la doze mari de levodopa (dac e exclus
malabsorbia)
Expunere la 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)
Diagnostic

Etapa 3: Diagnostic definit de BP ( 3/8 )
Debut unilateral
Prezena tremorului de repaus
Maladie progresiv
Asimetrie persistent mai ales a prii afectate
din debutul bolii
Rspuns excelent (70100%) la levodopa
Coree sever indus de levodopa
Rspuns la levodopa 5 ani
Evoluie clinic 10 ani
Diagnostic
Criteriile clinice diagnostice adiionale

(cel puin 3/7 necesit a fi prezente)
Debut unilateral al maladiei

Tremor de repaus/ori cel puin 2 din semnele
majore
Evoluie progresiv
Rspuns bun (70-100%) la L-dopa
Diskinezii induse de L-Dopa
Fluctuaii ale performanelor motorii
Lipsa semnelor atipice
Gerlach, Reichmann & Riederer, Springer Verlag, 2003
Stadiile evoluiei BP conform

Hoehn i Yahr (1967)
St. 1 simptome unilaterale
St. 1,5 simptome unilaterale plus implicarea musculaturii axiale
St. 2 simptome bilaterale fr instabilitate
St. 2,5 - simptome bilaterale, instabilitate postural compensat
St. 3 - simptome bilaterale, instabilitate postural
(pacientul are periodic nevoie de ajutor)
St. 4 handicap sever, dar n zile (ore) bune i poate

pstra ortostaiunea i merge fr ajutor
St. 5 fr ajutor rmne imobilizat la pat
(necesit ajutor permanent)
Investigaii suplimentare n diagnosticul

diferenial al parkinsonismului
I. Diagnosticul genetic
II. Teste olfactive
III. Diagnosticul neuroimagistic i nuclear
IV. Teste vegetative cardiovasculare
V. Diagnostic neurofiziologic
VI. Scanarea ultrosonografic a subst. nigra
VII. Diagnosticul de laborator

I. Diagnosticul genetic
II. Teste olfactive
III. Diagnosticul neuroimagistic i nuclear
IV. Teste vegetative cardiovasculare
V. Diagnostic neurofiziologic
VI. Scanarea ultrosonografic a subst.nigra
VII. Diagnosticul de laborator

Scanarea ultrosonografic a subst. nigra
25 pts BP (criterii clinice)
Hiperecogenitate 24/25
25 pts Parkinsonism atipic (MSA -16; PSP- 9)
Hiperecogenitatea 2/25
(P<0,001)
Walter U et al., Neurology 2003; 60: 64-67
Cnd ncepem tratamentul ?

Momentul oportun pentru iniierea tratamentului nu este
definit uniivoc:
Iniierea terapiei se recomand atunci cnd simptomele
interfereaz cu viaa pacientului
Alegerea medicamentului va fi condiionat de

combinarea factorilor obiectivi i subiectivi:
Consideraii ce in de produsul concret (eficiena, securitatea,
costul, etc.)
Consideraii ce in de pacient (vrsta, activitatea, comorbiditatea ,
etc.)
Consideraii ce in de ambian (disponibilitatea medicamentului,
tipul de asigurare medical, etc.)
Dou aspecte sunt eseniale :

Controlul simptomelor parkinsonismului
Prevenia complicaiilor motorii
Tratament

motorii
Levodopa
Eficien cert
Nu se utilizeaz
Eficien cert
Ineficien cert
Apomorfina
Bromocriptina
Eficien probabil
Eficien probabil
Cabergolina
Eficien probabil
Eficien cert
Dihidroergocriptina
Eficien cert
Date insuficiente
Lisuride
Eficien probabil
Eficien posibil
Pergolide
Eficien cert
Eficien probabil
Piribedil
Eficien possibil
Date insuficiente
Pramipexol
Eficien cert
Eficien cert
Ropinirol
Eficien cert
Eficien cert
Selegilina
Eficien cert
Ineficien cert
Rasagilina
Eficien cert
Date insuficiente
Entacapone
Date insuficiente
Date insuficiente
Tolcapone
Date insuficiente
Date insuficiente
Amantadina
Eficien probabil
Date insuficiente
Anticolinergicii
Eficien probabil
Date insuficiente
Reabilitare
Date insuficiente
Eficien probabil
Chirurgie
Tratament

motorii
Levodopa
Eficien cert
Nu se utilizeaz
Eficien cert
Ineficien cert
Apomorfina
Bromocriptina
Eficien probabil
Eficien probabil
Cabergolina
Eficien probabil
Eficien cert
Dihidroergocriptina
Eficien cert
Date insuficiente
Lisuride
Eficien probabil
Eficien posibil
Pergolide
Eficien cert
Eficien probabil
Piribedil
Eficien possibil
Date insuficiente
Pramipexol
Eficien cert
Eficien cert
Ropinirol
Eficien cert
Eficien cert
Selegilina
Eficien cert
Ineficien cert
Rasagilina
Eficien cert
Date insuficiente
Entacapone
Date insuficiente
Date insuficiente
Tolcapone
Date insuficiente
Date insuficiente
Amantadina
Eficien probabil
Date insuficiente
Anticolinergicii
Eficien probabil
Date insuficiente
Reabilitare
Date insuficiente
Eficien probabil
Chirurgie
Tratament

motorii
Levodopa
Eficien cert
Nu se utilizeaz
Eficien cert
Ineficien cert
Apomorfina
Bromocriptina
Eficien probabil
Eficien probabil
Cabergolina
Eficien probabil
Eficien cert
Dihidroergocriptina
Eficien cert
Date insuficiente
Lisuride
Eficien probabil
Eficien posibil
Pergolide
Eficien cert
Eficien probabil
Piribedil
Eficien possibil
Date insuficiente
Pramipexol
Eficien cert
Eficien cert
Ropinirol
Eficien cert
Eficien cert
Selegilina
Eficien cert
Ineficien cert
Rasagilina
Eficien cert
Date insuficiente
Entacapone
Date insuficiente
Date insuficiente
Tolcapone
Date insuficiente
Date insuficiente
Amantadina
Eficien probabil
Date insuficiente
Anticolinergicii
Eficien probabil
Date insuficiente
Reabilitare
Date insuficiente
Eficien probabil
Chirurgie
TOXICITATEA
Produii ergotaminici nu sunt recomandai
ca tratament de prim linie
Risc de valvulopatie
Tolcapone nu se recomand n tratamentul

de debut al B. Parkinson din cauza riscului
de toxicitate hepatic
Recomandri
Actualmente nu poate fi o indicaie unic n
tipul de terapie iniial
Opiuni posibile:
levodopa, agoniti dopaminergici, inhibitorii MAO
amantadina sau anticolinergice
Nu sunt date despre utilitatea tratamentului de

recuperare
Levodopa
Levodopa este cel mai eficient medicament n
terapia iniial
Dup civa ani - complicaii motorii
Utilizarea levodopa cu eliberare lent nu e eficace n
prevenirea acestor complicaii
Utilizarea precoce de levodopa e recomandat la
persoanele vrstnice:
Sensibilitate major la agonitii dopaminergici;
Risc minor de complicaii motorii
Agonitii dopaminergici
Agonitii non ergolinici sunt superiori n raport
cu levodopa n privina riscului fluctuaiilor
motorii
Cabergolina este cu certitudine eficient n
prevenia fluctuaiilor motorii
Terapia iniial cu agoniti e recomandat la
pacienii tineri
Agonitii dopaminergici
Agonitii prezint efecte adverse
agoniti ergolinici nu se recomand ca terapie de
prim alegere din cauza riscului de fibroz
se recomand monitorizarea (radiografia toracic
-fibroza pleuro-pulmonar; echo-cardiografia - fibroza
valvulelor mitrale)
Utilizarea precoce concomitent a levodopei i

agonitilor este o opiune posibil, deocamdat
neconfirmat
Alte medicamente
Inhibitorii MAO-B se utilizeaz n terapia
simptomatic a bolii Parkinson
Mai puin eficieni dect levodopa i agonitii
dopaminergici
Selegilina cu certitudine ineficient n prevenirea
complicaiilor motorii
Anticolinergicele i amantadina sunt probabil

eficiente
Mai puin eficiente dect levodopa
Anticolinergicele - de evitat n populaia vrstnic
Modificri terapeutice
Dac are loc o agravare a pacienilor n
tratamentul cu inhibitorii MAO, anticolinergicie sau
amantadina
Introducerea de levodopa sau a dopamin-agonitilor va
depinde de urmtoarele :
Necesitatea ameliorrii condiiei motorii (levodopa);

Risc de complicaii motorii (inferior cu agonitii);
Riscul complicaiilor neuropsihice (mai superior la agoniti);
Risc de complicaii motorii e major la pacienii tineri
(levodopa);
Riscul complicaiilor neuropsihice e major la pacienii vrstnici
Modificri terapeutice
Dac pacienii prezint o agravare n
tratamentul cu agoniti dopaminergici:
Majorarea dozei
Introducerea de levodopa
Schimbarea agonistului dopaminergic
Tremor invalidant
Dac pacienii cu tremor invalidant devin
rezisteni la terapia dopaminergic, este util:
Introducerea anticolinergicelor
Introducerea clozapinei
Introducerea beta blocanilor
Candidai pentru intervenii de neurostimulare
cerebral profund
NST
NSST
Terapia bolii Parkinson avansate
Complicaiile motori n BP
i tratamentul lor
Fenomenul wearing off

Fenomenul on-off imprevizibil
Diskinezia de vrf de doz
Distonia off (distonia matinal)
Fenomenul freezing
Tratamentul wearing off

Fracionarea administrrii
levodopa
Utilizarea levodopa cu
eliminare lent
Administrarea inhibitorilor
COMT i MAO-B (tolcapone)
Administrarea agonitilor
dopaminergici (pergolide )
Administrarea
anticolinergicelor sau
amantadinei pacienilor la
care anterior ele au fost
ineficiente
Tratamentul wearing off

resistent la terapia per os
1. Stimulare cerebral profund a NST
2. Gastrostomie percutanat endoscopic i
introducerea levodopei
3. Apomorfina n pomp sau levodopa
dispersabil
Tratamentul fluctuaiilor on-off

imprevizibile
Evidene insuficiente pentru a furniza
recomandri
E necesar de a fi luat n calcul

posibilitatea de levodopa dispersabil
Tratamentul diskineziei de vrf de doz

Se recomand:
1. Amantadina
2. Antipsihotice atipice (clozapina) sau quetiapina
(seroquel)
3. Stimulare cerebral profund
4. Apomorfina n infuzie continu sau reducerea
dozei unice de levodopa
5. Reducerea sau sistarea MAO-B i inhibitorilor
COMT
Tratamentul distoniei off

(i distoniei matinale)
Utilizarea strategiilor eficiente n wearing off
Administrare seral de levodopa sau
dopamino-agonitilor
Estimarea opiunii de stimulare cerebral
profund NST
Estimarea posibilitii tratamentului cu
toxina botulinic
Tratamentul freezing
n caz de freezing off acelai tratament
ca n wearing off
util stimularea verbal i vizual
n caz de freezing on (rar)
Se recomand o prob de reducere a terapiei
dopaminergice
Risc de agravare a wearing off
Depresia
La 40% pacieni
Terapia antiparkinsonian are efect
antidepresiv (confirmat convingtor n studii)
Recomandri:
Optimizarea terapiei antiparkinsoniene
Administrarea antidepresivelor triciclicie sau
SSRI
Hipotensiunea ortostatic
Disautonomia cardiovascular reprezint
un simptom al BP, agravat de terapia
dopaminergic
n caz de hipotensiune ortostatic:
Utilizarea ciorapilor elastici
Administrarea midodrinei (cert eficient)
Fludrocortisol - posibil eficient (efecte
adverse, hipertensiune clinostatic)
Using the clinical diagnostic criteria of the Parkinson's Disease Society Brain Bank,
London, England, Hughes et al 3 reported the same (76%) autopsy-confirmed
diagnostic accuracy in 100 brains of patients with parkinsonism. By modifying the
criteria to include asymmetric onset, no atypical features, and no possible cause for
another parkinsonian syndrome, the diagnostic accuracy was increased to 93% (truepositive cases), but 32% of pathologically proven cases of PD were not identified by
these criteria (false-negative cases). Thus, an increase in positive predictive value was
associated with a decrease in sensitivity.
Good response to levodopa is often used to support the diagnosis of PD. Of 100
pathologically proven cases from the United Kingdom, Hughes et al 4 reported that 77
(77%) had good or excellent initial levodopa response as did 16 (94%) of 17 patients
examined by Rajput et al. 5 However, rare cases of pathologically proven parkinsonism
with Lewy bodies, but without response to levodopa, have been reported. 6 Therefore,
while improvement with levodopa supports the diagnosis of PD, response to levodopa
cannot be used to reliably differentiate PD from other parkinsonian disorders. The
diagnosis of PD is reserved for those idiopathic cases that have pathological findings of
substantia nigra and Lewy bodies. 1 Future advances in imaging technology will
undoubtedly improve the diagnostic potential of magnetic resonance imaging, positron
emission tomography, and single photon emission computed tomography. 7-10 Until the
utility of these imaging techniques in the diagnosis of PD is established, the diagnosis of
PD will rest on a set of clinically defined criteria. We present herein the results of a study
of cases prospectively followed since the early stages of PD to examine the evolution of
clinical diagnosis.
Jankovic, et al.,Joseph MD; Rajput, Ali H. MD; McDermott, Michael P. PhD; Perl, Daniel
P. MD; for the Parkinson Study Group 2000
Using the clinical diagnostic criteria of the Parkinson's Disease Society Brain Bank,
London, England, Hughes et al 3 reported the same (76%) autopsy-confirmed
diagnostic accuracy in 100 brains of patients with parkinsonism. By modifying the
criteria to include asymmetric onset, no atypical features, and no possible cause for
another parkinsonian syndrome, the diagnostic accuracy was increased to 93% (truepositive cases), but 32% of pathologically proven cases of PD were not identified by
these criteria (false-negative cases). Thus, an increase in positive predictive value was
associated with a decrease in sensitivity.
Good response to levodopa is often used to support the diagnosis of PD. Of 100
pathologically proven cases from the United Kingdom, Hughes et al 4 reported that 77
(77%) had good or excellent initial levodopa response as did 16 (94%) of 17 patients
examined by Rajput et al. 5 However, rare cases of pathologically proven parkinsonism
with Lewy bodies, but without response to levodopa, have been reported. 6 Therefore,
while improvement with levodopa supports the diagnosis of PD, response to levodopa
cannot be used to reliably differentiate PD from other parkinsonian disorders. The
diagnosis of PD is reserved for those idiopathic cases that have pathological findings of
substantia nigra and Lewy bodies. 1 Future advances in imaging technology will
undoubtedly improve the diagnostic potential of magnetic resonance imaging, positron
emission tomography, and single photon emission computed tomography. 7-10 Until the
utility of these imaging techniques in the diagnosis of PD is established, the diagnosis of
PD will rest on a set of clinically defined criteria. We present herein the results of a study
of cases prospectively followed since the early stages of PD to examine the evolution of
clinical diagnosis.
Jankovic, et al.,Joseph MD; Rajput, Ali H. MD; McDermott, Michael P. PhD; Perl, Daniel
P. MD; for the Parkinson Study Group 2000
The Deprenyl and Tocopherol Antioxidative Therapy for

Parkinson's Disease (DATATOP) Briefly, 800 patients
with early PD (Hoehn and Yahr stages 1 and 2) 17 were
enrolled in 28 US and Canadian centers. The 34
investigators at the 28 centers were selected to
participate in the study because they had a major
interest in movement disorders and considerable
experience in treating patients with PD. Of the 800
patients, 528 (66%) were men and 272 (34%) were
women. The follow-up evaluations in the DATATOP study
included making clinical assessments using the Unified
Parkinson's Disease Rating Scale, 18 completing
standard case report forms designed to track the latest
clinical diagnosis, and documenting the reasons for any
change in diagnosis. The first patient was enrolled on
April 1, 1987, and the data on verification of diagnosis
included information to September 1996.
The Deprenyl and Tocopherol Antioxidative Therapy for

Parkinson's Disease (DATATOP) Briefly, 800 patients
with early PD (Hoehn and Yahr stages 1 and 2) 17 were
enrolled in 28 US and Canadian centers. The 34
investigators at the 28 centers were selected to
participate in the study because they had a major
interest in movement disorders and considerable
experience in treating patients with PD. Of the 800
patients, 528 (66%) were men and 272 (34%) were
women. The follow-up evaluations in the DATATOP study
included making clinical assessments using the Unified
Parkinson's Disease Rating Scale, 18 completing
standard case report forms designed to track the latest
clinical diagnosis, and documenting the reasons for any
change in diagnosis. The first patient was enrolled on
April 1, 1987, and the data on verification of diagnosis
included information to September 1996.
The mean SD duration of illness in the 800 cases at enrollment

was 2.2 1.3 years, and the mean SD Hoehn and Yahr stage was
1.6 0.5. The mean SD follow-up was 6.0 1.4 years (range, 0.27.6 years). In 5 cases, PD was not confirmed at autopsy, and in 15
patients, the results of imaging studies indicated the presence of
other pathological conditions. Of the 550 cases treated with
levodopa, 49 (8.9%) had little or no improvement; 6 of these cases
overlap with either autopsy or imaging study exclusion criteria. Two
other cases had at least 4 of the 6 atypical clinical features arguing
against the diagnosis of PD. Thus, of the 800 patients, 65 (8.1%) did
not have PD according to the study criteria. Compared with those
patients with the final diagnosis of PD, in the diagnoses of 60
patients without autopsy, the duration of symptoms (mean SD, 7.2
2.0 years vs 8.3 1.9 years; P<.001) and the duration of follow-up
(5.3 1.6 years vs 6.1 1.3 years; P<.001) were shorter.
Conclusions: We found that 65 (8.1%) of patients initially diagnosed
as having PD were later found to have an alternate diagnosis based
on multifactorial clinical diagnostic criteria. This alternate diagnosis
indicated that experts in PD changed their diagnoses infrequently
during the 7.6-year follow-up.
Jankovic, et al.,Joseph MD; Rajput, Ali H. MD; McDermott, Michael

P. PhD; Perl, Daniel P. MD; for the Parkinson Study Group 2000
Boala Parkinson
Un diagnostic dificil ?
Le diagnostic clinique de syndrome parkinsonien est relativement ais voquer,

mais la distinction entre la maladie de Parkinson idiopathique (MPI) et les autres
syndromes parkinsoniens (Parkinsonismes secondaires et Parkinsons plus ) peut
tre trs difficile notamment en dbut de maladie.
Un diagnostic exact est important non seulement pour conseiller les patients et
assurer la bonne conduite du traitement, mais aussi pour raliser des tudes
pharmacologiques et pidmiologiques.
Une analyse critique des critres de diagnostic de la MPI, confronte la vrification
neuropathologique, est prsente partir des donnes rcentes de la littrature.
En l'absence de critres disponibles et valids, issus de l'imagerie fonctionnelle ou de
la biologie molculaire, les critres diagnostiques les plus oprationnels restent
d'ordre clinique; les cinq critres privilgis sont
le tremblement de repos,
la rigidit,
la bradykinsie,
l'asymtrie au dbut et
la rponse marque la L-DOPA.
Le diagnostic de MPI doit tre rgulirement rvalu au cours du droulement de
son histoire naturelle.
Tratament
Levodopa
Levodopa a fost piatra de temelie n tratamentul
BP mai mult de 40 ani
Tratmentul este asociat cu descreterea
morbiditii i mortalitii vs. cu era prelevodopa
Cel mai eficient medicament in tratmentul MP
Virtual, toi patienii cu MP confirmat ncearc
un beneficiu clinic semnificativ
Olanow CW et al. Neurology. 2001;56(suppl 5):S9.
Factor SA. Med Clin North Am. 1999;83:415.
Tratament
Terapia cu L-Dopa
Suplinirea deficitului dopaminei n striatum*
L-Dopa este precursorul dopaminei, trece
bariera H-E
Eficiena i tolerabilitatea este mai mare fiind
asociat cu inhibitorii decarboxilasei
(benzerazid/carbidopa)
Efecte adverse:
Grea/vom/vertij
Hipotonie ortostatic
Psihoz
Sindromul L-dopa (administrarea de durat a L-dopa)
(lipsa efectului, fluctuaii motorii, diskinezii)
Levodopa
Problemele perioadei a II
Tratament
Fluctuaii motorii
- Pn la 50% pacieni dup 5 ani de tratament
- 70% pacieni sup 15 ani de tratament
- Fenomenul wearing off - de sfrit de doz
- Fluctuaii inprevizibile on-off
Diskineziile
Vrf de doz ori bifazic
Tulburri neuropsihice
Halucinaii
Psihoze
Confuzii
Lang AE et al. N Engl J Med. 1998;339(16):1134-36.
Tratament
Anticholinergicele
Tratament
Anticholinergicele
Opiune pentru pacienii tineri (<60 ani) cu
forme tremorigene i funcii cognitive pstrate
Ageni disponibili:
Trihexyphenidyl (Romparkin, Artan, Cyclodol)
Benztropine (Cogentin)
Biperidin (Akineton)
Efectele adverse pot limita utilizarea:
Alterarea memoriei Disforie

Confuzie acut
Efecte muscarinice
Halucinaii
uscciunea mucoasei bucale
Sedare
nceoarea vederii
Olanow CW et al. Neurology. 2001;56(suppl 5):S24-S25.
Tratament
Anticholinergicele
Opiune pentru pacienii tineri (<60 ani) cu
forme tremorigene i funcii cognitive pstrate
Ageni disponibili:
Trihexyphenidyl (Romparkin, Artan, Cyclodol)
Benztropine (Cogentin)
Biperidin (Akineton)
Mecanism de aciune:
- Rmne necunoscut
- Inhib recaptarea
DA n terminaiile
presinaptice
Efectele adverse pot limita utilizarea:
Alterarea memoriei Disforie

Confuzie acut
Efecte muscarinice
Halucinaii
uscciunea mucoasei bucale
Sedare
nceoarea vederii
Amantadina
Tratament
Amantadina
Obiune de monoterapie n cazul pacienilor primar
diagnosticai cu simptome uoare
Asigur un benefidiu terapeutic moderat
Blocheaz recaptarea dopaminei mrind cantitatea ei
n fanta sinaptic
Mendis T et al. Can J Neurol Sci. 1999;26:91.

Lang AE et al. N Engl J Med. 1998;339(16):1134.
Inhibitorii
MAO-B
Tratament
Inhibitorii MAO-B
Blocheaz enzima monoamin oxidaza B, care
catabolizeaz dopamina (contribuind la mrirea dopaminei
n fanta sinaptic i acumularea ei n neuronii dopaminergici nigro-striatali)
Selegilina este un inhibitor selectiv de MAO-B

ntrzie necesitatea administrrii terapiei cu levodopa la
pacienii cu MP netratat cu circa 9 luni ntr-un mare trial
clinic n comparaie cu placebo
Efect neuroprotector (de incetinire a evoluiei

maladiei) discutabil
Parkinson Study Group. Ann Neurol. 1996;39:37-38.
Inhibitorii
COMT
Catecol-Orto-Metil-Transferaz
Tratament
Inhibitorii COMT
Inhibitorii de Catecol-Orto-Metil-Transferaz (COMT) nu au
vre-un rol sinestttor n monoterapie; pot fi utilizai doar n
combinaie cu levodopa
Inhib catabolismul DA , extind durata efectului levodopa
Indicai n tratmentul patienilor cu MP cu fluctuaii motorii
de tipul wearing off n tratamentul cu levodopa
Inhibitorii COMT disponibili:
Entacapone
Tolcapone (toxicitatate hepatic)
Efectele adverse sunt n primul rnd dopaminergice

cauzate de creterea disponibilitii de levodopa n creier
Tasmar (tolcapone) Prescribing Information. Roche Laboratories, Inc. 1998.
Punctele de atac a terapiei

medicamentoase
Tratament
Agonist
Dopaminergic
Dopa
decarboxylase
L-Dopa
Antgonist
Glutamatic
Inhibitorii MAO-B
Glu
(3,4-Dihydr-oxy-phenyl-acetic acid)
Presynapse
Glial cell
Agoniti dopaminici:
Diapazonul posologic*
Disponibilitatea (mg)
Tratament
Diapazonul
(mg/zi)
REQUIP (ropinirole)
0.75-24
0.25, 0.5, 1, 2,
3, 4, 5
Bromocriptine
1.25-40
2.5, 5
Pergolide
0.05-4
0.05, 0.25, 1
Pramipexole
0.375-4.5
0.125, 0.25,
0.5, 1, 1.5
* Eficiena comparabil nu a fost stabilit

Factor SA. Med Clin North Am. 1999;83:419-428.
Trialuri clinice
REQUIP
(ropinirole)
Trialauri clinice
Trialuri clinice
N. 1
REQUIP - Placebo
(Studiu tratamentului MP n
stadiile precoce)
Trialauri clinice
REQUIP (ropinirol )-Placebo

Studiu MP stadiile precoce.
Ameliorare semnificativ Scorului Motor UPDRS
P < 0.001
% Modificri
24%
Ropinirole
n = 116
-3%
Placebo
Adler CH et al. Neurology. 1997;49:395.
n = 125
N. 2
REQUIP - Levodopa
(Studiu tratamentului MP n
stadiile precoce)
Incidena Diskineziei
incapacitante.
% pacieni
23%
P < 0.001
Patienii ce administrau
REQUIP au avut un risc
semnificativ mai redus de
diskinezii dizablitante
Aceasta rmne valabil
independent de terapia
adjuvant cu levodopa
8%
14/179
Trialauri clinice
20/89
P< 0.001
Tratament
REQUIP (ropinirole):modalitatea creterii dozei.

Orarul iniial recomendat:
0.25 mg 3 ori/zi 1 sptmn
1 mg 3 ori/zi 1 sptmn
0,75 mg/zi (0.25 mg per dose)

Dup sptmna a 4, mrirea cu 1.5 mg/zi (0.5 mg per
dose) sptmnal pn la 9 mg/zi
Dup 3 mg/zi creterea sptmnal ia n cont necesitile
individuale ale pacientului pn la doza zilnic de 24 mg
Diapazonul larg de doze este facilitat de diverse doze a
pastilelor: 0.25-mg, 0.5-mg, 1-mg, 2-mg, 3-mg, 4-mg, and 5mg
Tratament
Procentul cumulativ a rspunsurilor n funcie de
% cumulativ a rspunsului
doz REQUIP (ropinirole).
n=271
*Doza Maximal cotidian de REQUIP.

Korczyn AD, et al. Acta Neurol Scand 2002;106:200-204.
Tratament
REQUIP (ropinirole) vs. Levodopa in

MP stadiile precoce.
Concluzii
MP stadiile precoce poate fi tratat n monoterapie pn

la 5 ani cu ropinirol dar i suplementar cu levodopa ca un
a doilea pas dac e necesr
Riscul redus de diskinezii comparativ cu levodopa
Eficacitatea este comparabl cu levodopa n meninerea
activitii cotidiene
Hallucinaiile mai frecvente n grupul cu ropinirol dect in cel cu

levodopa ; ns ele sunt moderate i pot fi uor tratate la
majoritatea pacienilor
Rascol O et al. N Engl J Med. 2000;342:1488-90.
REQUIP (ropinirole)
Rezumat
Tratament
Indicat pentru monoterapie i terapie adjuvan

AD n monoterapie au o eficien i siguran dovedit
n perioada de 5 ani conform datelelor trialului clinic
Derivaii non-ergotici sunt recomendai
Economie de Levodopa
N. 3
REQUIP Levodopa
(PET)
(Studiu tratamentului MP n stadiile
precoce)
Trialauri clinice
Analiza Zonelor Investigate (AZI):

Pacient cu MP:
Imagini ADD
F-dopa
template
18
Imagine ADD
transformat
spaial
Datele
ADD
ROI on
18
F-dopa
template
Spatially
transformed
Ki map
Whone AL, et al. Neurology 2002;58(7 Suppl 3):A82-A83 (Abstr. #S11.006).

Whone AL, et al. Presented at: 54th Annual Meeting of the American Academy of Neurology; April 13-20, 2002; Denver,
Trialauri clinice
Analiza SPM : Metodologia

PD patient:
ADD image
F-dopa
template
18
Spatially
transformed
ADD image
Spatially
transforme
d Ki map
SPM data

Concluzii
Captarea 18F-dopa este un marker (indice) a
evoluiei MP
Modificrile n putamen i substana nigra
a fost seminificativ mai ncete n MP la
pacienii care au administrat Requip n
compataie cu L-dopa mai mult de 2 ani
CO.
Trialauri clinice
Incidena Diskineziilor
Riscul diskineziilor de circa 10 ori mai mare
cu L-dopa dect cu Requip
Incidena Diskineziilor (%)
30
27 %
25
P<0.0003
20
15
UPDRS item-ul 32 i
informaia despre
efectele adverse
10
5
0
3%
Requip
L-dopa

CO.
Ropinirol
Concluzii generale
(conform trialurilor realizate)
Concluzii generale (I)
Ropinirol
Ropinirolul ncetinete evoluia

modificrilor n putamen i
substana nigra confirmate
prin PET
Concluzii generale (II)

2
MP stadiile precoce poate fi tratat
n monoterapie pn la 5 ani cu
ropinirol.
Eficacitatea este comparabl cu
levodopa n meninerea activitii
cotidiene
Ropinirol
Concluzii generale (III)

3
Ropinirolul poate fi asociat cu
levodopa ca un a doilea pas de
terapie adjuvant dac e necesr
Ropinirol
Concluzii generale (IV)
Ropinirol
4
Riscul redus de diskinezi
comparativ cu levodopa este un
avantaj major al Ropinirolului
viznd prognoza ulterioar
Concluzii generale
Ropinirol

1. Ropinirolul ncetinete modificrile n putamen i
substana nigra confirmate prin PET
2. MP stadiile precoce poate fi tratat n monoterapie
pn la 5 ani cu ropinirol. Eficacitatea este
comparabl cu levodopa n meninerea activitii cotidiene
3. Ropinirolul poate fi asociat cu levodopa ca un a doilea
pas de terapie adjuvant dac e necesr
4. Riscul redus de diskinezii comparativ cu levodopa este un
avantaj major al Ropinirolului viznd prognoza ulterioar
5. Economie de Levodopa
V mulumim pentru atenie
Opiuni terapeutice n terapia

medicamentoas
Tratament
Antagonistul Glutamatului (amantadina)

Inhibiia hyperactivitii glutamatergice
Terapia cu L-Dopa /agoniti dopaminergici

Substituia Dopaminei
Inhibirori MAO-B
Inhibiia central a catabolismului i reducerii
dopaminei
Inhibitorii COMT
Inhibiia periferic a reducerii L-dopa
Opiuni terapeutice n terapia

medicamentoas
Tratament
Antagonistul Glutamatului (amantadina)

Inhibiia hyperactivitii glutamatergice
Terapia cu L-Dopa /agoniti

dopaminergici
Substituia Dopaminei
Inhibirori MAO-B
Inhibiia central a catabolismului i reducerii
dopaminei
Inhibitorii COMT
Inhibiia periferic a reducerii L-dopa
Early life
James Parkinson was born in Shoreditch,
London, England. He was the son of John
Parkinson, an apothecary and surgeon
practising in Hoxton Square in London. In 1784
James Parkinson was approved by the
Corporation of London as a surgeon.
On May 21, 1783, he married Mary Dale, with
whom he subsequently had six children. Soon
after he was married, James Parkinson
succeeded his father in his practice in 1, Hoxton
Square. He believed that any worthwhile
physician should know shorthand, at which he
was adept.
Dr. James Parkinson 11 April 1755 -December

21 1824
James Parkinson studied at the London Hospital
Medical College for 6 months when he was 20
and was then apprenticed to his father for 6
years, qualifying as a surgeon in 1784 when he
was 29. A year and half after becoming a
medical student, James became an honorary
medallist of the Royal Humane Society for
having assisted his father on 28 October 1777 in
using resuscitation methods on a Hoxton man
who had hanged himself.
interest in the welfare of people with mental illness. He wrote

extensively on medical subjects. Apart from the famous essay on 'the
Shaking Palsy', he wrote important papers and books on a diverse
range of medical subjects, including:
the effects of lightning
the distinction between disorders of memory, dysphasia and true
madness
texts to encourage parish fever wards;
a report of the first case of appendicitis to be found in English medical
literature which also was the first to recognise perforation (peritonitis)
as the cause of death
mental illness and reform in the Act regulating mad houses
gout
education of medical students and apothecaries
James Parkinson was involved in many medical associations of his
day, and served as President of the Association of Apothecaries for
two years. At the end of his distinguished medical career, James
Parkinson became the first recipient of the Honorary Gold Medal of
the Royal College of Surgeons in 1822.
Other achievements and interests
Other achievements and interests
Geology and science

James Parkinson is recognised as a founder of scientific palaeontology. He not
only wrote several books on geology but was also one of the thirteen founder
members of the British Geological Society, still in operation today. He was also an
enthusiastic member of several other scientific societies.
Social reform
James Parkinson was a controversial social reformer and political activist who championed
many causes and found it difficult to remain silent while people suffered. He lived during the
reign of King George III, at a time when the standard of living was declining as a result of war
and rising taxes. Representation in parliament for all citizens was non-existent and corruption
was rife.
Under the pen name of 'Old Hubert', he wrote many pamphlets which were highly critical of the
political system of the day and advocated the reform of popular representation in the House of
Commons and universal suffrage. He also highlighted social concerns such as poverty,
unfairness of taxes and wages, unfair imprisonment, poor prison conditions, education for the
poor, and care for the elderly and disabled.
James Parkinson also became a prominent member of two outspoken societies at the time,
the London Corresponding Society and the Society of Constitutional Information. The first
aimed to bring about reform of the parliamentary representation of the people and some of
their ideas were the foundation for the political system that exists in the UK today. However, in
a time when there was no freedom of speech, many members of these societies were tried and
convicted of treason, suffering severe punishment as a result.
As a result of his political activities, James played a key role in investigations into an alleged
conspiracy to kill King George III, allegedly by firing a poisoned dart from the pit of a theatre
(known as the 'Popgun Plot'). Five members of the London Corresponding Society were
arrested for high treason in relation to this apparent plan, which never existed except in the
mind of one man, Thomas Upton. Three of the others were accused based on letters forged by
Upton, and one by being associated with Upton. James Parkinson was a witness for the
defence during the Privy Council investigations and in the one trial which was subsequently
held. All the accused were eventually freed. James Parkinson, in appearing for the defence and
in his writings, took significant risks with regard to his own career and life because he could
have been prosecuted for his activities, the people and organisations he was associated with
and for writing against the monarchy. His involvement in this affair shows that he was a man of
principle and honour who believed these issues were too important to remain silent. This
earned him the respect of the Privy Council and he was not prosecuted.
In later life, James Parkinson took on other responsibilities with humanitarian goals. This
included highlighting the importance of the welfare of children who worked as apprentices,
uncovering abuse and encouraging law reform governing apprentices to make review and
inspection an integral part of the system.
Family and church

James Parkinson married Mary Dale in 1781
They had 6 children and his son, John William
Keys Parkinson's, also became a doctor and
eventually took over the Hoxton practice
James Parkinson was also churchwarden of St.
Leonard's Church in Shoreditch, where he was
baptised, married and buried. Although his grave
is no longer identifiable, there is a memorial to
him in the church, erected in 1955 to mark the
200th anniversary of his birth.
An Essay on the Shaking Palsy

In this famous essay, James Parkinson was the first
person to make a clear description of the condition.
This was based on observation of 6 cases he had
either observed in his own practice or seen during
walks in his neighbourhood. Only one of them did
he examine and as such the description is
incomplete. However, his account is still remarkable
for its accuracy and clarity of expression. One of the
aims of writing the essay was to encourage others
to study the condition.
It was a French doctor, Jean Martin Charcot who
really recognised his work some 60 years after
James Parkinson wrote it and called the condition
"Parkinson's disease"
Science
Parkinson's interest gradually turned from medicine to nature, specifically the
relatively new field of geology, and paleontology. He began collecting specimens and
drawings of fossils in the latter part of the eighteenth century. He took his children
and friends on excursions to collect and observe fossil plants and animals. His
attempts to learn more about fossil identification and interpretation were frustrated by
a lack of available literature, and so he took the decision to improve matters by
writing his own introduction to the study of fossils.
In 1804 the first volume of his Organic Remains of the Former World was published.
Gideon Mantell praised it as "the first attempt to give a familiar and scientific account
of fossils". A second volume was published in 1808, and a third in 1811. Parkinson
illustrated each volume, sometimes in color. The plates were later re-used by Gideon
Mantell. In 1822 he published the shorter "Elements of Oryctology: an Introduction to
the Study of Fossil Organic Remains, especially of those found in British Strata".
Parkinson also contributed several papers to William Nicholsons "A Journal of
Natural Philosophy, Chemistry and the Arts", and in the first, second, and fifth
volumes of the "Geological Societys Transactions".
On November 13, 1807, Parkinson and a number of other distinguished gentlemen
met at the Freemasons' Tavern in London. The gathering included such great names
as Sir Humphry Davy, Arthur Aikin, and George Bellas Greenough. This was to be
the first meeting of the Geological Society of London.
Parkinson belonged to a school of thought, Catastrophism, that concerned itself with
the belief that the Earth's geology and biosphere were shaped by recent large-scale
cataclysms. He cited the Noachian deluge of Genesis as an example, and he firmly
believed that creation and extinction were processes guided by the hand of God. His
view on Creation was that each 'day' was actually a much longer period, that lasted
perhaps tens of thousands of years in length.
Medicine
Parkinson turned away from his tumultuous political career, and
between 1799 and 1807 published a number of medical works,
including a work on gout in 1805. He was also responsible for the
earliest writings on the subject of peritonitis in English medical
literature.
Parkinson was the first person to systematically describe 6
individuals with symptoms of the disease that bears his name.
Unusually for such a description, he did not actually examine these
patients himself but observed them on daily walks. [1]
It was Jean Martin Charcot who coined the term "Parkinson's

Disease" over 60 years later.
Parkinson was also interested in improving the general health and

well-being of the population. He wrote several medical doctrines that
exposed a similar zeal for the health and welfare of the people that
was expressed by his political activism. He was a crusader for legal
protection for the mentally ill, as well as their doctors and families.
In 1812 Parkinson assisted his son with the first described case of
appendicitis in English, and the first instance in which perforation
was shown to be the cause of death.
Boala Parkinson
Movement Disorders Society Scientific Issues

Committee report: SIC Task Force appraisal of clinical
diagnostic criteria for Parkinsonian disorders
As there are no biological markers for the antemortem diagnosis of
degenerative parkinsonian disorders, diagnosis currently relies upon the
presence and progression of clinical features and confirmation depends on
neuropathology. Clinicopathologic studies have shown significant falsepositive and false-negative rates for diagnosing these disorders, and
misdiagnosis is especially common during the early stages of these
diseases. It is important to establish a set of widely accepted diagnostic
criteria for these disorders that may be applied and reproduced in a blinded
fashion. This review summarizes the findings of the SIC Task Force for the
study of diagnostic criteria for parkinsonian disorders in the areas of
Parkinson's disease, dementia with Lewy bodies, progressive supranuclear
palsy, multiple system atrophy, and corticobasal degeneration. In each of
these areas, diagnosis continues to rest on clinical findings and the
judicious use of ancillary studies. Copyright 2003 Movement Disorder
Society
PMID: 12722160 [PubMed - indexed for MEDLINE]
Litvan I, Bhatia KP,Burn DJ,Goetz CG, Lang AE, McKeith I, Quinn
N, Sethi KD, Shults C, Wenning GK; Movement Disorders Society
Scientific Issues Committee

Step 1: Diagnosis of Parkinsonism

Bradykinesia and at least one of the
following:
Muscular rigidity
46 Hz resting tremor
Postural instability not caused by primary
visual, vestibular, cerebellar or
proprioceptive dysfunction

Step 2: Features tending to exclude Parkinsons disease as the cause of

Parkinsonism
History of repeated strokes with stepwise progression of parkinsonian features
History of repeated head injury
History of definite encephalitis
Neuroleptic treatment at onset of symptoms
>1 affected relatives
Sustained remission
Strictly unilateral features after 3 years
Supranuclear gaze palsy
Cerebellar signs
Early severe autonomic involvement
Early severe dementia with disturbances of memory, language and praxis
Babinski's sign
Presence of a cerebral tumour or communicating hydrocephalus on computed
tomography scan
Negative response to large doses of levodopa (if malabsorption excluded)
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure
Stadiile evoluiei BP conform

Hoehn i Yahr (1967)
St. I simptome unilaterale
St. II simptome bilaterale
St. III simptome bilaterale + instabilitate postural
(are periodic nevoie de ajutor)
St. IV handicap sever, dar n zile (ore) bune -i poate
pstra ortostaiunea i merge fr ajutor
St. V fr ajutor rmne imobilizat la pat
(necesit ajutor permanent)
APPENDIX: PD - UK PDS BRAIN BANK DIAGNOSTIC CRITERIA
Step 1 - Diagnosis of Parkinsonian syndrome

Bradykinesia plus at least one of the following
Muscular rigidity
Rest tremor
Postural instability
Step 2 - Exclusion criteria including
History of repeated strokes
History of repeated head injury
History of definite encephalitis
Step 3 - Supportive prospective criteria (at least three required)
Unilateral onset
Rest tremor present
Evidence of progression
Persistent asymmetry
Excellent response to L-dopa
Severe L-dopa-induced chorea
L-dopa response for 5+ years
Clinical course of 10+ years
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Patologia

An Essay on the Shaking Palsy

60 de ani mai trziu

n afar de The Shaking Palsy', a scris

Repere istorice n cercetarea

Birkmayer & Hornykiewicz Utilizarea clinic a L-dopa

Calne Introducerea agonitilor dopaminergici

Idiopatic vs. formele

Lang & Lozano. N Engl J Med. 1998;339:1044-1053.

Incidena n funcie de vrst a cazurilor

(la 100,000 populaie)

Viaa n mediu rural

Butterfield PG et al. Neurology. 1993;43:1152. Lang AE et al. N Engl J Med. 1998;339(15):1050.

(Braak et al., 2002)

Semne clinice cardinale

Orphan Man with Cap and Walking Stick

by Vincent van Gogh, 1882

Simptomele principale: Rigiditatea

Simptomele asociate non-motorii

Simptome frecvente n debutul BP

Dureri cervicale i brahiale

Punctele de atac a terapiei

Se utilizeaz n terapia simptomatic

Selegilina (Selegos, Jumex, Cognitiv,

Agoniti dopaminergici derivai nonergolinici

Olanow CW et al. Neurology. 2001;56(suppl 5):S14.

Agonitii dopaminergici (I)

- AD: durata de aciune mult mai lung

Controlul simptomelor Prevenirea complicaiilor

Levodopa eliberare lent

Nu s-a utilizat n faza precoce

Nu s-a utilizat n faza precoce

Nu se utilizeaz in faza precoce

Nu se utilizeaz in faza precoce

Un viitor mai putin sumbru pentru

Diverse forme de Tremor

fibre nervoase extrinseci

Mentine la un nivel constant starea de excitatie a

Ataxia Paroxistic Ereditar

Boala Parkinson: un diagnostic dificil ?

Diagnosticul iniial al BP stabilit de neurologi generaliti n fazele

1/3 din pacienii cu MSA supravegheai de specialiti n micri

41-88% pacieni cu PSP au beneficiat de un diagnostic corect n

United Kingdom Parkinson's Disease Society Brain Bank Diagnostic

Practice Parameter: Diagnosis and

Practice Parameter: Treatment of

United Kingdom Parkinson's Disease Society Brain

Etapa 1: Diagnostic de Boala Parkinson

United Kingdom Parkinson's Disease Society Brain

Tremor de repaus (4 6 Hz)

United Kingdom Parkinson's Disease Society Brain

AVC repetate cu progresia fenomenelor parkinsoniene

United Kingdom Parkinson's Disease Society Brain

Tulburri vegetative precoce severe

United Kingdom Parkinson's Disease Society Brain

Criteriile clinice diagnostice adiionale

Debut unilateral al maladiei

Stadiile evoluiei BP conform

St. 4 handicap sever, dar n zile (ore) bune i poate

Investigaii suplimentare n diagnosticul

Investigaii suplimentare n diagnosticul