1. Learning objectives At the end of this section you will: Have applied the knowledge gained from the earlier sessions to: Understand the impact of pulsatile dopaminergic therapy-induced motor complications on patient functioning Identify which patient types could benefit from the three CDS treatments currently available

2. Diagnosed 1986 His life revolved around taking tablets Problems with sleep, which had an impact on his quality of life In 1999, he received carbidopa/levodopa infusion for the first time A PEG operation was performed in May 2000 Case study 1 Patient history

3. Q. What additional options are available to further improve the quality of life of this patient? Discussion

4. Results Since 2002, 24-hour infusion has improved his sleep Few drawbacks From having a life dominated by tablet-taking, increasingly severe motor functions and very poor sleep, patient feels that he can once again fill his time with meaningful activities At the latest follow-up, he described his motor functions and sleep as good

5. CDS impact on sleep Adapted from Nyholm et al. Neurology 2005;65: 1506-7 24-hour infusion – impact on sleep (N=1; PD sleep scale; maximum 150; HY stage 4-5:~90)

6. ‘On/off’ mobility chart Anders. Data on file On/Off mobility chart: conventional treatment versus intraduodenal carbidopa/levodopa gel infusion Intraduodenal carbidopa/levodopa gel infusion

8. Conclusions DBS not suitable due to previous depression Without pump therapy living alone would not have been possible Living alone is possible with intraduodenal carbidopa/levodopa gel infusion in some cases 24-hour infusion of great benefit for this patient

9. Case study 2 Patient history Male, 58 years old Occupation: teacher Parkinson‘s disease since the age of 45, otherwise healthy Motor fluctuations and dyskinesias since the age of 52

10. Patient history Symptoms and treatment 2005 ‘On-off‘ fluctuations; severe ‘off’ phases with freezing; ‘on’ phases with pronounced dyskinesias Depressive symptoms No dementia Medication: –Pramipexole 1.4 mg daily –Levodopa 525 mg daily –Entacapone 1400 mg daily –Amantadine 200 mg daily –Quetiapine 50 mg daily

11. Patient history Symptoms and behaviour Dopamine dysregulation syndrome (DDS) Went to several doctors for prescriptions Consumed up to 3 g of levodopa daily Did not follow advice to restrict medication at all Punding Impulse control disorder (ICD) Hypersexuality –Called sex hotlines –Visited prostitutes daily Gambling –Lost large parts of personal savings Dopaminergic psychotic symptoms Hallucinations Confusion

12. Patient history Consequences of actions Lost family, home Legal guardian necessary to control his economy Nursing home

13. Treatment Step 1 Levodopa monotherapy 800 mg daily Result: –Psychotic symptoms improved, but did not disappear –DDS and ICD did not change –Motor fluctuations and dyskinesias worsened

14. Treatment Step 2 Quetiapine raised to 200 mg daily Result –DDS and ICD did not change

15. Q. Considering the results from treatment step 2, which treatment option would be appropriate for the next treatment step: DBS? Subcutaneous apomorphine infusion? Intraduodenal carbidopa/levodopa gel infusion? Other? Discussion

16. Treatment Step 3 Treatment: Intraduodenal carbidopa/levodopa gel infusion 5.2 ml/h daytime, 3.6 ml/h night-time, bolus: 2 ml, max 5 per day Quetiapine 75 mg daily All other medication stopped Result: DDS resolved almost completely ICD resolved completely No psychotic symptoms, no confusion Cognitive functions normal Strong improvement of motor fluctuations Side effects: Percutaneous endoscopic jejunostomy (PEJ) problems x 2, replaced

17. Q. In your opinion, what was the underlying reason for the improvements observed with intraduodenal carbidopa/levodopa gel infusion? Discussion