High angular resolution diffusion tensor imaging may be more sensitive than conventional MRI or neurologic assessment to the upper motor neuron (UMN) pathology of ALS, but it lacks the specificity required of a diagnostic marker. Instead, it is potentially useful as a quantitative tool for monitoring the progression of UMN pathology.

ObjectiveThis systematic review and meta-analyses assessed seizure outcome following pediatric epilepsy surgery.MethodsMEDLINE, EMBASE, and Cochrane were searched for pediatric epilepsy surgery original research from 1990 to 2017. The outcome was seizure freedom at 12 months or longer follow-up. Using random-effects models, the effect sizes for controlled studies, uncontrolled studies on surgery locations (temporal lobe [TL], extratemporal lobe [ETL], or hemispheric surgery), pathologies, nonlesional epilepsy, and incomplete resection were estimated. Meta-regression assessed the relationship between age at surgery, age at seizure onset, and seizure outcome. Random-effects network meta-analysis was conducted for surgery locations.ResultsTwo hundred fifty-eight studies were included. Surgery achieved higher seizure freedom than medical therapy (odds ratio [OR] = 6.49 [95% confidence interval [CI]: 2.87–14.70], p < 0.001). Seizure freedom declined over time after surgery, from 64.8% (95% CI: 51.2%–76.4%; p = 0.034) at 1 year, to 60.3% (95% CI: 52.9%–67.4%; p = 0.007) at 5 years, and to 39.7% (95% CI: 28.4%–52.2%, p = 0.106) at 10 years. Seizure freedom was (1) highest for hemispheric surgery, followed by TL and ETL surgery, and (2) highest for tumor and lower for malformations of cortical development. Seizure freedom was lower for nonlesional than lesional epilepsy (OR = 0.54 [95% CI: 0.34, 0.88], p = 0.013) and incomplete than complete resection (OR = 0.13 [95% CI: 0.08, 0.21], p < 0.001). Age at surgery and age at seizure onset were associated with seizure freedom for mixed pathologies and surgery locations and TL surgery.ConclusionEpilepsy surgery was more effective than medical therapy to control seizures. Understanding seizure outcomes of different surgery locations, pathologies, nonlesional epilepsy, and incomplete resection will assist with presurgical counseling.

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Diffusion-weighted imaging studies performed within 6 days after initial hypoglycemia were sensitive in term but not preterm neonates. Diffusion restriction, with low apparent diffusion coefficient values, in the mesial occipital poles may indicate the prognosis for visual outcomes in acute settings after neonatal hypoglycemia.

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SUMMARYPurpose: To evaluate the magnetic resonance imaging (MRI) of pediatric patients with infantile spasms (IS) treated with vigabatrin (VGB) in order to investigate whether VGB affects the brain. Methods: One hundred seven pediatric patients diagnosed with IS and treated with (n = 95) ‡120 mg/kg/day VGB or without (n = 12) VGB were included. MRI and diffusion-weighted imaging (DWI) were retrospectively analyzed. Results: Of the patients who had MRI scans during, but not before, VGB treatment (n = 81), 25 (30.9%) exhibited abnormal MRI signal intensity and/or restricted DWI in the deep gray nuclei and brainstem. Follow-up scans (performed in 15 of the 25 patients) revealed that these changes were reversible upon withdrawal of the medication. Analysis of patients undergoing scans before, during, and after VGB treatment (n = 14) revealed that four patients had abnormal MRI signal during treatment with VBG, two of whom reversed with cessation of VGB, one reversed without cessation of VGB, and another had persistent abnormal signal while being weaned from the VGB. Patients who had not received VGB treatment (n = 12) displayed normal imaging. Younger infants (£12 months) and those with cryptogenic IS were more likely to develop abnormal signal changes on MRI during VGB treatment. Discussion: In pediatric patients, VGB induces reversible MRI signal changes and reversible diffusion restriction in the globi pallidi, thalami, brainstem, and dentate nuclei. The risk for this phenomenon was greater in younger infants and patients with cryptogenic IS.

Objective: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. Methods: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. Results: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). Interpretation: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753 N early one-third of children with epilepsy are refractory to medications. 1,2 Persistent seizures are associated with mortality, disability, psychosocial isolation, and diminished quality of life. 3-6 Vagus nerve stimulation (VNS) is an effective, safe, and well-tolerated intervention for a subset of patients with treatment-resistant epilepsy. 7-10 Although the goal of VNS is not complete resolution of seizures, many children will show a significant reduction in seizure frequency, as well as a reduction in hospitalizations and psychosocial comorbidities. 11,12 View this article online at wileyonlinelibrary.com.

Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5–21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.