Deep Venous Remodeling in Unilateral Sturge-Weber Syndrome: Robust Hemispheric Differences and Clinical Correlates.

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 correlates of EDMVs in SWS.

Methods: Fifty children (median age: 4.

Epilepsy Due to Mild TBI in Children: An Experience at a Tertiary Referral Center.

Rationale: Posttraumatic epilepsy (PTE) is a common cause of morbidity in children after a traumatic brain injury (TBI), occurring in 10-20% of children following severe TBI. PTE is diagnosed after two or more unprovoked seizures occurring 1-week post TBI. More often, studies have focused on children with epilepsy due to severe TBI.

Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations.

Background: Sturge-Weber syndrome (SWS) is a sporadic, neurocutaneous syndrome involving the skin, brain, and eyes. Because of the variability of the clinical manifestations and the lack of prospective studies, consensus recommendations for management and treatment of SWS have not been published.

Objective: This article consolidates the current literature with expert opinion to make recommendations to guide the neuroimaging evaluation and the management of the neurological and ophthalmologic features of SWS.

Hypermetabolism on Pediatric PET Scans of Brain Glucose Metabolism: What Does It Signify?

When one is interpreting clinical F-FDG PET scans of the brain (excluding tumors) in children, the typical abnormality seen is hypometabolism of various brain regions. Focal areas of hypermetabolism are noted occasionally, and the usual interpretation is that the hypermetabolic region represents a seizure focus. In this review, I discuss and illustrate the multiple causes of hypermetabolism on F-FDG PET studies that should not be interpreted as seizure activity, as such an interpretation could potentially be incorrect.

Evolution of Surgical Management for Intractable Epileptic Spasms.

The understanding and management of epileptic spasms has considerably evolved since the mid 19th century. The realization that epileptic spasms can be generated from a focal brain lesion played a pivotal role in the development of neurosurgical management for intractable forms of this epilepsy. During pre-surgical planning, the addition of functional FDG PET imaging has further refined the electroencephalographic localization of epileptogenic lesions.

Neuroinflammation in Children With Infantile Spasms: A Prospective Study Before and After Treatment With Acthar Gel (Repository Corticotropin Injection).

The selective effectiveness of adrenocorticotropic hormone (ACTH) in treating infantile spasms suggests an underlying neuroinflammation. Because neuroinflammation is mediated by activated microglia, which express translocator protein (TSPO), we imaged neuroinflammation in children with infantile spasms using positron emission tomography (PET) with C-PK11195 (PK), which selectively binds to TSPO. Children were studied prospectively before and following treatment with Acthar Gel (repository corticotropin injection).

Automated production of 1-(2-[F]fluoroethyl)-l-tryptophan for imaging of tryptophan metabolism.

Automated production of an fluorine-18 labeled tryptophan analogue, 1-(2-[F]fluoroethyl)-l-tryptophan (1-L-[F]FETrp) in a current Good Manufacturing Practice facility was achieved. 1-L-[F]FETrp was produced by a one-pot, two-step strategy with an overall synthesis time of approximately 100 min, a radiochemical yield of 20 ± 5% (decay corrected), radiochemical purity and enantiomeric excess over 90%, and a molar activity of 103 ± 15 GBq/μmol at the end of synthesis (EOS). The dose mass of 1-L-FETrp in four consecutive batches was less than 5 μg.

TLR7 activation in epilepsy of tuberous sclerosis complex.

Background: Neuroinflammation and toll-like receptors (TLR) of the innate immune system have been implicated in epilepsy. We previously reported high levels of microRNAs miR-142-3p and miR-223-3p in epileptogenic brain tissue resected for the treatment of intractable epilepsy in children with tuberous sclerosis complex (TSC). As miR-142-3p has recently been reported to be a ligand and activator of TLR7, a detector of exogenous and endogenous single-stranded RNA, we evaluated TLR7 expression and downstream IL23A activation in surgically resected TSC brain tissue.

Positron Emission Tomography in Pediatric Neurodegenerative Disorders.

Application of molecular neuroimaging using positron emission tomographic techniques to assess pediatric neurodegenerative disorders has been limited, unlike in adults where positron emission tomography has contributed to clinical diagnosis, monitoring of neurodegenerative disease progression, and assessment of novel therapeutic approaches. Yet, there is a huge unexplored potential of molecular imaging to improve our understanding of the pathophysiology of neurodegenerative disorders in children and provide radiological biomarkers that can be applied clinically. The obstacles in performing PET scans on children include sedation, radiation exposure, and access but, as will be illustrated, these barriers can be easily overcome.

Neurological Complications of Sturge-Weber Syndrome: Current Status and Unmet Needs.

Objective: We aimed to identify the current status and major unmet needs in the management of neurological complications in Sturge-Weber syndrome.

Methods: An expert panel consisting of neurologists convened during the Sturge-Weber Foundation Clinical Care Network conference in September 2018. Literature regarding current treatment strategies for neurological complications was reviewed.

Anatomical hemispherectomy revisited-outcome, blood loss, hydrocephalus, and absence of chronic hemosiderosis.

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.

Automated production of a N-methyl-D-aspartate receptor radioligand [F]GE179 for clinical use.

N-Methyl-d-aspartate (NMDA) receptors are ligand and voltage-gated heteromeric ion channel receptors. Excessive activation of NMDA receptors is implicated in many neurological and psychiatric disorders, including ischemic stroke, neuropathic pain, epilepsy, drug addition, Alzheimer's disease, and schizophrenia. [F]GE179 is a promising PET probe for imaging functional NMDA receptor alterations (activated or 'open' channel) with a high binding affinity (K = 2.

Linking spherical mean diffusion weighted signal with intra-axonal volume fraction.

Diffusion MRI has been widely used to assess brain tissue microstructure. However, the conventional diffusion tensor imaging (DTI) is inadequate for characterizing fiber direction or fiber density in voxels with crossing fibers in brain white matter. The constrained spherical deconvolution (CSD) technique has been proposed to measure the complex fiber orientation distribution (FOD) using a single high b-value (b ≥ 3000 s/mm) to derive the intra-axonal volume fraction (V) from the calculated FOD.

Evolution of Brain Glucose Metabolic Abnormalities in Children With Epilepsy and SCN1A Gene Variants.

Three children with drug-refractory epilepsy, normal magnetic resonance image (MRI), and a heterozygous SCN1A variant underwent 2-deoxy-2-[F]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.

Minimal number of gradient directions for robust measurement of spherical mean diffusion weighted signal.

Purpose: Determination of the minimum number of gradient directions (N) for robust measurement of spherical mean diffusion weighted signal (S¯).

Methods: Computer simulations were employed to characterize the relative standard deviation (RSD) of the measured spherical mean signal as a function of the number of gradient directions (N). The effects of diffusion weighting b-value and signal-to-noise ratio (SNR) were investigated.

Objective PET study of glucose metabolism asymmetries in children with epilepsy: Implications for normal brain development.

Clinical interpretation of cerebral positron emission tomography with 2-deoxy-2[F-18]fluoro-d-glucose (FDG-PET) images often relies on evaluation of regional asymmetries. This study was designed to establish age-related variations in regional cortical glucose metabolism asymmetries in the developing human brain. FDG-PET scans of 58 children (age: 1-18 years) were selected from a large single-center pediatric PET database.

Imaging Brain Metabolism in the Newborn.

In this review, we discuss molecular brain imaging studies using positron emission tomography (PET) with 2-deoxy-2(F)fluoro-d-glucose (FDG) in human newborns and infants, and illustrate how this technology can be applied to probe the neuropathophysiology of neonatal neurologic disorders. PET studies have been difficult to perform in sick babies because of patient transportation issues and suboptimal spatial resolution. With approval from the FDA and the institutional review board, we modified and installed the Focus 220 animal microPET scanner (Concorde Microsystems, Knoxville, TN) directly in our neonatal intensive care unit in Children's Hospital of Michigan and verified the high spatial resolution (<2 mm full-width-at-half-maximum) of this microPET.

A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome.

Background: Sturge-Weber syndrome is a neurocutaneous disorder associated with port-wine birthmark, leptomeningeal capillary malformations, and glaucoma. It is associated with an unpredictable clinical course. Because of its rarity and complexity, many physicians are unaware of the disease and its complications.

Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug-resistant epilepsy.

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.

Cognitive and motor outcomes in children with unilateral Sturge-Weber syndrome: Effect of age at seizure onset and side of brain involvement.

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.

Metabolic correlates of cognitive function in children with unilateral Sturge-Weber syndrome: Evidence for regional functional reorganization and crowding.

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[ 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.

A distinct microRNA expression profile is associated with α[C]-methyl-L-tryptophan (AMT) PET uptake in epileptogenic cortical tubers resected from patients with tuberous sclerosis complex.

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.

GNAQ Mutation in the Venous Vascular Malformation and Underlying Brain Tissue in Sturge-Weber Syndrome.

The recent identification of the somatic mutation (c.548G > A) provides insight into the pathogenesis of Sturge–Weber syndrome (SWS). Although the primary SWS brain pathology is the leptomeningeal angiomatosis (LMA), cerebral cortical and white matter abnormalities play a prominent role in the disease manifestations.

Corpus Callosotomy for Intractable Epilepsy Revisited: The Children's Hospital of Michigan Series.

Corpus callosotomy is a palliative procedure performed to reduce the severity of drug-resistant epilepsy. The authors assessed its efficacy on different seizure types in 20 subjects (age range 5-19 years); 8 with active vagus nerve stimulator. Fifteen had complete callosotomy, 3 had anterior 2/3, and 2 had anterior 2/3 followed later by complete callosotomy.