Parkinson's disease - University of Minnesota Continuing Medical ...
Parkinson's disease - University of Minnesota Continuing Medical ...
Parkinson's disease - University of Minnesota Continuing Medical ...
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Disclosure Information<br />
Parkinson’s s <strong>disease</strong><br />
Paul Tuite, MD<br />
<strong>University</strong> <strong>of</strong> <strong>Minnesota</strong><br />
Movement Disorders<br />
Paul J Tuite, M.D. 2008<br />
I have the following financial relationships to disclose:<br />
Speaker’s Bureau for: None<br />
Grant/Research support from: None<br />
Honoraria from: None<br />
I will discuss <strong>of</strong>f label use and/or investigational use in my<br />
presentation.<br />
Vignette #1:<br />
Suspect Parkinsonism<br />
Parkinsonism<br />
– Frozen shoulder<br />
– Altered gait<br />
– Tremor<br />
– Slowness/stiffness<br />
– Masked facies<br />
– Difficulty getting out <strong>of</strong><br />
chairs<br />
– Altered handwriting/voice<br />
– REM sleep disorder/vivid<br />
dreams<br />
– Loss <strong>of</strong> sense <strong>of</strong> smell<br />
– History <strong>of</strong><br />
anxiety/depression<br />
– Family history<br />
– Long standing constipation<br />
– Exposure to well water, prior<br />
head injury, pesticide<br />
exposure<br />
Tremor<br />
= rhythmical; typically a rest tremor<br />
Rigidity<br />
= resistance to movement<br />
Akinesia<br />
= slowness/absence <strong>of</strong> movement<br />
Postural changes = stooped posture
Resting Tremor<br />
Rigidity<br />
Spasticity<br />
Akinesia/Bradykinesia
Postural Changes Vignette #1:<br />
So it is Parkinsonism, what next?<br />
– Determine degree <strong>of</strong> disability from symptoms/signs<br />
– Decide on <strong>disease</strong> subtype<br />
• Tremor predominant<br />
• Akinetic-rigid variant<br />
– Age <strong>of</strong> individual?<br />
– Are they working?<br />
– Do they have pre-existing addictions/compulsions?<br />
– Sleep deprivation, RBD, Sleep apnea, driving for work?<br />
– Does insurance cover their medications?<br />
– Do they have pre-existing lower extremity edema?<br />
– Is there renal dysfunction? relates to ropinirole<br />
– Are they demented or have MCI? avoid certain drugs<br />
What if patients don’t want a Rx?<br />
Role <strong>of</strong> Coenzyme Q10 (CoQ)<br />
• Physical, Occupational & Speech Therapy<br />
– Training BIG THERAPY (Dr. Becky Farley)<br />
• Potentially useful compounds<br />
– Coenzyme Q10 400 mg TID (1200 mg/d) $$$$<br />
– Omega 3<br />
– Creatine<br />
– Selenium
Potentially Disease Altering<br />
Isradipine (Dynacirc®) shown to affect<br />
<strong>disease</strong> progression in mouse model <strong>of</strong> PD.<br />
Blockade <strong>of</strong> Ca channels forced utilization <strong>of</strong><br />
less toxic Na channels<br />
Symptomatic Medications<br />
– Dopamine agonists:<br />
• Rotigotine (Neupro) patch<br />
• Ropinirole (Requip) TID or QD (soon)<br />
• Pramipexole (Mirapex) TID<br />
– MAO b inhibitors:<br />
• Selegiline (Eldepryl) QD or AM & Noon<br />
• Rasagiline QD<br />
– Glutamate modulation:<br />
• Amantadine (Symmetrel) QD - TID<br />
– Anticholinergics:<br />
• Trihexyphenidyl (artane) BID<br />
• Benztropin (cogentin) BID<br />
Carbidopa/Ldopa<br />
Sinemet<br />
Substantia Nigra<br />
levodopa<br />
How do medications work?<br />
DA<br />
Amantadine*<br />
Selegiline<br />
Rasagiline<br />
GABA<br />
Dopamine agonists<br />
bromocriptine<br />
pramipexole<br />
ropinirole<br />
apomorphine<br />
rotigotine<br />
SHORT ACTING—<br />
IMMEDIATE RELEASE LEVODOPA<br />
GENERIC VS. TRADE<br />
carbidopa/levodopa Sinemet® (carbidopa/levodopa)<br />
10/100 25/100 25/250 10/100 25/100 25/250<br />
BBB<br />
carbidopa<br />
benserazide<br />
tolcapone<br />
entacapone<br />
ACh<br />
trihexiphenidyl<br />
Striatum<br />
www.wemove.org
SHORT ACTING—<br />
IMMEDIATE RELEASE LEVODOPA<br />
Carbidopa/levodopa: generic or trade<br />
Versus<br />
Parcopa: levodopa in a disintegrating tablet<br />
LONG ACTING LEVODOPA<br />
GENERIC OR TRADE<br />
EXTENDED RELEASE (ER)<br />
CONTINUOUS<br />
RELEASE (CR)<br />
SUSTAINED RELEASE (SR)<br />
PILLS NOT SHOWN<br />
25/100 ER 25/100 ER<br />
25/100 SR<br />
50/200 ER 50/200 SR<br />
0.05<br />
Rotigotine (Neupro)<br />
2,4,6 & ?8 mg<br />
2.0 mg<br />
DOPAMINE AGONISTS<br />
COMT INHIBITORS<br />
MIRAPEX<br />
REQUIP<br />
PARLODEL<br />
APOMORPHINE<br />
ROTIGOTINE
Monitoring Dopamine Agonists<br />
Pharmacorama.com<br />
Britaject<br />
http://www.shef.ac.uk/misc/groups/epda/drug4.htm<br />
• Addictions:<br />
gambling, internet, sex, shopping, sports,<br />
antiparkinsonian medications, eating, others<br />
• Obsessive compulsive behaviors: OCBs; Punding:<br />
Cleaning/tidying, Do-it-yourself, Gardening,<br />
Collecting things, Repairing/dismantling (computers<br />
televisions, radios); Sorting, e.g., papers, through<br />
drawers/handbag; On the computer<br />
Reward Pathways<br />
Leg/Foot Edema (Swelling)<br />
LIMBIC<br />
Nucleus accumbens<br />
interacts with<br />
dopaminergic agents,<br />
cocaine, opiates (heroin)<br />
and marijuana (THC)<br />
LIMBIC<br />
http://bill.innanen.com/parkinsons/graphics/200111/uglyFoot.jpg
DAYTIME SOMNOLENCE<br />
Stimulants<br />
• Sleep deprivation<br />
– Sleep apnea<br />
– Nocturia<br />
– Nocturnal akinesia<br />
– Insomnia<br />
• Sedating medications<br />
– Dopamine agonists<br />
– Benzodiazepines<br />
– Others<br />
• Dementia<br />
MONOAMINE OXIDASE TYPE B<br />
INHIBITORS<br />
Anticholinergic Medications<br />
Artane® (trihexyphenidyl)<br />
Cogentin® (benztropine)<br />
RASAGILINE (AZILECT®)<br />
SELEGILINE (ELDEPRYL®)<br />
0.5 and 1 MG<br />
Rasagiline<br />
5 MG<br />
Tyramine Diet restriction<br />
Avoid SSRIs serotonin syndrome<br />
Meperidine – selegiline interaction<br />
Avoid decongestants BP effect<br />
Anti-SLUD: dry mouth, dry<br />
eyes/blurred vision, decr voiding,<br />
constipation, light-headedness,<br />
altered memory
Glutamate Modulating Medications<br />
Symmetrel® (amantadine)<br />
<br />
Natural History <strong>of</strong> Parkinson’s <strong>disease</strong><br />
Neuroprotective Rx Research Symptomatic Medication Rx<br />
DBS surgery<br />
-5 0 .5 - 1 1-1.51.5 4-10<br />
8-15<br />
12-20<br />
20<br />
rimantadine<br />
Flumadine®<br />
(rimantadine)<br />
Leg swelling,<br />
livedo reticularis,<br />
confusion, etc.<br />
Livedo reticularis<br />
Skin changes<br />
Symptoms<br />
Treatment<br />
Falls, swallowing,<br />
first<br />
begins<br />
bladder, cognitive<br />
appear<br />
problems, etc.<br />
Onset <strong>of</strong><br />
Diagnosis is<br />
<strong>disease</strong><br />
made<br />
Motor Complications<br />
(dyskinesias/fluctuations) begin<br />
Walker,<br />
cane,<br />
wheelchair<br />
for balance<br />
Motor Features As PD<br />
Advances<br />
Motor fluctuations: varying states <strong>of</strong><br />
mobility, which may or may not occur at<br />
a specific time in relation to their<br />
medication<br />
Dyskinesias: involuntary movements (not<br />
tremor), record when they occur -<br />
specifically in relation to their medication<br />
& time <strong>of</strong> day<br />
Often after 5-10 years<br />
motor fluctuations and dyskinesias occur
Non Motor Difficulties in PD<br />
Vignette #2<br />
• Vision<br />
• Gastrointestinal<br />
• Musculoskeletal<br />
• Skin<br />
• Respiratory<br />
• Neuropsychiatric<br />
• Sleep<br />
• Bladder<br />
• Orthostatic<br />
hypotension<br />
• 52 yo race car mechanic, lives alone, no financial<br />
support other than from working<br />
• PD: 16 to 17 years; severe motor fluctuations,<br />
significant "<strong>of</strong>f" times, as well as prominent<br />
dyskinesias that can be disabling at times.<br />
• He continues to struggle significantly with<br />
depression.<br />
• Medications<br />
– Sinemet 25/100, 1 to 6 tablets per day;<br />
– Dopamine agonist 0 to 10 times per day;<br />
– Amantadine 100 mg 1 to 2 per day.<br />
DBS and Parkinsonian Sxs:<br />
Features helped by surgery (checked)<br />
DBS Surgery<br />
Motor Difficulties<br />
Tremor<br />
Slowness<br />
Balance/Falls<br />
Fluctuations/Dyskinesias<br />
Off-related freezing<br />
Neuropsychiatric<br />
Anxiety/Depression<br />
Dementia<br />
Hallucinations<br />
Psychosis<br />
Autonomic Dysfunction<br />
Bowel/Bladder<br />
Orthostatic Hypotension<br />
Other<br />
Sleep apnea/RBD<br />
Weight/diet/dentition<br />
Dermatological<br />
Ophthalmologic<br />
Musculoskeletal<br />
Factors determining who should go for surgery:<br />
– Age: < vs. > 70 years<br />
– Concomitant medical conditions<br />
– Diagnosis: PD vs. atypical PD<br />
– Disabling features: Motor vs. Non-motor<br />
– Duration <strong>of</strong> <strong>disease</strong><br />
– Proximity to health care<br />
– Family dynamics<br />
– Objectives <strong>of</strong> surgery
Presurgical Evaluation<br />
• Neurological consultation<br />
• Motor testing<br />
• MRI scan<br />
• Cognitive assessment<br />
• Neurosurgical consultation<br />
Screening MRI:<br />
Normal vs. Strokes<br />
<br />
<br />
DBS Safety/Care Issues<br />
• Avoid diathermy (electrically induced heat:<br />
heating pads, deep ultrasound, etc.) near the<br />
implanted pulse generator (IPG, aka battery)<br />
• Device may be turned <strong>of</strong>f with theft detectors,<br />
refrigerator magnets, etc.<br />
• Monitor for infection, etc.<br />
• Monitor for technical difficulties, etc.<br />
• Avoid MRI scans (unless guided by DBS team)<br />
• Dental care
Vignette #3<br />
Initial Symptoms<br />
Dementia<br />
Years Later<br />
Parkinsonism<br />
• 72 yo w/ 4 yr h/o parkinsonism<br />
• Present meds:<br />
– Sinemet 25/250 TID<br />
– Selegiline 5 QAM<br />
• Issues:<br />
– Falls/Gait instability<br />
– Hallucinations to some meds<br />
Parkinsonism<br />
Parkinsonism<br />
Dementia<br />
Dementia<br />
TIME (years)<br />
Dementia<br />
Alz<br />
Disease<br />
Lewy<br />
Body<br />
Dementia<br />
PD<br />
Dementia<br />
Lewy Body Dementia<br />
Lewy Body Dementia<br />
Major Criteria<br />
Parkinsonism<br />
Fluctuations<br />
Vis Hallucinations<br />
Minor Criteria<br />
Delusions<br />
Falls<br />
Anti-DA sensitivity<br />
If 3 or > features 75% it is LBD<br />
LBD Drawings<br />
Alzheimer Drawings
ANTIPSYCHOTIC<br />
MEDICATIONS<br />
MEMORY ENHANCING MEDICATIONS<br />
• Falls<br />
Suspect Diagnoses Other<br />
Than PD if Seen Early<br />
• Cognitive changes<br />
• Prominent sexual or bladder dysfunction<br />
• Lack <strong>of</strong> response to adequate Rx trial<br />
• Symmetric onset<br />
• Early bulbar dysfunction
Falls<br />
– Executive dysfunction: not thinking first<br />
– Orthostatic hypotension<br />
– Freezing: feet stick to the floor<br />
– Vertigo: benign positional<br />
– Impaired vision<br />
– Sensory problems<br />
– Sensory-motor integration difficulties<br />
Red Flags at Any Time During<br />
the Course <strong>of</strong> the Condition<br />
Cortical Sensory Signs<br />
Alien Limb/unilateral apraxia<br />
No response to L-dopa<br />
Impaired vertical eye movements<br />
Cerebellar features<br />
Corticobasal<br />
Degeneration
Gait Difficulties: Is It Really PD?<br />
Multifactorial Gait Disorder<br />
• Multifactorial gait disorder<br />
• Normal pressure hydrocephalus<br />
• Vascular parkinsonism<br />
• Progressive supranuclear palsy<br />
• Lewy body dementia<br />
• Multiple system atrophy<br />
• Corticobasal degeneration<br />
• Medication induced parkinsonism<br />
• Cervical spondyloarthropathy<br />
Continuum: Geriatric Neurology<br />
Normal Pressure Hydrocephalus (NPH)<br />
Vascular Gait Disorder<br />
Continuum: Geriatric Neurology<br />
Continuum: Geriatric Neurology
• Supranuclear palsy<br />
• Falls early in course<br />
• Dysarthria<br />
• Cognitive impairment<br />
• Emotional<br />
incontinence<br />
• Abducted arms when<br />
ambulating: “gunslinger’s<br />
gait”<br />
PSP<br />
Dudley Moore<br />
PSP: Abnormal<br />
Voluntary Eye Movements<br />
Baylor U<br />
Progressive Supranuclear Palsy
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