1,721,023 research outputs found
Preventing epileptogenesis: A realistic goal?
No full textThe definition of the pathologic process of epileptogenesis has considerably changed over the past few years due to a better knowledge of the dynamics of the associated molecular modifications and to clinical and experimental evidence of progression of the epileptic condition beyond the occurrence of the first seizures. Interference with this chronic process may lead to the development of novel preventive therapies which are still lacking. Notably, epileptogenesis is often associated with comorbid behaviors which are now considered primary outcome measures for novel therapeutics. Anti-epileptogenic interventions may improve not only seizure onset and their frequency and severity but also comorbidities and cell loss, and when applied after the onset of the disease may provide disease-modifying effects by favorably modifying the disease course. In the preclinical arena, several novel targets for anti-epileptogenic and disease-modifying interventions are being characterized and validated in rodent models of epileptogenesis. To move proof-of-concept anti-epileptogenesis studies to validation in preclinical trials and eventually to clinical translation is a challenging task which would be greatly facilitated by the development of non invasive biomarkers of epileptogenesis. Biomarker discovery together with testing potential novel drugs would provide a major advance in the treatment of human epilepsy beyond the pure symptomatic control of seizures
Reply to letter: "Brain MRI abnormalities resembling unidentified bright objects in a patient with Phelan- McDermid syndrome"
No full textInflammation and Epilepsy: Preclinical Findings and Potential Clinical Translation
No full textBACKGROUND:
The lack of treatments which can prevent epilepsy development or improve disease prognosis represents an unmet and urgent clinical need. The development of such drugs requires a deep understanding of the mechanisms underlying disease pathogenesis. In the last decade, preclinical studies in models of acute seizures and of chronic epilepsy highlighted that neuroinflammation arising in brain areas of seizure onset and generalization is a key contributor to neuronal hyper-excitability underlying seizure generation. Microglia and astrocytes are pivotal cells involved in both the induction and perpetuation of the inflammatory response to epileptogenic injuries or seizures; other cell contributors are neurons, cell components of the blood brain barrier and leukocytes.
METHODS:
From the clinical standpoint, neuroinflammation is now considered an hallmark of epileptogenic foci in various forms of focal onset pharmacoresistant epilepsies. Moreover, pharmacological studies in animal model with drugs targeting specific inflammatory molecules, and changes in intrinsic seizure susceptibility of transgenic mice with perturbed neuroinflammatory mechanisms, have demonstrated that neuroinflammation is not a bystander phenomenon but has a pathogenic role in seizures, cell loss and neurological co-morbidities. Understanding the role of neuroinflammation in seizure pathogenesis is instrumental for a mechanism-based discovery of selective therapies targeting the epilepsy causes rather than its symptoms, thereby allowing the development of novel disease-modifying treatments. Notably, clinical translation of laboratory findings may take advantage of anti-inflammatory drugs already in medical use for peripheral autoinflammatory or autoimmune disorders.
CONCLUSION:
This review reports key preclinical and clinical findings supporting a role for brain inflammation in the pathogenesis of seizures. It also highlights the emerging proof-of-concept studies showing signs of clinical efficacy of target-specific anti-inflammatory interventions in epilepsies of differing etiologies. We will discuss the need for biomarkers and novel clinical trial designs for anti-inflammatory therapies that have a mechanism of action very different than standard antiepileptic drugs
Epilessia da deficit di PNPO: follow-up di 5 anni.
No full textViene descritto il follow-up di una paziente con una rarissima forma di epilessia ad esordio neonatale
Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy
No full textAims. To further characterise CDKL5-related disorder, previously classified as an early-onset seizure variant of Rett syndrome, which is currently considered a specific and independent early-infantile epileptic encephalopathy.Methods. We describe the epileptic phenotype and neurocognitive development in three girls with CDKL5 mutations showing severe neurodevelopmental impairment, with different epileptic phenotypes and severity.Results. The patients differed regarding age at epilepsy onset, seizure frequency, duration of honeymoon periods, as well as EEG features. The honeymoon period, defined as a seizure-free period longer than two months, represented, in our case series, a good indicator of the epilepsy outcome, but not of the severity of developmental impairment. However, even during the honeymoon period, the interictal EEG showed epileptiform abnormalities, slowing, or a disappearance of physiological pattern. The natural history of CDKL5 disorder was compared between the three girls, focusing on the relationship between electroclinical features and neurological development.Conclusion. Our findings suggest that CDKL5 mutations likely play a direct role in psychomotor development, whereas epilepsy is one of the clinical features associated with this complex disorder
PP-8 ESOPHAGEAL HIGH RESOLUTION MANOMETRY IN NEUROLOGICALLLY IMPAIRED CHILDREN AND GASTRO-OESOPHAGEAL REFLUX DISEASE
No full textMechanism underlying the occurrence of Gastroesophageal reflux disease (GERD) in neurologically impaired children (NIC) is poorly understood. We sought to characterize, by Esophageal High Resolution Manometry (EHRM), alterations of esophageal motility associated with GERD in NIC and to compare with a group with a suspicion of GERD and normal psychomotor development (NDP)
Effects of antiepileptic therapy on bone mineral status evaluated by phalangeal quantitative ultrasound in pediatric patients with epilepsy and motor impairment.
No full textBACKGROUND:
In epileptic patients with motor disability, it's difficult to disentangle the effects of antiepileptic drugs (AEDs) on bone health from those provoked by impaired mobility. The aim of this study was to evaluate the effects of AEDs on bone mineral status by phalangeal quantitative ultrasound (QUS), a no-radiation and non-invasive method, in pediatric patients with motor impairment and epilepsy.
METHODS:
We enrolled 56 patients (31 females, 25 males) with epilepsy and motor impairment and 24 children with only motor disability (13 females, 11 males). Patients were stratified by Gross Motor Function Classification System Scale (GMFCS) in 4 groups: group A1 with epilepsy and mild motor impairment (GMFCS levels I-II), group A2 with only mild motor impairment, group B1 with epilepsy and severe motor impairment (GMFCS levels III-V), group B2 with only severe motor impairment. The bone mineral status was evaluated by QUS and amplitude-dependent speed of sound (AD-SoS) Z-score was calculated for each patient.
RESULTS:
The four groups showed no significant differences in age, gender and 25- hydroxyvitamin D levels. The group B1 had a statistically lower amplitude-dependent speed of sound Z-score as compared to group A2 (p<0.05). The multivariate analysis of independent factors revealed a significant correlation between amplitude-dependent speed of sound Z-score and Gross Motor Function Classification System levels (p=0.004). The mean Z-score value decreased by 0.53, increasing the motor impairment.
CONCLUSIONS:
The bone mineral status measured as AD-SoS strongly correlates with severity of motor disability evaluated by GMFCS as compared to antiepileptic therapy and 25-hydroxyvitamin D levels
The Pediatric Symptom Checklist as screening tool for neurological and psychosocial problems in a paediatric cohort of patients with coeliac disease.
No full textAIM:
To screen for neurological and behavioural disorders in a paediatric cohort of patients with coeliac disease (CD) in order to detect possible differences related to compliance with gluten-free diet (GFD).
METHODS:
We recruited a cohort of 139 patients divided into three groups: A (40 patients with newly diagnosed CD), B (54 patients with CD in remission after GFD) and C (45 patients with potential CD). Patients first underwent a screening neurological visit, detecting signs associated with CD, and then were evaluated with Pediatric Symptom Checklist (PSC), a psychosocial screen for cognitive, emotional and behavioural problems.
RESULTS:
In the group B as compared to group A, there was a statistically significant decrease (p < 0.05) in the incidence of chronic fatigue, headache and inattention. The same applied to patients compliant to GFD vs. non-compliant. Potential coeliacs turning into overt CD had a higher incidence of headache and inattention compared with potential coeliacs showing normal mucosa. The PSC mean score in group A was statistically higher than in group B.
CONCLUSION:
Gluten-free diet had a positive impact on neuropsychiatric symptoms. We suggest the use of PSC in the routine follow-up of coeliacs in order to allow an early detection of psychosocial problems
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
