Melatonin in sleep disorders.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.

Melatonina en los trastornos de sueño / Melatonin in sleep disorders

La melatonina es la principal hormona implicada en la regulación de la oscilación entre sueño y vigilia. Es fácilmente sintetizable y administrable por vía oral, lo que ha propiciado el interés para usarla en el tratamiento de una de las patologías humanas más prevalentes, el insomnio. Además, el hecho de que su producción se reduzca con la edad, en una relación inversamente proporcional a la frecuencia de mala calidad de sueño, ha reforzado la idea de que su déficit es, al menos en parte, responsable de estos trastornos. En esta línea de pensamiento, remontar el déficit que se va instaurando a medida que transcurre la vida sería un modo natural de restaurar la integridad del sueño, que se va perdiendo con la edad. Sin embargo, a pesar del innegable atractivo teórico de esta aproximación al problema del insomnio, la evidencia científica que sustenta el posible beneficio de esta terapia sustitutiva es escasa. Ni siquiera están bien definidos los rangos de dosis a los que administrarla o la formulación farmacológica más adecuada. En la presente revisión se repasa la fisiología de la melatonina, se revisan las características farmacológicas de su administración exógena y se analizan los datos existentes sobre su utilidad clínica. (AU)

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness. (AU)

Fatal case of simply influenza A (H3N2)-associated encephalitis in immunocompetent patient.

Influenza virus-associated encephalopathy/encephalitis is a rare entity in adults that can lead to severe neurological sequelae and even death. The clinical presentation can be quite diverse. This absence of a typical presentation along with the difficulty detecting the virus in the cerebrospinal fluid represents a diagnostic challenge. We present the case of a 79-year-old male with sudden onset of decreased consciousness and signs of right hemisphere damage. The presence of influenza A (H3N2) virus in respiratory sample along with compatible findings in cranial magnetic resonance led to the diagnosis. The patient died without responding to treatment with antivirals and immunomodulators and the anatomopathological study did not detect infectious agent. Early diagnostic suspicion is essential to establish adequate treatment and improve the prognosis.

Intraindividual Characterization of the Sleep Spindle Variability in Healthy Subjects.

Spatial and frequency characterization of sleep spindles have been extensively addressed using M/EEG or fMRI recordings. However, its intraindividual variability across time has not been addressed. Here we propose to assess the intraindividual variability of sleep spindles in a time-resolved way by means of a trial-to-trial-variability (TTV) measure. For that purpose, the EEG of 26 healthy subjects were recorded overnight. After an exhaustive preprocessing pipeline to remove artifacts, spindles were automatically detected using a complex demodulation-based method. Then, the Wavelet Scalogram was estimated to validate it. Spindle TTV of each participant was also computed for all the conventional EEG frequency bands. Root mean square (RMS) of each TTV signal was calculated as a measure of the total variability of each spindle. Results showed significant differences in the variability between frequencies. Specifically, RMS in the beta-1 frequency band showed higher values as compared to all the other frequency bands (p<0.001). TTV curves showed a dichotomic trend, with lower frequencies showing an increase in the variability before the spindle onset, and higher frequencies showing such increase after the onset. The dependence of the spindle variability with the frequency could be explained by the influence of the multiple cortical generators involved.Clinical Relevance- Sleep spindles are similarly affected in different cognitive-related disorders, which supports the relevance of assessing abnormal sleep patterns as a possible cause for such cognitive deficits.

Phenotypic correlations in a large single-center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle magnetic resonance imaging study.

BACKGROUND AND PURPOSE: BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2 patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated. METHODS: Twenty-six patients from five families carrying the p.N88S mutation were identified. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth, spastic paraplegia), physical examination, disability measured as a modified Rankin Scale score and neurophysiological findings were collected. A whole body muscle MRI had been performed in 18 patients. The pattern of muscle involvement on T1-weighted and short time inversion recovery sequences was analysed. Hierarchical analysis using heatmaps and an MRI Composite Score were generated. Statistical analysis was carried out with STATA SE v.15 (TX, USA). RESULTS: The mean age was 51.54 ± 19.94 years and 14 patients were men. dHMN was the most common phenotype (50%) and five patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (modified Rankin Scale score 1.34 ± 1.13) although median time since onset of disease was 32 years (range 10-47). Charcot-Marie-Tooth-like patients were more disabled and disability correlated with age. On muscle MRI, thenar eminence, soleus and tibialis anterior were most frequently involved, irrespective of clinical phenotype. MRI Composite Score was strongly correlated with disability. CONCLUSION: Patients with the p.N88S BSCL2 gene mutation are phenotypically variable, although dHMN is most frequent and generally slowly progressive. Muscle MRI pattern is consistent regardless of phenotype and correlates with disease severity, probably serving as a reliable outcome measure for future clinical trials.

Melatonin in sleep disorders. / Melatonina en los trastornos de sueño.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.

Familial amyloidosis with polyneuropathy type 1 caused by transthyretin mutation Val50Met (Val30Met): 4 cases in a non-endemic area. / Polineuropatía amiloidótica familiar I por mutación Val50Met (Val30Met) en el gen de la transtiretina.

INTRODUCTION: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas. OBJECTIVES AND METHODS: We described 4 cases from the Spanish province of Guipuzcoa, a non-endemic area, to highlight the clinical variability of this disease. PATIENTS AND RESULTS: Three patients presented a late-onset form manifesting after the age of 50, featuring a predominantly motor polyneuropathy initially causing distal impairment of the lower limbs followed by the upper limbs. One patient suffered severe neuropathic pain. None showed signs of autonomic involvement. The fourth patient, of Portuguese descent, presented a typical form with onset in her thirties, neuropathic pain and dysautonomia. All patients carry the Val50Met mutation in the TTR gene. CONCLUSION: FAP is a pleomorphic disease even in patients carrying the same mutation. In non-endemic areas, its main form of presentation may resemble a predominantly motor polyneuropathy developing in the sixth decade of life with no signs of dysautonomia. Given this non-specific presentation and the widely available technical means of studying the TTR gene, we believe that the protocol for the aetiological diagnosis of any polyneuropathy should include genetic sequencing of TTR.

EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: The FYDATA study.

BACKGROUND: Real-world data of current antiepileptic drugs (AEDs) used to treat focal seizures is of importance to understand the efficacy and safety outside of the clinical trial setting. Here we report real-world data from a large series of patients treated with perampanel for 1year. METHODS: FYDATA was a multicentre, retrospective, 1-year observational study assessing the efficacy and safety of adjuvant perampanel in patients ≥12 years of age with focal epilepsy in a real-world setting. At 12 months, the proportion of patients who were seizure free, median percentage seizure reduction, proportion of responders, retention rate and proportion of patients with adverse events (AEs) were assessed. Analyses were also performed to identify any patient-, medication- and disease-related factors associated with a large clinical response or carry a risk for AEs. RESULTS: A total of 464 patients were included in the study with a retention rate of 60.6% at 1year. The mean number of prior AEDs was 7.8. The median percentage reduction in overall seizures was 33.3% (75% for secondary generalised seizures) after 1year, with 7.2% of patients achieving seizure freedom. Furthermore, patients on non-enzyme-inducing AEDs were more likely to achieve seizure freedom, and logistic regression revealed that patients aged ≥65 years, those with epilepsy due to a vascular aetiology and those who had received fewer prior AEDs showed a better clinical response to perampanel. A total of 62.9% of the patients experienced AEs at 12 months; dizziness, somnolence and irritability were the most frequent AEs. Patients with prior psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs with perampanel, and slower titration schedules were associated with less AEs overall. CONCLUSION: Perampanel, for the treatment of focal epilepsy in a real-world setting in a refractory population, over 1year, demonstrates a similar efficacy and safety profile to that observed in clinical trials. Our results have implications for the optimisation of perampanel use in a clinical setting.

Analysis of the non-stationarity of neural activity during an auditory oddball task in schizophrenia.

The aim of this study was to characterize brain dynamics during an auditory oddball task. For this purpose, a measure of the non-stationarity of a given time-frequency representation (TFR) was applied to electroencephalographic (EEG) signals. EEG activity was acquired from 20 schizophrenic (SCH) patients and 20 healthy controls while they underwent a three-stimulus auditory oddball task. The Degree of Stationarity (DS), a measure of the non-stationarity of the TFR, was computed using the continuous wavelet transform. DS was calculated for both the baseline [-300 0] ms and active task [150 550] ms windows of a P300 auditory oddball task. Results showed a statistically significant increase (p<;0.05) in non-stationarity for controls during the cognitive task in the central region, while less widespread statistically significant differences were obtained for SCH patients, especially in the beta-2 and gamma bands. Our findings support the relevance of DS as a means to study cerebral processing in SCH. Furthermore, the lack of statistically significant changes in DS for SCH patients suggests an abnormal reorganization of neural dynamics during an oddball task.

Novel measure of the weigh distribution balance on the brain network: graph complexity applied to schizophrenia.

The aim of this study was to assess brain complexity dynamics in schizophrenia (SCH) patients during an auditory oddball task. For this task, we applied a novel graph measure based on the balance of the node weights distribution. Previous studies applied complexity parameters that were strongly dependent on network topology. This could bias the results, as well as making correction techniques, such as surrogating process, necessary. In the present study, we applied a novel graph complexity measure derived from the information theory: Shannon Graph Complexity (SGC). Complexity patterns from electroencephalographic recordings of 20 healthy controls and 20 SCH patients during an auditory oddball task were analyzed. Results showed a significantly more pronounced decrease of SGC for controls than for SCH patients during the cognitive task. These findings suggest an important change in the brain configuration towards a more balanced network, mainly in the connections related to long-range interactions. Since these changes are significantly more pronounced in controls, a deficit in the neural network reorganization can be associated with SCH. In addition, an accuracy of 72.5% was obtained using a receiver operating characteristic curve with a leave-one-out cross-validation procedure. The independence of network topology has been demonstrated by the novel complexity measure proposed in this study, therefore, it complements traditional graph measures as a means to characterize brain networks.

Inferior mesenteric venous thrombosis and 18F-FDG PET/CT / Trombosis venosa mesentérica inferior y 18F-FDG PET/TC

No disponible

Aplicación de métodos no lineales a las señales de magnetoencefalograma para valorar el daño cerebral en enfermos de deterioro cognitivo leve / Nonlinear analysis of magnetoencephalography recordings for evaluating the brain injury suffered by mild cognitive impairment patients

Objetivo: Analizar los registros cerebrales del deterioro cognitivo leve (DCL) con señales de magnetoencefalografía (MEG). Material y métodos: Se estudió la actividad MEG espontánea en 18 pacientes con DCL y en 24 sujetos de control de edad avanzada utilizando cinco métodos de análisis no lineal: complejidad de Lempel-Ziv, entropía espectral de Shannon, entropía aproximada, entropía muestral y análisis de fluctuaciones sin tendencias. Resultados: Los métodos no lineales reflejaron una alteración significativa en la actividad MEG de los pacientes. El DCL parece provocar una disminución en la complejidad e irregularidad de los registros y cambios en las fluctuaciones de las señales. Conclusiones: Los cambios en la actividad MEG pueden interpretarse como una pérdida de capacidad cognitiva debido al daño cerebral sufrido por los pacientes con DCL (AU)

Objective: Mild cognitive impairment (MCI) refers to the clinical state of subjects who suffer from some degree of cognitive deterioration but do not meet clinical criteria for dementia. Nowadays, magnetoencephalography (MEG) recordings are not used in MCI clinical diagnosis. Nevertheless, non-linear methods have demonstrated their usefulness for the analysis of brain recordings in this disease. Material and methods: We have examined the MEG background activity in 18 MCI patients and 24 elderly control subjects with five non-linear techniques: Lempel-Ziv complexity, Shannon spectral entropy, approximate entropy, sample entropy and detrended fluctuation analysis. Results: Our results suggest that MCI have an effect on the MEG background activity, producing a loss of complexity and irregularity on the recordings, and changes in the signals fluctuations. Conclusions: Our findings show the usefulness of non-linear measures to detect changes in the dynamical behaviour of brains injured by the development of MCI. Nevertheless, this study is only a first step for the use of non-linear analysis in the MCI diagnosis and further investigations are needed to confirm our results (AU)

Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1.

BACKGROUND: Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect. METHOD: We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders. RESULTS: Patients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence. CONCLUSIONS: Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.

[PET/CT: protocol aspects and legal controversies]. / PET/TC: aspectos de protocolo y controversias legales.

The combination of positron emission tomography (PET) and computed tomography (CT) in a single scanner (PET/CT) allows anatomic and metabolic images to be fused and correlated with a high degree of accuracy; this represents a very important landmark in the history of medicine and especially in the area of diagnostic imaging. Nevertheless, the implementation, startup, and operation of a PET/CT scanner presents particularly interesting challenges, because it involves the integration of two well-established and consolidated techniques (CT and PET, which provide complementary information) that have traditionally been carried out in the context of two different specialties (radiology and nuclear medicine). The rapid diffusion of this new integrated technology raises a series of questions related to the optimal protocols for image acquisition, the supervision of the examinations, image interpretation, and reporting, as well as questions related to the legal competence and responsibility of the specialists involved in a PET/CT study. The objective of this article is to approach these aspects from a constructive perspective and to stimulate the dialog between the specialties of radiology and nuclear medicine, with the aim of maximizing the diagnostic potential of PET/CT and thus of providing better care for patients.

PET/TC: aspectos de protocolo y controversias legales / PET/CT: protocol aspects and legal controversies

La combinación de una tomografía por emisión de positrones (PET) y de una tomografía computarizada (TC) en un único equipo (PET/TC) permite fusionar y correlacionar con un elevado grado de precisión imágenes anatómicas y metabólicas, y ha supuesto un hito reciente muy importante en la historia de la Medicina, y especialmente en el área del diagnóstico por la imagen. No obstante, la implementación, puesta en marcha y desarrollo de un equipo de PET/TC presenta desafíos particularmente interesantes, ya que supone la integración de dos técnicas diagnósticas reconocidas y consolidadas (la TC y la PET, que proporcionan información complementaria), pero que se han desarrollado tradicionalmente al amparo de dos especialidades diferentes (Radiología y Medicina Nuclear). La rápida difusión de esta nueva tecnología integrada plantea una serie de cuestiones relacionadas con los protocolos óptimos de adquisición de las imágenes, supervisión de los estudios, interpretación de las mismas, elaboración de informes y, especialmente, con la competencia y responsabilidad de los especialistas responsables de un estudio de PET/TC. El objetivo de este artículo es abordar estos aspectos desde una perspectiva constructiva, y estimular el diálogo entre las especialidades de Radiología y Medicina Nuclear, en un intento de maximizar el potencial diagnóstico de la PET/TC y así ofrecer una mejor atención a los pacientes (AU)

The combination of positron emission tomography (PET) and computed tomography (CT) in a single scanner (PET/CT) allows anatomic and metabolic images to be fused and correlated with a high degree of accuracy; this represents a very important landmark in the history of medicine and especially in the area of diagnostic imaging. Nevertheless, the implementation, startup, and operation of a PET/CT scanner presents particularly interesting challenges, because it involves the integration of two well-established and consolidated techniques (CT and PET, which provide complementary information) that have traditionally been carried out in the context of two different specialties (radiology and nuclear medicine). The rapid diffusion of this new integrated technology raises a series of questions related to the optimal protocols for image acquisition, the supervision of the examinations, image interpretation, and reporting, as well as questions related to the legal competence and responsibility of the specialists involved in a PET/CT study. The objective of this article is to approach these aspects from a constructive perspective and to stimulate the dialog between the specialties of radiology and nuclear medicine, with the aim of maximizing the diagnostic potential of PET/CT and thus of providing better care for patients (AU)

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.