Validation of the OPTIMIPARK Questionnaire: A Tool to Optimize Treatment in Parkinson's Disease.

Background: Dopamine replacement therapy reduces most motor and nonmotor features of Parkinson's disease. However, with disease progression, adjustments of dopaminergics and the application of advanced therapies must be considered. Objectives: To validate the OPTIMIPARK questionnaire as a tool to help clinicians make therapeutic decisions on patients treated with levodopa. Methods: We tested a questionnaire including 9 items encompassing motor and nonmotor signs, complications, and disability in a multicenter, observational, cross-sectional study. A neurologist (neurologist 1 [N1]) assessed patients according to regular clinical practice and blinded to the OPTIMIPARK questionnaire score. Therapeutic decisions were classified as "no changes," "adjustment of conventional treatment," and "advanced therapy indicated." External neurologists (neurologist 3 [N3] and neurologist 4 [N4]), who only knew the patient age, years of disease, and current treatment, made their therapeutic decisions based on the OPTIMIPARK score. Concordance between the criterion of the N1 versus the OPTIMIPARK-based N3-N4 consensus was analyzed applying weighted κ. The area under Receiving Operating Characteristic (ROC) curves was calculated for OPTIMIPARK scores. Results: A total of 113 patients with Parkinson's disease were included. The OPTIMIPARK-based decision led to a higher proportion of patients requiring therapeutic modification than N1 assessment (74% vs. 60%; P = 0.002). Concordance between the N1 and N3-N4 decisions was moderate, whereas interobserver agreement among N3 and N4 was high. Area Under the Curve(AUC) values of 0.83 and 0.82 were found for "no changes" and "advanced therapy indicated" decisions by the N1 neurologist. Conclusions: OPTIMIPARK might be more sensitive than regular clinical practice in suggesting the need for a therapeutic change. Furthermore, the low and high scores identify with high accuracy well-adjusted patients and candidates for advanced therapy, respectively.

Hemifacial spasm through the last three decades: From etiology to efficacy and safety of long-term botulinum toxin treatment.

BACKGROUND: Hemifacial spasm (HFS) is an uncommon movement disorder characterized by involuntary contractions of muscles innervated by the facial nerve. The aim of this study is to analyze the etiology of HFS as well as the efficacy and safety of long-term botulinum toxin type A (BTX-A) treatment. METHODS: Retrospective study including 125 patients with HFS treated with BTX-A from 1993 to 2019. Demographic and etiological variables as well as doses, number of sessions of BTX-A, infiltrated muscles, therapeutic response according to Patient Global Impression of Change Scale (PGIC-S), side effects and adjuvant treatments were analyzed. In addition, these variables were compared according to the etiology (idiopathic versus secondary). RESULTS: 92 patients (73.6%) were women and the mean age at diagnosis was 58.63 years (SD 15.4). The etiology was idiopathic in 79 patients (63.2%), 17.6% were secondary to Bell's palsy, 14.4% to vascular compression and 2.4% to tumors. A higher total dose per session was observed in the secondary group. PGIC-S showed a good response in 96% of cases. 16 patients (12.8%) required pharmacological concomitant treatment. 59 patients (47.2%) developed side effects. Transient eyelid ptosis and facial weakness were the most common. CONCLUSIONS: The structural origin of a significant number of cases of HFS makes essential to complete an etiological diagnosis in all patients. In addition, the existence of a secondary cause could be associated with greater doses of BTX-A to achieve a good response. Regardless the etiology, long-term treatment with BTX-A in HFS is safe and effective.

Estudio piloto de una nueva herramienta para optimizar el tratamiento dopaminérgico en la enfermedad de Parkinson: el cuestionario OPTIMIPARK / Pilot study of a new tool to optimise dopaminergic treatment in Parkinson's disease: the OPTIMIPARK questionnaire

INTRODUCCIÓN: La terapia dopaminérgica es eficaz en la enfermedad de Parkinson (EP), si bien debe ajustarse conforme progresa la neurodegeneración. OBJETIVOS: Desarrollar un cuestionario (OPTIMIPARK) para valorar el estado dopaminérgico del paciente y ayudar al clínico en el ajuste del tratamiento. PACIENTES Y MÉTODOS: La versión preliminar, autoadministrada, de OPTIMIPARK incluye nueve ítems que tienen en cuenta complicaciones motoras y no motoras, así como la discapacidad. Cada ítem se valora de 0 a 2, y se obtiene una puntuación global de 0 a 18. Treinta pacientes contestaron el cuestionario OPTIMIPARK y un cuestionario ad hoc sobre éste en un estudio piloto unicéntrico y observacional. Se analizaron la viabilidad, la aceptabilidad y la concordancia preliminar con los criterios clínicos. RESULTADOS: Treinta pacientes con EP (68,5 ± 7,5 años; rango: 43-80 años) en estadio de Hoehn & Yahr I-III completaron el OPTIMIPARK (media de la puntuación total: 6,7 ± 4; rango: 0-14) y el cuestionario ad hoc. Las decisiones clínicas se clasificaron como: sin cambios, ajustes en el tratamiento convencional y terapia quirúrgica o de infusión continua. Las puntuaciones totales de OPTIMIPARK (media ± desviación estándar) para cada opción fueron: 1,4 ± 1 (rango: 0-3); 7 ± 2,8 (rango: 2-11); y 10,8 ± 1,8 (rango: 9-14). El punto de corte 3/4 clasificó al 95,5% de los pacientes sin cambios frente a ajustes del tratamiento convencional, y el corte 9/10 discriminó al 78,3% de los pacientes de ajuste del tratamiento convencional frente a terapia quirúrgica o de infusión continua, con concordancia (coeficientes kappa y Lin) de 0,81. CONCLUSIONES: Pendiente del estudio de validación, OPTIMIPARK puede ser un cuestionario viable y útil para la toma de decisiones clínicas en el ajuste terapéutico de pacientes con EP y la identificación de candidatos para terapias avanzadas

INTRODUCTION: Dopaminergic therapy is effective in Parkinson's disease (PD), but should be adjusted as neurodegeneration progresses. AIMS: The aim of this study was to develop a questionnaire (OPTIMIPARK) to assess the patient's dopaminergic status and assist the clinician in adjusting treatment. PATIENTS AND METHODS: The preliminary, self-administered version of OPTIMIPARK includes nine items that take into account motor and non-motor complications as well as disability. Each item is given a score between 0 and 2, and an overall score from 0 to 18 is obtained. Thirty patients completed the OPTIMIPARK questionnaire and an ad hoc questionnaire about it in a single-centre, observational pilot study. Feasibility, acceptability and preliminary agreement with clinical criteria were analysed. RESULTS: Thirty patients with PD (68.5 ± 7.5 years; range: 43-80 years) in Hoehn & Yahr stage I-III completed OPTIMIPARK (mean total score: 6.7 ± 4; range: 0-14) and the ad hoc questionnaire. Clinical decisions were classified as: 'no change', 'adjustments to conventional treatment' and 'surgical or continuous infusion therapy'. The total OPTIMIPARK scores (mean ± standard deviation) for each option were: 1.4 ± 1 (range: 0-3); 7 ± 2.8 (range: 2-11); and 10.8 ± 1.8 (range: 9-14). The 3/4 cut-off point classified 95.5% of patients as 'no change' versus 'adjustment to conventional treatment', and the 9/10 cut-off point discriminated 78.3% of patients from 'adjustment to conventional treatment' versus 'surgical or continuous infusion therapy', with a concordance (kappa and Lin coefficients) of 0.81. CONCLUSIONS: Although still pending a validation study, OPTIMIPARK may be a viable and useful questionnaire for clinical decision-making in the therapeutic adjustment of PD patients and the identification of candidates for advanced therapies

Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo / Clinical experience in the treatment of motor fluctuations in Parkinsons disease. Delphi consensus of a group of experts in movement disorders

INTRODUCCIÓN: Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. DESARROLLO: Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. CONCLUSIÓN: El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motora

INTRODUCTION. Motor fluctuations are one of the most common complications of Parkinsons disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT. Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION. The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations

Efficacy and Safety of Long-Term Therapy with Type A Botulinum Toxin in Patients with Blepharospasm.

Blepharospasm (BPS) is one of the most frequent types of facial dystonia and, at the same time, one of the most disabling, being able to trigger functional blindness if not treated. Our aim with this work was to evaluate the efficacy and safety of long-term onabotulinum A toxin (BAT) treatment in a cohort of patients with BPS. The retrospective study was conducted on consecutive patients with BPS treated with subcutaneous BAT. The selection of muscles and dose was made based on each patient's needs. The clinical and demographic characteristics, number of sessions, dose, duration and effectiveness of treatment, and adverse events were analysed. 130 patients were included in the study. The median (95% confidence interval) length of follow-up was 14 (13-15.6) years with an average of 20.5 sessions (range from 10 to 57). Regarding the efficacy of the treatment, 114 (87.7%) experienced satisfactory results with functional and aesthetics recovery. Patient evaluation of global response suggested a clear improvement without adverse events in 72 (55.4%) patients. Adverse events developed at least once during the treatment in 39% of patients, with transient ptosis and haematoma the most common reported both by physician and patient. The results of our study suggest that botulin toxin A is a safe and effective long-term treatment for blepharospasm with mild, transient and well-tolerated side effects when they appear.

Estudio farmacoeconómico del tratamiento de la enfermedad de Parkinson avanzada / Pharmacoeconomic study of the treatment of advanced Parkinson’s disease

Introducción. Cuando el tratamiento farmacológico oral o transdérmico de la enfermedad de Parkinson pierde eficacia, se dispone de tres terapias mediante dispositivos asistidos que pueden reducir las complicaciones motoras y no motoras: la apomorfina en infusión subcutánea (ASBI), la bomba de infusión duodenal continua de levodopa/carbidopa (IDL) y la estimulación cerebral profunda (ECP). Objetivo. Efectuar un análisis farmacoeconómico comparativo del uso de ASBI con IDL y ECP; como objetivo secundario, discutir el perfil del candidato ideal para cada una de las técnicas. Pacientes y métodos. Se extrajo información sobre datos de años de vida ganados y años de vida ganados ajustados por calidad (AVAC) según la escala de Hoehn y Yahr, e información sobre costes y consumo de recursos para cada alternativa. La perspectiva del análisis fue la del Sistema Nacional de Salud, y el horizonte temporal fue de cinco años para los costes y toda la vida del paciente para las utilidades. Las medidas de resultado utilizadas fueron los años de vida ganados y AVAC, y en su comparación se usó la ratio coste-utilidad incremental. Resultados. El coste-utilidad obtenido para cada opción fue: 31.956 euros/AVAC para la ECP, 38.249 euros/AVAC para la ASBI y 75.206 euros/AVAC para la IDL. Conclusiones. Los resultados permiten evaluar la efectividad y utilidad de los diferentes tratamientos para la enfermedad de Parkinson avanzada, pues se presentan en ganancias de años vividos en plena salud. Los datos obtenidos contribuyen a la toma de decisiones que determinen la planificación y gestión de cada caso, sin olvidar las preferencias del paciente y del neurólogo, así como las limitaciones presupuestarias (AU)

Introduction. When oral or transdermal drug therapy in Parkinson’s disease becomes less effective, there are three therapies using assisted devices that can reduce motor and non-motor complications: subcutaneous apomorphine infusion pump (SAIP), continuous levodopa/carbidopa duodenal infusion (LDI) and deep brain stimulation (DBS). Aim. Conduct a comparative pharmacoeconomic analysis of the use of SAIP, with LDI and DBS. As a secondary objective arises discuss the profile of the ideal candidate for each of the technicals. Patients and methods. Information on life years gained and quality adjusted life years (QALY) according to Hoehn & Yahr scale was obtained, as well as data on costs and resource use for each of the alternatives. The perspective of the analysis was the National Health System and the time horizon was 5 years for costs and patient´s lifetime for utilities. Outcome measures used were life years gained and QALYs, and incremental cost/utility ratio for comparison. Results. Cost/utility ratio was obtained for each option: 31,956 euros/QALY for DBS, 38,249 euros/QALY for SAIP, and 75,206 euros/QALY for LDI. Conclusions. Our results allow us to add information about effectiveness of different treatments, as these are presented in gain of years lived in full health (QALY). Data obtained contribute to decision making that determine planning and management of each case, without forgetting patient and neurologist preferences, as well as budgetary limitations (AU)

A 17-year experience of abobotulinumtoxina in cervical dystonia.

OBJECTIVE: To investigate the long-term efficacy and safety of a botulinum toxin type A (BoNT-A) for the treatment of cervical dystonia (CD). METHODS: We conducted a retrospective chart review of patients with CD treated with abobotulinumtoxinA (Dysport™ 100-800 units [U] for injection) between 1993 and 2009 at the University Hospital "La Paz" (LPUH). Affected muscles were selected using electromyography (EMG). RESULTS: Thirty-seven patients were included in the study; most were female (62%) and had idiopathic CD (60%). Almost half (46%) of patients were diagnosed with the condition more than 10 years ago. The most common clinical presentations of CD were rotation (46%) and laterocollis (43%). On average, patients were treated with Dysport for 7 years (range: 1-17 years) and received 487 (range: 320 to 650) U over 15.9 (range: 1 to 40) injection cycles. Most (97%) patients maintained a response from treatment initiation to end of evaluation period. Overall, 70% of patients were taking concomitant oral medication. Dysport was generally well tolerated. Dysphagia was reported by 18.9% of patients, but this did not lead to discontinuation of Dysport treatment. CONCLUSION: These data confirm the long-term efficacy and safety of Dysport in CD over a period of up to 17 years.

Assessment of Parkinson disease: what do we need to show neuroprotection?

To date, no pharmacological agent has convincingly demonstrated the ability to slow the progression of Parkinson disease (PD). The development of treatments that slow down the progressive degeneration of the nigrostriatal dopaminergic system (true neuroprotection), which is ultimately responsible for the patients' functional decline, has become one of the basic goals of PD research. In this review, we have attempted to analyze the role of different methods that measure PD severity (basically, clinical scales, timed tests, and neuroimaging techniques) in the evaluation of the "neuroprotection" provided by different types of treatment for the disease, on the basis of clinical evidence.