Duodenal Levodopa Treatment in advanced Parkinson’s Disease Baciu Diana, MG, VI Scientific Advisor: Lecturer: Dr. Szász József-Attila UMF Târgu Mureș, Neurology II, Târgu Mureș Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Parkinson’s Syndrome: Hypo-kinetic hypertonic, extrapyramidal motor syndrome Progressive, neurodegenerative disease Heterogenous etiology Rather affects middle-age people The onset-age plays an important role in further evolution of the disease Parkinson’s Syndrome: Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Pathophysiology: Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Pathophysiology: Two major pathological mechanism: Loss of pigmented dopamine neurons The presence of Lewy bodies and Lewy neurites Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Clinical Presentation: Classic Symptoms Rest Tremor Bradykinesia/Hypokinesia/Akinesia Stiff Rigidity Early Symptoms Tremor at rest Muscle rigidity Stooped posture Expressionless face Slow movement Poor balance and coordination Advanced Symptoms Complications of L-Dopa therapy -Motor fluctuations -Dyskinesia and Dystonia Depression Dementia Psychosis Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Parkinson’s Disease: Diagnostic I. Clinical: Hoehn and Yahr Staging Scale: motor symptoms quantification Schwab and England activities of daily living (ADL)-scale Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) : Therapy monitoring I: non-motor experiences of daily living II: motor experiences of daily living III: motor examination IV: motor complications Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Parkinson’s Disease: Diagnostic II. Imaging: SPECT/PET CT/MRI for Diff. Dg. Transcranial Doppler- Sonography Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Motor Fluctuations incidence increase with use of Levodopa Treatment: Mild/Youg PD Patient Levodopa-Low Dose: MAOB Inhibitor/Dopamine Agonist ModeratePD.Pat. Monotherapy: Higher Doses of L-Dopa Combination: L-Dopa+ Dopa-Agonists/I-MAOB Severe/Od PD Pat. Duodopa: L-Dopa/Carbidopa intestinal delivery Deep Brain Stimulation Monotherapy >5 years of L-Dopa: 50% P.D.Pat-MF Motor Fluctuations incidence increase with use of Levodopa Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Complications of treatment with L-DOPA http://www.cnsspectrums/Volkmann_BigSlide_1.jpg Chorea, Benign Hereditary; Chorea, Chronic Progressive; Chorea, Rheumatic; Chorea, Senile; Chorea, Sydenham; Dyskinesias, Paroxysmal; Neuroacanthocytosis; Paroxysmal Dyskinesias; Senile Chorea; Sydenham Chorea) Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Motor Fluctuations: Hypokinetic symptoms: “wearing off ” end of dose akinesia “sudden off” “delayed on” “no on” “early morning akinesia” “peak-dose akinesia” “on-off” “freezing” Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Aim of the Study Material and Methods The follow-up of the patients who suffer motor fluctuations , with advanced Parkinson’s disease Which person requires treatment with intestinal gel Patients monitoring before and after Duodopa-medication Comparing performance of motor fluctuations Material and Methods The therapeutic method with intestinal gel Levodopa/Carbidopa has been firstly used in the Neurology Clinic II Tg. Mures in June 2011 Until December 2013 , 21 patients with advanced P.D and hypokinetic motor fluctuations were assesed with Duodopa-treatment Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results I. Distribution according to risc factors Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results I. Distribution according to risc factors Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results II. Distribution on motor fluctuations Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results III. Patient distribution of oral medications Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Treatment with Duodopa: Intestinal Gel Ideal Patient Advanced P.D with max. therapeutic dose Onset Dose Good response, without adverse effects: individualized doses Tester Test Period: Duodopa-effect was investigated in hospital Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results: Treatment with Duodopa Generally, most of the patients presented a decrease in the number of “off-hours” Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results IV. Clinical Quantification of motor fluctuations Daily activities of patients and motor symptoms were measured using international scales Hoehn-Yahr Scale Before and UPDRS II+III After Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results: Clinical Quantification of motor fluctuations: UPDRS II (Daily Activity): The amount of the grade scale for measuring daily activity before treatment was compared with the one after treatment. Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Results: Clinical Quantification of motor fluctuations: UPDRS III (Motor System):The total amount of the grade scale for measuring motor performance during “ON” before treatment was compared with the one after treatment Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Conclusions: Main causes in the occurrence of M.F are: Progressive degeneration of dopamine terminals Short Half-Life of L-Dopa, which produces a discontinous dopamine stimulation Gastric inactivation of L-Dopa or low absorbtion Duodopa – Intestinal Gel Administration can solve this issues - maintaining a constant level of dopamine in the blood Objectively, all 21 patients experienced a significant reduction in the fluctuations, while achieving a better gait function Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion

Thank you for your attention! Introduction-Pathophysiology-Diagnostic-Treatment-Material and Methods-Results-Conclusion