RESUMO
Safinamide (SF) is a third-generation monoamine-oxidase-B inhibitor that proved efficacy as add-on to levodopa in fluctuating Parkinson's disease (PD) patients. Despite the high prevalence of complicated PD in older population, the data on the tolerability, safety and efficacy of SF in elderly patients are rather poor. Here we studied retrospectively the consequences of add-on with SF in PD patients older than 65 years. Fifty-three fluctuating PD patients were included (30 subjects aged between 65 and 75 years, the remaining 23 subjects aged > 75 years). Patients were treated with either 50 (n = 27) or 100 mg (n = 26) SF for at least 6 months. In all patients, fluctuations were identified by the report of a Wearing-Off-Questionnaire-19 (WOQ-19) score ≥ 3 at baseline. Add-on with SF was well tolerated and safe. Adverse events occurred in 30% of patients and led to drug discontinuation in 11% of cases. At follow-up visits, 60% of patients reported lowering of the WOQ-19 score to ≤ 2. There were no significant differences related to age or daily drug dose in tolerability, safety or efficacy. The results of this study provide evidence of the efficacy, tolerability and safety of SF in elderly PD patients.
Assuntos
Doença de Parkinson , Idoso , Alanina/análogos & derivados , Antiparkinsonianos/efeitos adversos , Benzilaminas/efeitos adversos , Humanos , Doença de Parkinson/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. METHODS: This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0-9.0)). RESULTS: BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p < 0.001), higher modified Ashworth scale (Coeff = 0.796; p < 0.001) and non-ambulatory patients (Coeff = 209.382; p = 0.006). Lower BT dose was used in younger patients (Coeff = - 1.746; p = 0.009), with relapsing-remitting MS (Coeff = - 60.371; p = 0.012). BT dose was higher in patients with previous BT injections (Coeff = 5.167; p = 0.001), and with concomitant treatments (Coeff = 43.576; p = 0.022). Three patients (0.7%) reported on post-injection temporary asthenia/weakness (n = 2) and hypophonia (n = 1). CONCLUSION: BT was used for spasticity and its consequences from the early stages of MS, without significant adverse effects. MS-specific goals and injection characteristics can be used to refer MS patients to BT treatment, to decide for the strategy of BT injections and to guide the design of future clinical trials and observational studies.
Assuntos
Toxinas Botulínicas Tipo A , Esclerose Múltipla , Fármacos Neuromusculares , Atividades Cotidianas , Adulto , Estudos Transversais , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Fármacos Neuromusculares/uso terapêutico , Resultado do TratamentoRESUMO
The purpose of the present study was to investigate the long-term persistence to treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting. We retrospectively collected data of patients who started BoNT-A injections and underwent regular follow-up visits. Determinants of BoNT-A discontinuation were explored in a time-to-event Cox regression analysis which included as independent variables a large set of demographic and clinical characteristics. A total of 185 patients started BoNT-A injections from 2002 to 2014 and were followed up to September 2016. Of them, data on 121 were considered in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68 (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6 months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n = 45), logistic problems or barriers to reach the structure (n = 16), and adverse events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent predictors for BoNT-A discontinuation. Our study confirms the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Adesão à Medicação , Esclerose Múltipla/complicações , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Fármacos Neuromusculares/uso terapêutico , Adulto , Idoso , Cuidadores , Feminino , Seguimentos , Humanos , Injeções , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/reabilitação , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/reabilitação , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
INTRODUCTION: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting. METHODS AND ANALYSIS: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality. ETHICS AND DISSEMINATION: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05379413.
Assuntos
Toxinas Botulínicas Tipo A , Espasticidade Muscular , Fármacos Neuromusculares , Acidente Vascular Cerebral , Extremidade Superior , Humanos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Estudos Prospectivos , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/administração & dosagem , Extremidade Superior/fisiopatologia , Estudos Longitudinais , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Estudos Observacionais como Assunto , Feminino , MasculinoRESUMO
OBJECTIVE: To determine if segmental muscle vibration and botulinum toxin-A injection, either alone or in combination, reduces spasticity in a sample of patients with multiple sclerosis. DESIGN: Single-blind, randomized controlled trial. SETTING: Physical medicine and rehabilitation outpatients service. SUBJECTS: Forty-two patients affected by the secondary progressive form of multiple sclerosis randomized to group A (30 minutes of 120 Hz segmental muscle vibration over the rectus femoris and gastrocnemius medial and lateral, three per week, over a period of four weeks), group B (botulinum toxin in the rectus femoris, gastrocnemius medial and lateral and soleus, and segmental muscle vibration) and group C (botulinum toxin). MAIN MEASURES: Modified Ashworth Scale at knee and ankle, and Fatigue Severity Scale. All the measurements were performed at baseline (T0), 10 weeks (T1) and 22 weeks (T2) postallocation. RESULTS: Modified Ashworth Scale at knee and ankle significantly decreased over time (p < 0.001) in all groups. Patients in group C displayed a significant increase of knee and ankle spasticity at T2 when compared with T1 (p < 0.05). Fatigue Severity Scale values in groups A and C were significantly higher at T0 [A: 53.6 (2.31); C: 48.5 (2.77)] than at either T1 [A: 48.6 (2.21); p = 0.03; C: 43.5 (3.22); p = 0.03] or T2 [A: 46.7 (2.75); p = 0.02; 42.5 (2.17); p = 0.02], while no differences were detected in group B [T0: 43.4 (3.10); T1: 37.3 (3.15); T2: 39.7 (2.97)]. CONCLUSION: Segmental muscle vibration and botulinum toxin-A reduces spasticity and improves fatigue in the medium-term follow-up in patients with multiple sclerosis.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Esclerose Múltipla/complicações , Espasticidade Muscular/terapia , Fármacos Neuromusculares/uso terapêutico , Vibração/uso terapêutico , Avaliação da Deficiência , Fadiga/etiologia , Fadiga/terapia , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Método Simples-CegoAssuntos
Toxinas Botulínicas/administração & dosagem , Glicoproteína Associada a Mielina/imunologia , Fármacos Neuromusculares/administração & dosagem , Polirradiculoneuropatia/tratamento farmacológico , Idoso , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Feminino , Humanos , Pessoa de Meia-Idade , Polirradiculoneuropatia/fisiopatologia , Resultado do TratamentoRESUMO
Levodopa (LD) provides the most effective symptomatic treatment for Parkinson's disease (PD). Long-term treatment with LD, however, is often associated with the development of response fluctuations. Previous evidence suggests that the short half-life of LD is a major contributor to the development of response fluctuations and the wearing-off phenomenon in particular. Entacapone, a peripheral catechol-O-methyltransferase inhibitor has been shown to reduce OFF time and increase ON time in several therapeutic trials on PD patients treated with LD experiencing motor fluctuations. However, data are missing on the tolerability and efficacy of entacapone in elderly PD patients. This is of particular relevance, as most PD patients develop LD-related motor fluctuations after several years of disease duration. Here we report that addition of entacapone in a group of 45 elderly PD patients with LD-related motor fluctuations is well tolerated and efficacious in reducing the time, frequency and severity of the OFF periods. These data suggest that the drug can be used safely and efficaciously in elderly PD patients.
Assuntos
Antiparkinsonianos/administração & dosagem , Catecóis/administração & dosagem , Nitrilas/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Levodopa/administração & dosagem , Masculino , Projetos PilotoRESUMO
OBJECTIVE: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinson's disease. METHODS: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of (123)I-fluopane single-photon emission computed tomography in the same patients. RESULTS: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding. DISCUSSION: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinson's disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.
Assuntos
Núcleo Caudado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Linfócitos/metabolismo , Doença de Parkinson/metabolismo , Putamen/metabolismo , Adulto , Idoso , Núcleo Caudado/diagnóstico por imagem , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/patologia , Putamen/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , TropanosAssuntos
Toxinas Botulínicas Tipo A , Bloqueio Nervoso , Humanos , Pessoa de Meia-Idade , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Distonia/tratamento farmacológico , Distúrbios Distônicos/tratamento farmacológico , Extremidade Inferior , Bloqueio Nervoso/métodos , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/administração & dosagem , Fenol/uso terapêutico , Fenol/administração & dosagemRESUMO
BACKGROUND: Dopamine agonists (DA) are the first-choice drug for treatment of the early stage of Parkinson's disease (PD) in subjects younger than 70 years. Recently, a number of third generation DA have been marketed, including transdermal patch of rotigotine and extended release oral formulation of ropinirole and pramipexole.We investigated the impact of third generation DA on management of the early stage of PD in an outpatient service for Movement Disorders in Italy. METHODS: Two 12-month observation periods were selected (January - December, 2007, and January - December, 2011) as representative for prescription of immediate and extended release formulations of DA respectively. Within each period, PD patients were divided into subgroups according to age (<65 years; 65-75 years; >75 years) or functional requirement (high; moderate; low). For each period, the number of subjects receiving monotherapy with DA, monotherapy with levodopa (LD), or combined DA/LD therapy and the relative doses were calculated. The severity of parkinsonian motor symptoms was calculated by means of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The frequency and severity of side-effects leading to discontinuation or reduction of DA drugs at each time point were also calculated. RESULTS: We found a significant reduction of daily LD dose (both as mono- and combined therapy) between the second and the first observation period. There was also a significant increase of monotherapy with DA and corresponding reduction of monotherapy with LD in patients aged 65-75 years, as well as in PD patients with moderate functional requirements. A significant reduction of frequency of side-effects was measured with extended release DA as compared to immediate release formulations. There were no significant differences of the UPDRS-III scores between the 2 observation periods in any subgroup. CONCLUSIONS: Our results suggest that extended release DA might optimize therapeutic management of the early stages of PD even in patients older than 70 years of age.
Assuntos
Agonistas de Dopamina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Padrões de Prática Médica , Idoso , Preparações de Ação Retardada , Demografia , Feminino , Humanos , MasculinoRESUMO
Previous studies showed the reduction of dopamine transporter immunoreactivity (DAT-IR) in peripheral blood lymphocytes (PBL) in Parkinson's disease. Here we report the reduction of DAT-IR in PBL in the extrapyramidal variant of multiple system atrophy. These results suggest the reduction of DAT-IR in PBL in a variety of neurodegenerative disorders, provided the presence of damage of the central dopaminergic systems. The reduction of DAT-IR in PBL in these disorders may represent a compensatory phenomenon aimed at reducing intracellular dopamine influx and, consequently, dopamine-mediated aggravation of oxidative stress in these cells.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/biossíntese , Linfócitos/metabolismo , Atrofia de Múltiplos Sistemas/sangue , Idoso , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/tratamento farmacológicoRESUMO
The motor symptoms of Parkinson's disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents.
Assuntos
Doenças dos Gânglios da Base/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Núcleos Cerebelares/diagnóstico por imagem , Síncope/etiologia , Serviço Hospitalar de Emergência , Epilepsia/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
By analyzing the kinematics of repetitive, constant-amplitude, finger oppositions, we compared the impairment of individual and nonindividual finger movements in patients with Parkinson's disease. In one task, subjects tapped only the index finger against the thumb (individual oppositions); in the other task, they tapped all four fingers together against the thumb pad (nonindividual oppositions). We used an optoelectronic motion analysis system to record movements in three-dimensional space and recorded three 5-second trials for each task. We counted how many finger oppositions subjects performed during each trial and measured the duration and amplitude of the flexions and extensions. We also calculated the duration of the pauses after flexion and extension. We assessed the deterioration of motor performance in patients by investigating the changes in speed and amplitude with task completion. During both tasks, normal subjects and patients performed finger flexions faster than extensions, and they invariably paused longer after flexion than after extension. Patients performed individual and nonindividual finger movements slowly and with reduced amplitude. Patients were disproportionately slow during flexion and in switching from flexion to extension. Movement slowness increased as finger oppositions progressed but predominantly when patients had to move fingers individually. In conclusion, in patients with Parkinson's disease, the motor performance deteriorated with task completion more during individual than during nonindividual finger movements. Parkinson's disease, therefore, impairs individual finger movements more than gross hand movements. This distinction reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output.