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wearing off Parkinsonism

Hiroko Tsunekawa, Kazue Takahata, Motoki Okano, Toshiko Ishikawa, Hiroshi Satoyoshi, Tetsuya Nishimura, Naoya Hoshino, Shizuko Muraoka
3,4-Dihydroxy-L-phenylalanine (L-Dopa) remains the most effective drug for treating the motor symptoms of Parkinson's disease (PD). However, its long-term use is limited due to motor complications such as wearing-off and dyskinesia. A clinical study in PD patients with motor complications has demonstrated that selegiline, a monoamine oxidase type B inhibitor, is effective in reducing off time without worsening dyskinesia, although another study has shown worsening dyskinesia. Here, using unilateral 6-hydroxydopamine-lesioned rats showing degeneration of nigrostriatal dopaminergic neurons and L-Dopa-induced motor complications, we determined the efficacy of selegiline in controlling L-Dopa-induced motor fluctuations and exacerbated dyskinesia...
March 8, 2018: Behavioural Brain Research
Agostinho Lemos, Rita Meloc, Antonio J Preto, Jose G Almeida, Irina S Moreira, M Natalia D S Cordeiro
Parkinson's Disease (PD) is a long-term neurodegenative brain disorder that mainly affects the motor system. The causes are still unknown, and even though currently there is no cure, several therapeutic options are available to manage its symptoms. The development of novel anti-parkinsonian agents and an understanding of their proper and optimal use are, indeed, highly demanding. For the last decades, L-3,4-DihydrOxyPhenylAlanine or levodopa (L-DOPA) has been the gold-standard therapy for the symptomatic treatment of motor dysfunctions associated to PD...
March 8, 2018: Current Neuropharmacology
Miho Murata, Masahito Mihara, Kazuko Hasegawa, Beomseok Jeon, Chon-Haw Tsai, Noriko Nishikawa, Tomoko Oeda, Masayuki Yokoyama, Weining Z Robieson, Krai Chatamra, Maurizio F Facheris, Janet Benesh
Objectives: Levodopa-carbidopa intestinal gel (LCIG) was developed to reduce motor complications in Parkinson's disease (PD) caused by pulsatile levodopa plasma concentrations following oral levodopa administration. Dyskinesia and 'wearing off' symptoms can vary between Asian and Caucasian patients with PD, thus highlighting the importance of assessing the effectiveness of LCIG in an Asian population. Efficacy and safety of LCIG were previously assessed in a 12-week open-label study; we report the efficacy and safety of at least 52 weeks of LCIG treatment in Japanese, Taiwanese, and Korean patients with advanced PD in the ongoing extension study...
2018: Therapeutic Advances in Neurological Disorders
M Angela Cenci, Alan R Crossman
Understanding the biological mechanisms of l-dopa-induced motor complications is dependent on our ability to investigate these phenomena in animal models of Parkinson's disease. The most common motor complications consist in wearing-off fluctuations and abnormal involuntary movements appearing when plasma levels of l-dopa are high, commonly referred to as peak-dose l-dopa-induced dyskinesia. Parkinsonian models exhibiting these features have been well-characterized in both rodent and nonhuman primate species...
February 28, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Karina Lebel, Christian Duval, Hung Phuc Nguyen, Réjean Plamondon, Patrick Boissy
Background: Turning is a challenging mobility task requiring proper planning, coordination, and postural stability to be executed efficiently. Turn deficits can impair mobility and lead to falls in patients with neurodegenerative disease, such as Parkinson's disease (PD). It was previously shown that the cranio-caudal sequence involved during a turn (i.e., motion is initiated by the head, followed by the trunk) exhibits a signature that can be captured using an inertial system and analyzed through the Kinematics Theory...
2018: Frontiers in Neurology
Ires Ghielen, Erwin E H van Wegen, Sonja Rutten, Cees J T de Goede, Marieke Houniet-de Gier, Emma H Collette, Ingrid A L Burgers-Bots, Jos W R Twisk, Gert Kwakkel, Kees Vermunt, Bep van Vliet, Henk W Berendse, Odile A van den Heuvel
BACKGROUND: In Parkinson's disease (PD) patients, fluctuations in symptoms commonly occur after many years of dopamine replacement therapy. The so-called wearing-off phenomenon exists of both motor and non-motor symptoms, such as rigidity and anxiety. Current treatment options are limited and an integrated approach is needed to address the complex interactions between motor and non-motor symptoms. Since wearing-off is eventually inevitable, treatment needs to focus on coping, acceptance and self-efficacy...
December 2017: Journal of Psychosomatic Research
Michele Pistacchi, Manuela Gioulis, Flavio Sanson, Sandro Z Marsala
BACKGROUND: 'Wearing off' refers to the phenomenology of movement disorders in Parkinson's disease (PD) that appears early and is much commoner than generally believed. It may be present in the form of either motor symptoms or non-motor symptoms. AIM: To investigate the utility of wearing-off questionnaire (WOQ-19, Italian version) in the outpatient clinical practice to assess the suitability of different combinations of treatment, in various stages of PD. METHODS: 73 consecutive patients (58% male and 42% female) suffering from PD were recruited through the Santorso Hospital and San Martino Hospital from September 2012 to March 2014...
November 2017: Neurology India
Linda S David, Martine Saint-Pierre, Jérôme Lamontagne-Proulx, Francesca Cicchetti
Levo-dopa (L-DOPA) has shown significant and long-lasting efficacy in the treatment of motor features characteristic of Parkinson's disease (PD). However, the effects tend to wear off at a time typically when side-effects, such as L-DOPA induced dyskinesias (LIDs), start to emerge and for which the treatment options are very limited. In recent years, we have reported on the neuroprotective and neurorestorative properties of the compounds cystamine/cysteamine in ameliorating several aspects of PD. Building on these observations, we set out to further evaluate the benefits of cysteamine on LIDs...
October 31, 2017: Neuroscience Letters
Yasuyuki Okuma, Ana Lígia Silva de Lima, Jiro Fukae, Bastiaan R Bloem, Anke H Snijders
INTRODUCTION: Falls are a disabling feature of Parkinson's disease (PD). In this prospective study we investigated: (1) in which motor state patients with PD fallmost often; and (2) whether freezing of gait (FOG) and dyskinesias contribute to falls. METHODS: Patients with PD who had fallen at least once in the previous year and had wearing-off were recruited. During six months, patients complete a standardized fall report. We analyzed data regarding fall circumstances and motor state at the time of each first 10 falls...
October 19, 2017: Parkinsonism & related Disorders
Keita Matsuura, Hiroyuki Kajikawa, Ken-Ichi Tabei, Masayuki Satoh, Hirotaka Kida, Naoko Nakamura, Hidekazu Tomimoto
PURPOSE: Istradefylline is useful in treating the wearing-off state in Parkinson's disease (PD). We investigated the effectiveness of istradefylline (ISD) in improving arousal, sleep, and gait deficits in patients with PD. METHODS: We examined 14 patients with PD treated with ISD. We assessed the patients using the Unified Parkinson's Disease Rating Scale, Parkinson's Disease Questionnaire, Timed Up-and-Go test (TUG), Freezing of Gait Questionnaire (FOG-Q), Epworth Sleepiness Scale (ESS), and Parkinson's Disease Sleep Scale (PDSS) before and 1 month after ISD use...
October 13, 2017: Neuroscience Letters
Somayeh Aghanavesi, Mevludin Memedi, Mark Dougherty, Dag Nyholm, Jerker Westin
Parkinson's disease (PD) is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. There is a need for frequent symptom assessment, since the treatment needs to be individualized as the disease progresses. The aim of this paper was to verify and further investigate the clinimetric properties of an entropy-based method for measuring PD-related upper limb temporal irregularities during spiral drawing tasks. More specifically, properties of a temporal irregularity score (TIS) for patients at different stages of PD, and medication time points were investigated...
October 13, 2017: Sensors
Ichiro Yabe, Mayumi Kitagawa, Ikuko Takahashi, Masaaki Matsushima, Hidenao Sasaki
OBJECTIVES: The adenosine A2A antagonist istradefylline has been used to treat Parkinson disease (PD) with symptoms of wearing-off since 2013 in Japan. Previous randomized controlled trials of istradefylline compared with placebo included PD patients experiencing an average daily OFF time of more than 2 hours. The purpose of this study is to assess the efficacy of 20 mg/d istradefylline in PD subjects experiencing an average daily OFF time of 3 hours or less. METHODS: Fifteen patients were enrolled into this retrospective study...
November 2017: Clinical Neuropharmacology
Domiziana Rinaldi, Francesca Assogna, Michela Sforza, Stefania Tagliente, Francesco E Pontieri
Wearing-off refers to the predictable worsening of motor and sometimes non-motor symptoms of Parkinson's disease occurring at the end of levodopa dose that improves with the next drug dose. Here, we investigated the efficacy of rasagiline on executive functions at the end of levodopa dose in patients displaying symptoms of wearing-off. Rasagiline was well-tolerated and produced a significant improvement at the Frontal Assessment Battery, together with improvement of motor symptoms at the end of levodopa dose...
September 27, 2017: Neurological Sciences
Alejandro Rodríguez-Molinero, Albert Samà, Carlos Pérez-López, Daniel Rodríguez-Martín, Sheila Alcaine, Berta Mestre, Paola Quispe, Benedetta Giuliani, Gabriel Vainstein, Patrick Browne, Dean Sweeney, J Manuel Moreno Arostegui, Àngels Bayes, Hadas Lewy, Alberto Costa, Roberta Annicchiarico, Timothy Counihan, Gearòid Ò Laighin, Joan Cabestany
BACKGROUND: Our group earlier developed a small monitoring device, which uses accelerometer measurements to accurately detect motor fluctuations in patients with Parkinson's (On and Off state) based on an algorithm that characterizes gait through the frequency content of strides. To further validate the algorithm, we studied the correlation of its outputs with the motor section of the Unified Parkinson's Disease Rating Scale part-III (UPDRS-III). METHOD: Seventy-five patients suffering from Parkinson's disease were asked to walk both in the Off and the On state while wearing the inertial sensor on the waist...
2017: Frontiers in Neurology
Sanjay Pandey, Prachaya Srivanitchapoom
Levodopa-induced dyskinesia (LID) is commonly seen in Parkinson's disease patients treated with levodopa. This side effect is usually encountered after long duration of treatment, but occasionally, this may be seen even after few days or months of treatment. LID is broadly classified as peak-dose dyskinesia, wearing-off or off-period dyskinesia, and diphasic dyskinesia. Pathogenesis of LID is complex, and different neurotransmitters such as dopamine, glutamine, adenosine, and gamma-aminobutyric acid play important role altering the normal physiology of direct and indirect pathway of cortico-basal ganglia-thalamic loop responsible for fine motor control...
July 2017: Annals of Indian Academy of Neurology
Yuki Yasutaka, Shinsuke Fujioka, Hirotomo Shibaguchi, Fumiaki Kiyomi, Koyomi Hara, Kentaro Ogata, Yoshio Tsuboi, Hidetoshi Kamimura
Since the effect of a percutaneous absorption-type dopamine agonist (DA) preparation, rotigotine patch, stably persists by once-a-day application, this dosage form is appropriate for Parkinson's disease patients showing levodopa induced wearing off phenomenon. On the other hand, skin disorders, mainly application site reaction, are characteristic problems associated with use of the patch. In this study, to clarify the influence of a topical agent used to prevent or treat rotigotine patch-induced skin disorder on continuation of the patch application, patients who started rotigotine patch application at our hospital were retrospectively surveyed...
September 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
Keisuke Suzuki, Masayuki Miyamoto, Tomoyuki Miyamoto, Tomoyuki Uchiyama, Yuka Watanabe, Shiho Suzuki, Taro Kadowaki, Hiroaki Fujita, Takeo Matsubara, Hirotaka Sakuramoto, Koichi Hirata
BACKGROUND: Istradefylline, a selective adenosine A2A receptor antagonist, has been reported to improve daily "off time" and motor symptoms in patients with Parkinson's disease (PD). However, the effect of istradefylline on sleep problems has not been thoroughly investigated. METHODS: We evaluated the effect of istradefylline on daytime sleepiness, sleep disturbances, and motor symptoms in 22 PD patients who were affected by the wearing off phenomenon in an open-label, 3-month study...
September 15, 2017: Journal of the Neurological Sciences
Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period...
October 7, 2017: Lancet
Carlo Cattaneo, Thomas Müller, Erminio Bonizzoni, Gabriele Lazzeri, Ioannis Kottakis, Charlotte Keywood
BACKGROUND: Mood disorders are very frequent in Parkinson's Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible inhibition of the monoamine oxidase-B (MAO-B) enzyme and the modulation of excessive glutamate release through the use- and state-dependent blockade of the sodium channels...
2017: Journal of Parkinson's Disease
Hisanao Akiyama, Saki Nukui, Masashi Akamatu, Yasuhiro Hasegawa, Osamu Nishikido, Soichiro Inoue
BACKGROUND: Spinal cord stimulation (SCS) has recently been reported to be effective for truncal postural abnormalities such as camptocormia and Pisa syndrome in Parkinson's disease. In this case report, we describe a case of a woman with Parkinson's disease in whom SCS was effective for painful camptocormia with Pisa syndrome. CASE PRESENTATION: A 65-year-old woman was admitted to our hospital because of painful camptocormia. She had noticed resting tremor in the left upper limb and aprosody at 48 years of age...
August 3, 2017: BMC Neurology
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