Research

12 pages, 268 KiB

Open AccessArticle

Clinical, Sociodemographic, and Psychological Factors Associated with Transition Readiness in Patients with Epilepsy

by Mariacarolina Vacca, Mariana Fernandes, Lorenzo Veronese, Andrea Ballesio, Caterina Cerminara, Cinzia Galasso, Luigi Mazzone, Caterina Lombardo, Nicola Biagio Mercuri and Claudio Liguori

Brain Sci. 2024, 14(1), 21; https://doi.org/10.3390/brainsci14010021 - 24 Dec 2023

Viewed by 1160

Abstract

Background: The transition to adult care for patients with epilepsy is a complicated clinical issue associated with adverse outcomes, including non-adherence to treatment, dropout of medical care, and worse prognosis. Moreover, youngsters with epilepsy are notably prone to emotional, psychological, and social difficulties [...] Read more.

Background: The transition to adult care for patients with epilepsy is a complicated clinical issue associated with adverse outcomes, including non-adherence to treatment, dropout of medical care, and worse prognosis. Moreover, youngsters with epilepsy are notably prone to emotional, psychological, and social difficulties during the transition to adulthood. Transition needs depend on the type of epilepsy and the epileptic syndrome, as well as on the presence of co-morbidities. Having a structured transition program in place is essential to reduce poor health consequences. A key strategy to optimize outcomes involves the use of transition readiness and associated factors assessment to implement the recognition of vulnerability and protective aspects, knowledge, and skills of these patients and their parents. Therefore, this study aims to provide a comprehensive framework of clinical and psychosocial aspects associated with the transition from pediatric to adult medical care of patients with epilepsy. Methods: Measures examining different aspects of transition readiness and associated clinical, socio-demographic, psychological, and emotional factors were administered to 13 patients with epilepsy (M_age = 22.92, SD = 6.56) with (n = 6) or without (n = 7) rare diseases, and a respective parent (M_age = 56.63, SD = 7.36). Results: patients showed fewer problems in tracking health issues, appointment keeping, and pharmacological adherence as well as low mood symptoms and moderate resiliency. Moreover, they referred to a low quality of sleep. Notably, parents of patients with rare diseases reported a lower quality of sleep as compared to the other group of parents. Conclusions: Increasing awareness around transition readiness is essential to promote self-management skills of patients with epilepsy and their parents. Anticipating the period of transition could be beneficial, especially to prevent problematic sleep patterns and promote independence in health care management. Parents of patients with epilepsy and rare diseases should be monitored for their mental status which can affect patients’ well-being. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

13 pages, 656 KiB

Open AccessArticle

How the Spreading and Intensity of Interictal Epileptic Activity Are Associated with Visuo-Spatial Skills in Children with Self-Limited Focal Epilepsy with Centro-Temporal Spikes

by Pauline Dontaine, Coralie Rouge, Charline Urbain, Sophie Galer, Romain Raffoul, Antoine Nonclercq, Dorine Van Dyck, Simon Baijot and Alec Aeby

Brain Sci. 2023, 13(11), 1566; https://doi.org/10.3390/brainsci13111566 - 08 Nov 2023

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Abstract

This paper investigates brain–behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, [...] Read more.

This paper investigates brain–behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (p_corr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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13 pages, 4327 KiB

Open AccessArticle

Daytime-Restricted Feeding Ameliorates Oxidative Stress by Increasing NRF2 Transcriptional Factor in the Rat Hippocampus in the Pilocarpine-Induced Acute Seizure Model

by Octavio Fabián Mercado-Gómez, Virginia Selene Arriaga-Ávila, Angélica Vega-García, Sandra Orozco-Suarez, Vadim Pérez-Koldenkova, Juan José Camarillo-Sánchez, Marcelino Álvarez-Herrera and Rosalinda Guevara-Guzmán

Brain Sci. 2023, 13(10), 1442; https://doi.org/10.3390/brainsci13101442 - 10 Oct 2023

Cited by 1 | Viewed by 841

Abstract

Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed [...] Read more.

Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed a lipoperoxidation assay and dihydroethidium fluorescence to measure oxidative stress markers in the hippocampus (malondialdehyde and reactive oxygen species). The protein content of Nrf2 and its downstream protein SOD2 was evaluated using Western blotting. The cellular distribution of the Nrf2 and SOD2 proteins in the pyramidal cell layer of both the CA1 and CA3 hippocampal subfields and astrocytes (GFAP marker) were quantified using immunofluorescence and immunohistochemistry, respectively. Our results indicate that DRF reduced the malondialdehyde levels and the production of reactive oxygen species. Furthermore, a significant increase in Nrf2 and SOD2 protein content was observed in animals subjected to restrictive diet. In addition, DRF increased the relative intensity of the Nrf2 fluorescence in the perinuclear and nuclear compartments of pyramidal neurons in the CA1 subfield. Nrf2 immunoreactivity and the astrocyte marker GFAP also increased their colocalization under DRF conditions. Additionally, SOD2 immunoreactivity was increased in CA1 pyramidal neurons but not in the CA3 region. Our findings suggest that DRF partially prevents oxidative stress by increasing the Nrf2 transcriptional factor and the SOD2 enzyme during the development of SE. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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14 pages, 2515 KiB

Open AccessArticle

Modified Vertical Parasagittal Sub-Insular Hemispherotomy—Case Series and Technical Note

by Nicole Del Gaudio, Susana Ferrao Santos and Christian Raftopoulos

Brain Sci. 2023, 13(10), 1395; https://doi.org/10.3390/brainsci13101395 - 30 Sep 2023

Viewed by 773

Abstract

(1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug-resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon’s preference. Multiple technical variations have been proposed since Delalande first described his vertical technique. We propose a sub-insular variation of [...] Read more.

(1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug-resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon’s preference. Multiple technical variations have been proposed since Delalande first described his vertical technique. We propose a sub-insular variation of the vertical parasagittal hemispherotomy (VPH) and describe our case series of patients operated on using this procedure. (2) Methods: Data from a continuous series of patients with hemispheric DRE who were operated on by the senior author (CR) using the modified sub-insular VPH technique were analyzed retrospectively. Pre-operative demographic and epilepsy characteristics, functional outcome, and surgical complications were extracted from medical charts. (3) Results: Twenty-five patients were operated on between August 2008 and August 2023; 23 have at least 3 months of follow-up. Of this group, 20 (86.9%) patients are seizure-free. Only two patients developed postoperative hydrocephalus (8.7%). All patients who were able to walk autonomously preoperatively and 20 (86.9%) of those with follow-up were able to walk without assistance. A total of 17 (74%) patients were able to perform adapted social activities at the latest follow-up. (4) Conclusions: Modified sub-insular VPH is a successful surgical technique for hemispheric DRE with seizure freedom rates similar to the largest series reported in the literature. Compared to other series, patients who were operated on with our modified technique had a lower rate of postoperative hydrocephalus and excellent long-term motor and cognitive outcomes. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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13 pages, 3789 KiB

Open AccessArticle

Dehydroepiandrosterone Attenuates Astroglial Activation, Neuronal Loss and Dendritic Degeneration in Iron-Induced Post-Traumatic Epilepsy

by Chandra Prakash, Shyam Sunder Rabidas, Jyoti Tyagi and Deepak Sharma

Brain Sci. 2023, 13(4), 563; https://doi.org/10.3390/brainsci13040563 - 27 Mar 2023

Viewed by 1322

Abstract

Iron-induced experimental epilepsy in rodents reproduces features of post-traumatic epilepsy (PTE) in humans. The neural network of the brain seems to be highly affected during the course of epileptogenesis and determines the occurrence of sudden and recurrent seizures. The aim of the current [...] Read more.

Iron-induced experimental epilepsy in rodents reproduces features of post-traumatic epilepsy (PTE) in humans. The neural network of the brain seems to be highly affected during the course of epileptogenesis and determines the occurrence of sudden and recurrent seizures. The aim of the current study was to evaluate astroglial and neuronal response as well as dendritic arborization, and the spine density of pyramidal neurons in the cortex and hippocampus of epileptic rats. We also evaluated the effect of exogenous administration of a neuroactive steroid, dehydroepiandrosterone (DHEA), in epileptic rats. To induce epilepsy, male Wistar rats were given an intracortical injection of 100 mM solution (5 µL) of iron chloride (FeCl₃). After 20 days, DHEA was administered intraperitoneally for 21 consecutive days. Results showed epileptic seizures and hippocampal Mossy Fibers (MFs) sprouting in epileptic rats, while DHEA treatment significantly reduced the MFs’ sprouting. Astroglial activation and neuronal loss were subdued in rats that received DHEA compared to epileptic rats. Dendritic arborization and spine density of pyramidal neurons was diminished in epileptic rats, while DHEA treatment partially restored their normal morphology in the cortex and hippocampus regions of the brain. Overall, these findings suggest that DHEA’s antiepileptic effects may contribute to alleviating astroglial activation and neuronal loss along with enhancing dendritic arborization and spine density in PTE. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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13 pages, 1843 KiB

Open AccessArticle

Retrospective Clinical Analysis of Epilepsy Treatment for Children with Drug-Resistant Epilepsy (A Single-Center Experience)

by Changqing Liu, Yue Hu, Jian Zhou, Yuguang Guan, Mengyang Wang, Xueling Qi, Xiongfei Wang, Huawei Zhang, Aihemaitiniyazi Adilijiang, Tiemin Li and Guoming Luan

Brain Sci. 2023, 13(1), 14; https://doi.org/10.3390/brainsci13010014 - 21 Dec 2022

Cited by 2 | Viewed by 1557

Abstract

Objectives: This retrospective cohort study investigated the clinical characteristics and seizure outcomes of patients aged 1–14 years with drug-resistant epilepsy (DRE) who were treated by different typologies of therapy. Methods: Four hundred and eighteen children with DRE were recruited from Sanbo Brain Hospital [...] Read more.

Objectives: This retrospective cohort study investigated the clinical characteristics and seizure outcomes of patients aged 1–14 years with drug-resistant epilepsy (DRE) who were treated by different typologies of therapy. Methods: Four hundred and eighteen children with DRE were recruited from Sanbo Brain Hospital of Capital Medical University from April 2008 to February 2015. The patients were divided into three groups: medication (n = 134, 32.06%), resection surgery (n = 185, 44.26%), and palliative surgery (n = 99, 23.68%) groups. Demographic characteristics were attained from medical records. All patients were followed up for at least 5 years, with seizure outcomes classified according to International League Against Epilepsy criteria. The psychological outcome was evaluated with the development quotient and Wechsler Intelligence Quotient Scale for children (Chinese version). Results: The most frequent seizure type was generalized tonic seizure in 53.83% of patients. Age at seizure onset in 54.55% of patients was <3 years. The most frequent etiologies were focal cortical dysplasia (FCD). West syndrome was the most common epilepsy syndrome. Favorable seizure outcomes at the 5-year follow-up in the medication, resection surgery, and palliative surgery groups were 5.22%, 77.30%, and 14.14%, respectively. The patients showed varying degrees of improvement in terms of developmental and intellectual outcomes post-treatment. Conclusions: Pediatric patients with DRE were characterized by frequent seizures, a variety of seizure types, and complex etiology. Recurrent seizures severely affected the cognitive function and development of children. Early surgical intervention would be beneficial for seizure control and prevention of mental retardation. Palliative surgery was also a reasonable option for patients who were not suitable candidates for resection surgery. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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Review

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30 pages, 1472 KiB

Open AccessReview

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

by Ana Paula de Araújo Boleti, Pedro Henrique de Oliveira Cardoso, Breno Emanuel Farias Frihling, Luiz Filipe Ramalho Nunes de Moraes, Ellynes Amancio Correia Nunes, Lincoln Takashi Hota Mukoyama, Ellydberto Amancio Correia Nunes, Cristiano Marcelo Espinola Carvalho, Maria Lígia Rodrigues Macedo and Ludovico Migliolo

Brain Sci. 2024, 14(1), 71; https://doi.org/10.3390/brainsci14010071 - 10 Jan 2024

Viewed by 1878

Abstract

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the [...] Read more.

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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13 pages, 4380 KiB

Open AccessReview

Epilepsy Networks and Their Surgical Relevance

by Kevin Hines and Chengyuan Wu

Brain Sci. 2024, 14(1), 31; https://doi.org/10.3390/brainsci14010031 - 28 Dec 2023

Cited by 1 | Viewed by 1086

Abstract

Surgical epilepsy is a rapidly evolved field. As the understanding and concepts of epilepsy shift towards a network disorder, surgical outcomes may shed light on numerous components of these systems. This review documents the evolution of the understanding of epilepsy networks and examines [...] Read more.

Surgical epilepsy is a rapidly evolved field. As the understanding and concepts of epilepsy shift towards a network disorder, surgical outcomes may shed light on numerous components of these systems. This review documents the evolution of the understanding of epilepsy networks and examines the data generated by resective, ablative, neuromodulation, and invasive monitoring surgeries in epilepsy patients. As these network tools are better integrated into epilepsy practice, they may eventually inform surgical decisions and improve clinical outcomes. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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27 pages, 1281 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation

by Sahithi Madireddy and Samskruthi Madireddy

Brain Sci. 2023, 13(5), 784; https://doi.org/10.3390/brainsci13050784 - 11 May 2023

Cited by 9 | Viewed by 3902

Abstract

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative [...] Read more.

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative stress and mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation is increasingly understood to contribute to the pathogenesis of epilepsy. Mitochondrial dysfunction is also recognized for its contributions to neuronal excitability and apoptosis, which can lead to neuronal loss in epilepsy. This review focuses on the roles of oxidative damage, mitochondrial dysfunction, NAPDH oxidase, the blood–brain barrier, excitotoxicity, and neuroinflammation in the development of epilepsy. We also review the therapies used to treat epilepsy and prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, and antioxidant therapies. In addition, we review the use of neuromodulation and surgery in the treatment of epilepsy. Finally, we present the role of dietary and nutritional strategies in the management of epilepsy, including the ketogenic diet and the intake of vitamins, polyphenols, and flavonoids. By reviewing available interventions and research on the pathophysiology of epilepsy, this review points to areas of further development for therapies that can manage epilepsy. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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24 pages, 1227 KiB

Open AccessReview

A Comprehensive Review on Anti-Inflammatory Response of Flavonoids in Experimentally-Induced Epileptic Seizures

by Shyam Sunder Rabidas, Chandra Prakash, Jyoti Tyagi, Jyoti Suryavanshi, Pavan Kumar, Jaydeep Bhattacharya and Deepak Sharma

Brain Sci. 2023, 13(1), 102; https://doi.org/10.3390/brainsci13010102 - 05 Jan 2023

Cited by 5 | Viewed by 3081

Abstract

Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central [...] Read more.

Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central nervous system implicated with the activation of the inflammatory cascade in the brain. The aim of the present study was to summarize the role of various neuroinflammatory mediators in the onset and progression of epilepsy, and, thereafter, to discuss the flavonoids and their classes, including their biological properties. Further, we highlighted the modulation of anti-inflammatory responses achieved by these substances in different forms of epilepsy, as evident from preclinical studies executed on multiple epilepsy models. Overall, the review summarizes the available evidence of the anti-inflammatory potential of various flavonoids in epilepsy. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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15 pages, 4667 KiB

Open AccessSystematic Review

Neuromodulation Techniques in Children with Super-Refractory Status Epilepticus

by Ioannis Stavropoulos, Ho Lim Pak, Gonzalo Alarcon and Antonio Valentin

Brain Sci. 2023, 13(11), 1527; https://doi.org/10.3390/brainsci13111527 - 30 Oct 2023

Cited by 1 | Viewed by 1129

Abstract

Status epilepticus (SE) is a life-threatening condition and medical emergency which can have lifelong consequences, including neuronal death and alteration of neuronal networks, resulting in long-term neurologic and cognitive deficits in children. When standard pharmacological treatment for SE is not successful in controlling [...] Read more.

Status epilepticus (SE) is a life-threatening condition and medical emergency which can have lifelong consequences, including neuronal death and alteration of neuronal networks, resulting in long-term neurologic and cognitive deficits in children. When standard pharmacological treatment for SE is not successful in controlling seizures, the condition evolves to refractory SE (rSE) and finally to super-refractory SE (srSE) if it exceeds 24 h despite using anaesthetics. In this systematic review, we present literature data on the potential uses of clinical neuromodulation techniques for the management of srSE in children, including electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation. The evaluation of these techniques is limited by the small number of published paediatric cases (n = 25, one with two techniques) in peer-reviewed articles (n = 18). Although neuromodulation strategies have not been tested through randomised, prospective controlled clinical trials, this review presents the existing data and the potential benefits of neuromodulation therapy, suggesting that these techniques, when available, could be considered at earlier stages within the course of srSE intending to prevent long-term neurologic complications. Clinical trials aiming to establish whether early intervention can prevent long-term sequelae are necessary in order to establish the potential clinical value of neuromodulation techniques for the treatment of srSE in children. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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