Parkinson s Disease WHERE HAVE WE BEEN, WHERE ARE WE HEADING? CHARLECE HUGHES D.O.

Parkinson s Disease WHERE HAVE WE BEEN, WHERE ARE WE HEADING? CHARLECE HUGHES D.O.

Parkinson s Epidemiology AFFECTS 1% OF POPULATION OVER 65 MEAN AGE OF ONSET 65 MEN:WOMEN 1.5:1 IDIOPATHIC:HEREDITARY 90:10 CLINICAL SUBGROUPS (%) Tremor Dominant 8 Akinetic Rigid 26 Mixed 66

Motor and Non-Motor Symptoms of PD Primary Motor Symptoms Rest Tremor Bradykinesia Rigidity Early Non-Motor Symptoms Fatigue Depression Hyposmia Constipation REM Behavior Disorder

Motor and Non-Motor Symptoms of PD -2 Late Symptoms Treatment resistant axial sx freezing, falls, postural instability Dysphagia Psychiatric disturbances anxiety, depression, psychosis Autonomic dysfunction dizziness, drooling, nocturia, ED Cognitive impairment MCI 35% at diagnosis and 50% after 5 years Dementia - > 80% at 20 years after diagnosis

On Pt has good response to meds TERMS Common PD Terms Off Meds have worn off and PD symptoms reemerge. Motor Fluctuations - alternating between Off and On states. Dyskinesias - involuntary, non-rhythmic choreo-dystonic movements usually related to peak dopamine levels. Impulse Control Disorder - caused by DA. Pathological gambling, shopping, sexual activity, binge eating. Dopamine Dysregulation Synd compulsive overuse of dopamine meds, like an addiction impairing functioning.

Treating Early Motor Symptoms Levadopa Dopamine Agonist Provides greatest symptom control Associated with less freezing, somnolence, edema, hallucinations, and impulse control disorders than DA In older patients preferred tx due to fewer side effects Effective in early PD Less likely to cause dyskinesias Better in pts < 60 years More likely to cause impulse control disorders and hallucinations Peripheral Edema is common

Sinemet (Carbidopa/Levadopa) Carbidopa inhibits peripheral breakdown of levadopa. Levadopa converts at the BBB to dopamine 10/100, 25/100, 25/250 If taken with food, high protein diets impair absorption Taken in the waking hours is key. NOT at bedtime Start 4-5 hours apart before meals Nausea is the biggest side effect CR dosing has unreliable pharmacokinetics

Dopamine Agonist Mirapex (pramipexole), Requip (ropinirole), Neupro patch (rotigotine) Direct agonists of the dopamine system Effective monotherapy Given in waking hours 4-5 hours apart, NOT at bedtime unless treating RLS. Caution must be given about impulse control D/O

Managing Motor Flucutations MANAGING SYMPTOMS REEMERGENCE BETWEEN MEDICATION DOSES MANAGEMENT OF DYSKINESIAS

Off Time Strategies Increase the dose of dopaminergic medication Increase the time between dosing Add Comtan (catecho-o-methyltransferase inhibitor) Add Azilect (Rasagiline) OMG it s an MAO-B!!!

Comtan (catecho-o-methyltransferase inhibitor) Prolongs Levodopa serum levels allowing for increased CNS dopamine Always combine with Sinemet dosing May need to decrease Sinemet dose if dyskinesias develop Secretions turn orange 200mg dosed with each Sinemet dose Don t give with DA

Azilect (Rasagiline) A selective MAO-B inhibitor 0.5mg AM x 4 weeks, then 1mg AM Inhibits dopamine depletion in the brain. Possible neuroprotective benefit. May require dose reduction of Sinemet Avoid Flexeril, Demerol, Methadone, Dextromethorphan On SSRI pharmacist will tell your pts they will DIE No food restrictions

Management of Dyskinesias Not important to tx mild dyskinesias Develop earlier in younger patients Lower dose of Sinemet can help Decrease timing between dosing Adding Amantadine Levadopa-carbidopa intestinal gel is on the horizon

Managing Other Medication Effects NAUSEA IMPULSE CONTROL DISORDER PSYCHOSIS

Nausea Most common side effect of meds Slow GI motility is part of PD Slow titration of all meds is essential Food helps but dietary protein inhibits absorption Never give REGLAN dopamine antagonist Avoid Compazine and Phenergan

Impulse Control Disorder Usually related to DA use Hx of OCD, addictive behaviors, impulsive personality will increase risk Discuss before initiation of meds and inform S/O Can develop at any time while on DA DC meds usually resolves behaviors in 2-3 weeks Amantadine and Zonisamide may reduce symptoms in pts where behaviors persist despite removing meds

Psychosis Occur in late stage PD and as side effect of meds Initiation of DA or infections can trigger Clozapine is most effective but CBC troubles limit use in U.S. Quetiapine most used. Cyclical binding on the D2 receptor. Donepezil and Rivastigmine may help

Managing Nonmotor Symptoms REM BEHAVIOR DISORDER RESTLESS LEG SYNDROME DEPRESSION COGNITIVE IMPAIRMENT ORTHOSTATIC HYPOTENSION HYPERSALIVATION

Restless Leg Syndrome Urge to move the limbs, unpleasant, usually at night Overlap syndrome with PD Worsens with wearing off of Levadopa 30-40% of pts with iron deficiency anemia have RLS Akathisia mistaken for RLS

REM Behavior Disorder Vigorous movements during REM sleep Flailing, kicking, punching, shouting 15-50% of PD patients Usually unknown to the pt 1/3 of RBD patients develop PD Clonazepam is 1 st line therapy Melatonin option in clonazepam intolerant

Depression Very common in PD Can safely use SSRI, SNRI, or TCA Azilect (rasagilie) limits use to SSRIs at lower doses

Cognitive Impairment Cholinergic dysfunction may be partially responsible Cholinesterase inhibitors can be helpful for cognitive function, behavioral disturbances, and improved ADLs Exacerbation of tremor is a side effect GI side effects can be severe Conflicting data exists for memantine

Orthostatic Hypotension Is a manifestation of autonomic dysfunction and medication side effects Increase fluid intake, increase salt, compression stockings, slower position changes FIRST LINE Decrease blood pressure medications Midodrine, Fludrocortisone, Indomethacine

Hypersalivation Related to autonomic dysfunction Glycopyrrolate 1mg BID to TID Botulinum toxin A injections reduce saliva production parotid and submandibular injections

Melanoma and PD WHAT IS THIS ABOUT?

Melanoma PD pts have a 60% higher risk Initial reports pointed to levadopa, but now we know the risk precedes the diagnosis. LEVADOPA DOES NOT CAUSE MELANOMA

Deep Brain Stimulator THE FUTURE IS NOW!

Indications to Consider DBS Severe freezing and motor fluctuations requiring higher and higher doses of Sinemet Severe dyskinesias Younger patients (< 75) Must respond well to Sinemet No significant cognitive impairment or psychosis Mood is relatively stable

DEEP BRAIN STIMULATOR STN or GPi best for PD VIM best for ET