Program Highlights. Michael Pourfar, MD Co-Director, Center for Neuromodulation New York University Langone Medical Center New York, New York

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1 Program Highlights David Swope, MD Associate Professor of Neurology Mount Sinai Health System New York, New York Michael Pourfar, MD Co-Director, Center for Neuromodulation New York University Langone Medical Center New York, New York

2 Diagnosis: Motor Symptoms Four major motor symptoms Resting tremor Rigidity Slowness or bradykinesia Postural instability Usually look for 2 of 4 on exam Akinetic-rigid variant No tremor Occurs in ~1/3 of patients

3 Diagnosis: Nonmotor Symptoms Often arise earlier than motor symptoms Sleep disorders: sleepiness, sleep apnea, parasomnia, rapid eye movement sleep behavior disorder, insomnia, sleepwalking, excessive daytime somnolence, sudden onset of sleep, restless leg syndrome, and fatigue Autonomic symptoms: orthostatic hypotension, orthostasis, constipation, incomplete bowel emptying, fecal incontinence, nausea, vomiting, heat intolerance, urinary frequency, urinary incontinence, urinary urgency, nocturia, sweating, hypersalivation, drooling, seborrhea, and sexual dysfunction (in men and women) Psychological symptoms: anxiety, obsessive behaviors, delusions, decreased motivation, apathy, and decreased concentration Sensory dysfunction: smell, olfaction, taste, saliva, paresthesias, and visual disturbances Others: weight loss, anorexia, and leg edema Zesiewicz TA et al. Neurology. 2010;74:

4 Diagnosis: DaTscan Functional imaging of dopamine transporter (DaT) FDA approval in 2011 Defines integrity of striatal dopaminergic system Abnormal even in earliest clinical presentations of parkinsonism Normal scan suggests alternative diagnosis (eg, essential tremor, drug-induced parkinsonism, or psychogenic parkinsonism) Limited value in differentiating among degenerative causes of parkinsonism Gold standard remains clinical diagnosis by movement disorders neurologist Ba F, Martin WR. Parkinsonism Relat Disord. 2015;21: Sadasivan S, Friedman JH. Parkinsonism Relat Disord. 2015;21:42-5.

5 Patient Education Once diagnosed, patients and families/caregivers need education and support Understanding Parkinson s Disease improved management 8-session formal patient education program to improve skills related to self-monitoring, health promotion, stress management, depression, anxiety, social competence, and social support Patients reported mood elevations and reduced disease-related psychosocial problems, quality of life and depression Referral to support groups online or in person should be tailored to individual patient needs Macht M et al. Patient Educ Couns. 2007;65:

6 US PRELUDE Survey Patient education affects patient attitudes Perceived reasons for being switched to levodopa Patients PD symptoms getting progressively worse 55% PD not worsening but poorer control with previous treatments 16% Don t know why doctor recommended it 15% Could not tolerate side effects of previous treatments 10% Concerns about taking levodopa Long-term effects, such as dyskinesia 52% Benefits may begin to wear off sooner than desired 49% Indicates PD might have advanced to more severe stage 46% Immediate side effects (eg, nausea, vomiting) 34% Fear levodopa might make PD worse 23% Hattori N et al. Patient Relat Outcome Meas. 2012;3:31-8.

7 Treatment: Motor Symptoms Highest efficacy: levodopa-carbidopa Level of recommendation: A for monotherapy and adjunct therapy Adverse effects: dyskinesia, nausea, orthostatic hypotension, hallucinations High efficacy: dopamine agonists Pramipexole, ropinirole, rotigotine Level of recommendation: A for monotherapy and adjunct therapy Adverse effects: nausea, orthostatic hypotension, hallucinations, impulse control disorder, edema, increased sleepiness Connolly BS, Lang AE. JAMA. 2014;311:

8 Treatment: Motor Symptoms (cont.) Moderate efficacy: monoamine oxidase type B inhibitors (MAOBI) Rasagiline, selegiline Level of recommendation: rasagiline A for monotherapy and adjunct therapy; selegiline A for monotherapy and U adjunct therapy Adverse effects: headache, exacerbation of levodopa adverse effects; others depending on agent Moderate efficacy: catechol-o-methyltransferase inhibitors (COMTI) Entacapone, tolcapone Level of recommendation: A for adjunct therapy Adverse effects: dark-colored urine, diarrhea, exacerbation of levodopa adverse effects (tolcapone: hepatotoxicity) Other agents: anticholinergic agents, amantadine Connolly BS, Lang AE. JAMA. 2014;311:

9 Treatment: Managing Off Time Increase dosage of dopaminergic medication Adding another dopaminergic medication Levodopa dose fractionation Add COMTI or MAOBI Change delivery system of levodopa Transdermal patch, extended-release capsule, gel infusion Connolly BS, Lang AE. JAMA. 2014;311: LeWitt PA. Parkinsonism Relat Disord. 2016;22 Suppl 1:S37-40.

10 Early Deep Brain Stimulation 251 PD patients with early motor complications randomized to neurostimulation + medical therapy vs medical therapy alone Primary endpoint: quality of life (assessed with PDQ-39) Improved from baseline to 24 months by 26% in neurostimulation group vs -1% in medical-therapy group In the intention-to-treat population, the between-group difference in the mean change from baseline was 8.0 points (P=0.002) Neurostimulation significantly improved scores in all PDQ-39 domains except for communication and social support SCOPA-PS score for psychosocial performance also significantly better in neurostimulation group (P=0.02) Changes confirmed by further testing via generic and diseasespecific quality-of-life and disability scales Conclusion: Subthalamic stimulation superior to medical therapy in PD patients with early motor complications Schuepbach WM et al. N Engl J Med. 2013; 368:

11 Treatment: Nonmotor Symptoms Treat specific complication Keep it simple Make patient aware of adverse effects, interactions of treatment Insufficient evidence for guideline-recommended treatment for most common nonmotor symptoms Suggest multidisciplinary research effort needed to determine appropriate treatments Refer to specialist as needed Zesiewicz TA et al. Neurology. 2010;74:

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