Treatment of Parkinson’s Disease in the Geriatric · PDF file ·...

Treatment of Parkinson’s Disease in the Geriatric PopulationYvette M. Bordelon, MD, PhD

Notes:

33rd Annual UCLA Intensive Course in Geriatric Medicine + Pharmacy & Board Review

TREATMENT OF PARKINSON DISEASE IN THE GERIATRIC

POPULATIONYvette M. Bordelon, MD, PhDAssociate Clinical Professor

UCLA Neurology, Movement Disorders Program

Disclosures: Speakers Bureau, Teva Pharmaceuticals

Notes:


Parkinson Disease• Second most common neurodegenerative disease next to Alzheimer disease

• Estimated to affect 1-2% of the population over 65; 1 million people in the US

• Affects men:women in a 2:1 ratio• Mean age of onset 60• Young onset PD <50• Juvenile onset PD <18: rare

• Longevity not affected in mean onset PD• Heterogeneous: no two people with PD are alike. Treatment must be individualized

Notes:


Parkinson Disease Diagnosis• Clinical Diagnosis• UK PDS Brain Bank Criteria- Probable PD• Bradykinesia + at least one of the following: rigidity, 4-6 Hz

rest tremor, postural instability• Exclude other causes of parkinsonism• At least 3 of the following supportive criteria: unilateral

onset, rest tremor, progressive persistent asymmetry, L-dopa responsive, L-dopa effective > 5 yrs, L-dopa induced dyskinesias, clinical course > 10 yrs

• Potential PD subtypes• Tremor-dominant; postural instability/gait disorder (PIGD)

Notes:


PD Differential Diagnosis• Essential Tremor• Atypical Parkinsonian Disorders• Progressive Supranuclear Palsy• Corticobasal Syndrome• Dementia with Lewy Body disease• Multiple System Atrophy

• Drug-Induced Parkinsonism (neuroleptics, anti-emetics)

• Vascular parkinsonism• Normal Pressure Hydrocephalus

Notes:


PD Pathology• Degeneration of the striatonigraldopaminergic pathway• Substantia nigra pars compacta

(melanin containing cells) projecting to caudate and putamen (striatum)

• Pathologic hallmark is the Lewy body: dense cytoplasmic inclusion of alpha-synuclein

Normal PD

Lewybody

Notes:


PD Pathology

Location of Lewy bodies and Lewy neurites- Braak stagingNot only confined to the substantia nigra: widespread brain disease

Braak et al., Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging 2003; 24: 197-211.

Notes:


PD Imaging• Imaging of striatal dopaminergic terminal loss can support a clinical

diagnosis; may be useful in distinguishing between PD and essential tremor but not in differentiating among parkinsonisms

• DaT scan FDA approved; ioflupane-dopamine transporter ligand

Normal PD

[123I]Ioflupane SPECT scan (DaTscan)

Notes:


Sym

ptom

sParkinson Disease Treatment

Early PD• Which meds?• Start of meds?• Disease modification?

Late PD• Wearing Off• Dyskinesias• Which meds?

Notes:


Parkinson Disease Treatment

Levodopa

HVA

3MT

MAO-BCOMT

DOPAC

COMTMAO-B

Dopamine Agonists

MAO-B Inhibitors COMT Inhibitors

DopamineDopamine

Pre-synapticSNc

Post-synapticMedium-sized GABAergic

Striatal neuron

Increase dopamine releaseInhibit synaptic dopamine degradationActivate post-synaptic dopamine receptors

Dopamine Receptor

AADC

Dopaminergic Synapse

Notes:


• MAO-B inhibitors- rasagiline (Azilect)- selegiline (Eldepryl)- orally disintegrating selegiline (Zelapar)

• Dopamine agonists• pramipexole (Mirapex)• pramipexole ER• ropinirole (Requip)• ropinirole XL• rotigotine (Neupro) patch

• Levodopa- gold standardprovides greatest symptomatic benefit

• Carbidopa-levodopa (Sinemet) IR, CR, Rytary

• Carbidopa-levodopa-entacapone (Stalevo)

• Duopa (intestinal infusion)

• Anticholinergics

• Amantadine

PD Medical Management

Notes:


Early PD Management• Clinical Practice• Medications started when ‘function’ impaired • Different threshold for every patient• May change as neuroprotective agents are identified

• Choice dependent on patient age, med tolerability, symptom pattern and severity• Patients under 70 consider starting with dopamine

agonists or MAO-B inhibitors, older than 70 with levodopa

• Tremor may respond better to anticholinergics if not controlled by other meds

Notes:


Medication Options

• MAO-B inhibitors• Selegiline and Rasagiline• Mild symptomatic benefit and possibly disease-

modifying• Dopamine Agonists• Ropinirole, ropinirole XL, pramipexole, pramipexole ER,

rotigotine (patch)• Symptomatic benefit• Delays motor complications• More side effects than levodopa

Notes:


Early PD Medications• Levodopa• Most effective medication for PD motor symptoms• Consider as first-line agent in patients >70 due to side

effect profile of dopamine agents • With disease progression, levodopa can lead to motor

complications of wearing OFF of medication benefit and dyskinesias• 50% of patients develop motor complication after 5

years• More likely in young onset (<40)

• Many options available for initiating levodopa; no strong evidence for or against one strategy; practitioner dependent

Notes:


Early PD Medications• Levodopa• Many options available for initiating levodopa; general considerations• carbidopa-levodopa (Sinemet) IR 25/100• C-L-entacapone (Stalevo) 50, 75, 100, 125, 150, 200• C-L (Sinemet) CR 25/100, 50/200—70% bioavailable,

not as predictable onset and duration; used at bedtime

• C-L (Rytary) new formulation of mixture or short-acting and long-acting C-L beads: 95, 145, 195, 245; titration and conversion VERY challenging; perhaps 1/3 or 1/2 potency of Sinemet IR

Notes:


Early PD Management

• American Academy of Neurology Practice Parameter• Initiation with either dopamine agonist (DA) or levodopa (Level A evidence-established efficacy)• Levodopa: superior motor benefit but higher risk of dyskinesias

• No evidence of improved outcome initiating with sustained-release forms of levodopa (SinemetCR) Rytary not yet studied

Practice Parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review. Neurology 2002 58: 11-17.

Notes:


Early PD Management• Clinical Practice• Medications started when ‘function’ impaired • Different threshold for every patient• May change as neuroprotective agents are identified

• Choice dependent on patient age, med tolerability, symptom pattern and severity• Patients under 70 consider starting with dopamine agonists or MAO-B inhibitors, older than 70 with levodopa; amantadine sometimes useful but short-lived

• Tremor may repond better to anticholinergics if not controlled by other meds

Notes:


Early PD Management• Medication Doses

• Rasagiline 1 mg qam• Selegiline 5mg bid; 2nd dose no later than 2pm• Pramipexole 0.25mg tid to start, titrate up to 3-4.5mg/day divided

tid or qid; Pramipexole ER titrate up by 0.375 mg to 3-4.5 mg/day• Ropinirole 0.5 tid to start, titrate up to 9-16mg/day divided tid or

qid; Ropinirole XL titrate up by 2mg to 10-16 mg/day• Rotigotine patch titrate up by 2mg to 8mg/day• Agonist equivalents: pramipexole:ropinirole:rotigotine= 1:4:4• Amantadine 100 mg up to tid-qid• Trihexyphenidyl 1mg to start, titrate up to 2mg tid or higher if

tolerated• Carbidopa/levodopa titrate up by 25/100 increments to the dose

best tolerated and most effective• Rytary is newest formulation—titration not yet well established

Notes:


Early PD Management• Medication Side Effects

• Selegiline• Metabolized through methamphetamine path. Insomnia, cognitive side

effects• Rasagiline 1 mg qam

• Well tolerated. No need to keep tyramine restricted diet• Pramipexole, Ropinirole short-acting and controlled release

• Nausea, somnolence (rarely sleep attacks), leg swelling, hallucinations, hypotension, impulse control disorders

• Rotigotine• Same as pramipexole and ropinirole but less nausea and with skin irritation

possibly• Amantadine

• Hallucinations, livedo reticularis, leg swelling, constipation• Trihexyphenidyl

• Dry mouth, confusion, blurry vision, urinary retention• Carbidopa/levodopa

• Nausea, cognitive side effects, hypotension

Notes:


Dopamine Agonist Side Effects

• Impulse Control Disorders• Greater recognition of this side effect. Estimated

frequency of 13.6% (Weintraub et al., 2010). Also present with levodopa but lower incidence

• Uncontrolled compulsion for an activity: gambling, sex, shopping, eating, computer use, etc.

• More common with younger onset PD • Typically requires cessation of agonist.

Notes:


© 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

Therapies in Parkinson's disease. Jankovic, Joseph; Poewe, Werner. Current Opinion in Neurology. 25(4):433-447, August 2012.

FIGURE 1 . Suggested guideline for the treatment of Parkinson's disease from early to advanced staged. DA, dopamine; DAT, dopamine transporter; DBS, deep brain stimulation; MAO, monoamine oxidase; VMAT2, vesicular monoamine transporter type 2.

Notes:


Early Mid Late

Dyskinesia Threshold

Efficacy Threshold

L-DopaDoses

OFF

ON

6-8 h 3-5 h .5-2 h

Adapted from Jankovic

PD Progression

WEARING OFF

DYSKINESIAS

MOTOR COMPLICATIONS

Therapeutic Window Narrows with Progression

Notes:


Treatment of Motor Complications• Treatment of Wearing OFF

• Increase frequency of PD med dosing or individual doses• Add MAO-B inhibitor if not already used• Add dopamine agonist if not already used

• For severe or sudden OFF consider apomorphine SC• Add controlled release carbidopa/levodopa if not already used• Add COMT inhibitor

• Entacapone (200 mg always given with levodopa dose)• Increases serum transport of levodopa and prolongs half-life• Tolcapone requires LFT monitoring

• Treatment of Dyskinesias• Add amantadine• Decrease frequency of PD med dosing or individual doses• Decrease or remove MAO-B inhibitors, dopamine agonists or

COMT inhibitors if being used

Notes:


Motor Complications• Pulsatile stimulation of dopamine receptors believed to

underlie development of motor complications. Goals have been to develop continuous medication delivery systems• Ropinirole XL• Pramipexole ER• Rotigotine patch• Duopa- intraduodenal levodopa infusion pump• Rytary-longer-acting carbidopa-levodopa• No data yet to support that these medications delay motor

complications

Notes:


Late PD Management• American Academy of Neurology Practice Parameter• Treatment of wearing off• Level A evidence: Rasagiline and entacapone• Level B evidence: Pramipexole, ropinirole, tolcapone

(pergolide)• Level C evidence: Selegiline, apomorphine

(cabergoline)• No benefit: sustained release levodopa and

bromocriptine• Treatment of dykinesias• Level C evidence: Amantadine

Practice Parameter: Treatment of Parkinson disease with motor fluctuations and Dyskinesia (an evidence-based review) Pahwa et al., Neurology 2006 66: 983-995.

Notes:


Late PD Management• Clinical Practice• Treatment of wearing off• Add-on MAO-B inhibitors, COMT inhibitors and/or dopamine agonists

• More frequent levodopa dosing• Treatment of dyskinesias• Add-on Amantadine• Decrease individual doses of PD meds

•Consideration of DBS• If not a surgical candidate, consider Duopa: intestinal levodopa infusion

Notes:


Late PD Management• DBS

• Targets: GPi, STN• Patient selection is critical:

• Advanced PD with wearing off and dyskinesias• Good levodopa response (exception: tremor

dominant)• If gait/balance are primary problems then DBS

not likely to be helpful• No significant cognitive impairment• May worsen after surgery• Neuropsychological testing performed to

evaluate• Management of expectations

Notes:


Motor Complications

• Assessment is difficult• Day to day variation• Difficult for patients/families to

describe• Written diaries or logs are time-

intensive• New Devices under development to

track motor symptoms• PKG: watch-- monitor motor

symptoms with data downloaded at end of study period and analyzed.

• UCLA study underway in PD patients with motor fluctuations and dyskinesias preparing for DBS

Notes:


DBS in PD• Patient Selection• Accurate PD diagnosis. • Disabling motor fluctuations, dyskinesias or tremor. • Or difficulty tolerating med side effects• Age: no strict cut-off for consideration; chronological age

vs physiological age• Cognitive function• Detailed neuropsychological testing performed in all

cases• Impairment may worsen with surgery

Notes:


DBS in PD• Patient Selection

• Levodopa responsiveness: best predictor for DBS response (tremor excluded)• L-dopa response approximates DBS efficacy • Threshold of 30% improvement between OFF and

ON exams • non L-dopa responsive symptoms (axial-

speech/gait/balance) generally not improved with DBS

• Psychiatric disease: severe depression or anxiety• Psychosocial support

Notes:


DBS in PD• Patient Selection• No consensus on how to measure these criteria nor

what thresholds should be established for inclusion/exclusion of DBS consideration

Deep Brain Stimulation for Parkinson Disease. An Expert Consensus and Review of Key Issues. Bronstein et al., Arch Neurology 2011 68: 165-171.

Notes:


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Goal of DBS in PD:More time in best “on” condition

Notes:


Parkinson’s Disease – DBS

• Two Targets• Subthalamic Nucleus• Globus Pallidus Internus• EQUAL motor efficacy

• STN results in greater medication reduction

• STN has increased neurocognitive complications• Mood and cognitive problems,

impulse control disorders

Notes:


GPi vs STN Rematch

Adapted from Williams et al. 2014 Mov DisordClin Pract 1: 24-35

GPi STNTremor + +Rigidity +Bradykinesia +L-dopa responsive Gait and balance

+

Dyskinesias ++Cognition +Med Flexibility and Stability ++Programming Ease ++Med Reduction ++Overall Quality of Life + +Ability to use 1 lead ++Off period motor symptoms + +Mood/Behavior +

+ slight advantage++ definite advantage

Notes:


© 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

Therapies in Parkinson's disease. Jankovic, Joseph; Poewe, Werner. Current Opinion in Neurology. 25(4):433-447, August 2012.

FIGURE 2 . Suggested guideline for the treatment of levodopa-related motor fluctuations and dyskinesias. COMT, catechol-O-methyl transferase; CR, controlled release; DA, dopamine; ER, extended release; GPi, globuspallidus interna; MAO, monoamine oxidase; STN, subthalamic nucleus.

Notes:


Motor Symptoms Non-Motor Symptoms• Tremor• Rigidity (muscle stiffness)• Bradykinesia (slowness

of movement)• Walking difficulties• Postural Instability• Speech problems• Motor complications

(wearing off of meds,dyskinesias)

• Depression, Anxiety• Sleep Disorders• Cognitive decline• Autonomic nervous systemdysfunction (gastrointestinal complaints, orthostasis,incontinence, erectile dysfunction)

PD Treatment

Notes:


PD Management• Exercise• Improves muscle strength, flexibility, joint ROM• The only treatment for gait and balance impairment• Animal data suggest neuroprotection• Also improves non-motor PD symptoms• No specific exercise plan yet recommended although

several are under study• Often Physical, Occupation and Speech Therapy

helpful in designing treatments• BIG and LOUD therapies

• Rock-Steady Boxing, Yoga, Tai Chi….

Notes:


Essential Tremor• Diagnostic Criteria- Consensus Statement of the

Movement Disorder Society on Tremor• Bilateral postural tremor with or without kinetic tremor,

involving hands and forearms, that is visible and persistent

• Duration > 5 years• No other neurologic deficits or exposure to

tremorogenic drugs and not of abrupt onset

Notes:


Essential Tremor

• The most prevalent movement disorder.• Approximately 4-5% of the population over age 40, an estimated 10 million people in the US, many more worldwide; 10 times more common than PD• Risk Factors:•Age (prevalence of 9% over age 60)• Family History

• Typically alcohol responsive

Notes:


Essential Tremor Etiology• No cause yet clearly identified• Strongly familial –but no gene

mutations yet identified-recent association with LINGO1

• Pathology only recently reported through autopsy studies• 2/3 cases with cerebellar changes• 1/3 with Lewy bodies (seen in

Parkinson disease) but in different brainstem nucleus

• May provide clues as to why ET can be seen more commonly in families with PD

Notes:


ET Treatment• American Academy of Neurology Practice Parameter • First-line Medications (Level A evidence)• Propranolol and propranolol LA• Primidone

• Either Medication may reduce tremor by as much as 50%• Propranolol + Primidone may increase efficacy by another

10-15%• Second-line Medications (Level B evidence)• Gabapentin• Topiramate• Atenolol• Alprazolam• Sotalol

Evidence-based guideline update: Treatment of essential tremor., Zesiewicz et al., Neurology 2011 77: 1752-55.

Notes:


ET Management

• In addition to medications consider • botulinum toxin injections • Occupational Therapy/assist devices including weighted

utensils, etc.• Deep Brain Stimulation when medications not adequately

effective or not tolerated• Target: Vim nucleus of the thalamus

• Other surgical interventions when DBS not desired or too risky and only unilateral treatment necessary• Thalamotomy, focused ultrasound (investigational)

Notes:


ET Management

• Consideration of Deep Brain Stimulation• Patient Selection• Accurate ET diagnosis. •Must distinguish between ET and tremor-dominant PD•Consideration of DAT or F-DOPA imaging to establish diagnosis

• Age• Tremor refractory to medications or side effects not tolerated

• Cognitive function

Notes:


Atypical Parkinsonian Disorders• Variants of Parkinson Disease • Parkinsonism (characteristic stiffness and slowness) with additional signs or symptoms• Parkinson’s Plus Syndromes• Atypical Parkinsonian Disorders

• Parkinsonism not levodopa responsive• If so, small percentage of patients and benefit not usually sustained

• DBS usually not effective

Notes:


Atypical Parkinsonian DisordersParkinsonism plus….

• Dementia and hallucinations• Dementia with Lewy Body Disease (DLB)

Autonomic nervous system dysfunction-Fainting, Incontinence• Multiple System Atrophy (MSA)

• Eye movement limitations and falls• Progressive Supranuclear Palsy (PSP)

Asymmetric apraxia, myoclonus and dystonia• Corticobasal Degeneration/Syndrome (CBD/CBS)

Notes:


Classification by PathologyPathologic Cause: protein misfolding and aggregation

• Synucleinopathies (Lewy bodies)• Parkinson Disease• Dementia with Lewy Body disease• MSA

• Tauopathies (tau neurofibrillary tangles)• PSP• CBD• Frontotemporal Dementias (FTD)

Notes:


Atypical Parkinsonian Syndromes• Other Parkinsonisms• Vascular Parkinsonism: moderate-severe white matter

small vessel ischemic disease• Drug-Induced Parkinsonism• Dopamine Receptor Blockers: Neuroleptics (except

quetiapine and clozapine) and the anti-emetics metoclopramide (Reglan) and prochlorperazine(Compazine)

• Normal Pressure Hydrocephalus• Classic Triad: memory impairment, magnetic gait,

incontinence. Parkinsonism may be seen and improves with shunting

Notes:


Dementia with Lewy Bodies• Synucleinopathy• Clinical criteria for probable DLB: Dementia plus 2 of the following: • Parkinsonism (onset concurrent or after dementia)• Fluctuating cognition• Visual hallucinations

• Pathology reveals LB throughout cortex and brainstem

• FDG-PET: decreased metabolism in occipital cortex

Notes:


Dementia with Lewy Bodies• Difficult to distinguish from PD dementia (PDD). Clinical criteria for

probable PDD: preceding PD diagnosis and Dementia plus 2 of the following• Reduced attention• Memory impairment• Language impairment• Visuospatial dysfunction• Executive dysfunction

• Treatment • Levodopa as tolerated by cognitive impairment and hallucinations• Quetiapine or clozapine for psychosis as these are generally free

of parkinsonian side effects• Cholinesterase inhibitors for cognitve and behavioral symptoms

Notes:


MSA Clinical Diagnosis-updated• Clinical Criteria for Probable MSA

• Age of onset >30 and sporadic, progressive disorder characterized by:• Autonomic dysfunction involving urinary incontinence plus erectile

dysfunction in males, or an orthostatic decrease in 3 min of SBP by 30 mmHg or DBP by 15 and

• Poor levodopa response or• A cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb

ataxia or cerebellar oculomotor dysfunction)• Subtypes:• MSA-P (parkinsonism- previously striatonigral

degeneration)• MSA-C (cerebellar- previously olivopontocerebellar

atrophy)• (Autonomic predominance- previously Shy-Drager)

• Mean onset age 50s; prevalence 3-4 per 100,000; average duration 10 years

Gilman et al., Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71: 670-676.

Notes:


MSA Clinical Diagnosis• Clinically possible• Additional features also include: Atrophy on MRI of

putamen, MCP, pons or cerebellum, dopamine deficiency by SPECT or PET, or hypometabolism in putamen, brainstem or cerebellum by FDG-PET.

• Treatment• Levodopa is tried and may be responsive for a short

period• Fludrocortisone, midodrine for hypotension• Botulinum Toxin for dystonia• Amantadine trial

Notes:


PSP Clinical Diagnosis• NINDS-SPSP Criteria for PSP• Clinically Probable

• Gradually progressive disorder• Onset age 40 or above• No features suggestive of alternative diagnosis • Vertical supranuclear gaze palsy• Slowing of vertical saccades and prominent postural

instability with falls within the first year• Sensitivity 50%; Specificity 100%

• Clinically Possible• 1-3 above and • Vertical supranuclear gaze palsy OR slowing of vertical

saccades and falls within the first year• Sensitivity 83%; Specificity 93%

• Age of onset mid-60s, prevalence 5-6 per 100,000 average duration 5-9 years

• 4R TauopathyLitvan I et al., Neurology 1996; 47: 1-9.

Notes:


PSP: Clinical Features• Cardinal:

• Vertical gaze palsy (down>up) > horizontal• Axial>appendicular rigidity• Prominent postural instability with frequent falls

• Supportive:• Eyelid opening apraxia, blepharospasm, diplopia, photosensitivity,

square wave jerks, absent OKN• Frontalis, corrugator overactivity-PSP stare• Spastic/ataxic dysarthria, stuttering, tachyphemia, dysphagia• ‘Reckless’ gait, hyperextended posture, falls backward, freezing of gait,

‘rocket sign’• Dystonia, retrocollis• Emotional incontinence• Impulsive behavior• Executive dysfunction, apathy, bradyphrenia• ‘Applause sign’, repeated motor behaviors, perseveration• Urinary incontinence, constipation• Insomnia, daytime somnolence

Notes:


• Levodopa- some mild responsiveness in a portion of patients; CoQ10, amantadine and amitryptilline can be tried

• No other adequate symptomatic therapies available currently

• Clinical Trials underway

PSP Treatment

Notes:


CBD Clinical Diagnosis 4R Tauopathy The most difficult diagnosis to establish among Atypical Parkinsonisms

due to Overlap and variability of clinical symptoms Overlap of pathological contributions to similar clinical syndromes

Williams and Lees Lancet Neurology 2009 8:270-279.

Notes:


Revision of CBD Diagnostic Criteria• Clinical Criteria for Possible CBD-Broader definition

• Gradual onset and progression; Duration of at least 1 year• Possible CBS:

• May be symmetric; 1 of: a) limb rigidity or akinesia, b) limb dystonia, c) limb myoclonus plus 1 of: d) orobuccal or limb apraxia, e) cortical sensory deficit, f) alien limb phenomena

• Or Fronto-behavioral-spatial syndrome (FBS): 2 of: executive dysfunction; behavioral or personality changes; visuospatialdeficits; + 1 CBS feature

• Or Nonfluent/agrammatic variant (NAV) of primary progressive aphasia: effortful, agrammatic speech plus at least 1 of: impaired grammar/sentence comprehension; apraxia of speech; + 1 CBS feature

• Or Progressive Supranuclear Palsy syndrome (PSPS): 3 of: axial or symmetric limb rigidity or akinesia, postural instability with falls, urinary incontinence, behavioral changes, supranuclear vertical gaze palsy or slow saccades; + 1 CBS feature

Armstrong et al., 2013 Criteria for the diagnosis of corticobasal degeneration. Neurology 80: 496-503.

Notes:


CBD Clinical Diagnosis• Marked asymmetry of:• Limb rigidity or akinesia• Limb dystonia and myoclonus• Ideomotor apraxia, cortical sensory deficits, alien limb

phenomenon• Poor levodopa responsiveness• Gait and balance impairment• Often from rigidity/dystonia/apraxia of legs/arms

• Speech changes• Dysarthia, language impairment, apraxia of speech in

combination with dysphagia

Notes:


CBD Treatment• Levodopa-some mild responsiveness in a portion of

patients• Levetiracetam for myoclonus• Trihexyphenidyl, baclofen, benzodiazepines for dystonia• Cholinesterase inhibitors for cognitive impairment• Botulinum toxin injections for dystonia

Notes:


PSP clinical trials

• Observational• ARTFL: Advancing Research and Treatment

for Frontotemporal Lobar Degeneration• FTLD syndromes (bvFTD, PPA, FTD-ALS,

PSP, CBS)• Rating scales, cognitive battery, CSF, MRI for

biomarker development• FamPSP• Genetic testing on PSP probands with a first

degree relative with any neurological or psychiatric disorder

Notes:


PSP clinical trials

• Interventional• Tau Antibody Based Therapies• C2N-8E12 (ABBV-8E12) anti-tau antibody infused

intravenously Single Dose Phase 1 study ongoing; Multiple Dose Study planned for late 2016

• BMS-986168 anti-tau antibody infused intravenously; Multiple Dose Phase 1 study ongoing.

• Salsalate: Phase 1 open label study of oral salsalate

Notes:


Support: Parkinsonism

• UCLA Monthly Support Group• First Friday of the month 2-4pm• 300 medical plaza- Marisa Leif conference room

Now available on Amazon

Notes:


Diagnosis of PD and variants remains a clinical one Arsenal of treatment options continues to grow DBS effective in carefully selected patients ET more common than PD and responsive to meds

and DBS Atypical Parkinsonian Syndromes should be

considered and require different treatment approaches

Summary

Notes:


UCLA MOVEMENT DISORDERS

FacultyJeff BronsteinIndu SubramanianAllan WuCarlos Portera-CailliauYvette BordelonPaula RavinAdrienne KeenerNeurosurgery: Nader PouratianPsychology: Arik Johnson

CoordinatorsDolly WestHenrietta SalazarLiz QuinteroDiane Yang

FellowsMonica SkordilisTammy Pham

Treatment of Parkinson’s Disease in the Geriatric · PDF file ·...

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