Management of parkinson

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Management of parkinsons disease.

• Dr. Sanjiv Chandratre.
• Consultant in med. for elderly.
• 21 Jan. 2009

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What you should expect from this teaching session.

• How to diagnose PD.
• What is the D/D of PD
• How to treat PD ( Medical treatment.)
• When to refer pts to secondary care.
• Tricks of the trade in managing special problems
  related to PD.
• What services are available in our area for PD
  patients.
• Nice guidelines on PD and results of our audit.

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James parkinson 1817

• Involuntary tremulous motion, with lessened
  muscular power, in part not in action and even
  when supportedwith a propensity to bend the
  trunk forward, and to pass from a walking to a
  running pace the senses and intellect being
  uninjured.

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Terminology in P. D.

• Parkinsons disease or Idiopathic P. D.
• Parkinsonism / Parkinsonian syndrome.
• Drug induced Parkinsonism.
• Post encephalitic parkinsonism.
• Vascular pseudo Parkinsonism.
• Lower body parkinsonism.

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Terminology in P. D.

• Parkinsonism plus syndrome.
• PSP
• MSA
• CBD

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Parkinsons disease

• Progressive, disabling and distressing
• Appropriate management and planning right from
  the start can prevent some of the most
  distressing features
• Team work can solve most of the problems and can
  help deliver better care cost effectively
• The 4 stages.

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4 stage clinical management scale

• Diagnosis
• Maintenance therapy
• Complex
• Palliative care

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Incidence and Prevalence

• Incidence
• Number of new cases in a population, usually
  /100,000
• Around 11 per 100,000

• Prevalence
• Total number of people in a population with the
  condition,
• I.e.cumulative incidence per annum minus deaths.
• Around 100- 200 per 100,000

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Prevalence

• Per GP.
• Say 2500

• Per district / pct.
• Say 200,000

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Brain Bank Criteria

• Step 1
• Diagnosis of parkinsonian syndrome
• Step2
• Exclusion criteria for IPD
• Step3
• Supportive criteria for IPD

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Step1- Diagnosis of parkinsonian Syndrome.

• Bradykinesia at least one of the following
• Muscular rigidity
• 4 6 Hz resting tremor
• Postural instability

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Brady / Hypokinesia

• Hypokinesia poverty of movement
• Loss of facial expression, arm swing, gesture
  etc.
• Bradykinesia -Slowness of movement
• Decay finger/ heel tap

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Rigidity

• Resistance to passive movement
• Reinforcement froments manoeuvre
• Constant c. f. clasp-knife
• Lead pipe
• cogwheel
• Gagenhalten

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Tremor

• Involuntary rhythmical alternating movement
• Begins unilaterally upper limb
• 4 6 hertz, pill rolling
• First symptom in 75
• - 20 never develop it
• Postural tremor can also occur

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Postural instability.

• Last cardinal feature to appear
• Limited diagnostic specificity in the elderly.
• Pull test
• Early falls red flag

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Step 2 exclusion criteria

• History of repeated strokes.
• History of repeated head injury.
• History of definite encephalitis.
• Cerebellar signs.
• Early severe autonomic involvement
• Supranuclear gaze palsy
• Neuroleptic drugs
• Negative response to large doses of levodopa

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Step3- positive supportive criteria

• gt3 for definite PD
• Unilateral onset.
• Rest tremor
• Progressive
• Persistent asymmetry
• Excellent levodopa response
• Severe levodopa induced chorea
• Levodopa responsegt5years
• Clinical coursegt10 years

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Diagnosis- Accuracy

• Meara 1999 Age and ageing
• Community study- 402 cases
• 73 Parkinsonism
• 53 probable IPD
• Essential tremor
• Alzheimers disease
• vascular

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Accuracy of diagnosis

• Brain bank post mortem series
• 24 error rate.
• 10 latest studies.
• 2 MD specialists.
• Community series
• gt50 error rate

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Is the diagnosis correct?

• Diagnosis of P. D. can be very difficult.
• There is no diagnostic test.
• Diagnosis is made clinically.
• DAT scan of limited value.
• Error rate is high. 25 in the hands of
  neurologist. Upto 50 in the community.
• F.U. and review of diagnosis is important.

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The Dopaminergic Synapse- Basis for DaTSCAN
cellular response
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scanner
side
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Dopamine Transporter Imaging agent

• Parkinsons disease
• Progressive Supranuclear Palsy
• Multiple System Atrophy

• Essential Tremor
• Neuroleptic-induced Parkinsonism
• Vascular disease

Abnormal
Normal
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Differential diagnosis of parkinsonian syndrome

• Idiopathic Parkinsons disease
• Drug induced phenothiazines
• Multiple cerebral infarct state.
• Trauma pugilistic encephalopathy
• Toxin induced- MPTP, CO, Mn, Cu,
• Parkinsons plus syndromes

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Essential tremor

• Most common diagnostic error.
• 10 times more common than PD.
• Postural or action tremor.
• Titubation.
• Family history.
• B Blockers help.

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Drug induced parkinsonism.

• Causes
• Predictable Neuroleptic drugs (both typical
  and atypical)
• Hidden neuroleptics- metoclopromide,
  prochlorperazine Combination with
  antidepressants( fluphenazine )
• Calcium antagonist
• --Idiosyncratic
• Lithium, sodium valproate, amiodarone
• mainly tremor but parkinsonism
  reported.

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Multiple infarct state

• Synonymous with leucoariosis, Binswangers
  encephalopathy
• Related to hypertension and other risk factors
• Common misdiagnosis.
• Poor prognosis
• Aspirin and dipyridamole retard may be effective
  and safe

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Vascular parkinsonism

• PM studies 2-3 incidence of pure vascular
  causes
• -no lewy bodies or nigral degeneration
• Acute or abrupt onset
• basal ganglia infarct
• Insidious progression
• Diffuse sub cortical white matter ischaemia.

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Dementia with Lewy bodies

• Fluctuating alertness
• Hallucinations
• Mild parkinsonism
• Neuroleptic sensitivity

• Tremor less common
• More symmetrical
• Myoclonus more common
• More rigid, less bradykinetic

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Medical treatment of P. D.

• Only 18 drugs for PD in BNF 2008
• 14 Dopaminergic
• 4 Anticholinergic.

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Drugs to avoid 1

• Antiemetics
  
• Metoclopromide (Maxalon)
• Prochlorperazine (Stemetil)
• The only recommended antiemetics are
• Domperidone
• 5ht3 antagonists eg. Ondensetron.

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Drugs to avoid 2

• Antipychotics
• Chlorpromazine
• Sulpride
• Haloperidol
• Thioridazine.
• Newer antipsychotic can be used with caution

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When to start treatment ?

• Controversial
• Is the diagnosis certain.
• Age of patient.
• Effect on ADL.
• Patient Choice.

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Drugs in PD

• Levodopa preparations.
• Dopamine receptor agonists.
• Monoamine oxidase-B inhibitors.
• Catechol-o-methyltransferase inhibitors.
• Anticholinergics.
• Amantadine

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Levodopa

• Used since the 1960s
• Remains the gold standard
• Always used with dopa decarboxylase inhibitor.(
  either carbidopa or benserazide.)
• Side effects are common.

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Levo dopa preparations.

• Madopar or co beneldopaLevodopa with benserazide
• Sinemet or co careldopaLevodopa with carbidopa

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Levodopa formulations

• Effervescent or dispersible eg. Madopar
  dispersible.
• Conventional release.eg. Madopar
• Controlled release.eg. Madopar CR or Sinemet CR
• Duodopa As a gel.

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Levodopa preparations

• Dispersible preparationsUse for morning kick
  start or for on off fluctuations. Also in
  patients with swallowing difficulties.
• CR preparations unpredictable absorption. Use
  now mostly at night for nocturnal symptoms like
  difficulty turning in bed or AM dystonias

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Side effects of levodopa

• Very common
• Nausea, vomiting
• Excessive drowsiness
• Insomnia
• End of dose fluctuations.
• Nocturnal immobility.
• Motor fluctuations and dyskinesias.

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Dopamine agonists

• First available since 1970s
• Six DAs available for oral use.
• Apomorphine administered parenteraly
• Act directly on post synaptic receptors.
• Two types
• Ergot derived.
• Non ergot derived.

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Dopamine agonists

• ERGOT
• Bromocriptin
• Lisuride
• Pergolide
• Cabergoline

• Non ERGOT
• Ropinirole
• Pramipexol
• Apomorphine.

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Rotigotine

• DA
• Mono therapy or adjunct.
• Patches.

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Side effects of DAs

• Similar to levodopa
• Nausea.
• Vomiting.
• Postural hypotension.
• Confusion.
• Hallucinations.
• Somnolence.

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Side effects of ERGOT DAs

• Fibrotic reactions.
• Pulmonary, retroperitoneal and pericardial
  fibrosis.
• Cardiac valvulopathy.
• In most cases non ergot DAs preferred.
• CXR, PFTs, ESR,and S. creatinine before
  starting treatment.

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Unusual side effects of DAs

• Complex group of impulse control disorders
• Pathological gambling.
• Hypersexuality.
• Compulsive eating or shopping.
• . Repetitive perseverative behavior.
• -- Punding
• -- Excessive hobbyism.

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Unusual side effects of DAs 2

• Dopamine dysregulation syndrome
• Compulsive use of increasing doses of levodopa
• hedonistic homeostatic dysregulation syndrome.
• 14 prevalence of ICD.
• Eight fold increase in those taking DAs
• Young pts. are particularly prone.

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SOOS

• Excessive day time sleepiness and soos can occur
  with levodopa preparations and with DAs
• Warn patients about driving.

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Amantidine

• Antiviral properties.
• Weak DA
• Only for moderate to severe dyskinesia.
• Glutamate antagonist.
• 100 mg. BD or TDS

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COMT inhibitors

• Entacapone
• Talcapone
• In combination with levo dopa
• ( STALEVO)

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Stalevo

• Combination of Levodopa, carbidopa and
  Entacapone.
• 50 mg./12.5 mg./200 mg.
• 100 mg./25mg./200mg.
• 150 mg./37.5mg./200 mg.
• 200 mg./50 mg./ 200 mg.

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MAO -B inhibitors

• Selegiline
• 10 mg. Od or 5 mg. Bd
• 2.5 mg in elderly.
• Zelapar( oral lyophilisate ) 1.25 mg. Before
  breakfast. Place on tongue and allow to dissolve
• Neuroprotective??
• Rasagiline
• 1 mg. Expensive.

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Antimuscarinic drugs.

• - Benzatropine, Procyclidine,Orphenadrine
• - Limited use.
• - Cognitive impairment in elderly.
• - Useful in drug induced Parkinsonism.
• - can be used for excessive salivation.

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Apomorphine

• Potent dopamine agonist.
• Significant cost (10,000 PA for cont.
  infusion.) offset by keeping pts. Out of NHs
• Only parenteral use.
• Subcutaneous (rescue ) injections.
• SC continuous infusion.

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Apomorphine.

• Severely emetogenic.
• Needs priming with Domperidone.
• Only used in advanced PD with severe motor
  fluctuations.
• Injection site reactions.
• Could be an alternative to invasive surgical
  procedures.

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DO NOT MISS P. D. MEDICATION

• Akinetic Rigid Syndrome.
• Malignant neuroleptic syndrome.
• GET IT IN TIME

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Non motor symptoms in P. D.

• Constipation
• Hallucinations.
• Dementia / psychosis.
• Excessive salivation.
• Excessive sleep.
• REM behaviour disorders.

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P. D. and Driving

• Booklet from PDS.
• Diagnosis of P. D. does not necessarily
  disqualify people from driving
• Dopamine agonists-
• Drowsiness
• SOOS

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Do I have to inform DVLA

• Yes.Required by law.
• Drivers medical unit at DVLA
• Criminal offence under RTA 1988

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Take home messages

• Diagnosis of PD is clinical and can be difficult.
• Every patient should be referred to secondary
  care to confirm the diagnosis and initiate
  treatment
• Treatment should only be started if there is
  functional impairment
• Levodopa is the gold standard but DA cause much
  less diskinesia
• Follow up should be life long

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Thank you.

• .

ANY QUESTIONS ?
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Outline

• 1. History
• 2. Diagnosis
• 3.Differential diagnosis
• 4.Cost factors
• 5. Local scene
• 6. Take home messages

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Historical aspects

• James parkinson 1755- 1824 1817
• Charcot - la maladie de parkinson
• Lewy 1921
• Carlson 1958
• Birkmayer, Hornykiewicz 1961
• Cotzias 1967
• Hoehn and yahr 1967

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Why is diagnosis of PD and parkinsonian syndromes
challenging?

• Diagnosis is clinical
• Presence and progression of clinical
  features Supportive for PD
• Atypical for PD Red flags
• Most difficult in early stages
• Large number of imitators of PD
• Co morbidity and confounders increase with age
• Tremors, shaking
• Gait disorders
• Slowness and true bradykinesia

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Diagnostic Challenges

• Prevalence of Signs of Parkinsonism in the
  Normal Elderly Population
• Co-existent Pathology
• Cerebrovascular Disease
• Depression
• Arthritis
• Differential Diagnosis
• Essential Tremor
• Parkinsons Plus Syndromes
• Alzheimers
• Lewy Body Disease

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Challenge tests

• Oral levodopa/ subcutaneous apomorphine
• False positives e. g. M.S.A. and false
  negatives
• Lowest sensitivity / specificity in early disease
• Not recommended routinely
• Priming

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Cost Overview

• Direct Costs
• Indirect Costs
• TOTAL Direct Indirect

NHS
Social services
Private Expenditure
(Financial Benefits)
Lost earnings
OR
Lost leisure time
OR
Carer replacement cost
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Total Cost of PD Care 1994 382,705
, 000
Out-patient 19,147 5
Drugs 26,900 7
Hospital In-patients 49,386 13
Home Care 107,915 28
Residential Home 179,358 47
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Conclusions PD Economic Impact (1)

• Parkinsons Disease is an expensive condition
• The greatest single costs relate to lost earnings
  in younger patients long term institutional care
  in older patients
• Mean direct costs per patient is inversely
  proportional to age
• c4,000 per annum below 65 years
• c9,400 per annum over 85 years
• Mean direct annual costs is inversely
  proportional to disease severity
• Hoenhn Yahr stage (0-1) c3000
• Stage 5 c18,400
• Greater than five fold increase

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Previous Cost Estimates (2)

• Moving and Shaping PDS, 1999
• Estimated costs of PD
• 3,500-10,000 per patient
• 7-20,000 per GP
• 560,000-1.6m per PCG
• Dodel 2000 MoDis (Barcelona)
• Nuijten Oct. 2000 EFNS
• 50,000 Euro in 5 yrs (6k pp/pa)
• model used in justification of additional drug
  cost

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What can we except in the near future?

• Neuroprotective agents. Problems in trial
  designs.
• Continuous dopaminergic stimulation. Rotigotine
  patch,once daily formulations of pramipexol and
  Ropinirole.
• Neurorestoration- Stem cell implants, Nerve
  growth factors

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Conclusions the Economic Impact (3)

• Within NHS costs, the split between primary care
  (incl drugs) and secondary care is roughly equal
  across age groups.
• However, across HY stages secondary care
  accounts for an increasing proportion (27 in
  stages 0-1, 62 in stage V)

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Case history 1complex phase IPD

• A.L. 65 yrs. M
• Nov 02 .ref. by Dr omer( previously under Dr.
  Loisou )
• P. D. 12 yrs.
• Severe Dyskinesia End of dose? Random?
• On madopar, selegeline , Ropinirole and
  dispersible madopar
• Could not tolerate Entacapone
• Ref. to Leeds ( Dr. spokes ) after I. P. stay

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Case history 1( contin.)

• Decided to admit to LGI for trial of apomorphine
• 20 weeks in LG
• Aspiration pneumoniaITUVentilated-
  TracheostomyPEG.back to CRH
• Refused RH/ NH. Very dependent. Huge package of
  care.----Home.
• Managed for 5 months. Readmitted with aspiration
  pneumonia
• Died.

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Average total life expectancy uk 1999

• Age

Male Female
0 75.1 75.1 80.0 80.0
30 46.4 76.4 50.8 80.8
60 19.2 79.2 22.8 82.8
85 6.9 91.9 8.6 93.6
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European Parkinsons Association and WHO charter
of rights for people with PD

• People with Parkinsons have the right to
• Be referred to a doctor with a special interest
  in Parkinsons
• Receive an accurate diagnosis
• Have access to support services
• Receive continuous care and
• Take part in managing the illness
• Declared on this day the 11th day of April 1997

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Case 2

• H.J. 80 m . Rtd. Bank manager
• With wife, slight confusion
• Fully compesmentis
• No evidence of P.D.
• All investigations- NAD
• 9mths later---review
• Restless and agitated at night ,paranoid
• Walked slowly

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Case 2 (cont.)

• No definite evidence of P.D.
• ??parkinson plus syndrome
• Ref. to Dr.. Orange
• Admitted v. hallucinations.
• Confused, fluctuating cognition, hypomimia
• Pill rolling tremor---
• Rapid deterioration
• Needed N.H.

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case3

• H.B. 84 M , lives with wife at Hebden bridge. On
  holiday adm. To hospital in Lancashire chest
  infection. Started on madopar--- lack of facial
  expression
• Transferred to CRH
• Not convinced with diagnosis of PD
• Madopar stopped.
• No change
• F. u. in opd

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Case 1 GPs Letter

• Please see this 62 year old man with a 6 year
  history of an upper limb tremor. This interferes
  with eating and is a considerable embarrassment
  to him.
• I thought this was Parkinsons Disease and gave
  him Sinemet Plus 1 tds but there has been no
  response.
• I am not sure what is wrong with him and would
  value your advice.

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Case 1 GPs letter

• What is the most likely diagnosis and why?
• What is the relevance of the duration of the
  history?
• What is the relevance of the physical type of
  tremor and the trouble it is causing?
• Is the lack of response to Levodopa relevant?

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Case 1 Your history examination

• 6 years progressive postural action tremor
• Main problem with teacups and spoons
• No regular medication
• Brother has similar tremor
• Symmetrical upper limb postural and action tremor
• No features of Parkinsons Disease

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Case 1 Your history examination

• What is the diagnosis now?
• What is the relevance of the drug history?
• What is the relevance of the family history?
• Is this type of tremor always symmetrical?

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Case 1 Conclusions

• Diagnosis Essential Tremor
• Note duration, tremor with posture / action,
  family history and lack of response to Levodopa
• Beware Beta-agonist Inhalers for asthma
• Response to Ethanol
• Can effect head (titubation) and voice
• Prevalence 10 times more common than P.D.

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Case 1 - Conclusions

• Treatment
• None
• Propranolol LA 80 mg/d for one week then 80 mg
  bd. No better in 2 months 80 160 mg/d then
  another 2 months 160 mg bd.
• Primidone Syrup (250 mg/5 ml) 125 mg/d
  increased at weekly intervals by 125 mg/d
  depending on response and tolerance
• Other anti-epileptic drugs can be tried such as
  Gabapentin and Topiramate
• Botulinum toxin into forearm muscles controlling
  wrist action must be repeated at 3 monthly
  intervals
• Bilateral thalamic stimulation if very
  debilitating

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Case 2 GPs Letter

• This 82 year old man was diagnosed with
  Parkinsons Disease by Dr X last year. He has
  not responded to Sinemet and his wife would like
  an expert opinion.
• His gait has deteriorated over the last few years
  and now he is rather confused.
• He has mild angina and hypertension. He wears an
  urinary sheath for incontinence.
• The home situation is getting very precarious and
  the family desperately need him to be treated
  effectively.

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Case 2 GPs Letter

• Has he got Parkinsons Disease?
• What clinical features does he have?
• What is the most likely diagnosis?

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Case 2 Your history examination

• 7 year progressive history of
• Shuffling gait with recent falls
• Cognitive decline with poor short-term memory and
  confusion
• Urinary incontinence
• Normotensive on anti-hypertensives
• No cardiac signs
• No Parkinsonian features in the upper limbs
• Shuffling gait
• Reflexes marginally brisk with flexor plantar
  responses

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Case 2 Your history examination

• What is the most likely diagnosis?
• What are the alternatives?
• What investigations would you do?
• What treatment would you recommend?

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Case 2 - Conclusions

• Diagnosis Multiple Infarct State
• Synonymous with leucoariosis, Binswangers
  encephalopathy
• Related to hypertension and other risk factors
• Common misdiagnosis!
• Poor prognosis
• Aspirin and Dipyridamole retard may be effective
  and safe

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Case 3 GPs Letter

• This 58 year old man has been under the care of
  Urologists for many years with renal stones. His
  gait over the last year has been unsteady and he
  is generally a little slow.
• His wife is a nurse and wonders if he has a
  neurological disorder. I would very much value
  your opinion.

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Case 3 GPs Letter

• What are the possible diagnoses?

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Case 3 Your history examination

• 2 year history of tendency to shuffle and general
  slowness but no falls or tremor
• Symmetrical bradykinesia and hypokinesia
• Rigidity with reinforcing manoeuvres in both
  upper limbs
• No tremor
• Reflexes all pathologically brisk with flexor
  plantar responses
• Closer questioning reveals impotence for last 4
  years
• No postural drop in blood pressure

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Case 3 Your history examination

• What is the diagnosis?
• What are the diagnostic features?
• What systems are involved?
• What investigations can be performed?
• How would you treat him?

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Case 4 - Conclusions

• Diagnosis Progressive Supranuclear Palsy
• Systems involved
• Dementia
• Ophthalmoparesis downgaze, then upgaze then
  horizontal gaze palsy
• Extrapyramidal Parkinsonism, early falls!
• Corticospinal tracts upper motor neurone signs
  in limbs and bulbar musculature (dysphagia)
• Miscellaneous retrocollis
• Poorest prognosis median survival 7 years

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GP suspects PD
GP refers for specialist opinion
Specialist confirms diagnosis
Wait for significant functional disability
Levodopa
Dopamine agonist
Motor complications develop
Disease progression
Add small amounts of Levodopa
Motor complications develop
Consider CR Levodopa Consider agonist Consider
Entacapone
Consider CR Levodopa Consider Entacapone
Severe motor complications
Consider Apomorphine / Consider Surgery
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Fractionate dose of Levodopa
Consider modified-release Levodopa
Add modern Dopamine agonist
Add Entacapone
Consider Apomorphine Injections or infusions
Consider surgery
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Case 4 GPs Letter

• What is the likely diagnosis?
• What are the diagnostic features?

100
Case 4 GPs Letter

• Thank you for seeing this 56 year old man with
  unsteadiness and falls over the last 3 years.
• His wife says he is slowing down and mentally is
  not as agile as he was. As a result he took
  early retirement last year.
• He looks as though he has Parkinsons Disease to
  me but I would value your opinion.

101
Case 4 Your history examination

• 3 year history of progressive shuffling gait and
  falls for the last 12 months
• Possible dementia
• Normal eye movements and bulbar function
• Parkinsonian facies and rigidity with symmetrical
  hypokinesia and bradykinesia
• No tremor
• Very slow unsteady gait with tendency to fall
  backwards
• Reflexes brisk and plantar responses extensor

102
Case 3 - Conclusion

• Diagnosis Multiple System Atrophy
• Systems involved
• Extrapyramidal Parkinsonism
• Cerebellar signs ataxia, intention tremor,
  nystagmus
• Corticospinal tracts upper motor neurone signs
  in limbs
• Autonomic function impotence, bladder
  disturbance, postural hypotension
• Miscellaneous disproportionate antecollis,
  laryngeal dystonia (sudden death)
• No dementia!
• Intermediate prognosis median survival 9
  years
• Emotional incontinence

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Case 4 Your history examination

• What is the diagnosis?
• What are the diagnostic signs?
• What systems are involved?
• What investigations can be performed?
• How would you treat him?

104
Calne classification 1992

• Clinically possible IPD One of the following
  tremor, rigidity, bradykinesia
• Clinically probable IPD Two of the following
  cardinal features resting tremor, rigidity,
  bradykinesia,or postural instability or if
  resting tremor, rigidity, or bradykinesia are
  asymmetric
• Clinically definite IPD three of the cardinal
  features or two cardinal features with one of the
  first three presenting asymmetrically

105
Local scene

• PD clinic started 2 nd nov. 04
• PD nurse interviews in feb 05
• PD society in Halifax very active and has
  pledged 52,000 for pump priming a nurse post.
• Patients who need apomorphine have to travel to
  Leeds

106
What can we expect in the near future?
107
Everything that shakes is not Parkinsons

• Dr. S. N. Chandratre.
• Consultant Medicine for Elderly.
• Calderdale Royal Hospital.

108
Stages of P. D.

• Diagnostic phase
• Maintenance phase.
• Complex phase.
• Palliative phase.

109
Drugs used in P. D.

• Dopamine receptor agonists.
• Levo dopa preparations.
• MAO B Inhibitors
• COMT Inhibitors.
• Amantidine

110
Treatment of P. D.

• Medical
• Surgical
• Complementary
• Role of PDNS, OT, Physio, SALT, Dietetian, SW

111
Route of administration

• Oral Effect of meal ?
• Sub cuteneous
• Skin patch
• Effervescent tablets.
• Duodopa- via PEG