1. Mostly Parkinson’s disease but also few other movement disorders due to diseases of the basal ganglia

2. Direct and indirect pathways Dopamine excites the Direct pathway leading to cortical excitation and movement. Dopamine inhibits the Indirect pathway leading to cortical excitation and movement.

3. Hypokinetic disorders Lack of dopamine leads to over-activity of the indirect pathway and under-activity of the direct one.

4. Hyperkinetic disorders Dopamine excess leads to under-activity of the indirect pathway and over-activity of the direct one.

5. Hypokinetic disorders

6. Resting tremor, bradykinsesia, rigidity and postural instability Parkinsonism Neurodegenerative process Drug-induced Idiopathic Parkinson’s Disease Parkinson Plus Syndromes: 1.Multiple System Atrophy (MSA) 2.Progressive Supranuclear palsy (PSP) 3.Corticobasal Degeneration (CBD) 4.Others

7. Dopamine deficiency in the striatum Parkinsonism Neurodegenerative process Drug-induced Idiopathic Parkinson’s Disease Parkinson Plus Syndromes: 1.Multiple System Atrophy (MSA) 2.Progressive Supranuclear palsy (PSP) 3.Corticobasal Degeneration (CBD) 4.Others

8. Parkinson’s disease 1.Resting tremor - Usually involves a hand, “Pill-rolling” tremor. 2.Rigidity – increased resistance to passive movement. 3.Bradykinesia – slowness of voluntary movements, reduction of automatic movements (arm swinging, hypomimia, blinking) 4.Postural instability. Usually asymmetrical and responds to Levodopa.

9. Natural History of Parkinson’s Disease Time (years) Severity Of Disease Symptoms resistant to therapy (dementia, gait and balance, bulbar) Motor symptoms (tremor, rigidity, bradykinesia) Pre-motor symptoms (depression, constipation, Impaired smell sensation, acting out of dreams)

10. Epidemiology of Parkinson’s disease

11. Pathology Normal Parkinson’s Disease α-synuclein containing intracytosolic Lewy Bodies

12. Progression of Lewy bodies Braak staging

13. Etiology No clear etiology is found for the majority of patients. Organic solvents and rural living were associated with higher risk.

14. https://www.michaeljfox.org

15. Gan-Or, Neurogenetics, 2010

17. Treatment

18. Time (years) Severity Of Disease Diagnosis Motor complications Therapy honeymoon (minimal symptoms on treatment)

19. Levodopa induced dyskinesia

20. Surgical treatment Deep brain stimulation of substantia nigra or Glubus Pallidus interna has replaced palidotomy.

21. Hyperkinetic disorders

22. Chorea / Athetosis Tics Ballismus Dystonia

23. Example: Chorea Rapid, semi purposeful, graceful vs jerky, irregular movement that tends to occur in the distal limb or face. Inherited diseases – Huntington, Wilson Rheumatic – Sydenham, Chorea gravidarum Systemic – SLE, APLA Drug-induced – Neuroleptics, cocain, excess L-dopa

24. The End