Paroxysmal Activity Research Articles

The 2020–2022 paroxysmal episodes of the South-East Crater (Mt. Etna): insights into high-frequency eruptive activity from petrological monitoring

Over the last 20 years, the South-East Crater (SEC) of Etna has produced high-intensity explosive activity including Strombolian explosions and lava fountains associated with lava effusion. In the 2020–2022 period, SEC volcanic activity was characterized by two paroxysmal sequences from 13 December 2020 to 1 Apr 2021 (SEQ1) and from 19 May to 23 October 2021 (SEQ2); another two paroxysms occurred on 10 and 21 February 2022. The 2020–2022 eruptive activity was monitored by the Istituto Nazionale di Geofisica e Vulcanologia-Osservatorio Etneo (INGV-OE) with instrumental networks, field surveys, and laboratory analyses. A detailed record of the chemical variations of glass was acquired in the framework of the syn-eruptive petrological monitoring; chemical (major and trace elements) and isotopic (Sr and Nd) compositions of bulk rocks completed the study. The findings of the petrological monitoring, coupled with volcanological parameters and literature data, allowed magma evolution to be tracked and the subsurface magmatic processes responsible for the observed compositional variations to be inferred. Changes in magma supply rates and mixing between an evolved magma stored in the shallow reservoir and a more primitive magma ascending from intermediate depths controlled magma evolution during the 2020–2022 paroxysmal activity. We discuss magmatic processes in the plumbing system before and during the eruption and the relationship between rate of magma supply and the eruptive dynamics. Finally, the 2020–2022 paroxysmal activity of SEC tested the INGV-OE procedures of petrological monitoring, in the framework of monitoring best practices.

Generalized paroxysmal fast activity in a cohort of patients with epilepsy with eyelid myoclonia

ObjectiveThis study aimed to analyze and summarize the characteristics of generalized paroxysmal fast activity (GPFA) via electroencephalography (EEG) in patients with epilepsy with eyelid myoclonia (EEM) and to determine its relationship with clinical outcome. MethodsPatients with EEM were selected from our EEG database. The collected data included detailed clinical information, factors that triggered GPFA, and the relationship between GPFA and eyelid myoclonia seizures. The clinical data and EEG characteristics of patients with and without GPFA were compared. ResultsForty-seven patients with EEM were identified according to the clinical criteria, of whom 18 (38.3%) exhibited GPFA. GPFA can occur ictally or interictally. The difference in the response to antiseizure medication (ASM) between EEM patients with and without GPFA suggested that patients who had GPFA on EEG might have easier seizure control. ConclusionIn our study, 38.3% of EEM patients had GPFA on EEG. GPFA is an EEG pattern in individuals with EEM that can cause eyelid myoclonia. EEM patients with GPFA on their EEG had easier seizure control than those without GPFA. SignificanceThis study summarized the incidence and electroclinical features of GPFA in a cohort of patients with EEM.

Differences in subcortical functional connectivity in patients with epilepsy.

Epilepsy is a disease characterized by abnormal paroxysmal bioelectrical activity in the brain cortex and subcortical structures. Seizures per se change brain metabolism in epileptic focus and in distal parts of the brain. However, interictal phenomena can also affect functional connectivity (FC) and brain metabolism in other parts of the brain. We hypothesised that epilepsy affects functional connectivity not only among cortical, but also between subcortical, structures of the brain in a resting state condition. Investigating functional connectivity in patients with epilepsy could provide insights into the underlying pathophysiological mechanisms. Better understanding may lead to more effective treatment strategies. Functional connectivity was analysed in 35 patients with epilepsy and in 28 healthy volunteers. The group of patients was divided into generalised and focal epilepsy (temporal and extratemporal subgroups). Each patient and healthy volunteer underwent an fMRI resting-state session. During the study, EEG signals were simultaneously recorded with fMRI to facilitate the subsequent detection of potential interictal epileptiform discharges (IEDs). Their potential impact on BOLD signals was mitigated through linear regression. The data was processed and correlation coefficients (FC values) between the BOLD signal from selected structures of the central nervous system were determined and compared between study groups. The results were presented as significant differences in correlation coefficients between brain/subcortical structures in the epilepsy and control groups. Lower FC values for the epilepsy group compared to the control group were shown for connections related to the MPFC, hippocampus, thalamus, amygdala, and the parahippocampal gyrus. Epilepsy alters the functional connectivity of resting state subcortical networks. Patterns of pathological changes of FC differ between epilepsy subtypes, with predominant lower FC between the hippocampus, parahippocampal gyrus, amygdala and thalamus in patients with epilepsy. This study suggests that epilepsy affects subcortical structures. Identifying distinct patterns of altered FC in epilepsy subtypes may help to tailor treatment strategies. Changes in FC detected by fMRI may precede clinical symptoms, aiding in the early diagnosis of cognitive and emotional disorders in focal epilepsy.

Large (≥3-Millimeter) Parenchymal Brain Calcified Cysticerci Are More Often Associated with Hippocampal Atrophy than Smaller Ones in Seizure-Free Individuals with a Single Lesion.

Calcified cysticerci are often associated with hippocampal atrophy (HA). While most studies suggest that repetitive seizures cause HA in these patients, others have demonstrated that HA may also occur in persons without epilepsy. Little is known about mechanisms triggering HA in seizure-free individuals with calcified cysticerci. Here, we aimed to assess whether the size of the calcification is associated with HA. Using a population-based design, we selected apparently seizure-free individuals with a single calcified cysticercus in whom interictal paroxysmal activity and other causes of HA have been discarded. A total of 55 individuals (mean age, 58.3 ± 13 years, 62% women) fulfilled inclusion criteria. Unadjusted and multivariate models were fitted to assess the association between the size of the calcification dichotomized into <3 mm and ≥3 mm (exposure) and the presence of HA (outcome). Sixteen participants (29%) had HA, which was asymmetric in eight (50%) cases. Hippocampal atrophy was noted in 11/20 (55%) participants with large calcifications and in 5/35 (14%) with small calcifications (P = 0.001). A multivariate logistic regression model showed a significant association between the presence of large calcifications and HA, after adjustment for relevant confounders (odds ratio: 7.78; 95% CI: 1.72-35.1). Participants with calcifications ≥3 mm in diameter were 7.8 times more likely to have HA than those with smaller ones. Study results open avenues of research for the use of agents to prevent HA progression.

A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy.

Epilepsy and Cognition in GM2-Gangliosidosis B1 Variant – Experience of a Tertiary Hospital

Introduction: GM2 gangliosidosis B1 variant (GM2B1) is an autosomal recessive disorder due to deficiency of β-hexosaminidase A, leading to the lysosomal storage of GM2 gangliosides in neuronal tissue and neuronal death. Symptoms include progressive motor coordination impairment and neurodegeneration, in children with previously normal development, leading to early death. Objective: Clinical characterization of patients with GM2B1 with a focus on epileptic manifestations. Methods: A descriptive retrospective study was conducted, analyzing clinical records of patients diagnosed with GM2B1 and followed at our Hospital Neuropediatric Department in the decade 2013-2022. Results: Four patients (three female) from three families diagnosed with GM2B1 were identified. The median age at diagnosis was 70 months. The most frequent symptoms at presentation were developmental regression (all children), language impairment (three), and epileptic seizures (two). Enzymatic deficiency in leukocytes and pathogenic variants in the HEXA gene were demonstrated in all cases. The pathogenic variant c.533G&gt;A(p.R178H) in exon 5 was present in seven of the eight alleles. All patients experienced language impairment (Md=42 mos) with complete language loss (Md=78 mos). Loss of walking ability occurred in three patients (Md=96 mos). All patients experienced epileptic seizures during the course of the disease, with a median onset of seizures at 55 months. Initial seizures were classified as atypical absences (two), tonic seizures (one) and myoclonic seizures (one). Electroencephalographic evaluation revealed slow basal rhythm and focal paroxysmal activity in all cases. All were treated with antiseizure medication, two requiring a combination of three drugs. Conclusion: GM2B1 encompasses a wide clinical spectrum, with heterogenous age of symptom onset, clinical presentation and disease progression. Epilepsy is a common comorbidity in GM2B1, with variable seizure type and severity, and may be difficult to control. Timely diagnosis, coupled with multidisciplinary clinical follow-up, is crucial to improve quality of life of patients and enable genetic counseling.

Seizure Outcome and Predicting Factors in Adult Patients with Phenylketonuria: Single-center Experience

ABSTRACT Objective: Phenylketonuria (PKU) is one of the most common metabolic disorders worldwide. If left untreated, it causes neuropsychiatric sequelae, with seizures being a common occurrence. There is little information about the clinical features of epilepsy, electroencephalography (EEG) findings, and factors related to seizure outcomes in adult patients. We aimed to investigate these variables in adult PKU patients. Methods: We conducted a retrospective search in our database using the keywords “PKU and epilepsy” for the period between 2008 and 2022. Demographic, clinical, EEG, and cranial magnetic resonance imaging (MRI) findings of the patients were extracted from the electronic health records. Scalp EEG and MRI findings were reassessed. Phenylalanine (Phe) levels of the cases were retrieved. The potential correlation between seizure outcome and laboratory findings was analyzed. Results: Ten patients (4 females; aged: 19–55 years) were included. Seizure onset was various. The most common seizure type was bilateral tonic-clonic. Nine patients were on antiseizure medications (ASMs); seven were seizure-free. EEG background activity was slow in four patients, with paroxysmal discharges in eight individuals. The most frequent MRI finding was periventricular white matter hyperintensity. No correlation existed between seizure outcome and clinical, EEG, MRI results, or Phe levels. Seizure freedom was more common in patients with good dietary compliance. Conclusion: Bilateral tonic–clonic seizures were the most common type of seizure, accompanied by frequent paroxysmal activity in EEG. MRI scans revealed periventricular white matter hyperintensity. Seizure freedom was commonly achieved with ASMs, irrespective of blood Phe levels. Nevertheless, dietary compliance may play a role in seizure control.

Magma recharge in persistently active basaltic–andesite systems and its geohazards implications: the case of Villarrica volcano, Chile

We report whole-rock chemistry, mineral chemistry, and volatile content from Villarrica volcano’s major recent paroxysms and background activity. Composition of the volcanic products are basalt to basaltic andesite with whole-rock SiO2 content between 50 and 56 wt%, and a mineralogy dominated by olivine (Fo71-80), clinopyroxene (Mg# ~ 50) and plagioclase (An60–80). Volatile contents in melt inclusions are up to 1.5 wt% H2O, 500 ppm CO2, 1230 ppm sulfur and 580 ppm chlorine. Regardless of the type of activity, there are no substantial variations in whole-rock composition or the volatile content when the activity switches from background activity to a major paroxysm, strongly suggesting that this shift does not just depend on the arrival of new magma in the shallow magmatic system. Geothermobarometry constrains crystallization of the major mineral phases at various depths between 3 and 12.7 km, suggesting that degassing of a volatile-rich recharge magma occurs deeper than 12 km, producing efficient mixing throughout the whole system, and sustaining the lava lake activity in Villarrica’s summit crater. The occurrence of a permanent lava lake also suggests that the magma recharge must be close to continuous and therefore sudden changes between background and paroxysmal volcanic activity are likely controlled by relatively small changes in the rate of recharge and/or the volatile release rate in the magmatic system. This has important implications for the understanding of eruption triggers and the forecasting of volcanic eruptions.Graphical abstract

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.

Affective disorders in patients with epilepsy: primary process or consequence of paroxysmal activity?

The high prevalence of primary affective disorders in patients with epilepsy is beyond doubt. However, patients in this group are often identified as suffering from mood disorders that do not fulfil the criteria for primary mood disorders, such as recurrent depressive disorder and bipolar affective disorder. The aim of this paper is to analyze the classification and clinical picture of affective disorders in patients with epilepsy and differential diagnostic approaches to identify primary affective disorders and secondary affective disorders in epilepsy. A set of diagnostic signs for the differential assessment of affective disorders in patients with epilepsy is presented. Research of affective pathology in patients with epilepsy and the development of strategies for its successful treatment are still needed.

Stimulus-induced arousal with transient electroencephalographic improvement distinguishes nonictal from ictal generalized periodic discharges.

In the case of suspicion of nonconvulsive status epilepticus (NCSE), reactivity on electroencephalograms (EEGs) can provide valuable diagnostic information. Reactivity refers to responses to auditory or somatosensory stimulation, with changes in amplitude and frequency of background activity. Because of self-perpetuating processes and the failure of self-terminating mechanisms, status epilepticus is unlikely to cease when patients spontaneously move, and it cannot typically be stopped by external stimulation (i.e., auditory and tactile stimuli). The defining EEG characteristic of absence status epilepticus is the presence of bilateral, synchronous, symmetric, rhythmic paroxysmal activity that shows little or no reactivity to sensory stimulation. On the other hand, in metabolic/toxic or multifactorial encephalopathies, triphasic waves (TWs) are influenced by the level of vigilance. TWs may be transiently abolished when patients increase their level of alertness from a drowsy/lethargic state to a state of wakefulness. This reactivity is only observed when patients can be aroused by a somatosensory or auditory stimulus. This reactivity tends to disappear with increasing severity of the disease and in comatose patients. In patients without preexisting developmental and epileptic encephalopathy, this pattern of stimulus-induced wakefulness with transient improvement of the EEG is a major criterion in determining that the EEG patterns are not ictal. This criterion of reactivity on EEGs, beyond the classical clinical/EEG criteria of NCSE (Salzburg criteria), should now be systematically added.

Semiology and Neurophysiology of Clonic Seizures: A Report of 39 Patients.

Clonic seizures are currently defined as repetitive and rhythmic myoclonic contractions of a specific body part, producing twitching movements at a frequency of 0.2-5 Hz. There are few studies in the literature that have reported a detailed analysis of the semiology, neurophysiology, and lateralizing value of clonic seizures. In this article, we aim to report our findings from a retrospective review of 39 patients. We identified 39 patients (48 seizures) from our center who had been admitted with clonic seizures between 2016 and 2022. We performed a retrospective review of their video-EEG recordings for semiology and ictal EEG findings. Seventeen patients also had simultaneous surface-EMG (sEMG) electrodes placed on affected body parts, which were analyzed as well. The most common initial affected body parts were face, arm, and hand. In most of the cases, seizures propagated from lower face to upper face and distal hand to proximal arm. The most common seizure-onset zone was the perirolandic region, and the most common EEG seizure pattern was paroxysmal rhythmic monomorphic activity. The lateralizing value for EEG seizure onset to contralateral hemisphere in unilateral clonic seizures (n = 39) was 100%. All seizures recorded with sEMG electrodes demonstrated synchronous brief tetanic contractions of agonists and antagonists, alternating with synchronous silent periods. Arrhythmic clonic seizures were associated with periodic epileptiform discharges on the EEG, whereas rhythmic clonic seizures were associated with paroxysmal rhythmic monomorphic activity. Overall, the most common etiology was cerebrovascular injuries, followed by tumors. Clonic seizures are characterized by synchronized brief tetanic contractions of agonist and antagonistic muscles alternating with synchronized silent periods, giving rise to the visible twitching. The most common seizure onset zone is in the perirolandic region, which is consistent with the symptomatogenic zone being in the primary motor area. The lateralizing value of unilateral clonic seizures for seizure onset in the contralateral hemisphere is 100%.

195 Targeting Thalamocortical Circuits For Closed-Loop Stimulation in Lennox-Gastaut Syndrome

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy associated with frequent seizures, cognitive impairment, and high burden of care. Electrical stimulation of the thalamus can be an effective treatment for LGS, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. METHODS: Brain network maps from 3 group-level studies of LGS were averaged to define the area of peak overlap: combined electroencephalography-functional MRI (EEG-fMRI) of paroxysmal fast activity, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) of hypometabolism, and structural connectivity associated with efficacy in a previous trial of deep brain stimulation. The resulting “hotspot” was used as a seed in a normative fMRI connectivity analysis to identify connected networks. Two patients underwent bilateral thalamocortical implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analyzed for presence and synchrony of epileptiform activity. RESULTS: Peak overlap was in bilateral premotor cortex. Functional connectivity of this hotspot revealed a network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-fMRI and FDG-PET. Intracranial electrophysiology showed characteristic epileptiform activity of LGS in the cortical hotspot that preceded or co-occurred with similar thalamic activity. CONCLUSIONS: Premotor cortex shows peak involvement in LGS, and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for neuromodulation therapies, including thalamocortical stimulation. Compared to thalamus-only stimulation, addition of this cortical target may allow more rapid detections and responsive stimulations of seizures, and broader modulation of the brain network underlying LGS to achieve greater seizure control.

Learning Disabilities and Epilepsy: About a Clinical Case

Landau-Kleffner syndrome (LKS) is an epilepsy syndrome of childhood, characterized by auditory verbal agnosia and severe electroencephalographic abnormalities. It happens between 3-7 years of age, 20% without seizures. A 6-years-old boy, with normal psychomotor development, who begins to experience difficulties in understanding the meaning of words, sometimes with incoherent speech and writing difficulties (irregular handwriting, spelling mistakes). Neurological evaluation showed loss of comprehensive language with auditory verbal agnosia, difficulties in fine motor skills and in graphomotor coordination. After clinical suspicion, the diagnosis of SLK was confirmed by night video-electroencephalogram (EEG): abundant paroxysmal activity of bilateral and independent fronto-center-temporal spikes and spike-wave activity, with an almost continuous exacerbation during sleep. Initially treated with valproate and clobazam, without improvement, he started prednisolone, with improvement in language, writing and normalization of the EEG. Knowledge of this syndrome is important for differential diagnosis with other neurological disorders, especially learning difficulties.

Utility and limitations of EEG in the diagnosis and management of ALDH7A1-related pyridoxine-dependent epilepsy. A retrospective observational study.

Pyridoxine-dependent epilepsy due to ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE. A total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life. Median age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (< 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy. A neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available.

Correspondence between scalp-EEG and stereoelectroencephalography seizure-onset patterns in patients with MRI-negative drug-resistant focal epilepsy.

Our objective was to evaluate the relationship between scalp-EEG and stereoelectroencephalography (SEEG) seizure-onset patterns (SOP) in patients with MRI-negative drug-resistant focal epilepsy. We analyzed retrospectively 41 patients without visible lesion on brain MRI who underwent video-EEG followed by SEEG. We defined five types of SOPs on scalp-EEG and eight types on SEEG. We examined how various clinical variables affected scalp-EEG SOPs. The most prevalent scalp SOPs were rhythmic sinusoidal activity (56.8%), repetitive epileptiform discharges (22.7%), and paroxysmal fast activity (15.9%). The presence of paroxysmal fast activity on scalp-EEG was always seen without delay from clinical onset and correlated with the presence of low-voltage fast activity in SEEG (sensitivity = 22.6%, specificity = 100%). The main factor explaining the discrepancy between the scalp and SEEG SOPs was the delay between clinical and scalp-EEG onset. There was a correlation between the scalp and SEEG SOPs when the scalp onset was simultaneous with the clinical onset (p = 0.026). A significant delay between clinical and scalp discharge onset was observed in 25% of patients and featured always with a rhythmic sinusoidal activity on scalp, corresponding to similar morphology of the discharge on SEEG. The presence of repetitive epileptiform discharges on scalp was associated with an underlying focal cortical dysplasia (sensitivity = 30%, specificity = 90%). There was no significant association between the scalp SOP and the epileptogenic zone location (deep or superficial), or surgical outcome. In patients with MRI-negative focal epilepsy, scalp SOP could suggest the SEEG SOP and some etiology (focal cortical dysplasia) but has no correlation with surgical prognosis. Scalp SOP correlates with the SEEG SOP in cases of simultaneous EEG and clinical onset; otherwise, scalp SOP reflects the propagation of the SEEG discharge. We looked at the correspondence between the electrical activity recorded during the start of focal seizure using scalp and intracerebral electrodes in patients with no visible lesion on MRI. If there is a fast activity on scalp, it reflects similar activity inside the brain. We found a good correspondence between scalp and intracerebral electrical activity for cases without significant delay between clinical and scalp electrical onset (seen in 75% of the cases we studied). Visualizing repetitive epileptic activity on scalp could suggest a particular cause of the epilepsy: a subtype of brain malformation called focal cortical dysplasia.

Experimental study of the influence of phenozanic acid and its combination with valproic acid on the development of the epileptic system

To study the effect of phenosanic acid (PA) and its combination with valproic acid (VA) on the development of the Epi system. A model of focal chronic epilepsy in rats was created by applying metallic cobalt to the surface of the sensorimotor area of the cortex. Long-term electrodes were implanted in the sensorimotor cortex of the left and right hemispheres, the hippocampus, and the hypothalamus. The effect of PA (80 mg/kg) and its combination with VA (200 mg/kg) on discharge activity was carried out on the 2nd day and at the stage of generalization of the Epi system - on the 6th day. The stability of the Epi system on day 10 was assessed by provoking the development of epileptic status (Epi status) in response to the administration of thiolactone homocysteine (HMC) at a dose of 5.5 mmol/kg. In rats treated with PA, low discharge activity is observed, which is confirmed by the absence of EEG and motor manifestations of status epilepticus caused by HMC. PA does not suppress paroxysmal activity at the stages of development of the Epi system. VA significantly suppresses paroxysmal activity, but does not affect the formation of new foci of Epi activity in subcortical structures and the contralateral cortex. The epi system of rats treated with VA is characterized by high discharge activity by the 10th day of the experiment and lability to provocation of epi status. The combination of drugs is more pronounced than PA, but less than VA, reduces the numerical characteristics of paroxysmal activity in the brain structures of rats. PA when administered alone, in combination with VA, causes a slowdown in the generalization of convulsive foci of Epi activity and prevents the formation of a stable Epi system. VA, having a pronounced anticonvulsant effect, does not weaken the development of the Epi system in the model of focal cobalt-induced epilepsy.

A new approach to spatial localization of EEG-based electrical activity

Background. Accuracy and reliability of methods for spatial localization of brain activity based on electroencephalography (EEG) data do not lose relevance. Existing localization methods are coupled to specific difficulties due to ambiguity of the resulting solution.Ojective: verification of a new method for localizing brain activity using EEG data «Virtually Implanted Electrode» and demonstratoin of its capabilities.Material and methods. The new method was verified using deep brain stimulation (DBS) data. There were used the data from scalp electrical activity induced solely by potentials from two electrodes implanted into deep areas of human brain. It was achieved by filtering EEG signals at the stimulation frequency and excluding signals from other brain areas. A clinical case of applying the new method for EEG analysis of patient paroxysmal activity is presented as well.Results. «Virtually Implanted Electrode» method allowed to quite accurately determine the localization of DBS current sources. The effectiveness of using the method for analyzing the mechanisms of paroxysmal activity was demonstrated: based on change in potentials calculated in 33 sites of the brain (brain areas), three groups of areas were identified specifically contributing to development of paroxysmal activity. For comparison, the same artificial DBS sources were localized using other verified methods: the BrainLoc (Russia) and sLORETA (Switzerland) software providing substantially worse data.Conclusion. Identifying spatial localization of electrical potentials recorded on the scalp surface by using the new approach with the «Virtually Implanted Electrode» method shows high efficiency and reliability, demonstrating a clear advantage over other known localization methods.

Interrater reliability of interictal EEG waveforms in Lennox-Gastaut Syndrome.

Identification of EEG waveforms is critical for diagnosing Lennox-Gastaut Syndrome (LGS) but is complicated by the progressive nature of the disease. Here, we assess the interrater reliability (IRR) among pediatric epileptologists for classifying EEG waveforms associated with LGS. A novel automated algorithm was used to objectively identify epochs of EEG with transient high power, which were termed events of interest (EOIs). The algorithm was applied to EEG from 20 LGS subjects and 20 healthy controls during NREM sleep, and 1350 EOIs were identified. Three raters independently reviewed the EOIs within isolated 15-second EEG segments in a randomized, blinded fashion. For each EOI, the raters assigned a waveform label (spike and slow wave, generalized paroxysmal fast activity, seizure, spindle, vertex, muscle, artifact, nothing, or other) and indicated the perceived subject type (LGS or control). Labeling of subject type had 85% accuracy across all EOIs and an IRR of κ =0.790, suggesting that brief segments of EEG containing high-power waveforms can be reliably classified as pathological or normal. Waveform labels were less consistent, with κ =0.558, and the results were highly variable for different categories of waveforms. Label mismatches typically occurred when one reviewer selected "nothing," suggesting that reviewers had different thresholds for applying named labels. Classification of EEG waveforms associated with LGS has weak IRR, due in part to varying thresholds applied during visual review. Computational methods to objectively define EEG biomarkers of LGS may improve IRR and aid clinical decision-making.

Combined Oxidative Phosphorylation Deficiency Type-13 with Perinatal Presentation: A Case Report.

Polynucleotide phosphorylase is involved in RNA processing in mitochondria. Biallelic variants in PNPT1 cause mitochondrial RNA import protein deficiency and heterogeneous clinical manifestations. The patiest was the first child of remote consanguineous parents, born at 35 weeks by caesarean section due to fetal growth restriction. Apgar index was 9/10/10. Birth weight, length and head circumference were at 3rd, <3rd and 10th percentiles, respectively. In the first hours of life, respiratory distress, hypoglycaemia and seizures ensued. She started invasive mechanic ventilation, phenobarbital and was transferred to ICU. Physical examination showed minor facial dysmorphisms, brief eye-opening, hypotonia and hyporeflexia. Electroencephalogram showed immature pattern and multifocal paroxysmal activity. MRI at D8 of life showed severe reduced brain volume. Normal aminoacid screen was also observed. Expanded newborn screening was negative. Mitochondrial organic aciduria was seen. WES showed a homozygotic likely pathogenic variant in the PNPT1 gene. MRI at 6-months showed brain atrophy, thin corpus callosum, reduced brainstem volume. Bilateral and symmetrical lesions in globi pallidi, compatible with Leigh síndrome were observed. Currently, at 14 months, no neurodevelopment progress, dystonia, visual deficit, sensorineural deafness, hypertrophic cardiomyopathy and microcephaly are observed. The early and severe Leigh-like presentation of our patient expands the phenotype spectrum of this disease. As far as we know, this is the first reported case of PNPT1 mutation with onset in the perinatal period. Moreover, hypertrophic cardiomyopathy has not yet been described in association with mutation of the PNPT1 gene. WES was the key for early diagnosis in this patient. It should be done in all children with severe clinical presentation of unknown origin.