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.
RosatiAGuerriniR. What causes epilepsy? In: MillerJWGoodkinHP, eds. Epilepsy. Oxford, UK: John Wiley & Sons, 2014:15–27.
2.
NoebelsJL. The biology of epilepsy genes. Annu Rev Neurosci. 2003;26:599–625.
3.
SegalEPedroHValdez-GonzalezK. Diagnostic yield of epilepsy panels in children with medication-refractory epilepsy. Pediatr Neurol. 2016;64:66–71.
4.
MillerIOSotero de MenezesMA. SCN1A-Related Seizure Disorders. Published November 29, 2007 [updated May 15, 2014]. In:AdamMPArdingerHHPagonRA, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle, 1993-2018.
5.
WallaceRHSchefferIEBarnettS. Neuronal sodium-channel α1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet. 2001;68:859–865.
6.
LeeYJYumMSKimMJ. Large-scale structural alteration of brain in epileptic children with SCN1A mutation. Neuroimage Clin. 2017;15:594–600.
7.
StrianoPMancardiMMBiancheriR. Brain MRI findings in severe myoclonic epilepsy in infancy and genotype phenotype correlations. Epilepsia. 2007;48:1092–1096.
8.
GuerriniRStrianoPCatarinoC. Neuroimaging and neuropathology of Dravet syndrome. Epilepsia. 2011;52(suppl 2):30–34.
9.
BrunklausAEllisRReaveyE. Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. Brain. 2012;135(pt 8):2329–2336.
10.
KumarAChuganiHT. The role of radionuclide imaging in epilepsy, part 1: sporadic temporal and extratemporal lobe epilepsy. J Nucl Med. 2013;54:1775–1781.
11.
KumarAChuganiHT. The role of radionuclide imaging in epilepsy, part 2: epilepsy syndromes. J Nucl Med. 2013;54:1924–1930.
12.
SmailagicNVacanteMHydeC. 18F-FDG PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015;1:CD010632.
13.
Tro-BaumannBvon SpiczakSLotteJ. A retrospective study of the relation between vaccination and occurrence of seizures in Dravet syndrome. Epilepsia. 2011;52:175–178.
14.
ChuganiHTPhelpsMEMazziottaJC. Positron emission tomography study of human brain functional development. Ann Neurol. 1987;22:487–497.
15.
ArchambaudFBouilleretVHertz-PannierL. Optimizing statistical parametric mapping analysis of 18F-FDG PET in children. EJNMMI Res. 2013;3:2.
16.
JeongJWAsanoEKumar PilliV. Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy. Hum Brain Mapp. 2017;38:3098–3112.
17.
KimJAJeongJWBehenME. Metabolic correlates of cognitive function in children with unilateral Sturge-Weber syndrome: evidence for regional functional reorganization and crowding. Hum Brain Mapp. 2018;39:1596–1606.
18.
BenedekKJuhászCMuzikO. Metabolic changes of subcortical structures in intractable focal epilepsy. Epilepsia. 2004;45:1100–1105.
19.
BenedekKJuhászCChuganiDC. Longitudinal changes in cortical glucose hypometabolism in children with intractable epilepsy. J Child Neurol. 2006;21:26–31.
20.
DlugosDJJaggJO’ConnorWM. Hippocampal cell density and subcortical metabolism in temporal lobe epilepsy. Epilepsia. 1999;40:408–413.
21.
SpencerSS. Neural networks in human epilepsy: evidence of and implications for treatment. Epilepsia. 2002;43:219–227.
22.
ChassouxFArtigesESemahF. Determinants of brain metabolism changes in mesial temporal lobe epilepsy. Epilepsia. 2016;57:907–919.
23.
ChuganiHTContiJR. Etiologic classification of infantile spasms in 140 cases: role of positron emission tomography. J Child Neurol. 1996;11:44–48.
24.
SundaramSKChuganiHTTiwariVN. SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism. Pediatr Neurol. 2013;49:46–49.
25.
Dibué-AdjeiMFischerISteigerHJKampMA. Efficacy of adjunctive vagus nerve stimulation in patients with Dravet syndrome: a meta-analysis of 68 patients. Seizure. 2017;50:147–152.
