Early recognition of characteristic conventional and amplitude-integrated EEG patterns of seizures in <i>SCN2A </i>and <i>KCNQ3</i>-related epilepsy in neonates

Purpose: Early recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications but respond well to sodium channel blockers. Recently, a characteristic ictal amplitude-integrated electroencephalogram (aEEG) pattern was described in neonates with KCNQ2-related epilepsy. We report a similar aEEG pattern in seizures caused by SCN2A- and KCNQ3-pathogenic variants, as well as conventional EEG (cEEG) descriptions. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and cEEG findings of 13 neonates with seizures due to pathogenic SCN2A- and KCNQ3-variants. As a comparison group, aEEGs and cEEGs of neonates with seizures due to hypoxic-ischemic encephalopathy (n = 117) and other confirmed genetic causes affecting channel function (n = 55) were reviewed. Results: In 12 out of 13 patients, the aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral EEG onset attenuation, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. Apart from patients with KCNQ2-related epilepsy, none of the patients in the comparison groups had a similar aEEG or cEEG pattern. Discussion: Seizures in SCN2A- and KCNQ3-related epilepsy in neonates can usually be recognized by a characteristic ictal aEEG pattern, previously reported only in KCNQ2-related epilepsy, extending this unique feature to other channelopathies. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium channel blockers even before genetic results are available.</p

Endovascular treatment of patients with stroke caused by anterior cerebral artery occlusions

Background: Occlusion of the anterior cerebral artery (ACA) is uncommon but may lead to significant disability. The benefit of endovascular treatment (EVT) for ACA occlusions remains uncertain. Methods: We included patients treated with EVT and compared patients with ACA occlusions with patients who had internal carotid artery (ICA) or proximal (M1/M2) middle cerebral artery (MCA) occlusions from the MR CLEAN Registry. Primary outcome was the modified Rankin Scale score (mRS). Secondary outcomes were functional independence (mRS 0–2), National Institutes of Health Stroke Scale (NIHSS) score, delta-NIHSS (baseline minus NIHSS score at 24–48 h), and successful recanalization (expanded thrombolysis in cerebral infarction (eTICI) score 2b-3). Safety outcomes were symptomatic intracranial hemorrhage (sICH), periprocedural complications, and mortality. Results: Of 5193 patients, 11 (0.2%) had primary ACA occlusions. Median NIHSS at baseline was lower in patients with ACA versus ICA/MCA occlusions (11, IQR 9–14; versus 15, IQR 11–19). Functional outcome did not differ from patients with ICA/MCA occlusions. Functional independence was 4/11 (36%) in patients with ACA versus 1949/4815 (41%) in ICA/MCA occlusions; median delta-NIHSS was − 1 (IQR − 7 to 2) and − 4 (IQR − 9 to 0), respectively. Successful recanalization was 4/9 (44%), versus 3083/4787 (64%) in ICA/MCA occlusions. Mortality was 3/11 (27%) versus 1263/4815 (26%). One patient with ACA occlusion had sICH; no other complications occurred. Conclusion: In this cohort ACA occlusions were uncommon. Functional outcome did not differ between patients with ACA occlusions and ICA/MCA occlusions. Prospective research is needed to determine feasibility, safety, and outcomes of EVT for ACA occlusions.</p

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Translation from animal to clinical studies, choosing the optimal moment

Neurolog

The degree of prematurity affects functional brain activity in preterm born children at school-age: An EEG study

Prematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG) between extremely (EP) and very prematurely (VP) born children at 9–10 years of age. Fifty-five children born <32 weeks' of gestation underwent EEG at 9–10 years of age and were assessed for motor development and cognitive outcome. Relative frequency power and functional connectivity, as measured by the Phase Lag Index (PLI), were calculated for all frequency bands. Per subject, power spectrum and functional connectivity results were averaged over all channels and pairwise PLI values to explore differences in global frequency power and functional connectivity between EP and VP children. Brain networks were constructed for the upper alpha frequency band using the Minimum Spanning Tree method and were compared between EP and VP children. In addition, the relationships between upper alpha quantitative EEG results and cognitive and motor outcomes were investigated. Relative power and functional connectivity were significantly higher in VP than EP children in the upper alpha frequency band, and VP children had more integrated networks. A strong positive correlation was found between relative upper alpha power and motor outcome whilst controlling for gestational age, age during EEG recording, and gender (ρ = 0.493, p = 0.004). These results suggest that 9–10 years after birth, the effects of the degree of prematurity can be observed in terms of alterations in functional brain activity and that motor deficits are associated with decreases in relative upper alpha power

Erratum : De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders (The American Journal of Human Genetics (2019) 104(1) (139–156), (S0002929718304531) (10.1016/j.ajhg.2018.12.002))

(The American Journal of Human Genetics 104, 139–156; January 3, 2019) In the original version of this article published on December 27, 2018, Maura R.Z. Ruzhnikov's surname was unfortunately misspelled. It appears correctly here and online. The authors apologize for the error

Correction : Putting genome-wide sequencing in neonates into perspective

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article