Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download parkinson`s disease:: evaluation, rehabilitation and treatment
Document related concepts
Transcript
PARKINSON’S DISEASE:: EVALUATION, REHABILITATION AND TREATMENT Bradley R. Ertel MD Renee Ertel Puleo Pharm.D. Mercy Hospital of South Buffalo DISCLOSURES None 2 OBJECTIVES Discuss the pathophysiology of Parkinson’s Disease (PD) Define specific movement disorders associated with PD Discuss pharmacological and non‐pharmacological treatments 3 DEFINITIONS OF MOVEMENT DISORDERS Neurological dysfunctions in which there exists either: Hyperkinesia: excessive movement Hypokinesia: paucity of voluntary and automatic movements Not associated with weakness or spasticity 4 EXAMPLES OF HYPERKINESIA Akathisia: Restlessness, anxiety, inner tension Athetosis: Slow, writhing, involuntary movements that are usually distal Ballismus: Violent, involuntary movements involving one side of body Chorea: Brief, repetitive, jerky, involuntary movements Dystonia: Repetitive, twisting movements leading to abnormal posture 5 MORE EXAMPLES OF HYPERKINESIA Hemifacial spasm: Irregular, involuntary muscle contractions on one side of the face Myoclonus: Brief, shock‐like muscular contractions that can be regular or arrhythmic Restless Leg Syndrome: Urge to move the legs to relieve unpleasant sensations Tics: Sustained, nonrhythmic, rapid, and stereotyped muscle contractions Tremor: Rhythmic and oscillating movements 6 EXAMPLES OF HYPOKINESIA Parkinson’s Disease Secondary Parkinsonism Meningitis AIDS Reglan MPTP Parkinson’s Plus Syndromes Shy Drager: Autonomic dysfunction Olivopontocerebellar atrophy: Ataxia and dysarthria 7 PARKINSON’S DISEASE Progressive disorder of the basal ganglia due to loss of dopaminergic cells in the substantia nigra Hyperactivity of cholinergic neurons in the caudate nuclei Imbalanced cholinergic / dopaminergic transmission 8 9 INCIDENCE AND EPIDEMIOLOGY Prevalence Rate : 200 per 100,000 Rare for individuals < 40 years of age 1% for individuals > 60 years of age 2% for individuals > 85 years of age Men > Women Incidence rate : 20 per 100,000 (annually) The National Parkinson’s Foundation estimates that up to 1.5 million Americans have the disease Approximately 50,000 new cases are diagnosed each year 10 CLINICAL FEATURES OF PARKINSON’S DISEASE Resting tremor Lead pipe rigidity Cogwheel rigidity Bradykinesia / Masked Facies Postural instability Festinating (shuffling) gait Freezing phenomenon 11 RESTING TREMORS • Suppressed by activity or sleep • Intensified by stress or fatigue (pill rolling) 12 RIGIDITY Lead pipe • Smooth resistance to passive movement that is independent of velocity Cogwheel • Ratcheting through range of motion due to subtle tremor superimposed on rigidity 13 BRADYKINESIA Upper extremities • Begins distally with decreased manual dexterity of fingers • Typing • Tying shoelaces • Buttoning shirt 14 BRADYKINESIA Lower extremities Leg dragging Shuffling feet Difficulty standing up from a chair Difficulty getting out of a car 15 MASKED FACIES Occurs when bradykinesia affects the muscles of facial expression 16 POSTURAL INSTABILITY • Slumped over • Protracted shoulders • Flexed hips • Flexed knees 17 DIAGNOSIS OF PARKINSON’S DISEASE Primarily clinical Two groups of symptoms Minimal or no rest tremor (predominant rigidity and akinesia) Rest tremor predominant The use of laboratory or neuroimaging is for exclusionary purposes and atypical cases Routine electrodiagnostic studies will not aid in diagnosis of PD 18 STAGES OF PARKINSON’S DISEASE Early Mild Moderate Severe Late 19 STAGES OF PARKINSON’S DISEASE EARLY No functional impairment Mild symptoms Unilateral tremors Family members detect poor posture, loss of balance, and abnormal facial expressions MILD Bilateral symptoms Difficulty ambulating and maintaining balance Difficulty completing ADL 20 STAGES OF PARKINSON’S DISEASE MODERATE Multiple medications Occupational and social activities affected Inability to walk or stand straight Noticeable slowing of movements SEVERE Medication side effects Resistance to therapies Reduced quality of life Unable to perform ADL Cannot live independently Decreased tremors (mechanism unknown) LATE Dependent in ADL, wheelchair or bed bound 21 PROGNOSIS OF PARKINSON’S DISEASE Tremor predominant patients progress more slowly than patients with bradykinesia as the predominant complaint Bradykinesia is more disabling than tremors Akinesia can indicate a more rapidly progressing disease process Life expectancy is variable, but significantly improved with medical management Dysphagia is the most important risk factor associated with early demise 22 PROGNOSIS OF PARKINSON’S DISEASE Positive Prognostic Indicators Early tremor Rigidity Family history of Parkinson’s Disease Negative Prognostic Indicators Bradykinesia Akinesia Postural instability Gait dysfunction Cognitive deficits Late age of onset 23 PARKINSON’S DISEASE PET scans highlight the loss of dopamine storage capacity in Parkinson’s disease. In the scan of a disease‐free brain, made with [18F]‐ FDOPA PET (left image), the red and yellow areas show the dopamine concentration in a normal putamen, a part of the mid‐brain. Compared with that scan, a similar scan of a Parkinson’s patient (right image) shows a marked dopamine deficiency in the putamen. 24 PARKINSON’S DISEASE BCMJ, Vol. 43, No. 3, April 2001, page(s) 142‐147 25 IMPAIRMENTS IN PARKINSON’S DISEASE Gait Bladder Orthostatic hypotension Pain Gastrointestinal Cognition Depression Psychosis and Halluciniations Sleep 26 GAIT Can result from disease or secondary to medications Inefficient Compromised by bradykinesia, poor posture, and fear of falling 2 Stereotypical patterns Freezing: Inability to initiate gait after stopping Festination: Rapid shuffling steps with additional trunk flexion 27 BLADDER Most common abnormality: nocturia Urgency Frequency Detrusor hyperreflexia Treatment Timed voiding while awake Intermittent catheterization Anticholinergics 28 ORTHOSTATIC HYPOTENSION Due to autonomic dysfunction from sympathetic denervation Magnified by intravascular volume depletion due to poor fluid intake Elderly: Consider cardiovascular disease and other causes of hypotension, such as medications Treatment Avoid warm baths and heavy meals Avoid straining while defecating Avoid Valsalva maneuver Compression leg stockings Abdominal binders Arise slowly from a seated position Pause in a sitting position before arising from a supine position Tilt table test Antihypertensive medication management 29 PAIN Primary central processes Secondary to other conditions Aching pain in affected limb Most common cause of pain in PD limb rigidity Restless leg syndrome Headaches Treatment Pharmacological and non‐pharmacological Increase mobility and flexibility 30 GASTROINTENSTINAL Swallowing Decreased lingual control and bolus propulsion Due to abnormalities in striated muscle under DA control and smooth muscle under autonomic control Nutrition Restrict protein consumption Vitamin B6 supplementation Decreased gastric emptying Early satiety Nausea/vomiting Reglan worsens dyskinesia Decreased peristalsis and GERDheartburn Constipation Altered sympathetic innervation of GI tract Decreased mobility and hydration 31 COGNITION Psychomotor retardation, memory difficulty, and altered personality Anatomic and pathologic basis is not understood Dementia occurs late in the disease Risk factors Later age of onset Longer symptom duration Hallucinations Depressive symptoms Family history of dementia 32 DEPRESSION Most common psychiatric disturbance seen in PD Independent of disease severity and duration Features of depression and Parkinson’s are similar Deficits in serotonergic transmission Decreased norepinephrine and dopamine Treatment Counseling TCA SSRI 33 PSYCHOSIS / HALLUCINATIONS Visual hallucinations are the most common psychiatric symptom in PD patients Psychosis Underlying Lewy Body disease Antiparkinson drugs (Dopamine agonists) Generally resolves when medications are discontinued Single greatest reason for nursing home placement in patients with PD 34 SLEEP Ranked as one of the most troublesome nonmotor symptoms in early and late PD Most common sleep disturbances: Sleep fragmentation and early morning awakening Most common etiologies Nocturia Difficulty turning over in bed Cramps Vivid dreams Nightmares Pain (most commonly neck or back) 35 SURGICAL TREATMENT OF PARKINSON’S DISEASE DESTRUCTIVE SURGERY Thalamotomy Surgical destruction of specific cells in the thalamus Restricts contralateral tremor Pallidotomy Permanent ablation of a portion of the globus pallidus Indications Dyskinesias Stiffness Freezing Not effective for controlling tremors 37 DEEP BRAIN STIMULATION (DBS) DBS targets: Thalamus, Globus pallidus interna, and STN High frequency stimulation involves placing an electrode into the targeted brain area under electrophysiologic guidance Electrode is connected to a pulse generator, which is activated and deactivated by passing a magnet over the apparatus The precise mechanism of action is unknown, but DBS is purported to work by resetting abnormal firing patterns in the brain Associated with fewer complications than thalamotomy Is replacing thalamotomy as the procedure of choice for Parkinson’s 38 TYPES OF DEEP BRAIN STIMULATION Subthalamic Reduces tremor, rigidity, and bradykinesia Reduces antiparkinsonian medications by half Most common surgical procedure for Parkinson’s Disease Thalamic Reduces contralateral tremor Worsens bradykinesia, rigidity, and gait 39 DEEP BRAIN STIMULATION 40 PHARMACOLOGICAL TREATMENT 41 PHARMACOLOGICAL AGENTS FOR PD Carbidopa/Levodopa Dopamine Agonists Monoamine oxidase B (MAO‐B) inhibitors Catechol‐O‐methyltransferase (COMT) inhibitors Amantadine Anticholinergic agents Botulinum Neurotoxin (Botox) 42 CARBIDOPA/LEVODOPA Carbidopa/Levodopa (Sinemet) Carbidopa/Levodopa ODT (Parcopa) Carbidopa/Levodopa CR (Sinemet CR) Mechanism of Action Levodopa is the metabolic precursor of dopamine Levodopa crosses the blood‐brain barrier, where it is converted to dopamine Treats bradykinesia, rigidity, and tremor Adverse reactions GI: anorexia, n/v Cardiovascular: arrhythmia and orthostatic hypotension Psychiatric: mood disorders, sleep disturbances, hallucinations, and delusions Controlled by adjusting dose and frequency 43 CARBIDOPA/LEVODOPA DOSING Immediate release Initial: Carbidopa 25 mg/levodopa 100 mg PO TID Food to reduce nausea Orally disintegrating does not require water Sustained release Carbidopa 50 mg/levodopa 200 mg PO BID Decrease dose in elderly Do not crush 44 DOPAMINE AGONISTS Pramipexole (Mirapex) Apomorphine (Apokyn) Bromocriptine (Parlodel) Ropinirole (Requip) Rotigotine (Neupro) Mechanism of Action Exact unknown; stimulate dopamine receptors Treat bradykinesia and rigidity Reduce off time Adverse Reactions Somnolence, edema, n/v, hypotension, hallucinations, and peripheral edema Pulmonary fibrosis with bromocriptine 45 DOPAMINE AGONIST DOSING Pramipexole Initial: 0.125 mg PO TID Food to reduce nausea Adjust for renal impairment Ropinirole Initial: 0.25 mg PO TID, Max: 24 mg/day Rotigotine Apomorphine 0.06 mg/kg “rescue” subcutaneous injection Bromocriptine Initial: 1.25 mg PO BID Food to reduce nausea Transdermal patch applied daily Initial: 2mg/24hr (early), 4mg/24hr (advanced) 46 MAO‐B INHIBITORS Selegiline (Eldepryl) Selegiline ODT (Zelapar) Rasagiline (Azilect) Mechanism of Action Selectively inhibits MAO‐B from breaking down dopamine May be neuroprotective Treat motor fluctuations Reduce off time Adverse Reactions Headache, nausea, hypertension with >400mg tyramine Insomnia with selegiline 47 MAO‐B INHIBITOR DOSING Selegiline 5 mg PO BID with breakfast and lunch 10 mg PO daily in the morning Dose decrease in elderly Rasagiline 1 mg PO daily Dose decrease in mild hepatic impairment 48 COMT INHIBITORS Entacapone (Comtan) Tolcapone (Tasmar) Mechanism of Action Used in conjunction with carbidopa/levodopa Selectively inhibits peripheral COMT Treat motor complications Adverse Reactions Increased levodopa adverse reactions, brown‐orange urine Black Box Warning Hepatotoxicity with tolcapone 49 COMT INHIBITOR DOSING Entacapone 200 mg with each dose of carbidopa/levodopa Max: 1600 mg/day Tolcapone Initial: 100 mg PO TID 50 COMBINATION PRODUCT Carbidopa/Levodopa/Entacapone (Stalevo) Substitute for patients already stabilized on equivalent doses of each component Complication Neuroleptic Malignant Syndrome (NMS) is associated with dose reductions and withdrawal of levodopa preparations Muscle rigidity, fever, instability, and delirium 51 AMANTADINE (SYMMETREL) Mechanism of Action Stimulates dopamine release and inhibits glutamate neurotransmission Treats dyskinesia and tremor Adverse Reactions Edema, dizziness, confusion, and livedo reticularis 52 AMANTADINE (SYMMETREL) DOSING Initial: 100 mg BID if sole therapy, once daily if combination Adjust for renal impairment 53 ANTICHOLINERGIC DRUGS Benztropine (Cogentin) Trihexyphenidyl (Artane) Mechanism of Action Antagonize acetylcholine receptors Goal: regain balance between dopamine and acetylcholine Treat tremor and dystonia Adverse Reactions Dry mouth, blurred vision, constipation, and urinary retention More serious: forgetfulness, sedation, depression, and anxiety Trihexyphenidyl: glaucoma, need ophthalmic exam 54 ANTICHOLINERGIC DOSING Benztropine Initial: 0.5‐6 mg/day in 1‐2 divided doses Dose decrease in elderly Trihexyphenidyl Initial: 1‐2 mg/day in 2 divided doses Max: 5‐15 mg/day in 3‐4 divided doses 55 BOTULINUM NEUROTOXIN (BOTOX) Treatment Cervical dystonia, blepharospasm, focal upper extremity dystonia, laryngeal dystonia, essential tremor, and sialorrhea Mechanism of Action Blocks the release of acetylcholine at the neuromuscular junction Localized muscle weakness Adverse Reactions Local; only impacts areas into which it is injected Limited duration of action Reinjection every 3‐4 months 56 TREATMENT OF IMPAIRMENTS Gait: reduce pharmacology Bladder: anticholinergics or alpha blockers Orthostatic hypotension: midodrine Pain: symptomatic treatment Gastrointestinal: polyethylene glycol Cognition: reduce polypharmacy Depression: TCA & SSRI Psychosis and Hallucinations: reduce dopamine agonists Sleep: melatonin 57 CONCLUSIONS Parkinson’s disease results from a dopamine / acetylcholine transmission imbalance PD is a hypokinetic movement disorder There are a variety of debilitating impairments associated with PD There are several pharmacological and non‐pharmacological treatments for PD and its corresponding impairments There is no cure for PD, but managing the symptoms of the disease can lead to an improved quality of life 58 REFERENCES Braddom, Randall MD. Physical Medicine and Rehabilitation: Third Edition. Philadelphia: Elsevier. 2007 Chou, Kelvin MD. “Clinical Manifestations of Parkinson’s Disease.” www.uptodate.com. Ed. Howard Hurtig MD. July 25, 2014. Delisa, Joel MD. Physical Medicine and Rehabilitation: Principles and Practice (Fifth Edition). Philadelphia. Lippincott Williams and Wilkins. 2010. Pahwa, R. "Practice Parameter: Treatment of Parkinson Disease with Motor Fluctuations and Dyskinesia (an Evidence‐based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology." Neurology 66.7 (2006): 983‐95. Web. Simpson, D. M., A. Blitzer, A. Brashear, C. Comella, R. Dubinsky, M. Hallett, J. Jankovic, B. Karp, C. L. Ludlow, J. M. Miyasaki, M. Naumann, and Y. So. "Assessment: Botulinum Neurotoxin for the Treatment of Movement Disorders (an Evidence‐ based Review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology." Neurology 70.19 (2008): 1699‐706. Web. 59 REFERENCES Suchowersky, O. "Practice Parameter: Neuroprotective Strategies and Alternative Therapies for Parkinson Disease (an Evidence‐based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology." Neurology 66.7 (2006): 976‐82. Web. Trail, Marilyn, Elizabeth Protas, and Eugene C. Lai. Neurorehabilitation in Parkinson's Disease: An Evidence‐based Treatment Model. Thorofare, NJ: SLACK, 2008. Print. Wells, Barbara G. "Parkinson's Disease." Pharmacotherapy Handbook. New York: McGraw‐Hill Medical Pub. Division, 2009. 629‐36. Print. Zesiewicz, T. A., K. L. Sullivan, I. Arnulf, K. R. Chaudhuri, J. C. Morgan, G. S. Gronseth, J. Miyasaki, D. J. Iverson, and W. J. Weiner. "Practice Parameter: Treatment of Nonmotor Symptoms of Parkinson Disease: Report of the Quality Standards Subcommittee of the American Academy of Neurology." Neurology 74.11 (2010): 924‐31. Web. 60
