A 57-year-old man with decreased stamina, decline in cognition, and tremor Joe Kovaz, M.D. Clinical Assistant Professor of Medicine

History: Presented 10/20/05 requesting to transfer health care to the UW system Main concern—mgmt of neuropathic pain EMG in 1997 demonstrated mild sensorimotor polyneuropathy Possible etiologies included: –Alcohol abuse for 10 years –Type 2 Diabetes mellitus

Other ongoing problems: Hypertension Hyperlipidemia Gastroesophageal reflux disease Tremor Anxiety Depression

Furosemide Lisinopril Metoprolol Gabapentin Metoclopramide Clonazepam Sertraline Pantoprazole Sodium Medications:

Physical Exam: Initial exam significant for slowness of speech and movement Initiated therapy for diabetes and hyperlipidemia with metformin and niaspan Referral made to the diabetes clinic

Exam, (cont’d): Returned 11/08/05 with wife who expressed concern regarding slow decline in cognition and stamina beginning 10 years ago Metoprolol started for tremor, helped significantly Exam notable for diminished facial expression, tremor which extinguished with intention, and inability to tandem walk

Plan: Referral to Neurology Clinic Started on carbidopa/levodopa Returned for a follow up reporting significant improvement in energy level and desire to engage in activity

Movement Disorders Clinic: Seen by Dr. Montgomery on 2/6/06 Impression: Idiopathic Parkinson’s disease; cannot exclude drug-induced parkinsonism secondary to metoclopramide Recommendations: –Stop metoclopramide –Taper off carbidopa/levodopa –Begin selegiline (MAO-B inhibitor) in 3months if symptomatic –Consider Pramipexole (dopamine agonist)

Objectives: Heighten awareness of possible Parkinson’s disease in patient with non-specific complaints Review basics of pathophysiology, diagnosis, and therapy Encourage alertness for drug-induced illness

Parkinsonism: Clinical syndrome with multiple etiologies: Characterized by bradykinesia, tremor, rigidity and postural instability Dopamine deficiency in the putamen and caudate nucleus Degeneration of dopaminergic cells -PD

Parkinsonism: 75% due to Parkinson’s disease 1% of population over 55 Idiopathic: most common, onset over 60 Primary: Genetic, younger than 50, more severe

Parkinson’s Disease (PD) Diagnosis: Clinical--2 of the 3 aforementioned cardinal signs and a robust response to levodopa May be difficult unless tremor is present; nonspecific fatigue, weakness, muscle aches Up to 40% of Parkinson’s patients are not diagnosed, 25% misdiagnosed, 24% initially diagnosed, have other disorders

Clinical Features: Tremor-at-rest, attenuates with movement Essential tremor may coexist Rigidity, shuffling, freezing Impairment in cognition, depression (up to 50% in PD), and sleep

Figure 4 Face of a patient with Parkinson disease. Note the lack of expressivity and poor definition of the nasolabial fold. Scaling seborrhea is also common. Neuro XV PARKINSON DISEASE AND OTHER MOVEMENT DISORDERS-11 p. 5

Drug-induced Parkinsonism: Closely resembles PD Rest tremor is less prominent May unmask latent PD Metoclopramide—dopamine antagonist

Drugs: Neuroleptics (typical antipsychotics) Selected atypical antipsychotics Antiemetics (e.g., prochlorperazine, metoclopramide) Dopamine-depleting agents (e.g., reserpine, tetrabenazine) α-Methyldopa Lithium carbonate Valproic acid Fluoxetine Neuro XV PARKINSON DISEASE AND OTHER MOVEMENT DISORDERS-11 p. 4

Treatment Goals: Maintain function Slow progression of disease Maintain drug efficacy Avoid drug-induced dyskinesias

Treatment: 1969-Cotzias demonstrated that levodopa could alleviate Parkinsonism Patients typically experience: –smooth and even response to L-dopa But –motor fluctuations (“on/off” 20%) –dyskinesias (30%) frequently occur

Treatment (cont’d): Begin with levodopa in patients over 65 or with cognitive impairment Begin a dopamine agonist (Pramipexole) for patients under age 65 Consider an MAO-B inhibitor (Selegiline) both for levodopa augmentation and neuroprotective therapy

Treatment (cont’d): Amantadine (dyskinesias) Anticholinergics (tremor, rigidity, dystonia) but use limited in elderly Surgery –benefits do not exceed best benefits of medications –Elimination of dyskinesias and “on/off” periods

Adverse Drug Reactions: Any drug has the potential to do harm 3-5% of all hospitalizations (300,000 annually in the US) 30% chance of untoward event once hospitalized 3% chance of life-threatening reaction once hospitalized

Adverse Drug Reactions, (cont’d): Adverse drug reactions are most common cause of iatrogenic disease Mechanism-based adverse drug reactions- extensions of pharmacological action (metoclopramide) Off-target reaction—not a consequence of a drug’s primary mechanism

Improving Benefit-Harm Ratio: Determine need for a drug and use in the lowest possible dose Regular review of prescriptions Adhere to established guidelines (Medical Letter, Jan. 16, 2006) Involvement of pharmacists

References: 1. Gilman’s The pharmacologic basis of therapeutics. New York, NY: McGraw-Hill, 2006: Scientific American Medicine, 2005, Chapter 11, XV: Drugs in the Elderly. The Medical Letter. Vol. 48, 1226, Jan. 16, 2006: Tarsy, D. Motor fluctuations and dyskinesias in Parkinson’s disease. Up to Date. Version 13.3, May 11, 2005: Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology 2001;56:S1.