Disclosures

1. Case Presentations: Demonstrating the impact of DCBM on motor management and Deep Brain Stimulation in Parkinson’s disease Greg Pontone, MD, MHSDirector Parkinson’s Disease Neuropsychiatry Clinic Johns Hopkins University School of Medicine

2. Disclosures • No relevant financial relationships with commercial interests. • The following talk includes unlabeled/unapproved use of medications.

3. Parkinson’s disease and mental health Objectives: • To become familiar with how psychiatric disturbances in Parkinson’s disease (PD) may complicate motor management and DBS • Discuss how these disorders of cognition, behavior, and mood (DCMB) can be addressed using a multidisciplinary model • Learn the typical presentations of behavioral disturbances associated with dopamine replacement therapy

4. I. Case presentation: 65-year old male with Parkinson’s and anxietyII. Importance of multidisciplinary careIII. Behavioral disorders associated with dopamine replacement therapy in PD

5. Case presentation • 65-year-old married man with PD • Chief complaint: “my throat is closing off” • Education-professional degree • Successful, lucrative career, still working

6. Past psychiatric history • First depressive episode in his 30’s • Had recurrent episodes, treated with psychotherapy and medication • At 57 severe episode (1 yr) refractory to several antidepressant trials • Mood symptoms resolved, but he felt “physically slowed” and had left hand rest tremor

7. PD history • Diagnosed with PD age 58, clear improvement with levodopa • By age 64 levodopa wearing off before next dose • Complained of worsening bradykinesia, gait difficulty, cognitive slowing, voice changes when off

8. PD history cont’d • His work performance declined related to these fluctuations and he retired • Off periods became associated with intense anxiety and the sensation that his “airway was closing” • He began to take additional levodopa to prevent off periods and sought consultation at specialty clinic

9. HPI • During his drive to the clinic stopped at two hospitals seeking emergency services “throat was closing off” • Medical workup unremarkable

10. Initial movement disorders consultation • Found to have akathisia and severe dyskinesias • Admitted to the neurology service • Anxiety attacks associated with off-periods—levodopa reduced and pramipexole added to try to minimize fluctuations

11. Second inpatient admission • After discharge motor symptoms improved, but anxiety increased to full panic attacks within 2 weeks • He returned to clinic and was readmitted to neurology, but transferred to a neuropsychiatric floor for anxiety and “erratic behavior” (e.g., leaving the hospital to visit erotic establishments)

12. Second inpatient admission • His wife revealed that at home taking substantially more levodopa and pramipexole than prescribed • Frequent mood changes, elation to irritability, sleeping less than 2 hours, hypersexual behaviors, trading stocks online, trying to buy/sell houses • Rapid, pressured speech, flight of ideas

13. Psychiatric diagnosis • Bipolar disorder, type I, manic with comorbid dopamine dysregulation syndrome • Pramipexole was tapered and discontinued, however… • Remained manic and hospitalized 2+months; valproate and quetiapine • Psychiatrically improved, movement worsened

15. Teeter-totter: psychiatric symptoms improved, movement worse • Follow up in multidisciplinary clinic recommended bilateral subthalamic nucleus deep brain stimulation • Team: movement disorder neurologist, functional neurosurgeon, neuropsychiatrist, neuropsychologist, nurse specialist for coordination of care

16. DBS activated • DBS improved motor symptoms, eliminated wearing off, allowed lower doses of DRT • However, stimulation voltage increase triggered a manic episode and fully formed visual hallucinations of “cat-headed people” • Re-hospitalized for 6 weeks • Stabilized on quetiapine, valproate, lithium; stable 2+ years now

17. Impaired motor and cognitive volition: dyskinesias and impulse control disorders in Parkinson’s

18. Dopaminergic on-off motor fluctuations • Improvement in motor symptoms after L-dopa administration = “on” • Return of parkinsonian movement symptoms at the end of the dosing effect = “off”

19. Dopaminergic medication on-off fluctuations in PD Stacey M. and Hauser R. 2007

20. On-off motor fluctuations • Incidence: 10% per year develop motor fluctuations after initiation of l-dopa therapy • In the longest published follow-up of PD cohort, 100% at 20 years had motor fluctuations (and dyskinesia) As reviewed in Aquino and Fox 2015

21. Dyskinesias • Abnormal, involuntary movements associated with dopamine replacement therapy • Disease duration, rather than DRT exposure may be more important • Typically hyperkinetic and choreiform; constant writhing or wriggling movements of the arms, legs, trunk, and facial muscles

22. Impulse control disorders (ICDs) in PD • “An assortment of behaviors performed repetitively, excessively, and with a lack of self-control to an extent that interferes with life functioning” • Associated with dopamine agonist medications and other dopamine replacement therapies

23. Impulse control disorders in PD • Pathological gambling • Compulsive buying/shopping • Hypersexual behaviors • Binge eating

24. Dopamine dysregulation syndrome • Drug addiction-like state marked by self-medication with inappropriately high doses of dopaminergic medications • May be more common in early onset PD and males—prevalence 3%-4% • Co-occurs with ICDs, psychosis, panic attacks

26. Impaired cognitive volition and involuntary bodily movements • PD patients with moderate to severe dyskinesia are more likely to have ICDs or related behaviors than patients with mild or none • Signaling cascades implicated in substance use disorders are also altered in dyskinetic patients—suggesting overlap between altered reward processing and dyskinesias • DA replacement and ventral vs dorsal striatum

27. Questions?