Management in Parkinson s Disease

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(1)

Management

Management

in

in

Parkinson

Parkinson

s

s

Disease

Disease

Apichart Pisarnpong

Apichart Pisarnpong,, MM..DD..

Director of Parkinson

Director of Parkinson’’s Disease Clinic, s Disease Clinic, Siriraj Hospital,

(2)

overview

overview

„

„ History of ParkinsonHistory of Parkinson’’s Diseases Disease

„

„ Clinical manifestation of PDClinical manifestation of PD

„

„ Etiology and secondary cause of ParkinsonismEtiology and secondary cause of Parkinsonism

„ „ Classification Classification „ „ Treatment : Treatment : „ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

(3)

overview

overview

„

„

History of Parkinson

History of Parkinson

s Disease

s Disease

„

„ Clinical manifestation of PDClinical manifestation of PD

„

„ Etiology and secondary cause of ParkinsonismEtiology and secondary cause of Parkinsonism

„ „ Classification Classification „ „ Treatment : Treatment : „ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

(4)

History

History

1817

1817

:

:

James Parkinson

James Parkinson

“An Essay on the Shaking PalsyAn Essay on the Shaking Palsy”” Almost 200 years ago

Almost 200 years ago

ในประเทศไทยเคยเรียกวา

(5)
(6)
(7)
(8)

„

(9)

„

„ 1961 using IV levodopa to treat PD patients 1961 using IV levodopa to treat PD patients

„

„ 1966 combine with Decaboxylase inhibitor 1966 combine with Decaboxylase inhibitor

(benzerazide) less side effect and more potent

(10)

Pathology of Parkinson

(11)

Normal Basal Ganglia Functional

Normal Basal Ganglia Functional

Anatomy

Anatomy

Cortex Prefrontal Insular Cingulate Sensory Motor Suppl. Motor Premotor Premotor Prefrontal Striatum D2 D1 ThalamusVA/VL + = excitatory - = inhibitory Brainstem SC SNc SNr GPi STN GPe -+ + + -+ + + + + + Normal

(12)

Function Anatomy of Parkinson

Function Anatomy of Parkinson

s

s

Disease

Disease

Cortex Prefrontal Insular Cingulate Sensory Motor Suppl. Motor Premotor Premotor Prefrontal Striatum D2 D1 ThalamusVA/VL + = excitatory - = inhibitory Brainstem SC SNc SNr GPi STN GPe -+ + + + + + -+ + + + + + -Parkinson’s Disease

(13)

Cortex Prefrontal Insular Cingulate Sensory Motor Suppl. Motor Premotor Premotor Prefrontal Striatum D2 D1 ThalamusVA/VL + = excitatory - = inhibitory Brainstem SC SNc SNr GPi STN GPe -+ + + -+ + + + + + Normal Cortex Prefrontal Insular Cingulate Sensory Motor Suppl. Motor Premotor Premotor Prefrontal Striatum D2 D1 ThalamusVA/VL + = excitatory - = inhibitory Brainstem SC SNc SNr GPi STN GPe -+ + + + + + -+ + + + + + -Parkinson’s Disease

(14)

overview

overview

„

„ History of ParkinsonHistory of Parkinson’’s Diseases Disease „

„

Clinical manifestation of PD

Clinical manifestation of PD

„

„ Etiology and secondary cause of ParkinsonismEtiology and secondary cause of Parkinsonism

„ „ Classification Classification „ „ Treatment : Treatment : „ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

(15)

Signs and Symptoms

Signs and Symptoms

„

„ Cardinal CharacteristicsCardinal Characteristics

„

„ Resting tremorResting tremor

„

„ BradykinesiaBradykinesia

„

„ RigidityRigidity

„

„ Later; Postural instability (3Later; Postural instability (3--5 years after 5 years after

Dx)

Dx)

„

„ Gait disturbance esp. dystonic posture of Gait disturbance esp. dystonic posture of

feet, fluctuation of symptoms (YOPD)

(16)

Additional Signs and Symptoms

Additional Signs and Symptoms

„

„ Difficulty arising from a chairDifficulty arising from a chair

„

„ Difficulty turning in bedDifficulty turning in bed

„

„ Hypophonic speechHypophonic speech

„

„ SialorrheaSialorrhea

„

„ Loss of the sense of smellLoss of the sense of smell

„

(17)

„

„ OtherOther

„

„ MicrographiaMicrographia

„

„ Masked faceMasked face

„

„ Slowing of ADLsSlowing of ADLs

„

„ Stooped, shuffling gaitStooped, shuffling gait

„

(18)

Clues Suggesting

Clues Suggesting

Atypical Parkinsonism

Atypical Parkinsonism

„

„ Early onset Early onset ““offoff””, or rapidly progressing , or rapidly progressing

dementia

dementia

„

„ Rapidly progressive courseRapidly progressive course

„

„ Supranuclear gaze palsySupranuclear gaze palsy

„

„ Upper motor neuron signsUpper motor neuron signs

„

„ Cerebellar signsCerebellar signs——dysmetria, ataxiadysmetria, ataxia

„

„ Urinary incontinenceUrinary incontinence

„

(19)
(20)

Criteria for Diagnosis

Criteria for Diagnosis

„

„

At least two of three:

At least two of three:

„

„

rest tremor, bradykinesia, rigidity

rest tremor, bradykinesia, rigidity

„

„

Absence of a secondary cause; drugs,

Absence of a secondary cause; drugs,

metabolic, etc.

metabolic, etc.

„

„

Definitive diagnosis can only be made

Definitive diagnosis can only be made

by autopsy

(21)

overview

overview

„

„ History of ParkinsonHistory of Parkinson’’s Diseases Disease

„

„ Clinical manifestation of PDClinical manifestation of PD

„

„

Etiology and secondary cause of

Etiology and secondary cause of

Parkinsonism

Parkinsonism

„ „ Classification Classification „ „ Treatment : Treatment : „ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

(22)

Cause of PD

Cause of PD

Unknown in most cases

Unknown in most cases

10% associated with genetic

(23)

Parkinson

Parkinson

s Disease

s Disease

Risk Factors

Risk Factors

„

„ DefiniteDefinite: Old age: Old age

„

„ Highly likelyHighly likely: MZ co: MZ co--twin with earlytwin with early--onset PDonset PD

„

„ ProbableProbable: Positive family history: Positive family history

„

„ PossiblePossible: Herbicides, pesticides, heavy metals, proximity : Herbicides, pesticides, heavy metals, proximity to industry, rural residence, well water, repeated head

to industry, rural residence, well water, repeated head

trauma, etc.

trauma, etc.

„

(24)

overview

overview

„

„ History of ParkinsonHistory of Parkinson’’s Diseases Disease

„

„ Clinical manifestation of PDClinical manifestation of PD

„

„ Etiology and secondary cause of PDEtiology and secondary cause of PD „ „

Classification

Classification

„ „ Treatment : Treatment : „ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

(25)

Parkinsonian syndrome

Parkinsonian syndrome

Classification

Classification

1.

1. Idiopathic ParkinsonIdiopathic Parkinson’’s Diseases Disease 2.

2. Secondary ParkinsonismSecondary Parkinsonism 3.

3. Parkinson Plus syndromeParkinson Plus syndrome 4.

(26)

2.

2.

Secondary

Secondary

Parkinsonism

Parkinsonism

„

„

Drug

Drug

-

-

induced

induced

„

„

Toxin

Toxin

-

-

induced

induced

„

„

Metabolic

Metabolic

„

„

Structural lesions

Structural lesions

„

„

Hydrocephalus

Hydrocephalus

„

(27)

Drug

Drug

-

-

Induced Parkinsonism

Induced Parkinsonism

„

Antipsychotics

„

haloperidol, chlorpromazine,

thioridizine, perphenazine

„

risperidone, olanzapine

„

Antiemetics

„

metoclopramide, prochlorperazine

(28)

Drug

Drug

-

-

Induced Parkinsonism

Induced Parkinsonism

„

Dopamine depletors

„ methyldopa, reserpine, tetrabenazine

„

Antivertigo medications

„ Ca Channel blockers: flunarizine, cinnerizine

Treatment: Stop offending medications

(29)

Metabolic Causes of Parkinsonism

Metabolic Causes of Parkinsonism

„ Metabolic

„ Often reversible

„ Hypo- or hyper-thyroidism

„ Hypo- or hyper-parathyroidism „ Liver failure

(30)

Infectious Causes of Parkinsonism

Infectious Causes of Parkinsonism

„

„ InfectiousInfectious

„

„ PostPost--encephaliticencephalitic

„

„ CreutzfeldtCreutzfeldt--Jakob diseaseJakob disease

„

„ Infectious massesInfectious masses

„

(31)

Toxin

Toxin

-

-

induced Parkinsonism

induced Parkinsonism

„

„ MPTPMPTP

„

„ Carbon monoxideCarbon monoxide

„

„ ManganeseManganese

„

(32)

Structural Lesions Causing Parkinsonism Structural Lesions Causing Parkinsonism

„

„ Acute or subacute onsetAcute or subacute onset

„

„ Other signsOther signs——hemiparesis, hyperreflexia, hemiparesis, hyperreflexia,

aphasia, sensory loss, seizures

aphasia, sensory loss, seizures

„

„ Brain tumorBrain tumor

„

„ Infectious massInfectious mass

„

(33)

Vascular Parkinsonism

Vascular Parkinsonism

„

„ Abrupt onset, usually unilateralAbrupt onset, usually unilateral

„

„ StepStep--wise or no progressionwise or no progression

„

„ Other signsOther signs——hemiparesis, aphasia, hyperreflexiahemiparesis, aphasia, hyperreflexia

„

„ Infarcts on neuroimaging helpful in confirming Infarcts on neuroimaging helpful in confirming diagnosis

(34)

Hydrocephalus

Hydrocephalus

-

-

induced Parkinsonism

induced Parkinsonism

„

Can be communicating or obstructive

„

Normal pressure hydrocephalus—

idiopathic

„

Clinical triad:

„ parkinsonism/gait disorder „ urinary/fecal incontinence „ dementia

(35)

3. Parkinson Plus Syndrome

„

„

Progressive supranuclear palsy

Progressive supranuclear palsy

„

„

Multiple system atrophy

Multiple system atrophy

„

„

Corticobasal ganglia degeneration

Corticobasal ganglia degeneration

„

„

Diffused Lewy body disease

Diffused Lewy body disease

„

„

Parkinson

Parkinson

-

-

dementia complex

dementia complex

syndrome

(36)

4 Associated disease

4 Associated disease

„

„

Essential tremor

Essential tremor

„

(37)

Classification

Classification

by age of onset

by age of onset

„

„

Juvenile

Juvenile

-

-

onset

onset

„

„ Age of onset less than Age of onset less than 2121 years oldyears old

„

„

Young

Young

-

-

onset

onset

„

„ Age onset less than Age onset less than 4040 years old years old

but

(38)

„

„ Mean age of onset 60 to 65 yr.Mean age of onset 60 to 65 yr.

„

„ 55--10% start below age of 40 yr.10% start below age of 40 yr.

„

„ Incidence about 200Incidence about 200--250 : 100,000 in normal 250 : 100,000 in normal

population in developed country

population in developed country

„

(39)

Siriraj Parkinson's Disease Clinic Jan 2000- June 2002

242 medical records were enrolled

224 were reviewed 18 were excluded due

to incomplete data

174 medical records

of IPD 50 medical records

of other diagnosis Statistical analysis

(40)

Demographic data

Demographic data

„

„ Sex: Sex: 98 males 98 males (56.3%)(56.3%)

76 females

76 females (43.7%)(43.7%) M : F = 1.29 : 1

M : F = 1.29 : 1

„

„ Age of onset : 12Age of onset : 12--90 y (mean 55.6 y)90 y (mean 55.6 y)

age > 40 yr age > 40 yr = 82.3% = 82.3% age 20 age 20--40 yr 40 yr = 15.9%= 15.9% age < 20 yr age < 20 yr = 1.8% = 1.8% (age < 40 yr (age < 40 yr = 17.7%)= 17.7%)

(41)

Modified Hoehn and Yahr

Modified Hoehn and Yahr

Clinical staging of PD

Clinical staging of PD

Stage

Stage

0

0 no signs of diseaseno signs of disease

1

1 Unilateral diseaseUnilateral disease

1.5

1.5 Unilateral plus axial involvementUnilateral plus axial involvement 2

2 Bilateral disease, without impairment of balanceBilateral disease, without impairment of balance 2.5

2.5 Mild Bilateral disease, with recovery on pull testMild Bilateral disease, with recovery on pull test

3

3 Mild to moderate bilateral disease: some postural instability: Mild to moderate bilateral disease: some postural instability:

physical independent

physical independent

4

4 Severe disability: still able to walk or stand unassistedSevere disability: still able to walk or stand unassisted 5

(42)
(43)

Current concept in treating PD

Current concept in treating PD

(continuous dopaminergic

(continuous dopaminergic

stimulation)

stimulation)

Tonic and continuous dopaminergic

stimulation occurs in normal

(44)

Pulsatile dopaminergic stimulation

Pulsatile dopaminergic stimulation

promote more dopaminergic cell lost

promote more dopaminergic cell lost

(post synaptic change) resulting in

(post synaptic change) resulting in

development of motor fluctuation and

development of motor fluctuation and

dyskinesia

dyskinesia

(

(45)

Lost of striatal dopamine receptor that occurs

Lost of striatal dopamine receptor that occurs

with disease progression results in a diminished

with disease progression results in a diminished

capacity of these terminal to buffer in

capacity of these terminal to buffer in

fluctuation in plasma levodopa

fluctuation in plasma levodopa

Continuous delivery of dopaminergic agents can

Continuous delivery of dopaminergic agents can

prevent or attenuate the development of

prevent or attenuate the development of

dyskinesia

(46)

Motor complications associated with levodopa

Motor complications associated with levodopa

therapy include motor fluctuations and

therapy include motor fluctuations and

dyskinesia are

dyskinesia are

particular problems in younger patients

particular problems in younger patients

Less likely to occur in those whose symptoms

Less likely to occur in those whose symptoms

begin after the age of 70 years

begin after the age of 70 years

(Golbe LI, neurology 1991, Quinn N, Mov Disord 1987)

(47)

overview

overview

„

„ History of ParkinsonHistory of Parkinson’’s Diseases Disease

„

„ Clinical manifestation of PDClinical manifestation of PD

„

„ Etiology and secondary cause of ParkinsonismEtiology and secondary cause of Parkinsonism

„ „ Classification Classification „ „

Treatment :

Treatment :

„ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

(48)

When to start treatment

When to start treatment

Determine whether the patients have

Determine whether the patients have

functional impairment or not

functional impairment or not 1.

1. Whether the symptoms effect the dominant or nonWhether the symptoms effect the dominant or non-

-dominant hand

dominant hand

2.

2. Whether the patient is employed or employableWhether the patient is employed or employable

3.

3. The type of parkinsonian symptoms that are present The type of parkinsonian symptoms that are present

(e.g. bradykinesia tends to be more disabling than

(e.g. bradykinesia tends to be more disabling than

tremor)

tremor)

4.

4. Individual patient sentimentIndividual patient sentiment

5.

(49)

Symptomatic treatment

Symptomatic treatment

1.

1.

Levodopa

Levodopa

2.

2.

Dopamine agonist

Dopamine agonist

3.

3.

COMT inhibitor

COMT inhibitor

4.

4.

MAO

MAO

BB

inhibitor

inhibitor

5.

5.

Anticholinergic

Anticholinergic

6.

(50)

Sites of action for two types of

Sites of action for two types of

medical therapies to treat PD

medical therapies to treat PD

(51)

Decision tree for early management of PD

Decision tree for early management of PD

American Academy of Neurology, 2001 American Academy of Neurology, 2001

(52)

Levodopa

Levodopa

¾

¾

Most

Most

effective

effective

symptomatically

symptomatically

antiparkinsonian drug

antiparkinsonian drug

¾

¾

All PD patients respond

All PD patients respond

¾

¾

Improves disability and prolongs capacity

Improves disability and prolongs capacity

to maintain employment and independent

to maintain employment and independent

activities of daily living

activities of daily living

¾

(53)

0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 Control Group

Years after 1st presentation

Percent Survival P < 0.0001 with control group P = 0.024 with treated group Levodopa treated Group N = 565 Levodopa non-treated Group N = 215 P < 0.0292 with control group

Adapt from A.H. Rajput/ Parkinson and related Disorders 8 (2001) 95-100

Levodopa prolongs life expectancy

Levodopa prolongs life expectancy

and non

(54)

Is Levodopa Toxic?

Is Levodopa Toxic?

¾

¾ Early patients develop motor fluctuations, but may be a Early patients develop motor fluctuations, but may be a function of neuronal cell loss

function of neuronal cell loss

¾

¾ Increased life expectancy with LD introduction Increased life expectancy with LD introduction

¾

¾ LDLD--naive advanced PD patients develop fluctuations naive advanced PD patients develop fluctuations almost immediately with LD induction

almost immediately with LD induction

¾

¾ No LD neuronal dropout in laboratory animalsNo LD neuronal dropout in laboratory animals

¾

¾ Recent data suggest possible neuroprotectionRecent data suggest possible neuroprotection

¾

¾ Some believe continuous infusion may be safer than Some believe continuous infusion may be safer than pulsatile therapy

(55)

ELLDOPA study

ELLDOPA study

„

„ 360 never360 never--treated PD patients randomized to treated PD patients randomized to

placebo or carbidopa/levodopa (37.5/150,

placebo or carbidopa/levodopa (37.5/150,

75/300, 150/600 mg/day)

75/300, 150/600 mg/day)

„

„ No evidence that levodopa had any deleterious No evidence that levodopa had any deleterious

effect on disease progression and failed to

effect on disease progression and failed to

support the notion of levodopa toxicity

support the notion of levodopa toxicity

Levodopa is not harmful to

(56)

Levodopa

Levodopa

-

-

Induced Dyskinesias

Induced Dyskinesias

9

9 Manifestation of excessive dopaminergic stimulationManifestation of excessive dopaminergic stimulation

9

9 Typically late effect, and with higher dosesTypically late effect, and with higher doses

9

9 Narrowing of therapeutic windowNarrowing of therapeutic window

9

9 Rare in LDRare in LD--naive patients on DA monotherapy naive patients on DA monotherapy

9

9 Most common is Most common is ““peak dosepeak dose”” dyskinesiadyskinesia

9

9 disappears with dose reductiondisappears with dose reduction

9

9 Choreiform, ballistic and dystonic movementsChoreiform, ballistic and dystonic movements

9

9 Most patients prefer some dyskinesias over the Most patients prefer some dyskinesias over the alternative of akinesia and rigidity

(57)

Levodopa/Carbidopa Formulations

Levodopa/Carbidopa Formulations

Onset

Duration

Immediate Release 20-40 min 2-4 hr

10/100, 25/100, 25/250

Controlled Release 30-60 min 3-6 hr

25/100, 50/200

“Fast acting” 10-20 min 0.5-1 hr

(58)

„

„ Levodopa taking alone without DDC Levodopa taking alone without DDC inhinh. only 1 . only 1

% reach the brain

% reach the brain

„

(59)

Prospective, double blind trial in 618

Prospective, double blind trial in 618

levodopa

levodopa

-

-

na

na

ï

ï

ve patients

ve patients

sustained

sustained--release Sinemetrelease Sinemet intermidiate

intermidiate--release Sinemetrelease Sinemet

After 5 years there is no difference in the prevalence

After 5 years there is no difference in the prevalence

of motor complications between two groups

of motor complications between two groups

Similar result with Madopar HBS

Similar result with Madopar HBS

(Block G. Multicenter 5 years study.Eur Neurol 1997)

(60)

Control

Control

-

-

released levodopa

released levodopa

Indication

„ Early morning akinesia „ Night time wearing off

(61)

Fast acting levodopa

Fast acting levodopa

„

„ Madopar DT 125Madopar DT 125 „

„ Early morning dystonia or akinesiaEarly morning dystonia or akinesia

„

„ End of dose wearing offEnd of dose wearing off

„

„ DysphagiaDysphagia

„

(62)
(63)

DB RANDOMIZED

DB RANDOMIZED

DA

DA--AGONIST MONOTHERAPYAGONIST MONOTHERAPY--TRIALSTRIALS

-- DropDrop--outs resulting from outs resulting from AEsAEs-

-*Calculated from published figure

*Calculated from published figure

13%

13%

15%

15%

Pramipexole vs. L

Pramipexole vs. L--DopaDopa

10%

10%

18%

18%

Pergolide vs. L

Pergolide vs. L--DopaDopa

-20% 20% Bromocriptine Bromocriptine -20% 20% Ropinirole Ropinirole vsvs 33% 33% 27% 27% Ropinirole vs. L

Ropinirole vs. L--DopaDopa

13%

13%

16%

16%

Cabergoline

Cabergoline vs.Lvs.L--DopaDopa**

L

L--DopaDopa--ArmArm Agonist

Agonist--ArmArm Study

(64)

DB RANDOMIZED

DB RANDOMIZED

DA

DA--AGONIST MONOTHERAPYAGONIST MONOTHERAPY--TRIALSTRIALS

-- Incidence of Incidence of HallucinosisHallucinosis-

-*2

*2 –– monthsmonths--analysisanalysis

3.3%

3.3%

9.3%

9.3%

Pramipexole vs. L

Pramipexole vs. L--DopaDopa

0%

0%

3.4%

3.4%

Pergolide vs. L

Pergolide vs. L--DopaDopa

-7.7% 7.7% Bromocriptine Bromocriptine -9.0% 9.0% Ropinirole vs. Ropinirole vs. 5.6% 5.6% 17.3% 17.3% Ropinirole vs. L

Ropinirole vs. L--DopaDopa

1.5%

1.5%

1.4%

1.4%

Cabergoline

Cabergoline vs.Lvs.L--DopaDopa**

L

L--DopaDopa--ArmArm Agonist

Agonist--ArmArm Study

(65)
(66)

Motor Complication During

Motor Complication During

Long

Long--term Lterm L--DopaDopa TherapyTherapy

Dose

Dose

a: Lee et all 1971,

a: Lee et all 1971, BarbeauBarbeau and Roy 1976, and Roy 1976, BattistinBattistin et al 1978, et al 1978, RajputRajputet alet al 1984, power et al 1986

1984, power et al 1986

b: Shaw et al 1980, Sweet and McDowell 1975, Markham et al 197

b: Shaw et al 1980, Sweet and McDowell 1975, Markham et al 1974, 4, YahrYahr 1976,

1976, BarbeauBarbeau 1976, McDowell and Sweet 1979, 1976, McDowell and Sweet 1979, PoewePoewe et al 1986.et al 1986.

23

23--88%88% 41

41--64%64% Peak

Peak--dose dyskinesiasdose dyskinesias

65 65--80%80% 35 35--58%58% Motor fluctuations Motor fluctuations >950 mg/d >950 mg/dbb 400 400--800mg/d800mg/daa

(67)

Levodopa Overview

Levodopa Overview

(cont(cont’’d)d)

z Levodopa induces motor complications1-4

„ Up to 80% of Parkinson’s disease patients suffer from motor fluctuations and dyskinesias after

approximately 5 to 10 years of treatment with levodopa4

„ 50% to 75% of patients develop motor

fluctuations 3 to 6 years after initiating therapy1-3

1. Fahn S. Adv Neurol. 1996;69:477-486.

2. Poewe WH, Wenning GK. Neurology. 1996;47(suppl 3):S146-S152. 3. Parkinson Study Group. Ann Neurol. 1996;39:37-45.

(68)

Dykinesias

Dykinesias

and motor fluctuations in

and motor fluctuations in

a community

a community

-

-

based study of PD

based study of PD

Schrag

Schrag et al, 2000et al, 2000

„

„ DykinesiasDykinesias in 28% of the patients in 28% of the patients

„

„ Motor fluctuations in 40% of the patientsMotor fluctuations in 40% of the patients

„

„ Predictors for the evolution of motor fluctuation:Predictors for the evolution of motor fluctuation:

-- Disease durationDisease duration

-- LD doseLD dose

„

„ Predictors for the evolution of dyskinesias:Predictors for the evolution of dyskinesias:

(69)

Mortality of Parkinson

Mortality of Parkinson

s Disease

s Disease

-- Role of LRole of L--DopaDopa Therapy Therapy -

-* pre

* pre--LL--DopaDopa

1,58 1,58 48% 48% 13 years 13 years 130 130 Hely

Hely et al., 1999et al., 1999

0,8 0,8 17% 17% 8 years 8 years 800 800 DATATOP, 1988 DATATOP, 1988 1,43 1,43--2,662,66 34 34--63%63% 15 years 15 years 359 359 Diamond et al. 1987 Diamond et al. 1987 1,46 1,46 27% 27% 13 years 13 years 178 178 Shaw et al. 1980 Shaw et al. 1980 1, 46 1, 46 12% 12% 12 years 12 years 597 597 Yahr Yahr, 1976, 1976 2,90 2,90 38% 38% 9 years 9 years 241 241 * *Hoehn&YahrHoehn&Yahr, 1967, 1967 Mortality Mortality Ratio Ratio Death Death Rate Rate Follow Follow--upup n n

(70)

Mechanism of developing dyskinesia

Mechanism of developing dyskinesia

Risk factors

Risk factors

1.

1. Chronic exogenous exposure to dopaminergic Chronic exogenous exposure to dopaminergic

drugs (mainly when given intermittently);

drugs (mainly when given intermittently);

dopamine receptor

dopamine receptor supersensitivitysupersensitivity

2.

2. Severe dopamine depletion resulting from Severe dopamine depletion resulting from

nigrostriatal

nigrostriatal denervationdenervation

3.

3. The required presence of anatomically intact The required presence of anatomically intact

striatal neurons

(71)

Dopamine Receptor Subtypes

Dopamine Receptor Subtypes

„

„ D1, D2 subcorticalD1, D2 subcortical

„

„ D3, D4, D5 corticalD3, D4, D5 cortical

„

„ Differentiated biochemically & Differentiated biochemically &

pharmacologically into two families:

pharmacologically into two families:

„

„ D1 family: D1, D5D1 family: D1, D5

„

(72)

Dopamine agonist

Dopamine agonist

(1)

(1)

„ „

Ergotamine

Ergotamine

„ „

Bromocriptine

Bromocriptine

„ „

Pergolide

Pergolide

„ „

Lisuride

Lisuride

„ „

* Apomorpine

* Apomorpine

„ „

Carbergoline

Carbergoline

(73)

Dopamine agonist

Dopamine agonist

(2)

(2)

„

„

Non ergotamine

Non ergotamine

„ „

Ropinirole

Ropinirole

„ „

Pramipexole

Pramipexole

„ „

Piribedil

Piribedil

(74)

Dopamine agonist

Dopamine agonist

(3)

(3)

„

„

Reduced motor complication compare

Reduced motor complication compare

with levodopa

with levodopa

„

„

Antiparkinsonian effect superior to

Antiparkinsonian effect superior to

placebo in early

placebo in early

-

-

stage PD

stage PD

„

„

Antiparkinsonian effect comparable to

Antiparkinsonian effect comparable to

levodopa in early

levodopa in early

-

-

stage PD

stage PD

„

(75)

Dopamine agonist

Dopamine agonist

(4)

(4)

„

„

Supplementation with levodopa

Supplementation with levodopa

provides clinical benefits comparable

provides clinical benefits comparable

to levodopa alone but with reduced

to levodopa alone but with reduced

motor complications

motor complications

„

(76)
(77)

DAs: Common Adverse Effects

DAs: Common Adverse Effects

„

„

Nausea, vomiting

Nausea, vomiting

„

„

Dizziness, postural hypotension

Dizziness, postural hypotension

„

„

Headache

Headache

„

(78)

Association of

Association of

effusions

effusions

and

and

fibrosis

fibrosis

with

with

ergot vs.

ergot vs.

non

non

-

-

ergot

ergot

dopamine

dopamine

agonists

agonists

Cabergoline 1997 12 1 0 13 DHEC 1989 1 0 1 2 Lisuride 1968 6 0 1 7 Pergolide 1988 104 8 19 131 Pramipexole 1997 0 0 0 0

Müller T, Fritze J. Clinical Neuropharmacol 2003; 26: 109-111

Year of launch in PD Pleural Pericardial Peritoneal Total Bromocriptine 1979 215 0 29 244

(79)

DAs: Common Adverse Effects

DAs: Common Adverse Effects

„

„

Drowsiness & somnolence

Drowsiness & somnolence

„

„

Dyskinesias (less than Levodopa)

Dyskinesias (less than Levodopa)

„

„

Confusion, hallucinations, paranoid

Confusion, hallucinations, paranoid

„

(80)

DAs: Common Adverse Effects(2)

DAs: Common Adverse Effects(2)

„

„

Pulmonary & retroperitoneal fibrosis, pleural

Pulmonary & retroperitoneal fibrosis, pleural

effusion & pleural thickening, Raynaud

effusion & pleural thickening, Raynaud

s

s

phenomena.

phenomena.

(May be more common with ergotamine DAs)

(81)

Dopamine agonist dose ranges

Dopamine agonist dose ranges

Initiating

(mg)

Usual dose

range (mg)

Bromocripti

ne

1.25 bid-tid

7.5-40

Pergolide 0.05

qd 0.75-6

Pramipexole 0.125

tid 0.75-3

Ropinirole 0.25

tid 9-24

Cabergoline 0.25

qd 0.5-5

Peribedil 50

qd 50-250

(82)

Dopamine agonist

Dopamine agonist

Drug T

½ (h)

Carbidopa/levodopa 1-1.5

Pergolide 12-27

Pramipexole 8-12

Cabergoline 65+

Ropinirole

Bromocriptine

4

6

(83)

Dopamine Agonists in

Dopamine Agonists in

comparison

comparison

As As monotherapy monotherapy and adjunctive and adjunctive to levodopa to levodopa As adjunctive As adjunctive to levodopa to levodopa only only Not being Not being approved approved As As monotherapy monotherapy and and adjunctive to adjunctive to levodopa levodopa US FDA approval US FDA approval (http:// (http://www.accewww.acce ssdata.fda.gov/scri ssdata.fda.gov/scri pts/cder/drugsatf pts/cder/drugsatf da/index.cfm da/index.cfm)) 74.40 74.40 (10 mg/d) (10 mg/d) 137.60 137.60 (1 mg/d) (1 mg/d) 43.68 43.68 (150 mg/d) (150 mg/d) 135.00 135.00 (1.5 mg/d) (1.5 mg/d)

Daily cost (min.

Daily cost (min.

maint.dose maint.dose)) 18.60 18.60 15.00 15.00--34.4034.40 14.56 14.56 26.00 26.00--90.0090.00 Price/tab Price/tab Tab 2.5 mg. Tab 2.5 mg. Tab 0.05, Tab 0.05, 0.25 mg. 0.25 mg. Tab SR 50 Tab SR 50 mg. mg. Tab 0.25, 1 Tab 0.25, 1 mg. mg. Presentation Presentation 10 10--40 divided 40 divided t.i.d t.i.d.. 1 1--4 4 divided

divided t.i.dt.i.d.. 150 150--250 250 divided 3 divided 3--55 1.5 1.5--4.5 4.5 divided

divided t.i.dt.i.d.. Usual daily dosage

Usual daily dosage

(mg) (mg) Bromocriptine Bromocriptine Pergolide Pergolide Piribedil Piribedil Pramipexole Pramipexole

(84)

Assessment of Dopamine Agonists for the

Assessment of Dopamine Agonists for the

treatment of PD according to

treatment of PD according to

Evidence Based

Evidence Based

Medicine

Medicine

*

*

3 Efficacious (maximum strength of evidence)

± Likely efficacious

? Insufficient evidence 0 No studies

(*adapted from Rascol O. et al. Lancet 2002; 359: 1589-1598)

Category Bromocriptine Cabergoline Lisuride Pergolide Piribedil Pramipexole Ropinirole Monotherapy

in early PD ± ? ± 3 ? 3 3

Combination therapy

with L-Dopa in late PD 3 3 ± 3 ? 3 ?

Treatment of motor fluctuations ± ± ? 3 ? 3 3 Prevention of motor complications ± 3 ? ? ? 3 3 Imaging indicates slowed loss of 0 0 0 0 0 3 3 dopaminergic neurons

(85)

Dopamine agonist

Dopamine agonist

„

„ Start lowStart low,, go slow go slow

(

(gradually titrated over several weeks or monthsgradually titrated over several weeks or months))

„

„ Improved motor and ADL scoresImproved motor and ADL scores

„

„ Decreases Decreases ““offoff”” timetime

„

(86)

Apomorphine (1)

Apomorphine (1)

„

„ D1/D2 agonistD1/D2 agonist

„

„ Parenteral delivery (s.c., i.v., sublingual, Parenteral delivery (s.c., i.v., sublingual,

intranasal, rectal)

intranasal, rectal)

„

„ Rapid Rapid ““offoff”” period rescueperiod rescue „

(87)

Apomorphine (2)

Apomorphine (2)

„

„ Treatment of unpredictable, frequent motor Treatment of unpredictable, frequent motor

fluctuations

fluctuations

„

„ continuous s.c. infusion via minicontinuous s.c. infusion via mini--pumppump

„

„ SE: nausea, vomiting, hypotensionSE: nausea, vomiting, hypotension „

„ trimethobenzamide 250 mg t.i.d.trimethobenzamide 250 mg t.i.d.

„

(88)

COMT inhibitor

COMT inhibitor

„

„ No titration easy to administerNo titration easy to administer

„

„ Decreased Decreased ““offoff”” timetime,, increased increased ““onon”” time and time and

enhanced motor responses in patients with

enhanced motor responses in patients with

levodopa motor fluctuation

levodopa motor fluctuation

„

„ Improved motor and ADL scores in stable Improved motor and ADL scores in stable

levodopa responders

levodopa responders

„

„ May reduce risk for motor complications if used May reduce risk for motor complications if used

from onset of levodopa therapy

(89)

COMT inhibitor

COMT inhibitor

„

„

Entacapone

Entacapone

200

200

mg with each dose of

mg with each dose of

levodopa

levodopa

„

„

Talcapone

Talcapone

100

100

-

-

200

200

mg tid

mg tid

„

„

Side effect

Side effect

;

;

discoloration of urine

discoloration of urine

,

,

increase

increase

dyskinesia

(90)

COMT inhibitor

COMT inhibitor

„

„ Increase plasma levodopa elimination half life by Increase plasma levodopa elimination half life by

50%

50% and area under the curve by and area under the curve by 75%75% without without

rising of either the maximal plasma

rising of either the maximal plasma

concentration

concentration((CmaxCmax)) or the time to reach or the time to reach

maximal plasma concentration

(91)

Anticholinergics

Anticholinergics

„

„ Dopaminergic Dopaminergic depletiondepletion→→cholinergiccholinergic

overactivity

overactivity

„

„ Initially used in the 1950sInitially used in the 1950s

„

„ Effective mainly for tremor (rigidity)Effective mainly for tremor (rigidity)

„

„ Common agents (Start low, go slow):Common agents (Start low, go slow):

„

„ TrihexyphenidylTrihexyphenidyl: 2: 2--15 mg/day15 mg/day

„

(92)

Anticholinergics

Anticholinergics

„

„

Side effects:

Side effects:

„

„

Dry

Dry

mouth, sedation, delirium,

mouth, sedation, delirium,

confusion, hallucinations,

confusion, hallucinations,

constipation, urinary retention,

constipation, urinary retention,

impaired cognition

(93)

Selegiline

Selegiline

„

„

Irreversible MAO

Irreversible MAO

-

-

B inhibitor

B inhibitor

„

„

Clinically active by inhibiting dopamine

Clinically active by inhibiting dopamine

metabolism in brain

metabolism in brain

„

„

May be neuroprotective (DATATOP,

May be neuroprotective (DATATOP,

SINDEPAR)

SINDEPAR)

„

(94)

Selegiline

Selegiline

„

„

Side effects: insomnia, hallucinations,

Side effects: insomnia, hallucinations,

nausea (rarely), dyskinesia

nausea (rarely), dyskinesia

„

„

Potential interactions with tricyclics and

Potential interactions with tricyclics and

SSRI antidepressants

SSRI antidepressants

„

„

As adjunct to levodopa, provides reduced

As adjunct to levodopa, provides reduced

motor fluctuations and increased

motor fluctuations and increased

on

on

time

(95)

DATATOP Follow

DATATOP Follow

-

-

Up

Up

„

„ DATATOP: 3 year followDATATOP: 3 year follow--up studies (Ann Neurol up studies (Ann Neurol

1996)

1996)

„

„ subjects requiring levodopa (n=352)subjects requiring levodopa (n=352)

„

„ selegiline made no difference with regard to disease selegiline made no difference with regard to disease

severity, wearing

severity, wearing--off or dyskinesiasoff or dyskinesias

„

„ subjects not requiring levodopa (n=162)subjects not requiring levodopa (n=162)

„

„ No difference in parkinsonian disability between the two No difference in parkinsonian disability between the two

groups

groups

„

„ 8 year follow8 year follow--up (Ann Neurol 1998)up (Ann Neurol 1998)

„

(96)

overview

overview

„

„ History of ParkinsonHistory of Parkinson’’s Diseases Disease

„

„ Clinical manifestation of PDClinical manifestation of PD

„

„ Etiology and secondary cause of ParkinsonismEtiology and secondary cause of Parkinsonism

„ „ Classification Classification „ „ Treatment : Treatment : „ „ medical medical „

„ surgical (new in Thailand)surgical (new in Thailand)

„

„

Late complications:

Late complications:

motor VS non

(97)

Stages in Decline of Response to LD

Stages in Decline of Response to LD

„

„ I: Patient not aware of effect of individual doseI: Patient not aware of effect of individual dose

„

„ II: MidII: Mid--afternoon loss of benefitafternoon loss of benefit

„

„ III: Loss of sleep benefit; earlyIII: Loss of sleep benefit; early--morning akinesia, morning akinesia, possible foot dystonia

possible foot dystonia

„

„ IV: Regular IV: Regular ““wearing offwearing off”” every 4 hours at first, every 4 hours at first, shortens with time

shortens with time

„

„ V: Frequent wearing off, abrupt onV: Frequent wearing off, abrupt on--off, unpredictable off, unpredictable dose response

(98)

Late Complications

Late Complications

„

„ MotorMotor „

„ response fluctuations, dyskinesias, dystonia, freezing, response fluctuations, dyskinesias, dystonia, freezing,

falls

falls

„

„ NonNon--motor (Behavioral/neuropsychological)motor (Behavioral/neuropsychological) „

„ depression, sleep disorders, psychosisdepression, sleep disorders, psychosis

„

„ AutonomicAutonomic „

„ orthostatic hypotension; hyperhidrosis, constipation, orthostatic hypotension; hyperhidrosis, constipation,

impotence, urinary incontinence or retention

(99)
(100)

LD Response Fluctuations

LD Response Fluctuations

„

„ Peripheral causes:Peripheral causes: „

„ delayed gastric emptyingdelayed gastric emptying

„

„ dietary proteindietary protein

„

„ short plasma halfshort plasma half--lifelife

„

„ Central causes:Central causes: „

„ pulsatile delivery to striatal receptorspulsatile delivery to striatal receptors

„

„ impaired storage capacityimpaired storage capacity

„

(101)

Response Fluctuations: Treatment

Response Fluctuations: Treatment

„

„ Increase LD doseIncrease LD dose

„

„ Increase DCI doseIncrease DCI dose

„

„ Add dopamine agonistAdd dopamine agonist

„

„ Add COMT inhibitorAdd COMT inhibitor „

„ reduce LDreduce LD

„

„ liver function monitoringliver function monitoring

„

(102)

Peak Dose Dyskinesia or Dystonia

Peak Dose Dyskinesia or Dystonia

„

„ Chorea more common than dystoniaChorea more common than dystonia

„

„ May be worse on more affected sideMay be worse on more affected side

„

„ May not be as disabling as akinesia/rigidityMay not be as disabling as akinesia/rigidity

„

„ Dose adjustments, addDose adjustments, add--ons:ons: „

„ reduce LD dose, increase dose frequencyreduce LD dose, increase dose frequency

„

(103)

Off

Off

-

-

period Dystonia

period Dystonia

„

„ Appears when LD level is low, especially early Appears when LD level is low, especially early

AM

AM

„

„ w/ or w/o parkinsonismw/ or w/o parkinsonism

„

„ Dose adjustments, addDose adjustments, add--ons:ons: „

„ more frequent LD dosing to avoid low plasma levelsmore frequent LD dosing to avoid low plasma levels

„

(104)

Wearing Off

Wearing Off

„

„ Regular and predictable decline in response 2Regular and predictable decline in response 2--4 4

hours after LD dose

hours after LD dose

„

„ Most common motor fluctuationMost common motor fluctuation

„

„ Dose adjustments, addDose adjustments, add--ons:ons: „

„ change to LDchange to LD--CR, or increase LD frequencyCR, or increase LD frequency

„

(105)

On

On

-

-

off Response

off Response

„

„ Sudden and unpredictable off periods unrelated Sudden and unpredictable off periods unrelated

to dosing schedule

to dosing schedule

„

„ One of the hardest features to manageOne of the hardest features to manage

„

„ Dose adjustments, addDose adjustments, add--ons:ons: „

(106)

Other Motor Complications

Other Motor Complications

„

„ Diphasic dyskinesiaDiphasic dyskinesia

„

„ dyskinesia at beginning and end of dosedyskinesia at beginning and end of dose

„

„ Dose adjustments, addDose adjustments, add--ons: add DAons: add DA

„

„ Drug failureDrug failure

„

„ late afternoon, probably related to poor gastric emptying or late afternoon, probably related to poor gastric emptying or

absorption

absorption

„

„ liquid preparations; increase gastric motility; decrease dietaryliquid preparations; increase gastric motility; decrease dietary

protein

protein

„

(107)

Freezing and Falls

Freezing and Falls

„

„ FreezingFreezing

„

„ motoric block; at initiation of gait, turning, narrow spacesmotoric block; at initiation of gait, turning, narrow spaces

„

„ use auditory, visual, proprioceptive cuesuse auditory, visual, proprioceptive cues

„

„ FallsFalls

„

„ physical therapy evaluationphysical therapy evaluation

„

(108)

Psychosis

Psychosis

„

„ FeaturesFeatures

„

„ Vivid dreams/nightmares, disorientation, hallucinations, delusioVivid dreams/nightmares, disorientation, hallucinations, delusional nal

thought

thought

„

„ Simplify medical regimenSimplify medical regimen

„

„ Stop unnecessary nonStop unnecessary non--PD medsPD meds

„

„ Stop: anticholinergic drugs, amantadine, selegiline, dopamine agStop: anticholinergic drugs, amantadine, selegiline, dopamine agonists, onists,

COMT inhibitors

COMT inhibitors

„

„ Change from CR to standard carbidopa/levodopaChange from CR to standard carbidopa/levodopa

„

„ Try atypical antipsychotic agentsTry atypical antipsychotic agents

„

(109)

Depression

Depression

„

„ Reported in 30Reported in 30--90% of PD patients90% of PD patients

„

„ Difficult to discern from vegetative symptomsDifficult to discern from vegetative symptoms

„

„ Requires inquiry into depression symptomsRequires inquiry into depression symptoms

„

„ Usually responds quickly to medicationsUsually responds quickly to medications

„

„ Tricyclic agentsTricyclic agents

„

„ Selective serotonin reSelective serotonin re--uptake inhibitorsuptake inhibitors

„

(110)

Anxiety/Restlessness

Anxiety/Restlessness

„

„ Primary anxiety disorder: treat with Primary anxiety disorder: treat with

benzodiazepines

benzodiazepines

„

„ Associated with Associated with ““offoff--periodsperiods”” or lowor low--levodopa levodopa

levels: adjust levodopa dosing

levels: adjust levodopa dosing

„

„ Restless Leg Syndrome: benzodiazepines, Restless Leg Syndrome: benzodiazepines,

narcotics, levodopa, dopamine agonists

(111)

Sleep Disorders (1)

Sleep Disorders (1)

„

„ InsomniaInsomnia „

„ careful historycareful history

„

„ difficulty with sleep initiation: tricyclic agents, difficulty with sleep initiation: tricyclic agents,

benzodiazepines, diphenhydramine, chloral hydrate

benzodiazepines, diphenhydramine, chloral hydrate

„

„ treat depressiontreat depression

„

(112)

Sleep Disorders (2)

Sleep Disorders (2)

„

„ Excessive daytime sleepinessExcessive daytime sleepiness „

„ Correct poor sleep at nightCorrect poor sleep at night

„

„ Discontinue anticholinergics, amantadineDiscontinue anticholinergics, amantadine

„

„ Reduce dopamine agonist, levodopa dosages if Reduce dopamine agonist, levodopa dosages if

possible

possible

„

(113)

Orthostatic Hypotension

Orthostatic Hypotension

„

„ LightLight--headedness, dizziness, fatigue, shoulder or neck headedness, dizziness, fatigue, shoulder or neck pain, blood pressure drops when standing

pain, blood pressure drops when standing

„

„ Taper antiTaper anti--hypertensive agentshypertensive agents

„

„ Taper nonTaper non--PD drugsPD drugs

„

„ Increase salt intakeIncrease salt intake

„

„ Compression stockingsCompression stockings

„

„ Fludrocortisone (0.1Fludrocortisone (0.1--0.4 mg/d)0.4 mg/d)

„

(114)

Urinary Incontinence/Frequency

Urinary Incontinence/Frequency

„

„ Rule out urinary tract infectionRule out urinary tract infection

„

„ Bladder evaluation forBladder evaluation for

„

„ detrusor hyperactivitydetrusor hyperactivity

„

„ oxybutinin 5 oxybutinin 5 --30 mg/d; propanthaline 7.5 30 mg/d; propanthaline 7.5 -- 15 mg/d15 mg/d „

„ detrusor hypoactivitydetrusor hypoactivity

„

„ phenoxybenzamine; prazosinphenoxybenzamine; prazosin

„

„ Urinary frequencyUrinary frequency

„

„ avoid fluid pooling in feetavoid fluid pooling in feet

„

(115)

Sexual Dysfunction

Sexual Dysfunction

„

„ Medical screeningMedical screening „

„ depression, anxiety, iatrogenic causesdepression, anxiety, iatrogenic causes

„

„ Endocrinologic evaluationEndocrinologic evaluation „

„ prolactin, testosterone, lutenizing hormone, thyroid prolactin, testosterone, lutenizing hormone, thyroid

screen

screen

„

„ Urologic evaluationUrologic evaluation „

(116)

Nausea

Nausea

„

„ LevodopaLevodopa--related: take with meals, add related: take with meals, add

carbidopa, add domperidone

carbidopa, add domperidone

„

„ Other antiOther anti--PD medications: same. PD medications: same. „

„ If no improvement: withdraw newest agent, reIf no improvement: withdraw newest agent, re-

-initiate at minimal doses, slowly increase

(117)

Excessive Sweating

Excessive Sweating

„

„ Usually levodopa related, and may be seen at Usually levodopa related, and may be seen at

peak or trough dose drug levels

peak or trough dose drug levels

„

„ reduce levodopareduce levodopa

„

„ add dopamine agonist or COMT inhibitoradd dopamine agonist or COMT inhibitor

„

„ add carbidopaadd carbidopa

„

(118)

Surgical Treatment

Surgical Treatment

in

in

Parkinson

Parkinson

s Disease

s Disease

(119)

Surgical Treatments for Parkinson

Surgical Treatments for Parkinson’’s Diseases Disease

„ „ AblativeAblative „ „ thalamotomythalamotomy „ „ pallidotomypallidotomy „

„ Electrical stimulationElectrical stimulation „

„ VIM thalamus, globus pallidus internus, subVIM thalamus, globus pallidus internus, sub-

-thalamic nucleus

thalamic nucleus

„

„ TransplantTransplant „

„ autologous adrenal, human fetal, xenotransplants, autologous adrenal, human fetal, xenotransplants,

genetically engineered transplants

(120)

Thalamotomy

Thalamotomy

„

„ Significant improvement in contralateral tremorSignificant improvement in contralateral tremor „

„ depends on correct placementdepends on correct placement

„

„ Minimal improvement in other PD signsMinimal improvement in other PD signs

„

„ Bilateral procedures poorly toleratedBilateral procedures poorly tolerated

„

„ AEs: bulbar, sensory and motor deficits, gait, AEs: bulbar, sensory and motor deficits, gait,

surgical complications

surgical complications

„

(121)

Deep Brain Stimulation (DBS)

Deep Brain Stimulation (DBS)

„

„ High frequency, pulsatile, bipolar electrical High frequency, pulsatile, bipolar electrical

stimulation

stimulation

„

„ Stereotactically placed into target nucleusStereotactically placed into target nucleus

„

„ Can be activated and deactivated with an Can be activated and deactivated with an

external magnet

external magnet

„

„ Exact physiology unknown, but higher Exact physiology unknown, but higher

frequencies mimic cellular ablation, not

frequencies mimic cellular ablation, not

stimulation

(122)

Movement Disorder Surgery

Movement Disorder Surgery

ศรัณย นันทอารี Siriraj Movement Disorder Group อภิชาติ พิศาลพงศ กนกวรรณ บุญญพิสิฎฐ อรสา ชวาลภาฤทธิ์ นิพนธ พวงวรินทร ไพรัช สายวิรุณพร วรพรรณ เสนาณรงค นันทศักดิ์ ทิศาวิภาค

(123)

VIM Thalamic DBS

VIM Thalamic DBS

„

„ 80% reduction in contralateral arm and leg tremor80% reduction in contralateral arm and leg tremor

„

„ Possible mild improvement in bradykinesia and rigidityPossible mild improvement in bradykinesia and rigidity

„

„ No functional improvement (UPDRS part II), but No functional improvement (UPDRS part II), but significant improvement based upon global scores

significant improvement based upon global scores

„

„ No effect: gait and bulbar symptomsNo effect: gait and bulbar symptoms

„

(124)

Globus Pallidus internus DBS

Globus Pallidus internus DBS

„

„ Effects tend to mimic those of pallidotomyEffects tend to mimic those of pallidotomy

„

„ Significant improvement in dyskinesiaSignificant improvement in dyskinesia

„

„ Moderate improvement in cardinal Moderate improvement in cardinal ““offoff”” signssigns

„

„ No comparison between unilateral and bilateral No comparison between unilateral and bilateral

„

„ Bilateral DBS may be better tolerated than bilateral Bilateral DBS may be better tolerated than bilateral pallidotomy

pallidotomy

„

(125)

Bilateral Subthalamic DBS

Bilateral Subthalamic DBS

„

„ Bilateral placement appears to be superior to Bilateral placement appears to be superior to

unilateral placement

unilateral placement

„

„ Theorized neuroprotective mechanism, but no Theorized neuroprotective mechanism, but no

clinical evidence supporting this

clinical evidence supporting this

„

„ AE: confusion and hallucinations, increased AE: confusion and hallucinations, increased

dyskinesia before medication adjustments, eyelid

dyskinesia before medication adjustments, eyelid

opening apraxia, weight gain, surgical

opening apraxia, weight gain, surgical

complications

Figure

Updating...

References