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* For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. in the clinic Parkinson Disease © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Terms of Use The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-forprofit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets constitutes copyright infringement. © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What symptoms should prompt a clinician to consider a diagnosis of Parkinson disease? Tremor at rest (frequency: 3–7 Hz ) In hands; may also occur in legs, lips, jaw, tongue Bradykinesia (generalized slowness of movement) Patient may feel weakness, incoordination, tiredness Includes dragging the legs; shuffling; feeling unsteady Rigidity (increased resistance to passive joint movement) “Cogwheel rigidity”: ratchet-like pattern of catch and release as examiner moves patient’s limb thru ROM “Lead-pipe rigidity”: smooth resistance thru ROM Affects any part of body and contributes to pain, stiffness Features typically start on one side… then spread to other Initially affected side more severely affected © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What should clinicians ask patients when evaluating them for Parkinson disease? Tremor at rest, bradykinesia, stiffness (rigidity) Decreased volume of speech (hypophonia) Smaller handwriting (micrographia) Drooling or excess saliva in the mouth Difficulty turning over in bed Changes in posture (especially stooping), changes in gait Constipation Anxiety, depression Olfactory dysfunction or REM sleep behavior Exposure to drugs that cause parkinsonism but not PD itself Family history (1st-degree relative with PD = 2-fold higher risk) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What should clinicians do during the physical exam of patients with possible PD? Neurologic examination ? decreased eye blinking, ? diminished expression Tremor: check with patient sitting, hands resting on lap When patient does mental calculation or repetitive movement of contralateral limb: ? tremor Bradykinesia With rapid and repetitive movement—does slowing occur? Movements less coordinated as PD progresses Rigidity Passively manipulate limbs Have patient do repetitive maneuvers w/ contralateral limb Ask patient to stand up from chair without using the arms Assess postural stability with “pull” test © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How does the clinician establish a diagnosis of Parkinson disease? Diagnosis is clinical Depends on the history & physical exam Bradykinesia plus tremor or rigidity should be present Asymmetrical onset with persistent asymmetry as disease progresses (initially symptomatic side remains more severely affected) Sustained clinical improvement with levodopa or dopamine agonist highly supportive of diagnosis Rule out signs of alternative condition (see next slide) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Features Suggesting Another Diagnosis History encephalitis History repeated head injury History recurrent strokes + stepwise progression of parkinsonism History oculogyric crisis Dementia preceding or concurrent with onset of parkinsonism Cerebellar signs Autonomic dysfunction Spasticity, hyperreflexia, or Babinski responses Current or recent use of dopaminergic blockers or depletors Apraxia Structural abnormality on brain imaging Abrupt symptom onset or sustained spontaneous remission Supranuclear gaze palsy Unilateral features after 3 y Frequent falls early in disease Symmetrical motor signs Impaired sensation with intact primary sensory systems © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What tests should be considered in the evaluation of possible Parkinson disease? Brain MRI (or CT, if contraindicated) If diagnosis uncertain May show abnormalities explaining cause for symptoms (severe vascular changes, tumor, hydrocephalus) PET scan and SPECT scan May detects abnormalities of dopaminergic system SPECT: differentiates parkinsonism from essential tremor ? Wilson disease (patients <40yo with parkinsonism) To rule-out: measure serum ceruloplasmin; order 24-h urinary copper test; check for Kayser-Fleischer rings (eyes) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What other conditions should be considered in the differential diagnosis? Parkinson disease with known genetic cause LRRK2-associated Parkinson disease Autosomal recessive juvenile parkinsonism Autosomal-dominant Parkinson disease Other conditions Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration Dementia with Lewy bodies Essential tremor Vascular parkinsonism Normal pressure hydrocephalus Dopa-responsive dystonia Medication-induced or toxin- or metabolic-related parkinsonism Post-traumatic or psychogenic parkinsonism Post-encephalitic parkinsonism Parkinsonism from tumor, subdural hematoma, or infection Wilson disease, Alzheimer dementia © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should a specialist be consulted for the diagnosis of Parkinson disease? Refer all patients with early symptoms to neurologist Guides diagnosis Helps rule-out atypical parkinsonian syndromes Consider PD or movement disorders specialist May diagnose more accurately than general neurologist Not necessarily more cost-effective or more acceptable to patients © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Diagnosis… Consider Dx when rest tremor, bradykinesia, or rigidity present Conduct thorough history and neurologic examination Pay attention to medications that may cause parkinsonism Base diagnosis on clinical findings MRI & SPECT imaging may help rule out differential Dx Consult neurologist if atypical signs or symptoms present © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Is there any role for exercise or diet modifications? Exercise Modestly benefits motor & functional outcomes Regular activity needed to maintain gains Diet Adequate fiber and hydration to reduces constipation Calcium & vitamin D important to reduce risk for bone loss Low-protein diet may reduce “on-off” phenomenon © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should drug therapy be started? No medication is available that slows disease progression Start treatment when symptoms limit patient’s activities © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What drugs should be used for initial treatment and how should they be chosen? Levodopa Most effective medication for motor symptoms Complications long-term (dyskinesia + “wearing-off”) Often initial treatment used in patients >70 years; all patients eventually require levodopa Dopamine agonist (pramipexole, rotigotine, ropinirole) May delay motor complications when used as initial Rx Often initial treatment in patients <50 years Anticholinergics and MAO-B inhibitors Prevent dopamine breakdown No consensus: initial Rx for those between 50-70 years © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should pharmacotherapy be adjusted as motor symptoms worsen? Increase dopaminergic medications as symptoms worsen Dyskinesia Don’t treat if it doesn’t disturb patient Reduce levodopa, add amantadine or dopamine agonist Carbidopa-levodopa: try decreased dose at shorter intervals Wearing off COMT inhibitors: prolong levodopa’s therapeutic effect Alternative: selegiline (MAO-B inhibitor) Other strategies: add dopamine agonist, increase levodopa dosage or frequency of administration Apomorphine: rescue therapy until next levodopa dose © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians manage the adverse effects of pharmacotherapy? Nausea (from carbidopa-levodopa, dopamine agonists) Often mild; taking medication with food may alleviate Additional carbidopa may help If persistent, domperidone may be effective Metoclopramide and prochlorperazine block dopamine receptors and worsen parkinsonism (don’t use) Excessive sleepiness (from dopamine agonists) Discontinue all meds that may contribute to sleepiness Teach good sleep hygiene Evaluate patients for underlying sleep disorders more… © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Peripheral edema (from amantadine or dopamine agonists) Doesn’t always need treated, especially if mild Disappears when offending medication discontinued; reducing dose won’t help Impulse control disorders (from dopamine agonists) Occur in ≈14% of treated patients Ask all patients about these behaviors If treatment needed, reduce or discontinue offending medication (worsening motor symptoms may require return to original dose) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What are the nonmotor symptoms? Sleep disorders Neuropsychiatric complications GI symptoms Symptoms of autonomic dysfunction © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should sleep problems be managed? Educate patients about proper sleep hygiene Discontinue drugs that inhibit sleep initiation, if possible Decrease evening fluid intake / prescribe anticholinergic Treat anxiety / depression XR carbidopa-levodopa: for tremor, difficulty turning over Levodopa or dopamine agonists: for restless leg syndrome Mechanical devices: for obstructive sleep apnea Clonazepam: for REM sleep behavior disorder © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians manage neuropsychiatric complications? Depression Under-recognized: PD features overlap with somatic features SSRIs often used (due to favorable adverse effect profile) Apathy Can occur independently; distinguish from depression Anxiety More anxiety during “off ” periods, less during “on” periods May help to adjust medications to prolong “on” times more… © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Psychosis (especially visual hallucinations) Treat reversible causes (infection, metabolic disturbance) Consult neurologist for reducing/eliminating Parkinson meds If pharmacotherapy warranted: use cholinesterase inhibitor If antipsychotic necessary: use clozapine or quetiapine only Cognitive impairment (especially of executive function) Can present in early stages of Parkinson disease Treat any reversible causes; then try cholinesterase inhibitor © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should gastrointestinal symptoms be managed? Dysphagia Refer patient to speech pathologist Order modified barium swallow with videofluoroscopy Adjust medications to improve “on” time, if appropriate Teach safe swallowing techniques; consider changing diet Constipation Modify diet, use bulking agents, stool softeners, laxatives Consider domperidone / tegaserod Consider Isosmotic macrogol electrolyte solution © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should symptoms of autonomic dysfunction be managed? Urinary symptoms Rule-out bladder infection Reduce evening fluid intake Try timed voiding to lessen urgency, incontinence For storage symptoms: solifenacin or darifenacin; consider anticholinergics (may contribute to cognitive impairment) Options: desmopressin, botulinum toxin in bladder muscle Urodynamic studies, referral to urologist may be warranted Orthostatic hypotension Increase salt and fluid intake; try small, frequent meals Use high-compression stockings If neurogenic: fludrocortisone; midodrine (pyridostigmine less effective, but doesn’t exacerbate supine hypertension) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should a specialist be consulted? When should is hospitalization warranted? Consult neurologist: at least annually May lower morbidity and mortality Hospitalize: when symptoms can’t be managed on outpatient basis Psychosis (hallucinations, delirium) Significant mood disturbances (mania or depression) Profound fluctuations in mobility Frequent or serious falls Infections (UTI, aspiration pneumonia) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Which surgical interventions are effective? Lesioning therapies (thalamotomy, pallidotomy) Effective for treating symptoms But irreversible, and may cause AEs, esp bilateral lesions Deep-brain stimulation (current practice) Of subthalamic nucleus or globus pallidus interna: alleviates tremor, bradykinesia, rigidity; increases “on” time; reduces wearing off & dyskinesia Of ventralis intermedius nucleus: disables tremor only For major motor fluctuations + dyskinesia Rx can’t control For severe, isolated, disabling tremor Inappropriate for atypical parkinsonian syndromes Inappropriate if dementia or untreated depression present © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What is the prognosis of a patient with Parkinson disease? Unpredictable: Progression varies by individual Progressive neurologic disorder Tremor-dominant: tends to progress more slowly + have less cognitive impairment Akinetic-rigid: tends to progress more quickly + have more cognitive impairment Many patients live with minimal functional impairment for substantial period (due to dopaminergic Rx) © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Treatment… Refer patients to a neurologist for co-management Begin drug Rx when symptoms cause functional impairment Start with levodopa / dopamine agonists / MAO-B inhibitors (depending on severity, motor complications, age, drug AEs) Adjust drug regimen + add other agents as PD progresses Treat nonmotor symptoms Sleep disorders, neuropsychiatric complications, GI symptoms, autonomic dysfunction Encourage regular exercise to maintain physical functioning Consider deep-brain stimulation when substantial motor fluctuations, dyskinesia, or disabling tremor can’t be managed © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1.