[Neuroprotection in Parkinson's disease: analysis though group of experts' methodology]. / Neuroprotección en la enfermedad de Parkinson: análisis a través de la metodología de informadores clave.

INTRODUCTION: Currently used antiparkinsonian drugs neither stop nor slow-down the progressive nature of the disease. The final phase of PD is characterized by the presence of symptoms and signs resistant to dopaminergic agents, such as depression, dementia, freezing and falls. Therefore, it is urgent to develop therapies able to positively modify this outcome. Despite neuroprotection is a research priority in PD, no effective strategies have been found so far. METHOD: A key informants study was conducted. A group of experts in PD fulfilled a questionnaire of 10 questions to explore the most important topics related to neuroprotection. Afterwards a consensus about the current situation of neuroprotection in PD was established and future directions of development were suggested. RESULTS: Most of the answers emphasized the need of new concepts, the limitations of animal models and the difficulties in the difficulties in demonstrating a neuroprotective effects in humans owing to a lack of biomarkers. Some of the experts believe that we are already exerting a disease modifying effect. CONCLUSIONS: The concept of neuroprotection should be widened. Animal models should be improved. A reliable biomarker to start neuroprotective therapies long before the appearance of motor symptoms and to evaluate the neuroprotective effect of any therapy should be urgently developed.

Neuroprotección en la enfermedad de Parkinson: análisis a través de la metodología de informadores clave / Neuroprotection in Parkinson’s disease: analysis though group of expert’s methodology

Introducción. La terapia convencional basada en fármacos dopaminérgicosno frena ni ralentiza de modo significativo el cursoprogresivo de la enfermedad de Parkinson (EP). La fase final de la EPse caracteriza por la presencia de síntomas y signos resistentes a laterapia dopaminérgica (depresión, demencia, disartria, caídas, etc.).Es urgente desarrollar terapias que eviten llegar a estas fases deteniendoo retardando la progresión de la enfermedad. Sin embargo,no se dispone de estrategias neuroprotectoras efectivas.Método. Se realizó un estudio de informadores clave en el queexpertos en EP que cumplimentaron un cuestionario de 10 preguntassobre la problemática más importante en el área de la neuroprotecciónen la EP. Tras ello se estableció un consenso sobre la situaciónactual y se sugirieron nuevas direcciones de investigación.Resultados. La mayoría de respuestas coincidieron en la necesidadde nuevos conceptos, en las limitaciones de los actuales modelosanimales o las dificultades de demostrar un efecto protector en humanospor la falta de biomarcadores. Algunos participantes opinanque ya se está ejerciendo un cierto efecto modificador del curso dela enfermedad.Conclusiones. El concepto de neuroprotección debe ser ampliado,los modelos animales deben mejorarse y urge encontrar un biomarcadorfiable para planificar la terapia en fases más precoces ypara determinar el efecto neuroprotector (AU)

Introduction. Currently used antiparkinsonian drugs neitherstop nor slow-down the progressive nature of the disease. The finalphase of PD is characterized by the presence of symptomsand signs resistant to dopaminergic agents, such as depression,dementia, freezing and falls. Therefore, it is urgent to develop therapies able to positively modify this outcome. Despite neuroprotectionis a research priority in PD, no effective strategieshave been found so far.Method. A key informants study was conducted. A group ofexperts in PD fulfilled a questionnaire of 10 questions to explorethe most important topics related to neuroprotection. Afterwardsa consensus about the cur-rent situation of neuroprotection inPD was established and future directions of development weresuggested.Results. Most of the answers emphasized the need of newconcepts, the limitations of animal models and the difficulties inthe difficulties in demonstrating a neuroprotective effects in humansowing to a lack of biomarkers. Some of the experts believethat we are already exerting a disease modifying effect.Conclusions. The concept of neuroprotection should be widened.Animal models should be improved. A reliable biomarkerto start neuroprotective therapies long before the appearance ofmotor symptoms and to evaluate the neuroprotective effect ofany therapy should be urgently developed (AU)

Tics and myoclonus.

This article describes advances occurring over the last year in the pathophysiology, etiology and treatment of tics and myoclonus. Progress is being made in the clinical definition of Tourette syndrome (TS). The search for the TS gene has already excluded more than 50% of the autosomal genome. Progress in the understanding of myoclonus is slow but continuous. Several paper are devoted to clinical aspects but much recent attention has been focused on the pathophysiological mechanisms underlying myoclonus.

Purkinje cells in degenerative diseases of the cerebellum and its connections: a Golgi study.

The cellular pathology of Purkinje cells in several degenerative diseases of the cerebellum and its connections was studied with the rapid Golgi method. Purkinje cells from a patient with Creutzfeldt-Jakob disease (case 1) showed decreased numbers of spiny branchlets. In a patient with a cystic infarct of the cerebellar white matter and chronic deafferentation of the cerebellar cortex (case 2) there was a striking increase in the density of spines on the primary dendrites. No abnormalities were observed in Purkinje cells from two patients with hereditary spinocerebellar degeneration (cases 3 and 4). Purkinje cells in two patients with olivopontocerebellar atrophy (OPCA) had severely reduced numbers of dendritic branches. Ballooned proximal axons were found in Purkinje cells with severely damaged dendrites (cases 5 and 6). In contrast to experimental olivary degeneration in laboratory animals, Purkinje cells from patients with OPCA did not have increased numbers of stubby spines in stout proximal dendrites but few spines with long pedicles were observed in the proximal segment of the primary dendrites and in the cellular body.