Neurodevelopmental and Functional Outcomes Following In Utero Exposure to Antiseizure Medication: A Systematic Review.

BACKGROUND AND OBJECTIVES: To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal neurodevelopmental outcomes, focusing on social, emotional, behavioral, and adaptive domains of human function, and the frequency of neurodevelopmental and psychiatric disorders in ASM-exposed offspring. METHODS: Electronic searches of MEDLINE, PsychINFO, and EMBASE were conducted and limited to studies published between 1990 and 2023 in English. Studies were eligible if they prospectively or retrospectively reported neurodevelopmental outcomes of ASM-exposed offspring. The Newcastle-Ottawa scale was used to conduct methodologic quality assessments of included studies, and a narrative synthesis integrated the review findings. RESULTS: Forty-three studies were included. Valproate has been consistently associated with a 2- to 4-fold increased risk of autism spectrum disorder (ASD), 2- to 5-fold increased risk of intellectual disability (ID), and poor adaptive functioning. Growing evidence indicates that topiramate is associated with a 2-fold increased risk of ASD and 3- to 4-fold increased risk of ID. The risks of adverse neurodevelopmental outcomes for valproate and topiramate seem to be dose dependent. Phenobarbital has been suggested to be associated with deleterious neurodevelopmental effects, but data are limited. Levetiracetam has recently been linked with an increased risk of attention deficit hyperactivity disorder and anxiety disorders in a single study. Carbamazepine has been associated with variable neurodevelopmental outcomes. Lamotrigine seems to be "safe" in terms of postnatal neurodevelopment. Data for oxcarbazepine, phenytoin, and clonazepam are limited but seem to have little-to-no risk of adverse outcomes. Evidence for the remaining ASMs, including gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is lacking. Several methodologic limitations impeded data synthesis, including heterogeneity in outcome measures and small samples of monotherapy exposures. DISCUSSION: The findings of this review support the conclusion that valproate and topiramate use during pregnancy is associated with a significantly increased risk of neurodevelopmental effects on the fetus. Apart from lamotrigine, which seems to be free of adverse neurodevelopmental effects, data for the other ASMs are mixed or inadequate to draw definite conclusions. Further research into the neurodevelopmental effects of prenatal exposure to ASMs, including most newer agents, is much needed.

An international survey of SEEG cortical stimulation practices.

OBJECTIVE: Cortical stimulation is an important component of stereoelectroencephalography (SEEG). Despite this, there is currently no standardized approach and significant heterogeneity in the literature regarding cortical stimulation practices. Via an international survey of SEEG clinicians, we sought to examine the spectrum of cortical stimulation practices to reveal areas of consensus and variability. METHODS: A 68-item questionnaire was developed to understand cortical stimulation practices including neurostimulation parameters, interpretation of epileptogenicity, functional and cognitive assessment and subsequent surgical decisions. Multiple recruitment pathways were pursued, with the questionnaire distributed directly to 183 clinicians. RESULTS: Responses were received from 56 clinicians across 17 countries with experience ranging from 2 to 60 years (M = 10.73, SD = 9.44). Neurostimulation parameters varied considerably, with maximum current ranging from 3 to 10 mA (M = 5.33, SD = 2.29) for 1 Hz and from 2 to 15 mA (M = 6.54, SD = 3.68) for 50 Hz stimulation. Charge density ranged from 8 to 200 µC/cm2 , with up to 43% of responders utilizing charge densities higher than recommended upper safety limits, i.e. 55 µC/cm2 . North American responders reported statistically significant higher maximum current (P < 0.001) for 1 Hz stimulation and lower pulse width for 1 and 50 Hz stimulation (P = 0.008, P < 0.001, respectively) compared to European responders. All clinicians evaluated language, speech, and motor function during cortical stimulation; in contrast, 42% assessed visuospatial or visual function, 29% memory, and 13% executive function. Striking differences were reported in approaches to assessment, classification of positive sites, and surgical decisions guided by cortical stimulation. Patterns of consistency were observed for interpretation of the localizing capacity of stimulated electroclinical seizures and auras, with habitual electroclinical seizures induced by 1 Hz stimulation considered the most localizing. SIGNIFICANCE: SEEG cortical stimulation practices differed vastly across clinicians internationally, highlighting the need for consensus-based clinical guidelines. In particular, an internationally standardized approach to assessment, classification, and functional prognostication will provide a common clinical and research framework for optimizing outcomes for people with drug-resistant epilepsy.

Investigating the Effect of Fatigue and Psychological Distress on Information Processing Speed in the Postacute Period After Mild Traumatic Brain Injury in Premorbidly Healthy Adults.

Impairments in processing speed under conditions of increasing cognitive load have been reported in individuals with mild traumatic brain injury (mTBI). In other conditions that are also associated with white matter disruption, both psychological distress and fatigue have been shown to underlie this impairment. OBJECTIVE: the current study aimed to investigate whether slowing of processing abilities under conditions of greater cognitive load is independent of fatigue and psychological status in premorbidly healthy individuals with subacute mTBI. METHOD: using a prospective observational design, we examined 84 individuals with mTBI approximately 8 weeks after injury and 47 healthy control (HC) participants. They were assessed with the Symbol Digit Modality Test, an n-back task and a rate of gain of information choice reaction time task that conforms to Hick's law. Participants were also assessed with measures of fatigue and psychological status. RESULTS: as expected, findings revealed no group differences on simple reaction time tasks, but as task complexity increased, the mTBI group performed more slowly than the HC group. This group difference occurred independently of fatigue and psychological distress levels and was associated with a moderate effect size. CONCLUSIONS: during the subacute period after mTBI, premorbidly healthy individuals demonstrate impairment in their ability to rapidly process information as the cognitive load of the task increases beyond simple reaction time requirements. Examination of whether these changes affect resumption of premorbid roles is warranted.