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INTRODUCTION: Restless legs syndrome (RLS) is a sensory-motor sleep disorder that affects up to 13% of adults in the Western world and 2-4% of children. It impairs night sleep with an impact on daily performances and life quality. Thus, moderate-to-severe RLS requires pharmacological treatment. AREAS COVERED: In the present review, which is based on PubMed searches with no time limits, the authors discuss the recommended pharmacotherapy for RLS in addition to other emerging treatment options. The authors provide coverage to the current recommendations for both adults and pediatric patients with RLS. EXPERT OPINION: Current evidence suggests removing all causes of secondary RLS, including iron deficiency, chronic renal failure, drugs, and treating other sleep disorders that may worsen symptoms. Also, intermittent RLS should be addressed with behavioral measures and on-demand therapy. For chronic persistent RLS, α2δ calcium channel ligands are a first-line pharmacological approach, whereas dopamine agonists are associated with increased risk and should be spared. When RLS is refractory to first-line treatment, polytherapy, or opioid monotherapy should be considered. Nonetheless, some patients may not reach sustained symptom relief. Further research is needed to better understand the pathophysiology of RLS and to develop newer more effective drugs.
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The identification of the epileptogenic zone (EZ) boundaries is crucial for effective focal epilepsy surgery. We verify the value of a neurophysiological biomarker of focal ictogenesis, characterized by a low-voltage fast-activity ictal pattern (chirp) recorded with intracerebral electrodes during invasive presurgical monitoring (stereoelectroencephalography [SEEG]). The frequency content of SEEG signals was retrospectively analyzed with semiautomatic software in 176 consecutive patients with focal epilepsies that either were cryptogenic or presented with discordant anatomoelectroclinical findings. Fast activity seizure patterns with the spectrographic features of chirps were confirmed by computer-assisted analysis in 95.4% of patients who presented with heterogeneous etiologies and diverse lobar location of the EZ. Statistical analysis demonstrated (1) correlation between seizure outcome and concordance of sublobar regions included in the EZ defined by visual analysis and chirp-generating regions, (2) high concordance in contact-by contact analysis of 68 patients with Engel class Ia outcome, and (3) that discordance between chirp location and the visually outlined EZ correlated with worse seizure outcome. Seizure outcome analysis confirms the fast activity chirp pattern is a reproducible biomarker of the EZ in a heterogeneous group of patients undergoing SEEG.
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Electroencefalografía , Epilepsias Parciales , Humanos , Femenino , Masculino , Adulto , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/cirugía , Epilepsias Parciales/diagnóstico , Electroencefalografía/métodos , Estudios Retrospectivos , Adolescente , Persona de Mediana Edad , Adulto Joven , Niño , Electrodos Implantados , Preescolar , Electrocorticografía/métodosRESUMEN
OBJECTIVE: As autoimmune encephalitis (AE) often involves the mesial temporal structures which are known to be involved in both sudden unexpected death in epilepsy (SUDEP) and ictal asystole (IA), it may represent a good model to study the physiopathology of these phenomena. Herein, we systematically reviewed the occurrence of SUDEP and IA in AE. METHODS: We searched 4 databases (MEDLINE, Scopus, Embase, and Web of Science) for studies published between database inception and December 20, 2022, according to the PRISMA guidelines. We selected articles reporting cases of definite/probable/possible/near-SUDEP or IA in patients with possible/definite AE, or with histopathological signs of AE. RESULTS: Of 230 records assessed, we included 11 cases: 7 SUDEP/near-SUDEP and 4 IA. All patients with IA were female. The median age at AE onset was 30 years (range: 15-65), and the median delay between AE onset and SUDEP was 11 months; 0.9 months for IA. All the patients presented new-onset seizures, and 10/11 also manifested psychiatric, cognitive, or amnesic disorders. In patients with SUDEP, 2/7 were antibody-positive (1 anti-LGI1, 1 anti-GABABR); all IA cases were antibody-positive (3 anti-NMDAR, 1 anti-GAD65). Six patients received steroid bolus, 3 intravenous immunoglobulin, and 3 plasmapheresis. A pacemaker was implanted in 3 patients with IA. The 6 survivors improved after treatment. DISCUSSION: SUDEP and IA can be linked to AE, suggesting a role of the limbic system in their pathogenesis. IA tends to manifest in female patients with temporal lobe seizures early in AE, highlighting the importance of early diagnosis and treatment.
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Encefalitis , Paro Cardíaco , Muerte Súbita e Inesperada en la Epilepsia , Humanos , Encefalitis/complicaciones , Encefalitis/fisiopatología , Paro Cardíaco/complicaciones , Paro Cardíaco/mortalidad , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/fisiopatología , Femenino , Adolescente , Adulto , Epilepsia/complicaciones , Epilepsia/mortalidad , Epilepsia/fisiopatología , Adulto Joven , Persona de Mediana EdadRESUMEN
OBJECTIVE: Encephaloceles (ENCs) may cause clinical complications, including drug-resistant epilepsy that can be cured with epilepsy surgery. METHODS: We describe clinical, diagnostic, and neuropathological findings of 12 patients with temporal ENC and epilepsy evaluated for surgery and compare them with a control group of 26 temporal lobe epilepsy (TLE) patients. RESULTS: Six patients had unilateral and 6 bilateral temporal ENCs. Compared to TLEs, ENCs showed i) later epilepsy onset, ii) higher prevalence of psychiatric comorbidities, iii) no history of febrile convulsions, and iv) ictal semiology differences. Seven patients had MRI signs of gliosis, and 9 of intracranial hypertension. Interictal EEG analysis in ENCs demonstrated significant differences with controls: prominent activity in the beta/gamma frequency bands in frontal regions, interictal short sequences of low-voltage fast activity, and less frequent and more localized interictal epileptiform discharges. Ictal EEG patterns analyzed in 9 ENCs showed delayed and slower contralateral spread compared to TLEs. All ENCs that underwent surgery (7 lobectomies and 1 lesionectomy) are in Engel class I. Neuropathological examination revealed 4 patterns: herniated brain fragments, focal layer I distortion, white matter septa extending into the cortex, and altered gyral profile. CONCLUSIONS AND SIGNIFICANCE: The described peculiarities might help clinicians to suspect the presence of largely underdiagnosed ENCs.
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Epilepsia del Lóbulo Temporal , Epilepsia , Humanos , Electroencefalografía/métodos , Encefalocele/complicaciones , Encefalocele/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Epilepsia/etiología , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Neuroimagen , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: We use co-registration of foramen-ovale and scalp-EEG to investigate network alterations in temporal-lobe epilepsy during focal seizures without (aura) or with impairment of awareness (SIA). METHODS: One aura and one SIA were selected from six patients. Temporal dynamic among 4 epochs, as well as the differences between aura and SIA, were analyzed through partial directed coherence and graph theory-based indices of centrality. RESULTS: Regarding the auras temporal evolution, fronto-parietal (FP) regions showed decreased connectivity with respect to the interictal period, in both epileptogenic (EH) and non-epileptogenic hemisphere (nEH). During SIAs, temporal dynamic showed more changes than auras: centrality of mesial temporal (mT) regions changes during all conditions, and nEH FP centrality showed the same dynamic trend of the aura (decreased centrality), until the last epoch, close to the impaired awareness, when showed increased centrality. Comparing SIA with aura, in proximity of impaired awareness, increased centrality was found in all the regions, except in nEH mT. CONCLUSIONS: Our findings suggested that the impairment of awareness is related to network alterations occurring first in neocortical regions and when awareness is still retained. SIGNIFICANCE: The analysis of 'hub' alteration can represent a suitable biomarker for scalp EEG-based prediction of awareness impairment.
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Concienciación/fisiología , Encéfalo/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Red Nerviosa/fisiopatología , Adulto , Mapeo Encefálico/métodos , Electroencefalografía , Femenino , Foramen Oval/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Cuero Cabelludo/fisiopatologíaRESUMEN
Familiarity in music has been reported as an important factor modulating emotional and hedonic responses in the brain. Familiarity and repetition may increase the liking of a piece of music, thus inducing positive emotions. Neuroimaging studies have focused on identifying the brain regions involved in the processing of familiar and unfamiliar musical stimuli. However, the use of different modalities and experimental designs has led to discrepant results and it is not clear which areas of the brain are most reliably engaged when listening to familiar and unfamiliar musical excerpts. In the present study, we conducted a systematic review from three databases (Medline, PsychoINFO, and Embase) using the keywords (recognition OR familiar OR familiarity OR exposure effect OR repetition) AND (music OR song) AND (brain OR brains OR neuroimaging OR functional Magnetic Resonance Imaging OR Position Emission Tomography OR Electroencephalography OR Event Related Potential OR Magnetoencephalography). Of the 704 titles identified, 23 neuroimaging studies met our inclusion criteria for the systematic review. After removing studies providing insufficient information or contrasts, 11 studies (involving 212 participants) qualified for the meta-analysis using the activation likelihood estimation (ALE) approach. Our results did not find significant peak activations consistently across included studies. Using a less conservative approach (p < 0.001, uncorrected for multiple comparisons) we found that the left superior frontal gyrus, the ventral lateral (VL) nucleus of the left thalamus, and the left medial surface of the superior frontal gyrus had the highest likelihood of being activated by familiar music. On the other hand, the left insula, and the right anterior cingulate cortex had the highest likelihood of being activated by unfamiliar music. We had expected limbic structures as top clusters when listening to familiar music. But, instead, music familiarity had a motor pattern of activation. This could reflect an audio-motor synchronization to the rhythm which is more engaging for familiar tunes, and/or a sing-along response in one's mind, anticipating melodic, harmonic progressions, rhythms, timbres, and lyric events in the familiar songs. These data provide evidence for the need for larger neuroimaging studies to understand the neural correlates of music familiarity.
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Splicing is the most frequently altered biological process by mutations within gene regions. Information for splicing is recognized by several factors that bind pre-mRNA sequence and, through coordinated interaction, yield mature transcripts. Some in silico methods have been developed to predict if a mutation leads to aberrant splicing patterns. We previously created SpliceAid tool that is able to minimize false positive predictions because it adopts strictly experimental RNA target motifs bound by splicing proteins in humans. In order to improve prediction accuracy and better understand the splicing outcome, the tissue specificity of each splicing regulatory factor has to be taken into account. Here, we have developed SpliceAid 2 by adding the expression data related to the splicing factors extracted from the main proteomic and transcriptomic databases, true 5' and 3' splice sites, polypyrimidine tracts, and branch point sequences. The new version collects 2,220 target sites of 62 human splicing proteins and their expression data in 320 tissues per cell. SpliceAid 2 can be useful to foresee the splicing pattern alteration, to guide the identification of the molecular effect due to the mutations and to understand the tissue-specific alternative splicing. SpliceAid 2 is freely accessible at www.introni.it/spliceaid.html.