scholarly journals Effect of lacosamide on epileptiform activity and structure-function relations in the brain of rats with chronic focal epilepsy

2019 ◽  
Vol 11 (1) ◽  
pp. 37-45 ◽  
Author(s):  
S. A. Litvinova ◽  
G. G. Avakyan ◽  
L. N. Nerobkova ◽  
T. A. Voronina ◽  
N. A. Gladysheva
Keyword(s):  
Structure Function ◽  
Drug Administration ◽  
Focal Epilepsy ◽  
Epileptiform Activity ◽  
Rat Cortex ◽  
Contralateral Cortex ◽  
Stage 1 ◽  
The Brain ◽  
Epileptic System ◽  
Topical Applications

The aim was to study the effect of lacosamide on epileptiform activity (EрA) and structure-function relations in the brain in the course of development of the epileptic system in rats with cobalt-induced chronic epilepsy. Materials and methods. To model chronic focal epilepsy, we used topical applications of cobalt on the sensorimotor zone of the rat cortex. The effect of lacosamide (20 mg/kg) on the cobalt-induced epileptiform activity was analyzed in parallel with with the monitoring of spectral-coherent changes in the brain during the development of the epileptic system (ES). Results. In the first 30 minutes after the administration, lacosamide briefly enhanced the EрA in the hippocampus and ipsilateral cortex, and also strengthened the cortical-hippocampal (at stage 1) and cortical-hypothalamic connections (at stage 2). Two hours after the drug administration, a decrease in EрA was observed at stages 1 and 2 of the ES development, especially in the contralateral cortex and hippocampus. At all frequency ranges, the level of the inter-center connections decreased (most pronounced in the cortical-hippocampal links). Conclusion. The effect of lacosamide on EрA in the rat brain with cobalt-induced epileptogenic focus is characterized by a decrease in EрA, two hours after the drug administration. This effect is most expressed in the cortex and hippocampus, and is accompanied by a decrease in the level of the corticalhippocampal connections.

COMPUTATIONAL MODELING OF TRANSCRANIAL DIRECT CURRENT STIMULATION IN THE CHILD BRAIN: IMPLICATIONS FOR THE TREATMENT OF REFRACTORY CHILDHOOD FOCAL EPILEPSY

2014 ◽  
Vol 24 (02) ◽  
pp. 1430006 ◽  
Author(s):  
MARTA PARAZZINI ◽  
SERENA FIOCCHI ◽  
ILARIA LIORNI ◽  
ALBERTO PRIORI ◽  
PAOLO RAVAZZANI
Keyword(s):  
Electric Field ◽  
Computational Modeling ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Focal Epilepsy ◽  
Brain Area ◽  
Epileptiform Activity ◽  
Brain Regions ◽  
Direct Current Stimulation ◽  
The Brain

Transcranial direct current stimulation (tDCS) was recently proposed for the treatment of epilepsy. However, the electrode arrangement for this case is debated. This paper analyzes the influence of the position of the anodal electrode on the electric field in the brain. The simulation shows that moving the anode from scalp to shoulder does influence the electric field not only in the cortex, but also in deeper brain regions. The electric field decreases dramatically in the brain area without epileptiform activity.

scholarly journals Distinct structure-function relationships across cortical regions and connectivity scales in the rat brain

2019 ◽  
Author(s):  
Milou Straathof ◽  
Michel R.T. Sinke ◽  
Theresia J.M. Roelofs ◽  
Erwin L.A. Blezer ◽  
R. Angela Sarabdjitsingh ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Structure Function ◽  
Rat Brain ◽  
Resting State ◽  
Structural Connectivity ◽  
Distinct Structure ◽  
Macro Scale ◽  
Function Relationship ◽  
The Brain ◽  
Meso Scale

AbstractAn improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in many disorders. We integrated high-field resting-state fMRI-based functional connectivity with high-resolution macro-scale diffusion-based and meso-scale neuronal tracer-based structural connectivity, to obtain an accurate depiction of the structure-function relationship in the rat brain. Our main goal was to identify to what extent structural and functional connectivity strengths are correlated, macro- and meso-scopically, across the cortex. Correlation analyses revealed a positive correspondence between functional connectivity and macro-scale diffusion-based structural connectivity, but no correspondence between functional connectivity and meso-scale neuronal tracer-based structural connectivity. Locally, strong functional connectivity was found in two well-known resting-state networks: the sensorimotor and default mode network. Strong functional connectivity within these networks coincided with strong short-range intrahemispheric structural connectivity, but with weak heterotopic interhemispheric and long-range intrahemispheric structural connectivity. Our study indicates the importance of combining measures of connectivity at distinct hierarchical levels to accurately determine connectivity across networks in the healthy and diseased brain. Distinct structure-function relationships across the brain can explain the organization of networks and may underlie variations in the impact of structural damage on functional networks and behavior.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

scholarly journals Oxcarbazepine as the initial monotherapy of focal epilepsy in adolescents and adults

2021 ◽  
Vol 13 (3) ◽  
pp. 67-74
Author(s):  
T. N. Pushkar ◽  
A. M. Azhigova ◽  
P. N. Vlasov ◽  
A. B. Kozhokaru
Keyword(s):  
Side Effects ◽  
Treatment Effectiveness ◽  
Focal Epilepsy ◽  
Activity Index ◽  
Retention Rate ◽  
Epileptiform Activity ◽  
Initial Therapy ◽  
Sustained Remission ◽  
Fold Reduction ◽  
Frequency Changes

Oxcarbazepine (OXC) is an antiepileptic drug (AED) used in children and adults as initial and adjunctive therapy for focal epilepsy (FE). It has been used in Russia since 2007; however, only a few studies have been published on its use in Russian patients to date.Objective: to assess the effectiveness and tolerability of OXC as initial therapy for FE in adults and adolescents, as well as to study epileptiform activity index (EAI) changes during treatment and its relationship with treatment effectiveness and tolerability.Patients and methods. We evaluated treatment effectiveness and tolerability and EAI in 89 adults with newly diagnosed FE aged 15–75 years for 12 months. Patients were divided into three subgroups according to the OXC treatment regimen. Side Effects of Anti-Epileptic Drugs (SIDAED) scale was used to assess treatment tolerability. Retention rate and seizure frequency changes were used to evaluate treatment effectiveness. EAI changes were assessed with video electroencephalography monitoring (4–24 h) during each visit (baseline, after 1, 3, 6, and 12 months).Results and discussion. The retention rate in patients on OXC monotherapy after 12 months was 71.9%, almost one-half of them (46.1%) achieved sustained remission. More than half of patients (52.9%) were prescribed 1200 mg/day of OXC, 12.3% – <1200 mg/day, and only in 6.7% of patients the dose exceeded 1200 mg/day. Side effects were observed in 9% of the cases. A 2.54-fold reduction in mean EAI index was observed during follow-up representing treatment effectiveness.Conclusion. OXC, as the initial AED for FE, has demonstrated high treatment effectiveness and tolerability. In addition, total EAI 2.5-fold reduction allows its usage as an additional quantitative marker of OXC treatment effectiveness.

Musical hallucinations: a rare and atypical presentation of anti-IgLON5 disease responsive to immunosuppressive therapy

2021 ◽  
Vol 14 (2) ◽  
pp. e236963
Author(s):  
Alex Stoyanov ◽  
Alan McDougall ◽  
Nicolas Urriola
Keyword(s):  
Immunosuppressive Therapy ◽  
Complete Resolution ◽  
Epileptiform Activity ◽  
Oral Prednisone ◽  
Visual Hallucinations ◽  
Variable Response ◽  
Abnormal Movements ◽  
Central Nervous System Disorders ◽  
Insidious Onset ◽  
The Brain

IgLON5 antibodies are typically associated with the insidious onset of sleep disorder, parasomnia, gait disturbance and abnormal movements, with variable response to immunosuppressive therapy. We describe a case of a 50-year-old man who presented with acute speech difficulties, headache and focal seizures followed by well-formed visual hallucinations, and later, musical hallucinations of mainstream popular music. MRI of the brain demonstrated right temporal lobe changes with corresponding epileptiform activity seen on electroencephalogram. Subsequently, IgLON5 antibodies were detected in the serum. The patient was treated with anticonvulsants, as well as azathioprine with a tapering oral prednisone course with a complete resolution of the symptoms. Our case demonstrates an unusual presentation of the rare but increasingly described anti-IgLON5 disease, with musical hallucinations. The case highlights the variable and evolving clinical phenotypes that can be seen in autoimmune central nervous system disorders.

Efficacy of Low-dose Dextromethorphan in the Treatment of Nonketotic Hyperglycinemia

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 924-926
Author(s):  
Ramin Alemzadeh ◽  
Karsten Gammeltoft ◽  
Karla Matteson
Keyword(s):  
Sodium Benzoate ◽  
Low Dose ◽  
Epileptiform Activity ◽  
Therapeutic Effects ◽  
Psychomotor Delay ◽  
Aspartate Receptor ◽  
Nonketotic Hyperglycinemia ◽  
Electroencephalographic Activity ◽  
The Brain ◽  
Stimulation Of

Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degradation causing muscular hypotonia, seizures, apnea, and lethargy; it has a poor prognosis. Accumulation of glycine in the brain is thought to cause excessive stimulation of the N-methyl-D-aspartate receptor. Dextromethorphan (DM), an N-methyl-D-aspartate receptor antagonist, in doses of 5 to 35 mg/kg per day has been shown to have beneficial therapeutic effects in some patients with NKH. We report the case of a 1-year-old infant with NKH, seizure disorder, and psychomotor delay who was clinically seizure free during treatment with sodium benzoate, arginine, benzodiazepam, and phenobarbital. Although sodium benzoate normalized serum glycine levels (103 to 125 µmol/L), cerebrospinal fluid glycine levels remained elevated (42 to 47 µmol/L), with epileptiform activity on electroencephalography. The addition of low-dose DM (0.25 mg/kg per day) to the treatment led to improvement of electroencephalographic activity, resolution of nystagmus with increased eye contact, and modest progression of developmental milestones. These data suggest that DM at doses significantly lower than previously reported may be beneficial in some patients with NKH. Treatment with low-dose DM needs further evaluation.

Burster Reconstruction Considering Unmeasurable Variables in the Epileptor Model

2021 ◽  
pp. 1-46
Author(s):  
João Angelo Ferres Brogin ◽  
Jean Faber ◽  
Douglas Domingues Bueno
Keyword(s):  
Computational Neuroscience ◽  
Dynamic Models ◽  
Epileptiform Activity ◽  
Convergence Speed ◽  
Brain Disorders ◽  
Feedback Controllers ◽  
Control Techniques ◽  
The Brain ◽  
Significant Effort ◽  
Theoretical Standpoint

Abstract Epilepsy is one of the most common brain disorders worldwide, affecting millions of people every year. Although significant effort has been put into better understanding it and mitigating its effects, the conventional treatments are not fully effective. Advances in computational neuroscience, using mathematical dynamic models that represent brain activities at different scales, have enabled addressing epilepsy from a more theoretical standpoint. In particular, the recently proposed Epileptor model stands out among these models, because it represents well the main features of seizures, and the results from its simulations have been consistent with experimental observations. In addition, there has been an increasing interest in designing control techniques for Epileptor that might lead to possible realistic feedback controllers in the future. However, such approaches rely on knowing all of the states of the model, which is not the case in practice. The work explored in this letter aims to develop a state observer to estimate Epileptor's unmeasurable variables, as well as reconstruct the respective so-called bursters. Furthermore, an alternative modeling is presented for enhancing the convergence speed of an observer. The results show that the proposed approach is efficient under two main conditions: when the brain is undergoing a seizure and when a transition from the healthy to the epileptiform activity occurs.

Classification of seizures and epilepsy

2019 ◽  
pp. 935-944
Author(s):  
Andrew McEvoy ◽  
Tim Wehner ◽  
Victoria Wykes
Keyword(s):  
Focal Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Hippocampal Sclerosis ◽  
Epileptic Seizures ◽  
Recurrence Risk ◽  
Medical Emergency ◽  
Unprovoked Seizure ◽  
Generalized Seizures ◽  
The Brain

Epileptic seizures are transient neurologic alterations due to abnormal excessive or synchronous neuronal cerebral activity. They may cause subjective symptoms (aura), and objective autonomic, behavioural, or cognitive alterations in any combination. Focal seizures are initially generated in one circumscribed area in the brain, whereas generalized seizures involve bihemispheric neuronal networks from the seizure onset. Epilepsy is a brain disease defined by the occurrence of two unprovoked seizures more than 24 h apart or one unprovoked seizure with underlying pathological or genetic factors resulting in a similar recurrence risk. Focal epilepsy syndromes are best classified by aetiology or anatomical area of origin. A seizure that does not self-terminate results in status epilepticus, and constitutes a medical emergency that requires immediate treatment. Focal cortical dysplasia and hippocampal sclerosis are the commonest aetiologies of epilepsy amenable to surgical treatment and are reviewed here. The limbic pathway may be involved in seizure propagation, and the anatomy is described.

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