Parkinson’s disease

PARKINSON’S DISEASE

ROHAN DEOKAR

CONTENTS DEFINITION OUTLINE STAGES SYMPTOMS CAUSES EVALUATION PROGRESSION PATHOLOGY PATHOPHYSIOLOGY

MANAGEMENT TREATMENT

OPTIONS PROGNOSIS SIDE EFFECTS HISTORY NOTABLE CASES RESEARCH SUMMARY

WHAT IS Parkinson’s Disease ??

Parkinson’s Disease can be defined as a progressive disease of the brain and nervous system which is marked by tremors, muscular rigidity, and slow, imprecise movements.

Movement is normally controlled by dopamine, a chemical that carries signals between the nerves in the brain.

When up to 90% of the cells producing dopamine die, the symptoms of Parkinson’s appear.

The disease is named after the English doctor James Parkinson.

OUTLINE Parkinson’s is a neurogenerative disorder that

impairs motor movement due to the loss of dopaminergic neurons. It occurs mainly in elders over the age of 60.

This neurogeneration is due to genetic as well as environmental factors, such as toxins and drugs.

Main symptoms are MIST-Muscular rigidity, Impaired balance, Slow/Stiff and Tremors.

There is no cure. Treatment targets the alleviation of symptoms only.

Non-pharmacological therapy includes speech, occupational, physical therapy.

Pharmacological treatment includes dopamine agonists, replacement therapy and surgery.

STAGES OF PARKINSON'S DISEASE

Parkinson's disease is described as early, moderate, or advanced. Early disease describes the stage when a person has a mild tremor or

stiffness but is able to continue normal daily activities. This refers to a person who has been newly diagnosed.

Moderate disease describes the stage when a person begins to experience limited movement. A person with moderate Parkinson's disease may have a mild to moderate tremor with slow movement.

Advanced disease describes the stage when a person is significantly limited in his or her activity, despite treatment. Daily changes in symptoms, medicine side effects that limit treatment, and loss of independence in activities of daily living are common.

Parkinson's disease may also be described by five stages: Stage I: Symptoms affect only one side of the body. Stage II: Both sides of the body are affected, but posture remains normal. Stage III: Both sides of the body are affected, and there is mild

imbalance during standing or walking. But the person remains independent.

Stage IV: Both sides of the body are affected, and there is disabling instability while standing or walking. The person in this stage requires substantial help.

Stage V: Severe, fully developed disease. The person is restricted to a bed or chair.

MOTOR SYMPTOMS Soft speech Small

handwriting Muscle pain Stooped posture Lack of facial

expression Stooping Slowed activity

NON MOTOR SYMPTOMS

Constipation Fatigue Dizziness Depression Memory problems Bladder urgency and

frequency Increased sweating

CAUSES Results from the loss of

dopaminergic neurons of the basal ganglia

As with most brain tissue, the neurons atrophy with age.

This results in increased difficulty in initiating movements.

Imbalance primarily between excitatory neurotransmitter acetylcholine, and inhibitory neurotransmitter Dopamine in the basal ganglia.

EVALUATION The severity of Parkinson’s

is rated by trained observers on a scale of 0(normal) to 17 (severe) which includes-

Movement Attention and Blinking

posture Balance and Coordination

Reactions Vocalizations

PROGRESSION OF PARKINSON’S

Currently, there is no cure. progresses at different rates for each person. Medications need to be adjusted as

symptoms change. May progress more quickly in elder people. May progress slowly when main symptom is

tremors. Parkinson’s is not a mental disease, although

30% will eventually develop dementia.

PATHOLOGY Anatomical The basal ganglia innervated by the

dopaminergic system, are the most seriously affected brain areas in PD. The main pathological characteristic of PD is cell death in the substantia nigra.

Macroscopic alterations can be noticed on cut surfaces of the brainstem, where neuronal loss can be inferred .The histopathology of the substantia nigra and several other brain regions shows neuron loss and Lewy bodies in many of the remaining nerve cells.

Neuronal loss is accompanied by death of astrocytes and activation of the microglia. Lewy bodies are a key pathological feature of PD.

PATHOLOGY Brain cell death There is speculation of several mechanisms by which

the brain cells could be lost. Lewy bodies first appear in the olfactory lobe and

medulla with individuals at this stage being asymptomatic. As the disease progresses, Lewy bodies later develop in the substantia nigra, areas of the midbrain and basal forebrain.  These brain sites are the main places of neuronal degeneration in PD; however, Lewy bodies may not cause cell death and they may be protective.

 In patients with dementia, a generalized presence of Lewy bodies is common in cortical areas. 

Other cell-death mechanisms include lysosomal system dysfunction and reduced mitochondrial activity. It may be related to oxidative stress and neuronal death.

MANAGEMENT There is no cure for Parkinson's disease, but

medications, surgery and multidisciplinary management can provide relief from the symptoms.

The main families of drugs useful for treating motor symptoms are levodopa, dopamine agonists and MAO-B inhibitors.

The stage of the disease determines which group is most useful. Two stages are usually distinguished: an initial stage in which the individual with PD has already developed some disability for which he needs pharmacological treatment, and a second stage in which an individual develops motor complications related to levodopa usage.

Treatment in the initial stage aims for an optimal tradeoff between good symptom control and side-effects resulting from enhancement of dopaminergic function.

TREATMENT OPTIONS Drug therapy is only for symptom

management, only to slow the progression of the disease.

Physical therapy helps mobility, flexibility and balance.

Occupational therapy helps with daily routine.

Speech therapy helps with voice control.

Dopamine agonists directly stimulate dopamine receptors. Used for a relatively young patient.

Dopamine replacement therapy. Anticholinergics block increased

acetylcholine effects. Surgery deep brain stimulation for

severe disabling dyskinesias.

SURGICAL TREATMENT Treating PD by surgery

was a common practice before the introduction of Levodopa, and is done by deep brain stimulation or implanting brain pacemaker.

Dopamine agonists are used which reduce the symptoms and reduce the death of brain cells.

REHABILITATION AND DIET Regular physical exercise

can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life.

Muscles and nerves that control the digestive process may be affected by PD, resulting in constipation.

A balanced diet is recommended to avoid weight loss or gain and minimize consequences of GI dysfunction.

Prognosis

PD invariably progresses with time.  Motor symptoms, if not treated, advance

aggressively in the early stages of the disease and more slowly later. Untreated, individuals are expected to lose independent ambulation after an average of eight years and be bedridden after ten years.

As the disease advances, disability is more related to motor symptoms, such as swallowing/speech difficulties, and gait/balance problems; and also to motor complications.

The life expectancy of people with PD is reduced. Mortality ratios are around twice those of unaffected people.

Cognitive decline and dementia, old age at onset, a more advanced disease state and presence of swallowing problems are all mortality risk factors.

SIDE EFFECTS

L-Dopa is effective in elimination of symptoms of Parkinson’s, but is less effective in treating gait and postural instability.

It increases patient sense of well-being. Can lead to cardiovascular problems like

tachycardia or hypertension. It can also induce psychosis, delusions,

etc.

HISTORY In 1817 an English doctor, James Parkinson,

published his essay An Essay on the Shaking Palsy describing the characteristic resting tremor, abnormal posture and gait, paralysis and diminished muscle strength, and the progression over time.

Jean-Martin Charcot made the distinction between rigidity, weakness and bradykinesia.

In 1912,Frederick Lewy described microscopic particles in affected brains, later named “Lewy bodies “. 

In 1919, Konstantin Tretiakoff reported the substantia nigra as the main cerebral structure affected.

Levodopa was first synthesized in 1911 by Casimir Funk but it entered clinical practice in 1967. 

By the late 1980s deep brain stimulation emerged as a possible treatment.

COST AND ADVOCACY The costs of PD to society are high,

but precise calculations are difficult due to methodological issues in research and differences between countries.

In addition to economic costs, PD reduces quality of life of those with the disease and their caregivers.

April 11, the birthday of James Parkinson, has been designated as Parkinson's disease day.

A red tulip was chosen by international organizations as the symbol of the disease in 2005.

Advocacy organizations include the National Parkinson’s Foundation and Parkinson’s Disease Foundation.

NOTABLE CASES Actor Michael Fox has

greatly increased the public awareness of the disease. Fox was diagnosed at 30.

Cyclist and Olympic medalist Davis Phinney, was diagnosed with young onset Parkinson's at 40.

Muhammad Ali has been called the "world's most famous Parkinson's patient.

Other notable cases are Yasser Arafat and Pope John Paul II.

RESEARCH There is little prospect of dramatic new

PD treatments expected in a short time frame.

 Currently active research directions include the search for new animal models of the disease and studies of the potential usefulness of gene therapy, stem cells transplants and neuroprotective agents.

Investigations on neuroprotection are at the forefront of PD research. Several molecules have been proposed as potential treatments . However, none of them have been conclusively demonstrated to reduce degeneration.

SUMMARY

1-2% of general population are the sufferers.

Occur due to imbalance in neurotransmitters

Muscular rigidity, Impaired balance, Slow/Stiff and Tremors are main symptoms.

Levodopa and other dopaminergic drugs are used.

No treatment possible, only reduction of symptoms.

THANK YOU !!!