Transcript 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
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
Additional Signs & Symptoms
Micrographia Masked face Slowing of ADLs Stooped, shuffling gait Decreased arm swing when walking
Additional Signs and Symptoms
Difficulty arising from a chair Difficulty turning in bed Hypophonic speech
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
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
Non-Motor Symptoms
Sensory Pain Paresthesia Olfactory disturbance Other Fatigue Diplopia Blurred vision Seborrhea Weight loss
Epidemiology
Incidence 5-24/ 10 5 worldwide (USA: 20.5/10 5 ) Incidence of PS/PD rising slowly with aging population Prevalence 57-371/10 5 worldwide (USA/Canada 300/10 5 ) 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
What Happened?
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
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
Progressive supranuclear palsy
Supranuclear downgaze palsy, square wave jerks Upright posture/frequent falls Pseudobulbar emotionality Furrowed brow/stare
Corticobasal degeneration
Unilateral, coarse tremor Limb apraxia/limb dystonia/alien limb
Multiple system atrophy
Shy-Drager syndrome Autonomic insufficiency—orthostasis, impotence Striatonigral degeneration Tremor less prominent Olivopontocerebellar atrophy Cerebellar signs
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
Hydrocephalus-induced Parkinsonism Normal pressure hydrocephalus Clinical triad: parkinsonism/gait disorder urinary/fecal incontinence dementia
Drug Classes in PD
Dopaminergic agents Levodopa Dopamine agonists COMT inhibitors MAO-B inhibitors Anticholinergics Amantadine
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
Levodopa (cont’d)
Rapid peripheral decarboxylation to dopamine without a decarboxylase inhibitor (DCIs: carbidopa, benserazide) Side effects: nausea, postural hypotension, dyskinesias, motor fluctuations
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
Treatment Options
Preventive treatment No definitive treatment available Symptomatic treatment Pharmacological Surgical Non-motor management Restorative—experimental only Transplantation Neurotrophic factors
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
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
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
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)
DAs: Common Adverse Effects
Nausea, vomiting Dizziness, postural hypotension Headache Drowsiness & somnolence Dyskinesias Confusion, hallucinations, paranoia
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
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
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
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
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
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
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
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
Psycho-Social Aspects of Parkinson's disease Children and their fears Chronic, progressive, incurable Off the wall cures Depression (like stroke, assume they all are depressed) Housing – the move to the NH Resuscitation issues Artificial nutrition issues
Other Parkinson’s Meds
MAO Inhibitors rasagaline selegilene zydis carbidopa/levodopa rotigotine patch
Hoehn and Yahr Staging
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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