Brief outline of Parkinsons.

1. Parkinson’s Disease
-Paralysis agitans; Shaking palsy
Presented by: Tenzin Dolma
Biomedical Science 2nd year
Shaheed Rajguru College,DU
Pathology presentation @ Tenzin Dolma

2. General Introduction:
• It is one among the disease affecting the basal
ganglia( basal nuclei) and the brain stem( mid
brain+ Medulla oblongata+ Pons).There is
degeneration of dopaminergic neuron.
• There is either reduction of voluntary
movement or abundance of involuntary
movements
• It is the second most common disorder next to
Alzheimer’s disease
Pathology presentation@ Tenzin Dolma

3. Basal Nuclei/ Basal Ganglia
(Controls Voluntary Movement)
Caudate
Caudate
Nucleus
Nucleus
Putamen
Putamen
Lentiform
Lentiform
Nucleus
Nucleus Globus
Globus
Pallidus
Pallidus
Pathology presentation@ Tenzin Dolma

4. Production, Release, reuptake and inactivation of
monoamine neurotransmitters
Trp
Trp
TT
YY
RR
OO
SS
II
NN
EE
Pathology presentation@ Tenzin Dolma

5. Dopaminergic pathway in Brain:
Nigrostraital
Nigrostraital
pathway
pathway
Degeneration
Degeneration
cause Parkinson
cause Parkinson
symptoms.
symptoms.
Degeneration
Degeneration
cause Chorea
cause Chorea
Mesolimbic
Mesolimbic
pathway
pathway
Pathology presentation@ Tenzin Dolma

6. The Motor Circuit
Glutamate
(excitatory)
GABA
(inhibi
tory)
Dopamine
( Excitatory)
Pathology presentation@ Tenzin Dolma

7. Parkinsonism:
. Diminished expression in the face
• Slowness of voluntary movement, Rigid or stiff muscles, often beginning in the legs
– Difficulty starting movement, such as starting to walk or getting out of a chair
– Slowed movements and loss of fine movements
• Shaking, called tremors
– Usually occurs in the limbs at rest, or when the arm or leg is held out
– Goes away when you move
– Eventually may be seen in the head, lips, tongue, and feet
– May be worse when tired, excited, or stressed
– Finger-thumb rubbing (pill-rolling tremor) may be present
• Slowed, quieter speech and monotone voice
• Stooped position
• Anxiety, stress, and tension
• Other symptoms for PD:
• Confusion
• Dementia
• Depression
• Fainting
• Hallucinations
• Memory loss
Pathology presentation@ Tenzin Dolma

8. Causes/Etiology..
The exact cause of the disease is not known.
• Genetic factor plays a role but it varies from person to person. It can be
autosomal dominant or recessive too. (> 10%)
• Sporadic/ Idiopathic
• The effect of aging ; 13% decrease in dopamine level per decade but
syndrome seen at 80% fall.
• Toxins such as Pesticides and other endogenous and exogenous factors
• Oxidative free radical toxicity,
• Impaired mitochondrial function, which may shift the balance regulating
apoptotic cell death.
Pathology presentation@ Tenzin Dolma

9. Pathogenesis and Molecular genetics
Inherited
A .dominant
Juvenile
A. recessive
Inherited
PD
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10. MPTP
• Destruction of neurons in Substantia Nigra
Exposure to MPTP( 1-
Exposure to MPTP( 1-
methyl-4- phenyl-1,2,3,6
methyl-4- phenyl-1,2,3,6
tetrahydropyridine)
tetrahydropyridine) ( tox Monoamine oxidase B
icity)
• (During synthesis of psychoactive meperidine)
• Toxicity of MPTP was used in experimental
experimental study of PD involving
transplantation.
Pathology presentation@ Tenzin Dolma

11. Morphologic changes
• Neurons of the substantia nigra show severe morphological
changes in Parkinson's disease. There is pallor and local
ceruleus.
• Decrease of dendritic length, loss of dendritic spines and
several types of dendritic varicosities were found only in the
melanin-containing pars compacta neurons. Surviving cells
contain eosinophilic inclusions Lewy bodies.
• Lewy body in basal nucleus of Meynert .
Pathology presentation@ Tenzin Dolma

12. Diagnosis
• The symptoms can be difficult to assess, particularly in the
elderly. They become more clear as the illness gets worse.
• A doctor's examination may show:
• Difficulty starting or finishing voluntary movements
• Jerky, stiff movements
• Muscle atrophy
• Shaking (tremors)
• Changes in your heart rate
• Reflexes should be normal.
• Symptomatic response to L-DOPA therapy supports PD
diagnosis.
• Tools: PET and SPET
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13. Microscopic Pathology
This is an example of a normal substantia nigra at medium power.
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14. This is the substantia nigra of the current case taken at the same magnification.
Note the extensive loss of pigmented neurons, corresponding to the lack of
pigment seen grossly.
All types of Parkinsonism have a minimum 80% loss of neurons in the substantia
nigra
Pathology presentation@ Tenzin Dolma

15. At high power we can see that this surviving neuron contains a Lewy body (arrow). These
were seen in many of the surviving neurons in this case.
Lewy bodies are cytoplasmic eosinophilic masses made up of alpha synuclein and other
proteins.
In Parkinson's disease they can be found not only in the substantia nigra, but also in the
locus coeruleus, sympathetic ganglia, basal nucleus of Meynert and cerebral cortex.
Pathology presentation@ Tenzin Dolma

16. How Treatment Works?
• There is no known cure for Parkinson's disease. The goal of treatment is to
control symptoms.
• Medications control symptoms, mostly by increasing the levels of
dopamine in the brain. At certain points during the day, the helpful effects
of the medication often wears off, and symptoms can return. If this
happens to you, your health care provider may need to change the:
medicine is taken.Sugeries reduce the symptoms.
• Work closely with your doctors and therapists to find a treatment
program that works best for you. Never change or stop taking any
medications without talking with your doctor.
• Many medications can cause severe side effects, including hallucinations,
nausea, vomiting, diarrhea, and delirium. Monitoring and follow-up by the
health care provider is important.
• Eventually, symptoms such as stooped posture, frozen movements, and
speech difficulties may not respond very well to drug treatment.
Pathology presentation@ Tenzin Dolma

17. Treatment
• Drugs • Surgeries
1. Levodopa (L-dopa), Sinemet, 1. Stereotactic implants of fetal
levodopa and carbidopa (Atamet) mesencephalic tissue into stratium
2. MAO inhibitors(Selegiline and 2. Involves placing electrical stimulators in
Rasagiline) specific areas of the brain that control
3. Anticholinergic medications to movement. Deep brain stimulation.
reduce early or mild tremors 3. placement of lesion to compensate loss of
nigrostraital pathway
4. Stem cell transplant and other clinical
trials are currently ongoing in the USA.
Pathology presentation@ Tenzin Dolma

18. Terminologies to Look For
• Lewy Bodies
- Single or multiple cytoplasmic, eosinophilic, round to elongated inclusions with a dense core.
• Dementia
- It is a loss of brain function that occurs with certain diseases. It affects memory,
thinking, language, judgment, and behavior.
• Parkin
-protein is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of
the ubiquitin-proteasome system that mediates the targeting of proteins for degradation
• Ubiquitin
- a small regulatory protein that has been found in almost all tissues ( ubiquitously) of eukaryotic
organisms. It directs proteins to compartments in the cell, including the proteasome which destroys
and recycles proteins.
• α- synuclein ( abundant lipid binding protein)
• Chorea: Hyperkinetic disorder with rapid, uncontrolled, jerky movements.
Pathology presentation@ Tenzin Dolma

19. References
• Robbins and Cotrans, Pathologic Basis of
Disease, 7th edition, Elsevier and Saunders
• Struat Ira Fox, Human Physiology, 11th edition,
McGraw Hill international Edition
• FOYE’S Principle Of Medicinal Chemistry, 6th
Edition, Wolters Kluwel/Lippincot Williams
and Wilkins
Pathology presentation@ Tenzin Dolma

20. Help Old People in their later years..
Thank
You!!! Pathology presentation@ Tenzin Dolma