Multicenter Validation of Metabolic Abnormalities Related to PSP According to the MDS-PSP Criteria.

It remains unclear whether the supportive imaging features described in the diagnostic criteria for progressive supranuclear palsy (PSP) are suitable for the full clinical spectrum. The aim of the current study was to define and cross-validate the pattern of glucose metabolism in the brain associated with a diagnosis of different PSP variants. A retrospective multicenter cohort study performed on 73 PSP patients who were referred for a fluorodeoxyglucose positron emission tomography PET scan: PSP-Richardson's syndrome, n = 47; PSP-parkinsonian variant, n = 18; and progressive gait freezing, n = 8. In addition, we included 55 healthy controls and 58 Parkinson's disease (PD) patients. Scans were normalized by global mean activity. We analyzed the regional differences in metabolism between the groups. Moreover, we applied a multivariate analysis to obtain a PSP-related pattern that was cross-validated in independent populations at the individual level. Group analysis showed relative hypometabolism in the midbrain, basal ganglia, thalamus, and frontoinsular cortices and hypermetabolism in the cerebellum and sensorimotor cortices in PSP patients compared with healthy controls and PD patients, the latter with more severe involvement in the basal ganglia and occipital cortices. The PSP-related pattern obtained confirmed the regions described above. At the individual level, the PSP-related pattern showed optimal diagnostic accuracy to distinguish between PSP and healthy controls (sensitivity, 80.4%; specificity, 96.9%) and between PSP and PD (sensitivity, 80.4%; specificity, 90.7%). Moreover, PSP-Richardson's syndrome and PSP-parkinsonian variant patients showed significantly more PSP-related pattern expression than PD patients and healthy controls. The glucose metabolism assessed by fluorodeoxyglucose PET is a useful and reproducible supportive diagnostic tool for PSP-Richardson's syndrome and PSP-parkinsonian variant. © 2020 International Parkinson and Movement Disorder Society.

Mitos y evidencias en el empleo de la toxina botulínica: neurofarmacología y distonías / Myths and evidence on the use of botulinum toxin: neuropharmacology and dystonia

Introducción. La toxina botulínica de tipo A (TBA) ha supuesto una verdadera revolución terapéutica en neurología, y en la actualidad es el tratamiento rutinario en las distonías focales y la espasticidad. Objetivo. Plantear, revisar y responder cuestiones controvertidas en relación con la neurofarmacología de a TBA y su uso en las distonías en la práctica clínica habitual. Desarrollo. Un grupo de expertos en trastornos del movimiento revisó una lista de temas controvertidos relacionados con la farmacología de la TBA y su uso en las distonías. Revisamos la bibliografía e incluimos artículos relevantes especialmente en inglés, pero también, si su importancia lo merece, en castellano y en francés, hasta junio de 2016. El documento se estructuró como un cuestionario que incluyó las preguntas que podrían 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 neurofarmacología, especialmente el mecanismo de acción, la bioequivalencia de los diferentes preparados y la inmunogenicidad. En relación con el subapartado de las distonías, se incluyeron aspectos sobre la evaluación y el tratamiento de las distonías focales. Conclusiones. Esta revisión no pretende ser una guía, sino una herramienta práctica destinada a neurólogos y médicos internos residentes interesados en esta área, dentro de diferentes ámbitos específicos del manejo de la TBA (AU)

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 (AU)

[Predictive factors of the response to treatment with onabotulinumtoxinA in refractory migraine]. / Factores predictores de respuesta al tratamiento con onabotulinumtoxina A en la migraña refractaria.

AIM: To identify the clinical features that predict a favourable response to onabotulinumtoxinA (OnabotA) treatment in patients with refractory migraine. PATIENTS AND METHODS: Retrospective analysis of patients with refractory migraine who underwent at least two pericranial injections of OnabotA between 2008 and 2012. Patients were divided into responders and non-responders. Some clinical features including unilateral location of headache, presence of pericranial muscle tension, type of pain (imploding or exploding), duration of migraine (less than or greater than 10 years) and medication overuse were compared between the two groups. RESULTS: 39 patients were included (35 women) with a mean age of 46 years. 18 patients (46.2%) showed a greater than 50% reduction in the number of headache days/month (responders). When analyzing the different features of migraine, we observed that all were equally prevalent in responders and non-responders (p > 0.05): unilateral location (66.7% vs 66.6% respectively), implosive pain (27.8% vs 38.1%), presence of pericranial muscle tension (33.3% vs 38.1%), duration of migraine more than 10 years (77.8% vs 69.2%) and presence of medication overuse (50% vs 81%). CONCLUSION: We failed to identify any clinical feature in our patients with refractory migraine that predicts a favourable response to OnabotA treatment.

TITLE: Factores predictores de respuesta al tratamiento con onabotulinumtoxina A en la migraña refractaria.Objetivo. Identificar las caracteristicas clinicas que predicen una respuesta favorable al tratamiento con onabotulinumtoxina A (OnabotA) en pacientes con migraña refractaria. Pacientes y metodos. Estudio retrospectivo de pacientes con migraña refractaria que recibieron al menos dos infiltraciones de OnabotA entre los años 2008 y 2012. Los pacientes fueron divididos en respondedores y no respondedores a OnabotA y se compararon entre ambos grupos, y de forma retrospectiva, una serie de caracteristicas clinicas consideradas predictoras de respuesta en estudios previos: localizacion unilateral de la cefalea, presencia de tension muscular pericraneal, tipo de dolor (implosivo, explosivo u ocular), tiempo de evolucion de la migraña (menor o mayor de 10 años) y abuso de medicacion analgesica. Resultados. Se incluyeron 39 pacientes (35 mujeres) con una edad media de 46 años. En 18 pacientes (46,2%) se observo una reduccion mayor del 50% en el numero de dias de cefalea/mes (pacientes respondedores). Al analizar las diferentes caracteristicas de la migraña, se observo que todas ellas fueron igualmente prevalentes en los pacientes respondedores y en los no respondedores (p > 0,05): localizacion unilateral (66,7% frente a 66,6%, respectivamente), dolor implosivo (27,8% frente a 38,1%), presencia de tension muscular pericraneal (33,3% frente a 38,1%), tiempo de evolucion de la migraña mayor de 10 años (77,8% frente a 69,2%) y presencia de abuso de medicacion analgesica (50% frente a 81%). Conclusion. En esta serie de pacientes no se ha identificado ningun rasgo clinico que permita predecir en pacientes con migraña refractaria una respuesta favorable al tratamiento con OnabotA.

Factores predictores de respuesta al tratamiento con onabotulinumtoxina A en la migraña refractaria / Predictive factors of the response to treatment with onabotulinumtoxinA in refractory migraine

Objetivo. Identificar las características clínicas que predicen una respuesta favorable al tratamiento con onabotulinumtoxina A (OnabotA) en pacientes con migraña refractaria. Pacientes y métodos. Estudio retrospectivo de pacientes con migraña refractaria que recibieron al menos dos infiltraciones de OnabotA entre los años 2008 y 2012. Los pacientes fueron divididos en respondedores y no respondedores a OnabotA y se compararon entre ambos grupos, y de forma retrospectiva, una serie de características clínicas consideradas predictoras de respuesta en estudios previos: localización unilateral de la cefalea, presencia de tensión muscular pericraneal, tipo de dolor (implosivo, explosivo u ocular), tiempo de evolución de la migraña (menor o mayor de 10 años) y abuso de medicación analgésica. Resultados. Se incluyeron 39 pacientes (35 mujeres) con una edad media de 46 años. En 18 pacientes (46,2%) se observó una reducción mayor del 50% en el número de días de cefalea/mes (pacientes respondedores). Al analizar las d ferentes características de la migraña, se observó que todas ellas fueron igualmente prevalentes en los pacientes respondedores y en los no respondedores (p > 0,05): localización unilateral (66,7% frente a 66,6%, respectivamente), dolor implosivo (27,8% frente a 38,1%), presencia de tensión muscular pericraneal (33,3% frente a 38,1%), tiempo de evolución de la migraña mayor de 10 años (77,8% frente a 69,2%) y presencia de abuso de medicación analgésica (50% frente a 81%). Conclusión. En esta serie de pacientes no se ha identificado ningún rasgo clínico que permita predecir en pacientes con migraña refractaria una respuesta favorable al tratamiento con OnabotA (AU)

Aim. To identify the clinical features that predict a favourable response to onabotulinumtoxinA (OnabotA) treatment in patients with refractory migraine. Patients and methods. Retrospective analysis of patients with refractory migraine who underwent at least two pericranial injections of OnabotA between 2008 and 2012. Patients were divided into responders and non-responders. Some clinical features including unilateral location of headache, presence of pericranial muscle tension, type of pain (imploding or exploding), duration of migraine (less than or greater than 10 years) and medication overuse were compared between the two groups. Results. 39 patients were included (35 women) with a mean age of 46 years. 18 patients (46.2%) showed a greater than 50% reduction in the number of headache days/month (responders). When analyzing the different features of migraine, we observed that all were equally prevalent in responders and non-responders (p > 0.05): unilateral location (66.7% vs 66.6% respectively), implosive ain (27.8% vs 38.1%), presence of pericranial muscle tension (33.3% vs 38.1%), duration of migraine more than 10 years (77.8% vs 69.2%) and presence of medication overuse (50% vs 81%). Conclusion. We failed to identify any clinical feature in our patients with refractory migraine that predicts a favourable response to OnabotA treatment (AU)

Límites de la medicación oral y transdérmica convencional en la enfermedad de Parkinson / Limits of conventional oral and transdermal medication in Parkinson’s disease

En el momento actual, contamos con medicación antiparkinsoniana eficaz y potente, lo que permite una capacidad funcional aceptable durante los primeros años de la enfermedad de Parkinson. Sin embargo, con el paso del tiempo, existe un deterioro motor y funcional en parte por la presencia de complicaciones motoras y no motoras. La medicación convencional no es capaz de dar respuesta suficiente si las fluctuaciones motoras son superiores a 3-4 horas. En ese punto es razonable evaluar otras terapias; entre ellas hay que considerar, por su sencillez y eficacia, la apomorfina en inyección subcutánea y posteriormente la apomorfina en infusión. La apomorfina es un tratamiento muy efectivo y claramente infrautilizado en la enfermedad de Parkinson avanzada (AU)

At the present time, we have effective and potent antiparkinsonian drugs available which allow patients to have an acceptable functional capacity during the early years of Parkinson’s disease. Yet, as time goes by, motor and functional deterioration develop, partly due to the presence of motor and non-motor complications. The conventional medication is unable to provide an adequate response if the motor fluctuations are beyond 3-4 hours of duration. At this point, it is reasonable to consider other therapies; among them subcutaneous apomorphine injection must be taken into account due to its simplicity and efficacy and later on, subcutaneous apomorphine infusion. Apomorphine is a very effective and clearly underused drug in the treatment of advanced Parkinson’s disease (AU)

[Limits of conventional oral and transdermal medication in Parkinson's disease]. / Límites de la medicación oral y transdérmica convencional en la enfermedad de Parkinson.

At the present time, we have effective and potent antiparkinsonian drugs available which allow patients to have an acceptable functional capacity during the early years of Parkinson's disease. Yet, as time goes by, motor and functional deterioration develop, partly due to the presence of motor and non-motor complications. The conventional medication is unable to provide an adequate response if the motor fluctuations are beyond 3-4 hours of duration. At this point, it is reasonable to consider other therapies; among them subcutaneous apomorphine injection must be taken into account due to its simplicity and efficacy and later on, subcutaneous apomorphine infusion. Apomorphine is a very effective and clearly underused drug in the treatment of advanced Parkinson's disease.

Mecanismos de compensación en la enfermedad de Parkinson / No disponible

No disponible

Does increased excitatory drive from the subthalamic nucleus contribute to dopaminergic neuronal death in Parkinson's disease?

Excitotoxicity has been suggested to play a pivotal role in the pathogenesis of Parkinson disease (PD). As subthalamic nucleus (STN) neurons express glutamate and are overactivated in parkinsonism, it seems that in PD dopaminergic (DA) neurons are under the influence of abnormally high levels of glutamate and consequently might be more vulnerable to neurodegeneration. To determine the contribution of the overactivated STN-SN pathway to the progression of PD, we studied the effect of prior unilateral STN lesion on the toxicity induced by subsequent administration of 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP) to non-human primates. In animals from group 1, kainic-induced lesion of the STN was performed prior to the administration of MPTP whereas in animals from group 2, STN lesion was caused after animals had been chronically treated with MPTP. The lesion of the STN elicited a contralateral hemiballism in animals from group 1, and they developed an asymmetrical parkinsonism after being exposed to MPTP. The STN lesion produced an improvement in the contralateral parkinsonism and mild choreic movements in animals from group 2. Cell counting of tyrosine hydroxylase immunoreactive (TH-ir) cells was performed by stereology and showed a similar loss of TH-ir cells (approximately 85%) in the ipsilateral and contralateral SN to the lesioned STN. These data indicate that the surgical removal of the excitatory drive from the STN to SN neurons does not protect dopaminergic neurons against a chronic and extended toxic effect of MPTP and do not support the assumption that STN blockade might delay the progression of PD.