Parkinson Disease

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Parkinson is common in old age!

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Parkinson Disease:

Parkinson Disease Muhammad Nisar Aga Khan University SON Karachi

Parkinson disease:

Parkinson disease A disorder of the brain characterized by shaking and difficulty with walking , movement, and coordination. The disease is associated with damage to a part of the brain that controls muscle movement.

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History of Parkinson´s disease (PD) 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.

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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).

Incidence of PD:

Incidence of PD Age Incidence / 100 000

Prevalence of PD:

Prevalence of PD Age Prevalence / 100 000

Epidemiology of PD:

Epidemiology of PD May be less prevalent in China and other Asian countries, and in African-Americans. Prevalence rates in men are slightly higher than in women ; Higher incidence in men (62%) compared to women (38%) reason unknown, though a role for estrogen has been debated.

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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.

Parkinson’s Disease - Pathophysiology:

Substantia Nigra Thalamus Cortex Subthalamic nucleus Globus Pallidus Parkinson’s Disease - Pathophysiology The Basal Ganglia Striatum In PD, cellular degeneration starts in the substantia nigra of the basal gangla, where dopamine-producing nerve cells, called nigral cells, are formed. Porth , 2012

Parkinson’s Disease - Pathophysiology:

Substantia Nigra Thalamus Cortex Subthalamic nucleus Globus Pallidus Parkinson’s Disease - Pathophysiology The Basal Ganglia Striatum In PD the striatum portion of the basal ganglia receives an inadequate amount of nigral cells, which impairs a person’s ability to control movement. The basal ganglion’s connection to the cortex and the thalamus also affects movement . Porth , 2012 Muscle control Dopamine Nigral cells

Parkinson’s Disease - Pathophysiology:

Cells degenerate in substantia nigra ( Sn ) Substantia nigra destroyed Dopamine decreases Muscle cell activation decreases Movement control decreases Parkinson’s Disease - Pathophysiology Healthy Sn PD Sn Porth, 2005

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Neuropathology of PD Eosinophilic, round intracytoplasmic inclusions called lewy bodies and Lewy neurites. First described in 1912 by a German neuropathologist - Friedrich Lewy. Inclusions particularly numerous in the substantia nigra pars compacta .

Lewy bodies:

Lewy bodies

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Pathological hallmarks of PD 1- loss of nigrostriatal dopaminergic neurons 2-presence of proteinacious cytoplasmic inclusions, called Lewy Bodies (LBs) 3-At the onset of symptoms, DA is depleted ~80% and ~60% of Substantia Nigra Pars Compacta ( SNpc ) is lost. 4 -More damage occurs at the nerve terminals, suggesting that dopaminergic nerve terminals are the primary target for the neurodegeneration .

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Lewy Bodies 1-Intracellular lesions not specific of PD, but present also in certain cases of Dementia ( Lewy Bodies Dementia) 2-Spherical eosinophilic cytoplasmic protein aggregates, measuring more than 15mm in diameter composed of : a- synuclein , parkin , ubiquitin and neurofilaments 3- Mechanism of toxicity not known: these aggregates could directly damage the cell by disrupting the intraneuronal protein traffic, or by removing soluble proteins crucial for the life of the cell. 4-These inclusions may result from a process aimed at removing soluble proteins in the cytosol .

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Deposition of fibrillar proteinacious material in Parkinson’s disease Parkinson’s disease : characterized by dopaminergic neuronal loss and by intracellular depositions, the Lewy bodies , comprised of a-synuclein and ubiquitin, as the major components. Other components are proteasome and cytoskeletal proteins and other proteins that interact with a-synuclein.

Clinical features of PD:

Clinical features of PD Three cardinal symptoms: ® resting tremor ® bradykinesia (generalized slowness of movements ) ® muscle rigidity Symptoms worsen as disease progresses.

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Resting tremor: Most common first symptom, most evident in one hand with the arm at rest. ♦ usually unilateral ♦ becomes bilateral ♦ worsens with stress

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Tremors Usually -- ♦ first symptom ♦ occurs in the hands or arms can occur in head, face, jaw, & leg ♦ disappears with purposeful movement such as picking up an object

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Postural manifestations – ■ postural instability ■ rigidity ■ stooped Postural changes cause balance instability

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Patients also suffer from non-motor symptoms such as: ♦ cognitive impairments ♦ olfactory impairments ♦ dysphagia ♦ GI dysfunction ♦ sleep disturbances ♦ depression

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Stage Symptoms One Unilateral Two Bilateral No balance impairment Three Balance impairment Mild to moderate disease Physically independent Four Severe disability Still able to walk & stand unassisted Five Wheelchair-bound or bedriddened unless assisted

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Question: Does daily stress worsen PD symptoms?

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Answer: Yes, but only temporarily ♦ Stress is not the cause of PD ♦ Any stress can briefly worsen PD symptoms ♦ Stress-related symptoms resolve after stress is relieved.

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Are all the following symptoms of PD? bradykinesia tremor rigidity gastrointestinal dysfunction postural instability sleep disturbances cognitive impairments. True or False

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P ostural instability, rigidity, and stooped posture places the PD patient at greatest risk for: Sleeping Sneezing Falling Dying

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What causes the movement problems of PD?

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Answer: Degenerative changes in the substantia nigra and striatum portions of the basal ganglia reduce dopamine production. Substantia nigra Cross section of striatum

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What causes PD?

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Answer: Process not understood completely - May be combination of factors involving genetics, environmental agents,& abnormalities in cellular process.

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What causes the movement problems of PD? Excess amount of epinephrine Inadequate amount of epinephrine Excess amount of dopamine Inadequate amount of dopamine

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Question: Is Genetics a Factor in PD?

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Answer: ♦ Recent discoveries support a genetic component to some familial forms of PD in both early-age and late-age onset ♦ 15-25% of PD patients have relative with PD ♦ Majority of PD cases occur without apparent genetic factor Recent studies discovered several genes that can cause PD ♦ Some genes effect dopamine cell functions ♦ Some genes affects are unknown ♦ PD genetics research is on-going

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Question: Is PD an immune/inflammatory response?

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Answer: Not certain. ♦ Pathogenesis of PD as an immune response being studied ♦ Link between PD and a pro-inflammatory cytokine shown in three recent studies ♦ Indications are present but inconclusive

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Question: Do environmental agents cause PD?

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Answer: Not certain. ♦ Environmental link may be present it increase risk when exposed to environmental factors ♦ Indications present but inconclusive

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All of the following are true except : A. Majority of PD cases are due to an inherited gene. B. PD is contagious C. A link between PD and a pro-inflammatory cytokine shown in three recent studies D. Pesticide exposure may be linked to PD.