Joohi Jimenez-Shahed, MDAssistant Professor of Neurology

Baylor College of Medicine

8th Annual IMHO ConventionApril 30, 2011 – Houston, TX

Parkinson’s disease

April is Parkinson’s Awareness

MonthThe 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 FeaturesLoss of facial expression (“masked”, “poker face”)

Speech: low volume, stuttering, echoing syllables

Swallowing problemsDroolingStooped posture: bending at the neck and at the waist

Dystonia: involuntary cramping or twisting of a muscle

Small, illegible handwritingVision: intermittent double vision

Non-motor symptoms in PD• Mood• Cognition (thinking/memory)

• Sleep• Loss of bladder control*

• Constipation*• Low or fluctuating blood pressure*

• Sweating*• Sexual dysfunction*

PainLoss of smell and taste

Impulse control disorders

Fatigue / lack of energy

Skin problems

*symptom complex termed “dysautonomia”

Epidemiology of PD7-10 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 60Avg. patient with PD onset at 62 yrs will live approx. 20 yrs.

Genetic factorsEnvironmental factors

Only about 10% of cases are truly 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

Environmental factors linked with 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

What causes PD?

PD probably represents a group of disorders resulting in a final common pathway

DopamineDopamine is a neurotransmitter responsible for cell to cell signaling in the brainstem and deep brain structures

Dopaminergic cells influence the speed, regularity, coordination, and control of movement.

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 non-movement brain areas, and can influence mood, reward seeking, motivation

PD is more than a “shaking palsy”

Diagnosis of PDNo 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

National Parkinson Foundation Web site. www.parkinson.org.

PreclinicalPreclinical SymptomaticSymptomatic

DiagnosisDiagnosis

Dopamine neuronsDopamine neurons

Motor ratingsMotor ratings

TimeTime

Threshold for some Threshold for some non-motor symptomsnon-motor symptoms

Threshold for motor signsThreshold for motor signsand symptomsand symptoms

Symptoms maySymptoms maynot requirenot requiremedication formedication forseveral yearsseveral yearspost diagnosispost diagnosis

Patients may have 1 yearPatients may have 1 yearbetween appearance ofbetween appearance ofmotor symptomsmotor symptomsand diagnosisand diagnosis

(up to 70% lost by (up to 70% lost by the time symptoms the time symptoms appear)appear)

PD Treatment: General PrinciplesNo 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 PDSymptom 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 optionsDopamine-related treatments

Non-dopamine, symptom-related treatments

Replace dopamine levodopa

Stimulate dopamine receptors dopamine agonists

Prevent dopamine from breaking down MAO-inhibitorsCOMT inhibitors

Just for tremor anticholinergics

Just for dyskinesia amantadine

Muscle relaxersMedicines for non-motor features

Disease progression

• Mild symptoms• Still independent

• “Honeymoon period”

• Meds control symptoms

• Motor complications: freezing, falls

• Symptoms less easily controlled with medications

• Disability and dependence on others

• Cognitive decline

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

Symptoms get worse over timeRequires higher doses and addition of new drugs over timeIn advanced stages, patients may require 5-7 different

drugs

Surgical therapies for PDGenerally 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 PDGenerate 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 diseaseDefine early diagnostic algorithmsIdentify 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 deliveryGene therapy – e.g., neurotrophic factors

Thank you!

Questions?