( enviromental MPTP like herbicide?) - ? Genetic factors, clusters of early onset Parkinson’s
in some families ? Mutation in parkin gene on
- progressive degeneration with eosinophilic
inclusion bodies ( Lewy bodies) in za neurones
of substantia nigra & other basal ganglia nuclei
- loss of melanin & dopamine that correlate with the degree of akinesia
- imbalance between dopaminergic & cholinergic
- Symptoms develop over moths & several years
1-Pill rolling tremors of za hands, often unilateral, is the most common initial feature. It is eventually becomes bilateral involving the UL, LL & jaw. It diminishes on voluntary movement an increases by emotion.
2- Slowness of movement or bradykinesia is
usually by za family. There is difficulty in
initiating movements including fine finger move
3- Rigidity causes stiffness . It is lead pipe and
4- Stooping posture, festinant & shuffling
gait wz reduced limb swinging
Propulsion & retropulsion are characteri
There is postural instability & falls.
5- Masked expressionless face wz reduced
6- Monotonous speech progressing to
slurring & eventually lost.
8- Drooling of saliva, dysphagia, constipati
9- Excessive sweating & greasy skin.
10- Power remains normal, reflexes may
be increased, planters remain flexor
and sensations are normal.
11- Cognitive fns preserved at least early,
dementia develops in late stages,
anxiety & depression are common
12- No remission & za rate of progression
is variable wz death resulting from
chest infection, UTI & bed sores
- characteristic clinical picture
- careful history & examination to exclude other
causes of Akinetic – rigid syndromes i.e.
secondary causes of parkinsonism
1- Drug induced parkinsonism e.g neuroleptics,
reserpine, methyldopa, tricyclic antidepressants
mainly cause slowness & rigidity wz little tremor
2- Post encephalitis lethargica
3- Toxins e.g MPTP, CO, Mn
4- CVAs, hypoparathyroidism, trauma & SOL
5- Wilson’s disease & athetoid C. palsy in childr
6- Progressive supranuclear palsy
7- Multiple system atrophies:
- Olivo – ponto – cerebellar degeneration
- Pry autonomic failure ( Shy Drager syndr)
8- Alzeheimer disease
9- Huntington's chorea
Management of Parkinson’s disease
A- identify 2ry causes of parkinsonism & TR
e.g withdrawal of neuroleptics, penicillamine
B- Drug therapy to restore dopaminergic/
cholinergic balance, but
- not curative
- greatly improve za quality of life
- should only be started when za functional
disability interferes wz life.
1- Dopaminergic drugs act through
- replacement of neuronal dopamine e.g
L dopa which is za natural precursor of
dopamine & crosses BBB ( dopamine not)
- releasing dopamine from its stores and
inhibiting its re uptake e.g amantadine
- prolonging za action of dopamine by selectiv
inhibition of its metabolism e.g selegline
- dopamine receptor agonists e.g bromocriptine
2- Anti muscarinic anti cholinergics reduce
cholinergic activity by inhibiting acetyl choline
esterase e.g benzhexol.
** drug induced parkinsonism is best treated by anti muscarinic drugs & not by L dopa since
neuroleptic drugs block dopamine receptors.
1- Levodopa (L dopa )
- a a precursor of dopamine wz short ½ life 1,5h
- dopamine can not be used as it is rapidly
destroyed peripherally (gut, liver & blood) by
MAO inhibitor & catechol O –methyl transferase
and does not cross BBB.
- peripheral dopa decarboxylase inhibitors which
do not cross BBB are combined with L dopa in
therapeutic doses to avoid large doses of L dopa
e.g Sinemet ( cabidopa + L dopa 1 : 10) :
110, 250mg. OR Madopar ( benserazide + L dop
1:4: 65.5, 125, 250mg.
- With combination low doses of L dopa are used
and side effects are reduced:
(N, V, post hypotension, arrhythmias, dyskin
confusion, agitation, hallucination, depressio
long term problems of end of dose deterior
and on off swings)
- L dopa interaction wz non selective MAO-I
causes hypertensive crisis. In this situation L dopa dopamine Noradrenaline HT.
- anti viral
- less effective than L dopa but may
enhance its effect
- mainly used in early mild cases
- dose: 100-300mg/d
- SE= post hypot, ankle edema & livedo
- dopamine receptor agonist
- ½ life 5hrs, therefore smoother action than
L dopa & no fluctuation in action
- dose: 10-80mg starting wz 1.25mg e.g
Parlodel (2.5 &10mg)
- used in long term L dopa problems
- SE= similar to L dopa.
- selective B MAO-I
- It delays break down of dopamine & prolongs
- main use in those wz long term L dopa
problems e.g end of dose deterioration
- anti depressant also
- e.g eldepryl 5mg X2. SE= similar to L dopa.
- no hypertensive cheese reaction (tyramine)
which occur wz non selective MAO-I which
prevent degradation of dietary amines by
MAO-I. Tyramine is degraded by type A MAO-I
- COMT inhibitor
- Used to reduce end- of- dose fluctuation
in response to L dopa.
6- Anti muscarinic anti cholinergics
- Act by blocking Ach in za CNS restoring the
imbalance created by decreased dopaminergi
- most effective in drug induced parkinsonism and in mild cases sp. tremor, rigidity and sialorrhMoea. Not used I n > 65, glucoma & BPH. SE= those of anti cholinergics.
- trihexyphenidyl (benzhexol 2mg), benz atropin
3- General management of parkinsonism
- Positive attitude by encouraging physical
activity, physiotherapy & speech therapy
- Early mild cases: anti muscarinic & amantadine
-With progression of za disease dose of L dopa
needs to be increased wz more SEs which may
be overcome by reducing individual doses
and increasing za frequency of administration or
by using bromocriptine & selegline
- L dopa + carbidopa restore near normal
physical activity in 75%. Ultimately higher doses are required.
- long term therapy is associated with:
1- end- of- dose fluctuation= swings from early morning akinesia to peak
2- on- off swings= random fluctuation
from mobility to dyskinesia wz peak
- Long term problems wz L dopa is treated
by: - gradual & partial substitution of
L dopa wz bromocriptine & selegline
effective in end- of- dose deterioration
- decreasing dose of L dopa & shortening za interval between doses.