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Parkinson Syndrome

A collective term referring to a class of extrapyramidal diseases where the primary deficit is akinesia or hypokinesia.

Bradykinesia

Poverty of movement, reaction time delay and slow execution

Rigidity

increased muscle tone (plastic type) without significant loss of muscle power and increase in tendon reflexes

Resting Tremor

3 to 5 per second involving the fingers, arm and chin

Parkinson Syndrome

These abnormalities are associated with a tendency to flexed postures –head down on chest, shoulders rounded, and arms and

knees slightly flexed

Disorders of posture and equilibrium

Disordered gait (series of quickening steps forward or backward as though chasing the center of gravity (festination)

Parkinsonism (Secondary Parkinson’s Disease)

Occurs with treatment with dopamine-depleting agents such as reserpine or antipsychotic dopamine-receptor antagonists such as phenothiazines or butyrophenones.

Women and elderly patients with an increased risk

Parkinsonism

Tremor is relatively uncommon

Hypokinesia tends to be symmetric, and the most conspicuous neurologic feature

History of drug ingestion

Signs usually develop within 3 months after starting the offending drug and disappear over weeks or months following discontinuance.

Paralysis Agitans

Primary Parkinson’s Disease is AKA what?

Primary Parkinson’s Disease

An adult-onset neurodegenerative disorder of the extrapyramidal system characterized by a combination of tremor at rest, rigidity and bradykinesia.

To Levodopa

The diagnosis requires therapeutic response

to what?  Which implies normal striatal neurons.

This is the only neurodegenerative disease which is treatable long-term

Nervous & Musculoskeletal

What are the system (s) affected by Primary Parkinson’s Disease?

May be a genetic role with risk 2.95-fold in patients with positive family history in late onset

disease

7.76-fold increase in early onset disease (<50)

Genetics of Primary Parkinson’s Disease?

50,000 per year; 0.3% 55-64, 1% 65-74, 3.1% 75-84;

4.3% 85-94

Incidence/ Prevalence in USA of Primary Parkinson’s Disease?

Age 60 with 5% between the ages of 21 and 39

Predominant age of Primary Parkinson’s Disease?

Male > Female (1.4:1)

Predominant sex of Primary Parkinson’s Disease?

Unknown in the idiopathic disease

Association between smoking and increased caffeine intake and reduced risk for Parkinson disease has been reported

Risk Factors of Primary Parkinson’s Disease?

Extrapolated Prevalence of Primary Parkinson’s Disease

317,065 out of 86,241, 697

(0.36%)

US Census Bureau, International Data Base, 2004

Loss of pigmented cells in the substantia nigra (pars compacta) and other pigmented nuclei in the brainstem

What are the pathological findings of Primary Parkinson’s Disease?

Lewy bodies- cytoplasmic inclusions

Typical changes that allow precise pathological diagnosis.

Biochemical Abnormality

Population of nigral cells fall from 425,000 to 100,000

As a result deficiency of dopamine both in the nigral cells in which dopamine is synthesized and at the synaptic endings of the nigral fibers in the striatum

Responsible for the signs and symptoms

Differential Diagnosis

Parkinsonism: bradykinesia and occasionally tremor with little or no response to levodopa indicating that the striatal neurons are also degenerated

▪  Progressive supranuclear palsy

▪ Multisystem atrophy

▪  Alzheimer with extrapyramidal features

▪  Side effects of neuroleptic medications

▪  Infectious - postencephalitic

▪  Vascular - lacunar state

▪  Toxins

▪  Metabolic - Wilson disease: onset <40

▪ Benign essential tremor: positive family history and relief with

alcohol

CT or MRI help rule out other disorders

PET scanning

Special Tests ( NOT APPLICABLE IMAGING)

• Rest tremor

• Rigidity

• Bradykinesia

Diagnosis Criteria - Clinically possible - any one of:

• Rest tremor

• Rigidity

• Bradykinesia

• Impaired postural reflexes, or one of the first three displaying asymmetry

Diagnosis Criteria - Clinically probable - any 2 of:

• Rest tremor

• Rigidity

• Bradykinesia

• Impaired postural reflexes, or Any 2 of above with one of first 3 displaying asymmetry

Diagnosis Criteria - Clinically definite - any 3 of:

TRAP

What is the Tell-Tale Signs of PD?

Tremor, Rigidity, Akinesia, Postural instability

What does TRAP mean?

Tremor

Involuntary trembling of the limbs

Rigidity

Stiffness of the muscles

Akinesia

Lack of movement or slowness in initiating and maintaining movement

Postural instability

Characteristic bending or flexion of the body, associated with difficulty in balance and disturbances in gait

Tremor (4-8 Hz) in repose, Bradykinesia and Rigidity

What are the 3 Cardinal Signs?

Tremor (4-8 Hz) in repose

Diagnostic, but not required; relieved with activity, concentration, and sleep; increases with stress; 10% of patients present with only tremor, 30% present without; most begin with unilateral tremor.

Bradykinesia

required for diagnosis; most disabling symptom; movement initiation diffi cult, can be overcome with will; causes the gait and postural abnormalities

Rigidity

lead pipe type; cog-wheeling with tremor

Dementia in 20% of patients; more common in patients whose disease onset was bilateral - mild to moderate, 90% with Folstein MMSE >15

Gait disturbances including no arm swing, en mass turning, problems getting up from chair, festination, freezing

Leaning posture

Propulsion or retropulsion

Mask facies

Neglect of swallowing with drooling

Excessive daytime sleepiness increases with severity of disease and medication use

What are the other signs and symptoms?

5 stages

How many stages does the Hoehn and Yahr scale of disability in

Parkinson disease have?

stage 1

unilateral, minimal functional impairment

stage 2

bilateral without impairment of balance

stage 3

bilateral, positive instability, physically

Independent

stage 4

severe disability, can walk or stand without assist, but markedly incapacitated

stage 5

wheelchair bound or bedridden unless aided

General Measures of PD

• Drugs have therapeutic and toxic effects

• Acute worsening may indicate depression, non-compliance or supervening illness

• Course is progressive with or without drugs.

• Life-long therapy directed toward symptom control - treat disability

• Investigate for drug-induced cause; if found, discontinue drug. Symptom resolution may take weeks to months.

• Physical, occupational and speech therapy

• Physical limitations require adjustments in the home, e.g., special chairs, elevated toilet seat, eating utensils, dressing oneself

Activity

Maintain activity to whatever degree possible; use a cane for walking

Diet

• Small frequent meals if difficulty in eating

• High liquid intake is important; high bulk foods

• Reduced protein diet is unnecessary

Patient Education

Local support groups

Levodopa-carbidopa (Sinemet)

Therapy of PD

Levodopa-carbidopa (Sinemet)

May be the initial drug of choice in older patients with more severe symptoms, although neuro-vegetative symptoms such as speech disorders and falls are resistant to levodopa

Levodopa

Mechanism of Action: Resolves dopamine deficiency by being converted to dopamine after crossing the blood-brain barrier.

Special comments: Still the best drug for resolving Parkinsonian symptoms; long-term use is limited by side effects and decreased efficacy.

Dopamine agonists

• Bromocriptine

• Cabergoline

• Pergolide

• Pramipexole

• Ropinirole

Mechanism of Action: Directly stimulates dopamine receptors in basal

ganglia.

Special comments: May produce fewer side effects (dyskine-sias, fluctuations in response) than lev-odopa; preliminary evidence suggests that early use may also delay the progression of Parkinson disease.

Anticholinergics

Mechanism of Action: Inhibit excessive acetylcholine influence caused

by dopamine deficiency.

Special comments: Use in Parkinson disease limited by frequent side effects.

Amantadine

Mechanism of Action: Unclear; may inhibit the effects of excitatory amino acids in the basal ganglia.

Special comments: May be used alone during early/mild stages or added to drug regimen when levodopa loses effectiveness.

Selegiline

Mechanism of Action: Inhibits the enzyme that breaks down dopamine in the basal ganglia: enables dopamine to remain active for longer periods of time.

Special comments: May improve symptoms, especially in early stages of Parkinson disease; ability to produce long-term benefits unclear.

COMT nhibitors (catechol-O-methyltransferase)

• Entacapone

• Tolcapone

Mechanism of Action: Help prevent breakdown of dopamine in peripheral tissues; allows more levodopa to reach the brain.

Special comments: Useful as an adjunct to levodopa/carbidopa administration; may improve and prolong effects of levodopa.

Benztropine mesylate

Trade Name: Cogentin

Daily Dosage (mg/d): 1.0 - 2.0

Prescribing Limit (mg/d): 6

Biperiden

Trade Name: Akineton

Daily Dosage (mg/d):  6.0 - 8.0

Prescribing Limit (mg/d): 16

Diphenhydramine ( Antihistamine drug with anticholinergic properties)

Trade Name: Benadryl

Daily Dosage (mg/d): 75 - 200

Prescribing Limit (mg/d): 300

Ethopropazine

Trade Name: Parsidol

Daily Dosage (mg/d): 50 - 100

Prescribing Limit (mg/d): 600

Procyclidine

Trade Name: Kemadrin

Daily Dosage (mg/d): 7.5 - 15.0

Prescribing Limit (mg/d): 20

Trihexyphenidyl

Trade Name: Artane

Daily Dosage (mg/d): 6.0 - 10.0

Prescribing Limit (mg/d): 15