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•Epileptic high frequency brain signals have significantly elevated kurtosis and skewness.•Sources of epileptic high frequency brain signals pinpoint to epileptogenic ...zones.•Magnetoencephalography can noninvasively localize epileptic high frequency activity.
Neuromagnetic high frequency brain signals (HFBS, > 80 Hz) are a new biomarker for localization of epileptogenic zones (EZs) for pediatric epilepsy.
Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). Epileptic HFBS in 80−250 Hz and 250−600 Hz were quantitatively determined by comparing with normative controls in terms of kurtosis and skewness. Magnetic sources of epileptic HFBS were localized and then compared to clinical EZs determined by invasive recordings and surgical outcomes.
Kurtosis and skewness of HFBS were significantly elevated in epilepsy patients compared to healthy controls (p < 0,001 and p < 0.0001, respectively). Sources of elevated MEG signals in comparison to normative data were co-localized to EZs for 22 (22/23, 96 %) patients.
The results indicate, for the first time, that epileptic HFBS can be noninvasively quantified by measuring kurtosis and skewness in MEG data. Magnetic source imaging based on kurtosis and skewness can accurately localize EZs.
Source imaging of kurtosis and skewness of MEG HFBS provides a novel way for preoperative localization of EZs for epilepsy surgery.
Tethered cord syndrome (TCS) is a clinical condition of various origins that arises from tension on the spinal cord. Radiographic findings may include the conus medullaris in a lower than normal ...position, fatty infiltration of the filum terminale, lipomyelomeningocele, myelomeningocele, myelocystocele, meningocele, split cord malformations, dermal sinus, anorectal malformations, and intraspinal tumors. The clinical constellation of signs and symptoms associated with TCS may include dermatologic, urological, gastrointestinal, neurological, and orthopedic findings. The current review focuses on TCS by age group of the more common causes of the condition, including myelomeningocele, lipomyelomeningocele, as well as the adult presentation of occult TCS. Pertinent review of the neuroembryology and normal anatomical position of the conus medullaris is included.
Summary
Purpose
Implantation of subdural grids and invasive electroencephalography (EEG) monitoring is important to define the ictal‐onset zone and eloquent cortex in selected patients with medically ...refractory epilepsy. The objective of this systematic review is to summarize data about adverse events related to this procedure.
Methods
English‐language studies published up to July 2012, reporting such adverse events were reviewed. Outcome measures included demographic variables; surgical protocol including number of subdural electrodes implanted per patient, duration of monitoring, antibiotic, and steroid prophylaxis; and adverse events.
Key Findings
Twenty‐one studies were identified including a total of 2,542 patients. The reported mean number of electrodes per patient and duration of monitoring varied from 52 to 95 and 5 to 17 days, respectively. There is a trend toward more uniform use of antibiotics and steroids in the perioperative period. Neurologic infections (pooled prevalence 2.3%, 95% confidence interval 1.5–3.1), superficial infections (3.0%, 1.9–4.1), intracranial hemorrhage (4.0%, 3.2–4.8), and elevated intracranial pressure (2.4%, 1.5–3.3) were found to be the most common adverse events. Up to 3.5% of patients required additional surgical procedure(s) for management of these adverse events. Increased number of electrodes (≥67) was found to be independently associated with increased incidence of adverse events.
Significance
Although providing critical information for patients with medically refractory epilepsy, subdural grids implantation and invasive EEG monitoring entails risks of infection, hemorrhage, and elevated intracranial pressure. The prevalence estimates, likely to be conservative due to selective reporting, are expected to be helpful in counseling patients.
Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the ...molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (
) is responsible for early postnatal hydrocephalus in the
(
) mouse mutant.
is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The
ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of
in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development.
•During visual naming, high-gamma modulation occurs in a posteroanterior sequential pattern with overlapping temporal profiles.•Cortical activations during visual naming represent cognitive ...sub-components with different relative contributions from the left and right cerebral hemispheres.•Post-surgical neuropsychological deficits correlated with the location of resected parcels within the visual naming network.
Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring.
Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50–150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM.
In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings.
Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles.
Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks.
Summary
Invasive electroencephalographic monitoring with implantable subdural electrodes and intraparenchymal depth electrodes has become a basic tenet of epilepsy surgery. Improved localization of ...epileptic foci justifies the secondary procedure and monitoring period in many patients. Informed use of invasive monitoring in conjunction with imaging and functional studies makes epilepsy surgery a smaller, safer, and more effective endeavor. Herein we review the history, indications, implementation, and foreseeable future of grid, strip, and depth electrode use.
Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We ...previously reported elevated neuroinflammation and severe periventricular white matter damage in the
(
) mutant which contains a point mutation in the
gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal
mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy postnatal cerebral cortical development in the
mutant. While bindarit only mildly reduced the ventricular volume, it significantly improved the edematous appearance and myelination of the corpus callosum. Moreover, the treatment attenuated thinning in cortical Layers II-IV, excitatory synapse formation, and interneuron morphogenesis, by supporting the ramified-shaped homeostatic microglia from excessive cell death. Also, the therapeutic effect led to the alleviation of a spastic locomotor phenotype of the mutant. We found that microglia, but not peripheral monocytes, contribute to amoeboid-shaped activated myeloid cells in
mutants' corpus callosum and the proinflammatory cytokines expression. Bindarit blocks nuclear factor (NF)-kB activation and its downstream proinflammatory cytokines, including monocyte chemoattractant protein-1, in the
mutant. Collectively, we revealed that amelioration of neuroinflammation is crucial for white matter and neuronal maturation in neonatal hydrocephalus. Future studies of bindarit treatment combined with CSF diversion surgery may provide long-term benefits supporting neuronal development in neonatal hydrocephalus.
In neonatal hydrocephalus, little is known about the signaling cascades of neuroinflammation or the impact of such inflammatory insults on neural cell development within the perinatal cerebral cortex. Here, we report that proinflammatory activation of myeloid cells, the majority of which are derived from microglia, impairs periventricular myelination and cortical neuronal maturation using the mouse
genetic model of neonatal hydrocephalus. Administration of bindarit, an anti-inflammatory small molecule that blocks nuclear factor (NF)-kB activation, restored the cortical thinning and synaptic maturation defects in the
mutant brain through suppression of microglial activation. These data indicate the potential therapeutic use of anti-inflammatory reagents targeting neuroinflammation in the treatment of neonatal hydrocephalus.
•Epileptic brain generates interictal high frequency spikes (HFSs) in 80–600 Hz.•HFSs include spikelets (80–250 Hz) and fast spikelets (250–600 Hz).•HFSs are a new epileptogenic biomarker for ...localizing epileptogenic zones.•HFSs can be noninvasively detected and localized by magnetoencephalography.
One barrier hindering high frequency brain signals (HFBS, >80 Hz) from wide clinical applications is that the brain generates both pathological and physiological HFBS. This study was to find specific biomarkers for localizing epileptogenic zones (EZs).
Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). High frequency oscillations (HFOs, > 4 oscillatory waveforms) and high frequency spikes (HFSs, > 1 spiky or sharp waveforms) in 80–250 Hz and 250–600 Hz bands were blindly detected with an artificial intelligence method and validated with visual inspection. The magnitude of HFOs and HFSs were quantified with spectral analyses. Sources of HFSs and HFOs were localized and compared with clinical EZs determined by invasive recordings and surgical outcomes.
HFOs in 80–250 Hz and 250–600 Hz were identified in both epilepsy patients (18/23, 12/23, respectively) and healthy controls (6/23, 4/23, respectively). HFSs in 80–250 Hz and 250–600 Hz were detected in patients (16/23, 11/23, respectively) but not in healthy controls. A combination of HFOs and HFSs localized EZs for 22 (22/23, 96%) patients.
The results indicate, for the first time, that HFSs are a newer and more specific biomarker than HFOs for localizing EZs because HFOs appeared in both epilepsy patients and healthy controls while HFSs appeared only in epilepsy patients.
Emergence of CRISPR/Cas9 genome editing provides a robust method for gene targeting in a variety of cell types, including fertilized rat embryos. The authors used this method to generate a transgenic ...rat L1cam knockout model of X-linked hydrocephalus (XLH) with human genetic etiology. The object of this study was to use diffusion tensor imaging (DTI) in studying perivascular white matter tract injury in the rat model and to characterize its pathological definition in histology.
Two guide RNAs designed to disrupt exon 4 of the L1cam gene on the X chromosome were injected into Sprague-Dawley rat embryos. Following embryo transfer into pseudopregnant females, rats were born and their DNA was sequenced for evidence of L1cam mutation. The mutant and control wild-type rats were monitored for growth and hydrocephalus phenotypes. Their macro- and microbrain structures were studied with T2-weighted MRI, DTI, immunohistochemistry, and transmission electron microscopy (TEM).
The authors successfully obtained 2 independent L1cam knockout alleles and 1 missense mutant allele. Hemizygous male mutants from all 3 alleles developed hydrocephalus and delayed development. Significant reductions in fractional anisotropy and axial diffusivity were observed in the corpus callosum, external capsule, and internal capsule at 3 months of age. The mutant rats did not show reactive gliosis by then but exhibited hypomyelination and increased extracellular fluid in the corpus callosum.
The CRISPR/Cas9-mediated genome editing system can be harnessed to efficiently disrupt the L1cam gene in rats for creation of a larger XLH animal model than previously available. This study provides evidence that the early pathology of the periventricular white matter tracts in hydrocephalus can be detected in DTI. Furthermore, TEM-based morphometric analysis of the corpus callosum elucidates the underlying cytopathological changes accompanying hydrocephalus-derived variations in DTI. The CRISPR/Cas9 system offers opportunities to explore novel surgical and imaging techniques on larger mammalian models.
Objective
Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an ...alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM‐induced seizures (EISs) between the two electrode types.
Methods
Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates.
Results
We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication.
Significance
SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.
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