Parkinson s Disease Update. Presented by Joanna O Leary, MD Movement disorder neurologist Providence St. Vincent s

Transcription

1 Parkinson s Disease Update Presented by Joanna O Leary, MD Movement disorder neurologist Providence St. Vincent s

2 What is a movement disorder? Neurological disorders that affect ability to move by causing too much or too little movement or by affecting rhythm of movement. Examples: Parkinson s disease Essential tremor Dystonia Ataxia

3 Parkinson s disease Lifetime risk: 1.5% Prevalence: Younger than 45 years old ~ 10% of PD pts 93/100,000 in patient s yo Mean age of onset: 60 years old Mean duration of disease from dx to death: 15 years Men: female ratio: 1.5:1

4 Cause of Parkinson s Unclear Increased risk with age Never smokers have 2x risk Lower risk in caffeine drinkers Weaker associations: Head injury, rural living, lack of exercise, middle age obesity, pesticide exposure, Agent Orange exposure, middle age obesity Some genetic associations ~2x risk with first degree relative

5 Cardinal Features of Parkinson s Need 2/3 features to make diagnosis

6 Cardinal Features of Parkinson s Need 2/3 features to make diagnosis Rest tremor Coarse tremor (3-5 Hz) that occurs while relaxing or walking Improves with voluntary movement

7 Rest tremor

8 Cardinal Features of Parkinson s Need 2/3 features to make diagnosis Rest tremor Rigidity inability to relax muscles, can be noted in arms, legs, neck in Parkinson s

9 Rigidity

10 Cardinal Features of Parkinson s Need 2/3 features to make diagnosis Rest tremor Rigidity Bradykinesia slowed, effortful movement

11 Bradykinesia

12 Postural Instability Poor balance Becomes a prominent feature as disease course progresses Other gait features: Shuffling Freezing Narrowed base

13 Freezing gait

14 Other Features Highly Suggestive of Parkinson s Unilateral onset Levodopa response Dyskinesia with levodopa Decreased sense of smell REM sleep behavior disorder

15 Neuropsych symptoms Cognitive decline Dementia Psychosis Depression Anxiety Anhedonia

16 Sleep abnormalities REM sleep behavior disorder Restless leg syndrome Insomnia Daytime somnolence Sleep apnea

17 REM sleep behavior disorder

18 Autonomic dysfunction Urinary incontinence Orthostatic hypotension lightheaded with standing Excessive sweating Sexual dysfunction

19 Other symptoms GI symptoms: Dysphagia Constipation Drooling Reduced facial expression Reduced voice volume

20 How to diagnose Parkinson s History Clinical exam Slowness, stiffness, rest tremor Sometimes imaging: MRI brain - normal DAT scan asymmetry of dopamine transporter in basal ganglia Helps distinguish between parkinsonian and other tremor disorder

21 DAT scan image

22 Other parkinsonian disorders or mimics Lewy Body dementia Progressive supranuclear palsy Multiple systems atrophy Corticobasal degeneration Medication side effects (from some anti-psychotics and anti-emetics) Pugilistic parkinsonism Vascular parkinsonism Normal pressure hydrocephalus Essential tremor Psychogenic disorder Frontal gait disorder

23 Parkinson s plus features Rapid progression of symptoms Lack of tremor or myoclonic tremor Symmetric onset Minimal response to levodopa

24 Parkinson s plus features Early onset: Falls (PSP, MSA) Eye abnormalities (PSP) Psychosis or dementia (LBD) Autonomic dysfunction (MSA) Dysarthria or dysphonia (MSA) Cerebellar features (MSA) Apraxia, alien limb, myoclonus (CBD)

25 Progressive Supranuclear Palsy

26 Corticobasal Degeneration

27 Vascular parkinsonism

28 Non-medical Treatment of Parkinson s Exercise beneficial with regards to physical functioning, health-related quality of life, strength, balance and gait speed Physical therapy Balance and strength Speech therapy Lee Silverman Voice therapy Swallow therapy Goodwin, et al

29 Medications for Parkinson s Anticholinergics MAO-B inhibitors Dopamine Agonists Carbidopa-levodopa COMT inhibitors

30 Lesser Used Meds Anticholinergics Trihexyphenidyl, benztropine Confusion, hallucinations, fatigue, urinary retention MAO-B Inhibitor Rasagiline, selegiline Possible disease modification ADAGIO study supported use of 1mg daily, but no improvement at 2mg daily Olanow et al.

31 Dopamine Agonists Ropinirole, pramipexole, rotigotine patch Use in younger patient s Less risk dyskinesia Increased fatigue, edema, compulsions, sleep attacks

32 Levodopa Sinemet (carbidopa-levodopa IR/CR), Rytary and Duopa Most effective treatment for Parkinson s Risk of dyskinesia Worsens fatigue, hallucinations, orthostatic hypotension Higher and more doses needed Motor fluctuations

33 Common Side effects to Levodopa Dyskinesia Motor fluctuations Psychosis Orthostatic hypotension

34 Rytary Time release CD/LD microbeads Plasma concentration sustained longer at greater amount IR: <10% at hrs Rytary: <10% at 10 hours Less frequent dosing (e.g. TID vs 5 + times daily) Less OFF time ~ 2 hours difference/day More ON time without troublesome dyskinesia (~1h) Converting from IR to Rytary can be rocky 2 Rytary : 1 IR

35 Duopa intestinal gel formulation of carbidopa/levodopa continuously delivered via J-PEG 16 hour infusion Rest time for gut wear cartridge of med like an insulin pump Decreased OFF time (2h) and increased ON time without troublesome dyskinesia (2h) Risks: malfunction, infection, intestinal complications Requires A LOT OF TIME to determine infusion rate

36 Dyskinesia Involuntary dance-like movement Occurs when Sinemet is peak dose 64% develop dyskinesia in 4-5 years after onset of treatment with levodopa Treatment: Amantadine Reduce levodopa and give more frequently Deep brain stimulation Grandas, F. et al.

37 Dyskinesia

38 Motor Fluctuations Fluctuating between being ON and OFF levodopa ON symptoms tremor, slowness controlled, sometimes with dyskinesia OFF symptoms tremor, slowness, stiffness occur as medication wears off Treatment: Decreased dose and increase frequency levodopa Entecapone (COMT inhibitor) Rytary DBS

39 Psychosis Increases with disease progression Increases with medications to treat Parkinson s Treatment: Reduce amantadine, benzodiazepines, dopamine agonists, entacapone first Then reduce levodopa Anti-psychotics only seroquel or clozapine Cholinesterase inhibitor e.g. donepezil Newer medication, Nuplazid (pimavanserin) Serotonin inverse agonist

40 Pimavanserin Pimvavanserin: selective serotonin receptor (5-HT2A) inverse agonist, no blockade of dopamine neurons Nature 2009: Double blind randomized study versus placbo Primary endpoint (SAPS-PD) positive trend, no significance. Significant - hallucination and psychosis sub scores. No change UPDRS, hypotension and sedation vs placebo

41 Cholinesterase inhibitors Dual purpose: Cognitive decline Balance 2016 study of Rivastigmine vs placebo Step time variability improved normal walk Simple dual task improved No improvement with complex dual task 45% reduction in falls/month Small increase in gait speed

42 Neurogenic orthostatic hypotension Blood pressure lowers when patient changes position to sitting or standing Due to inability of sympathetic nerves to release norepinephrine upon standing Fludrocortisone, midodrine, droxidopa All worsen supine BP

43 Surgical Interventions Deep Brain Stimulation Subthalamic Nucleus reduction in levodopa Globus Pallidus interna fewer issues with cognition and postural instability,? better treatment for dyskinesia Thalamus more for essential tremor Pallidomtomy Rarely performed now only unilateral, not reversible Focused ultrasound? Stem Cell treatment studies don t support yet

44 Deep Brain Stimulation

45 Deep brain stimulation surgery

46 Pre-DBS

47 Post-DBS

48 Summary Send us your Parkinson s patients and we will help make some of these complicated decisions easier!!

49 citations Lees, Andrew J et al. (2009), Parkinson's disease, The Lancet, Volume 373, Issue 9680, Goodwin, V. A. et al. (2008), The effectiveness of exercise interventions for people with Parkinson's disease: A systematic review and meta-analysis. Mov. Disord., 23: Grandas, F. et al. (1999), Risk factors for levodopa-induced dyskinesias in Parkinson's disease. J. Neurol., 46(12): Olanow, CW. Et al (2009), A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease. NEJM 361: (accessed 11/11/16)

50 citations Kaufmann, H. et. al., Droxidopa in neurogenic orthostatic hypotension. Expert Rev Cardiothoracic Ther 2015 Aug 13(8): Meltzer, H. et al., Pimavanserin, a Serotonin 2A Receptor Inverse Agonist, for the Treatment of Parkinson's Disease Psychosis. Neuropsychopharmacology (2010) 35, ; doi: /npp Henderson, E. et al., Rivastigmina for gait stability in patiens with Parkinson s disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol (2016); 15: Dhall R, et al., Advances in levodopa therapy for Parkinson disease. Neurology 2016;86 (Suppl 1):S13-S24