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Parkinson ’ s disease

Parkinson ’ s disease. דר' דורון מרימס המרכז הגריאטרי שהם . Parkinson ’ s disease. Resting tremor Rigidity Bradykinesia Postural reflex impairment. Epidemiology. Begins between age 40-70 Peak age – sixth decade M:F 3:2 1% of the population over age 65.  -Synuclein and Lewy bodies.

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Parkinson ’ s disease

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  1. Parkinson’s disease דר' דורון מרימס המרכז הגריאטרי שהם

  2. Parkinson’s disease • Resting tremor • Rigidity • Bradykinesia • Postural reflex impairment

  3. Epidemiology • Begins between age 40-70 • Peak age – sixth decade • M:F 3:2 • 1% of the population over age 65

  4. -Synuclein and Lewy bodies • neurotoxicity from mutations of the -synuclein gene is the production of proteins that are more prone to self-aggregation • -Synuclein is a major constituent of Lewy bodies. Two opposing theories for a Lewy body: • (i) toxic aggregation • (ii) protective aggregation

  5. Etiology • Multi-factorial • Heredity • Environmental toxins • aging

  6. Heredity • First degree relative – 20% PD or essential tremor • Twin study • Genes • LRRK2, PARK2, PARK7, PINK1, SNCA • risk for Parkinson's disease is 5 times greater in individuals carrying glucocerebrosidase gene mutations

  7. Environment • MPTP : sudden onset of PD symptoms After drug use; no Lewy bodies (MPPP; MPP+) • Pesticides • Manganese • Carbon monoxide • Smoking – inverse correlation

  8. Motor symptoms • Mask face • Decreased blinking • Dysarthria • Dysphagia • Drooling • Dystonia: (blepharospsm)

  9. Motor symptoms • Slow shuffling gait • Festinations • Reduced arm swing • Freezing • Difficulties turning in bed • Micrographia

  10. Autonomic symptoms • GI motility • Orthostatic hypotension • Bladder dysfunction • Sexual dysfunction

  11. Natural history • Insidious onset • Asymmetric • Good response to dopaminergic treatment • Depression may be an early symptom

  12. Parkinson’s disease – tremor dominant • A family history of tremor • Earlier age at onset • Less functional impairment • Preservation of mental function

  13. Hoehn and Yahr staging • Stage One • Signs and symptoms on one side only • Symptoms mild, not disabling • Stage Two • Symptoms are bilateral Minimal disability • Stage Three • Significant slowing of body movements • Early impairment of equilibrium on walking or standing • Stage Four • Severe symptoms, Can still walk • Stage Five • Cannot stand or walk • Requires constant nursing care

  14. treatment • Multi-disciplinary • Drug treatment • For motor and non motor symptoms • Surgical treatment • Neuro-protective • Restorative

  15. Medications to Treat PD • selegiline; rasageline • amantadine • Dopamine Agonists • Requip (ropinirole) • Mirapex (pramipexole) • Cabergoline • Apomorphine

  16. Medications to Treat PD • Dopicar; Sinemet (levodopa/carbidopa) • COMT inhibitors, (Comtan, Tasmar) • Stalevo (levodopa/carbidopa/entecapone) • Artane (Trihexyphenidyl)

  17. “Levodopa is the most effective drug in the treatmentof PD.” Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology 2001 Jun;56(11 Suppl 5):S1-S88

  18. Levodopa strengths • most effective drug for parkinsonian symptoms - produces robust effect • relatively rapid onset of action • well tolerated(with slow titration rate)

  19. Levodopalimitations • posturalinstability and falling • freezing episodes • autonomic dysfunction • mood disturbances • dementia

  20. peripheral side effects nausea vomiting orthostatic hypotension centralside effects motor fluctuations dyskinesias psychiatric problems psychosis hallucinations delusions Side effects - levodopa

  21. “ON” phase • Almost normal motor response

  22. Motor Bradykinesia Rigidity Tremor Dystonia Non motor Panic attacks Irritability Anxiety Depression “OFF” - Symptoms Withdrawal symptoms ?

  23. Peak dose dyskinesia • Choreic • Upper limbs, face, trunk • Homolateral to the side most affected by Parkinson’s disease

  24. Dystonic Lower limbs Homolateral to the side most affected by Parkinson’s disease Biphasic: onset and end-of-dose dyskinesia

  25. Dyskinesias - clinical risk factors • Duration of the disease • Duration of levodopa treatment • Levodopa dose

  26. Pathophysiology • Levodopa effect. • Nigrostriatal neuronal degeneration.

  27. Prevention of l-dopa induced dyskinesias • Delaying l-dopa treatment • Dopamine agonists treatment • Slowing disease progression • Smoothening the pulsatility of dopamine receptor stimulation

  28. Symptomatic antidyskinetic treatment • Reduction of l-dopa dose • Serotonin: Fluoxetine, Buspirone, Ritanserin. • Noradrenaline: Yohimbine, Idazoxane • Opiate system: Naloxone (P.O & I.V) • Adenosine: KW-60002 • NMDA: LY23595, Amantadine, Dextromethorphan. • Incidental findings: Propranolol, diphenylhydantoin, estrogens.

  29. Dopamine agonists Do not require conversion and storage Lower risk to develop dyskinesias Apomorphine – early effect

  30. Surgery • Ablative surgery – pallidotomy, thalamotomy • Deep brain stimulation – a functional lesion (modifiable, reversible) • various sites in the brain: • Thalamus • Subthalamic nucleus • Globus pallidum

  31. Ablative Surgery • lesion on one or both sides of brain (pallidotomy, thalamotomy) • Addresses motor symptoms; particularly side effects of l-dopa (dyskinesias) • Significant side effects/adverse events, particularly for bilateral surgery • Permanent (unable to reverse or modify)

  32. Deep Brain Stimulation • the surgical treatment of choice for PD • Create a functional lesion using electrical stimulation • Two primary “targets” for DBS • Globus pallidus (GPi) • Subthalamic nucleus (STN)

  33. DBS side effectsBehavioral and Affective changes • Depression and suicide attempts • Mania • Aggression • Marked improvement of severe OCD in patient with advanced PD

  34. Parkinsonism • Primary – Parkinson’s disease • Secondary parkinsonism • Vascular, drugs, trauma, NPH • Parkinson’s plus syndromes • Hereditary degenerative diseases

  35. Dementia with Lewy bodies • Early dementia • Hallucinations • Fluctuations • Neuroleptic sensitivity

  36. Multiple system atrophy • Symmetric onset • Absence of tremor • Poor response to dopaminergic therapy • Severe and early autonomic dysfunction

  37. Progressive supranuclear palsy • Axial rigidity • Gaze paralysis • Falls • Dementia • Apathy

  38. Case 1 • M 78 • Rehabilitation post femoral neck fracture • Parkinsonism; Autonomic disturbances; cognitive impairment. • Medications: Gutron, Exelon patch, Dopicar trial failed • Diagnosis? • Periods of either Agitation or sleepiness • With gait improvement – freezing appeared • Treatment?

  39. Case 2 • M 69 • 6 months general deterioration, bed ridden, decubitus ulcers, • 2 weeks increased tone and tremor , diagnosed with PD; Dopicar treatment • Heart implantation (1996); DM; IHD; small bowl perforations • Lethargy, increased tone , tremor, myoclonus

  40. Case 3 • M 83 • Rehabilitation post femoral neck fracture • Recurrent strokes; DM; HTN • Increased rigidity right arm , resting tremor. Severe dysarthria • Cognitive impairment MMSE 20/30

  41. Non Motor symptoms Parkinson’s disease

  42. Sleep and PD-D • Insomnia • REM sleep behaviour disorder (RBD) • loss of skeletal muscle atonia • excessive motor activity during dreaming • RBD is associated with increased risk of hallucinations and delusions • Increased frequency of psychotic symptoms has also been related to daytime somnolence

  43. Sleep disorders in PD • Selegiline timing • Avoid nocturia • Antidepressants • Long acting levodopa • Sleep attacks –(dopamine agonists) • Restless leg syndrome

  44. Pain as Presenting Symptom of PD • Pain has been reported in about 25% of 388 PD patients as the presenting symptom or present at time of diagnosis • Shoulder pain is frequently reported presenting symptom of PD (also back and leg pain) • The mechanism of those early pain syndromes is not fully known (peripheral or central) but pain is commonly improved by dopaminergic treatment

  45. Cognitive impairment in PD • clinical diagnostic criteria for PD-D • diagnosis of PD according to Queen Square Brain Bank criteria • dementia syndrome within the context of established PD.

  46. cognitive deficits in attention executive functions, visuospatial functions memory behavioural features Hallucinations delusions Apathy excessive daytime sleepiness personality and mood changes PD-D Associated clinical features • Language functions are largely preserved • word finding difficulties • Impaired comprehension of complex sentences.

  47. Cognitive impairment and motor disability • Impaired attention and reduced ability to carry out dual tasks • gait disturbances • falls

  48. Psychiatric symptoms • Depression • Anxiety • Vivid dreams • Hallucinations • Benign • malignant • Delusions • Paranoia

  49. Psychotic features in PD-D • present in 6–40% of patients with PD • Visual hallucinations – most common • Presence hallucinations • Passage hallucinations • Hallucinations are a risk factor for • nursing home placement • higher mortality in advanced stages of PD

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