Transcript Parkinson disease

Movement disorder
Movement disorders (sometimes called extrapyramidal
disorders) impair the regulation of voluntary motor activity
without directly affecting strength, sensation, or cerebellar
function. They include hyperkinetic disorders associated with
abnormal, involuntary movements and hypokinetic disorders
characterized by poverty of movement.
hyperkinetic disorders of abnormal movements can be
classified as tremor, chorea, athetosis or dystonia, ballismus,
myoclonus, or tics. And examlpe of Hypokinetic is Parkinson .
Parkinson disease
Parkinson's disease is one the commonest neurodegenerative
disease. Parkinson’s disease (PD) is a neurodegenerative
disorder associated with a loss of dopamine-producing
neurons in the substantia nigra.
The disease was described by James Parkinson in 1817.
PD slightly more common in men than women. The mean age
of onset is about 60 years, but cases can be seen in patients
in their 20s, and even younger.
Diagnosis of a parkinsonian syndrum
•Bradykinesia (slowness of initiation of voluntary movement
with progressive reduction in speed and amplitude of
repetitive actions)
••Muscular rigidity
••4–6 Hz rest tremor
••Postural instability not caused by primary visual, vestibular,
cerebellar or proprioceptive dysfunction.
Other Motor Features
Micrographia
Masked facies (hypomimia)
Reduced eye blink
Soft voice (hypophonia)
Dysphagia
Freezing
Nonmotor Features
•Anosmia
•pain
•Mood disorders (e.g. depression)
•Sleep disturbances
Epidemiology and Pathologenesis
Hallmark features of PD are degeneration of dopaminergic
neurons in the substantia nigra.
The studies suggest that environmental factors likely play the
more important role in patients older than 50 years, with
genetic factors being more important in younger patients.
Epidemiologic studies suggest increased risk with exposure to
pesticides, rural living, and drinking well water and reduced
risk with cigarette smoking and caffeine.
Differential diagnosis
Secondary Parkinsonism
• Drug-induced (Dopamine-blocking agents such as the
Antipsychotic )
• Infection
• Vascular
• Normal-pressure hydrocephalus
• Trauma
• Liver failure
• Toxins (e.g., carbon monoxide, manganese, cyanide,
hexane, methanol, carbon disulfide)
Other Neurodegenerative Disorders
• Wilson's disease
• Huntington's disease
------------------------------------------------------
Treatment of Parkinson's Disease
1- Levo Dopa
Dopamine does not cross the blood-brain barrier (BBB), so
clinical trials were initiated with levodopa, a precursor of
dopamine. Levodopa is routinely administered in combination
with a peripheral decarboxylase inhibitor (carbidopa or
benserazide) to prevent its peripheral metabolism to
dopamine and the development of nausea and vomiting
levodopa is still the most potent and effective symptomatic
treatment for PD, and remain the ‘gold standard’.
It is usual to start with half a tablet of 25/100
(PDI/levodopa)strength b.d. or t.d. for a couple of weeks,
then doubling the dose and waiting to judge the effect over
time with continued treatment, however, the duration of
benefit following an individual dose becomes progressively
shorter until it approaches the half-life of the drug. This loss
of benefit is known as the wearing-off effect. At the same
time, many patients develop dyskinesias,these tend to occur
at the time of maximal clinical benefit and peak plasma
concentration (peak-dose dyskinesia). In more advanced
states, patients may cycle between "on" periods complicated
by disabling dyskinesias and "off" periods in which they suffer
severe parkinsonism.
Strategies to Treat Motor Fluctuations
End-of-Dose Deterioration
‘‘Off ’’ Dystonia at night
(1) Increase LD/CD from 3 to 4 times daily
(2) Substitute sustained release LD/CD
(3) Add dopamine agonist
(4) Add COMT inhibitor
(1) Add sustained-release LD/CD at bedtime
(2) Add dopamine agonist at bedtime
Peak-Dose Dyskinesia
(1) Smaller doses of levodopa taken more
frequently
(2) Add dopamine agonist, decrease
levodopa
(3) Add amantadine
2-Dopamine agonists
Dopamine agonists stimulate dopamine receptors directly. Six
oral agonists (bromocriptine, lisuride, pergolide ,
cabergoline,ropinirole and pramipexole) ,one transdermal
agonist (rotigotine) and Apomorphine administered SC are
available,thsese agonist may given before levodopa is
introduced especially in young age , these drugs cause
fluctuations and dyskinesias much less frequently.
,
3- Catechol-O-methyl transferase (COMT) inhibitors
Entacapone (peripheral) and tolcapone (peripheral and
central COMT inhibitor) block the conversion of levodopa to
3-O-methyldopa, its principal metabolite so increase the
duration effect of levodopa.A combined tablet containing
levodopa, carbidopa and entacapone (Stalevo) is available.
4-Monoamine oxidase B (MAO-B) inhibitors
Selegiline and rasagiline are inhibitors of MAO-B, the isoenzyme (MAO-B) responsible for catabolizing dopamine to
homovanillic acid (HVA).lead to increase the duration effect of
levodopa.
5-Anticholinergics
Anticholinergics often restricted to reducing tremor. eg.
trihexyphynidyl ,procyclidin .
6-Amantadine
This drug has several actions: an amphetamine-like effect
(releasing presynaptic dopamine stores); a mild
anticholinergic effect.
Surgery for PD
it was appreciated that lesions placed into the nucleus of the
thalamus reduced contralateral tremor without inducing
hemiparesis, but these lesions did not meaningfully help
other more disabling features of PD. Lesions placed in the GPi
(globus palidus interna) improved rigidity and bradykinesia as
well as tremor
Deep brain stimulation (DBS)
Most surgical procedures for PD performed today utilize deep
brain stimulation (DBS). Here, an electrode is placed into the
target area and connected to a stimulator inserted SC over
the chest wall. DBS simulates the effects of a lesion without
necessitating a brain lesion, Stimulation of thalamus lead to
decrease tremor ,stimulation of Globus Pallidus Interna lead
to decrease rigidity and bradykinesia.
TREMOR
A tremor is a rhythmic oscillatory movement best
characterized by its relationship to voluntary motor activity,
i.e., according to whether it occurs at rest, during
maintenance of a particular posture, or during movement so
tremor can be classified to: rest and action tremor
Action tremor is classified into:
postural tremor
intention tremor
Action tremor
1-Postural tremor
 Physiologic tremor
Enhanced physiologic tremor causes are:
Anxiety or fear
Excessive physical activity or sleep deprivation
Sedative drug or alcohol withdrawal
Drug toxicity (lithium, bronchodilators, sodium valproate,
tricyclic anti depressants)
Thyrotoxicosis
Carbon monoxide poisoning
Familial (autosomal dominant) or idiopathic (benign
essential) tremor
Wilson disease
Asterixis
2-Intention tremor
Cerebellar disorders
Wilson disease
Drug toxicity (e.g., alcohol, anticonvulsants, sedatives)
Rest tremor
oParkinsonism
oWilson disease
--------------------------------------------PHYSIOLOGIC TREMOR
An 8- to 12-Hz tremor of the outstretched hands is a normal
finding. Its physiologic basis is uncertain.
ENHANCED PHYSIOLOGIC TREMOR
Physiologic tremor may be enhanced by fear or anxiety. A
more conspicuous postural tremor may also be found
following excessive physical activity or sleep deprivation and
other causes mentioned above.
Benign essential tremor
This is commonly inherited as an autosomal dominant trait.
Most people with essential tremor (ET) have little or no
disability ET is a 4-Hz to 12-Hz postural tremor, typically seen
as adduction-abduction of the fingers or flexion-extension of
the wrist; pronation-supination of the wrist can occur, but it is
more typical of PD. The tremor may start on one side, but as a
rule it becomes bilateral with time. The handwriting remains
large (unlike PD) but may often be severely affected and
illegible. The head is the next most frequent area to be
affected, with a vertical ‘‘yes-yes’’ or horizontal ‘‘no-no’’
tremor. The voice, tongue, and chin may all be involved as
well.
Criteria of essential tremor
Core Criteria
Bilateral action tremor of the hands and forearms (not rest
tremor)
Absence of other neurologic signs
May have isolated head tremor
Secondary Criteria
Long duration (>3 years)
Positive family history
Beneficial response to alcohol
Treatment
Propranolol
About 50% of patients will experience relief with propranolol
and other B-adrenergic antagonists. Doses generally are
rather large, with optimal response in the 240 mg to 320 mg
range.
Primidone
Because the main side effect of primidone is sedation, it
should be started at 25 mg at bedtime and increased very
slowly by 25-mg increments. If needed, a low dose may be
added in the morning. Doses above 250 mg to 350 mg are
rarely needed.
Topiramate
have suggested some improvement in ET
Surgical treatment
 Stereotactic lesioning of the ventral intermediate
nucleus (VIM) of the thalamus has produced the greatest
response in patients with severe tremor.
deep brain stimulation (DBS) of the VIM nucleus of the
thalamus , has become the surgical procedure of choice
Befor treatment
After treatment