Late infantile epileptic encephalopathy: A distinct developmental and epileptic encephalopathy syndrome

Objective: Within the spectrum of developmental and epileptic encephalopathy (DEE), there are a group of infants with features that are distinct from the well-recognized syndromes of early infantile developmental and epileptic encephalopathy (EIDEE), infantile epileptic spasm syndrome (IESS), and Lennox-Gastaut syndrome (LGS). We refer to this condition as late infantile epileptic encephalopathy (LIEE). Our objective is to highlight the characteristics of this group by analyzing patients who exhibit prototypical features. Methods: From July 2022 to May 2023, we searched for LIEE features in pediatric patients who underwent epilepsy follow-up at the University of Chicago Comer Children's Hospital. Results: Out of 850 patients evaluated, thirty patients (3.5%) were identified with LIEE based on electroclinical characteristics. These patients had an average onset of epilepsy at 6.8 months and an average onset of LIEE features at 18.1 months. The epilepsy etiology was most commonly genetic and metabolic (50%), followed by congenital cortical malformations (23%), acquired structural abnormalities (20%), and unknown (7%). The predominant seizure types were myoclonic-tonic (70%), spasm-tonic (50%), epileptic spasms (47%), tonic (43%), and myoclonic (43%) seizures. All patients reported a history of either spasm-tonic or myoclonic-tonic seizures in addition to other types. All patients had EEGs showing discontinuity, electro-decrements, or both along with diffuse slowing, background voltages between 100-300 μV, and superimposed multifocal, diffuse epileptiform discharges. Every patient, except one, fulfilled the definition of drug-resistant epilepsy and all reported either moderate to severe developmental delay. Significance: Late infantile epileptic encephalopathy (LIEE) is characterized by several unique clinical and electrographic features. Typically, LIEE manifests in patients during the second year of life and occurs before two years of age, hence late-infantile onset. The condition is commonly observed in infants with symptomatic epilepsy. Myoclonic-tonic and spasm-tonic seizures are the quintessential seizure types. The inter-ictal EEG exhibits more organization and lower voltages than seen with hypsarhythmia and lacks the defining EEG characteristics of EIDEE, IESS, or LGS. We propose that LIEE is a distinct electroclinical syndrome within the spectrum of developmental and epileptic encephalopathies

Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd

The International Surface Pressure Databank version 2

The International Surface Pressure Databank (ISPD) is the world's largest collection of global surface and sea-level pressure observations. It was developed by extracting observations from established international archives, through international cooperation with data recovery facilitated by the Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative, and directly by contributing universities, organizations, and countries. The dataset period is currently 1768–2012 and consists of three data components: observations from land stations, marine observing systems, and tropical cyclone best track pressure reports. Version 2 of the ISPD (ISPDv2) was created to be observational input for the Twentieth Century Reanalysis Project (20CR) and contains the quality control and assimilation feedback metadata from the 20CR. Since then, it has been used for various general climate and weather studies, and an updated version 3 (ISPDv3) has been used in the ERA-20C reanalysis in connection with the European Reanalysis of Global Climate Observations project (ERA-CLIM). The focus of this paper is on the ISPDv2 and the inclusion of the 20CR feedback metadata. The Research Data Archive at the National Center for Atmospheric Research provides data collection and access for the ISPDv2, and will provide access to future versions

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Paradigm found: Epileptogenic zone identified by fMRI in ictal fixation off sensitivity

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Electroclinical features of myoclonic-tonic and spasm-tonic seizures in childhood

Myoclonic-tonic (MT) and spasm-tonic (ST) seizures represent distinctive features in late infantile epileptic encephalopathy (LIEE). This commentary aims to delineate the electroclinical characteristics of MT and ST seizures, setting them apart from other seizure types. Our analysis encompasses 211 ST and MT seizures observed in 31 patients diagnosed with LIEE, providing a comprehensive overview of video-EEG features and polygraphic signatures. In MT seizures, EEG findings reveal a high-voltage diffuse spike/polyspike and wave discharge, often succeeded by diffuse electrodecrements. The amplitude-integrated EEG (aEEG) signature is described as a “reversed checkmark.” Conversely, ST seizures exhibit EEG findings such as a vertex positive deflection after a slow-wave and relative electrodecrement, with intermixed epileptiform discharges. In comparison to MT seizures, polygraphic characteristics in ST seizures appear more distinct, featuring a brief rhomboid shape corresponding to the spasm, followed by a lengthier rectangular shape indicative of the tonic phase of the ST seizure. While the pathophysiology of ST and MT seizures remains inadequately understood, their concurrent occurrence and association with other seizure types (tonic, epileptic spasm, myoclonic) within the temporal context of LIEE and other epileptic encephalopathies prompt us to anticipate advancements in our understanding through future research. We hope that this study serves as a foundation for unraveling these complexities in the times to come

Pediatric epilepsy syndromes with associated developmental impairment

In 2022, the International League Against Epilepsy revised their classification of epilepsy syndromes for clinicians to better understand the relationships between different epilepsy syndromes, their underlying causes, and their associated developmental and behavioral features. This review highlights portions of the current classification with an emphasis on epilepsy syndromes that readily present with developmental challenges and provides a unique framework, based on electroencephalography, to easily identify and understand these syndromes. Included in this review are a helpful categorization scheme with visual aid, descriptions of updated epilepsy syndromes, figures of relevant identifiers of syndrome and information regarding future directions toward treatment and research. Covered syndromes include developmental and epileptic encephalopathy, Dravet syndrome, Rasmussen syndrome, and infantile epileptic spasm syndrome, among others

Diagnosis and management of nonconvulsive status epilepticus in children

Nonconvulsive status epilepticus (NCSE) encompasses a wide range of diagnoses with variable outcomes and treatment recommendations. In children, NCSE can be observed in various conditions, including acute neurological injuries, specific childhood epilepsy syndromes and other neurological conditions, and can also be observed in individuals with learning difficulties. NCSE in children is thought to be under-recognized, and further studies examining the electrographic characteristics of very young children in NCSE would aid the prompt recognition of additional patients. Some subtypes of NCSE are probably more harmful than others, and long-term prospective studies are needed to evaluate the damaging potential of NCSE itself as opposed to that of the underlying circumstances in which it occurs. Specific data in childhood are clearly lacking, but extrapolation from adult studies indicates that aggressive treatment is most warranted in comatose patients. By contrast, a cautious approach seems to be indicated for absence status epilepticus, complex partial status epilepticus and electrical status epilepticus during sleep