Trastornos del sueño en la enfermedad de Parkinson y otros trastornos del movimiento

Neurodegenerative processes with movement disorders is predominant features show a high incidence of sleep alterations at some point in their evolution. The degeneration of structures responsible for maintaining the sleep-wakefulness cycles and the architecture of sleep could be at their root. Other factors like the drugs employed in the treatment of motor problems, the limitations to movement, etc., aggravate the problem. Although, at present, there is no medical therapy able to restore the defects derived from the degeneration of the key structures of sleep, an individual analysis of the coadyuvant factors in each patient could help to improve these problems. In this article we describe the main sleep disorders in Parkinson’s disease and other degenerative diseases such as multi-system atrophies or progressive supranuclear paralysis

Revisión crítica de la estimulación subtalámica en la enfermedad de Parkinson

The authors critically review subthalamic nucleus (STN) stimulation for Parkinson's disease (PD) at long follow-up (3-5 years). Subthalamic stimulation induce a significant improvement during the "off" medication in the assessment motor score UPDRS (Unified Parkinson Disease Rating Scale) 3-5 years after surgery. Results show that the benefits obtained in tremor, rigidity, bradykinesia, dyskinesias induced by medication and levodopa reduction are significantly maintained during long term. The improvement in other clinical signs as gait and postural stability at long follow-up are not maintained comparing with the benefits obtained one year after surgery. A high percentage of patients show a cognitive disturbance during the follow-up period that may be correlated with the disease progression. The conclusion is that bilateral STN stimulation is an effective treatment for PD patients at long term but it should be considered earlier in the course of P

A model of increased impulsivity in rats with bilateral parkinsonism treated with Pramipexole

Impulse control disorders (ICD) is a common side effect of the dopaminergic treatment in patients with Parkinson's disease, which is more associated with dopamine agonists than with levodopa. To understand its pathophysiology, reliable animal models are essential. Using the variable delay-to-signal (VDS) paradigm, impulsivity was evaluated in bilateral parkinsonian rats treated with pramipexole (PPX). In this test, rats have to introduce the snout into a nose poke that is signaled by a light (presented at variable delays) triggering the delivery of a food reward after a correct response. Reaching a stable baseline performance, a partial bilateral dopaminergic lesion with 6-OHDA was induced in the dorsolateral striatum (AP: +1mm, L: ±3.4mm, V:-4.7 mm, Bregma). Rats undertook the VDS test under 5 conditions: basal state, 6-OHDA-induced lesion, the effect of two doses of PPX (0,25mg/kg and 3mg/kg; Latin-square design), and the day after the last dose of PPX. Only the acute administration of 3 mg/kg of PPX significantly rised the number of premature responses, indicating an increase of impulsive behavior, in parkinsonian but not in sham rats. Both doses of PPX significantly decreased the accuracy of responding (correct/total number of responses) and increased the incorrect and perseverative (compulsive behavior) responses in both parkinsonian and sham treated groups when compared with saline-treated groups. In conclusion, PPX induced attention deficit (lack of accuracy) as well as compulsive behavior in control and parkinsonian rats, but increased impulsivity only in the parkinsonian animals. This model could constitute a valid tool to investigate the pathophysiology of ICD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orientin

Digital Platform for Automatic Qualitative and Quantitative Reading of a Cryptococcal Antigen Point-of-Care Assay Leveraging Smartphones and Artificial Intelligence

This work was presented in part at 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), which will take place online from 9 – 12 July 2021. Abstract number 03467.Cryptococcosis is a fungal infection that causes serious illness, particularly in immunocompromised individuals such as people living with HIV. Point of care tests (POCT) can help identify and diagnose patients with several advantages including rapid results and ease of use. The cryptococcal antigen (CrAg) lateral flow assay (LFA) has demonstrated excellent performance in diagnosing cryptococcosis, and it is particularly useful in resource-limited settings where laboratory-based tests may not be readily available. The use of artificial intelligence (AI) for the interpretation of rapid diagnostic tests can improve the accuracy and speed of test results, as well as reduce the cost and workload of healthcare professionals, reducing subjectivity associated with its interpretation. In this work, we analyze a smartphone-based digital system assisted by AI to automatically interpret CrAg LFA as well as to estimate the antigen concentration in the strip. The system showed excellent performance for predicting LFA qualitative interpretation with an area under the receiver operating characteristic curve of 0.997. On the other hand, its potential to predict antigen concentration based solely on a photograph of the LFA has also been demonstrated, finding a strong correlation between band intensity and antigen concentration, with a Pearson correlation coefficient of 0.953. The system, which is connected to a cloud web platform, allows for case identification, quality control, and real-time monitoring.CrAg LFA tests were provided by IMMY at no cost. This research was funded by Global Action For Fungal Infections (www.GAFFI.org), JYLAG, a charity Foundation based in Geneva, Switzerland, and Fondo de Investigación Sanitaria from Instituto de Salud Carlos III (PI20CIII/00043). D.B.-P. was supported by grant PTQ2020-011340/AEI/10.13039/501100011033 funded by the Spanish State Investigation Agency. J.C.S.-D. was supported by a fellowship from the Fondo de Investigación Sanitaria (grant FI17CIII/00027).S

Methodology for registration of distended recutms in pelvic CT studies

Purpose: Accurate delineation of the rectum is of high importance in off-line adaptive radiation therapy since it is a major dose-limiting organ in prostate cancer radiotherapy. The intensity-based deformable image registration (DIR) methods cannot create a correct spatial transformation if there is no correspondence between the template and the target images. The variation of rectal filling, gas, or feces, creates a noncorrespondence in image intensities that becomes a great obstacle for intensity-based DIR. Methods: In this study the authors have designed and implemented a semiautomatic method to create a rectum mask in pelvic computed tomography (CT) images. The method, that includes a DIR based on the demons algorithm, has been tested in 13 prostate cancer cases, each comprising of two CT scans, for a total of 26 CT scans. Results: The use of the manual segmentation in the planning image and the proposed rectum mask method (RMM) method in the daily image leads to an improvement in the DIR performance in pelvic CT images, obtaining a mean value of overlap volume index = 0.89, close to the values obtained using the manual segmentations in both images. Conclusions: The application of the RMM method in the daily image and the manual segmentations in the planning image during prostate cancer treatments increases the performance of the registration in presence of rectal fillings, obtaining very good agreement with a physician's manual contours

Terapia celular “neuro-restauradora” en la enfermedad de Parkinson: un debate pendiente

Existe en la actualidad un gran entusiasmo sobre las perspectivas derivadas de la denominada terapia celular en la enfermedad de Parkinson. Este entusiasmo ha sobrepasado la esfera de la comunidad médica, llegando hasta el público general, y se ha venido alimentando de un considerable debate ético y político, hurtándose en todo momento la necesidad de un análisis realmente científico sobre las cualidades y limitaciones reales del tratamiento con células madre en las enfermedades neurodegenerativas. La enfermedad de Parkinson con frecuencia se observa desde una perspectiva simplista, como una mera neurodegeneración de la vía dopaminérgica nigroestriada, punto de vista bajo el que se colocan diferentes diseños tendentes a reemplazar la falta de dopamina en el estriado, mediante el empleo de distintos tipos de terapia celular. En este sentido, es necesario señalar por un lado la naturaleza multisistémica y generalizada de la enfermedad, y por otro lado el carácter progresivo del proceso neurodegenerativo de la enfermedad de Parkinson. Bajo este enfoque, pretender que el mero reemplazo de la dopamina estriatal mediante terapia celular sustitutiva, pueda corregir el carácter generalizado y progresivo de la enfermedad es una aspiración quimérica, que únicamente contribuye a generar expectativas infundadas en el público general. Este artículo pretende argumentar desde un punto de vista puramente científico las dudas sobre las expectativas creadas con estos nuevos diseños terapéuticos.At present there is great enthusiasm over the perspectives deriving from so-called cell therapy in Parkinson’s disease. This enthusiasm has spread beyond the ambit of the medical community, reaching the general public, and has been fuelled by a considerable ethical and political debate, sidestepping the need for a really scientific analysis of the real qualities and limitations of treatment with stem-cells in neurodegenerative diseases. Parkinson’s disease is frequently observed from a simplistic perspective, as a mere neurodegeneration of the nigrostriatal dopaminergic pathway. This viewpoint encompasses different designs that tend to replace the lack of dopamine in the striatum through the use of different types of cell therapy. In this respect, it is important to indicate, on the one hand, the multisystemic and generalised nature of the disease and, on the other, the progressive character of the neurodegenerative process of Parkinson’s disease. With this approach, to claim that the mere replacement of striatal dopamine through replacement cell therapy can correct the generalised and progressive character of the disease is a fanciful aspiration, which can only contribute to generating unfounded expectations in the general public. This article attempts to set out from a purely scientific point of view the doubts over the expectations created by these new therapeutic designs

Mobile based surveillance platform for detecting Zika virus among Spanish Delegates attending the Rio de Janeiro Olympic Games

Background: Zika virus has created a major epidemic in Central and South America, especially in Brazil, during 2015-16. The infection is strongly associated with fetal malformations, mainly microcephaly, and neurological symptoms in adults. During the preparation of the Rio de Janeiro Olympic Games in 2016, members of Olympic Delegations worldwide expressed their concern about the health consequences of being infected with Zika virus. A major risk highlighted by the scientific community was the impact on the spreading of the virus into new territories immediately after the Games. Objectives: To detect real-time incidence of symptoms compatible with arboviral diseases and other tropical imported diseases among the Spanish Olympic Delegation (SOD) attending the Rio Olympic Games in 2016. Methods: We developed a surveillance platform based on a mobile application installed in participant's smartphones that monitored the health status of the SOD through a daily interactive check of the user health status including geo-localization data. The results were evaluated by a study physician on-call through a web-based platform monitoring system. Participants presenting severe symptoms or those compatible with Zika infection prompted an alarm in the system triggering specialized medical assistance and allowing early detection and control of the introduction of arboviral diseases in Spain. Summary of the results: The system was downloaded by 189 participants and used by 143 of them (76%). Median age was 38 years (IQR 16), and 134 (71%) were male. Mean duration of travel was 19 days (+/-9SD). During the Games the highest accumulated incidence observed was for headache: 6.06% cough: 5.30% and conjunctivitis: 3.03%. The incidence rate of cough during the Olympic Games was 1.1% per day per person, followed by headache 0.8% and 0.4% conjunctivitis or diarrhea. In our cohort we observed that non-athletes experienced more incidence of symptoms, except for incidence of cough which was the same in the two groups (1.1%). No participants reported symptoms fulfilling Zika definition case. Conclusion: Our system did not find cases fulfilling Zika definition amongst participants of the SOD during the Games, consistent with limited cases of Zika in Rio during the Games. The app showed good usability and the web based monitoring platform allowed to manage infectious cases in real-time. The overall system has proven to serve as a real-time surveillance platform for detecting symptoms that could be present in tropical imported diseases, especially arboviral diseases, contributing to the preparedness for the introduction of vector borne-diseases in non-endemic countries

Different susceptibility to pramipexole-induced impulsivity in a rat model of parkinson’s disease

Impulse Control Disorders (ICD) in patients with Parkinson’s disease are abnormal behaviors caused by long-term use of dopamine agonists, which pathophysiology is poorly understood. Using parkinsonian rats (adeno-associated viral vectors-mediated overexpression of A53T human α-synuclein in the substantia nigra compacta), we evaluated the impulsive behaviour under acute (0.25 and 3 mg/kg) and chronic (0.25 mg/kg for 4 weeks) administration of pramipexole (PPX) with the Variable Delay-to-Signal (VDS) task (motor and choice impulsivities). Changes in striatal D1 and D2 receptors expression were also analysed. Before treatment, the striatal dopaminergic depletion caused a significant increase of both impulsivity domains with respect to basal condition. In lesioned rats, acutely given PPX 0.25 mg/kg dose increased choice impulsivity only with regard to basal values. Meanwhile, 3 mg/kg PPX increased choice impulsivity compared to their own values at different conditions: basal, before treatment and after acute 0.25 mg/kg PPX administration. After chronic administration, two populations of lesioned animals were distinguished, one showing the same behaviour as control animals and other displaying an increased motor/response (first week of treatment) and cognitive/choice impulsivities (third week of treatment) compared to control animals. This impulsive behaviour disappeared when animals were tested in OFF state. Lower D2 expression in both Caudate-Putamen and Nucleus Accubens and lower D1 levels in Nucleus Accumbens in lesioned rats than in control animals were observed. Therefore, our results indicate that the pro-impulsive effect of PPX in this animal model of PD depends on the dose and administration paradigm employed and the individual predisposition, and it is associated to striatal dopamine receptors expression changes, especially in Nucleus Accumbens. Thus, this model could constitute a valid tool to investigate the pathophysiology of ICD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. DFG11/019, PI11/0210