Background: Most patients with Sturge-Weber syndrome (SWS) have unilateral brain involvement associated with a wide range of neurocognitive outcomes. Aims: To evaluate cognitive deficit patterns in young patients with unilateral SWS and identify clinical and imaging variables associated with the various cognitive deficit patterns. Methods: Forty-six young patients with SWS were stratified by the side of brain involvement and assigned to four cognitive groups, based on formal neuropsychology evaluation: 1-no deficit, 2-traditional deficit (verbal deficit in left, non-verbal in right SWS), 3-reorganized with crowding (e.g., only non-verbal deficit in left-hemispheric cases), and 4-global (verbal and non-verbal) deficit. Age, seizure variables, motor functions, and the extent of brain magnetic resonance imaging abnormalities were compared among the cognitive groups. Results: The reorganized/crowding pattern was seen only in patients with left SWS (6/20, 30%), most of whom were young with extensive abnormalities. Traditional cognitive deficit was seen mostly in right SWS (7/26, 27%). Global deficit was equally common (35%) in left- and right SWS and was associated with extensive hemispheric abnormalities, early seizure onset, and severe motor deficits. In multivariate analysis, extensive calcifications and severe motor deficits were independently associated with global cognitive deficit. Conclusions: Early, extensive left hemispheric abnormalities can be associated with preserved verbal but impaired non-verbal functions consistent with right-hemispheric reorganization and crowding. However, more than onethird of both left and right-hemispheric patients may develop a global cognitive impairment. This severe cognitive outcome is associated with extensive hemispheric calcification and severe motor deficit.

RATIONALE AND OBJECTIVES:Sturge-Weber syndrome (SWS) is a sporadic neurocutaneous disorder marked by cerebral venous abnormalities, progressive parenchymal damage, and early-onset neuro-cognitive complications. Existing imaging assessments lack standardized, quantitative approaches to capture the full disease burden. Here we tested an magnetic resonance imaging (MRI)-based scoring system that comprehensively captures both vascular and parenchymal brain abnormalities in SWS. MATERIALS AND METHODS:Twenty-five young patients (mean age, 9.5 years; range, 1-24 years) with unilateral SWS brain involvement underwent 3 T MRI using a standardized protocol (with pre- and post-contrast sequences) and formal neuro-cognitive evaluation. Six imaging features, four vascular and two parenchymal, were scored by two investigators across lobes using a 3-point scale. Interrater reliability was assessed using intra-class correlation coefficients (ICC), and associations with neuro-cognitive variables were tested using Spearman's rank correlations. RESULTS:Both the total MRI score and each MRI subscore demonstrated excellent interrater reliability (ICC range: 0.91-0.99). Motor functions showed strong inverse correlations with the total MRI scores (ρ = -0.82, p < 0.0001). Low verbal IQ correlated with extensive calcifications (ρ = -0.55, p < 0.01). High seizure frequency correlated with greater pial enhancement (p < 0.05) and choroid plexus scores (p < 0.01). The new multiparametric score outperformed a previously established asymmetry-based MRI score in its associations with cognitive outcomes and seizure frequency. CONCLUSION:This reliable and user-friendly MRI scoring system, that integrates multiple vascular and parenchymal features relevant to SWS pathophysiology, can be highly suitable for longitudinal monitoring, prognostication, and standardized outcome assessment in multicenter research and therapeutic trials.

BACKGROUND:Common intracranial vascular abnormalities in Sturge-Weber syndrome (SWS) include leptomeningeal venous malformations (LVMs) and enlarged deep veins. A few small studies have reported absent deep veins in some patients. We used susceptibility-weighted imaging (SWI), a magnetic resonance imaging (MRI) sequence sensitive to detecting small veins, to evaluate deep cerebral veins and the basal vein of Rosenthal (BVR) and assess the radiological correlates and clinical impact of their absence. METHODS:Fifty young subjects, including 30 patients with unilateral SWS and 20 healthy controls, underwent 3T brain MRI prospectively. The presence or absence of the internal cerebral vein (ICV), its two main tributaries, and the BVR were evaluated on SWI in all 50 subjects and correlated with other brain abnormalities and clinical symptoms in the SWS group. RESULTS:Although deep veins and the BVR were identified bilaterally in all control subjects, absent veins were observed in 70% of patients with SWS: in the SWS-affected hemisphere, absent ICV in 15 (50%), thalamostriate vein in 11 (37%), septal vein in seven (23%), and BVR in nine (30%) patients. Absent contralateral veins were also observed. Absent veins were associated with enlarged and collateral veins. Absent BVR and ICV were associated with extensive LVM, brain atrophy, and worse motor functions (P < 0.05); absent BVR was also associated with stroke-like episodes. CONCLUSIONS:Absence of deep and/or basal cerebral veins is common in SWS and is associated with venous vascular anomalies, parenchymal damage, and motor impairment. Absent BVR may also increase the risk for stroke-like episodes.

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.

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.

Background: Enlarged deep medullary veins (EDMVs) in patients with Sturge-Weber syndrome (SWS) may provide compensatory venous drainage for brain regions affected by the leptomeningeal venous malformation (LVM). We evaluated the prevalence, extent, hemispheric differences, and clinical corre-lates of EDMVs in SWS. Methods: Fifty children (median age: 4.5 years) with unilateral SWS underwent brain magnetic reso-nance imaging prospectively including susceptibility-weighted imaging (SWI); children aged 2.5 years or older also had a formal neurocognitive evaluation. The extent of EDMVs was assessed on SWI by using an EDMV hemispheric score, which was compared between patients with right and left SWS and correlated with clinical variables.Results: EDMVs were present in 89% (24 of 27) of right and 78% (18 of 23) of left SWS brains. Extensive EDMVs (score >6) were more frequent in right (33%) than in left SWS (9%; P = 0.046) and commonly occurred in young children with right SWS. Patients with EDMV scores >4 had rare (less than monthly) seizures, whereas 35% (11 of 31) of patients with EDMV scores <= 4 had monthly or more frequent seizures (P = 0.003). In patients with right SWS and at least two LVM-affected lobes, higher EDMV scores were associated with higher intelligence quotient (P < 0.05).Conclusions: Enlarged deep medullary veins are common in unilateral SWS, but extensive EDMVs appear to develop more commonly and earlier in right hemispheric SWS. Deep venous remodeling may be a compensatory mechanism contributing to better clinical outcomes in some patients with SWS.(c) 2022 Elsevier Inc. All rights reserved.

This study investigated whether current state‐of‐the‐art deep reasoning network analysis on psychometry‐driven diffusion tractography connectome can accurately predict expressive and receptive language scores in a cohort of young children with persistent language concerns (n = 31, age: 4.25 ± 2.38 years). A dilated convolutional neural network combined with a relational network (dilated CNN + RN) was trained to reason the nonlinear relationship between “dilated CNN features of language network” and “clinically acquired language score”. Three‐fold cross‐validation was then used to compare the Pearson correlation and mean absolute error (MAE) between dilated CNN + RN‐predicted and actual language scores. The dilated CNN + RN outperformed other methods providing the most significant correlation between predicted and actual scores (i.e., Pearson's R/p‐value: 1.00/<.001 and .99/<.001 for expressive and receptive language scores, respectively) and yielding MAE: 0.28 and 0.28 for the same scores. The strength of the relationship suggests elevated probability in the prediction of both expressive and receptive language scores (i.e., 1.00 and 1.00, respectively). Specifically, sparse connectivity not only within the right precentral gyrus but also involving the right caudate had the strongest relationship between deficit in both the expressive and receptive language domains. Subsequent subgroup analyses inferred that the effectiveness of the dilated CNN + RN‐based prediction of language score(s) was independent of time interval (between MRI and language assessment) and age of MRI, suggesting that the dilated CNN + RN using psychometry‐driven diffusion tractography connectome may be useful for prediction of the presence of language disorder, and possibly provide a better understanding of the neurological mechanisms of language deficits in young children.

To characterize structural white matter substrates associated with language functions in children with language disorders (LD), a psychometry-driven diffusion tractography network was investigated with canonical correlation analysis (CCA), which can reliably predict expressive and receptive language scores from the nodal efficiency (NE) of the obtained network. The CCA found that the NE values of six regions: left inferior-frontal-opercular, left insular, left angular gyrus, left superior-temporal-gyrus, right hippocampus, and right cerebellar-lobule were highly correlated with language scores (rho(expressive)/rho(receptive) = 0.609/0.528), yielding significant differentiation of LD from controls using new imaging predictors u(expressive) (F = 15.024, p = .0003) and u(receptive) (F = 7.421, p = .009). This study demonstrates the utility of intrinsic language network analyses in distinguishing and potentially subtyping the type and severity of language deficit, especially in very young children (<= 3 years) with LD. The use of structural imaging to identify children with persisting language disorder could prove useful in understanding the etiology of language disorder.

Summary Objective We analyzed long‐term changes of lobar glucose metabolic abnormalities in relation to clinical seizure variables and development in a large group of children with medically refractory epilepsy. Methods Forty‐one children (25 males) with drug‐resistant epilepsy had a baseline positron emission tomography ( PET ) scan at a median age of 4.7 years; the scans were repeated after a median of 4.3 years. Children with progressive neurological disorders or space‐occupying lesion–related epilepsy and those who had undergone epilepsy surgery were excluded. The number of affected lobes on 2‐deoxy‐2( 18 F)‐fluoro‐D‐glucose– PET at baseline and follow‐up was correlated with epilepsy variables and developmental outcome. Results On the initial PET scan, 24 children had unilateral and 13 had bilateral glucose hypometabolism, whereas 4 children had normal scans. On the follow‐up scan, 63% of the children showed an interval expansion of the hypometabolic region, and this progression was associated with persistent seizures. In contrast, 27% showed less extensive glucose hypometabolism at follow‐up; most of these subjects manifested a major interval decrease in seizure frequency. Delayed development was observed in 21 children (51%) at baseline and 28 (68%) at follow‐up. The extent of glucose hypometabolism at baseline correlated with developmental levels at the time of both baseline ( r = .31, P = .05) and follow‐up scans ( r = .27, P = .09). Significance In this PET study of unoperated children with focal epilepsy, the lobar pattern of glucose hypometabolism changed over time in 90% of the cases. The results support the notion of an expansion of metabolic dysfunction in children with persistent frequent seizures and its association with developmental delay, and support that optimized medical treatment to control seizures may contribute to better neurocognitive outcome if no surgery can be offered.

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 6.1 years) 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 1.3 years (0.1-6 years) 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 1 year, 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 7 months 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 1 year 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. (C) 2018 Elsevier Inc. All rights reserved.

Three children with drug-refractory epilepsy, normal magnetic resonance image (MRI), and a heterozygous SCN1A variant underwent 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) scanning between age 6 months and 1 year and then at age 3 years 6 months to 5 years 5 months. Regional FDG uptake values were compared to those measured in age- and gender-matched pseudo-controls. At baseline, the brain glucose metabolic pattern in the SCN1A group was similar to that of the pseudo-controls. At follow-up, robust decreases of normalized FDG uptake was found in bilateral frontal, parietal and temporal cortex, with milder decreases in occipital cortex. Children with epilepsy and an SCN1A variant have a normal pattern of cerebral glucose metabolism at around 1 year of age but develop bilateral cortical glucose hypometabolism by age 4 years, with maximal decreases in frontal, parietal, and temporal cortex. This metabolic pattern may be characteristic of epilepsy associated with SCN1A variants and may serve as a biomarker to monitor disease progression and response to treatments.

We present longitudinal imaging data of a child with Sturge–Weber syndrome ( SWS ). At age 8 months, 3 weeks after initial seizures and prolonged motor deficit, MRI showed extensive right hemispheric SWS involvement with severe glucose hypometabolism on PET . She was treated with levetiracetam and aspirin. Follow‐up imaging at age 29 months showed a robust interval expansion of enlarged deep medullary veins throughout the affected hemisphere along with a dramatic recovery of hemispheric metabolism and normalized neurocognitive functioning. These findings demonstrate a robust, multilobar hemispheric remodeling of deep venous collaterals that likely contributed to reversal of initial metabolic and neurocognitive deficits.

AIM:To evaluate clinical and metabolic correlates of cerebral calcifications in children with Sturge-Weber syndrome (SWS). METHOD:Fifteen children (11 females, four males; age range 7mo-9y, mean 4y 1mo) with unilateral SWS underwent baseline and follow-up magnetic resonance imaging (MRI) with susceptibility weighted imaging (SWI), glucose metabolism positron emission tomography (PET), and neurocognitive assessment (mean follow-up 1y 8mo). Calcified brain volumes measured on SWI were correlated with areas of abnormal glucose metabolism, seizure variables, and cognitive function (IQ). RESULTS:Ten children had brain calcification at baseline and 11 at follow-up. Mean calcified brain volume increased from 1.69 to 2.47cm3 (p=0.003) in these children; the rate of interval calcified volume increase was associated with early onset of epilepsy (Spearman's rho [rs ]=-0.63, p=0.036). Calcified brain regions showed a variable degree of glucose hypometabolism with the metabolic abnormalities often extending to non-calcified cerebral lobes. Larger calcified brain volumes at baseline were associated with longer duration of epilepsy (rs =0.69, p=0.004) and lower outcome IQ (rs =-0.53, p=0.042). INTERPRETATION:Brain calcifications are common and progress faster in children with SWS with early epilepsy onset, and are associated with a variable degree of hypometabolism, which is typically more extensive than the calcified area. Higher calcified brain volumes may indicate a risk for poorer neurocognitive outcome.