Parkinson’s Disease: An Overview

Samuel Frank, MD
Associate Professor of Neurology, HMS & BIDMC

Worldwide prevalence

Epidemiology

1% of population greater than 65 years
3% of population greater than 85 years
– 187/100,000
US prevalence
1.6% of population over 65
– In MA = 860,000 x 1.6% = 13,760 people
North American prevalence
~1 million people
Annual incidence (new cases) of 20/100,000

Epidemiology
M:F about 2:1
Less common in blacks and Asians
HOWEVER, PD is generally not well studied in diverse populations
Average onset age = 63
5-10% of people have symptoms < 45

PD Projection
In the most populous nations will double by 2030 from 4.3 million to 9.5 million worldwide.
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease
Enormous public health challenge
We need to plan for diagnosis, treatment and research purposes

Dorsey et al, Neurology 2007;68:384- 386

Cardinal Signs
Onset of (at least 2):
Tremor
Rigidity
Bradykinesia
Postural instability
Later in the course
Typical asymmetrical
Absence of another cause

Probable & Possible Diagnostic Criteria
Group A Features: Characteristic of Parkinson disease
Resting tremor
Bradykinesia
Rigidity
Asymmetric onset
Group B features: suggestive of alternative diagnoses
Features unusual early in the clinical course
Prominent postural instability in the first 3 years after symptom onset
Freezing phenomena in the first 3 years
Hallucinations unrelated to medications in the first 3 years
Dementia preceding motor symptoms or in the first year
Supranuclear gaze palsy (other than restriction of upward gaze) or slowing of vertical saccades
Severe symptomatic dysautonomia unrelated to medications
Documentation of a condition known to produce parkinsonism and plausibly connected to the patient’s symptoms (such as suitably located focal brain lesions or neuroleptic use within the past 6 months)

Gelb, Arch Neur. 1999

MDS 2015 Revised Criteria

Associated Problems - Early

Loss of smell
Depression/anxiety
Sleep disturbance
REM behavior d/o
Small handwriting
Constipation
Dizziness

Urinary urgency
Blurred vision/dry eyes
Pain in shoulders/hip
Dystonia

How to Make the Diagnosis
Clinical
Based on symptoms and exam findings
Confirmatory tests
May be needed to evaluate for other diseases
MRI of brain or cervical spine, EMG (PD is NOT a “pinched nerve”)
DaTscan SPECT
Skin biopsy
>90% sensitivity and specificity

DaTscan

What Causes Parkinson’s Disease?
Unknown
Probable combination of factors:
Genetic (<10% of cases)
Toxic
Infectious
Other/unknown
First degree relatives have increased risk of developing PD in their lifetime.

Various Inheritance Patterns

ATP13A2, DNAJC6, FBXO7, PRKN/PARK2, PARK7, PINK1, PLA2G6, SLC6A3, SPR, SYNJ1, VPS13C

Autosomal recessive (11 genes)

CHCHD2, LRRK2, SNCA, and VPS35

Autosomal dominant (4 genes)

RAB39B and TAF1

X-linked recessive (2 genes)

Pathogenic variants in GCH1

AD or AR

GBA and MAPT, EIF4G1, GIGYF2, HTRA2, UCHL1

Susceptibility genes

Source: Prevention Genetics

Drugs

Some Causes of “Parkinsonism”
Vascular disease

Anti-psychotics
Anti-nausea
Illicit drugs
Multi-Systems Atrophy
Shy-Drager
Striato-nigral degen.
OPCA
Progressive Supranuclear Palsy
CBGD

Dementia with Lewy Bodies
Normal Pressure Hydrocephalus
Wilson’s disease
Huntington’s disease
Alzheimer’s Disease
Dystonia
Structural lesion

PD vs. ET
James Parkinson:
“In the real Shaking Palsy, the agitation continues full force whilst the limb is at rest and unemployed; and even if sometimes diminished by calling the muscles into employment.”
He noted tremors liable to be confused include those due to alcohol abuse, tea and coffee abuse, and old age.

Time Course of PD Progression

Kalia & Lang Lancet 2015

Non-motor Symptoms of PD

Psychiatric
Mood disturbance
Depression
Agitation
Anxiety and panic attacks
Dementia
Hallucinations
Delirium

Autonomic
Orthostatic hypotension
Constipation
Urinary problems
Sexual problems
Sweating and thermoregulation

Sleep disorders
Parasomnias
REM Sleep behavior disorder
Insomnia – maintenance or early awakening
Sleep fragmentation
Restless legs syndrome
PLMS
Excessive daytime sleepiness
Sudden onset of sleep
Sensory
Hyposmia
Pain
Paresthesias
Altered sensation
Restless legs

FDA-Approved Medications for PD

Carbidopa/levodopa
Sinemet®
(10/100), 25/100, 25/250
Sinemet CR®
25/100, 50/200
Rytary®
Stalevo® (carbidopa/levodopa/entacapone)
Duopa®
Parcopa® (dissolvable carbidopa/levodopa)
Inbrejia®
COMT Inhibitors
Entacapone
Tolcapone
Opicapone
Dopamine agonists
Ropinirole (and XL)
Pramipexole (and ER)
Rotigotine (topical patch)
Apomorphine (injectable and SL)

MAOB Inhibitors
Selegiline
Zydis® selegiline
Rasagiline
Safinamide
Anti-cholinergic
Trihexyphenidyl
Benztropine
Amantadine
Immediate release
GoCovri®
Osmolex ER®
Adenosine A2A Receptor Antagonist
Istradefylline
Other
Rivastigmine
Pimavanserine
Droxidopa

When to Start What
Treatment should start anytime function is impaired by physical manifestations of PD.
Levodopa remains most effective symptomatic therapy.
Delayed use of levodopa may delay onset of dyskinesias and response fluctuations, particularly in young onset (<40)
LD vs. DA agonist: controversial
No difference in quality of life after 6 years

Complications of Medical Therapy
50% after 5 years, 80% after 10 years
Dyskinesia
Wearing off
Freezing
Dystonia
On/Off

Motor fluctuations and dyskinesias in Parkinson's disease: Clinical manifestations

Movement Disorders, Volume: 20, Issue: S11, Pages: S11-S16, First published: 08 April 2005, DOI: (10.1002/mds.20458)

Surgery for PD
Deep Brain Stimulation (DBS)
Patient selection important
Does not alter course of disease
STN vs. GPi
Other approaches under investigation
High frequency ultrasound
Gene transfer/therapy

Other Treatments
Education of patient and family
Support for patient and family
Counseling (professional, legal and financial)
PT, OT, SLP
Exercise (including Yoga, Tai Chi, Dance)
Relaxation Therapy
Nutritional consultation
Home Health Services
Respite
Palliative Care

Complementary & Alternative Interventions
Various supplements
Beware of amino acid compounds
Chiropractors and/or massage therapy
Acupuncture
Yoga
Stem cell treatments
Caveat emptor

PD Model of Care

Bunting-Perry, L. (2006). Journal of Neuroscience Nursing, 38(2), 105-112