3. Definition
• Neurodegenerative disease is a condition which affects
brain function. Neurodegenerative diseases result from
deterioration of neurons.
• They are divided into two groups:
– conditions causing problems with movements
– conditions affecting memory and conditions related to
dementia.
– Examples:
• Alzheimer’s
• Parkinson’s
• Huntington’s
• Creutzfeldt-Jakob disease
• Multiple Sclerosis
• Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's
Disease)
4. Risk Factors
• Known
– Certain genetic
polymorphisms
– Increasing age
Possible
Gender
Poor education
Endocrine conditions
Oxidative stress
Inflammation
Stroke
Hypertension
Diabetes
Head trauma
Depression
Infection
Tumors
Vitamin deficiencies
Immune and metabolic
conditions
Chemical exposure
Smoking??
5. PARKINSON`S DISEASE is movement
disorder of unknown etiology due to
degeneration of neurons in the nigrostrial
dopamine system.
History:
First described in 1817 by an English physician,
James Parkinson, in “An Essay on the Shaking
Palsy.”
The famous French neurologist, Charcot, further
described the syndrome in the late 1800s.
6. Epidemiology of PD
The most common movement disorder
affecting 1-2 % of the general population over
the age of 65 years.
The second most common neurodegenerative
disorder after Alzheimer s disease (AD).
7. Causes of Parkinsonism
• Impaired release of dopamine- Idiopathic
parkinsonism.
• Drug depleting dopamine store-reserpine,
tetrabenzine.
• Toxin damaging dopaminergic neuron.
• Viral infection- Encephalitis ,Japanese encephalitis
• Trauma-repeated head injury[punch drunk syndrome]
• Miscellaneus-wilson disease,huntingtion,s disease
10. Risk factors of PD
Age - the most important risk factor
Positive family history
Male gender
Environmental exposure: Herbicide and pesticide
exposure, metals (manganese, iron), well water, farming,
rural residence, wood pulp mills; and steel alloy
industries
Race
Life experiences (trauma, emotional stress, personality
traits such as shyness and depressiveness)?
An inverse correlation between cigarette smoking and
caffeine intake in case-control studies.
11. Clinical features of PD
• Three cardinal
symptoms:
resting tremor
bradykinesia
(generalized
slowness of
movements)
muscle rigidity
12. CLINICAL FEATURE
• TREMORS(4-6hz):
• tremors[pill rolling] at rest, decreases on action.
Usually first in finger/thumb.
• Coarse flexion/extension of finger[pill rolling &
drum beating]
• RIGIDITY-
• Cog wheel type especially in upper limb
{stiffness in all direction of movement}.
• Plastic type {lead type} mostly appreciated in
legs. In trunk rigidity manifest by flexed& stooped
posture
13. Hypokinesis
• Charactrized by poverty & slowness of
movement. Slowness in initiating
movement. Handwriting micrographia.
• GAIT-patient walk with short step , with a
tendency to run{as they are catching their
own centre of gravity}-festinating gait
• General-expressionless face with staring
look with infrequent blinking. Monotonus
speech. Dementia & Depression in
advance stage
16. Therapy of PD: levodopa
Late 1950s: L-dihydroxyphenylalanine (L-DOPA;
levodopa), a precursor of DA that crosses the blood-brain
barrier, could restore brain DA levels and motor
functions in animals treated with catecholamine depleting
drug (reserpine).
First treatment attempts in PD patients with levodopa
resulted in dramatic but short-term improvements; took
years before it become an established and succesfull
treatment.
Still today, levodopa cornerstone of PD treatment;
virtually all the patients benefit.
17. Therapy of PD: limitations of levodopa
Efficacy tends to decrease as the disease progresses.
Chronic treatment associated with adverse events
(motor fluctuations, dyskinesias and
neuropsychiatric problems).
18. Inhibition of peripheral COMT by entacapone increases the amount
of L-DOPA and dopamine in the brain and improves the alleviation
of PD symptoms.
19. Therapy of PD: limitations of levodopa
Does not prevent the continuous degeneration
of nerve cells in the subtantia nigra, the
treatment being therefore symptomatic.
20. Therapy of PD: Other treatments
DA receptor agonists:
Bromocriptine Pergolide
