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INS;carbidopa intestinal gel in advanced Parkinson's disease patients: safety and motor-symptom endpoints
Abstracts / Journal of the Neurological Sciences 333 (2013) e109–e151
Abstract — WCN 2013 No: 382 Topic: 2 — Movement Disorders Long-term complications of Parkinson's disease — 15th year, 20th year, and beyond; A hospital-based observational study H. Shibayama, S. Kaji, D. Nishida, S. Hirata, F. Katada, S. Sato, T. Fukutake. Neurology, Kameda Medical Center, Kamogawa, Japan Background: Long-term complications of Parkinson's disease (PD) based on regular follow-up in a local neurological center is insufficiently appreciated. Patients and methods: From registered PD patients, we selected those who have been examined in 15th and/or 20th year of the disease (YD) and information about motor status, levodopa equivalent daily dosage (LEDD), hallucination, cognitive disturbance, and dysphagia in each year was collected. Results: Of all PD patients between April 1995 and December 2012 (n = 538, male/female 222/316), 72 patients (13.4%) were examined in their 15th YD (Group PD ≥ 15; age at onset (AO) 58.1 ± 8.1 yearold; modified Hoehn and Yahr stage (mHY) at on/off, 3.3 ± 0.9/3.9 ± 0.9; LEDD 567 ± 239 mg/day) and only 18 patients (3.3%) have taken their 20th YD examination (Group PD ≥ 20; AO 53.4 ± 6.6, mHY at on/off, 3.8 ± 0.9/4.4 ± 0.7; LEDD 703 ± 208 mg/day). Groups PD ≧ 15 and PD ≥ 20 have significantly younger AO (p = 0.0001, p b 0.0001) than patients who have less than 15th YD history (PD b 15, n = 466, AO 67.4 ± 8.8). In Group PD ≥ 15/PD ≥ 20, troublesome hallucination (mainly visual, n = 36/13, 50.0/72.2%) appeared in 15.1 ± 2.8/17.7 ± 2.6th year, cognitive disturbance (n = 27/10, 37.5/55.6%) in 16.0 ± 2.9/18.0 ± 2.5th year, and dysphagia (n = 29/ 13, 40.3/72.2%) in 18.1 ± 3.4/21.0 ± 2.3th year. Follow-up periods after appearance of hallucination, cognitive disturbance, and dysphagia in Group PD ≧ 15 are 4.2 ± 2.7, 3.2 ± 2.6, 1.7 ± 2.1 years, respectively. The longest treated patient had AO at 54 year-old and was in mHY 3/0/ 4.0 in 29th YD without these 3 complications. Conclusions: During long-term treatment of PD, hallucination, cognitive disturbance and swallowing problem appear in near half or more of the patients after 15th YD and seem to contribute to lost follow-up. doi:10.1016/j.jns.2013.07.424
Abstract — WCN 2013 No: 995 Topic: 2 — Movement Disorders Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies I. El-Banhawya, M. El-Toukhyb, I. Fahmya, N.M. Shalabya, M.A. Nadaa, H.S. Shehataa, I. Ismaiela. aNeurology, Cairo University, Cairo, Egypt; b Radiology, Cairo University, Cairo, Egypt Background: Parkinsonism is not a single disease entity as it has a number of causes that differ in the pathology according to the affected brain region. To our knowledge, no previous studies have been published to investigate the role of magnetic resonance spectroscopy (MRS) in the differentiation between idiopathic Parkinson's disease (IPD), druginduced parkinsonism (DIP) and Wilson's disease (WD). Objective: Investigating the role of MRS in the differentiation between various parkinsonian syndromes. Subjects & methods: The study was conducted on 40 parkinsonian patients: 27 patients with IPD, 6 patients with DIP, and 7 patients with WD, and 15 normal control subjects. All were examined using single voxel proton MRS study of striatum, frontal cortex and subcortical white matter. Measured MRS parameters were N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine–phosphocreatine (Cr) and with peak area ratios (NAA/Cr, Cho/Cr, NAA/Cho ratios).
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Results: Patients with parkinsonism had significantly more cortical Cr and less NAA/Cr ratio and more subcortical NAA, Cr, Cho, and Cho/Cr ratios compared to control subjects. DIP patients showed significantly lower striatal Cho/Cr ratio and significantly higher subcortical Cho/Cr ratio compared to IPD. While comparing WD and IPD patients, a significantly lower cortical Cho/Cr ratio and significantly higher subcortical NAA/Cr and cortical NAA/Cho ratios were found in WD. Patients with WD had significantly higher cortical and subcortical NAA/Cho and striatal NAA/Cr ratios compared to DIP patients. Conclusion: MRS can be used as a useful in vivo investigative tool in differentiating between parkinsonian syndromes of various etiologies. doi:10.1016/j.jns.2013.07.425
Abstract — WCN 2013 No: 203 Topic: 2 — Movement Disorders A long-term, open-label study of levodopa–carbidopa intestinal gel in advanced Parkinson's disease patients: safety and motor-symptom endpoints A.J. Espaya, P. Odinb,c, H.H. Fernandezd, R.A. Hausere, D.G. Standaertf, A.E. Langg, V.S. Fungh, F. Klostermanni, W.Z. Robiesonj, K. Chatamraj, J. Beneshj. aUniversity of Cincinnati Academic Health Center, Cincinnati, OH, USA; bKlinikum-Bremerhaven, Bremerhaven, Germany; cSkane University Hospital, Lund, Sweden; dCleveland Clinic, Cleveland, OH, USA; eUniversity of South Florida, Tampa, FL, USA; fUniversity of Alabama at Birmingham, Birmingham, AL, USA; gUniversity of Toronto, Toronto, ON, Canada; h Westmead Hospital and Sydney Medical School, Sydney, NSW, Australia; i Charite-University Medicine Berlin, Berlin, Germany; jAbbVie Inc., North Chicago, IL, USA Background: Motor complications in Parkinson's disease (PD) are associated with pulsatile dopaminergic stimulation. Levodopa– carbidopa intestinal gel (LCIG) provides continuous drug infusion via an intrajejunal percutaneous gastrostomy tube. Objective: To present safety and efficacy results of an international, 54-week, open-label study of LCIG in patients with advanced PD. Patients and methods: PD patients experiencing severe motor fluctuations (≥3 h/d OFF-time) despite optimized medical therapy were enrolled. Individualized LCIG dosing was permitted up to 16 h/d; other PD medications were allowed after 28 days. Efficacy outcomes included OFF-time, ON-time with- and ON-time without troublesome dyskinesias (TSD) (patient-diary-assessed), and UPDRS. AEs were monitored. Results: 272 (76.8%) of 354 patients completed the study. Mean (SD) exposure to LCIG was 328.5 (132.3) days. Mean [SD] OFF-time (baseline = 6.8[2.4] h/d, endpoint = 2.3[2.1], P b .001) and ON-time with TSD (baseline = 1.6[2.0], endpoint = 1.2[2.1], P = .002) were reduced, while ON-time without TSD (baseline = 7.6[2.5], endpoint = 12.4[2.6], P b .001) was increased. UPDRS scores were improved (Part II: change at endpoint = -4.4[6.5]; Part III: change = −7.4[13.2]; P b .001 both). Mean total daily dose of levodopa (mg) was steady (Week 4 = 1613.7; Endpoint = 1620.9). Ninety subjects (27.8%) took only LCIG; 158 (48.8%) took only concomitant oral levodopa formulations. While AEs occurred in 323 (91.2%) patients, most were mild or moderate and transient, and only 27 (7.6%) withdrew due to an AE. Complication of device insertion (34.9%) and abdominal pain (31.2%) was most common. Conclusion: In this large, long-term, prospective study, LCIG provided advanced PD patients with significant and clinically meaningful improvements in motor function and acceptable safety. Support: AbbVie. doi:10.1016/j.jns.2013.07.426
Abstract — WCN 2013 No: 382 Topic: 2 — Movement Disorders Long-term complications of Parkinson's disease — 15th year, 20th year, and beyond; A hospital-based observational study H. Shibayama, S. Kaji, D. Nishida, S. Hirata, F. Katada, S. Sato, T. Fukutake. Neurology, Kameda Medical Center, Kamogawa, Japan Background: Long-term complications of Parkinson's disease (PD) based on regular follow-up in a local neurological center is insufficiently appreciated. Patients and methods: From registered PD patients, we selected those who have been examined in 15th and/or 20th year of the disease (YD) and information about motor status, levodopa equivalent daily dosage (LEDD), hallucination, cognitive disturbance, and dysphagia in each year was collected. Results: Of all PD patients between April 1995 and December 2012 (n = 538, male/female 222/316), 72 patients (13.4%) were examined in their 15th YD (Group PD ≥ 15; age at onset (AO) 58.1 ± 8.1 yearold; modified Hoehn and Yahr stage (mHY) at on/off, 3.3 ± 0.9/3.9 ± 0.9; LEDD 567 ± 239 mg/day) and only 18 patients (3.3%) have taken their 20th YD examination (Group PD ≥ 20; AO 53.4 ± 6.6, mHY at on/off, 3.8 ± 0.9/4.4 ± 0.7; LEDD 703 ± 208 mg/day). Groups PD ≧ 15 and PD ≥ 20 have significantly younger AO (p = 0.0001, p b 0.0001) than patients who have less than 15th YD history (PD b 15, n = 466, AO 67.4 ± 8.8). In Group PD ≥ 15/PD ≥ 20, troublesome hallucination (mainly visual, n = 36/13, 50.0/72.2%) appeared in 15.1 ± 2.8/17.7 ± 2.6th year, cognitive disturbance (n = 27/10, 37.5/55.6%) in 16.0 ± 2.9/18.0 ± 2.5th year, and dysphagia (n = 29/ 13, 40.3/72.2%) in 18.1 ± 3.4/21.0 ± 2.3th year. Follow-up periods after appearance of hallucination, cognitive disturbance, and dysphagia in Group PD ≧ 15 are 4.2 ± 2.7, 3.2 ± 2.6, 1.7 ± 2.1 years, respectively. The longest treated patient had AO at 54 year-old and was in mHY 3/0/ 4.0 in 29th YD without these 3 complications. Conclusions: During long-term treatment of PD, hallucination, cognitive disturbance and swallowing problem appear in near half or more of the patients after 15th YD and seem to contribute to lost follow-up. doi:10.1016/j.jns.2013.07.424
Abstract — WCN 2013 No: 995 Topic: 2 — Movement Disorders Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies I. El-Banhawya, M. El-Toukhyb, I. Fahmya, N.M. Shalabya, M.A. Nadaa, H.S. Shehataa, I. Ismaiela. aNeurology, Cairo University, Cairo, Egypt; b Radiology, Cairo University, Cairo, Egypt Background: Parkinsonism is not a single disease entity as it has a number of causes that differ in the pathology according to the affected brain region. To our knowledge, no previous studies have been published to investigate the role of magnetic resonance spectroscopy (MRS) in the differentiation between idiopathic Parkinson's disease (IPD), druginduced parkinsonism (DIP) and Wilson's disease (WD). Objective: Investigating the role of MRS in the differentiation between various parkinsonian syndromes. Subjects & methods: The study was conducted on 40 parkinsonian patients: 27 patients with IPD, 6 patients with DIP, and 7 patients with WD, and 15 normal control subjects. All were examined using single voxel proton MRS study of striatum, frontal cortex and subcortical white matter. Measured MRS parameters were N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine–phosphocreatine (Cr) and with peak area ratios (NAA/Cr, Cho/Cr, NAA/Cho ratios).
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Results: Patients with parkinsonism had significantly more cortical Cr and less NAA/Cr ratio and more subcortical NAA, Cr, Cho, and Cho/Cr ratios compared to control subjects. DIP patients showed significantly lower striatal Cho/Cr ratio and significantly higher subcortical Cho/Cr ratio compared to IPD. While comparing WD and IPD patients, a significantly lower cortical Cho/Cr ratio and significantly higher subcortical NAA/Cr and cortical NAA/Cho ratios were found in WD. Patients with WD had significantly higher cortical and subcortical NAA/Cho and striatal NAA/Cr ratios compared to DIP patients. Conclusion: MRS can be used as a useful in vivo investigative tool in differentiating between parkinsonian syndromes of various etiologies. doi:10.1016/j.jns.2013.07.425
Abstract — WCN 2013 No: 203 Topic: 2 — Movement Disorders A long-term, open-label study of levodopa–carbidopa intestinal gel in advanced Parkinson's disease patients: safety and motor-symptom endpoints A.J. Espaya, P. Odinb,c, H.H. Fernandezd, R.A. Hausere, D.G. Standaertf, A.E. Langg, V.S. Fungh, F. Klostermanni, W.Z. Robiesonj, K. Chatamraj, J. Beneshj. aUniversity of Cincinnati Academic Health Center, Cincinnati, OH, USA; bKlinikum-Bremerhaven, Bremerhaven, Germany; cSkane University Hospital, Lund, Sweden; dCleveland Clinic, Cleveland, OH, USA; eUniversity of South Florida, Tampa, FL, USA; fUniversity of Alabama at Birmingham, Birmingham, AL, USA; gUniversity of Toronto, Toronto, ON, Canada; h Westmead Hospital and Sydney Medical School, Sydney, NSW, Australia; i Charite-University Medicine Berlin, Berlin, Germany; jAbbVie Inc., North Chicago, IL, USA Background: Motor complications in Parkinson's disease (PD) are associated with pulsatile dopaminergic stimulation. Levodopa– carbidopa intestinal gel (LCIG) provides continuous drug infusion via an intrajejunal percutaneous gastrostomy tube. Objective: To present safety and efficacy results of an international, 54-week, open-label study of LCIG in patients with advanced PD. Patients and methods: PD patients experiencing severe motor fluctuations (≥3 h/d OFF-time) despite optimized medical therapy were enrolled. Individualized LCIG dosing was permitted up to 16 h/d; other PD medications were allowed after 28 days. Efficacy outcomes included OFF-time, ON-time with- and ON-time without troublesome dyskinesias (TSD) (patient-diary-assessed), and UPDRS. AEs were monitored. Results: 272 (76.8%) of 354 patients completed the study. Mean (SD) exposure to LCIG was 328.5 (132.3) days. Mean [SD] OFF-time (baseline = 6.8[2.4] h/d, endpoint = 2.3[2.1], P b .001) and ON-time with TSD (baseline = 1.6[2.0], endpoint = 1.2[2.1], P = .002) were reduced, while ON-time without TSD (baseline = 7.6[2.5], endpoint = 12.4[2.6], P b .001) was increased. UPDRS scores were improved (Part II: change at endpoint = -4.4[6.5]; Part III: change = −7.4[13.2]; P b .001 both). Mean total daily dose of levodopa (mg) was steady (Week 4 = 1613.7; Endpoint = 1620.9). Ninety subjects (27.8%) took only LCIG; 158 (48.8%) took only concomitant oral levodopa formulations. While AEs occurred in 323 (91.2%) patients, most were mild or moderate and transient, and only 27 (7.6%) withdrew due to an AE. Complication of device insertion (34.9%) and abdominal pain (31.2%) was most common. Conclusion: In this large, long-term, prospective study, LCIG provided advanced PD patients with significant and clinically meaningful improvements in motor function and acceptable safety. Support: AbbVie. doi:10.1016/j.jns.2013.07.426