Parkinson’s disease Joohi Jimenez-Shahed, MD Assistant Professor of Neurology Baylor College of Medicine 8th Annual IMHO Convention April 30, 2011 – Houston, TX
April is Parkinson’s Awareness Month The tulip was first recognized as a symbol for Parkinson’s in 1980. At that time, a Dutch horticulturalist named J.W.S.Van der Wereld decided to honor Dr. James Parkinson, the first person to describe Parkinson’s in 1817, by naming a tulip after him. It thus became a symbol for Parkinson’s disease.
James Parkinson 1817: Essay on the Shaking Palsy
What is Parkinson’s disease? Parkinson’s disease (PD) is a chronic and progressive
movement disorder that involves the malfunction and death of vital nerve cells in the brain, called neurons. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As Parkinson’s progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.
What is PD? PD is a neurodegenerative brain condition 2nd most common after Alzheimer’s
The major PD symptoms are caused by loss of cells in the
brain that produce dopamine
Up to 70% of dopamine-producing cells in the substantia nigra are lost by the time symptoms first appear.
Cardinal Motor Symptoms of PD •Resting tremor •Bradykinesia •Rigidity •Postural instability
Other Motor Features Loss of facial expression (“masked”, “poker face”) Speech: low volume, stuttering, echoing syllables Swallowing problems Drooling Stooped posture: bending at the neck and at the waist Dystonia: involuntary cramping or twisting of a muscle Small, illegible handwriting Vision: intermittent double vision
Non-motor symptoms in PD • Mood • Cognition
Pain Loss of smell and taste
•
Impulse control disorders Fatigue / lack of energy
• • • • •
(thinking/memory) Sleep Loss of bladder control* Constipation* Low or fluctuating blood pressure* Sweating* Sexual dysfunction*
Skin problems
*symptom complex termed “dysautonomia”
Epidemiology of PD 7-10 million people worldwide live with Parkinson’s disease. In the U.S., as many as one million individuals live with PD more than the combined number of people diagnosed with multiple
sclerosis, muscular dystrophy and Lou Gehrig's disease. Approximately 60,000 Americans are diagnosed each year. Men are slightly more likely to have PD than women. Incidence of Parkinson’s increases with age ~4% of people with PD are diagnosed before the age of 50. Affects 1/100 people over the age of 60
Avg. patient with PD onset at 62 yrs will live approx. 20 yrs.
What causes PD? Genetic factors
Environmental factors
Only about 10% of cases are truly
Environmental factors linked with
genetic People with an affected 1st degree relative have a 2-3-fold increased risk of developing PD as compared to the general population Cannot test for all 13 genes that are known to be associated with PD
genetic susceptibility may underlie PD No specific toxin is the sole cause of the disease Rural living, well water, herbicide/pesticide use, MPTP are associated with increased risk Caffeine, smoking associated with decreased risk
PD probably represents a group of disorders resulting in a final common pathway
Dopamine ď‚— Dopamine is a neurotransmitter
responsible for cell to cell signaling in the brainstem and deep brain structures
ď‚— Dopaminergic cells influence the
speed, regularity, coordination, and control of movement.
ď‚— Complex interactions between
these brain structures allow us to control and fine tune all movements that we make.
Dopamine Dopamine-producing cells
also connect to other nonmovement brain areas, and can influence mood, reward seeking, motivation PD is more than a “shaking palsy”
Diagnosis of PD No diagnostic test for idiopathic Parkinson’s disease. Diagnosis rests on history and neurological examination. Blood tests and scans are ordered to check for other
conditions that could cause parkinsonism. GE’s DaTscan™: First and only FDA-approved visual adjunct imaging agent to aid in differentiation between essential tremor and parkinsonian syndromes (does not diagnose PD)
Natural Progression of PD with No Treatment Preclinical
Symptomatic Diagnosis
Dopamine neurons (up to 70% lost by the time symptoms appear)
Motor ratings
Symptoms may not require medication for several years post diagnosis
Time Threshold for some non-motor symptoms Threshold for motor signs and symptoms National Parkinson Foundation Web site. www.parkinson.org.
Patients may have 1 year between appearance of motor symptoms and diagnosis
PD Treatment: General Principles No therapy is curative Treatment is directed at maintaining
functional independence Levodopa therapy is the “gold standard” First described to improve parkinsonian symptoms in the 1960s “Awakenings”
There is no single correct way to treat PD; individualize therapy
for each patient
Treatment goals in PD Symptom control
Maintain functional independence: work, hobbies, leisure activities Maintain quality of life Improve social functioning (e.g., embarrassment by symptoms)
Address non-motor features Minimize long-term complications Disease modification/Neuroprotection
No cure No treatment clearly slows the progression of disease Major focus of research and many new therapies – invasive or otherwise
Treatment options Non-dopamine, Dopamine-related treatments
symptom-related treatments
Replace dopamine
Just for tremor
levodopa
Stimulate dopamine
receptors
dopamine agonists
Prevent dopamine from
breaking down
MAO-inhibitors COMT inhibitors
anticholinergics
Just for dyskinesia amantadine
Muscle relaxers Medicines for non-motor
features
Disease progression • • • •
Mild symptoms Still independent “Honeymoon period” Meds control symptoms
Moderate stage - I • Motor fluctuations (on/off) are mild • Symptoms begin to affect daily functions • Additional medications needed Moderate stage - II • More obvious motor fluctuations (on/off) • Dyskinesias • Levodopa and adjunct treatments
• Motor complications: freezing, falls • Symptoms less easily controlled with medications • Disability and dependence on others • Cognitive decline
Symptoms get worse over time Requires higher doses and addition of new drugs over time In advanced stages, patients may require 5-7 different drugs
Surgical therapies for PD Generally reserved for patients
who have developed complications of therapy. Previous lesioning procedures (e.g., pallidotomy and thalamatomy) have been abandoned in favor of deep brain stimulation (DBS) due to side effects and loss of effect over time. DBS has been shown to significantly improve motor function and quality of life compared to continued best medical management
Can people die from Parkinson’s? Parkinson’s disease is a progressive disorder, but is not
considered to be a fatal disease People with Parkinson’s experience a significantly decreased quality of life and are often unable to perform daily movement functions, such as getting out of bed unaided and driving. Most individuals are eventually forced to stop working due to the unavoidable progression of disabling symptoms. In some cases, people have died from Parkinson’s-related complications, such as pneumonia.
What is the cost of Parkinson’s? The combined direct and indirect cost of Parkinson’s disease,
including treatment, social security payments and lost income from inability to work, is estimated to be nearly $25 billion per year in the United States alone. Medication costs for an individual person with Parkinson’s average $2,500 a year, and therapeutic surgery can cost up to $100,000 per individual.
Research Initiatives Basic sciences research directed at understanding the
pathophysiologic mechanisms in PD
Generate targets for non-dopaminergic or neuroprotective therapies
Parkinson’s Progression Markers Initiative (PPMI, MJFF)
5-year clinical study aiming to identify the earliest biomarkers of
disease
Define early diagnostic algorithms Identify biologic metrics of disease progression
NIH Exploratory Trials in PD (NET-PD, NINDS)
5-yr study in 1720 patients to determine of creatine can slow the
progression of PD
Novel drug design and delivery Gene therapy – e.g., neurotrophic factors
Thank you!
Questions?