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- Hippotherapy improves gross motor function in children with cerebral palsy: evidence from a systematic reviewPublication . Bernardino, Inês; Borges, Daniel Filipe; Casalta Lopes, João; Soares, Joana Isabel; Borges, Daniel Filipe"Hippotherapy uses horse movement to promote physical and psychosocial rehabilitation and may benefit children with cerebral palsy (CP). Standardised instruments such as the Activity Scale for Kids-Performance (ASK©), the Gross Motor Function Classification System (GMFCS) and the Gross Motor Function Measure (GMFM) are needed to quantify effects on motor function. To systematically review the effects of hippotherapy on gross motor skills in children with CP. Although autism spectrum disorder (ASD) was included in the search strategy, no eligible ASD studies were identified. Following PRISMA guidelines, six databases (PubMed, EMBASE, Web of Science, SCOPUS, Cochrane and SciELO) were searched for English, Portuguese or Spanish studies employing ASK©, GMFCS or GMFM. Two reviewers independently screened records, extracted data and assessed risk of bias. Twenty-five studies (602 participants, mean age 7.1 years, 3–14) met inclusion criteria; all involved CP, none ASD. Interventions lasted 8–24 weeks (1–3 sessions/week). Two ASK© studies showed significant motor gains (Hedges g=0.48–0.62). GMFM was used in 22 studies; 20 reported clinically relevant improvements, particularly in dimensions D (standing) and E (walking, running, jumping). The sole GMFCS study reported no change in classification. Methodological quality was moderate, limited by small samples and lack of blinding. Hippotherapy improves gross motor function in CP, best demonstrated with GMFM. Evidence for ASD is absent, highlighting a research gap. Broader application of ASK© and GMFCS is still needed to better define benefits across neurodevelopmental disorders."
- The left-right side-specific neuroendocrine signaling from injured brain: An organizational principlePublication . Watanabe, Hiroyuki; Henrique Maia, Gisela Maria; Kobikov, Yaromir; Nosova, Olga; Sarkisyan, Daniil; Galatenko, Vladimir; Carvalho, Liliana; Maia, Gisela H.; Lukoyanov, Nikolay; Lavrov, Igor; Ossipov, Michael H.; Hallberg, Mathias; Schouenborg, Jens; Zhang, Mengliang; Bakalkin, GeorgyA neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene–gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.
- The role of actigraphy in the assessment of central disorders of Hypersomnolence: A systematic review and meta-analysisPublication . Maia, Susana; Soares, Joana Isabel; Borges, Daniel Filipe; Lopes, João Casalta; Gonçalves, Marta; Borges, Daniel FilipeActigraphy provides an objective measure of sleepiness and is recommended by the American Academy of Sleep Medicine for use 7–14 days prior to multiple sleep latency testing. It plays a valuable role in the differential diagnosis of hypersomnolence. Our aim was to provide a comprehensive summary of actigraphy features in central disorders of hypersomnolence (CDH). Data were sourced from six bibliographic databases. Fixed- or random-effects models were applied to compare patients with narcolepsy type 1 (NT1) to controls. Of the 1,737 publications identified in our search, 8 studies met the inclusion criteria. The total sample consisted of 473 participants, encompassing patients with NT1, idiopathic hypersomnia (IH), hypersomnolence with normal CSF hypocretin-1 levels, Kleine–Levin syndrome (KLS), traumatic brain injury (TBI), major depressive disorder (MDD), myotonic dystrophy (MD), primary insomnia and healthy controls. Actigraphy devices varied across studies. Compared to control subjects, NT1 patients had lower total sleep time (TST), sleep efficiency and daytime motor activity, with increased wake after sleep onset, awakenings, nocturnal motor activity and longest nap duration. In KLS, TST was higher during hypersomnia episodes than during asymptomatic phases. TBI and MDD patients had a higher TST than the control group, while MD patients had a lower TST than patients with IH. Actigraphy is a valuable tool for objectively assessing sleep and can assist in detecting CDH. However, the absence of standardized guidelines limits their broader implementation in clinical practice.
- Validity of central pain processing biomarkers for predicting the occurrence of oncological chronic pain: a study protocolPublication . Carrillo‑de‑la‑Peña, M. T.; Fernandes, C.; Castro, Catarina; Medeiros, R.Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms. We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables. This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making.
- The prevalence of post-therapy epilepsy in patients treated for high-grade glial tumors: a systematic review and meta-analysisPublication . Ferreira, Marta Pereira; Carvalho, Ruben Lopes; Soares, Joana Isabel; Casalta‑Lopes, João; Borges, Daniel Filipe; Borges, Daniel Filipe; Soares, Joana I.Gliomas are the most prevalent type of primary brain tumor of the adult central nervous system. High-grade gliomas (HGG) are the most common type of glioma. Epilepsy is often the first clinical manifestation of HGG. Since epilepsy leads to increased morbidity and mortality rates, seizure control is one of the main therapeutic goals for patients with glioma-related epilepsy. Post-therapy epilepsy is observed in a significant percentage of patients, hence, this work aimed to quantify the prevalence of post-therapy epilepsy after HGG treatment. Our search was conducted across PubMed®, EMBASE®, Web of Science™, Cochrane Library, Sicelo and Scopus, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review included articles published in Portuguese or English that evaluate adult patients with newly diagnosed HGG, who were treated with at least surgery or radiation. Thirty-six studies reporting on 4036 HGG patients were included in our meta-analysis. The mean age ranged from 44 to 73 years. Glioblastoma was the most commonly observed HGG, representing 77,8% of all glioma patients. The pre-treatment seizure frequency was observed in 21,2%. All patients underwent surgery as the main therapy, and 1842 patients received standard adjuvant therapy. We also observed a pooled prevalence of post-therapy seizures of 25.5% (95% confidence interval of [19.9%; 31.1%]). Substantial heterogeneity in all assessed variables was observed. Conducting larger prospective studies with suitable epilepsy diagnostic methods would help provide a more precise estimate of the number of HGG patients who develop post-therapy epilepsy.
- Spike detection in the wild: Screening of suspected temporal lobe epilepsy cases using a tailored 2-channel wearable EEGPublication . Borges, Daniel Filipe; Soares, Joana Isabel; Dias, Daniela; Cordeiro, Helena; Leal, Alberto; Borges, Daniel FilipeTo clinically validate the contribution of a custom-built-wearable device (waEEG) compared to a full 10–20 electrode array ambulatory EEG (aEEG) for screening epilepsy cases in patients with suspected temporal lobe epilepsy (TLE) but negative routine EEGs. Patients (aged 16–91 years) with clinically suspected TLE who were referred for a 24 h aEEG were fitted with an additional 2-channel bipolar waEEG device and prospectively enrolled in the study until 20 TLE diagnoses were confirmed by aEEG. 41 patients were included and their waEEG was blindly reviewed by two experienced clinical neurophysiologists and a semi-automated spike detection software to categorize patients into TLE (spikes present) and non-TLE (no spikes) groups. The experts achieved good sensitivity (95%–100%) and accuracy (98%–93%) with excellent interrater agreement (kappa>0.80) in patient labelling. The semi-automated software performed poorly (40% sensitivity, 68% accuracy) and failed to classify TLE in more than half the cases. Classification was not affected by restricting spike detection to the evening and night time, which reduced the average length of the analyzed EEG from 23.4 to 10.4 h. Three false-positive spike detections were thoroughly analyzed and reclassified as artifacts due to eye and body movements and electrocardiographic contamination. To better control cardiac artifacts, the addition of an ECG channel to the waEEG is recommended. Detection of spikes with waEEG allows accurate detection of epilepsy in suspected TLE cases, with less technical and professional effort and improved acceptance. This screening tool could improve the yield of follow-up with a conventional aEEG and provide an accessible method for monitoring interictal epileptiform activity in TLE. Epilepsy is a chronic short circuit in the brain. In adults, it most often affects the temporal lobes, resulting in temporal lobe epilepsy (TLE). Seizures are infrequent but difficult to treat. Electroencephalography (EEG) is the best method to detect the electrical disturbances and is crucial to distinguish epilepsy from other non-epileptic disorders. Developing simple, inexpensive and easily accessible portable EEG methods that complement in-hospital assessment could significantly impact patient care. Our study aims to clinically validate a wearable epilepsy screening device to aid in TLE management, reduce delays in diagnosis and enable straightforward assessment of epileptic activity.
- The Dianalund experience: A review of the 6th ILAE School on Advanced EEG and EpilepsyPublication . Borges, Daniel Filipe; Primicerio, Giulia; Perjoc, Radu‐Ștefan; Bloch, Lars Ølgaard; Cacic Hribljan, MelitaThe 6th International League Against Epilepsy (ILAE)School on Advanced EEG and Epilepsy (DSSEE6) tookplace between July 20 and 28, 2024. It is a biennial courseheld in Dianalund @ Danish Epilepsy Center—Filadelfia,Denmark, since 2012. This year's event was hosted in ahybrid format and was organized under the auspices ofthe ILAE Academy and the Danish Epilepsy Society.
- The sound of silence: Quantification of typical absence seizures by sonifying EEG signals from a custom‐built wearable devicePublication . Borges, Daniel Filipe; Fernandes, João; Soares, Joana Isabel; Casalta‐Lopes, João; Carvalho, Daniel; Beniczky, Sándor; Leal, AlbertoObjective: To develop and validate a method for long- term (24- h) objective quantification of absence seizures in the EEG of patients with childhood absence epilepsy (CAE) in their real home environment using a wearable device (waEEG), comparing automatic detection methods with auditory recognition after seizure sonification. Methods: The waEEG recording was acquired with two scalp electrodes. Automatic analysis was performed using previously validated software (Persyst® 14) and then fully reviewed by an experienced clinical neurophysiologist. The EEG data were converted into an audio file in waveform format with a 60- fold time compression factor. The sonified EEG was listened to by three inexperienced observers and the number of seizures and the processing time required for each data set were recorded blind to other data. Quantification of seizures from the patient diary was also assessed. Results: Eleven waEEG recordings from seven CAE patients with an average age of 8.18 ± 1.60 years were included. No differences in the number of seizures were found between the recordings using automated methods and expert audio assessment, with significant correlations between methods (ρ > .89, p < .001) and between observers (ρ > .96, p < .001). For the entire data set, the audio assessment yielded a sensitivity of .830 and a precision of .841, resulting in an F1 score of .835. Significance: Auditory waEEG seizure detection by lay medical personnel provided similar accuracy to post- processed automatic detection by an experienced clinical neurophysiologist, but in a less time- consuming procedure and without the need for specialized resources. Sonification of long- term EEG recordings in CAE provides a user- friendly and cost- effective clinical workflow for quantifying seizures in clinical practice, minimizing human and technical constraints.
- A custom-built single-channel in-ear electroencephalography sensor for sleep phase detection: an interdependent solution for at-home sleep studiesPublication . Borges, Daniel Filipe; Soares, Joana Isabel; Silva, Heloísa; Felgueiras, João; Batista, Carla; Ferreira, Simão; Rocha, Nuno; Leal, AlbertoSleep is vital for health. It has regenerative and protective functions. Its disruption reduces the quality of life and increases susceptibility to disease. During sleep, there is a cyclicity of distinct phases that are studied for clinical purposes using polysomnography (PSG), a costly and technically demanding method that compromises the quality of natural sleep. The search for simpler devices for recording biological signals at home addresses some of these issues. We have reworked a single-channel in-ear electroencephalography (EEG) sensor grounded to a commercially available memory foam earplug with conductive tape. A total of 14 healthy volunteers underwent a full night of simultaneous PSG, in-ear EEG and actigraphy recordings. We analysed the performance of the methods in terms of sleep metrics and staging. In another group of 14 patients evaluated for sleep-related pathologies, PSG and in-ear EEG were recorded simultaneously, the latter in two different configurations (with and without a contralateral reference on the scalp). In both groups, the in-ear EEG sensor showed a strong correlation, agreement and reliability with the ‘gold standard’ of PSG and thus supported accurate sleep classification, which is not feasible with actigraphy. Single-channel in-ear EEG offers compelling prospects for simplifying sleep parameterisation in both healthy individuals and clinical patients and paves the way for reliable assessments in a broader range of clinical situations, namely by integrating Level 3 polysomnography devices. In addition, addressing the recognised overestimation of the apnea-hypopnea index, due to the lack of an EEG signal, and the sparse information on sleep metrics could prove fundamental for optimised clinical decision making.
- The sound of silence: Quantification of typical absence seizures by sonifying EEG signals from a custom‐built wearable devicePublication . Borges, Daniel Filipe; Fernandes, João; Soares, Joana Isabel; Casalta‐Lopes, João; Carvalho, Daniel; Beniczky, Sándor; Leal, AlbertoTo develop and validate a method for long-term (24-h) objective quantification of absence seizures in the EEG of patients with childhood absence epilepsy (CAE) in their real home environment using a wearable device (waEEG), comparing automatic detection methods with auditory recognition after seizure sonification. The waEEG recording was acquired with two scalp electrodes. Automatic analysis was performed using previously validated software (Persyst® 14) and then fully reviewed by an experienced clinical neurophysiologist. The EEG data were converted into an audio file in waveform format with a 60-fold time compression factor. The sonified EEG was listened to by three inexperienced observers and the number of seizures and the processing time required for each data set were recorded blind to other data. Quantification of seizures from the patient diary was also assessed. Eleven waEEG recordings from seven CAE patients with an average age of 8.18 ± 1.60 years were included. No differences in the number of seizures were found between the recordings using automated methods and expert audio assessment, with significant correlations between methods (ρ > .89, p < .001) and between observers (ρ > .96, p < .001). For the entire data set, the audio assessment yielded a sensitivity of .830 and a precision of .841, resulting in an F1 score of .835. Auditory waEEG seizure detection by lay medical personnel provided similar accuracy to post-processed automatic detection by an experienced clinical neurophysiologist, but in a less time-consuming procedure and without the need for specialized resources. Sonification of long-term EEG recordings in CAE provides a user-friendly and cost-effective clinical workflow for quantifying seizures in clinical practice, minimizing human and technical constraints.