Deep Venous Remodeling in Unilateral Sturge-Weber Syndrome: Robust Hemispheric Differences and Clinical Correlates
Juhász, Csaba; Luat, Aimee F; Behen, Michael E; Gjolaj, Nore; Jeong, Jeong-Won; Chugani, Harry T; Kumar, Ajay
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: 4.5 years) with unilateral SWS underwent brain magnetic resonance 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.
NEUROLOGY, NEUROIMAGING, and OPHTHALMOLOGY CONSENSUS RECOMMENDATIONS for MANAGEMENT of STURGE-WEBER SYNDROME [Meeting Abstract]
Sabeti, S; Ball, K L; Bhattacharya, S K; Bitrian, E; Blieden, L S; Brandt, J D; Burkhart, C; Chugani, H T; Falchek, S J; Jain, B G; Juhasz, C; Loeb, J A; Luat, A; Pinto, A; Salvin, J; Kelly, K M
Background: Sturge-Weber syndrome (SWS) involves the skin, brain, and eyes. The dermatologic manifestation is the facial port wine birthmark (PWB), while there are several potential neurologic and ophthalmologic manifestations, notably epilepsy and glaucoma, respectively. This consensus aims to develop evidence-based expert-defined recommendations for management of the neurologic and ophthalmic features and provides a framework for dermatologists to determine workup for patients with PWB who seek laser treatment. Study Design/Materials and Method: Thirteen national experts in neurology, radiology, and ophthalmology were assembled as part of a larger consensus statement for the management of SWS. Key topics and questions regarding risk stratification, referral indications, and treatment were formulated. A systematic PubMed search was performed. Evidence-based recommendations were developed.
Result(s): High-risk PWB distributions involve the hemifacial, forehead, or median locations, including the upper eyelids, especially when concerned for glaucoma. Any child with a high-risk facial PWB should be referred to a pediatric neurologist and pediatric ophthalmologist for a baseline evaluation, with periodic follow-up. Routine screening for brain involvement is not recommended for newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms but can be performed in cases of extreme parental anxiety, an abnormal EEG, or when presymptomatic treatment is contemplated such as with extensive bilateral PWB. In children with stable neurocognitive symptoms, routine follow-up neuroimaging is not advised. In adults with a high-risk PWB and no prior imaging, neuroimaging should be obtained, but follow-up neuroimaging is not recommended in adults with established SWS and stable neurocognitive symptoms. The treatment of glaucoma varies depending on the patient's age and clinical presentation.
Conclusion(s): Recommendations were developed by experts in neurology, neuroradiology, and ophthalmology. These guidelines can guide evidence-based discussions between patients and providers and increase dermatologists' awareness regarding when and what workup is necessary in patients seeking laser treatment for PWB
PET imaging in epilepsy
Chapter by: Kumar, Ajay; Shandal, Varun; JuhÃ¡sz, Csaba; Chugani, Harry T.
in: Nuclear Medicine and Molecular Imaging: Volume 1-4 by
[S.l.] : Elsevier, 2022
Epilepsy Due to Mild TBI in Children: An Experience at a Tertiary Referral Center
Park, Jun T; DeLozier, Sarah J; Chugani, Harry T
RATIONALE/BACKGROUND: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. We aim to understand the utility of head computed tomography (HCT), EEG, and the risk of developing drug-resistant epilepsy in children after mild TBI. METHOD/METHODS:We retrospectively studied 321 children with TBI at a tertiary pediatric referral center during a 10-year period. Mild TBI was defined as loss of consciousness (LOC) or amnesia < 30 min, moderate TBI as LOC or amnesia between 30 min and 1 day, and severe TBI as LOC or amnesia > 1 day, subdural hemorrhage, or contusion. Multiple clinical variables were reviewed, including past and present antiepileptic drug(s), seizure control, and mode of injury. First and subsequent post-TBI EEGs/prolonged video-EEGs were obtained acutely, subacutely, and/or chronically (range, day 1-3 years, median 1 month). Descriptive analyses were conducted using medians and ranges for continuous data. Categorical data were reported using frequencies and percentages, while comparisons between groups were made using Fisher's exact test for small sample sizes. RESULTS:< 0.005. Six patients (75%) had MRIs, of which five (63%) were normal. Two patients (#1, 7) did not have MRIs, while one patient's (#4) MRI was unavailable. Five patients (63%) had a seizure <24 h post TBI, while the rest had seizures after the first week of injury. CONCLUSION/CONCLUSIONS:Children with epilepsy due to mild TBI, loss of consciousness, or amnesia < 30 min are more likely to have normal HCT and EEG and to be on 0-1 AED. Limitations of our study include the small sample size and retrospective design. The current findings add to the paucity of data in children who suffer from epilepsy due to mild TBI.
HYPERMETABOLISM ON PEDIATRIC POSITRON EMISSION TOMOGRAPHY SCANS OF BRAIN GLUCOSE METABOLISM: What does it signify?
Chugani, Harry T
When interpreting clinical 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography (FDG-PET) scans of the brain (excluding tumors), the typical abnormality 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, we discuss and illustrate the multiple causes of hypermetabolism that should not be interpreted as seizure activity could potentially lead to an incorrect interpretation of FDG-PET studies. Various causes or conditions where focal hypermetabolism can be encountered on FDG-PET studies include interictal hypermetabolism, Sturge-Weber syndrome, changes associated with brain plasticity following injury, Rett syndrome, hypoxic-ischemic brain injury, various inborn errors of metabolism, and autoimmune encephalitis. The radiologist or nuclear medicine physician interpreting clinical FDG-PET studies should be aware of these circumstances to provide accurate assessment of the study.
Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations
Sabeti, Sara; Ball, Karen L; Bhattacharya, Sanjoy K; Bitrian, Elena; Blieden, Lauren S; Brandt, James D; Burkhart, Craig; Chugani, Harry T; Falchek, Stephen J; Jain, Badal G; Juhasz, Csaba; Loeb, Jeffrey A; Luat, Aimee; Pinto, Anna; Segal, Eric; Salvin, Jonathan; Kelly, Kristen M
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. METHODS:Thirteen national peer-recognized experts in neurology, radiology, and ophthalmology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included (1) risk stratification, (2) indications for referral, and (3) optimum treatment strategies. An extensive PubMed search was performed of English language articles published in 2008 to 2018, as well as recent studies identified by the expert panel. The panel made clinical practice recommendations. CONCLUSIONS:Children with a high-risk facial port-wine birthmark (PWB) should be referred to a pediatric neurologist and a pediatric ophthalmologist for baseline evaluation and periodic follow-up. In newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms, routine screening for brain involvement is not recommended, but brain imaging can be performed in select cases. Routine follow-up neuroimaging is not recommended in children with SWS and stable neurocognitive symptoms. The treatment of ophthalmologic complications, such as glaucoma, differs based on the age and clinical presentation of the patient. These recommendations will help facilitate coordinated care for patients with SWS and may improve patient outcomes.
Evolution of Surgical Management for Intractable Epileptic Spasms
Rashid, Salman; Chugani, Harry T
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. In some cases, neurosurgical resection of a focus that is co-localized by the FDG PET scan and electroencephalography can lead to partial or complete reversal of developmental delay along with reduced seizure frequency or seizure freedom. In cases where near-complete hemispheric cortex is implicated in spasm generation, subtotal hemispherectomy has shown encouraging results. Moreover, palliative resection of the major perpetrating focus in carefully chosen patients with bilateral multifocal spasms has also led to favorable outcomes. However, in patients with tuberous sclerosis with high tuber burden, the localizing value of FDG PET imaging may be limited. In such cases, employment of AMT PET technology has become a valuable tool for localization of actively epileptogenic tubers. This article highlights the historic steps in the successful advancements of neurosurgical interventions for the treatment of intractable epileptic spasms.
Response to Letter by Yue and Yang [Letter]
Chugani, Harry T; Kumar, Ajay
The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder
Herscu, Paul; Handen, Benjamin L; Arnold, L Eugene; Snape, Michael F; Bregman, Joel D; Ginsberg, Lawrence; Hendren, Robert; Kolevzon, Alexander; Melmed, Raun; Mintz, Mark; Minshew, Nancy; Sikich, Linmarie; Attalla, Ashraf; King, Brian; Owley, Thomas; Childress, Ann; Chugani, Harry; Frazier, Jean; Cartwright, Charles; Murphy, Tanya
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17Â years). Following 14 treatment weeks (mean dose 11.8Â mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320.
Neuroinflammation in Children With Infantile Spasms: A Prospective Study Before and After Treatment With Acthar Gel (Repository Corticotropin Injection)
Chugani, Harry T; Kumar, Ajay
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 11C-PK11195 (PK), which selectively binds to TSPO. Children were studied prospectively before and following treatment with Acthar Gel (repository corticotropin injection). We hypothesized that PK-PET would show neuroinflammation (increased PET uptake) in cortical and/or subcortical structures before treatment, and that this inflammation will be abolished/reduced following Acthar Gel treatment. Eight children with infantile spasms (5 males; mean age 1.8Â±1.1, range 0.9-4.1 years) were recruited. After clinical and video electroencephalograph (EEG) evaluation and dynamic PK-PET scan, children underwent treatment with Acthar Gel over 4 weeks, followed by repeat clinical evaluation/video-EEG 2 weeks after initiation of treatment and repeat PK-PET 2 weeks after treatment completion. Visual and quantitative analysis of PK-PET scans were performed. We calculated regional binding potential (measure of receptor-ligand binding) using a reference tissue model. Focal areas of increased PK-binding were found in the pretreatment PK-PET in 5 children. Following treatment, these increases were either reduced or normalized and were associated with cessation (n=4) or significant reduction (n=1) of spasms and complete disappearance of hypsarrhythmia. One child showed increased binding potential in basal ganglia and thalamus, despite normalization of cortical binding potential; however, these increases were likely associated with death-related causes. This study suggests Acthar Gel-responsive neuroinflammatory changes in children with infantile spasms, supporting a potential role of neuroinflammation in the pathogenesis of infantile spasms.