Post on 05-Aug-2020
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Intro to Parkinson's Disease
Justin P Martello, MDChristiana Care Neurology Specialists
Newark, DE
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Objectives Current epidemiology of PD Brief pathophysiology Criteria for the diagnosis of PD Medical management updates Future Directions of Therapy
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
What is PD? Neurodegenerative disease Attacks dopamine producing cells in substantia
nigra in the brain Causes slowness, stiffness, tremors, balance
impairment And much more...
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
PD Epidemiology• PD affects ~ 1-2/1000
– 1% over 60• annual incidence of 4–20 per 100,000• rising prevalence with age
– ~Average life expectancy• 2011 University of Delaware Study:
~2000 in DE
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
• ~1 million in USA: > multiple sclerosis, muscular dystrophy and ALS combined
• ~60,000 Americans dx’d with PD each year• >10 million worldwide• Men: Women 1.5: 1
NPF Data 2016
PD Epidemiology
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Parkinsonism Bradykinesia Cogwheel rigidity Resting tremor (“pill rolling”) (absent in ~20-30% with PD)
Postural instability (not at presentation in PD)
Most people with parkinsonism have PD.
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Cognitive ImpairmentNightmares/vivid dreamsInsomniaREM sleep behavioral disorderApathyDepression, anxietyHallucinations/delusions
FatigueDystonia
Blurred vision
Orthostatic hypotension
Hypophonia/dysarthriaDrooling, nasal dripDysphagia
Erectile dysfunctionUrinary incontinence
BradykinesiaRigidityTremors
Gait and balance impairment
ConstipationGastroparesis
Anosmia
The PD Body
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Cognitive ImpairmentNightmares/vivid dreamsInsomniaREM sleep behavioral disorderApathyDepression, anxietyHallucinations/delusions
FatigueDystonia
Blurred vision
Orthostatic hypotension
Hypophonia/dysarthriaDrooling, nasal dripDysphagia
Erectile dysfunctionUrinary incontinence
BradykinesiaRigidityTremors
Gait and balance impairment
ConstipationGastroparesis
Anosmia
The PD Body
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Additional Motor Featuresof Parkinsonism
Decreased arm swing while walking Micrographia (small
handwriting) Decreased blink rate
and facial expression (hypomimia) Shuffling gait Difficulty arising
from a chair, car, or turning in bed
Soft, monotone voice (Hypophonia)
Freezing En bloc turning Flexed posture Festination Drooling
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
35% incorrect at initial diagnosis Rajput AH. Can J Neurol Sci 1991
24% incorrect at final diagnosis Hughes AJ, et al. JNNP 1992
How well do movement disorders specialists do? 8.1% revision of diagnosis (DATATOP Study- Jankovic J, et
al. Arch Neurol 2000)
Positive predictive value: 98.6% at final diagnosis- Hughes AJ, et al. Brain 2002
How accurate is the clinical diagnosis of PD?
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
MDS Clinical Diagnostic Criteria
Bradykinesia (slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions)
And at least one of the following: Muscular rigidity 4-6 Hz rest tremor
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Ancillary Testing CT or MRI is not necessary in “typical” (most) cases of
PD DA transporter imaging (DaT scan) is not necessary!
Only FDA indication to distinguish PD tremor from ET Cannot be used for disease severity or prognosis Can help with drug-induced parkinsonism, vascular
parkinsonism, NPH, psychogenic DaT scan cannot distinguish PD from a parkinsonian syndrome
due to nigrostriatal degeneration (PSP, MSA, CBD, LBD) Insurance issues…
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Marked asymmetry of dopamine loss is a hallmark of early Parkinson’s Disease
PET scan showing striatal fluorodopa uptake of a normal brain versus early PD
Gross pathology of the mid brain showing a normal brain versus early PD
Normal Parkinson’s disease
Substantia nigraBrooks 1993
Marsden 1994 Lang & Lozano 1998
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Early, Typical PD
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Atremulous PD “Pseudo-hemiplegic PD”
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Plasma Levodopa Concentrations Smooth, extended
response Absent or infrequent
dyskinesia
Diminished duration Increased incidence of
dyskinesia
Short, unpredictable response
OFF times “On” time is
associatedwith dyskinesias
Dyskinesiathreshold
Efficacythreshold
Advanceddisease
Earlydisease
Moderatedisease
Ther
apeu
tic w
indo
w
Progression and Prognosis
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Medications and Treatment
1. MAO-B Inhibitors– Rasagaline (Azilect)– Selegeline– Safinamide (Xadago)
2. Dopamine Agonists– Ropinirole (ReQuip)– Pramipexole (Mirapex)– Rotigotine (Neupro)
3. COMT Inhibitors– Entacapone (Comtan)– Tolcapone
4. Levodopa (Carbidopa/Levodopa)- Sinemet IR/CR, Rytary, Duopa, Inbrija5. Others: Amantadine (Gocovri), trihexiphenidyl (Artane), apomorphine
(Apokyn)
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Medical Marijuana and PD
• FDA approved in PD with painful spasms• Not an exact science…• No long term risk data… dementia?• Not a miracle cure, no thanks to FB• Insurance does not cover; ≈ $60-80/wk
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Therapy Updates since 2015
Jan 2015
Sept 2019
Duopa04/’15
Rytary04/’15
Nuplazid(pimavanserin)08/’16
Focused Ultrasound for Essential Tremor and PD tremor08/’16
Gocovri(Amantadine ER)08/’17
Xadago(safinamide)04/’17
Abbott St. Jude DBS11/’16
Boston ScientificDBS12/’17
Inbrija(inh levodopa)01/’19
Nourianz(istradefylline)12/’17
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Advanced Therapy Management
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Deep Brain Stimulation (DBS)
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
St. Jude Abbott Directional Lead System
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Boston ScientificDirectional Lead System
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Levodopa Intestinal Gel Infusion(DUOPA)
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Physical Therapy
• Balance training • Teaches adaptive strategies• Trains in the use of assistive devices• Methods/cues to break freezing• PD experience is important!
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Speech Therapy
• LOUD technique proven to be the one helpful method to improve hypophonia in PD
• Need to keep up with exercises• Audio cues and more recently singing to oneself
can help break freezing of gait
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Nutrition and Supplements
• No proven supplements are helpful except melatonin for sleep and RBD
• Mediterranean diet– helpful for brain health – ward off dementia– No diet specific for PD
• The protein issue…
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
Wearable Technologies
• Analyzing gait, fall risk, exercise relationships
• Feasibility?• Costs?• Adherence?
International Parkinson and Movement Disorder Society | 555 East Wells Street, Suite 1100, Milwaukee WI 53202-3823 USA
Tel: +1 414-276-2145 | www.movementdisorders.org | info@movementdisorders.org
The Future for PD
• New levodopa delivery systems (e.g. inhalers, subcutaneous pumps, patch systems)
• True disease modifying therapy (e.g. Nilotinib, GLP-1 agonists, stem cells)
• Blood markers for PD and other parkinsonian plus syndromes
• FUS (MRI-guided focused ultrasound)