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Comprehensive Overview of Parkinson’s Disease Diagnosis and Treatment Options

This detailed guide discusses the key diagnostic criteria and treatment options for Parkinson’s disease, drawing from research at the University of South Carolina School of Medicine. It outlines hallmark symptoms such as resting tremors, bradykinesia, and rigidity, along with non-motor symptoms like depression and sleep disorders. The document also reviews various drug classes, including dopaminergic agents and levodopa, while exploring the impact of atypical Parkinsonism and the role of surgical and non-motor management strategies.

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Comprehensive Overview of Parkinson’s Disease Diagnosis and Treatment Options

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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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