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PARKINSON’S DISEASE

PARKINSON’S DISEASE. Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia, SC 29224 (803) 422-2985. Cardinal Characteristics. Resting tremor Bradykinesia Rigidity Postural instability.

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PARKINSON’S DISEASE

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  1. PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia, SC 29224 (803) 422-2985

  2. Cardinal Characteristics • Resting tremor • Bradykinesia • Rigidity • Postural instability

  3. Beware the Old Man (or woman) • Difficulty initiating movement (akinesia) • Small amplitude movements (hypokinesia) • Reduced motor velocity (bradykinesia) • Loss of postural reflexes • Stooped body posture

  4. Additional Signs & Symptoms • Micrographia • Masked face • Slowing of ADLs • Stooped, shuffling gait • Decreased arm swing when walking

  5. Additional Signs and Symptoms • Difficulty arising from a chair • Difficulty turning in bed • Hypophonic speech

  6. Non-Motor Symptoms • Neuropsychiatric • Depression • Anhedonia • Attention deficit • Hallucinations • Delusions • Obsessional behavior • Cognitive disorder • Sleep disorders • Restless legs • Periodic limb movements • REM behavior disorder • Excessive daytime somnolence • Vivid dreaming • Non-REM sleep-related movement disorders • Insomnia

  7. Non-Motor Symptoms • Autonomic symptoms • Bladder urgency, nocturia, frequency • Sweating • Orthostatic hypotension • Hypersexuality • Erectile impotence hypotestosterone state • GI symptoms • Sialorrhea • Ageusia • Dysphagia • Reflux • Vomiting • Nausea • Constipation • Fecal incontinence

  8. Non-Motor Symptoms • Sensory • Pain • Paresthesia • Olfactory disturbance • Other • Fatigue • Diplopia • Blurred vision • Seborrhea • Weight loss

  9. Epidemiology • Incidence • 5-24/ 105 worldwide (USA: 20.5/105) • Incidence of PS/PD rising slowly with aging population • Prevalence • 57-371/105 worldwide (USA/Canada 300/105) • 35%-42% of cases undiagnosed at any time • Onset • mean PS 61.6 years; PD 62.4 years • rare before age 30; 4-10% cases before age 40

  10. What Happened?

  11. Mortality in PS • Reduced life expectancy • Mean survival after onset ~ 15 years • longer in non-demented PD cases • longer with L-dopa use • PD survival >MSA, PSP • The most common causes of death: • pulmonary infection/aspiration, urinary tract infection, pulmonary embolism and complications of falls and fractures

  12. Atypical Parkinsonism • Early onset of, or rapidly progressing, dementia • Rapidly progressive course • Supranuclear gaze palsy • Upper motor neuron signs • Cerebellar signs—dysmetria, ataxia • Urinary incontinence • Early symptomatic postural hypotension

  13. Progressive supranuclear palsy • Supranuclear downgaze palsy, square wave jerks • Upright posture/frequent falls • Pseudobulbar emotionality • Furrowed brow/stare

  14. Corticobasal degeneration • Unilateral, coarse tremor • Limb apraxia/limb dystonia/alien limb

  15. Multiple system atrophy • Shy-Drager syndrome • Autonomic insufficiency—orthostasis, impotence • Striatonigral degeneration • Tremor less prominent • Olivopontocerebellar atrophy • Cerebellar signs

  16. Diffuse Lewy Body Disease • Early onset of dementia • Delusions and hallucinations • Agitation • Alzheimer’s disease • Dementia is the primary clinical syndrome • Rest tremor is rare

  17. Hydrocephalus-induced Parkinsonism • Normal pressure hydrocephalus • Clinical triad: • parkinsonism/gait disorder • urinary/fecal incontinence • dementia

  18. Drug Classes in PD • Dopaminergic agents • Levodopa • Dopamine agonists • COMT inhibitors • MAO-B inhibitors • Anticholinergics • Amantadine

  19. Levodopa • Most effective drug for parkinsonian symptoms • First developed in the late 1960s; rapidly became the drug of choice for PD • Large neutral amino acid; requires active transport across the gut and blood-brain barriers

  20. Levodopa (cont’d) • Rapid peripheral decarboxylation to dopamine without a decarboxylase inhibitor (DCIs: carbidopa, benserazide) • Side effects: nausea, postural hypotension, dyskinesias, motor fluctuations

  21. Amantadine • Antiviral agent; PD benefit found accidentally • Tremor, bradykinesia, rigidity & dyskinesias • Exact mechanism unknown; possibly: • enhancing release of stored dopamine • inhibiting presynaptic reuptake of catecholamines • dopamine receptor agonism • NMDA receptor blockade • Side effects —autonomic, psychiatric • 200-300 mg/day

  22. Treatment Options • Preventive treatment • No definitive treatment available • Symptomatic treatment • Pharmacological • Surgical • Non-motor management • Restorative—experimental only • Transplantation • Neurotrophic factors

  23. Levodopa-Induced Dyskinesias • Most common is “peak dose” dyskinesia • disappears with dose reduction • Choreiform, ballistic and dystonic movements • Most patients prefer some dyskinesias over the alternative of akinesia and rigidity

  24. COMT Inhibitors • Newest class of antiparkinsonian drugs: tolcapone, entacapone • Potentiate LD: prevent peripheral degradation by inhibiting catechol O-methyl transferase • Reduces LD dose necessary for a given clinical effect

  25. COMT Inhibitors (cont’d) • Helpful for both early and fluctuating Parkinson’s disease • May be particularly useful for patients with “brittle” PD, who fluctuate between off and on states frequently throughout the day

  26. Dopamine Agonists: Distinguishing Features • Directly stimulate dopamine receptors • No competition with dietary amino acids • Longer half-life than levodopa • Monotherapy or adjunct therapy • May delay or reduce motor fluctuations & dyskinesias associated with levodopa • May be neuroprotective • “The Patch” – rotigotine (Neupro)

  27. DAs: Common Adverse Effects • Nausea, vomiting • Dizziness, postural hypotension • Headache • Drowsiness & somnolence • Dyskinesias • Confusion, hallucinations, paranoia

  28. Clinical Decision-Making in Early PD • Disease severity • degree of functional impairment • impact on quality of life • Age of patient • comorbidities • risk of acute drug intolerance • risk of long-term complications • Neuroprotection

  29. Initial Therapy: The Elderly Patient • Shorter treatment horizon • Lower risk of long-term complications • Higher likelihood of comorbidities • Carbidopa/Levodopa: well tolerated, effective • Use adjunctive medications cautiously • Avoid sedating medications

  30. Initial Therapy: The Young Patient • Long-term treatment horizon • Increased risk of long-term complications • Increased patient responsibilities • Dopamine agonist monotherapy • Levodopa-sparing strategies • Putative neuroprotective strategies • Role of levodopa is not adequately defined

  31. Levodopa: Guidelines in Early PD • Start low and increase slowly • Titrate dosage to efficacy (~200-600 mg/day) • Immediate release • Controlled release • Acute side effects: nausea, dizziness, somnolence

  32. Managing Early Complications: Wearing Off/Mild Dyskinesia • For pts on DA monotherapy: • elevate dosage of agonist • add LD, w/ or w/o COMT inhibitor • For pts on LD: • add DA, COMT inhibitor, or MAO inhibitor • reduce LD dosage • use combination of immediate and CR

  33. Managing Early Complications: Altered Mental States • Confusion, sedation, dizziness, hallucinations, delusions • Reduce or eliminate CNS-active drugs of lesser priority • anticholinergics – sedatives • amantadine – muscle relaxants • hypnotics – urinary spasmodics • Reduce dosage of DA, COMT inhibitor, or LD

  34. Surgical Treatments for Parkinson’s Disease • Ablative • thalamotomy • pallidotomy • Electrical stimulation • VIM thalamus, globus pallidus internus, sub-thalamic nucleus • Transplant • autologous adrenal, human fetal, xenotransplants, genetically engineered transplants

  35. Deep Brain Stimulation (DBS) • High frequency, pulsatile, bipolar electrical stimulation • Stereotactically placed into target nucleus • Exact physiology unknown, but higher frequencies mimic cellular ablation, not stimulation

  36. Psycho-Social Aspects of Parkinson's disease • Chronic, progressive, incurable • Off the wall cures • Depression (like stroke, assume they all are depressed) • Housing – the move to the NH • Children and their fears • Resuscitation issues • Artificial nutrition issues

  37. Other Parkinson’s Meds • MAO Inhibitors • rasagaline • selegilene • zydis carbidopa/levodopa • rotigotine patch

  38. Hoehn and Yahr Staging • Unilateral disease only • Bilateral mild disease, with or without axial involvement • Mild-to-moderate bilateral disease, with first signs of deteriorating balance • Severe disease requiring considerable assistance • Confinement to wheelchair or bed unless aided

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