Analysis of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with monogenic PRKN and LRRK2 forms of Parkinson's disease.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most common surgical treatment for Parkinson's disease (PD). Patient selection and genetic background can modify the response to this treatment. The objective of this study was to compare both clinical and pharmacologic response of STN-DBS between patients with monogenic forms of PD and non-mutation carriers with idiopathic PD. METHODS: A retrospective analysis among 23 carriers of genetic mutations (8 PRKN and 15 LRRK2) and 74 patients with idiopathic PD was performed. The study included comparisons of Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, Schwab and England (S&E) scale values, Hoehn & Yahr (H&Y) stage scores, and equivalent doses of levodopa before and after the surgery (at 6 and 12 months) between both groups. RESULTS: The mean age at the time in which STN-DBS was performed was 59.5 ± 8.6. Linear mixed models showed the absence of statistically significant differences between mutation and non-mutation carriers regarding levodopa doses (p = 0.576), UPDRS II (p = 0.956) and III (p = 0.512) scores, and S&E scale scores (0.758). The only difference between the two groups was observed with respect to H&Y stage in OFF medication/ON stimulation status being lower in genetic PD at 6 months after surgery (p = 0.030). CONCLUSION: Clinical and pharmacological benefit of bilateral STN-DBS is similar in PRKN and LRRK2 mutation carriers and patients with idiopathic PD.

Consenso de expertos españoles sobre el uso de la safinamida en la enfermedad de Parkinson / Spanish expert consensus on the use of safinamide in Parkinson's disease

La safinamida es un nuevo fármaco para el tratamiento de pacientes con enfermedad de Parkinson (EP) con fluctuaciones como tratamiento complementario a levodopa. Dado que por el momento aún no existen estudios de fase IV postautorización debido a la reciente incorporación de la safinamida a la práctica clínica habitual, el interés de este proyecto radica en el desarrollo de una guía de manejo clínico de la safinamida basada en las opiniones de expertos de trastornos del movimiento. Este proyecto se desarrolló en 2 fases: una primera fase que constó de 16 reuniones locales y una segunda fase que consistió en una reunión nacional. Dichas reuniones siguieron un guion de trabajo preestablecido. Tras la reunión nacional se recopilaron las principales conclusiones de los expertos, que han supuesto la base para redactar la presente guía clínica. Se concluyó que la safinamida es eficaz en la reducción de las fluctuaciones motoras y no motoras. Los pacientes con EP con fluctuaciones leves-moderadas son los que más se benefician del tratamiento, si bien el fármaco puede contribuir a mejorar diversos problemas clínicos en pacientes con EP avanzada. Se ha destacado la posibilidad de reducir la dosis de otros fármacos dopaminérgicos tras la introducción de la safinamida, lo cual contribuiría a reducir efectos adversos como el trastorno de control de impulsos. Se hipotetizó sobre el posible efecto de la safinamida sobre la mejoría de las discinesias a dosis más altas de las habitualmente utilizadas. Se ha consensuado que la safinamida es bien tolerada y presenta un perfil de efectos adversos favorable frente a placebo. (AU)

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo. (AU)

Spanish expert consensus on the use of safinamide in Parkinson's disease.

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Edema cerebral idiopático de inicio tardío asociado a estimulación cerebral profunda / Idiopathic delayed-onset edema associated with deep brain stimulation

No disponible

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression.

BACKGROUND: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. MATERIAL AND METHODS: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. RESULTS: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ±â€¯12.8 vs 11.6 ±â€¯10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ±â€¯0.5 vs 4 ±â€¯0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ±â€¯32 vs 29.1 ±â€¯25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. CONCLUSIONS: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.

Spanish expert consensus on the use of safinamide in Parkinson's disease. / Consenso de expertos españoles sobre el uso de la safinamida en la enfermedad de Parkinson.

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.

[Myths and evidence on the use of botulinum toxin: neuropharmacology and dystonia]. / Mitos y evidencias en el empleo de la toxina botulinica: neurofarmacologia y distonias.

INTRODUCTION: Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. AIM: To analyze and summarize different questions about the use of BTA in our clinical practice. DEVELOPMENT: A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia. A literature search at PubMed, mainly for English language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of neuropharmacology, such as mechanism of action, bioequivalence of the different preparations, immunogenicity, etc. were included. Regarding dystonia, the document included questions about methods of evaluation, cervical dystonia, blepharospasm, etc. CONCLUSION: This review does not pretend to be a guide, but rather a tool for continuous training of residents and specialists in neurology, about different specific areas of the management of BTA.

TITLE: Mitos y evidencias en el empleo de la toxina botulinica: neurofarmacologia y distonias.Introduccion. La toxina botulinica de tipo A (TBA) ha supuesto una verdadera revolucion terapeutica en neurologia, y en la actualidad es el tratamiento rutinario en las distonias focales y la espasticidad. Objetivo. Plantear, revisar y responder cuestiones controvertidas en relacion con la neurofarmacologia de la TBA y su uso en las distonias en la practica clinica habitual. Desarrollo. Un grupo de expertos en trastornos del movimiento reviso una lista de temas controvertidos relacionados con la farmacologia de la TBA y su uso en las distonias. Revisamos la bibliografia e incluimos articulos relevantes especialmente en ingles, pero tambien, si su importancia lo merece, en castellano y en frances, hasta junio de 2016. El documento se estructuro como un cuestionario que incluyo las preguntas que podrian generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. Incluimos preguntas sobre diferentes aspectos de la neurofarmacologia, especialmente el mecanismo de accion, la bioequivalencia de los diferentes preparados y la inmunogenicidad. En relacion con el subapartado de las distonias, se incluyeron aspectos sobre la evaluacion y el tratamiento de las distonias focales. Conclusiones. Esta revision no pretende ser una guia, sino una herramienta practica destinada a neurologos y medicos internos residentes interesados en esta area, dentro de diferentes ambitos especificos del manejo de la TBA.

[Psychiatric symptoms of Parkinson's disease following deep brain stimulation surgery on the subthalamic nucleus]. / Manifestaciones psiquiátricas de la enfermedad de Parkinson tras la cirugía de estimulación cerebral profunda del núcleo subtalámico.

AIM: To review the increasing number of papers that report diverse neuropsychiatric disorders that happen in patients diagnosed of Parkinson's disease submitted to brain deep stimulation of subthalamic nuclei with high frequency current. DEVELOPMENT: It is a fact the need to evaluate carefully all the patients who have to submit to this surgical procedure analyzing previous psychiatric history, and the possible appearance of psychiatric sphere symptoms after surgery. The acute depression and the euphoric moods (than can occur immediately after surgery) and major depression, obsession, widespread anxiety and substance abuse (among those of more delayed appearance) constitute examples of this pathology. The treatment of previous psychiatric disorders is forced in all cases and specially relevant in the major depression when suicide ideas coexist. CONCLUSIONS: Information that allow to predict the risk of developing depressive disorders in the postoperative period does not exist at present time, though it is more predictable that it happens in those patients with previous severe depressive history. In general, euphoric moods, apathy and depression, usually are transient and of multifactorial origin that includes the existence of endogenous predisposition, the change to an independence pattern after surgery, the psychotropic effect of levodopa, and the high frequency current stimulation effect on the non motor structures target and in the adjacent regions. It must be outlined that it is possible the appearance of psychotic symptoms after brain deep stimulation of subthalamic nuclei in patients with ideal results on motor disability.