Assessment Of The Severity And Cognitive Function Of Pediatric Patients With Epilepsy:Clinical Application Of PET Molecular Imaging

Epilepsy is considered as one of the most common neurological condition,and a major proportion of patients falls in the pediatric group.Uncontrolled epilepsy is associated with higher rates of physical and psychiatric comorbidities,which severely influnce the quality of life.Despite adequate trials of appropriate anticonvulsants,roughly 30%of individuals with epilepsy are estimated to be drug resistant.Early surgery can diminish the detrimental effects of persistent seizures and unnecessary anticonvulsants on cerebral function,which underlined the importance of early identification of the latent refractory epilepsy.Based on the metabolic abnormallity induced by epileptic activity,interictal positron emission tomography?PET?with ¹⁸F-fluorodeoxyglucose(¹⁸F-FDG)has been used as a powerful neuroimaging technology for presurgical evaluation of epileptogenic foci.However,for the non-surgical patients,especially for the non-surgical pediatric epilepsy,the clinical diagnostic and prognostic values of ¹⁸F-FDG PET remain unclear.Cognitive impairment is the most common side effect of anticonvulsant,and the risk may accumulate when anticonvulsants are combined.Particularly,the developing brains of pediatric patients appear to be particularly sensitive to the cognitive adverse effects of anticonvulsants.Hence,the adverse side effects of anticonvulsant therapy can negatively affect adherence and long-term retention rates.Cognitive impairment is the result of a complex and not fully elucidated interplay among different neurotransmitters.Monoamine neurotransmitters system,including dopamine?DA?and serotonin?5-HT?,has wide-ranging effects on many types of cerebral functions instrumental to cognition.In addition,these two neurotransmitter systems are supposed to be involved in epileptogenesis.Therefore,we hypothesized that the change in DA and 5-HT neurotransmission contributed to the anticonvulsant-induced cognitive impairment.In this study,statistical parametric mapping?SPM?analysis of ¹⁸F-FDG PET images and PET/MRI coregistration were used to assess the pediatric epilepsy.The aim was to explore the glucose metabolic profile,and its relation to clinical severity or progress in these patients.Additionally,we performed 11C-N-methylspiperone?11C-NMSP?PET studies to examine the alteration of monoamine receptor activity in pediatric patients with anticonvulsant-induced cognitive impairment.Part 1:Glucose Metabolic Profile by Visual Assessment Combined with SPM Analysis in Pediatric Patients with EpilepsyOne hundred pediatric epilepsy patients who have received ¹⁸F-FDG PET/CT,magnetic resonance imaging?MRI?and electroencephalography?EEG?examinations were respectively included.Fifteen age-matched controls were included for SPM analysis.¹⁸F-FDG PET images were analyzed by using visual assessment combined with SPM analysis.Absolute asymmetry index?|AI|?and its relation to severity and prognosis,were calculated in patients with regional abnormal glucose metabolism.Visual assessment combined with SPM analysis of ¹⁸F-FDG PET images detected more patients with abnormal glucose metabolism compared to the visual assessment only.The|AI| significantly positively correlated with seizure frequency?P<0.01?,but negatively correlated with the time since last seizure?P<0.01?in patients with abnormal glucose metabolism.According to multivariate linear regression analysis,the only significant contributing variable to the |AI| was the time since last seizure,both in patients with hypo-metabolism?P = 0.001?and hyper-metabolism?P = 0.005?.For patients with either hypo-metabolism?P<0.01?or hyper-metabolism?P = 0.209?,higher values of|AI| were found in those with drug resistance than with seizure remission.In the post 1-year follow-up PET studies,significant change of |AI|?%?was found in patients with clinical improvement compared to those with persistence/progression?P<0.01?.¹⁸F-FDG PET imaging by using visual assessment combined with SPM analysis could provide cerebral glucose metabolic profile in epilepsy patients.|AI| might be used for evaluation of clinical severity and progress in these patients.The clinical value of PET might be enhanced by timing the scan closer to clinical seizure?s?.Part 2:Alteration of Monoamine Receptor Activity in Pediatric Patients with Anticonvulsant-induced Cognitive ImpairmentTwenty-five patients had PET imaging with both monoamine receptor binding agent,11C-NMSP,and glucose metabolic agent,¹⁸F-FDG.Tests of intelligence quotient?IQ?,including verbal IQ?VIQ?,performance IQ?PIQ?and full-scale IQ?FSIQ?were performed in each patient.Compared to the patients with mono-therapy,patients with poly-therapy had significantly lower VIQ,PIQ and FSIQ?P<0.01 in each comparison?,as well as significantly lower monoamine receptor activities detected in the caudate nucleus,prefrontal cortex,dorsal anterior cingulate cortex and amygdale?P<0.05 in each comparison?.It is recommended that epilepsy patients should be treated with single anticonvulsant wherever possible.Monoamine receptor-PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.