Parkinson's disease and diabetes mellitus: common mechanisms and treatment repurposing.

In the last decade, attention has become greater to the relationship between neurodegeneration and abnormal insulin signaling in the central nervous system, as insulin in the brain is implicated in neuronal survival, plasticity, oxidative stress and neuroinflammation. Diabetes mellitus and Parkinson's disease are both aging-associated diseases that are turning into epidemics worldwide. Diabetes mellitus and insulin resistance not only increase the possibility of developing Parkinson's disease but can also determine the prognosis and progression of Parkinsonian symptoms. Today, there are no available curative or disease modifying treatments for Parkinson's disease, but the role of insulin and antidiabetic medications in neurodegeneration opens a door to treatment repurposing to fight against Parkinson's disease, both in diabetic and nondiabetic Parkinsonian patients. Furthermore, it is essential to comprehend how a frequent and treatable disease such as diabetes can influence the progression of neurodegeneration in a challenging disease such as Parkinson's disease. Here, we review the present evidence on the connection between Parkinson's disease and diabetes and the consequential implications of the existing antidiabetic molecules in the severity and development of Parkinsonism, with a particular focus on glucagon-like peptide-1 receptor agonists.

Oral Anticoagulation and Risk of Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Mechanical Thrombectomy: Data From the Nordictus Registry.

Introduction: We aimed to evaluate if prior oral anticoagulation (OAC) and its type determines a greater risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke (AIS) subjected to mechanical thrombectomy. Materials and Methods: Consecutive patients with AIS included in the prospective reperfusion registry NORDICTUS, a network of tertiary stroke centers in Northern Spain, from January 2017 to December 2019 were included. Prior use of oral anticoagulants, baseline variables, and international normalized ratio (INR) on admission were recorded. Symptomatic intracranial hemorrhage (sICH) was the primary outcome measure. Secondary outcome was the relation between INR and sICH, and we evaluated mortality and functional outcome at 3 months by modified Rankin scale. We compared patients with and without previous OAC and also considered the type of oral anticoagulants. Results: About 1.455 AIS patients were included, of whom 274 (19%) were on OAC, 193 (70%) on vitamin K antagonists (VKA), and 81 (30%) on direct oral anticoagulants (DOACs). Anticoagulated patients were older and had more comorbidities. Eighty-one (5.6%) developed sICH, which was more frequent in the VKA group, but not in DOAC group. OAC with VKA emerged as a predictor of sICH in a multivariate regression model (OR, 1.89 [95% CI, 1.01-3.51], p = 0.04) and was not related to INR level on admission. Prior VKA use was not associated with worse outcome in the multivariate regression model nor with mortality at 3 months. Conclusions: OAC with VKA, but not with DOACs, was an independent predictor of sICH after mechanical thrombectomy. This excess risk was associated neither with INR value by the time thrombectomy was performed, nor with a worse functional outcome or mortality at 3 months.

Estimulación magnética transcraneal theta-burst intermitente para el tratamiento de la espasticidad en pacientes con esclerosis múltiple recurrente: resultados de un ensayo clínico aleatorizado doble ciego / Intermittent theta-burst transcranial magnetic stimulation for the treatment of spasticity in patients with recurring multiple sclerosis: the results of a double-blind randomised clinical trial

Objetivo. La estimulación magnética transcraneal repetitiva podría ser útil como tratamiento no farmacológico para la espasticidad. El objetivo de este estudio es reevaluar el efecto clínico y los cambios neurofisiológicos que produce la estimulación theta-burst intermitente (ETBi) sobre la espasticidad de las extremidades inferiores en pacientes con esclerosis múltiple recurrente en un ensayo aleatorizado, doble ciego, controlado con placebo. Pacientes y métodos. Diecisiete pacientes en la fase remitente de la enfermedad fueron aleatoriamente asignados al grupo placebo o al grupo de tratamiento activo mediante estimulación magnética transcraneal repetitiva con protocolo ETBi sobre la corteza motora contralateral de la pierna más afectada. El procedimiento consistió en 10 sesiones diarias durante dos semanas. Cada sesión consistió en 10 ráfagas que contenían tres pulsos a 50 Hz repetidos a intervalos de 200 ms (5 Hz) cada 10 s para un total de 600 estímulos. El efecto de ETBi se evaluó mediante el uso de parámetros clínicos (como la escala de Ashworth modificada) y neurofisiológicos (ratio de amplitud H/M y duración del período cortical silente). Resultados. Dos semanas de ETBi sobre la corteza motora de la pierna más afectada no produjeron ningún efecto clínico significativo sobre la espasticidad en pacientes con esclerosis múltiple recurrente. Sin embargo, aunque de forma no significativa, se observó disminución de la ratio de amplitud H/M y un aumento de la duración del período cortical silente. Conclusión. El protocolo de estimulación utilizado en este estudio no parece tener un efecto terapéutico significativo. Sin embargo, recomendamos estudios adicionales, ya que los cambios neurofisiológicos fueron evidentes

Aim. It has been suggested that the repetitive transcranial magnetic stimulation could be useful as a non-pharmacological treatment for spasticity. The aim of this study was to evaluate the clinical and neurophysiological effects of high-frequency intermittent theta burst stimulation (iTBS) on lower limb spasticity in patients with relapsing multiple sclerosis in a randomized, double-blind placebo controlled trial. Patients and methods. Seventeen patients in the remitting phase of the disease were randomly allocated to sham or magnetic therapy group and underwent iTBS over contralateral motor cortex of the most affected leg once a day for two weeks. Each session consisted of 10 bursts containing three pulses at 50 Hz repeated at 200 ms intervals (5 Hz) every 10 s for a total of 600 stimuli. The iTBS effect was assessed by using clinical (such as the Modified Ashworth Scale) and neurophysiological (H/M amplitude ratio and cortical silent period duration) parameters. Results. Two-week iTBS over motor cortex of the most affected leg did not produce any significant clinical effect on spasticity. However, it decreases the H/M amplitude ratio and increases duration of cortical silent period but not significantly, in patients with relapsing multiple sclerosis. CONCLUSION. The stimulation protocol used in this study does not have significant therapeutic effect. Therefore, we do recommend further studies as neurophysiological changes were evident

Variante conductual de la demencia frontotemporal como forma de presentación de la degeneración corticobasal / Behavioural variant of frontotemporal dementia as the presenting symptom of corticobasal degeneration

Introducción. La variante conductual de la demencia frontotemporal se caracteriza por el deterioro progresivo de la personalidad, social y cognitivo que se asocia con diversas patologías moleculares de la degeneración lobar frontotemporal (DLFT): DLFT-tau, DLFT-TDP y DLFT-FUS. El estudio anatomopatológico es necesario para su diagnóstico. Caso clínico. Varón de 61 años, con un cuadro progresivo de tres años de evolución de trastorno conductual, apatía, lenguaje pobre, perseveración, falta de empatía, bulimia y disfunción ejecutiva. En la neuroimagen se objetivó una atrofia cortical frontal de predominio derecho, y en la tomografía simple por emisión de fotón único cerebral, una hipoperfusión frontoparietotemporal bilateral con afectación de tálamos y caudados. Clínicamente, se le diagnosticó probable demencia frontotemporal, variante conductual. Tras su fallecimiento, se donó el cerebro al Banco de Tejidos Neurológicos y el diagnóstico neuropatológico fue el de degeneración corticobasal. Conclusiones. La degeneración corticobasal es una de las taupatías de la DLFT-tau. Los criterios diagnósticos de degeneración corticobasal de 2013 contemplan como fenotipo clínico la disfunción ejecutiva, las alteraciones conductuales y de personalidad similar al de este paciente. El caso anatomoclínico presentado ilustra la falta de correlación entre el fenotipo clínico y el diagnóstico neuropatológico subyacente en la demencia frontotemporal, y la necesidad de realizar el estudio histopatológico para llegar al diagnóstico definitivo

Introduction. The behavioural variant of frontotemporal dementia is characterised by progressive social, cognitive and personality deterioration associated with several molecular pathologies of frontotemporal lobar dementia (FTLD): FTLD-tau, FTLD-TDP and FTLD-FUS. Its diagnosis requires pathological studies. Case report. A 61-year-old male, with a three-year progressive history of behavioural disorder, apathy, poor language skills, perseveration, lack of empathy, bulimia and executive dysfunction. Neuroimaging revealed right-dominant frontal cortical atrophy, and a single-photon emission tomography brain scan showed bilateral frontal hypoperfusion with thalamic and caudate involvement. Clinically, he was diagnosed with probable frontotemporal dementia, behavioural variant. On his death, his brain was donated to the Neurological Tissue Bank and the neuropathological diagnosis was corticobasal degeneration. Conclusions. Corticobasal degeneration is one of the FTLD-tau tauopathies. The 2013 diagnostic criteria for corticobasal degeneration include executive dysfunction and behavioural and personality disorders similar to those of this patient as a clinical phenotype. The anatomoclinical case presented illustrates the absence of any correlation between the clinical phenotype and the underlying neuropathological diagnosis in frontotemporal dementia, and the need to conduct a histopathological study in order to reach a definitive diagnosis