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2. Worldwide barriers to genetic testing for movement disorders

Author

Gatto, E. M., Walker, R. H., Gonzalez, C., Cesarini, M., Cossu, G., Stephen, C. D., Balint, B., Rodriguez-Violante, M., Jankovic, J., Morgante, F., Jinnah, H. A., Albanese, A., Amorin, I., Bhatia, K., Brandabur, M., Canals, F., Cardoso, F., Cardozo, A., Carvalho, V., Chade, A., Chana, P., Darling, A., Correia Guedes, L., De la Cerda, A., de Koning-Tijssen, M., Della Coletta, M. V., Duquette, A., Espay, A., Etcheverry, J., Ferreira, J., Friedman, J., Fung, V., Ganos, C., Ruiz, P. G., Gershanik, O., Gross, K. B. V., Han-Joon, K., Kaji, R., Kotschet, K., Rosa, A. L. D., Litvan, I., Lubarr, N., Marano, M., Josep Marti, M., Martinez Ramirez, D., Miyasaki, J., Munchau, A., Chesta, D. M., Pal, P., Peralta, M. C., Phielipp, N., Maria Riboldi, G., Oroz, M. C. R., Rodriguez-Porcel, F., Sarva, H., Schoels, L., Stamelou, M., and Uribe Roca, C.

Subjects
Asia, Movement disorders, Disease, Limited access, Middle East, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Genetic Testing, 030212 general & internal medicine, Public funding, Genetic testing, Dystonia, Movement Disorders, medicine.diagnostic_test, business.industry, Chorea, medicine.disease, Europe, Neurology, Neurology (clinical), medicine.symptom, business, chorea, dystonia, genetic and inherited disorders, genetic diagnosis, genetic testing, movement disorders, Parkinson's disease, whole exome sequencing, 030217 neurology & neurosurgery, Demography
Abstract

Author(s): Gatto, Emilia M; Walker, Ruth H; Gonzalez, Claudio; Cesarini, Martin; Cossu, Giovanni; Stephen, Christopher D; Balint, Bettina; Rodriguez-Violante, Mayela; Jankovic, Joseph; Morgante, Francesca; Jinnah, Hyder A; Rare Movement Disorders Study Group of the International Parkinson Disease, Movement Disorders Society | Abstract: Background and purposeDespite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization.MethodsThe Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members.ResultsSurvey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe.ConclusionsThis survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.

Published
2021

9. A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease

Author

Olanow, Cw, Rascol, O, Hauser, R, Feigin, Pd, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E, ADAGIO STUDY INVESTIGATORS, Collaborators, Bueri, J, Garretto, N, Gershanik, O, Giannaula, R, Micheli, F, Wolf, E, Guttman, M, Hobson, D, Jog, M, King, D, Mendis, T, Miyasaki, J, Panisset, M, Pourcher, E, Rajput, A, Ranawaya, R, Tsui, J, Cesaro, P, Damier, P, Destee, A, Durif, F, Slaoui, T, Tison, F, Viallet, F, Deuschl, G, Gasser, T, Ludolph, A, Oehlwein, C, Przuntek, H, Reifschneider, G, Schnitzler, A, Trenkwalder, C, Bokor, M, Katona, A, Lajtos, J, Nikl, J, Takats, A, Valikovics, A, Badarny, S, Djaldetti, R, Giladi, N, Hassin, S, Rabey, Jm, Reches, A, Schwartz, M, Wirguin, I, Albanese, A, Bentivoglio, A, Bonuccelli, U, Calzetti, S, Comi, G, Curatola, L, Ferrarese, C, Lamberti, P, Marconi, R, Martignoni, E, Meco, Giuseppe, Ruggieri, Stefano, Bomhof, Ma, Hovestadt, A, Krul, Jm, Leenders, Kl, Cunha, L, Ferreira, J, Bajenaru, Oa, Carciumaru, N, Bulboaca, Ac, Pascu, I, Simu, M, Calopa, M, FERNÁNDEZ GARCÍA JM, Kulisevsky, J, Linazasoro, C, Miquel, F, Posada, Ij, Martí, Mj, Burn, D, Macmahon, D, Barker, R, Allen, N, Barbour, P, Bertoni, J, Bharucha, K, Bose, S, Drasby, E, Elble, R, Elmer, L, Evans, B, Factor, S, Fernandez, H, Friedman, J, Hull, K, Golbe, L, Goudreau, J, Guttuso, T, Hassan, M, Hermanowicz, N, Houser, M, Hurtig, H, Isaacson, S, Jennings, D, Kompoliti, A, Morgan, J, Murphy, J, Nausieda, P, Pahwa, R, Parashos, S, O'Suilleabhain, P, Racette, B, Reich, S, Roberts, J, Rothstein, T, Sahay, A, SAINT HILAIRE, M, Schiess, M, Scott, B, Shahed, J, Simuni, T, Singer, C, Smith, R, Struck, L, Sutton, J, Swope, D, Tagliati, M, Tetrud, J, Togasaki, D, Watts, R., Olanow, C, Rascol, O, Hauser, R, Feigin, P, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E, ADAGIO Study, I, Bueri, J, Garretto, N, Gershanik, O, Giannaula, R, Micheli, F, Wolf, E, Guttman, M, Hobson, D, Jog, M, King, D, Mendis, T, Miyasaki, J, Panisset, M, Pourcher, E, Rajput, A, Ranawaya, R, Tsui, J, Cesaro, P, Damier, P, Destee, A, Durif, F, Slaoui, T, Tison, F, Viallet, F, Deuschl, G, Gasser, T, Ludolph, A, Oehlwein, C, Przuntek, H, Reifschneider, G, Schnitzler, A, Trenkwalder, C, Bokor, M, Katona, A, Lajtos, J, Nikl, J, Takats, A, Valikovics, A, Badarny, S, Djaldetti, R, Giladi, N, Hassin, S, Rabey, J, Reches, A, Schwartz, M, Wirguin, I, Albanese, A, Bentivoglio, A, Bonuccelli, U, Calzetti, S, Comi, G, Curatola, L, Ferrarese, C, Lamberti, P, Marconi, R, Martignoni, E, Meco, G, Ruggieri, S, Bomhof, M, Hovestadt, A, Krul, J, Leenders, K, Cunha, L, Ferreira, J, Bajenaru, O, Carciumaru, N, Bulboaca, A, Pascu, I, Simu, M, Calopa, M, Fernández García, J, Kulisevsky, J, Linazasoro, C, Miquel, F, Posada, I, Martí, M, Burn, D, Macmahon, D, Barker, R, Allen, N, Barbour, P, Bertoni, J, Bharucha, K, Bose, S, Drasby, E, Elble, R, Elmer, L, Evans, B, Factor, S, Fernandez, H, Friedman, J, Hull, K, Golbe, L, Goudreau, J, Guttuso, T, Hassan, M, Hermanowicz, N, Houser, M, Hurtig, H, Isaacson, S, Jennings, D, Kompoliti, A, Morgan, J, Murphy, J, Nausieda, P, Pahwa, R, Parashos, S, O'Suilleabhain, P, Racette, B, Reich, S, Roberts, J, Rothstein, T, Sahay, A, Saint Hilaire, M, Schiess, M, Scott, B, Shahed, J, Simuni, T, Singer, C, Smith, R, Struck, L, Sutton, J, Swope, D, Tagliati, M, Tetrud, J, Togasaki, D, and Watts, R

Subjects
Adult, Male, medicine.medical_specialty, Monoamine Oxidase Inhibitors, Parkinson's disease, Neuroprotective Agent, Severe disease, Placebo, Severity of Illness Index, Placebo group, Drug Administration Schedule, Central nervous system disease, Double blind, chemistry.chemical_compound, Double-Blind Method, Severity of illness, Humans, Rasagiline, Medicine, Monoamine Oxidase Inhibitor, Aged, Dose-Response Relationship, Drug, business.industry, Indan, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, Surgery, Neuroprotective Agents, chemistry, Research Design, Anesthesia, Indans, Female, business, Human
Abstract

BACKGROUND: A therapy that slows disease progression is the major unmet need in Parkinson's disease. METHODS: In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72. RESULTS: Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P

Published
2009

10. A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease

Author

Kieburtz, K, Landwehrmeyer, GB, Cudkowicz, M, Dorsey, ER, Feigin, A, Hunt, V, Kayson, E, McDermott, M, Noonberg, S, Seitz, W, Soliveri, P, Walker, F, Burgunder, J-M, Romero, I, Magara, A, Stebler, Y, Rickards, H, Wright, J, De Souza, J, Barker, RA, Mason, S, Di Pietro, A, Goodman, A, O'Keeffe, D, Langlois, M, Ferland, G, Verret, L, Chouinard, S, Paris, S, LePage, C, Nemeth, AH, Merritt, C, Cox, C, Astbury, T, Murphy, S, Ahmed, A, St Marie, P, Berila, RA, Kubu, C, Segro, V, Kumar, R, Erickson, D, Schneiders, J, Frucht, S, Wasserman, P, Moskowitz, C, Scott, B, Perry-Trice, P, Wyne, S, Parida, D, Redaelli, V, Soltan, W, Robowski, P, Nowak, M, Schinwelski, M, Dziadkiewicz, A, Andrews, T, Ruddy, D, Dougherty, A, Boelmans, K, Schmalfeld, J, Muenchau, A, Zittel, S, Mallonee, W, Suter, G, Tan, J, Seeberger, L, Harris, J, Champion, J, Wojcieszek, J, Belden, J, Price, K, Hughes-Gay, M, Sprehn, G, Squitieri, F, Martino, T, De Gregorio, F, De Nicola, A, Elifani, F, Rosenblatt, A, Yoritomo, N, Margolis, R, Nichols, P, Palhagen, SE, Hoglund, AV, Paucar, M, Reza-Soltani, TW, Beister, A, Raab, T, Kieni, J, Schrenk, C, Banaszkiewicz, K, Misztela, J, Wojcik, M, Szczygiel, E, Golosz, M, Rudzinska, M, Roos, RAC, van den Bogaard, SJA, Bos, R, Booij, SJ, Hyson, C, Megens, J, Makaji, E, Jenkins, M, Hersch, S, Maya, S, Dresser, C, Rosas, D, Blindauer, K, Schindler, C, Hung, S, McNees, AA, Tabrizi, S, Novak, M, Say, M, Patel, A, Panegyres, P, Lewis, N, Jukich, S, Faull, C, Hjermind, LE, Jakobsen, O, Vogel, A, Nielsen, TR, Nielsen, JE, Kostyk, S, Seward, A, Agrawal, P, Kraakevik, J, Hogarth, P, Wilson, A, Lear, J, Kraus, PH, Saft, C, Steiner, T, Hoffmann, R, Stamm, C, Schollhammer, J, Uhl, I, Kaminski, B, O'Donovan, K, Quarrell, O, Nevitt, L, Kipps, C, Hare, A, Gunner, K, Hayward, E, Nance, M, Hamerlinck, J, Wielinski, C, Yastrubetskaya, O, Chiu, E, Chua, P, Mannaa, B, de Tommaso, M, Serpino, C, Cormio, C, Sciruicchio, V, De Michele, G, Di Maio, L, Russo, CV, Sacca, F, Salvatore, E, Tucci, T, Wolz, M, Klingelhoefer, L, Wolz, A, Schmidt, S, Storch, A, Spruth, E, Thiel, S, Neumann, B, Gelderblom, H, Priller, J, Sass, C, Probst, D, Werner, C, Leavitt, BR, Coleman, A, Raymond, L, Wheelock, V, Tempkin, T, Baynes, K, Hermanowicz, N, Niswonger, S, Haske-Palomino, M, Bordelon, Y, Gratiano, A, Johnson, A, Corey-Bloom, J, Goldstein, J, Peavy, G, Geschwind, M, Gooblar, J, Barton, C, Fernandez, H, Rodriguez, R, Suelter, M, Daniels, M, Romrell, J, Swartz, C, Beglinger, L, Epping, E, Waterman, E, Smith, MM, Dubinsky, R, Dubinsky, H, Gray, C, Craufurd, D, Howard, E, Jones, M, Murphy, H, Anderson, K, Nickerson, C, De Santo, J, Rigaud, T, Zappala, N, Robottom, B, Singer, C, Quesada, M, Rodriguez-Spengler, K, Cardenache, RH, Reilmann, R, Bohlen, S, Hoelzner, E-M, Colcher, A, Maccarone, H, Altin, L, Siderowf, A, Greenamyre, TJ, Lucarelli, N, Ivanco, L, Marshall, F, Hickey, C, Deuel, L, Biglan, K, Sussmuth, SD, Orth, M, Trautmann, S, Eschenbach, C, Samii, A, Macaraeg, A, Zielonka, D, Ciesielska, A, Marcinkowski, JT, Sempolowicz, J, Karaskiewicz, H, O'Neill, C, Haq, I, Witkowski, G, Antczak, J, Rola, R, Richter, P, Rakowicz, M, Jachinska, K, Criswell, S, Deppen, P, Wharton, K, Mahant, N, McCusker, E, Griffith, J, Loy, C, Stewart, L, Fisher, D, Holt, D, Orme, C, Watts, A, Weber, J, White, K, Hauser, RA, Albin, R, Coffey, C, Fischer, W, Miyasaki, J, Investigators, HORIZON, HORIZON Investigators of the Huntington Disease Study, Group, European Huntington's Disease, Network, Salvatore, Elena, DE MICHELE, Giuseppe, and Sacca', Francesco

Subjects
Male, medicine.medical_specialty, Indoles, Placebo-controlled study, Comorbidity, Placebo, Severity of Illness Index, law.invention, Placebos, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Dementia, Humans, Donepezil, Adverse effect, Rivastigmine, Psychiatric Status Rating Scales, business.industry, Australia, Latrepirdine, Middle Aged, medicine.disease, Huntington Disease, Treatment Outcome, North America, Physical therapy, Female, Neurology (clinical), business, medicine.drug
Abstract

BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26). INTERVENTION Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks. MAIN OUTCOME MEASURES The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety. RESULTS The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P = .39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P = .84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00920946.

Published
2013

11. Task force report on scales to assess dyskinesia in Parkinson's disease: critique and recommendations

Author

Colosimo, Carlo, Martinez Martin, P., Fabbrini, Giovanni, Hauser, R. A., Merello, M., Miyasaki, J., Poewe, W., Sampaio, C., Rascol, O., Stebbins, G. T., Schrag, A., and Goetz, C. G.

Subjects
validity, Dyskinesia, Drug-Induced, reliability, Psychometrics, Reproducibility of Results, Parkinson Disease, parkinson's disease, rating scales, dyskinesia, clinimetrics, Severity of Illness Index, Disability Evaluation, Evaluation Studies as Topic, Surveys and Questionnaires, Humans
Abstract

Drug-induced dyskinesia is a common phenomenon in Parkinson's disease (PD) and is often socially as well as physically disabling for patients. The Movement Disorders Society commissioned a task force to assess available clinical rating scales, critique their clinimetric properties, and make recommendations regarding their clinical utility. A task force composed six clinical researchers who systematically searched the literature for scales measuring dyskinesia in PD, evaluated the scales' previous use, performance parameters, and quality of validation data (if available). A scale was designated "Recommended" if the scale has been used in clinical studies beyond the group that developed it, has been specifically used in PD reports, and if clinimetric studies have established that it is a valid, reliable, and sensitive. "Suggested" scales met two of the above criteria and those meeting one were "Listed." Based on the systematic review, eight rating scales for dyskinesia that have either been validated or used in PD were identified. These were the Abnormal Involuntary Movement Scale (AIMS), The Unified Parkinson's Disease Rating Scale (UPDRS) part IV, the Obeso Dyskinesia Rating Scale, the Rush Dyskinesia Rating Scale, the Clinical Dyskinesia Rating Scale (CDRS), the Lang-Fahn Activities of Daily Living Dyskinesia Scale, the Parkinson Disease Dyskinesia Scale (PDYS-26), and the Unified Dyskinesia Rating Scale (UDysRS). Based on this review, at present two of the reviewed dyskinesia scales (AIMS and the Rush Dyskinesia Rating Scale) fulfill criteria for Recommended for use in PD populations, albeit weakly so; all of the remaining met criteria to be Suggested. However, the two most recent scales (PDYS-26 and UDysRS) have excellent clinimetric properties and appear to provide a reliable and valid assessment tool of dyskinesia in PD. If they are used successfully beyond the groups that developed them, both have the potential to be re-ranked as Recommended. As further testing of these scales in PD is warranted, no new scales are needed until the available scales are fully tested clinimetrically.

Published
2010

14. A double-blind, delayed-start trial of rasagiline in Parkinson's disease

Author

Olanow, C, Rascol, O, Hauser, R, Feigin, P, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E, ADAGIO Study, I, Bueri, J, Garretto, N, Gershanik, O, Giannaula, R, Micheli, F, Wolf, E, Guttman, M, Hobson, D, Jog, M, King, D, Mendis, T, Miyasaki, J, Panisset, M, Pourcher, E, Rajput, A, Ranawaya, R, Tsui, J, Cesaro, P, Damier, P, Destee, A, Durif, F, Slaoui, T, Tison, F, Viallet, F, Deuschl, G, Gasser, T, Ludolph, A, Oehlwein, C, Przuntek, H, Reifschneider, G, Schnitzler, A, Trenkwalder, C, Bokor, M, Katona, A, Lajtos, J, Nikl, J, Takats, A, Valikovics, A, Badarny, S, Djaldetti, R, Giladi, N, Hassin, S, Rabey, J, Reches, A, Schwartz, M, Wirguin, I, Albanese, A, Bentivoglio, A, Bonuccelli, U, Calzetti, S, Comi, G, Curatola, L, Ferrarese, C, Lamberti, P, Marconi, R, Martignoni, E, Meco, G, Ruggieri, S, Bomhof, M, Hovestadt, A, Krul, J, Leenders, K, Cunha, L, Ferreira, J, Bajenaru, O, Carciumaru, N, Bulboaca, A, Pascu, I, Simu, M, Calopa, M, Fernández García, J, Kulisevsky, J, Linazasoro, C, Miquel, F, Posada, I, Martí, M, Burn, D, Macmahon, D, Barker, R, Allen, N, Barbour, P, Bertoni, J, Bharucha, K, Bose, S, Drasby, E, Elble, R, Elmer, L, Evans, B, Factor, S, Fernandez, H, Friedman, J, Hull, K, Golbe, L, Goudreau, J, Guttuso, T, Hassan, M, Hermanowicz, N, Houser, M, Hurtig, H, Isaacson, S, Jennings, D, Kompoliti, A, Morgan, J, Murphy, J, Nausieda, P, Pahwa, R, Parashos, S, O'Suilleabhain, P, Racette, B, Reich, S, Roberts, J, Rothstein, T, Sahay, A, Saint Hilaire, M, Schiess, M, Scott, B, Shahed, J, Simuni, T, Singer, C, Smith, R, Struck, L, Sutton, J, Swope, D, Tagliati, M, Tetrud, J, Togasaki, D, Watts, R, Olanow, CW, Feigin, PD, ADAGIO Study Investigators, Rabey, JM, FERRARESE, CARLO, Bomhof, MA, Krul, JM, Leenders, KL, Bajenaru, OA, Bulboaca, AC, Fernández García, JM, Posada, IJ, Martí, MJ, MacMahon, D, Watts, R., Olanow, C, Rascol, O, Hauser, R, Feigin, P, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E, ADAGIO Study, I, Bueri, J, Garretto, N, Gershanik, O, Giannaula, R, Micheli, F, Wolf, E, Guttman, M, Hobson, D, Jog, M, King, D, Mendis, T, Miyasaki, J, Panisset, M, Pourcher, E, Rajput, A, Ranawaya, R, Tsui, J, Cesaro, P, Damier, P, Destee, A, Durif, F, Slaoui, T, Tison, F, Viallet, F, Deuschl, G, Gasser, T, Ludolph, A, Oehlwein, C, Przuntek, H, Reifschneider, G, Schnitzler, A, Trenkwalder, C, Bokor, M, Katona, A, Lajtos, J, Nikl, J, Takats, A, Valikovics, A, Badarny, S, Djaldetti, R, Giladi, N, Hassin, S, Rabey, J, Reches, A, Schwartz, M, Wirguin, I, Albanese, A, Bentivoglio, A, Bonuccelli, U, Calzetti, S, Comi, G, Curatola, L, Ferrarese, C, Lamberti, P, Marconi, R, Martignoni, E, Meco, G, Ruggieri, S, Bomhof, M, Hovestadt, A, Krul, J, Leenders, K, Cunha, L, Ferreira, J, Bajenaru, O, Carciumaru, N, Bulboaca, A, Pascu, I, Simu, M, Calopa, M, Fernández García, J, Kulisevsky, J, Linazasoro, C, Miquel, F, Posada, I, Martí, M, Burn, D, Macmahon, D, Barker, R, Allen, N, Barbour, P, Bertoni, J, Bharucha, K, Bose, S, Drasby, E, Elble, R, Elmer, L, Evans, B, Factor, S, Fernandez, H, Friedman, J, Hull, K, Golbe, L, Goudreau, J, Guttuso, T, Hassan, M, Hermanowicz, N, Houser, M, Hurtig, H, Isaacson, S, Jennings, D, Kompoliti, A, Morgan, J, Murphy, J, Nausieda, P, Pahwa, R, Parashos, S, O'Suilleabhain, P, Racette, B, Reich, S, Roberts, J, Rothstein, T, Sahay, A, Saint Hilaire, M, Schiess, M, Scott, B, Shahed, J, Simuni, T, Singer, C, Smith, R, Struck, L, Sutton, J, Swope, D, Tagliati, M, Tetrud, J, Togasaki, D, Watts, R, Olanow, CW, Feigin, PD, ADAGIO Study Investigators, Rabey, JM, FERRARESE, CARLO, Bomhof, MA, Krul, JM, Leenders, KL, Bajenaru, OA, Bulboaca, AC, Fernández García, JM, Posada, IJ, Martí, MJ, MacMahon, D, and Watts, R.

Abstract

BACKGROUND: A therapy that slows disease progression is the major unmet need in Parkinson's disease. METHODS: In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72. RESULTS: Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P<0.001). All three end points were not met with rasagiline at a dose of 2 mg per day, since the change in the UPDRS score between baseline

Published
2009

26. Invited Article: Neurology and quality improvement: An introduction

Author

Bever, C. T., primary, Holloway, R. G., additional, Iverson, D. J., additional, Dubinsky, R. M., additional, Richardson, R. M., additional, Sheffield, J. K., additional, Wang, D. Z., additional, Franklin, G. M., additional, Miyasaki, J. M., additional, Tonn, S. T., additional, and Stevens, J. C., additional

Published
2008
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34. Subthalamic DBS replaces levodopa in Parkinson's disease: Two-year follow-up

Author

Lang, A.E., primary, Kleiner-Fisman, G., additional, Saint-Cyr, J.A., additional, Miyasaki, J., additional, Lozano, A., additional, Houeto, J.L., additional, Mesnage, V., additional, Welter, M.L., additional, Mallet, L., additional, Agid, Y., additional, Bejjani, B.P., additional, Berney, A., additional, Ghika, J., additional, Villemure, J.G., additional, and Vingerhoets, F.J. G., additional

Published
2003
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42. Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study.

Author

Steeves, T. D. L., Miyasaki, J., Zurowski, M., Lang, A. E., Pellecchia, G., Van Eimeren, T., Rusjan, P., Houle, S., and Strafella, A. P.

Subjects
*DRUG therapy for Parkinson's disease, *PARKINSON'S disease patients, *IMPULSE control disorders, *DOPAMINE, *DOPAMINERGIC mechanisms, *POSITRON emission tomography, *NEUROBIOLOGY, *PATHOLOGICAL physiology
Abstract

Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinsons disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinsons disease patients with impulse control disorders. We describe results of a [11C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinsons disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinsons disease patients may provide a model into the pathophysiology of this disorder. [ABSTRACT FROM AUTHOR]

Published
2009
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47. On the cause of hyporeflexia in the HolmesAdie syndrome

Author

Miyasaki, J. M., Ashby, P., Sharpe, J. A., and Fletcher, W. A.

Abstract

Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Adie patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Adie syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons.

Published
1988

50. AAN guidelines

Author

Getchius, T.S.D., Moses, L.K., French, J., Gronseth, G.S., England, J.D., and Miyasaki, J.

Published
2010
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