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1.
Pediatr Neurol. 2018 Jul;84:11-20. doi: 10.1016/j.pediatrneurol.2018.04.005. Epub 2018 Apr 18.

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

Author information

1
Department of Neurology, Northwestern University, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
2
Department of Pediatrics and Neurology, Wayne State University, Children's Hospital of Michigan, Detroit, Michigan.
3
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
4
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
5
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
6
School of Communication Studies, Ohio University, Athens, Ohio.
7
Department of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin.
8
Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina.
9
Department of Neurology, Nemours DuPont Hospital for Children, Wilmington, Delaware.
10
The Sturge-Weber Foundation, Houston, Texas.
11
Department of Neurology, Harvard Medical School, Children's Hospital Boston, Boston, Massachusetts.
12
Department of Neurology and Rehabilitation, University of Illinois, Chicago, Illinois. Electronic address: jaloeb@uic.edu.

Abstract

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. A major focus moving ahead will be to turn knowledge gaps and unmet needs into new research directions.

METHODS:

On October 1-3, 2017, the Sturge-Weber Foundation assembled clinicians from the Clinical Care Network with patients from the Patient Engagement Network of the Sturge-Weber Foundation to identify our current state of knowledge, knowledge gaps, and unmet needs.

RESULTS:

One clear unmet need is a need for consensus guidelines on care and surveillance. It was strongly recommended that patients be followed by multidisciplinary clinical teams with life-long follow-up for children and adults to monitor disease progression in the skin, eye, and brain. Standardized neuroimaging modalities at specified time points are needed together with a stronger clinicopathologic understanding. Uniform tissue banking and clinical data acquisition strategies are needed with cross-center, longitudinal studies that will set the stage for new clinical trials. A better understanding of the pathogenic roles of cerebral calcifications and stroke-like symptoms is a clear unmet need with potentially devastating consequences.

CONCLUSIONS:

Biomarkers capable of predicting disease progression will be needed to advance new therapeutic strategies. Importantly, how to deal with the emotional and psychological effects of Sturge-Weber syndrome and its impact on quality of life is a clear unmet need.

KEYWORDS:

Consensus statement; Imaging; Sturge-Weber syndrome; Treatment

Publication type

Publication type

2.
Epilepsia. 2018 Jul;59(7):1307-1315. doi: 10.1111/epi.14404. Epub 2018 May 22.

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

Govil-Dalela T1,2, Kumar A1,2,3,4, Behen ME1,4, Chugani HT1,2,4,5,6, Juhász C1,2,4,7.

Author information

1
Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA.
2
Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.
3
Department of Radiology, Wayne State University School of Medicine, Detroit, MI, USA.
4
PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA.
5
Division of Pediatric Neurology, Nemours A. I. DuPont Hospital for Children, Wilmington, DE, USA.
6
Departments of Neurology and Pediatrics, Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, PA, USA.
7
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.

Abstract

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.

KEYWORDS:

development; follow-up; pediatric epilepsy; positron emission tomography; seizure frequency

PMID:
29786852
PMCID:
PMC6031462
[Available on 2019-07-01]
DOI:
10.1111/epi.14404
Icon for Wiley
3.
Ann Clin Transl Neurol. 2018 Mar 12;5(4):502-506. doi: 10.1002/acn3.546. eCollection 2018 Apr.

Deep cerebral vein expansion with metabolic and neurocognitive recovery in Sturge-Weber syndrome.

Author information

1
Departments of Pediatrics and Neurology Wayne State University School of Medicine Children's Hospital of Michigan Detroit Medical Center Detroit Michigan.
2
Texas Child Neurology Plano Texas.

Abstract

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.

4.
J Neurooncol. 2018 Sep;139(2):239-249. doi: 10.1007/s11060-018-2869-6. Epub 2018 Apr 17.

Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors.

Author information

1
Department of Neurosurgery, Wayne State University, Detroit, MI, USA.
2
Department of Oncology, Wayne State University, Detroit, MI, USA.
3
Department of Pathology, Wayne State University, Detroit, MI, USA.
4
Department of Neurology, Wayne State University, Detroit, MI, USA.
5
Department of Pediatrics, Wayne State University, Detroit, MI, USA.
6
PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA.
7
Karmanos Cancer Institute, Detroit, MI, USA.
8
Department of Neurosurgery, Wayne State University, Detroit, MI, USA. smittal@med.wayne.edu.
9
Department of Oncology, Wayne State University, Detroit, MI, USA. smittal@med.wayne.edu.
10
Department of Biomedical Engineering, Wayne State University, Detroit, MI, USA. smittal@med.wayne.edu.
11
Karmanos Cancer Institute, Detroit, MI, USA. smittal@med.wayne.edu.

Abstract

INTRODUCTION:

There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment.

METHODS:

We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites. In addition, we utilized commercially available small-molecules to pharmacologically modulate IDO1, IDO2, TDO2, and AhR in patient-derived glioma and meningioma cell lines (n = 9 each).

RESULTS:

We observed a positive trend between the grade of the tumor and the average immunohistochemical staining score for IDO1, IDO2, and TDO2, with TDO2 displaying the strongest immunostaining. AhR immunostaining was present in all grades of gliomas and meningiomas, with the greatest staining intensity noted in glioblastomas. Immunocytochemical staining showed a positive trend between nuclear localization of AhR and histologic grade in both gliomas and meningiomas, suggesting increased AhR activation with higher tumor grade. Unlike enzyme inhibition, AhR antagonism markedly diminished patient-derived tumor cell viability, regardless of tumor type or grade, following in vitro drug treatments.

CONCLUSIONS:

Collectively, these results suggest that AhR may offer a novel and robust therapeutic target for a patient population with highly limited treatment options.

KEYWORDS:

Aryl hydrocarbon receptor; Gliomas; Immunosuppressive kynurenine pathway; Meningiomas; Primary patient-derived tumor cells; Tryptophan metabolism

PMID:
29667084
PMCID:
PMC6092214
[Available on 2019-09-01]
DOI:
10.1007/s11060-018-2869-6
Icon for Springer
5.
Epilepsy Behav. 2018 Mar;80:202-207. doi: 10.1016/j.yebeh.2018.01.012. Epub 2018 Feb 3.

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

Author information

1
Departments of Pediatrics and Neurology, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit Medical Center, 3901 Beaubien St., Detroit, MI 48201, USA. Electronic address: aluat@dmc.org.
2
Departments of Pediatrics and Neurology, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit Medical Center, 3901 Beaubien St., Detroit, MI 48201, USA.
3
Departments of Pediatrics and Neurology, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit Medical Center, 3901 Beaubien St., Detroit, MI 48201, USA; Department of Neurology, School of Medicine, Thomas Jefferson University, Philadelphia, PA, USA; Division of Pediatric Neurology, Nemours A.I. DuPont Hospital for Children, 1600 Rockland Rd., Wilmington, Delaware, 19803, USA.

Abstract

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.

KEYWORDS:

Cognitive function; Epilepsy; Outcome; Seizure onset; Sturge–Weber syndrome

PMID:
29414553
PMCID:
PMC5845773
[Available on 2019-03-01]
DOI:
10.1016/j.yebeh.2018.01.012
Icon for Elsevier Science
6.
Hum Brain Mapp. 2018 Apr;39(4):1596-1606. doi: 10.1002/hbm.23937. Epub 2017 Dec 23.

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

Kim JA1,2, Jeong JW1,2,3, Behen ME1,2, Pilli VK1,2, Luat A2,3, Chugani HT1,2,3,4,5, Juhász C1,2,3.

Author information

1
PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan, USA.
2
The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USA.
3
Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
4
Department of Neurology, Nemours DuPont Hospital for Children, Wilmington, Delaware, USA.
5
Department of Neurology, School of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Abstract

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.

KEYWORDS:

PET; cognitive function; crowding; metabolic connectivity; reorganization; sturge-weber syndrome

PMID:
29274110
PMCID:
PMC5847469
[Available on 2019-04-01]
DOI:
10.1002/hbm.23937
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7.
Neuropediatrics. 2017 Oct;48(5):385-389. doi: 10.1055/s-0037-1603515. Epub 2017 Jun 1.

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

Author information

1
Department of Pediatrics, Wayne State University, Detroit, Michigan, United States.
2
Children's Hospital of Michigan, Detroit, Michigan, United States.
3
Department of Neurology, Wayne State University, Detroit, Michigan, United States.
4
Department of Neurosurgery, Wayne State University, Detroit, Michigan, United States.
5
Department of Pathology, Wayne State University, Detroit, Michigan, United States.
6
Division of Pediatric Neurology, Nemours Alfred I. DuPont Hospital for Children, Wilmington, Delaware, United States.
7
Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania, United States.
8
Department of Oncology, Wayne State University, Detroit, Michigan, United States.
PMID:
28571101
PMCID:
PMC5587372
DOI:
10.1055/s-0037-1603515
[Indexed for MEDLINE]
Free PMC Article
Icon for Georg Thieme Verlag Stuttgart, New York Icon for PubMed Central
8.
Dev Med Child Neurol. 2017 Sep;59(9):952-958. doi: 10.1111/dmcn.13433. Epub 2017 Apr 11.

Clinical and metabolic correlates of cerebral calcifications in Sturge-Weber syndrome.

Author information

1
Division of Pediatric Neurology, The Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, MI, USA.
2
Department of Radiology, Wayne State University, Detroit, MI, USA.
3
Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI, USA.
4
Division of Neurology, Nemours/Alfred I DuPont Hospital for Children, Wilmington, DE, USA.

Abstract

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.

PMID:
28397986
PMCID:
PMC5568960
[Available on 2018-09-01]
DOI:
10.1111/dmcn.13433
[Indexed for MEDLINE]
Icon for Wiley
9.
Hum Brain Mapp. 2017 Jun;38(6):3098-3112. doi: 10.1002/hbm.23577. Epub 2017 Mar 21.

Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy.

Author information

1
Departments of Pediatrics and Neurology, School of Medicine, Wayne State University, Detroit, Michigan.
2
Translational Imaging Laboratory, PET Center, Children's Hospital of Michigan, Detroit, Michigan.
3
Department of Neurology, Nemours DuPont Hospital for Children, Wilmington, Delaware.
4
Thomas Jefferson University School of Medicine, Philadelphia, Pennysylvania.

Abstract

To determine the spatial relationship between 2-deoxy-2[18 F]fluoro-D-glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two-stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo- and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG-PET scans of 37 children with intractable epilepsy (31 with non-localizing MRI) were compared with age-matched pseudo-normal pediatric control PET data. Hypo-/hypermetabolic maps were transformed to 3D-MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG-defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface-distance analysis demonstrated that large portions of ECoG-defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18-0.25/0.94-0.90 for overlap 3-cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG-PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age-matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp 38:3098-3112, 2017.

KEYWORDS:

FDG PET; SPM; electrocorticography; epilepsy surgery; pediatric epilepsy; seizure onset

PMID:
28322026
PMCID:
PMC5475408
DOI:
10.1002/hbm.23577
[Indexed for MEDLINE]
Free PMC Article
Icon for Wiley Icon for PubMed Central
10.
J Neurosurg. 2018 Feb;128(2):414-421. doi: 10.3171/2016.9.JNS16452. Epub 2017 Feb 24.

Alternating electric tumor treating fields for treatment of glioblastoma: rationale, preclinical, and clinical studies.

Author information

1
Departments of 1 Neurosurgery.
2
Oncology.
3
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
4
Neurology, and.
5
Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York; and.
6
Department of Biomedical Engineering, Cornell University, Ithaca, New York.
7
Pediatrics.

Abstract

OBJECTIVE Treatment for glioblastoma (GBM) remains largely unsuccessful, even with aggressive combined treatment via surgery, radiotherapy, and chemotherapy. Tumor treating fields (TTFs) are low-intensity, intermediate-frequency, alternating electric fields that have antiproliferative properties in vitro and in vivo. The authors provide an up-to-date review of the mechanism of action as well as preclinical and clinical data on TTFs. METHODS A systematic review of the literature was performed using the terms "tumor treating fields," "alternating electric fields," "glioblastoma," "Optune," "NovoTTF-100A," and "Novocure." RESULTS Preclinical and clinical data have demonstrated the potential efficacy of TTFs for treatment of GBM, leading to several pilot studies, clinical trials, and, in 2011, FDA approval for its use as salvage therapy for recurrent GBM and, in 2015, approval for newly diagnosed GBM. CONCLUSIONS Current evidence supports the use of TTFs as an efficacious, antimitotic treatment with minimal toxicity in patients with newly diagnosed and recurrent GBM. Additional studies are needed to further optimize patient selection, determine cost-effectiveness, and assess the full impact on quality of life.

KEYWORDS:

GBM = glioblastoma; LYG = life years gained; MDR = multidrug resistant; NSCLC = non–small cell lung cancer; NovoTTF-100A; OS = overall survival; Optune; PFS = progression-free survival; QALY = quality-adjusted life year; QOL = quality of life; TMZ = temozolomide; TTF = tumor treating field; TTP = time to disease progression; alternating electric fields; newly diagnosed glioblastoma; oncology; recurrent glioblastoma; tumor treating fields

11.
Clin Nucl Med. 2017 May;42(5):341-347. doi: 10.1097/RLU.0000000000001577.

Prognostic Molecular and Imaging Biomarkers in Primary Glioblastoma.

Author information

1
From the Department of *Pediatrics, Wayne State University, Detroit; †PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit; Departments of ‡Neurosurgery, and §Neurology, Wayne State University, Detroit; ∥Karmanos Cancer Institute, Detroit; and ¶Deparment of Oncology, Wayne State University, Detroit, Michigan.

Abstract

PURPOSE:

Several molecular glioma markers (including isocitrate dehydrogenase 1 [IDH1] mutation, amplification of the epidermal growth factor receptor [EGFR], and methylation of the O6-methylguanine-DNA methyltransferase [MGMT] promoter) have been associated with glioblastoma survival. In this study, we examined the association between tumoral amino acid uptake, molecular markers, and overall survival in patients with IDH1 wild-type (primary) glioblastoma.

PATIENTS AND METHODS:

Twenty-one patients with newly diagnosed IDH1 wild-type glioblastomas underwent presurgical MRI and PET scanning with alpha[C-11]-L-methyl-tryptophan (AMT). MRI characteristics (T2- and T1-contrast volume), tumoral tryptophan uptake, PET-based metabolic tumor volume, and kinetic variables were correlated with prognostic molecular markers (EGFR and MGMT) and overall survival.

RESULTS:

EGFR amplification was associated with lower T1-contrast volume (P = 0.04) as well as lower T1-contrast/T2 volume (P = 0.04) and T1-contrast/PET volume ratios (P = 0.02). Tumors with MGMT promoter methylation showed lower metabolic volume (P = 0.045) and lower tumor/cortex AMT unidirectional uptake ratios than those with unmethylated MGMT promoter (P = 0.009). While neither EGFR amplification nor MGMT promoter methylation was significantly associated with survival, high AMT tumor/cortex uptake ratios on PET were strongly prognostic for longer survival (hazards ratio, 30; P = 0.002). Estimated mean overall survival was 26 months in patients with high versus 8 months in those with low tumoral AMT uptake ratios.

CONCLUSIONS:

The results demonstrate specific MRI and amino acid PET imaging characteristics associated with EGFR amplification and MGMT promoter methylation in patients with primary glioblastoma. High tryptophan uptake on PET may identify a subgroup with prolonged survival.

PMID:
28195901
PMCID:
PMC5380523
DOI:
10.1097/RLU.0000000000001577
[Indexed for MEDLINE]
Free PMC Article
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12.
Pediatr Neurol Briefs. 2016 Nov;30(11):43.

Predicting and Preventing Epilepsy in Sturge-Weber Syndrome?

Author information

1
Department of Pediatrics and Neurology, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI.

Abstract

Investigators from the University of Montreal studied potential predictors of epilepsy in young patients with Sturge-Weber syndrome (SWS).

KEYWORDS:

Developmental Venous Anomaly; Epilepsy; Sturge-Weber syndrome

13.
Neurology. 2017 Jan 3;88(1):103-105. doi: 10.1212/WNL.0000000000003455. Epub 2016 Nov 18.

Enlargement of deep medullary veins during the early clinical course of Sturge-Weber syndrome.

Author information

1
From Wayne State University (V.K.P., H.T.C., C.J.); Children's Hospital of Michigan (V.K.P., H.T.C., C.J.), Detroit; and Nemours/Alfred I. DuPont Hospital for Children (H.T.C.), Wilmington, DE.
2
From Wayne State University (V.K.P., H.T.C., C.J.); Children's Hospital of Michigan (V.K.P., H.T.C., C.J.), Detroit; and Nemours/Alfred I. DuPont Hospital for Children (H.T.C.), Wilmington, DE. juhasz@pet.wayne.edu.
PMID:
27864521
PMCID:
PMC5200860
DOI:
10.1212/WNL.0000000000003455
[Indexed for MEDLINE]
Free PMC Article
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14.
J Nucl Med. 2017 Feb;58(2):208-213. doi: 10.2967/jnumed.116.179994. Epub 2016 Oct 20.

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts.

Author information

1
Department of Neurosurgery, Wayne State University, Detroit, Michigan.
2
Department of Pediatrics, Wayne State University, Detroit, Michigan.
3
Department of Radiology, Wayne State University, Detroit, Michigan.
4
PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan.
5
Department of Oncology, Wayne State University, Detroit, Michigan.
6
Karmanos Cancer Institute, Detroit, Michigan.
7
Department of Radiology and Advanced Imaging Research Center, University of Texas Southwestern, Dallas, Texasand.
8
Department of Neurology, Wayne State University, Detroit, Michigan.
9
Department of Neurosurgery, Wayne State University, Detroit, Michigan smittal@med.wayne.edu.

Abstract

Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. α-11C-methyl-l-tryptophan (11C-AMT) PET imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of 11C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-18F-fluoroethyl)-l-tryptophan (18F-FETrp) may be useful to assess tryptophan metabolism via the kynurenine pathway. In this study, we tested in vivo organ and tumor uptake and kinetics of 18F-FETrp in patient-derived xenograft mouse models and compared them with 11C-AMT uptake.

METHODS:

Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with 18F-FETrp and 11C-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared.

RESULTS:

18F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas 11C-AMT showed higher uptake in the kidneys. Both tracers showed uptake in the xenograft tumors, with a plateau of approximately 30 min after injection; however, 18F-FETrp showed higher tumoral SUV than 11C-AMT in all 3 tumor types tested. The radiation dosimetry for 18F-FETrp determined from the mouse data compared favorably with the clinical 18F-FDG PET tracer.

CONCLUSION:

18F-FETrp tumoral uptake, biodistribution, and radiation dosimetry data provide strong preclinical evidence that this new radiotracer warrants further studies that may lead to a broadly applicable molecular imaging tool to examine abnormal tryptophan metabolism in human tumors.

KEYWORDS:

brain metastasis; glioblastoma; indoleamine 2,3-dioxygenase

PMID:
27765857
PMCID:
PMC5288739
DOI:
10.2967/jnumed.116.179994
[Indexed for MEDLINE]
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15.
Childs Nerv Syst. 2016 Oct;32(10):1823-32. doi: 10.1007/s00381-016-3125-z. Epub 2016 Sep 20.

PET and SPECT studies in children with hemispheric low-grade gliomas.

Juhász C1,2,3,4, Bosnyák E5,6.

Author information

1
Departments of Pediatrics, Wayne State University, Detroit, MI, USA. juhasz@pet.wayne.edu.
2
Departments of Neurology, Wayne State University, Detroit, MI, USA. juhasz@pet.wayne.edu.
3
PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Wayne State University School of Medicine, 3901 Beaubien Street, Detroit, MI, 48201, USA. juhasz@pet.wayne.edu.
4
Karmanos Cancer Institute, Detroit, MI, USA. juhasz@pet.wayne.edu.
5
Departments of Pediatrics, Wayne State University, Detroit, MI, USA.
6
PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Wayne State University School of Medicine, 3901 Beaubien Street, Detroit, MI, 48201, USA.

Abstract

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.

KEYWORDS:

Amino acid; Glucose; Low-grade; MRI; Pediatric glioma; Positron emission tomography

PMID:
27659825
PMCID:
PMC5120676
DOI:
10.1007/s00381-016-3125-z
[Indexed for MEDLINE]
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16.
J Neurol Sci. 2016 Sep 15;368:97-103. doi: 10.1016/j.jns.2016.06.065. Epub 2016 Jun 29.

Cortical thickness asymmetries and surgical outcome in neocortical epilepsy.

Author information

1
Department of Pediatrics, Wayne State University, 3901 Beaubien St., Detroit, MI 48201, United States; PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, 3901 Beaubien St., Detroit, MI 48201, United States.
2
Department of Pediatrics, Wayne State University, 3901 Beaubien St., Detroit, MI 48201, United States; Department of Neurology, Wayne State University, Harper University Hospital, 3990 John R. St, Detroit, MI 48201, United States.
3
Department of Pediatrics, Wayne State University, 3901 Beaubien St., Detroit, MI 48201, United States; Department of Neurosurgery, Wayne State University, Harper University Hospital, 3990 John R. St, Detroit, MI 48201, United States.
4
Department of Pediatrics, Wayne State University, 3901 Beaubien St., Detroit, MI 48201, United States; PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, 3901 Beaubien St., Detroit, MI 48201, United States; Department of Neurology, Wayne State University, Harper University Hospital, 3990 John R. St, Detroit, MI 48201, United States. Electronic address: juhasz@pet.wayne.edu.
5
Department of Pediatrics, Wayne State University, 3901 Beaubien St., Detroit, MI 48201, United States; PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, 3901 Beaubien St., Detroit, MI 48201, United States; Department of Neurology, Wayne State University, Harper University Hospital, 3990 John R. St, Detroit, MI 48201, United States.

Abstract

PURPOSE:

We evaluated if cortical thickness measures were associated with surgical outcome in patients with non-lesional neocortical epilepsy.

METHODS:

Twenty-one young patients (age: 2.4-19.7years) with epilepsy of neocortical origin and normal MRI underwent two-stage epilepsy surgery with subdural EEG monitoring. Cortical thickness was measured on presurgical volumetric MRI using the FreeSurfer software. The prognostic value of hemispheric and lobar/regional cortical thickness measures for 1-year and 2-year post-surgical seizure outcome has been analyzed.

RESULTS:

At one-year follow-up, 14 patients (67%) were seizure-free. Hemispheric and frontal lobe cortical thickness showed no/minimal asymmetry in seizure-free patients but thinner cortex ipsilateral to the seizure focus in those with recurrent seizures (p=0.02). More robust differences were found in patients≥6years of age (p=0.006 for frontal asymmetries), whose cortical thickness asymmetries remained prognostic for 2-year post-surgical outcome (p=0.007). By using an optimal cutoff threshold based on a receiver operating characteristic analysis, mean hemispheric asymmetry predicted one-year seizure freedom with 93% sensitivity and 71% specificity in the whole group, and with 100% sensitivity and 92% specificity in patients≥6years of age.

CONCLUSION:

In patients with neocortical epilepsy and normal MRI, neocortical thinning in the epileptic hemisphere, particularly in frontal cortex, is associated with poor surgical outcome. Although these results require validation in a larger cohort prospectively, these data suggest that presurgical evaluation of cortical thickness may assist in identification of patients at high risk for surgical failure.

KEYWORDS:

Cortical thickness; Epilepsy; Epilepsy surgery; Frontal lobe; MRI; Surgical outcome

PMID:
27538609
PMCID:
PMC4996370
DOI:
10.1016/j.jns.2016.06.065
[Indexed for MEDLINE]
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17.
Pediatr Neurol. 2016 Aug;61:38-45. doi: 10.1016/j.pediatrneurol.2016.05.012. Epub 2016 May 30.

Predictors of Cognitive Functions in Children With Sturge-Weber Syndrome: A Longitudinal Study.

Author information

1
Department of Pediatrics, Wayne State University and Children's Hospital of Michigan, Detroit, Michigan.
2
Department of Pediatrics, Wayne State University and Children's Hospital of Michigan, Detroit, Michigan; Department of Neurology, Wayne State University, Detroit, Michigan.
3
Department of Pediatrics, Wayne State University and Children's Hospital of Michigan, Detroit, Michigan; Department of Neurology, Wayne State University, Detroit, Michigan; Division of Pediatric Neurology, Nemours A.I. duPont Hospital for Children, Wilmington, Delaware; Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania.
4
Department of Pediatrics, Wayne State University and Children's Hospital of Michigan, Detroit, Michigan; Department of Neurology, Wayne State University, Detroit, Michigan. Electronic address: juhasz@pet.wayne.edu.

Abstract

BACKGROUND:

Sturge-Weber syndrome is often accompanied by seizures and neurocognitive deterioration, although previous studies have suggested that early functional brain reorganization may diminish the cognitive sequelae in some children with unilateral Sturge-Weber syndrome. The "rules" governing these plasticity mechanisms are poorly understood. In this study, we evaluated longitudinal changes of cognitive functioning (intelligence quotient [IQ]) and assessed the performance of clinical, electroencephalography (EEG), and magnetic resonance imaging (MRI) variables for predicting IQ in children with Sturge-Weber syndrome.

METHODS:

Thirty-three young children (mean age: 3.3 years at baseline) with unilateral Sturge-Weber syndrome underwent MRI, scalp EEG, and neuropsychology evaluation twice, with a median follow-up of 2 years. None of the children had epilepsy surgery. Longitudinal IQ changes were calculated. Seizure variables, interictal EEG abnormalities, and extent and location of MRI brain involvement were correlated with IQ assessed at follow-up.

RESULTS:

Global IQ showed a highly variable course with both increases and decreases over time. Lower IQ at baseline was associated with interval IQ increase. In univariate analyses, lower outcome IQ was associated with baseline EEG abnormalities (P < 0.001), young age at seizure onset (P = 0.001), high seizure frequency (P = 0.02), and early frontal-lobe involvement on MRI (P = 0.01). In multivariate analysis, EEG abnormalities at baseline remained a robust, independent predictor of outcome IQ.

CONCLUSIONS:

The early trajectory of cognitive changes in children with unilateral Sturge-Weber syndrome is highly variable; children with improving IQ likely undergo effective unimpeded functional reorganization. Early onset, frequent seizures, and interictal epileptiform abnormalities on EEG likely interfere with this process resulting in poor cognitive functions. Future studies assessing interventions should target this high-risk subgroup to optimize cognitive outcome in Sturge-Weber syndrome.

KEYWORDS:

EEG; MRI; Sturge–Weber syndrome; cognitive functions; epilepsy; longitudinal study

[Indexed for MEDLINE]
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18.
Hum Brain Mapp. 2016 Nov;37(11):3946-3956. doi: 10.1002/hbm.23287.

Postoperative axonal changes in the contralateral hemisphere in children with medically refractory epilepsy: A longitudinal diffusion tensor imaging connectome analysis.

Author information

1
Departments of Pediatrics and Neurology, School of Medicine, Wayne State University, Detroit, Michigan. jeongwon@pet.wayne.edu.
2
Translational Imaging Laboratory, PET Center, Children's Hospital of Michigan, Detroit, Michigan. jeongwon@pet.wayne.edu.
3
Departments of Pediatrics and Neurology, School of Medicine, Wayne State University, Detroit, Michigan.
4
Translational Imaging Laboratory, PET Center, Children's Hospital of Michigan, Detroit, Michigan.
5
Department of Neurology, Nemours DuPont Hospital for Children, Wilmington, Delaware.
6
Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania.

Abstract

To determine brain plasticity changes due to resective epilepsy surgery in children, we performed a longitudinal connectome analysis on the pattern of axonal connectivity in the contralateral hemisphere. Pre- and postoperative diffusion tensor imaging (DTI) data were acquired from 35 children with intractable focal epilepsy. A total of 54 brain regions of interest (ROIs) were generated in the hemisphere contralateral to the resection. Within a 54 × 54 connectivity matrix, a pairwise connectivity score was calculated for each connection between two ROIs, based on the DTI fiber streamline number in each connection. A permuted Spearman's ρ-rank analysis was used to identify specific inter-regional connections showing a significant association between the postoperative change of connectivity score and clinical variables. Nineteen connections in the contralateral hemisphere showed postoperative increases in the strength of connectivity. Postoperative increase in connectivity between insular-inferior frontal operculum regions as well as that between superior frontal orbital and mid frontal orbital regions were both significantly associated with a larger surgical resection volume (ρ > +0.40) and a younger patient age (ρ > -0.34). These increases were more robust in patients with frontal resection and in those achieving seizure freedom. Neuropsychological evaluation on subsets of patients revealed that such increases in connectivity were associated with preserved or improved cognitive functions such as visual memory and planning. Resective epilepsy surgery may lead to increased contralateral axonal connectivity in children with focal epilepsy. Our data lead to a hypothesis that such increased connectivity may be an imaging marker of postoperative brain plasticity to compensate for cognitive function. Hum Brain Mapp 37:3946-3956, 2016.

KEYWORDS:

axonal plasticity; contralateral reorganization; diffusion tensor imaging; epilepsy surgery

PMID:
27312605
PMCID:
PMC5053859
DOI:
10.1002/hbm.23287
[Indexed for MEDLINE]
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19.
Pediatr Neurol. 2016 May;58:12-24. doi: 10.1016/j.pediatrneurol.2015.11.009. Epub 2016 Mar 16.

Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research.

Author information

1
Department of Neurology, Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: comi@kennedykrieger.org.
2
Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
3
Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
4
Department of Neurology, Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland.
5
Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan; Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan.
6
Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin.
7
The Sturge-Weber Foundation, Randolph, New Jersey.
8
Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College, Thomas University, Philadelphia, Pennsylvania; Department of Pediatrics, Wills Eye Hospital, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
9
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
10
National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
11
Departments of Pediatrics and Neurology, The Ohio State University College of Medicine and Nationwide Children's Hospital, Columbus, Ohio.

Abstract

Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS.

KEYWORDS:

GNAQ; Sturge-Weber syndrome; glaucoma; port-wine birthmark; seizures; somatic mutation

[Indexed for MEDLINE]
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20.
Clin Neurophysiol. 2016 Jun;127(6):2489-99. doi: 10.1016/j.clinph.2016.03.022. Epub 2016 Apr 6.

Interictal high-frequency oscillations generated by seizure onset and eloquent areas may be differentially coupled with different slow waves.

Author information

1
Pediatrics, Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA.
2
Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA.
3
Pediatrics, Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA; Neurology, Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA.
4
Neurosurgery, Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA.
5
Pediatrics, Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA; Neurology, Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA. Electronic address: eishi@pet.wayne.edu.

Abstract

OBJECTIVE:

High-frequency oscillations (HFOs) can be spontaneously generated by seizure-onset and functionally-important areas. We determined if consideration of the spectral frequency bands of coupled slow-waves could distinguish between epileptogenic and physiological HFOs.

METHODS:

We studied a consecutive series of 13 children with focal epilepsy who underwent extraoperative electrocorticography. We measured the occurrence rate of HFOs during slow-wave sleep at each electrode site. We subsequently determined the performance of HFO rate for localization of seizure-onset sites and undesirable detection of nonepileptic sensorimotor-visual sites defined by neurostimulation. We likewise determined the predictive performance of modulation index: MI(XHz)&(YHz), reflecting the strength of coupling between amplitude of HFOsXHz and phase of slow-waveYHz. The predictive accuracy was quantified using the area under the curve (AUC) on receiver-operating characteristics analysis.

RESULTS:

Increase in HFO rate localized seizure-onset sites (AUC⩾0.72; p<0.001), but also undesirably detected nonepileptic sensorimotor-visual sites (AUC⩾0.58; p<0.001). Increase in MI(HFOs)&(3-4Hz) also detected both seizure-onset (AUC⩾0.74; p<0.001) and nonepileptic sensorimotor-visual sites (AUC⩾0.59; p<0.001). Increase in subtraction-MIHFOs [defined as subtraction of MI(HFOs)&(0.5-1Hz) from MI(HFOs)&(3-4Hz)] localized seizure-onset sites (AUC⩾0.71; p<0.001), but rather avoided detection of nonepileptic sensorimotor-visual sites (AUC⩽0.42; p<0.001).

CONCLUSION:

Our data suggest that epileptogenic HFOs may be coupled with slow-wave3-4Hz more preferentially than slow-wave0.5-1Hz, whereas physiologic HFOs with slow-wave0.5-1Hz more preferentially than slow-wave3-4Hz during slow-wave sleep.

SIGNIFICANCE:

Further studies in larger samples are warranted to determine if consideration of the spectral frequency bands of slow-waves coupled with HFOs can positively contribute to presurgical evaluation of patients with focal epilepsy.

KEYWORDS:

EEGLAB; High-gamma activity; Intracranial electrocorticography (ECoG) recording; Neurophysiology; Pathological and physiological high-frequency oscillations (HFOs); Pediatric epilepsy surgery; Phase–amplitude coupling; Receiver-operating characteristics (ROC) curve; Ripples; Subdural electroencephalography (EEG); Subtraction modulation index co-registered to MRI (SMICOM)

PMID:
27178869
PMCID:
PMC4867192
DOI:
10.1016/j.clinph.2016.03.022
[Indexed for MEDLINE]
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