Management of parkinson’s disease. Dr. Sanjiv Chandratre. Consultant in med. for elderly 2010 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. James parkinson 1817 • Involuntary tremulous motion, with lessened muscular power, in part not in action and even when supported;with a propensity to bend the trunk forward, and to pass from a walking to a running pace: the senses and intellect being uninjured. Terminology in P. D. • • • • • • Parkinson’s disease or Idiopathic P. D. Parkinsonism / Parkinsonian syndrome. Drug induced Parkinsonism. Post encephalitic parkinsonism. Vascular pseudo Parkinsonism. Lower body parkinsonism. Terminology in P. D. • Parkinsonism plus syndrome. – PSP – MSA – CBD Parkinson’s 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…. 4 stage clinical management scale • • • • Diagnosis Maintenance therapy Complex Palliative care 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 Prevalence • Per GP. • Say 2500 • Per district / pct. • Say 200,000 Brain Bank Criteria • • • • • • Step 1 Diagnosis of parkinsonian syndrome Step2 Exclusion criteria for IPD Step3 Supportive criteria for IPD Step1- Diagnosis of parkinsonian Syndrome. • • • • Bradykinesia +at least one of the following Muscular rigidity 4 –6 Hz resting tremor Postural instability Brady / Hypokinesia • Hypokinesia –poverty of movement • Loss of facial expression, arm swing, gesture etc. • Bradykinesia -Slowness of movement • ‘Decay’ – finger/ heel tap Rigidity • Resistance to passive movement – Reinforcement – ‘froment’s manoeuvre’ • Constant [ c. f. ‘clasp-knife’] – ‘Lead pipe’ – ‘cogwheel’ • Gagenhalten 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 Postural instability. • • • • Last cardinal feature to appear Limited diagnostic specificity in the elderly. Pull test Early falls – ‘red flag’ 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 Step3- positive supportive criteria • • • • • • • • • [>3 for ‘definite’ PD ] Unilateral onset. Rest tremor Progressive Persistent asymmetry Excellent levodopa response Severe levodopa induced chorea Levodopa response>=5years Clinical course>=10 years Diagnosis- Accuracy • • • • • • • Meara 1999 Age and ageing Community study- 402 cases 73 % Parkinsonism 53% ‘probable’ IPD Essential tremor Alzheimer’s disease vascular Accuracy of diagnosis • • • • Brain bank post mortem series 24 % error rate. 10 % latest studies. 2% MD specialists. • Community series • >50 % error rate 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. Dopamine Transporter Imaging agent •Parkinson’s disease •Progressive Supranuclear Palsy •Multiple System Atrophy •Essential Tremor •Neuroleptic-induced Parkinsonism •Vascular disease Differential diagnosis of parkinsonian syndrome • • • • • • Idiopathic Parkinson’s disease Drug induced – phenothiazines Multiple cerebral infarct state. Trauma – pugilistic encephalopathy Toxin induced- MPTP, CO, Mn, Cu, Parkinson’s plus syndromes Essential tremor • • • • • • Most common diagnostic error. 10 times more common than PD. Postural or action tremor. Titubation. Family history. B – Blockers help. 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. Multiple infarct state • Synonymous with leucoariosis, Binswanger’s encephalopathy • Related to hypertension and other risk factors • Common misdiagnosis. • Poor prognosis • Aspirin and dipyridamole retard may be effective and safe 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. Dementia with Lewy bodies • • • • Fluctuating alertness Hallucinations Mild parkinsonism Neuroleptic sensitivity • Tremor less common • More symmetrical • Myoclonus more common • More rigid, less bradykinetic Medical treatment of P. D. Only 18 drugs for PD in BNF 2008 14 Dopaminergic 4 Anticholinergic. Drugs to avoid 1 • Antiemetics – Metoclopromide (Maxalon) – Prochlorperazine (Stemetil) • The only recommended antiemetics are – Domperidone – 5ht3 antagonists eg. Ondensetron. Drugs to avoid 2 • Antipychotics – – – – Chlorpromazine Sulpride Haloperidol Thioridazine. • Newer antipsychotic can be used with caution When to start treatment ? • • • • • Controversial Is the diagnosis certain. Age of patient. Effect on ADL. Patient Choice. Drugs in PD • • • • • • Levodopa preparations. Dopamine receptor agonists. Monoamine oxidase-B inhibitors. Catechol-o-methyltransferase inhibitors. Anticholinergics. Amantadine Levodopa • Used since the 1960’s • Remains the ‘gold standard’ • Always used with dopa decarboxylase inhibitor.( either carbidopa or benserazide.) • Side effects are common. Levo dopa preparations. • Madopar or co beneldopa—Levodopa with benserazide • Sinemet or co careldopa—Levodopa with carbidopa Levodopa formulations • Effervescent or dispersible eg. Madopar dispersible. • Conventional release.eg. Madopar • Controlled release.eg. Madopar CR or Sinemet CR • Duodopa– As a gel. Levodopa preparations • Dispersible preparations—Use 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 Side effects of levodopa • • • • • • • Very common Nausea, vomiting Excessive drowsiness Insomnia End of dose fluctuations. Nocturnal immobility. Motor fluctuations and dyskinesias. Dopamine agonists • • • • • First available since 1970’s Six DA’s available for oral use. Apomorphine administered parenteraly Act directly on post synaptic receptors. Two types – Ergot derived. – Non ergot derived. Dopamine agonists • ERGOT – – – – Bromocriptin Lisuride Pergolide Cabergoline • Non ERGOT – Ropinirole – Pramipexol – Apomorphine. Rotigotine • DA • Mono therapy or adjunct. • Patches. Side effects of DA’s • Similar to levodopa – – – – – – Nausea. Vomiting. Postural hypotension. Confusion. Hallucinations. Somnolence. Side effects of ERGOT DA’s • Fibrotic reactions. • Pulmonary, retroperitoneal and pericardial fibrosis. • Cardiac valvulopathy. • In most cases non ergot DA’s preferred. • CXR, PFT’s, ESR,and S. creatinine before starting treatment. Unusual side effects of DA’s • Complex group of impulse control disorders – Pathological gambling. – Hypersexuality. – Compulsive eating or shopping. . Repetitive perseverative behavior. -- Punding -- Excessive hobbyism. Unusual side effects of DA’s 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 DA’s • Young pts. are particularly prone. SOOS • Excessive day time sleepiness and soos can occur with levodopa preparations and with DA’s • Warn patients about driving. Amantidine • • • • • Antiviral properties. Weak DA Only for moderate to severe dyskinesia. Glutamate antagonist. 100 mg. BD or TDS COMT inhibitors • Entacapone • Talcapone • In combination with levo dopa – ( STALEVO) 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. 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. Antimuscarinic drugs. - Benzatropine, Procyclidine,Orphenadrine Limited use. Cognitive impairment in elderly. Useful in drug induced Parkinsonism. can be used for excessive salivation. Apomorphine • Potent dopamine agonist. • Significant cost (10,000 £ PA for cont. infusion.) offset by keeping pts. Out of NH’s • Only parenteral use. – Subcutaneous (rescue ) injections. – SC continuous infusion. 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. DO NOT MISS P. D. MEDICATION • Akinetic Rigid Syndrome. • Malignant neuroleptic syndrome. • ‘GET IT IN TIME’ Non motor symptoms in P. D. • • • • • • Constipation Hallucinations. Dementia / psychosis. Excessive salivation. Excessive sleep. REM behaviour disorders. P. D. and Driving • Booklet from PDS. • Diagnosis of P. D. does not necessarily disqualify people from driving • Dopamine agonists– Drowsiness – SOOS Do I have to inform DVLA Yes.Required by law. Drivers medical unit at DVLA Criminal offence under RTA 1988 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 Thank you. • . ANY QUESTIONS ? Outline 1. History 2. Diagnosis 3.Differential diagnosis 4.Cost factors 5. Local scene 6. Take home messages 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] 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 Diagnostic Challenges • Prevalence of Signs of Parkinsonism in the “Normal” Elderly Population • Co-existent Pathology – Cerebrovascular Disease – Depression – Arthritis • Differential Diagnosis – – – – Essential Tremor Parkinson’s Plus Syndromes Alzheimer’s Lewy Body Disease 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’ 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 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 Conclusions: PD Economic Impact (1) • Parkinson’s 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: • c£4,000 per annum below 65 years • c£9,400 per annum over 85 years • Mean direct annual costs is inversely proportional to disease severity • Hoenhn & Yahr stage (0-1) c£3000 • Stage 5 c£18,400 • Greater than five fold increase 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 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 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 H&Y stages secondary care accounts for an increasing proportion (27% in stages 0-1, 62% in stage V) Case history 1 complex 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 Case history 1( contin.) • Decided to admit to LGI for trial of apomorphine • 20 weeks in LG • Aspiration pneumonia—ITU—VentilatedTracheostomy—PEG.—back to CRH • Refused RH/ NH. Very dependent. Huge package of care.----Home. • Managed for 5 months. Readmitted with aspiration pneumonia • Died. 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 European Parkinson’s Association and WHO charter of rights for people with PD • People with Parkinson’s have the right to: • Be referred to a doctor with a special interest in Parkinson’s • 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 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 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. 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 Case 1 – GP’s 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 Parkinson’s 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. Case 1 – GP’s 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? 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 Parkinson’s Disease 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? 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. 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 Case 2 – GP’s Letter This 82 year old man was diagnosed with Parkinson’s 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. Case 2 – GP’s Letter • Has he got Parkinson’s Disease? • What clinical features does he have? • What is the most likely diagnosis? 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 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? Case 2 - Conclusions • Diagnosis – Multiple Infarct State • Synonymous with leucoariosis, Binswanger’s encephalopathy • Related to hypertension and other risk factors • Common misdiagnosis! • Poor prognosis • Aspirin and Dipyridamole retard may be effective and safe Case 3 – GP’s 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. Case 3 – GP’s Letter • What are the possible diagnoses? 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 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? 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 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 Fractionate dose of Levodopa Consider modified-release Levodopa Add modern Dopamine agonist Add Entacapone Consider Apomorphine Injections or infusions Consider surgery Case 4 – GP’s Letter • What is the likely diagnosis? • What are the diagnostic features? Case 4 – GP’s 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 Parkinson’s Disease to me but I would value your opinion. 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 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 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? 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 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 What can we expect in the near future? Everything that shakes is not Parkinson’s… Dr. S. N. Chandratre. Consultant Medicine for Elderly. Calderdale Royal Hospital. Stages of P. D. • • • • Diagnostic phase Maintenance phase. Complex phase. Palliative phase. Drugs used in P. D. • Dopamine receptor agonists. • Levo dopa preparations. • MAO B Inhibitors • COMT Inhibitors. • Amantidine Treatment of P. D. • • • • Medical Surgical Complementary Role of PDNS, OT, Physio, SALT, Dietetian, SW Route of administration • • • • • Oral – Effect of meal ? Sub cuteneous Skin patch Effervescent tablets. Duodopa- via PEG