Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases / Atrofia multisistémica: características clínicas, anatomopatológicas y evolución de una serie de casos

Background and objective: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.(AU)

Antecedentes y objetivo: La atrofia multisistémica es un trastorno neurodegenerativo raro y letal que se caracteriza por una disfunción autonómica en asociación con parkinsonismo o signos cerebelosos. La marca anatomopatológica es la presencia de agregados de α-sinucleína en los oligodendrocitos, que forman inclusiones citoplasmáticas gliales. Desde un punto de vista clínico, puede ser difícil de distinguir de otros parkinsonismos o ataxias, particularmente en las primeras etapas de la enfermedad. En esta serie de casos, nuestro objetivo es describir en detalle las características de los pacientes con atrofia multisistémica. Material y métodos: Se resumen los datos objetidos de la puntuación de la Escala de calificación unificada de la atrofia multisistémica (UMSARS), imágenes estructurales y funcionales y las pruebas autonómicas cardiovasculares realizadas desde las primeras etapas de la enfermedad. Resultados: La escala UMSAR demostró ser útil para hacer un seguimiento: el examen longitudinal esencial fue para estratificar el riesgo de peor evolución. El diagnóstico neuropatológico mostró un solapamiento entre los subtipos parkinsoniano y cerebeloso, con algunas peculiaridades que podrían ayudar a distinguir los subtipos. Conclusión: Una mejor descripción de las características de la atrofia multisistémica en casos confirmados mediante neuropatología podría ayudar a aumentar la sensibilidad del diagnóstico.(AU)

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. METHODS: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. RESULTS: Statistically significant differences were found between groups in heart rate using the Kruskal-Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. CONCLUSIONS: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population. / SYNAPSES. Estudio observacional europeo para evaluar la seguridad y la efectividad de la safinamida en la práctica clínica habitual: análisis post hoc de la población española del estudio.

INTRODUCTION: Parkinson's Disease (PD) is a progressive age-related neurodegenerative condition requiring new therapeutic alternatives. Safinamide, a novel levodopa add-on therapy, positively affects disease fluctuations by modulating both dopaminergic and glutamatergic systems. To further investigate the use of safinamide in European routine clinical practice, the present post-hoc analysis aimed to understand safinamide's safety profile within the Spanish study population. PATIENTS AND METHODS: Five hundred eleven Spanish patients with PD were evaluated at baseline, four (±1), eight (±1), and 12 (±1) months after initiating safinamide treatment. Unified Parkinson's Disease Rating Scale (UPDRS) total score and UPDRS part III score during on time were used to measure the overall severity of PD and motor complications, respectively, while the severity of adverse events was evaluated following the investigators' criteria. RESULTS: Safinamide showed a favourable safety profile within the Spanish study population, although prescription to patients with psychiatric conditions and off-label use were more frequent than in the European study population. In Spain, clinically meaningful improvements were observed in UPDRS scores when safinamide was used as the only add-on therapy to levodopa (57.4% and 53.7% of patients) and when switching from rasagiline (55.1% of patients). Motor complications were reduced from 83.2% to 63.3% after the study period. Increased safety concerns were undetected in any patient subgroup, although patients with cognitive impairment showed a slightly higher frequency of adverse events. CONCLUSIONS: This subanalysis further supports safinamide use as a safe and efficacious option for the management of motor fluctuations in different subgroups of levodopa-treated patients. However, safinamide should be used with caution in patients with cognitive impairment.

TITLE: SYNAPSES. Estudio observacional europeo para evaluar la seguridad y la efectividad de la safinamida en la práctica clínica habitual: análisis post hoc de la población española del estudio.Introducción. La enfermedad de Parkinson (EP) es una enfermedad neurodegenerativa progresiva relacionada con la edad que requiere nuevas alternativas terapéuticas. La safinamida, un nuevo tratamiento add-on a la levodopa, afecta positivamente a las fluctuaciones de esta enfermedad al modular los sistemas dopaminérgico y glutamatérgico. Para investigar más a fondo el uso de la safinamida en la práctica clínica rutinaria europea, el presente análisis post hoc tiene como objetivo comprender el perfil de seguridad de la safinamida dentro de la población española del estudio. Pacientes y métodos. Se evaluó a 511 pacientes españoles con EP al inicio, cuatro (±1), ocho (±1) y 12 (±1) meses después de iniciar el tratamiento con safinamida. Se utilizaron la puntuación total de la escala unificada de puntuación de la enfermedad de Parkinson (UPDRS) y la puntuación de la UPDRS III, durante el tiempo en on para medir la gravedad general de la EP y las complicaciones motoras, respectivamente, mientras que la gravedad de los acontecimientos adversos se evaluó siguiendo los criterios de los investigadores. Resultados. La safinamida mostró un perfil de seguridad favorable en la población española del estudio, aunque la prescripción a pacientes con enfermedades psiquiátricas y el uso para indicaciones no autorizadas fueron más frecuentes que en la población europea del estudio. En España se observaron mejoras clínicamente significativas en las puntuaciones de la UPDRS cuando se utilizó la safinamida como único tratamiento add-on a la levodopa (el 57,4 y el 53,7% de los pacientes) y cuando se venía de administrar rasagilina (el 55,1% de los pacientes). Las complicaciones motoras se redujeron del 83,2 al 63,3% tras el período de estudio. No se detectaron mayores problemas de seguridad en ningún subgrupo de pacientes, aunque los pacientes con deterioro cognitivo mostraron una frecuencia algo superior de acontecimientos adversos. Conclusiones. Este subanálisis respalda el uso de la safinamida como opción segura y eficaz para el tratamiento de las fluctuaciones motoras en diferentes subgrupos de pacientes tratados con levodopa. Sin embargo, la safinamida debe utilizarse con precaución en pacientes con deterioro cognitivo.

SYNAPSES. Estudio observacional europeo para evaluar la seguridad y la efectividad de la safinamida en la práctica clínica habitual: análisis post hoc de la población española del estudio / SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population

Introducción La enfermedad de Parkinson (EP) es una afección neurodegenerativa progresiva relacionada con la edad que requiere nuevas alternativas terapéuticas. La safinamida, un nuevo tratamiento complementario de la levodopa, afecta positivamente a las fluctuaciones de esta enfermedad al modular los sistemas dopaminérgico y glutamatérgico. Para investigar más a fondo el uso de la safinamida en la práctica clínica rutinaria europea, el presente análisis post hoc tiene como objetivo comprender el perfil de seguridad de la safinamida dentro de la población española del estudio. Pacientes y métodos Se evaluó a 511 pacientes españoles con EP al inicio, cuatro (±1), ocho (±1) y 12 (±1) meses después de iniciar el tratamiento con safinamida. Se utilizaron la puntuación total de la escala unificada de puntuación de la enfermedad de Parkinson (UPDRS) y la puntuación de la UPDRS III, durante el tiempo en on para medir la gravedad general de la EP y las complicaciones motoras, respectivamente, mientras que la gravedad de los acontecimientos adversos se evaluó siguiendo los criterios de los investigadores. Resultados La safinamida mostró un perfil de seguridad favorable en la población española del estudio, aunque la prescripción a pacientes con enfermedades psiquiátricas y el uso para indicaciones no autorizadas fueron más frecuentes que en la población europea del estudio. En España se observaron mejoras clínicamente significativas en las puntuaciones de la UPDRS cuando se utilizó la safinamida como único tratamiento complementario a la levodopa (el 57,4 y el 53,7% de los pacientes) y cuando se venía de administrar rasagilina (el 55,1% de los pacientes). Las complicaciones motoras se redujeron del 83,2 al 63,3% tras el período de estudio. No se detectaron mayores problemas de seguridad en ningún subgrupo de pacientes, aunque los pacientes con deterioro cognitivo mostraron una frecuencia algo superior de acontecimientos adversos. Conclusiones ... (AU)

Introduction. Parkinson’s Disease (PD) is a progressive age-related neurodegenerative condition requiring new therapeutic alternatives. Safinamide, a novel levodopa add-on therapy, positively affects disease fluctuations by modulating both dopaminergic and glutamatergic systems. To further investigate the use of safinamide in European routine clinical practice, the present post-hoc analysis aimed to understand safinamide’s safety profile within the Spanish study population. Patients and methods. Five hundred eleven Spanish patients with PD were evaluated at baseline, four (±1), eight (±1), and 12 (±1) months after initiating safinamide treatment. Unified Parkinson’s Disease Rating Scale (UPDRS) total score and UPDRS part III score during on time were used to measure the overall severity of PD and motor complications, respectively, while the severity of adverse events was evaluated following the investigators’ criteria. Results. Safinamide showed a favourable safety profile within the Spanish study population, although prescription to patients with psychiatric conditions and off-label use were more frequent than in the European study population. In Spain, clinically meaningful improvements were observed in UPDRS scores when safinamide was used as the only add-on therapy to levodopa (57.4% and 53.7% of patients) and when switching from rasagiline (55.1% of patients). Motor complications were reduced from 83.2% to 63.3% after the study period. Increased safety concerns were undetected in any patient subgroup, although patients with cognitive impairment showed a slightly higher frequency of adverse events. Conclusions. This subanalysis further supports safinamide use as a safe and efficacious option for the management of motor fluctuations in different subgroups of levodopa-treated patients. However, safinamide should be used with caution in patients with cognitive impairment. (AU)

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome.

INTRODUCTION: We propose a protocol for study of complex regional pain syndrome (CRPS) based on a battery of quantitative measures (skin thermography, electrochemical skin conductance and sensory thresholds) and apply such protocol to 5 representative cases of CRPS. PATIENTS AND METHODS: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for the diagnosis of CRPS. RESULTS: All patients showed spontaneous pain and allodynia. Two cases correspond to a stage I, in both the resting basal temperature was increased in the affected limb. Three cases reflect more advanced stages with a decrease in resting temperature and a delay in the recovery of the temperature when compared to contralateral limb. DISCUSSION: These non-invasive quantitative functional tests not only improve the diagnostic accuracy of CRPS but also, they help us to stratify and understand the pathological processes of the disease.

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome / Utilidad de la termografía en el diagnóstico y clasificación del síndrome de dolor regional complejo

Introduction: We propose a protocol for study of complex regional pain syndrome (CRPS) basedon a battery of quantitative measures (skin thermography, electrochemical skin conductanceand sensory thresholds) and apply such protocol to 5 representative cases of CRPS.Patients and methods: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for thediagnosis of CRPS. Results: All patients showed spontaneous pain and allodynia. Two cases correspond to a stageI, in both the resting basal temperature was increased in the affected limb. Three cases reflectmore advanced stages with a decrease in resting temperature and a delay in the recovery ofthe temperature when compared to contralateral limb.Discussion: These non-invasive quantitative functional tests not only improve the diagnosticaccuracy of CRPS but also, they help us to stratify and understand the pathological processesof the disease.(AU)

Introducción: Proponemos un protocolo para el estudio del síndrome de dolor regionalcomplejo (SDRC) basado en una batería de medidas cuantitativas (termografía cutánea, con-ductancia electroquímica cutánea y umbrales sensoriales en la prueba sensorial cuantitativa[QST]) y aplicamos dicho protocolo a cinco casos representativos de SDRC. Pacientes y métodos: Se presentan cinco casos de SDRC (dos mujeres/tres hombres) quecumplieron con los criterios de Budapest para el diagnóstico de SDRC. Resultados: Todos los pacientes presentaron dolor espontáneo y alodinia. Dos casos correspon-den a un estadio I, en ambos, la temperatura basal de reposo se incrementó en el miembroafectado. Tres casos muestran estadios más avanzados con disminución de la temperatura dereposo y retraso en la recuperación de la temperatura, en comparación con la extremidadcontralateral, que reflejan fases más avanzadas de la enfermedad. Discusión: Estas pruebas funcionales cuantitativas no invasivas no solo mejoran la precisióndiagnóstica del SDRC sino que también nos ayudan a estratificar las diferentes fases y compren-der los procesos patológicos de la enfermedad.(AU)

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? OBJECTIVE: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. METHODS: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. RESULTS: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. CONCLUSIONS: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

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.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

Management of Parkinson's disease and other movement disorders in woman of childbearing age: Part 1. / Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: Parte 1.

INTRODUCTION: The main challenge of Parkinson's disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. OBJECTIVES: This study aims to define the clinical characteristics of women of childbearing age with Parkinson's disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: Parkinson's disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account.

Management of Parkinson's disease and other movement disorders in women of childbearing age: Part 2. / Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: parte 2.

INTRODUCTION: Many diseases associated with hyperkinetic movement disorders manifest in women of childbearing age. It is important to understand the risks of these diseases during pregnancy, and the potential risks of treatment for the fetus. OBJECTIVES: This study aims to define the clinical characteristics and the factors affecting the lives of women of childbearing age with dystonia, chorea, Tourette syndrome, tremor, and restless legs syndrome, and to establish guidelines for management of pregnancy and breastfeeding in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the content by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: We must evaluate the risks and benefits of treatment in all women with hyperkinetic movement disorders, whether pre-existing or with onset during pregnancy, and aim to reduce effective doses as much as possible or to administer drugs only when necessary. In hereditary diseases, families should be offered genetic counselling. It is important to recognise movement disorders triggered during pregnancy, such as certain types of chorea and restless legs syndrome.

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome.

INTRODUCTION: We propose a protocol for study of complex regional pain syndrome (CRPS) based on a battery of quantitative measures (skin thermography, electrochemical skin conductance and sensory thresholds) and apply such protocol to 5 representative cases of CRPS. PATIENTS AND METHODS: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for the diagnosis of CRPS. RESULTS: All patients showed spontaneous pain and allodynia. Two cases correspond to a stage I, in both the resting basal temperature was increased in the affected limb. Three cases reflect more advanced stages with a decrease in resting temperature and a delay in the recovery of the temperature when compared to contralateral limb. DISCUSSION: These non-invasive quantitative functional tests not only improve the diagnostic accuracy of CRPS but also, they help us to stratify and understand the pathological processes of the disease.

New therapeutic approaches to target alpha-synuclein in Parkinson's disease: The role of immunotherapy.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by a slow and progressive loss of dopaminergic neurons. Its neuropathological hallmark is the accumulation of aggregated form of α-synuclein (α-syn) protein in intracellular inclusions known as Lewy bodies. This aggregated α-syn is believed to be central to the pathogenesis of PD. Emerging evidence suggests that aggregated forms of α-syn self-amplificates and propagates spreading from cell-to-cell in a "prion-like" fashion. Genetics and environmental factors are known causes for the pathogenesis of PD. In last years, inflammation in the pathophysiology of PD is gaining more importance. This neuroinflammation seems to contribute to the progressive degeneration of dopaminergic neurons. The currently available therapies for PD fail to modify the disease progression and neurodegeneration. The connection between α-syn and PD makes α-syn the major therapeutic target. We summarize the possible therapeutic strategies to target α-syn according to the steps in the molecular pathogenesis. The contribution of neuroinflammation to the progression of the disease and the "prion-like" hypothesis which enables targeting the extracellular phase of transmission of α-syn, make immunotherapy probably the most promising therapeutic approach for PD.

Long-term impact of subthalamic stimulation on cognitive function in patients with advanced Parkinson's disease. / Impacto de la estimulación subtalámica a largo plazo sobre la situación cognitiva de los pacientes con enfermedad de Parkinson avanzada.

OBJECTIVE: The aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery. MATERIAL AND METHODS: We conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2±8.2 years; mean progression time of 14.1±6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Patients were found to score lower on the MMSE (-0.89%), clock-drawing test (-2.61%), MDRS (-1.72%), and especially phonemic (-13.28%) and sematic verbal fluency tests (-12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (-10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (-16.87%), WAIS-III-LN (-16.67%), and JLO test (-11.56%). DISCUSSION: In our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD.

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.

Long-term effects of cognitive rehabilitation on brain, functional outcome and cognition in Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive rehabilitation has demonstrated efficacy in producing short-term cognitive and brain changes in patients with Parkinson's disease (PD). To date, no study has assessed the long-term effects of cognitive rehabilitation using neuroimaging techniques in PD. The aim was to assess the longitudinal effects of a 3-month cognitive rehabilitation programme evaluating the cognitive, behavioural and neuroimaging changes after 18 months. METHODS: Fifteen patients with PD underwent a cognitive, behavioural and neuroimaging assessment at pre-treatment (T0 ), post-treatment (T1 ) and after 18 months (T2 ). This study examined the long-term effects (from T0 to T2 ) and the maintenance of the changes (from T1 to T2 ). T1-weighted, diffusion-weighted, functional magnetic resonance imaging during both a resting-state and a memory paradigm were acquired. Voxel-based morphometry and tract-based spatial statistics were used for grey and white matter analyses. A region-of-interest-to-region-of-interest approach was used for resting-state functional connectivity (FC) and a model-based approach was used for brain activation during the memory paradigm. RESULTS: Patients with PD showed increased cognitive performance, decreased functional disability, increased brain FC and activation at T2 compared with T0 (P < 0.05, FDR). Moreover, patients showed maintenance of the improvements in cognition and functionality, and maintenance of the increased brain FC and activation at T2 compared with T1 . However, significant grey matter reduction and alterations of white matter integrity were found at T2 (P < 0.05, FWE). CONCLUSIONS: Findings suggest that the improved cognitive performance and increased brain FC and activation after cognitive rehabilitation were significantly maintained after 18 months in patients with PD, despite the structural brain changes, consistent with a progression of neurodegenerative processes.

Dysautonomia Differentially Influences the Effect of Affective Pain Perception on Quality of Life in Parkinson's Disease Patients.

Background. Our aim was to evaluate the real effect of dysautonomic symptoms on the influence of affective pain perception on quality of life in PD patients. Methods. An observational cross-sectional study was carried out using 105 Parkinson's disease (PD) patients of the Movement Disorders Unit, Hospital de Cruces (Bilbao, Spain) [men 59 (56.2%), women 46 (43.85%)]. Statistical analysis was made in order to evaluate the possible association of pain with life quality. Results. Quality of life measured by PDQ-39 (Parkinson's Disease Questionnaire for quality of life) was statistically associated with affective dimension of pain (PRIA, affective pain rating index). However, the influence of this dimension on PDQ-39 was different in the specific case of PD patients that experimented a high score (>12) in SCOPA-AUT (Scale for Outcomes in PD-Autonomic scale). Conclusions. These results confirm the effect of affective perception of pain in life quality of PD patients, indicating the critical role of autonomic symptoms in the modulation of the influence of pain on quality of life and showing the possible utility of dysautonomia as clinical prognostic indicator of quality of life in PD patients affected by pain.