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The "crowding" effect (CE), wherein verbal functions are preserved presumably at the expense of nonverbal functions, which diminish following inter-hemispheric transfer of language functions, is recognized as a specific aspect of functional reorganization, offering an insight about neural plasticity in children with neural insult to the dominant hemisphere. CE is hypothesized as a marker for language preservation or improvement after left-hemispheric injury, yet it remains challenging to fully discern it in preoperative evaluation. We present a novel DWI connectome (DWIC) approach to predict the presence of CE in 24 drug-resistant epilepsy (DRE) patients with a left-hemispheric focus and 29 young healthy controls. Psychometry-driven DWIC analysis was applied to create verbal and non-verbal modular networks. Local efficiency (LE) was assessed at individual regions of the two networks and its Z-score was compared to predict the presence of CE. Compared with a traditional organization (TO) group, wherein verbal functions are adversely affected, while non-verbal functions are preserved, the CE group showed significantly higher Z-scores in verbal network and significantly lower Z-scores in non-verbal network, corresponding to network reorganization in CE. A larger number of antiseizure drugs was significantly associated with more decreased Z-score in the right non-verbal network of the CE group and left verbal network of the TO group. These findings hold great potential to identify DRE patients whose verbal/language skills may over time be preserved due to effective inter-hemispheric reorganization and identify those whose verbal/language impairments may persist due to lack of inter-hemispheric reorganization.
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We built normative brain atlases that animate millisecond-scale intra- and inter-hemispheric white matter-level connectivity dynamics supporting object recognition and speech production. We quantified electrocorticographic modulations during three naming tasks using event-related high-gamma activity from 1,114 nonepileptogenic intracranial electrodes (i.e., non-lesional areas unaffected by epileptiform discharges). Using this electrocorticography data, we visualized functional connectivity modulations defined as significant naming-related high-gamma modulations occurring simultaneously at two sites connected by direct white matter streamlines on diffusion-weighted imaging tractography. Immediately after stimulus onset, intra- and inter-hemispheric functional connectivity enhancements were confined mainly across modality-specific perceptual regions. During response preparation, left intra-hemispheric connectivity enhancements propagated in a posterior-to-anterior direction, involving the left precentral and prefrontal areas. After overt response onset, inter- and intra-hemispheric connectivity enhancements mainly encompassed precentral, postcentral, and superior-temporal (STG) gyri. We found task-specific connectivity enhancements during response preparation as follows. Picture naming enhanced activity along the left arcuate fasciculus between the inferior-temporal and precentral/posterior inferior-frontal (pIFG) gyri. Nonspeech environmental sound naming augmented functional connectivity via the left inferior longitudinal and fronto-occipital fasciculi between the medial-occipital and STG/pIFG. Auditory descriptive naming task enhanced usage of the left frontal U-fibers, involving the middle-frontal gyrus. Taken together, the commonly observed network enhancements include inter-hemispheric connectivity optimizing perceptual processing exerted in each hemisphere, left intra-hemispheric connectivity supporting semantic and lexical processing, and inter-hemispheric connectivity for symmetric oral movements during overt speech. Our atlases improve the currently available models of object recognition and speech production by adding neural dynamics via direct intra- and inter-hemispheric white matter tracts.
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Idioma , Fala , Humanos , Fala/fisiologia , Mapeamento Encefálico/métodos , Encéfalo , Percepção Visual/fisiologiaRESUMO
This prospective study determined the use of intracranially recorded spectral responses during naming tasks in predicting neuropsychological performance following epilepsy surgery. We recruited 65 patients with drug-resistant focal epilepsy who underwent preoperative neuropsychological assessment and intracranial EEG recording. The Clinical Evaluation of Language Fundamentals evaluated the baseline and postoperative language function. During extra-operative intracranial EEG recording, we assigned patients to undergo auditory and picture naming tasks. Time-frequency analysis determined the spatiotemporal characteristics of naming-related amplitude modulations, including high gamma augmentation at 70-110 Hz. We surgically removed the presumed epileptogenic zone based on the intracranial EEG and MRI abnormalities while maximally preserving the eloquent areas defined by electrical stimulation mapping. The multivariate regression model incorporating auditory naming-related high gamma augmentation predicted the postoperative changes in Core Language Score with r2 of 0.37 and in Expressive Language Index with r2 of 0.32. Independently of the effects of epilepsy and neuroimaging profiles, higher high gamma augmentation at the resected language-dominant hemispheric area predicted a more severe postoperative decline in Core Language Score and Expressive Language Index. Conversely, the model incorporating picture naming-related high gamma augmentation predicted the change in Receptive Language Index with an r2 of 0.50. Higher high gamma augmentation independently predicted a more severe postoperative decline in Receptive Language Index. Ancillary regression analysis indicated that naming-related low gamma augmentation and alpha/beta attenuation likewise independently predicted a more severe Core Language Score decline. The machine learning-based prediction model suggested that naming-related high gamma augmentation, among all spectral responses used as predictors, most strongly contributed to the improved prediction of patients showing a >5-point Core Language Score decline (reflecting the lower 25th percentile among patients). We generated the model-based atlas visualizing sites, which, if resected, would lead to such a language decline. With a 5-fold cross-validation procedure, the auditory naming-based model predicted patients who had such a postoperative language decline with an accuracy of 0.80. The model indicated that virtual resection of an electrical stimulation mapping-defined language site would have increased the relative risk of the Core Language Score decline by 5.28 (95% confidence interval: 3.47-8.02). Especially, that of an electrical stimulation mapping-defined receptive language site would have maximized it to 15.90 (95% confidence interval: 9.59-26.33). In summary, naming-related spectral responses predict neuropsychological outcomes after epilepsy surgery. We have provided our prediction model as an open-source material, which will indicate the postoperative language function of future patients and facilitate external validation at tertiary epilepsy centres.
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Epilepsia Resistente a Medicamentos , Epilepsia , Complicações Cognitivas Pós-Operatórias , Mapeamento Encefálico/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia/métodos , Epilepsia/cirurgia , Humanos , Estudos ProspectivosRESUMO
OBJECTIVE: Our daily activities require frequent switches among competing responses at the millisecond time scale. We determined the spatiotemporal characteristics and functional significance of rapid, large-scale brain network dynamics during task switching. METHODS: This cross-sectional study investigated patients with drug-resistant focal epilepsy who played a Lumosity cognitive flexibility training game during intracranial electroencephalography (iEEG) recording. According to a given task rule, unpredictably switching across trials, participants had to swipe the screen in the direction the stimulus was pointing or moving. Using this data, we described the spatiotemporal characteristics of iEEG high-gamma augmentation occurring more intensely during switch than repeat trials, unattributable to the effect of task rule (pointing or moving), within-stimulus congruence (the direction of stimulus pointing and moving was same or different in a given trial), or accuracy of an immediately preceding response. Diffusion-weighted imaging (DWI) tractography determined whether distant cortical regions showing enhanced activation during task switch trials were directly connected by white matter tracts. Trial-by-trial iEEG analysis deduced whether the intensity of task switch-related high-gamma augmentation was altered through practice and whether high-gamma amplitude predicted the accuracy of an upcoming response among switch trials. RESULTS: The average number of completed trials during five-minute gameplay was 221.4 per patient (range: 171-285). Task switch trials increased the response times, whereas later trials reduced them. Analysis of iEEG signals sampled from 860 brain sites effectively elucidated the distinct spatiotemporal characteristics of task switch, task rule, and post-error-specific high-gamma modulations. Post-cue, task switch-related high-gamma augmentation was initiated in the right calcarine cortex after 260 ms, right precuneus after 330 ms, right entorhinal after 420 ms, and bilateral anterior middle-frontal gyri after 450 ms. DWI tractography successfully showed the presence of direct white matter tracts connecting the right visual areas to the precuneus and anterior middle-frontal regions but not between the right precuneus and anterior middle-frontal regions. Task-related high-gamma amplitudes in later trials were reduced in the calcarine, entorhinal and anterior middle-frontal regions, but increased in the precuneus. Functionally, enhanced post-cue precuneus high-gamma augmentation improved the accuracy of subsequent responses among switch trials. CONCLUSIONS: Our multimodal analysis uncovered two temporally and functionally distinct network dynamics supporting task switching. High-gamma augmentation in the visual-precuneus pathway may reflect the neural process facilitating an attentional shift to a given updated task rule. High-gamma activity in the visual-dorsolateral prefrontal pathway, rapidly reduced through practice, may reflect the cost of executing appropriate stimulus-response translation.
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Encéfalo , Epilepsia Resistente a Medicamentos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Estudos Transversais , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Humanos , Tempo de Reação/fisiologiaRESUMO
PURPOSE: A prominent view of language acquisition involves learning to ignore irrelevant auditory signals through functional reorganization, enabling more efficient processing of relevant information. Yet, few studies have characterized the neural spatiotemporal dynamics supporting rapid detection and subsequent disregard of irrelevant auditory information, in the developing brain. To address this unknown, the present study modeled the developmental acquisition of cost-efficient neural dynamics for auditory processing, using intracranial electrocorticographic responses measured in individuals receiving standard-of-care treatment for drug-resistant, focal epilepsy. We also provided evidence demonstrating the maturation of an anterior-to-posterior functional division within the superior-temporal gyrus (STG), which is known to exist in the adult STG. METHODS: We studied 32 patients undergoing extraoperative electrocorticography (age range: eight months to 28 years) and analyzed 2,039 intracranial electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI lesions. Patients were given forward (normal) speech sounds, backward-played speech sounds, and signal-correlated noises during a task-free condition. We then quantified sound processing-related neural costs at given time windows using high-gamma amplitude at 70-110 Hz and animated the group-level high-gamma dynamics on a spatially normalized three-dimensional brain surface. Finally, we determined if age independently contributed to high-gamma dynamics across brain regions and time windows. RESULTS: Group-level analysis of noise-related neural costs in the STG revealed developmental enhancement of early high-gamma augmentation and diminution of delayed augmentation. Analysis of speech-related high-gamma activity demonstrated an anterior-to-posterior functional parcellation in the STG. The left anterior STG showed sustained augmentation throughout stimulus presentation, whereas the left posterior STG showed transient augmentation after stimulus onset. We found a double dissociation between the locations and developmental changes in speech sound-related high-gamma dynamics. Early left anterior STG high-gamma augmentation (i.e., within 200 ms post-stimulus onset) showed developmental enhancement, whereas delayed left posterior STG high-gamma augmentation declined with development. CONCLUSIONS: Our observations support the model that, with age, the human STG refines neural dynamics to rapidly detect and subsequently disregard uninformative acoustic noises. Our study also supports the notion that the anterior-to-posterior functional division within the left STG is gradually strengthened for efficient speech-sound perception after birth.
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Córtex Auditivo , Epilepsia Resistente a Medicamentos , Percepção da Fala , Estimulação Acústica/métodos , Adulto , Córtex Auditivo/diagnóstico por imagem , Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia/métodos , Humanos , Lactente , IdiomaRESUMO
During a verbal conversation, our brain moves through a series of complex linguistic processing stages: sound decoding, semantic comprehension, retrieval of semantically coherent words, and overt production of speech outputs. Each process is thought to be supported by a network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected inter-lobar neocortical networks support distinct stages of linguistic processing across brain development. Novel six-dimensional tractography was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar effective connectivity between cortical areas activated during each linguistic processing stage. We analysed 3401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (aged 5-20 years) who underwent extra-operative electrocorticography recording. Principal component analysis of auditory naming-related high-gamma modulations determined the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal and 1581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between extratemporal and temporal lobe site pairs, which were simultaneously activated between sentence offset and verbal response onset (i.e. response preparation period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with increased strength of inter-lobar effective connectivity especially between those activated during response preparation. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of <2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. We, for the first time, provided an atlas which quantifies and animates the strength, dynamics, and direction specificity of inter-lobar neural communications between language areas via the white matter pathways. Language-related effective connectivity may be strengthened in an age-dependent manner even after the age of 5.
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Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Conectoma/métodos , Idioma , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Adolescente , Atlas como Assunto , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Eletrocorticografia , Feminino , Humanos , Masculino , Modelos Neurológicos , Adulto JovemRESUMO
OBJECTIVE: This study was undertaken to build and validate a novel dynamic tractography-based model for localizing interictal spike sources and visualizing monosynaptic spike propagations through the white matter. METHODS: This cross-sectional study investigated 1900 spike events recorded in 19 patients with drug-resistant temporal lobe epilepsy (TLE) who underwent extraoperative intracranial electroencephalography (iEEG) and resective surgery. Twelve patients had mesial TLE (mTLE) without a magnetic resonance imaging-visible mass lesion. The remaining seven had a mass lesion in the temporal lobe neocortex. We identified the leading and lagging sites, defined as those initially and subsequently (but within ≤50 ms) showing spike-related augmentation of broadband iEEG activity. In each patient, we estimated the sources of 100 spike discharges using the latencies at given electrode sites and diffusion-weighted imaging-based streamline length measures. We determined whether the spatial relationship between the estimated spike sources and resection was associated with postoperative seizure outcomes. We generated videos presenting the spatiotemporal change of spike-related fiber activation sites by estimating the propagation velocity using the streamline length and spike latency measures. RESULTS: The spike propagation velocity from the source was 1.03 mm/ms on average (95% confidence interval = .91-1.15) across 133 tracts noted in the 19 patients. The estimated spike sources in mTLE patients with International League Against Epilepsy Class 1 outcome were more likely to be in the resected area (83.9% vs. 72.3%, φ = .137, p < .001) and in the medial temporal lobe region (80.5% vs. 72.5%, φ = .090, p = .002) than those associated with the Class ≥2 outcomes. The resulting video successfully animated spike propagations, which were confined within the temporal lobe in mTLE but involved extratemporal lobe areas in lesional TLE. SIGNIFICANCE: We have, for the first time, provided dynamic tractography visualizing the spatiotemporal profiles of rapid propagations of interictal spikes through the white matter. Dynamic tractography has the potential to serve as a unique epilepsy biomarker.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Epilepsia , Estudos Transversais , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , HumanosRESUMO
This retrospective cohort study investigated 53 patients with drug-resistant focal epilepsy and identified factors predictive of long-term satisfaction of patients and families following extraoperative intracranial EEG (iEEG) recording. The mixed model analysis assessed the utility of intracranial EEG (iEEG) predictor variables, including the seizure-onset zone (SOZ), modulation index (MI), and naming-related high-gamma activity. Modulation index, quantifying the coupling between high-frequency activity at >80â¯Hz and local slow wave at 3-4â¯Hz, effectively functions as a surrogate marker of the burden of interictal spike-and-slow-wave discharges. The mixed model specifically incorporated 'subtraction-MI', defined as the subtraction of mean z-score normalized MI across all preserved sites from that across all resected sites. Auditory naming-related high-gamma activity at 70-110â¯Hz is a biomarker to characterize the underlying language and speech function. The model incorporated 'maximum resected high-gamma', defined as the high-gamma percent change largest among sites included in the resected language-dominant hemispheric region. The model also incorporated the clinical and imaging profiles of given patients. The analysis revealed that complete removal of SOZ (pâ¯=â¯0.003) and younger patient age (pâ¯=â¯0.040) were independently associated with greater satisfaction. Neither 'subtraction-MI' nor 'maximum naming-related high-gamma' showed a significant and independent association with long-term satisfaction in our patient cohort. The observed impact of complete resection of SOZ and early surgery can be considered when counseling candidates for epilepsy surgery.
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OBJECTIVE: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants. METHODS: A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. RESULTS: Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. SIGNIFICANCE: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.
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Epilepsias Parciais/genética , Epilepsias Parciais/patologia , Epilepsias Parciais/terapia , Proteínas do Tecido Nervoso/genética , Canais de Potássio Ativados por Sódio/genética , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Dieta Cetogênica , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/terapia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Quinidina , Estudos RetrospectivosRESUMO
INTRODUCTION: Drug-resistant seizures due to hemimegalencephaly in neonates and infants are a unique surgical and anesthesia challenge. While early surgery in these patients may predict a better seizure control, a lower body weight, limited blood volume, and surgical blood loss may make hemispherectomy prohibitive. METHODS: Two infants (weight, 8.7 kg and 3.7 kg) underwent interhemispheric vertical hemispherotomy with endoscope assistance. In the first case, during the lateral disconnection, excessive bleeding prompted the surgeon to coagulate the lenticulostriate arteries at the origin from the middle cerebral artery to reduce bleeding. In the second infant, the lenticulostriate arteries were coagulated before initiating the lateral disconnection. RESULTS: In both infants, the blood loss from lateral dissection was reduced by coagulation of lenticulostriate arteries. CONCLUSION: The authors suggest that early coagulation of the lenticulostriate arteries is a useful strategy to minimize blood loss in low-weight infants undergoing hemispherotomy.
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Hemimegalencefalia , Hemisferectomia , Hemimegalencefalia/etiologia , Hemimegalencefalia/cirurgia , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Convulsões/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: The strength of presurgical language mapping using electrocorticography (ECoG) is its outstanding signal fidelity and temporal resolution, but the weakness includes limited spatial sampling at an individual patient level. By averaging naming-related high-gamma activity at nonepileptic regions across a large number of patients, we provided the functional cortical atlases animating the neural dynamics supporting visual-object and auditory-description naming at the whole brain level. METHODS: We studied 79 patients who underwent extraoperative ECoG recording as epilepsy presurgical evaluation, and generated time-frequency plots and animation videos delineating the dynamics of naming-related high-gamma activity at 70-110 Hz. RESULTS: Naming task performance elicited high-gamma augmentation in domain-specific lower-order sensory areas and inferior-precentral gyri immediately after stimulus onset. High-gamma augmentation subsequently involved widespread neocortical networks with left hemisphere dominance. Left posterior temporal high-gamma augmentation at several hundred milliseconds before response onset exhibited a double dissociation; picture naming elicited high-gamma augmentation preferentially in regions medial to the inferior-temporal gyrus, whereas auditory naming elicited high-gamma augmentation more laterally. The left lateral prefrontal regions including Broca's area initially exhibited high-gamma suppression subsequently followed by high-gamma augmentation at several hundred milliseconds before response onset during both naming tasks. Early high-gamma suppression within Broca's area was more intense during picture compared to auditory naming. Subsequent lateral-prefrontal high-gamma augmentation was more intense during auditory compared to picture naming. SIGNIFICANCE: This study revealed contrasting characteristics in the spatiotemporal dynamics of naming-related neural modulations between tasks. The dynamic atlases of visual and auditory language might be useful for planning of epilepsy surgery. Differential neural activation well explains some of the previously reported observations of domain-specific language impairments following resective epilepsy surgery. Video materials might be beneficial for the education of lay people about how the brain functions differentially during visual and auditory naming.
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Encéfalo/fisiopatologia , Epilepsias Parciais/fisiopatologia , Epilepsia/fisiopatologia , Idioma , Adolescente , Adulto , Mapeamento Encefálico/métodos , Criança , Pré-Escolar , Eletrocorticografia/métodos , Eletrodos Implantados , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Adulto JovemRESUMO
PURPOSE: To evaluate microsurgical trans-sylvian trans-ventricular anatomical hemispherectomy with regard to seizure outcome, risk of hydrocephalus, blood loss, and risk of chronic hemosiderosis in patients with intractable seizures selected for surgery using current preoperative assessment techniques. METHODS: Out of 86 patients who underwent hemispherectomy between February 2000 and April 2019, by a single surgeon, at a tertiary care referral center, 77 patients (ages 0.2-20 years; 40 females) who had an anatomical hemispherectomy were analyzed. Five of these were 'palliative' surgeries. One-stage anatomical hemispherectomy was performed in 55 children, two-stage anatomical hemispherectomy after extraoperative intracranial monitoring in 16, and six hemispherectomies were done following failed previous resection. Mean follow-up duration was 5.7 years (range 1-16.84 years). Forty-six patients had postoperative MRI scans. RESULTS: Ninety percent of children with non-palliative hemispherectomy achieved ILAE Class-1 outcome. Twenty-seven patients were no longer taking anticonvulsant medications. Surgical failures (n = 4) included one patient with previous meningoencephalitis, one with anti-GAD antibody encephalitis, one with idiopathic neonatal thalamic hemorrhage, and one with extensive tuberous sclerosis. There were no failures among patients with malformations of cortical development. Estimated average blood loss during surgery was 387 ml. Ten (21%) children developed hydrocephalus and required a shunt following one-stage hemispherectomy, whereas 10 (50%) patients developed hydrocephalus among those who had extraoperative intracranial monitoring. Only 20% of the shunts malfunctioned in the first year. Early malfunctions were related to the valve and later to fracture disconnection of the shunt. One patent had a traumatic subdural hematoma. None of the patients developed clinical signs of chronic 'superficial cerebral hemosiderosis' nor was there evidence of radiologically persistent chronic hemosiderosis in patients who had postoperative MRI imaging. CONCLUSION: Surgical results of anatomical hemispherectomy are excellent in carefully selected cases. Post-operative complications of hydrocephalus and intraoperative blood loss are comparable to those reported for hemispheric disconnective surgery (hemispherotomy). The rate of shunt malfunction was less than that reported for patients with hydrocephalus of other etiologies Absence of chronic 'superficial hemosiderosis', even on long-term follow-up, suggests that anatomical hemispherectomy should be revisited as a viable option in patients with intractable seizures and altered anatomy such as in malformations of cortical development, a group that has a reported high rate of seizure recurrence related to incomplete disconnection following hemispheric disconnective surgery.
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Epilepsia Resistente a Medicamentos/cirurgia , Hemisferectomia/efeitos adversos , Hemisferectomia/métodos , Complicações Pós-Operatórias/etiologia , Adolescente , Perda Sanguínea Cirúrgica , Criança , Pré-Escolar , Feminino , Hemossiderose/epidemiologia , Hemossiderose/etiologia , Humanos , Hidrocefalia/epidemiologia , Hidrocefalia/etiologia , Lactente , Masculino , Complicações Pós-Operatórias/epidemiologia , Adulto JovemRESUMO
Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in various organs and arises due to mutations in the TSC1 or TSC2 genes. TSC mutations lead to a range of neurological manifestations including epilepsy, cognitive impairment, autism spectrum disorders (ASD), and brain lesions that include cortical tubers. There is evidence that seizures arise at or near cortical tubers, but it is unknown why some tubers are epileptogenic while others are not. We have previously reported increased tryptophan metabolism measured with α[11C]-methyl-l-tryptophan (AMT) positron emission tomography (PET) in epileptogenic tubers in approximately two-thirds of patients with tuberous sclerosis and intractable epilepsy. However, the underlying mechanisms leading to seizure onset in TSC remain poorly characterized. MicroRNAs are enriched in the brain and play important roles in neurodevelopment and brain function. Recent reports have shown aberrant microRNA expression in epilepsy and TSC. In this study, we performed microRNA expression profiling in brain specimens obtained from TSC patients undergoing epilepsy surgery for intractable epilepsy. Typically, in these resections several non-seizure onset tubers are resected together with the seizure-onset tubers because of their proximity. We directly compared seizure onset tubers, with and without increased tryptophan metabolism measured with PET, and non-onset tubers to assess the role of microRNAs in epileptogenesis associated with these lesions. Whether a particular tuber was epileptogenic or non-epileptogenic was determined with intracranial electrocorticography, and tryptophan metabolism was measured with AMT PET. We identified a set of five microRNAs (miR-142-3p, 142-5p, 223-3p, 200b-3p and 32-5p) that collectively distinguish among the three primary groups of tubers: non-onset/AMT-cold (NC), onset/AMT-cold (OC), and onset/AMT-hot (OH). These microRNAs were significantly upregulated in OH tubers compared to the other two groups, and microRNA expression was most significantly associated with AMT-PET uptake. The microRNAs target a group of genes enriched for synaptic signaling and epilepsy risk, including SLC12A5, SYT1, GRIN2A, GRIN2B, KCNB1, SCN2A, TSC1, and MEF2C. We confirmed the interaction between miR-32-5p and SLC12A5 using a luciferase reporter assay. Our findings provide a new avenue for subsequent mechanistic studies of tuber epileptogenesis in TSC.
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MicroRNAs/metabolismo , Tomografia por Emissão de Pósitrons , Convulsões/metabolismo , Triptofano/metabolismo , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/metabolismo , Criança , Pré-Escolar , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , Convulsões/complicações , Convulsões/diagnóstico por imagem , Convulsões/genética , Simportadores/metabolismo , Triptofano/análogos & derivados , Triptofano/análise , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genéticaRESUMO
To evaluate metabolic changes in the ipsi- and contralateral hemisphere in children showing a cognitive profile consistent with early reorganization of cognitive function, we evaluated the regional glucose uptake, interhemispheric metabolic connectivity, and cognitive function in children with unilateral SWS. Interictal 2-deoxy-2[18 F]fluoro-D-glucose (FDG)-PET scans of 27 children with unilateral SWS and mild epilepsy and 27 age-matched control (non-SWS children with epilepsy and normal FDG-PET) were compared using statistical parametric mapping (SPM). Regional FDG-PET abnormalities calculated as SPM(t) scores in the SWS group were correlated with cognitive function (IQ) in left- and right-hemispheric subgroups. Interhemispheric metabolic connectivity between homotopic cortical regions was also calculated. Verbal IQ was substantially (≥10 points difference) higher than non-verbal IQ in 61% of the right- and 71% of the left-hemispheric SWS group. FDG SPM(t) scores in the affected hemisphere showed strong positive correlations with IQ in the left-hemispheric, but not in right-hemispheric SWS group in several frontal, parietal, and temporal cortical regions. Significant positive interhemispheric metabolic connectivity, present in controls, was diminished in the SWS group. In addition, the left-hemispheric SWS group showed inverse metabolic interhemispheric correlations in specific parietal, temporal, and occipital regions. FDG SPM(t) scores in the same regions of the right (unaffected) hemisphere showed inverse correlations with IQ. These findings suggest that left-hemispheric lesions in SWS often result in early reorganization of verbal functions while interfering with ("crowding") their non-verbal cognitive abilities. These cognitive changes are associated with specific metabolic abnormalities in the contralateral hemisphere not directly affected by SWS.
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Encéfalo/metabolismo , Cognição/fisiologia , Síndrome de Sturge-Weber/metabolismo , Síndrome de Sturge-Weber/psicologia , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fluordesoxiglucose F18 , Lateralidade Funcional , Glucose , Humanos , Inteligência/fisiologia , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Síndrome de Sturge-Weber/diagnóstico por imagem , Síndrome de Sturge-Weber/tratamento farmacológicoRESUMO
OBJECTIVE: We hypothesized that the modulation index (MI), a summary measure of the strength of phase-amplitude coupling between high-frequency activity (>150 Hz) and the phase of slow waves (3-4 Hz), would serve as a useful interictal biomarker for epilepsy presurgical evaluation. METHODS: We investigated 123 patients who underwent focal cortical resection following extraoperative electrocorticography recording and had at least 1 year of postoperative follow-up. We examined whether consideration of MI would improve the prediction of postoperative seizure outcome. MI was measured at each intracranial electrode site during interictal slow-wave sleep. We compared the accuracy of prediction of patients achieving International League Against Epilepsy class 1 outcome between the full multivariate logistic regression model incorporating MI in addition to conventional clinical, seizure onset zone (SOZ), and neuroimaging variables, and the reduced logistic regression model incorporating all variables other than MI. RESULTS: Ninety patients had class 1 outcome at the time of most recent follow-up (mean follow-up = 5.7 years). The full model had a noteworthy outcome predictive ability, as reflected by regression model fit R2 of 0.409 and area under the curve (AUC) of receiver operating characteristic plot of 0.838. Incomplete resection of SOZ (P < 0.001), larger number of antiepileptic drugs at the time of surgery (P = 0.007), and larger MI in nonresected tissues relative to that in resected tissue (P = 0.020) were independently associated with a reduced probability of class 1 outcome. The reduced model had a lower predictive ability as reflected by R2 of 0.266 and AUC of 0.767. Anatomical variability in MI existed among nonepileptic electrode sites, defined as those unaffected by magnetic resonance imaging lesion, SOZ, or interictal spike discharges. With MI adjusted for anatomical variability, the full model yielded the outcome predictive ability of R2 of 0.422, AUC of 0.844, and sensitivity/specificity of 0.86/0.76. SIGNIFICANCE: MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome.
Assuntos
Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Curva ROC , Estudos Retrospectivos , Sono/fisiologia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Most children with Sturge-Weber syndrome (SWS) develop seizures that may contribute to neurocognitive status. In this study, we tested the hypothesis that very early seizure onset has a particularly detrimental effect on the cognitive and/or motor outcomes of children with unilateral SWS. We also tested whether side of SWS brain involvement modulates the effect of seizure variables on the pattern of cognitive abnormalities. METHODS: Thirty-four children (22 girls; mean age 6.1years) with unilateral SWS and history of epilepsy in a longitudinal cohort underwent neurological and cognitive evaluations. Global intelligent quotient (GIQ), verbal intelligent quotient (VIQ), nonverbal intelligent quotient (IQ), and motor function were correlated with epilepsy variables, side and extent of brain involvement on magnetic resonance imaging (MRI). RESULTS: Mean age at seizure onset was 1.3years (0.1-6years) and mean IQ at follow-up was 86 (45-118). Age at seizure onset showed a logarithmic association with IQ, with maximum impact of seizures starting before age 1year, both in uni- and multivariate regression analyses. In the left SWS group (N=20), age at seizure onset was a strong predictor of nonverbal IQ (p=0.001); while early seizure onset in the right-hemispheric group had a more global effect on cognitive functions (p=0.02). High seizure frequency and long epilepsy duration also contributed to poor outcome IQ independently in multivariate correlations. Children with motor involvement started to have seizures at/before 7months of age, while frontal lobe involvement was the strongest predictor of motor deficit in a multivariate analysis (p=0.017). CONCLUSION: These findings suggest that seizure onset prior to age 1year has a profound effect on severity of cognitive and motor dysfunction in children with SWS; however, the effect of seizures on the type of cognitive deficit is influenced by laterality of brain involvement.
Assuntos
Idade de Início , Encéfalo/diagnóstico por imagem , Cognição , Inteligência , Imageamento por Ressonância Magnética/métodos , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/psicologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Epilepsia/etiologia , Epilepsia/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Lateralidade Funcional , Humanos , Lactente , Testes de Inteligência , Estudos Longitudinais , Masculino , Análise Multivariada , Estudos Prospectivos , Convulsões/complicações , Convulsões/etiologia , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/fisiopatologiaRESUMO
INTRODUCTION: Rett syndrome is a neurodevelopmental genetic disorder, characterized by developmental delay, hand stereotypies, abnormal gait, and acquired microcephaly. Epilepsy is very common in Rett syndrome and can be medically intractable. It remains uncertain if a patient with epileptic drop attacks associated with this genetic disease can benefit from corpus callosotomy. CASE REPORT: We report an 8-year-old girl with Rett syndrome and medically intractable epileptic drop attacks who underwent endoscopic total corpus callosotomy without any complications that led to the successful elimination of her seizures. CONCLUSION: Total corpus callosotomy is a feasible treatment option for medically intractable epileptic drop attacks in Rett syndrome and should not be considered as a contraindication in this condition. This is the first reported case of corpus callosotomy in Rett syndrome.
Assuntos
Descorticação Cerebral/métodos , Corpo Caloso/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Síndrome de Rett/cirurgia , Criança , Epilepsia Resistente a Medicamentos/etiologia , Feminino , Humanos , Neuroendoscopia/métodos , Síndrome de Rett/complicaçõesRESUMO
BACKGROUND: Postcontrast magnetic resonance imaging (MRI), obtained under anesthesia, is often used to evaluate brain parenchymal and vascular abnormalities in young children, including those with Sturge-Weber syndrome. However, anesthesia and contrast administration may carry risks. We explored the feasibility and potential diagnostic value of a noncontrast, nonsedate MRI acquisition in Sturge-Weber syndrome children and their siblings with a wide range of cognitive and behavioral functioning. METHODS: Twenty children (10 with Sturge-Weber syndrome and 10 healthy siblings; age: 0.7-13.5 years) underwent nonsedate 3-tesla (T) brain MRI acquisition with noncontrast sequences (including susceptibility-weighted imaging) prospectively along with neuropsychology assessment. All images were evaluated for quality, and MRI abnormalities identified in the Sturge-Weber syndrome group were compared to those identified on previous clinical pre- and postcontrast MRI. RESULTS: Nineteen participants (95%) completed the MRI with good (n = 18) or adequate (n = 1) quality, including all children with Sturge-Weber syndrome and all 5 children ≤5 years of age. The Sturge-Weber syndrome group had lower cognitive functions than the controls, and both groups had several children with behavioral issues, without an apparent effect on the success and quality of the MR images. Susceptibility-weighted imaging detected key venous vascular abnormalities and calcifications and, along with the other noncontrast sequences, provided diagnostic information comparable to previous clinical MRI performed with contrast administration under anesthesia. CONCLUSION: This study demonstrates the feasibility and the potential diagnostic value of a nonsedate, noncontrast MRI acquisition protocol in young children including those with cognitive impairment and/or behavioral concerns. This approach can facilitate clinical trials in children where safe serial MRI is warranted.
RESUMO
Background: Enlarged deep medullary veins (EDMVs) in patients with Sturge-Weber syndrome (SWS) may channel venous blood from the surface to the deep vein system in brain regions affected by the leptomeningeal venous malformation. Thus, the quantification of EDMV volume may provide an objective imaging marker for this vascular compensatory process. The present study proposes a novel analytical method to quantify enlarged EDMV volumes in the affected hemisphere of patients with unilateral SWS. Methods: Twenty young subjects, including 10 patients with unilateral SWS and 10 healthy siblings (age 14.5±6.7 and 16.0±7.0 years, respectively) underwent 3T brain MRI scanning using susceptibility-weighted imaging (SWI) and volumetric T1-weighted sequences. The proposed image analytic steps segmented EDMVs in white matter regions, defined on the volumetric T1-weighted images, by statistically associating the likelihood of intensity, location, and tubular shape on SWI. The volumes of the segmented EDMVs, calculated in each hemisphere, were compared between affected and unaffected hemispheres. EDMV volumes were also correlated with visually assessed EDMV scores, hemispheric white matter volumes, and cortical surface areas. Parametric tests including Pearson's correlation, unpaired and paired t-tests, were used. A P value <0.05 was considered statistically significant. Results: It was found that EDMVs were identified well in SWS-affected hemispheres while calcified regions were excluded. Mean EDMV volumes in the SWS-affected hemispheres were 10-12-fold greater than in the unaffected or healthy control hemispheres; while white matter volumes and cortical surface areas were lower. EDMV volumes in the SWS-affected hemispheres showed a strong positive correlation with the visual EDMV scores (r=0.88, P=0.001) and an inverse correlation with cortical surface area ratios (r=-0.65, P=0.04) but no correlation with white matter volume ratios. Conclusions: EDMVs were detected in the SWS-affected atrophic hemispheres reliably while avoiding calcified regions. The approach can be used to quantify enlarged deep cerebral veins in the human brain, which may provide a potential marker of cerebral venous remodeling.
RESUMO
OBJECTIVE: In tasks involving new visuospatial information, we rely on working memory, supported by a distributed brain network. We investigated the dynamic interplay between brain regions, including cortical and white matter structures, to understand how neural interactions change with different memory loads and trials, and their subsequent impact on working memory performance. METHODS: Patients undertook a task of immediate spatial recall during intracranial EEG monitoring. We charted the dynamics of cortical high-gamma activity and associated functional connectivity modulations in white matter tracts. RESULTS: Elevated memory loads were linked to enhanced functional connectivity via occipital longitudinal tracts, yet decreased through arcuate, uncinate, and superior-longitudinal fasciculi. As task familiarity grew, there was increased high-gamma activity in the posterior inferior-frontal gyrus (pIFG) and diminished functional connectivity across a network encompassing frontal, parietal, and temporal lobes. Early pIFG high-gamma activity was predictive of successful recall. Including this metric in a logistic regression model yielded an accuracy of 0.76. CONCLUSIONS: Optimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways. SIGNIFICANCE: This study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts.