nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2011-341nnp-101Research ArticleORIGINAL INVESTIGATIONSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ И МЕТОДИКИParkinson's disease fatigability and its correction with the dopamine receptor agonist pramipexoleУтомляемость при болезни Паркинсона и ее коррекция агонистом дофаминовых рецепторов прамипексоломНодельМ. Р.NodelM. R.

Department of Nervous Diseases

nodell_m@yahoo.comКафедра нервных болезней Первого МГМУ им. И.М. СеченоваРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation20111412201134NO4 (2011)2226Copyright © Nodel M.R., 20112011Нодель М.Р.Nodel M.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/101

Fatigability is a common nonmotor symptom in Parkinson's disease (PD), which worsens quality of life in patients. Objective: to analyze the association of fatigability with the duration of PD and the degree of movement and neuropsychic (depression, nocturnal sleep disorders, daytime sleepiness) disorders; to evaluate changes in the manifestations of fatigability during therapy with the dopamine receptor agonist pramipexole (Mirapex). Patients and methods. Sixty patients with PD (disease duration 6.02±3.47 years; stage 2.68±0.62) without dementia were examined using the PD fatigue scale (PFS-16), unified PD rating scale (Part 2), the Beck depression inventory, the PD sleep scale, and the Epworth sleeping scale. Results. 66% of the patients were found to consider fatigability to be one of the three most daily life-limiting manifestations of the disease. The integrated rating of fatigability significantly correlated with total depression scores and sleep scores. During pramipexole therapy, there were statistically significant positive changes in fatigability, which did not correlate with those in motor functions, depression, and sleep problems. It is concluded that fatigability substantially impairs the daily activities of patients with PD and is associated with neuropsychic symptoms to a greater extent than with the degree of movement disorders in PD. This may be due to both the common pathophysiological mechanisms of these abnormalities and their comorbidity in PD. The fact that there is no significant association of the time course of changes in fatigability with alterations in the parameters of other neuropsychic functions during therapy conceivably indicated the independent genesis of this symptom.

Утомляемость – частый недвигательный симптом болезни Паркинсона (БП), значимо ухудшающий качество жизни пациентов в пожилом возрасте. Цель исследования – анализ взаимосвязи утомляемости с длительностью БП, тяжестью двигательных расстройств, показателями нервно-психических нарушений (депрессией, нарушениями ночного сна, дневной сонливостью); оценка динамики проявлений утомляемости на фоне терапии агонистом дофаминовых рецепторов прамипексолом (мирапекс). Пациенты и методы. Обследовано 60 пациентов с БП (длительность болезни – 6,02±3,47 года, стадия – 2,68±0,62) без деменции. Применялись шкала утомляемости при БП (PFS-16); Унифицированная шкала оценки БП (УШОБП, часть 2); опросник депрессии Бека; шкала оценки сна при БП (PDSS), шкала сонливости Эпворта. Результаты исследования. Установлено, что 66% пациентов считают утомляемость одним из трех наиболее ограничивающих повседневную жизнь проявлений болезни. Интегративная оценка утомляемости достоверно коррелировала с суммарным показателем депрессии, показателями шкалы оценки сна. На фоне терапии прамипексолом отмечена статистически значимая положительная динамика утомляемости, которая не соотносилась с динамикой показателей двигательных функций, депрессии, нарушений сна. Сделан вывод, что утомляемость значимо нарушает повседневную активность пациентов с БП и в большей степени связана с нервно-психическими симптомами, чем со степенью тяжести двигательных нарушений БП. Это может быть обусловлено как общими патофизиологическими механизмами этих расстройств, так и их коморбидностью при БП. Отсутствие достоверной связи динамики утомляемости с изменениями показателей других нервно-психических функций на фоне терапии, возможно, указывает на самостоятельный генез данного симптома.

болезнь ПаркинсонаутомляемостьпрамипексолParkinson's diseasefatigabilitypramipexoleReferences<div><p>Нодель М.Р., Яхно Н.Н. Нервно-психические нарушения болезни Паркинсона. Неврол нейропсихиатр психосом 2009;2:3–8.</p><p>McKinlay A., Grace R.C., Dalrymple-Alford J.C. et al. A profile of neuropsychiatric problems and their relationship to quality of life for patients with Parkinsons disease. Park Relat Dis 2008;14:37–42.</p><p>Soh Sze-Ee, Morris Meg E., Mc-inley J.L. Determinants of health-related quality of life in Parkinsons disease: a systematic review. Park Relat Dis 2011;17:1–9.</p><p>Martinez-Martin P., Rodriguez-Blazquez C., Kurtis M.M. et al. The impact of non-motor symptoms on health-related quality of life in Parkinsons disease. Mov Dis 2011;26(3):399–406.</p><p>Gallagher D.A., Lees A.J., Shrag A. What are the most important non-motor symptoms in patients with Parkinsons disease and are we missing them- Mov Dis 2011;25(15):2493–500.</p><p>Елагина И.А., Шмидт Т.Е. Утомляемость при рассеянном склерозе. Неврол журн 2008;1:37–45.</p><p>Hoehn M.M., Yahr M.D. Parkinsonism: onset, progression and mortality. Neurology 1967;17:427–42.</p><p>Alves G., Wentzel-Larsen T., Larsen J.P. Is fatigue an independent and persistent symptom in patients with Parkinsons disease. Neurology 2004;63:1908–11.</p><p>Friedman J.H., Friedman H. Fatigue in Parkinsons disease: a nine-year follow-up. Mov Dis 2001;16:1120–2.</p><p>Herlofson K., Larsen J.P. Measuring fatigue in patients with Parkinsons disease-the Fatigue Severity Scale. Eur J Neurol 2002;9:595–600.</p><p>Van Hilten J.J., Weggman M., Velde E.A. Sleep , excessive daytime sleepiness and fatigue in Parkinsons disease. J Neural Transm Park Dis Dement Sect 1993;5:235–44.</p><p>Schifitto G., Friedman J.H., Oakes D. et al.. Fatigue in levodopa-naive subjects with Parkinsons disease. Neurology 2008;71:481–5.</p><p>Van Hilten J.J., Weggman M., Velde E.A. Sleep, excessive daytime sleepiness and fatigue in Parkinsons disease. J Neural Transm Park Dis Dement Sect 1993;5:235–44.</p><p>Van Hilten J.J., Hoogland G., Velde E.A. Diurnal effects of motor activity and fatigue in Parkinsons disease. J Neurol Neurosurg Psychiatr 1993;56:874–7.</p><p>Chaudhuri A., Behan P.O. Fatigue and basal ganglia. J Neurol Sci 2000;179:34–42.</p><p>Abe K., Takanashi M., Yanagihara T. Fatigue in patients with Parkinsons disease. Behav Neurol 2000;12:103–6.</p><p>Ziv I., Avraham M., Michaelov Y. et al. Enhanced fatigue during motor performance in patients with Parkinson’s disease. Neurology 1998;51:1583–6.</p><p>Havlicova E., Rosenberger J., Nagyova I. et al. Clinical and psychosocial factors associated with fatigue in patients with Parkinsons disease. Park Relat Dis 2008;14:187–92.</p><p>Nakamura T., Hirayama M., Hara T. et al. Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinsons diseaseMov Dis 2011;26:1869–74.</p><p>Herlofson K., Larsen J.P. The influence fatigue on health-related quality of life in patients with Acta Neurol Scand 2003;107:1–6.</p><p>Karlsen K., Larsen J.P., Tandberg E. et.al. Fatigue in patients with Parkinsons disease. Mov Dis 1999;14:237–41.</p><p>Shulman L.M., Taback R.L., Bean J. et.al. Comorbidity of the nonmotor symtoms of Parkinsons disease. Mov Dis 2001;16:507–10.</p><p>Chaudhuri K.R., Pal S., Marco Di A. et.al. The sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinsons disease. J Neurol Neurosurg Psychiatr 2002;73:629–35.</p><p>Alves G., Wentzel-Larsen T., Larsen J.P. Is fatigue an independent and persistent symptom in patients with Parkinsons disease. Neurology 2004;63:1908–11.</p><p>Valko P.O., Waldvogel D., Weller M. et al. Fatigue and excessive daytime sleepness in idiopathic Parkinsons disease differently correlate with motorsymtoms, depression and dopaminergic therapy. Eur J Neurol 2010;17:1428–35.</p><p>Lemke M.R., Raethjen J. Depression and Parkinsons disease- pathophysiology, diagnosis, treatment. 1st ed. Bremen: UNI-MED, 2007;27–8.</p><p>Brown R.G., Dittner A., Findley L. et al. The Parkinson fatigue scale. Park Relat Dis 2005;11:49–55.</p><p>Johns M.W. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:5420–545.</p><p>Murray T.J. Amantadine therapy for fatigue in multiple sclerosis. Can J Neurol Sci 1985;12:251–54.</p><p>Abe K., Takanashi M., Yanagihara T. et al. Pergolide mesilate may improve fatigue in patients with Parkinson’s disease. Behav Neurol 2001–2002;13:117–21.</p><p>Pogarell O., Gasser T., van Hilten J.J. et al. Pramipexole in patients with Parkinson’s disease and marked resistant tremor: a randomized, double blind, placebo controlled multicenter study. J Neurol Neurosurg Psychiatr 2002;72:713–20.</p><p>Нодель М.Р., Артемьев Д. В., Яхно Н.Н. Эффективность дофаминового агониста Мирапекса при болезни Паркинсона. Неврол журн 1999;6:45–9.</p><p>Левин О.С., Смоленцева И.Г., Сэрэнсодном Б. и др. Влияние дофаминергической терапии на нейропсихологические функции у больных болезнью Паркинсона. Неврол журн 2004;3:31–57.</p><p>Нодель М.Р., Яхно Н.Н. Мирапекс (прамипексол) в лечении недвигательных нарушений при болезни Паркинсона. Журн неврол и психиатр 2008;108(5):32–8.</p><p>Barone P., Scarzella L., Antonini A. et al. Pramipexole versus sertraline in the treatment of depression in Parkinsons disease. J Neurol 2005;4:1–7.</p><p>Lemke M.P., Brecht H.M., Koester J.K. et.al. Anhedonia, depression, and motor functioning in Parkinsons disease during treatment with Pramipexole. J Neuropsych Clin Neurosci 2005;17:214–20.</p></div><br /><div><p>Нодель М.Р., Яхно Н.Н. Нервно-психические нарушения болезни Паркинсона. Неврол нейропсихиатр психосом 2009;2:3–8.</p><p>McKinlay A., Grace R.C., Dalrymple-Alford J.C. et al. A profile of neuropsychiatric problems and their relationship to quality of life for patients with Parkinsons disease. Park Relat Dis 2008;14:37–42.</p><p>Soh Sze-Ee, Morris Meg E., Mc-inley J.L. Determinants of health-related quality of life in Parkinsons disease: a systematic review. Park Relat Dis 2011;17:1–9.</p><p>Martinez-Martin P., Rodriguez-Blazquez C., Kurtis M.M. et al. The impact of non-motor symptoms on health-related quality of life in Parkinsons disease. Mov Dis 2011;26(3):399–406.</p><p>Gallagher D.A., Lees A.J., Shrag A. What are the most important non-motor symptoms in patients with Parkinsons disease and are we missing them- Mov Dis 2011;25(15):2493–500.</p><p>Елагина И.А., Шмидт Т.Е. Утомляемость при рассеянном склерозе. Неврол журн 2008;1:37–45.</p><p>Hoehn M.M., Yahr M.D. Parkinsonism: onset, progression and mortality. Neurology 1967;17:427–42.</p><p>Alves G., Wentzel-Larsen T., Larsen J.P. Is fatigue an independent and persistent symptom in patients with Parkinsons disease. Neurology 2004;63:1908–11.</p><p>Friedman J.H., Friedman H. Fatigue in Parkinsons disease: a nine-year follow-up. Mov Dis 2001;16:1120–2.</p><p>Herlofson K., Larsen J.P. Measuring fatigue in patients with Parkinsons disease-the Fatigue Severity Scale. Eur J Neurol 2002;9:595–600.</p><p>Van Hilten J.J., Weggman M., Velde E.A. Sleep , excessive daytime sleepiness and fatigue in Parkinsons disease. J Neural Transm Park Dis Dement Sect 1993;5:235–44.</p><p>Schifitto G., Friedman J.H., Oakes D. et al.. Fatigue in levodopa-naive subjects with Parkinsons disease. Neurology 2008;71:481–5.</p><p>Van Hilten J.J., Weggman M., Velde E.A. Sleep, excessive daytime sleepiness and fatigue in Parkinsons disease. J Neural Transm Park Dis Dement Sect 1993;5:235–44.</p><p>Van Hilten J.J., Hoogland G., Velde E.A. Diurnal effects of motor activity and fatigue in Parkinsons disease. J Neurol Neurosurg Psychiatr 1993;56:874–7.</p><p>Chaudhuri A., Behan P.O. Fatigue and basal ganglia. J Neurol Sci 2000;179:34–42.</p><p>Abe K., Takanashi M., Yanagihara T. Fatigue in patients with Parkinsons disease. Behav Neurol 2000;12:103–6.</p><p>Ziv I., Avraham M., Michaelov Y. et al. Enhanced fatigue during motor performance in patients with Parkinson’s disease. Neurology 1998;51:1583–6.</p><p>Havlicova E., Rosenberger J., Nagyova I. et al. Clinical and psychosocial factors associated with fatigue in patients with Parkinsons disease. Park Relat Dis 2008;14:187–92.</p><p>Nakamura T., Hirayama M., Hara T. et al. Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinsons diseaseMov Dis 2011;26:1869–74.</p><p>Herlofson K., Larsen J.P. The influence fatigue on health-related quality of life in patients with Acta Neurol Scand 2003;107:1–6.</p><p>Karlsen K., Larsen J.P., Tandberg E. et.al. Fatigue in patients with Parkinsons disease. Mov Dis 1999;14:237–41.</p><p>Shulman L.M., Taback R.L., Bean J. et.al. Comorbidity of the nonmotor symtoms of Parkinsons disease. Mov Dis 2001;16:507–10.</p><p>Chaudhuri K.R., Pal S., Marco Di A. et.al. The sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinsons disease. J Neurol Neurosurg Psychiatr 2002;73:629–35.</p><p>Alves G., Wentzel-Larsen T., Larsen J.P. Is fatigue an independent and persistent symptom in patients with Parkinsons disease. Neurology 2004;63:1908–11.</p><p>Valko P.O., Waldvogel D., Weller M. et al. Fatigue and excessive daytime sleepness in idiopathic Parkinsons disease differently correlate with motorsymtoms, depression and dopaminergic therapy. Eur J Neurol 2010;17:1428–35.</p><p>Lemke M.R., Raethjen J. Depression and Parkinsons disease- pathophysiology, diagnosis, treatment. 1st ed. Bremen: UNI-MED, 2007;27–8.</p><p>Brown R.G., Dittner A., Findley L. et al. The Parkinson fatigue scale. Park Relat Dis 2005;11:49–55.</p><p>Johns M.W. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:5420–545.</p><p>Murray T.J. Amantadine therapy for fatigue in multiple sclerosis. Can J Neurol Sci 1985;12:251–54.</p><p>Abe K., Takanashi M., Yanagihara T. et al. Pergolide mesilate may improve fatigue in patients with Parkinson’s disease. Behav Neurol 2001–2002;13:117–21.</p><p>Pogarell O., Gasser T., van Hilten J.J. et al. Pramipexole in patients with Parkinson’s disease and marked resistant tremor: a randomized, double blind, placebo controlled multicenter study. J Neurol Neurosurg Psychiatr 2002;72:713–20.</p><p>Нодель М.Р., Артемьев Д. В., Яхно Н.Н. Эффективность дофаминового агониста Мирапекса при болезни Паркинсона. Неврол журн 1999;6:45–9.</p><p>Левин О.С., Смоленцева И.Г., Сэрэнсодном Б. и др. Влияние дофаминергической терапии на нейропсихологические функции у больных болезнью Паркинсона. Неврол журн 2004;3:31–57.</p><p>Нодель М.Р., Яхно Н.Н. Мирапекс (прамипексол) в лечении недвигательных нарушений при болезни Паркинсона. Журн неврол и психиатр 2008;108(5):32–8.</p><p>Barone P., Scarzella L., Antonini A. et al. Pramipexole versus sertraline in the treatment of depression in Parkinsons disease. J Neurol 2005;4:1–7.</p><p>Lemke M.P., Brecht H.M., Koester J.K. et.al. Anhedonia, depression, and motor functioning in Parkinsons disease during treatment with Pramipexole. J Neuropsych Clin Neurosci 2005;17:214–20.</p></div><br />

The authors declare that there are no conflicts of interest present.