10/11/17 Disclosures Consulting services for Bagatto, Inc. to guide - - PDF document

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10/11/17 Disclosures Consulting services for Bagatto, Inc. to guide - - PDF document

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10/11/17 Disclosures Consulting services for Bagatto, Inc. to guide the PARKINSONS DISEASE FOR THE development of improved deep brain stimulation clinician programming systems and cognitive testing PRIMARY CARE CLINICIAN applications

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UCSF Primary Care Medicine: Principles and Practice Maya Katz, M.D. Assistant Professor of Neurology UCSF Medical Center October 2017

PARKINSON’S DISEASE FOR THE PRIMARY CARE CLINICIAN

— Consulting services for Bagatto, Inc. to guide the

development of improved deep brain stimulation clinician programming systems and cognitive testing applications

— Consulting services for Putnam Associates and

Gerson Lehrman Group to help identify treatment gaps for people with Parkinson’s disease

— Consulting services for SchlessingerAssociates,

ExpertConnect, KeyQuestHealth, Seagrove Partners, Cowen and Company, LLC to understand physician perspectives on current and future treatments for people with Parkinson’s disease

Disclosures

— Parkinson’s Disease Demographics — Parkinson’s Disease Motor Symptoms — Parkinson’s Disease Progression — Parkinson’s Disease Pathophysiology — Parkinson’s Disease Treatment Motor Symptoms — Parkinson’s Disease Treatment Non-motor Symptoms — Parkinson’s Disease Treatment Supportive Care Model

Outline Parkinson’s disease: Demographics

Wickremaratchi et al. 2009. J Neurol Neurosurg Psych; Walker et al. 2010. Parkinsonism and Related Disorders Lees et al. 2009. The Lancet; Moisan et al. 2015, Journal of Neurology, Neurosurgery, & Psychiatry

1-2% of people 60 years of age or older (~130-140 per 100,000) 2nd most common neurodegenerative disorder Average age of onset: 60 years old (range 20-95) Males are 1.5 times more likely to develop Parkinson’s disease Typical life expectancy: 12-20 years (range: 12-40)

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Cardinal motor symptoms: Tremor

Cardinal motor symptoms: Bradykinesia Cardinal motor symptoms: Gait Impairment

OFF MEDICATIONS ON MEDICATIONS

Parkinson’s disease progression: Motor Fluctuations

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Parkinson’s disease progression: Dyskinesias

Cenci, 2014, Frontiers Neurology

Parkinson’s disease progression: Motor Fluctuations

Stage 5: ~2 years

Wheelchair bound or bedridden Can only ambulate with another person assisting

Zhao et al. 2010, Mov Disord

Stage 4: ~2 years

Severe disability, Needs an assistive device to walk or stand

Stage 3: ~2 years

Mild to moderate bilateral involvement, Postural instability, Still independent

Stage 2: ~7 years

Mild bilateral involvement

Stage 1: ~2 years

Unilateral involvement

Parkinson’s disease progression: Hoehn & Yahr staging Parkinson’s pathology: Substantia nigra pars compacta degeneration

UCSF Department of Pathology

Parkinson’s disease Normal

Scarr et al., 2013, Front. Cell. Neurosci.

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Olanow and Brundin, 2013, Movement Disorders

Parkinson’s pathology: Lewy body Parkinson’s pathology: prion-like disease

§

DaTSCANs detect presynaptic dopaminergic neuronal loss using SPECT imaging

§

Measures Ioflupane (123I), which is a DAT ligand that binds to presynaptic dopamine transporters in the striatum

de la Feunte-Fernandez 2012. Neurology Ba and Martin, 2015, Parkinsonism and Related Disorders

Parkinson’s pathology: DaTSCAN

The basal ganglia has 2 major pathways:

Direct and Indirect

  • The direct pathway facilitates movement.
  • The indirect pathway inhibits movement
  • Striatal dopamine excites the direct pathway

(increasing movement), and suppresses the indirect pathway (increasing movement)

Calabresi et al. 2014, NatureNeuroscience

Parkinson’s pathology: Rate model

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Phase amplitude coupling

— Increased bursting of

neuronal activity

— Increased synchronization

in neuronal activity

— Increased oscillatory

activity

de Hemptinne et al. 2013, PNAS

Parkinson’s pathology: Brain arrhythmia

  • Complex interplay between
  • genetics (ingredients)
  • environment (recipe)

Tanner et al. 2011, Envi Health Perspectives

Parkinson’s etiology: gene-environment interaction

Treatment for Parkinson’s Disease Motor Symptoms: Medications

Carbidopa/Levodopa: Effects

— The most effective and generally well-tolerated medicine for PD — Short half-life (~45 to 90 minutes), needs to be taken frequently as PD progresses — Ideally should be taken 1 hour before or 2 hours after a protein-rich meal — Main side effects: nausea, lightheadedness, hallucinations, and dyskinesias

Sinemet CR Carbidopa/Levodopa: Formulations Sinemet IR Rytary Parcopa

~2 to 2.5 hours increased sustained concentration compared to sinemet IR ~60 minutes increased sustained concentration compared to sinemet IR, impaired bioavilability, lower peak dose, time to peak concentration can be up to 120 minutes longer than sinemet IR Orally disintegrating tablets, not sublingually absorbed, similar time to peak concentration compared to sinemet IR Short half-life (45-90 minutes)

Treatment for Parkinson’s Disease Motor Symptoms: Medications

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PD Treatment: Medications

Carbidopa/Levodopa: Dosing Guidelines

— Start with sinemet 25/100mg IR: ½ tab three times per day — Increase to sinemet 25/100mg IR: 1 tab three times per day after 2 weeks — Increase to sinemet 25/100mg IR: 1.5 tabs three times per day after 2 weeks — Increase to sinemet 25/100mg IR: 2 tabs three times per day after 2 weeks — Instruct patients to increase the dose of sinemet only if motor

symptoms are not well controlled on the lower dose

— Can ultimately increase the dose up to 3.5 tabs per dose, if needed — No maximum total daily dose, based on need and tolerance — Advanced PD patients may take sinemet every 90 minutes

PD Treatment: Medications

Carbidopa/Levodopa ER: (Rytary) Dosing Guidelines

Carbidopa/Levodopa Extenders: Effects Entacapone (Comtan) Rasagaline (Azilect)

Tolcapone (Tasmar)

Selegiline (Eldepryl)

1 hour increased on-time Side effects: drug interactions 1 hour increased on-time Side effects: drug interactions, HTN, insomnia, delirium 1 hour increased on-time Side effects: diarrhea, orange urine 2-3 hours increased on-time Side effects: Liver failure

Treatment for Parkinson’s Disease Motor Symptoms: Medications

Dopamine Agonist: Effects

— Compared to carbidopa/levodopa — Lasts longer, half-life: ~6 hours — Lower risk of causing dyskinesias — More mild benefit — Main side effects: sleep attacks, ICDs, sedation, confusion, hallucinations,

cognitive deficits, dry mouth, lightheadedness

— Usually not prescribed to people over 70 years of age

Treatment for Parkinson’s Disease Motor Symptoms: Medications

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Levodopa sparing therapy: Effects Trihexyphenidyl Dopamine agonists Zonisamide

Mild-moderate reduction in parkinsonism Side effects: ICD, sleep attacks, hallucinations, cognitive deficits Reduces tremor, mild benefit Side effects: nephrolithiasis, somnolence, ataxia, confusion, cognitive deficits Reduces tremor and dystonia Side effects: sedation, delirium, hallucinations, increased risk of dementia, dry mouth, constipation

Treatment for Parkinson’s Disease Motor Symptoms: Medications

Levodopa sparing therapy: Effects MAO-B inhibitors Amantadine

Very mild reduction in parkinsonism, if any Side effects: drug interactions, depends on whether rasagaline or selegiline are used Mild reduction in parkinsonism, Reduces dyskinesias Side effects: confusion, hallucinations, dry mouth, constipation,

Treatment for Parkinson’s Disease Motor Symptoms: Medications

CALM-PD PSG Study Group, 2000, JAMA

§ CALM-PD Clinical Trial

Dosing strategy Percentage developing dyskinesia after 2 years Improvement in movement and function scale (UPDRS) Pramipexole 10% 4.5 points Levodopa 30% 9.2 points

Treatment for Parkinson’s Disease Motor Symptoms: Risk of developing dyskinesias

§ Prochlorperazine (Compazine) § Promethazine (Phenergan) § Metoclopramide (Reglan) § Most anticholinergics (e.g. benadryl or oxybutynin) § Most antipsychotics (only quetiapine, clozaril and pimavanserin are safe)

Treatment for Parkinson’s Disease Motor Symptoms: Medication Tips

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OUTPATIENT PHYSICAL THERAPY

  • Parkinson Wellness Recovery (PWR!)
  • Lee Silverman Voice Training (LSVT)
  • Balance vest

REHABILITATION

Treatment for Parkinson’s Disease Motor Symptoms:

HOME SAFETY EVALUATION

  • skilled nursing
  • physical therapy
  • ccupational therapy
  • custodial non-skilled care

REHABILITATION

Treatment for Parkinson’s Disease Motor Symptoms:

MEDICARE COVERS 'SKILLED MAINTENANCE’ REHABILITATION

Treatment for Parkinson’s Disease Motor Symptoms:

  • Medicare covers rehab services to maintain or manage a patient’s current condition

when no functional improvement is possible

  • Therapy services to maintain a patient’s current condition or slow decline are covered

NON-PHARMACOLOGICAL TREATMENTS

  • Reduce multi-tasking to reduce freezing episodes
  • During a freezing episode: come to a complete stop (to abort the malfunctioning

automatic gait program causing the freezing episode)

  • Then try any of the following techniques:
  • Count to 3 and take a large high step with one foot.
  • Try another movement (e.g. raise an arm, touch your head) and then restart walking
  • Turn in a U-shape
  • Change direction: step sideways and then go forward
  • Weight-shifting from side to side
  • Step over a target (e.g. a laser pointer using U-step walker/cane)
  • Metronome or musical cueing
  • Stress-reduction techniques to minimize emotional triggers of freezing episodes

FREEZING OF GAIT

Treatment for Parkinson’s Disease Motor Symptoms:

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PHARMACOLOGICAL TREATMENTS

  • Methylphenidate 1mg/kg/day divided TID was shown to reduce freezing of gait

[Moreau et al. 2012] FREEZING OF GAIT

Treatment for Parkinson’s Disease Motor Symptoms:

PHARMACOLOGICAL TREATMENTS

  • Donepezil 10mg daily was shown to reduce falls in PD by almost 50% in a small

clinical trial [Chung et al. 2010]

  • Vitamin D supplementation 1200 units daily was shown to reduce decline in balance in

a small clinical trial [Suzuki et al. 2013]

  • Cyanocobalamin supplementation 1000mcg daily if a deficiency is identified
  • Consider starting a bisphosphonate (e.g. zoledronic acid) to reduce the risk of

fractures secondary to falls IMBALANCE

Treatment for Parkinson’s Disease Motor Symptoms:

USE OF ASSISTIVE DEVICES

  • Cane, walking sticks, walker (U-step vs. Life walker vs. Other rolling walkers)
  • Consider knee protectors for frequent fallers
  • Recommend Lifeline or MedAlert System
  • Wheelchair optimization

IMBALANCE

Treatment for Parkinson’s Disease Motor Symptoms:

Physical activity must be challenging to have a benefit

Treatment for Parkinson’s Disease Motor Symptoms:

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Cenci, 2014, Frontiers Neurology

Parkinson’s disease progression: Motor Fluctuations

Intestinal infusion of dopamine (levodopa)

— Reduces off-medication time and reduces dyskinesias — Most patients are on duopa monotherapy

Nyholm et al. MDS Conference abstract. 2012; Olanow et al. 2014, The Lancet Neurology

Treatment for Parkinson’s Disease Motor Symptoms:

Duopa infusion therapy

Intestinal infusion of dopamine (levodopa)

— Possible side effects:

— Post-surgical complications — Tubing issues — Cases of severe neuropathy

Olanow et al. 2014, The Lancet Neurology

Treatment for Parkinson’s Disease Motor Symptoms:

Duopa infusion therapy

Ideal Candidate for DBS

  • Parkinson’s disease for at least 5 years
  • Robust improvement in motor symptoms with dopaminergic therapy
  • Consider as soon as motor symptoms are no longer easily managed with

medications alone

  • Freezing of gait and postural instability should not be the primary symptoms
  • Good social support
  • Ability to comply with complex life-long therapy
  • Reasonable expectations for the surgery
  • No medical contraindications for surgery
  • No untreated severe psychiatric disease
  • No dementia (PD-MCI can still be considered for unilateral, staged surgery)

Treatment for Parkinson’s Disease Motor Symptoms:

Deep Brain Stimulation

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  • In general, only what levodopa can do

Exceptions: tremor and peak dose dyskinesias

  • Increases the best “on-medication” state by 4-5 hours daily
  • Improves motor function by 25-50%
  • Raises the ceiling for off-medication times
  • Reduction in medication dosing (30-50%)

Marks et al., Editor, 2015, Deep Brain Stimulation Management

Treatment for Parkinson’s Disease Motor Symptoms:

Deep Brain Stimulation

What can DBS do?

Marks et al., Editor, 2015, Deep Brain Stimulation Management

Treatment for Parkinson’s Disease Motor Symptoms:

Deep Brain Stimulation

What are the limitations of DBS?

  • Less effective for midline symptoms
  • Will not treat non-motor symptoms
  • Can make certain symptoms worse

(e.g. speech, falls, behavior and cognition)

Deep Brain Stimulation Awake Surgery Deep Brain Stimulation Asleep Surgery

physiology-guided implantation iMRI-guided implantation

Treatment for Parkinson’s Disease Motor Symptoms:

DBS Surgical Techniques

PRE-DBS POST-DBS

Treatment for Parkinson’s Disease Motor Symptoms:

Deep Brain Stimulation: Pre- and Post-Surgery

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PRE-DBS POST-DBS

Treatment for Parkinson’s Disease Motor Symptoms:

Deep Brain Stimulation: Pre- and Post-Surgery

Fasano & Deuschl 2012, Basal Ganglia

Treatment for Parkinson’s Disease Motor Symptoms:

Deep Brain Stimulation: Timing of Surgery

Langston, 2006, Ann Neurol Weintraub et al. 2004, J Am Geriatr Soc.; Shulman et al., 2002, Parkinsonism and Related Disorders;

— Most motor symptoms (fluctuations

and dyskinesias) can be treated with advanced surgical therapies, but freezing of gait and imbalance are usually refractory

— Most PD patients report an

average of 8 non-motor symptoms

— Non-motor symptoms are often: — under-recognized and unseen — more difficult to treat — impair quality of life more than

motor symptoms

— have a greater impact on care-

partner strain than motor symptoms

Motor symptoms are just the tip of the iceberg

Treatment for Parkinson’s Disease Non-motor Symptoms: PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Cognitive deficits Non-Pharmacological Treatments

  • Reduce or withdraw offending mediations
  • Rule out infections, dehydration and metabolic derangements
  • Rule out depression and anxiety
  • Rule out obstructive sleep apnea or chronic insomnia
  • Rule out B12 deficiency
  • Rule out illicit drug use
  • Cognitive leisure activities
  • Regular exercise

Pharmacological Treatments

  • Optimize dopaminergic medications (may need to be reduced)
  • Cholinesterase inhibitors (e.g. donepezil, rivastigmine, galantamine)
  • NMDA receptor antagonist (e.g.memantine)

Dubois et al., 2012, Mov Disord

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PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Non-Pharmacological Treatments

  • Psychotherapy (e.g. CBT)
  • Mindfulness Based Stress Reduction (MBSR course)
  • Gratitude Therapy

Depression/Anxiety Pharmacological Treatments

  • Optimize levodopa dose to reduce non-motor off time (which can include mood symptoms)
  • Mirtazapine (can also improve insomnia and appetite)
  • Duloxetine or Venlafaxine (can also improve neuropathic pain)
  • Sertraline (generally well tolerated, prefer to escitalopram given no black box warning)
  • Buproprion (caution, can cause hallucinations and agitation in advanced PD)
  • Methylphenidate (for treatment resistant depression, can see rapid improvements in mood)
  • Deplin as an adjunct therapy
  • Buspar for anxiety (can also be given prn for breakthrough anxiety)
  • Trazodone 25mg TID for anxiety (can also be given prn for breakthrough anxiety)
  • Transcranial magnetic stimulation (TMS)
  • Electroconvulsive therapy (ECT)

Chang and Foz, 2016, Drugss

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Non-Pharmacological Treatments

  • Rule out concurrent illness and/or metabolic derangements
  • Rule out medication side effects
  • Minimize disruptions at night time
  • Optimize light exposure and activities during the day
  • Place calendar in clear view
  • Minimize immobilization by reducing catheters and restraints
  • Glasses and hearing aids optimized to reduce sensory deprivation

Psychosis Pharmacological Treatments

  • Consider tapering off dopamine agonists, amantadine and anticholinergics
  • Consider reducing levodopa dose
  • Maximize cholinesterase inhibitors
  • Quetiapine, Pimavanserin, or Clozaril (black box warning with use in those with dementia)

Chang and Foz, 2016, Drugss

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Non-Pharmacological Treatments

  • Rule out delirium due to underlying medical cause
  • Rule out medication side effects
  • Minimize disruptions at night time
  • Optimize light exposure and activities during the day
  • Glasses and hearing aids optimized to reduce sensory deprivation

Agitation (seen in advanced PD dementia) Pharmacological Treatments

  • Taper off dopamine agonists, amantadine and anticholinergics
  • Consider reducing levodopa dose
  • Maximize cholinesterase inhibitors
  • Consider morphine if underlying pain could be causing the agitation
  • Quetiapine, Pimavanserin, or Clozaril (black box warning with use in those with dementia)
  • Consider low dose depakote (may worsen tremor or cause over-sedation)

Chang and Foz, 2016, Drugs

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Non-Pharmacological Treatments

  • Rule out sleep deprivation and depression
  • Pacing activities
  • Strength training to increase capacity for energy expenditure
  • Forced exercise (e.g. Theracycle or tandem bike)
  • Group exercise
  • Yoga to increase endurance
  • Acupuncture

Fatigue

Pharmacological Treatments

  • Modafanil
  • Methylphenidate
  • Amantadine

Kluger B. 2017. International Review of Neurobiology

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PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Poor sleep onset and maintenance Non-Pharmacological Treatments

  • Sleep study to rule out obstructive sleep apnea
  • Encourage good sleep hygiene
  • No caffeine at least 4 hours before bedtime
  • Get regular exercise (avoid 2 hours before bedtime)
  • Keep a regular schedule for bedtime and wakeup time
  • Keep the bedroom quiet and dark during the night
  • Keep the bedroom mainly for sleep, avoid watching television,

listening to the radio or eating in the bedroom

  • Get out of bed if not sleeping
  • Get sunlight and exercise in the morning

Albers and Anch, 2017, Sleep Medicine

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Poor sleep maintenance Pharmacological Treatments

  • Ensure adequate levodopa coverage overnight (consider Rytary)
  • Melatonin (ideally taken 2 hours prior to bedtime)
  • Mirtazapine (lower doses are optimal to treat insomnia, 7.5mg or 15mg at bedtime)
  • Trazodone (main potential side effect is orthostatic hypotension)
  • Quetiapine (particularly useful if there is sundowning or psychosis at bedtime)
  • Gabapentin (particularly useful if nighttime leg cramps or RLS disrupt sleep)
  • Doxepin (caution, may contribute to daytime confusion, useful if unable to add a

serotonergic medication such as mirtazapine or trazodone to improve sleep)

Albers and Anch, 2017, Sleep Medicine

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

REM Behavior Disorder Non-Pharmacological Treatments

  • Maintain a safe sleep environment to prevent injuries
  • Move furniture away from the bed
  • Place padding on corners of furniture
  • Consider placing a mattress on the floor near the bed
  • Bed-partner may need to sleep in a separate bed until RBD is well

controlled with pharmacological treatments Pharmacological Treatments

  • Melatonin (3-15mg, ideally taken 2 hours before bedtime)
  • Clonazepam (start at 0.25mg at bedtime, caution - may cause daytime sedation,

confusion and falls, may worsen OSA)

  • Quetiapine (start at 12.5mg at bedtime, can increase by 12.5mg as needed)

Albers and Anch, 2017, Sleep Medicine

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Constipation Non-pharmacological Treatments

  • Dietary adjustments:
  • Daily prunes or prune juice
  • Fruits, vegetables, whole grain breads
  • Stay hydrated (6-8 glasses of liquid daily)
  • Avoid bulk fiber supplements (e.g. psyllium)
  • Consider prebiotics and probiotics
  • Electro-acupuncture

Miyasaki, 2013; Curr Neurol Neurosci Rep

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PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Constipation Pharmacological Treatments

  • First line: miralax 1-4 times daily and senna daily (up to 4 tablets twice daily)
  • Second line: can add lubiprostone or linactolide
  • If no BM in 3-5 days: dulcolax suppository +/- enema (short-term use only)
  • If no BM in >7 days: magnesium citrate 150-300mg followed by 250ml of water (short-term use only)

Miyasaki, 2013; Curr Neurol Neurosci Rep

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Dysphagia Non-pharmacological Treatments

  • All meals should be given when the person is alert & sitting upright at 90 degrees
  • Use a chin-tuck position when swallowing
  • Small bites of food, chew thoroughly [slow intake rate, “put your fork or spoon

down between mouthfuls”]

  • “Mindful eating” [reduce distractions while eating]
  • Alternate between one bite of food and one sip of liquid
  • Make sure all food is cleared from the mouth before another bite or sip is taken.
  • Double swallow and clear throat every 2-3 bites
  • Avoid dry foods and nuts as dysphagia worsens
  • Adding sauces to food can help with swallowing safely
  • Upright position recommended for 30-45 minutes after a meal
  • Consider brushing teeth after meals
  • Eventually, mincing or pureeing food becomes necessary

Suttrup and Warnecke, 2017, Dysphagia

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Speech Language Pathology Evaluation

  • To assess severity of dysphagia and rule out other causes
  • Recommend additional behavioral interventions
  • Recommend swallowing rehab exercises (e.g. expiratory muscle strength training)
  • Assess for the Provale cup, the Nosey cup, or the Safe straw
  • We do not support thickening liquids (not palatable, can lead to dehydration)
  • Carbonated thin liquids can reduce aspiration
  • In the setting of severe dysphagia, we typically do not generally recommend a

percutaneous gastrostomy (PEG) tube, since this symptom is a sign of the disease being at end-stage, with dementia, psychosis and chair/bed-bound status. A PEG in advanced dementia has not been shown to improve survival. Dysphagia

Suttrup and Warnecke, 2017, Dysphagia

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Pharmacological Treatments

  • Rectal Levodopa and rotigotine patch can be considered in the short-term when

patients are unable to swallow due to concurrent illness (e.g. delirium in the setting

  • f sepsis). See the reference below for instructions on formulating rectal levodopa

from oral levodopa. The rotigotine patch may worsen delirium and is contraindicated in those with advanced PD.

  • Parcopa is a dissolvable form of carbidopa/levodopa that is indicated in the setting
  • f dysphagia

Dysphagia

Suttrup and Warnecke, 2017, Dysphagia

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PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Sialorrhea Non-pharmacological Treatments

  • Sugar-free chewing gum or hard candy may remind the patient to swallow

Pharmacological Treatments

  • Optimize dopaminergic medications (sialorrhea may improve when off-

medication time is reduced

  • Botulinum toxin (myobloc)
  • Sublingual application of atropine opthalmic solution
  • Glycopyrrolate (caution, may cause urinary retention and constipation)

Srivanitchapoom et al., 2015, Parkinsonism Relat Disord

Central Pain Syndrome Non-pharmacological and Pharmacological Treatments

  • Optimize dopaminergic medications to reduce “off time”
  • Mindfulness based stress reduction
  • Acupuncture

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Ford, 2010, Movement Disorders

Non-Pharmacological Treatments

  • Adequate fluid intake (6-8 glasses of liquid per day). Drinks like Gatorade, Poweraide,

coconut water and V8 have salt and sugar, so they are more hydrating than plain water

  • Head of bed elevated (wedge pillow, 7-10 inches)
  • Sit-up and Stand-up slowly
  • Exercises to activate calf muscles prior to standing up (e.g. repetitive foot raises, leg crossing)
  • Abdominal compression bands (more comfortable than compression stockings)
  • Avoid prolonged exposure to hot weather
  • Eat small low-carbohydrate meals
  • For acute symptomatic events: counsel patients tie sit down & drink 16 ounces as a bolus

Orthostatic hypotension

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Miyasaki, 2013; Curr Neurol Neurosci Rep

Pharmacological Treatments

  • Withdraw or reduce any offending medications (e.g. reduce antihypertensives)
  • Liberalize salt in the diet (if there are no medical contraindications)
  • Salt tablets (1gram with each meal)
  • Caffeine (1-2 cups of coffee daily, avoid in the evenings)
  • Midodrine (last dose should be no later than 6pm to avoid supine hypertension overnight)
  • Fludrocortisone (requires monitoring of potassium)
  • Pyridostigmine (use for patients with supine hypertension)
  • Droxidopa

Orthostatic hypotension

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Miyasaki, 2013; Curr Neurol Neurosci Rep

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Non-Pharmacological Treatments

  • Exclude urinary tract infections
  • Urology evaluation for BPH in males (appropriate treatment if identified)
  • Timed voiding during the daytime “bladder training” (every 2-3 hours)
  • Improve access to bathroom or bedside commode (to prevent functional incontinence)
  • Physical therapy focused on pelvic floor muscles (e.g. Kegl maneuvers)
  • Prior to bedtime - elevate legs for 30 minutes using a 7-10 inch wedge for 30 minutes,

and then urinate before going to sleep

  • Elevate head of the bed (7-10 inch wedge)
  • Limit liquids after 6pm
  • Condom catheter overnight may improve sleep maintenance
  • If needed, recommend high absorbency pads (gel briefs are the most absorbent)

Overactive Bladder Symptoms

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Sanford et al., 2017, Current Bladder Dysfunction Reports

Pharmacological Treatments

  • Specific anticholinergic medications (trospium, darifenacin, solifenacin)
  • β-3 agonist (Mirabegron)

Overactive Bladder Symptoms

Invasive Treatments (referral to urology)

  • Intravesicular botulinum toxin injections
  • Electro-acupuncture
  • Percutaneous tibial nerve stimulation
  • Sacral nerve stimulation

PARKINSON’S DISEASE SYMPTOM MANAGEMENT

Sanford et al., 2017, Current Bladder Dysfunction Reports

Mediterranean Diet

PD Neuroprotection: Role of nutrition

Parkinson’s Disease Supportive and Palliative Care Clinic

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Palliative care principles address “Total Pain”

The suffering that encompasses all of a person’s physical, psychological, social, spiritual and practical struggles in the setting of serious illness

Creutzfield et al., 2016, Neurology Clinical Practice

Palliative model of care for Parkinson’s disease

ROLE OF PALLIATIVE CARE IN THE TREATMENT OF PARKINSON’S DISEASE

— Albers JA, et al. Multifactorial sleep disturbance in Parkinson’s disease. Sleep Medicine.2017 July;35: 41-8 — Ba F, et al. Dopamine transporter imaging as a diagnostic tool for parkinsonism and related disorders in clinical

  • practice. Parkinsonism Relat Disord. 2015 Feb;21(2):87-94.

— Calabresi P, et al. Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat Neuroscience. 2014 Aug;17(8):1022-30. — Cenci MA. Presynaptic mechanisms of L-dopa-induced dyskinesias: The findingsm the debate and the therapeutic

  • implications. Front Neurol. 2014 Dec;5:242.

— Chang A and Fox SH. Psychosis in Parkinson’s disease. Drugs.2016;76(11):1093-118. — Chung KA, et al. Effects of a central cholinesterase inhibitor

  • n reducing falls in Parkinson disease. Neurology. 2010

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UCSF MOVEMENT DISORDER AND NEUROMODULATION CENTER (MDNC) SFVA PARKINSON’S DISEASE RESEARCH, EDUCATION AND CLINICAL CENTER (PADRECC)

Jill L. Ostrem, M.D. – MDNC Medical Director Philip A. Starr, M.D., Ph.D. – MDNC Surgical Director Caroline M. Tanner, M.D., Ph.D. – PADRECC Director

Neurology Jill L. Ostrem, M.D. Caroline Tanner, M.D., Ph.D. Ian Bledsoe, M.D., M.S. Nicholas Galifianakis,M.D., M.P.H. Marta San Luciano, M.D., M.S. Maya Katz, M.D. Jim Mass, M.D., Ph.D. Amy Viehoever, M.D., Ph.D. Nijee Luthra, M.D., Ph.D. Cameron Dietiker, M.D. Melanie Brandabur, M.D. Neurosurgery Philip A. Starr, M.D., Ph.D. Paul S. Larson, M.D. Edward F. Chang, M.D., Ph.D. Dan Lim, M.D., Ph.D. Coralie de Hemptinne, Ph.D.. Doris Wang, M.D., Ph.D. Witney Chen, Ph.D. candidate Psychiatry Andreea Seritan, M.D. Tobias Marton, M.D. Occupational and Environmental Medicine Samuel Goldman, M.D., M.P.H. Clinical Fellows Mitra Afshari, M.D. Kyle Mitchell, M.D. Ethan Brown, M.D. Melissa Heiry, M.D. Jennifer Choi, M.D. Jessica Weinstein, M.D. Rory Murphy, M.D. Physical Therapy Heather Bhide, P.T. Social Work Monica Eisenhardt, LCSW Chaplain Judy Long, M.S., M.A. Carolyn Talmadge, M.Div. Research Staff Sarah Wang, Ph.D Nieves Lopez-Barrera, M.D. Kathleen Comyns, M.P.H Cheryl Meng, M.P.H.. Farah Kausar, Ph.D.

  • C. Kevin Park, M.D.

Kristen Dodenhoff, B.A Jana Guenther, B.A. Clinic Support Staff Shatara Blackmon Yasmeen Gonzalez Christine Jiunti Jeverly Calaunan Janet Allen Lorraine Anzaldo Neuropsychology Caroline A. Racine, Ph.D. Johannes Rothlind, Ph.D. Nursing Monica Volz, N.P. Susan Heath, M.S., R.N Annie Li Wong, N.P. Karen Merchant, R.N. Gina Bringas-Cinco, R.N.