1,721,662 research outputs found
Switching on the lights of dyskinesia: Perspectives and limits of the optogenetic approaches
No full textN/
Dystonia and levodopa-induced dyskinesias in Parkinson's disease: Is there a connection?
No full textDystonia and levodopa-induced dyskinesia (LID) are both hyperkinetic movement disorders. Dystonia arises most often spontaneously, although it may be seen after stroke, injury, or as a result of genetic causes. LID is associated with Parkinson's disease (PD), emerging as a consequence of chronic therapy with levodopa, and may be either dystonic or choreiform. LID and dystonia share important phenomenological properties and mechanisms. Both LID and dystonia are generated by an integrated circuit involving the cortex, basal ganglia, thalamus and cerebellum. They also share dysregulation of striatal cholinergic signaling and abnormalities of striatal synaptic plasticity. The long duration nature of both LID and dystonia suggests that there may be underlying epigenetic dysregulation as a proximate cause. While both may improve after interventions such as deep brain stimulation (DBS), neither currently has a satisfactory medical therapy, and many people are disabled by the symptoms of dystonia and LID. Further study of the fundamental mechanisms connecting these two disorders may lead to novel approaches to treatment or prevention
Late onset epilepsy and Alzheimer's disease: Exploring the dual pathogenic role of amyloid-b
No full textN/
Drug-induced Creutzfeldt-Jakob disease-like syndrome: Early CSF analysis as useful tool for differential diagnosis
No full textWe report the case of a 78-year-old man who showed a subacute onset of severe cognitive impairment, ataxia, tremor, stimulus sensitive myoclonus and hypophonia. Since a few weeks, he received a treatment with a combination of tricyclic antidepressants for mood disorder. The clinical picture mimicked Creutzfeldt-Jakob disease (CJD), but we could rule out this diagnosis by means of cerebrospinal fluid (CSF) analysis, which showed normal level of tau protein and Aß1-42, being also negative for CSF 14-3-3 protein. A complete clinical recovery was observed after the discontinuation of antidepressants. So far, some cases of drug-induced CJD-like syndrome have been described. In our experience, early CSF analysis shows high diagnostic usefulness in order to exclude CJD
Continuous Dopaminergic Stimulation as a Treatment for Parkinson's Disease: Current Status and Future Opportunities
No full textLevodopa-induced motor complications remain an important source of disability for many patients with Parkinson's disease. Substantial laboratory evidence indicates that motor complications relate to the nonphysiological restoration of brain dopamine with intermittent doses of standard oral levodopa. Dopamine levels are normally maintained at a relatively constant level, even following a dose of levodopa. However, in the Parkinsonian state, where dopamine terminals have degenerated with a loss of their buffering capacity, intermittent doses of levodopa lead to dramatic peak and trough fluctuations in striatal dopamine levels. This results in pulsatile stimulation of dopamine receptors, molecular changes in striatal neurons, physiological changes in pallidal neurons, and ultimately the development of motor complications. These observations led to the hypothesis that continuous delivery of levodopa might be associated with a reduced risk of motor complications. This concept is known as continuous dopamine stimulation (CDS). Preliminary studies in animal models and patients with Parkinson's disease supported this hypothesis, suggesting a reduced risk of both motor fluctuations and dyskinesias. The present review considers the scientific advances and the more definitive clinical trials testing this concept that have taken place during the past decade and considers ongoing experimental studies and future opportunities. © 2020 International Parkinson and Movement Disorder Society
Liverpool Adverse Events Profile: Italian validation and predictive value for dropout from antiepileptic treatment in people with epilepsy
No full textIntroduction: Adverse events (AEs) of antiepileptic drugs (AEDs) affect patient compliance and dropout. No questionnaire measuring AEs of AEDs is available for Italian-speaking people with epilepsy. Moreover, no questionnaire has been shown to predict patient dropout. Objective: The aim of this study was to provide a validated Italian version of the Liverpool Adverse Events Profile (iLAEP) and to define iLAEP reliability in AE monitoring and dropout risk prediction. Methods: The original LAEP was translated and tested for internal consistency and reliability. Patients with epilepsy who are on stable AED regimen completed the questionnaire as well as a 3-month follow-up to assess dropouts. Results: Overall, 204 patients with epilepsy were enrolled (mean age: 47.1 ± 21.5). High internal consistency (Cronbach's α = 0.88) was demonstrated, and very quick completion time was registered (mean = 9 min). A 3-month follow-up was performed to assess treatment discontinuation and potential predictive value of the iLAEP score. Treatment was discontinued in 33.3% of the cohort. Moreover, iLAEP scores (mean = 30.71) significantly differed between patients interrupting (39.15 ± 5.66) and those prosecuting treatment (29.4 ± 6.54, p <.001). A cutoff of 36.5 had an 85% accuracy in predicting treatment discontinuation (85% sensitivity, 79% specificity). Scores > 36.5 were associated with a 20.27-fold increase in dropout relative risk (RR), with a 66% positive predictive value. Conclusions: The iLAEP represents a reliable, quick, and inexpensive assessment tool for patient-reported AEs of AEDs. An iLAEP cutoff of 36.5 differentiates patients unlikely to interrupt treatment from those more prone to stop AEDs in the following 3 months. The iLAEP might help clinicians in weighting the risk of dropout and better tailor treatment to patients
Magnetization transfer MRI in dementia disorders, Huntington's disease and parkinsonism
No full textMagnetic resonance imaging is the most used technique of neuroimaging. Using recent advances in magnetic resonance application it is possible to investigate several changes in neurodegenerative disease. Among different techniques, magnetization-transfer imaging (MTI), a magnetic resonance acquisition protocol assessing the magnetization exchange between protons bound to water and those bound to macromolecules, is able to identify microstructural brain tissue changes peculiar of neurodegenerative diseases. This review provides a report on the MTI technique and its use in the dementia disorders, Huntington's disease and parkinsonisms, comprehensive of the predictive values of MTI in the identification of early-phase disease
Transcranial doppler examination in the early diagnosis of arteriovenous malformation presenting as migraine with aura
No full textHypoxia in striatal and cortical neurones: membrane potential and Ca2+ measurements
No full textSimultaneous measurements of membrane potential and intracellular Ca2+ were used to study the effects of hypoxia on striatal and cortical neurones. Striatal neurones responded to hypoxia with a reversible membrane depolarization coupled with a transient increase in intracellular Ca2+. Thirty minutes of hypoxia caused an irreversible membrane depolarization associated with a massive raise in Ca2+ levels, leading to cell death. Conversely, cortical neurones were more resistant to O2 deprivation. Hypoxia (4-10 min) induced minimal changes in both membrane potential and Ca2+ signals. Longer periods (20-30 min) caused an initial membrane hyperpolarization followed by a large but reversible depolarization coupled with a transient increase in Ca2+ signals. These results support the hypothesis of a differential sensitivity of central neurones to hypoxia, suggesting that striatal neurones are more vulnerable than cortical cells
- …
