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

Distribution and differential induction of CYP2E1 by ethanol and acetone in the mesocorticolimbic system of rat.

AIMS: The expression of cytochrome P4502E1 (CYP2E1) in the brain has been demonstrated in several regions, nevertheless there is a lack of specific studies on the constitutive expression and induction at the mesocorticolimbic system, the most relevant brain pathway in the context of drug addiction and alcoholism. Hence, we have performed a detailed study of the CYP2E1 expression and induction in three key areas of the mesocorticolimbic system of the rat brain: prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). METHODS: Expression levels of CYP2E1 were analyzed by Western blot. The induction of the enzyme in the selected brain areas by chronic acetone (1% v/v acetone in drinking water for 11 days) and ethanol (3 g/kg by gavage for 7 days) was also assessed. RESULTS: (i) CYP2E1 was expressed in PFC, Nac, and VTA, with the order of magnitude of the levels being VTA approximately PFC > Nac, and approximately 3-13% of it was encountered in liver; (ii) acetone treatment significantly increased CYP2E1 expression in Nac, up to 212% of the control levels, whereas not significant changes were observed in VTA and PFC; (iii) chronic ethanol treatment only resulted in a significant induction of enzyme levels in VTA (124%). A similar enhancement, though not significant, was found to occur in NAc. CONCLUSIONS: CYP2E1 was present in the mesocorticolimbic system at different levels of expression. Chronic acetone and ethanol treatments are able to increase enzyme levels in specific areas of this system with the pattern of induction of the two agents being different.

Quality of life of caregivers in Parkinson's disease.

OBJECTIVE: To assess the impact of PD on informal caregivers of patients and identify the main factors related to caregiver strain. PATIENTS AND METHODS: Pairs of PD patients and their caregivers. Evaluation by neurologists included the Hoehn and Yahr, Schwab and England, UPDRS (parts 1-3), ISAPD, and Pfeiffer's SPMSQ rating scales. Patients completed the Euro-QoL 5D, PDQ-8, and Hospital Anxiety and Depression Scale. The SQLC was used to assess caregivers' quality of life (QoL), with caregivers, in turn, applying the Euro-QoL and PDQ-8 to assess patients' health-related quality of life (HRQoL). Multiple linear regression models were fitted to ascertain factors linked to the SQLC. RESULTS: Significant correlations were in evidence between the following scores: SQLC and clinical rating scales and SQLC and patients' HRQoL. Based on multiple regression analysis, patients' functional state (ADL) proved to be the main predictor of caregivers' QoL. Self- and caregiver-assessed patients' HRQoL also proved to be a relevant factor. CONCLUSIONS: (1) Patients' functional state was significantly related to caregivers' psychosocial burden; (2) patients' HRQoL proved to be an additional factor linked to caregiver QoL; (3) improvement of patient disability and HRQoL might alleviate caregiver strain.

Patients', doctors', and caregivers' assessment of disability using the UPDRS-ADL section: are these ratings interchangeable?

This multicenter study sought to analyze the validity and reliability of the Unified Parkinson's Disease Rating Scale (UPDRS)-section 2 (Activities of Daily Living, ADL) as applied by patients and caregivers. Sixty pairs of PD patients-caregivers were enrolled for study purposes. Neurologists used a set of scales to determine disease severity and patients' functional state. Patients and caregivers used adapted versions of the UPDRS-section 2 in tandem with other measures. Wilcoxon and Mann-Whitney tests, weighted kappa, intraclass and Spearman's correlation coefficients, as well as multivariate linear regression models were applied. On the whole, PD patient self-assessment and caregiver evaluation of patients' disability showed close concordance with neurologists' ratings. Correlation between caregiver ratings and clinical evaluation tended to be slightly lower than that for patient-based self-assessment. Depression showed a positive correlation with disability and had a nonsystematic influence on UPDRS-section 2 (ADL) scores. As expected, there was a significant correlation between perceived disability and health-related quality of life measures. Caregiver burden did not reduce the level of agreement with neurologists as to the overall rating of any given patient's disability. In PD, UPDRS-section 2-based assessment of disability by patients themselves and caregivers is a valid and reliable outcome.