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Georgian Medical News Apr 2024Improvement of methods and criteria for diagnostics of human blastocystosis and selection of drugs for etiotropic therapy remain urgent scientific tasks of the present...
Improvement of methods and criteria for diagnostics of human blastocystosis and selection of drugs for etiotropic therapy remain urgent scientific tasks of the present day. Clinical manifestations of blastocystosis in humans are diverse, and in this regard, their influential role on the effectiveness of blastocystosis therapy cannot be excluded. To assess the predictor properties of clinical symptoms, we retrospectively analyzed them in 300 patients with blastocystosis in alternative groups: group A - with good therapeutic effect (n=162) and group B - with satisfactory effect (n=138). Group A included patients who had an overall regression rate of clinical symptoms ≥33% after 1 month from the start of treatment and ≤32% in group B. Preliminary analysis showed that reliable differences between the groups were established for most clinical symptoms, which provided the basis for the development of a prognostic algorithm using a heterogeneous sequential Wald-Henkin procedure. It was found that high prognostic informativity was shown by liver enlargement (J=3,38), the presence of heaviness in the right subcostal area (J=2,45), tachycardia (J=1,76), decreased efficiency (J=1,63), the degree of manifestation of clinical symptoms in general (J=1,74), the nature of body temperature (J=1,56), the presence of dizziness (J=1,46) and duration of the disease (J=1,07). Moderate predictive properties were characterized for the patient's age (J=0,67) and the presence of vegeto-visceral dysfunction (J=0,96), joint pain (J=0,87), headache (J=0,67), heart pain (J=0,64), and muscle pain (J=0,53). Low prognostic informativeness was established with regard to the presence of seizures (J=0,42), lymphoadenopathy (J=0,33) and spleen enlargement (J=0,30). No predictor value was found for symptoms such as abdominal pain syndrome (J=0,09), memory impairment (J=0,008), skin manifestations (J=0,04), jaundice (J=0,02), and patient gender (J=0,01). The testing of the predictive algorithm on the training group (n=300) established its high efficiency, as the erroneous predictions amounted to 3% and did not exceed the specified (5%; p<0.05) level of reliability. Correct predictions amounted to 77% and uncertain predictions amounted to 20% of cases. Using the heterogeneous sequential Wald-Genkin procedure, an algorithm was created to predict the effectiveness of therapy for patients with blastocystosis, which determined the values of the prognostic coefficients of each gradation of indicators and their general prognostic information content. The highest prognostic informativeness was found for clinical symptoms such as liver enlargement (J=3,38), right subcostal heaviness (J=2,45), tachycardia (J=1,76), degree of manifestation of clinical symptoms (J=1,74) and body temperature (J=1,56). Testing the algorithm at 95% reliability level on the training group (n=300) revealed its high efficiency, as the erroneous predictions amounted to 3% and did not exceed the specified (5%; p<0,05) reliability level. Correct predictions amounted to 77% and uncertain predictions amounted to 20% of cases.
Topics: Humans; Female; Retrospective Studies; Male; Adult; Treatment Outcome; Prognosis; Algorithms
PubMed: 38963214
DOI: No ID Found -
Epilepsia Open Jul 2024Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic... (Review)
Review
Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥2 years old and as add-on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early-line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4-29 years old in whom up to 14 ASMs had previously failed, to illustrate real-world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug-drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well-tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS. PLAIN LANGUAGE SUMMARY: Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox-Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors' everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine.
PubMed: 38962968
DOI: 10.1002/epi4.12998 -
Frontiers in Neurology 2024To analyze the local field potentials (LFPs) in patients with focal drug-resistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal...
OBJECTIVE
To analyze the local field potentials (LFPs) in patients with focal drug-resistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state.
METHOD
ANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus pre-ictal baseline segments.
RESULT
The LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures.
INTERPRETATION
Our observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies.
PubMed: 38962474
DOI: 10.3389/fneur.2024.1419835 -
Frontiers in Pharmacology 2024The quest for effective epilepsy treatments has spotlighted natural alkaloids due to their broad neuropharmacological effects. This review provides a comprehensive... (Review)
Review
The quest for effective epilepsy treatments has spotlighted natural alkaloids due to their broad neuropharmacological effects. This review provides a comprehensive analysis of the antiseizure properties of various natural compounds, with an emphasis on their mechanisms of action and potential therapeutic benefits. Our findings reveal that bioactive substances such as indole, quinoline, terpenoid, and pyridine alkaloids confer medicinal benefits by modulating synaptic interactions, restoring neuronal balance, and mitigating neuroinflammation-key factors in managing epileptic seizures. Notably, these compounds enhance GABAergic neurotransmission, diminish excitatory glutamatergic activities, particularly at NMDA receptors, and suppress proinflammatory pathways. A significant focus is placed on the strategic use of nanoparticle delivery systems to improve the solubility, stability, and bioavailability of these alkaloids, which helps overcome the challenges associated with crossing the blood-brain barrier (BBB). The review concludes with a prospective outlook on integrating these bioactive substances into epilepsy treatment regimes, advocating for extensive research to confirm their efficacy and safety. Advancing the bioavailability of alkaloids and rigorously assessing their toxicological profiles are essential to fully leverage the therapeutic potential of these compounds in clinical settings.
PubMed: 38962319
DOI: 10.3389/fphar.2024.1418555 -
Frontiers in Neuroscience 2024Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in... (Review)
Review
Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.
PubMed: 38962179
DOI: 10.3389/fnins.2024.1420255 -
Frontiers in Human Neuroscience 2024Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and...
OBJECTIVE
Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE.
METHODS
PubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis.
RESULTS
A total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50-62%, > 0.05) and 61% (95% CI 54-68%, > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58-76%, > 0.05) and 71% (95% CI 64-78%, > 0.05). Different targets of DBS did not show significant effect on seizure reduction ( > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, < 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS ( > 0.05).
CONCLUSION
Both DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.
PubMed: 38962148
DOI: 10.3389/fnhum.2024.1429223 -
Frontiers in Microbiology 2024The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the...
INTRODUCTION
The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.
METHODS
We aimed to unravel the intrinsic mechanisms through rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.
RESULTS
We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of and significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, , and showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.
CONCLUSION
In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.
PubMed: 38962126
DOI: 10.3389/fmicb.2024.1403892 -
Epilepsy & Behavior Reports 2024Epilepsy may be drug-resistant in a third of patients necessitating alternative treatments, such as surgery. Among refractory epilepsy patients, the most common...
Epilepsy may be drug-resistant in a third of patients necessitating alternative treatments, such as surgery. Among refractory epilepsy patients, the most common etiologies are tumors and focal cortical dysplasia (FCD). Surgical management of tumor-related epilepsy has one of the highest rates of seizure freedom, whereas FCD represents some of the lowest success rates in epilepsy treatment. This study investigates the pre-operative characteristics associated with differences in postsurgical seizure outcomes in patients with FCD and tumors. We completed a retrospective cross-sectional review of epilepsy surgery patients with tumors (n = 29) or FCD (n = 44). Participants had a minimum medical follow-up at least 6 months after surgery (FCD M = 2.1 years; Tumors M = 2.0 years). Patients with FCD trended toward an earlier age of onset (t = -4.19, p = 0.058) and longer epilepsy duration (t = 3.75, p < 0.001). Epilepsy surgery is highly effective in reducing seizures in patients with FCD or tumors with over 70 % of all patients achieving seizure freedom. We found a higher rate of seizure freedom in patients with tumors than FCD, but this difference did not reach significance (79 vs. 66 %). Predictive factors of outcomes for FCD and tumors differ. Findings indicate that diagnostic tests may be differentially sensitive to patients with tumors, and future research is needed.
PubMed: 38962068
DOI: 10.1016/j.ebr.2024.100680 -
Scientific Reports Jul 2024Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of...
Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) - short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation.
Topics: Animals; MicroRNAs; RNA, Messenger; Rats; Gene Regulatory Networks; Seizures; Epilepsy; Gene Expression Profiling; Male; Gene Expression Regulation; Bayes Theorem; Disease Models, Animal; Transcriptome
PubMed: 38961125
DOI: 10.1038/s41598-024-66117-7 -
Child's Nervous System : ChNS :... Jul 2024Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent,...
Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.
PubMed: 38960918
DOI: 10.1007/s00381-024-06502-9