Long-term memory consolidation of new words in children with self-limited epilepsy with centro-temporal spikes.

Accelerated long-term forgetting has been studied and demonstrated in adults with epilepsy. In contrast, the question of long-term consolidation (delays > 1 day) in children with epilepsy shows conflicting results. However, childhood is a period of life in which the encoding and long-term storage of new words is essential for the development of knowledge and learning. The aim of this study was therefore to investigate long-term memory consolidation skills in children with self-limited epilepsy with centro-temporal spikes (SeLECTS), using a paradigm exploring new words encoding skills and their long-term consolidation over one-week delay. As lexical knowledge, working memory skills and executive/attentional skills has been shown to contribute to long-term memory/new word learning, we added standardized measures of oral language and executive/attentional functions to explore the involvement of these cognitive skills in new word encoding and consolidation. The results showed that children with SeLECTS needed more repetitions to encode new words, struggled to encode the phonological forms of words, and when they finally reached the level of the typically developing children, they retained what they had learned, but didn't show improved recall skills after a one-week delay, unlike the control participants. Lexical knowledge, verbal working memory skills and phonological skills contributed to encoding and/or recall abilities, and interference sensitivity appeared to be associated with the number of phonological errors during the pseudoword encoding phase. These results are consistent with the functional model linking working memory, phonology and vocabulary in a fronto-temporo-parietal network. As SeLECTS involves perisylvian dysfunction, the associations between impaired sequence storage (phonological working memory), phonological representation storage and new word learning are not surprising. This dual impairment in both encoding and long-term consolidation may result in large learning gap between children with and without epilepsy. Whether these results indicate differences in the sleep-induced benefits required for long-term consolidation or differences in the benefits of retrieval practice between the epilepsy group and healthy children remains open. As lexical development is associated with academic achievement and comprehension, the impact of such deficits in learning new words is certainly detrimental.

Modulation of epileptic networks by transient interictal epileptic activity: A dynamic approach to simultaneous EEG-fMRI.

Epileptic networks, defined as brain regions involved in epileptic brain activity, have been mapped by functional connectivity in simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. This technique allows to define brain hemodynamic changes, measured by the Blood Oxygen Level Dependent (BOLD) signal, associated to the interictal epileptic discharges (IED), which together with ictal events constitute a signature of epileptic disease. Given the highly time-varying nature of epileptic activity, a dynamic functional connectivity (dFC) analysis of EEG-fMRI data appears particularly suitable, having the potential to identify transitory features of specific connections in epileptic networks. In the present study, we propose a novel method, defined dFC-EEG, that integrates dFC assessed by fMRI with the information recorded by simultaneous scalp EEG, in order to identify the connections characterised by a dynamic profile correlated with the occurrence of IED, forming the dynamic epileptic subnetwork. Ten patients with drug-resistant focal epilepsy were included, with different aetiology and showing a widespread (or multilobar) BOLD activation, defined as involving at least two distinct clusters, located in two different lobes and/or extended to the hemisphere contralateral to the epileptic focus. The epileptic focus was defined from the IED-related BOLD map. Regions involved in the occurrence of interictal epileptic activity; i.e., forming the epileptic network, were identified by a general linear model considering the timecourse of the fMRI-defined focus as main regressor. dFC between these regions was assessed with a sliding-window approach. dFC timecourses were then correlated with the sliding-window variance of the IED signal (VarIED), to identify connections whose dynamics related to the epileptic activity; i.e., the dynamic epileptic subnetwork. As expected, given the very different clinical picture of each individual, the extent of this subnetwork was highly variable across patients, but was but was reduced of at least 30% with respect to the initially identified epileptic network in 9/10 patients. The connections of the dynamic subnetwork were most commonly close to the epileptic focus, as reflected by the laterality index of the subnetwork connections, reported higher than the one within the original epileptic network. Moreover, the correlation between dFC timecourses and VarIED was predominantly positive, suggesting a strengthening of the dynamic subnetwork associated to the occurrence of IED. The integration of dFC and scalp IED offers a more specific description of the epileptic network, identifying connections strongly influenced by IED. These findings could be relevant in the pre-surgical evaluation for the resection or disconnection of the epileptogenic zone and help in reaching a better post-surgical outcome. This would be particularly important for patients characterised by a widespread pathological brain activity which challenges the surgical intervention.

Clinical and genetic spectrum of SCN2A-associated episodic ataxia.

BACKGROUND: Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability. Few reports have recently described SCN2A-associated episodic ataxia (EA). Our study identifies its broader clinical and genetic spectrum, and describes pharmacological approaches. RESULTS: We report 21 patients with SCN2A-associated EA, of which 9 are unpublished cases. The large majority of patients present with epileptic seizures (18/21, 86%), often starting within the first three months of life (12/18, 67%). In contrast, onset of episodic ataxia ranged from 10 months to 14 years of age. The frequency of EA episodes ranged from brief, daily events up to 1-2 episodes per year each lasting several weeks. Potential triggers include minor head traumas and sleep deprivation. Cognitive outcome is favorable in most patients with normal or mildly impaired cognitive development in 17/21 patients (81%). No clear genotype-phenotype correlations were identified in this cohort. However, two mutational hotspots were identified, i.e. 7/21 patients (33%) harbor the identical pathogenic variant p.A263V, whereas 5/21 (24%) carry pathogenic variants that affect the S4 segment and its cytoplasmic loop within the domain IV. In addition, we identified six novel pathogenic variants in SCN2A. While acetazolamide was previously reported as beneficial in SCN2A-associated EA in one case, our data show a conflicting response in 8 additional patients treated with acetazolamide: three of them profited from acetazolamide treatment, while 5/8 did not. CONCLUSIONS: Our study describes the heterogeneous clinical spectrum of SCN2A-associated EA, identifies two mutational hotspots and shows positive effects of acetazolamide in about 50%.

What to do in failed hemispherotomy? Our clinical series and review of the literature.

Hemispherotomy is an established surgical technique to cure or palliate selected, mostly young patients suffering from refractory epilepsy. However, a few patients continue to have seizures despite the surgical hemispherical disconnection. We present a case series of patients who underwent redo hemispherotomy after a first unsuccessful hemispherical disconnection and provide a roadmap for subsequent workup and treatment. The institutional database of epilepsy surgery was reviewed. Twenty-four patients who underwent hemispherotomies for refractory epilepsy were identified between 2007 and 2016. Patients' notes were checked for demographics, history, clinical presentation, preoperative workup, medical treatment, age at first hemispherotomy, and surgical technique. Complications, histopathology, postoperative antiepileptic drug, and postoperative neurological follow-up were documented. Engel class was used to determine the outcome after surgery. Three patients (one hemimegalencephaly, one perinatal stroke, and one Rasmussen's disease) underwent redo hemispherotomy after electroencephalography and MRI studies with particular importance given to diffusion tensor imaging (DTI) to demonstrate residual connection between hemispheres. In one case, redo disconnection followed by a frontal lobectomy rendered the patient seizure-free (Engel class I). In one case, the seizure frequency remained the same but generalized seizures disappeared (Engel class III), and in one case, seizure frequency was considerably reduced after the redo disconnection (Engel class II), with a minimum follow-up of 2 years. Surgical aspects, possible reasons of failure of first hemispherotomy, and rationale that led to second-look surgery are presented. Reasons for failure can be related to patient's selection and/or surgical aspects. Hemispherotomy is a technically demanding procedure and requires accurate preoperative workup. Redo hemispherotomy is a valid option on the basis of further epileptological and radiological workup to demonstrate residual interhemispheric connections and/or rule out bi-hemispheric epileptic activity.

Successful treatment of neonatal atypical hemolytic uremic syndrome with C5 monoclonal antibody.

Hemolytic uremic syndrome (HUS) is rare in neonates. We report the case of atypical HUS (aHUS) revealed by neonatal seizures. This 18-day-old baby presented with repeated clonus of the left arm and eye deviation. Four days earlier, she had suffered from gastroenteritis (non-bloody diarrhea and vomiting without fever). Her work-up revealed hemolytic anemia (120 g/L), thrombocytopenia (78 g/L), and impaired renal function (serum creatinine=102 µmol/L) compatible with the diagnosis of HUS. Levels of C3 and C4 in the serum were normal. Shiga-toxin in the stools as well as the IgM and IgG against Escherichia coli O157 were negative. ADAMTS 13 deficiency, inborn error of the cobalamin pathway, deficiency in the H and I protein, and factor H antibodies were excluded and we concluded in aHUS. Genetic screening of the alternative complement pathway was normal. Cerebral magnetic resonance imaging performed after 24 h and 1 week showed restricted diffusion areas with periventricular white matter ischemic-hemorrhagic lesions. Extensive infectious work-up was negative. Upon admission the baby received antiepileptic drugs and 2 days later C5 monoclonal antibody (eculizumab) and two transfusions of packed erythrocytes because the hemoglobin value had dropped to 55 g/L. The platelet value was minimal at 30 g/L. Renal function normalized in 48 h without dialysis and neurological examination was normal in 1 week. She was discharged from the hospital at day 10 with eculizumab perfusions (300 mg) planned every 3 weeks. After 24 months, she was relapse-free and seizure-free, with a normal neurological examination.

Widespread intracranial calcifications in the follow-up of a patient with cartilage-hair hypoplasia--anauxetic dysplasia spectrum disorder: a coincidental finding?

BACKGROUND/PURPOSE: Intracranial calcifications have been identified in many neurological disorders. To our knowledge, however, such findings have not been described in cartilage-hair hypoplasia - anauxetic dysplasia spectrum disorders (CHH-AD), a group of conditions characterized by a wide spectrum of clinical manifestations. METHODS/RESULTS: We report a 22-year old female patient, diagnosed with this disorder during her first year of life, and in whom bilateral intracranial calcifications (frontal lobes, basal ganglia, cerebellar dentate nuclei) were discovered by brain MRI at the age of 17 years. CONCLUSION: The etiology of this finding remains unclear. Some causes of such deposits can be of a reversible nature, thus prompting early recognition although their consequences on clinical outcome remain mostly unknown.

Early-onset or rapidly progressive scoliosis in children: check the eyes!

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder characterized by the absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence, caused by mutations in the ROBO3 gene which has an important role in axonal guidance and neuronal migration. We describe two female children aged 12 years and 18 months, with progressive scoliosis, in whom the neurological examination showed absent conjugate horizontal eye movements, but preserved vertical gaze and convergence. Cerebral Magnetic resonance imaging findings included pontine hypoplasia, absent facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft, while Diffusion tensor imaging (DTI) maps showed the absence of decussating ponto-cerebellar fibers and superior cerebellar peduncles. Somatosensory and motor evoked potential studies demonstrated ipsilateral sensory and motor responses. The diagnosis was confirmed by the identification of bi-allelic mutations in the ROBO3 gene.

"Gourmand syndrome" in a child with pharmacoresistant epilepsy.

We report the case of a 10-year-old boy with pharmacoresistant epilepsy, symptomatic of a right temporoparietal hemorrhagic lesion, who displayed an eating passion as described for the gourmand syndrome (GS) in adults and discuss the role of epilepsy in GS. This patient presented with a significant change in his eating habits (abnormal preoccupation with the preparation and eating of fine-quality food) concordant with the onset of his seizure disorder, without any previous history of eating disorders or psychiatric illness. This observation corroborates the important role of the right cerebral hemisphere in disturbed eating habits, including the relatively benign GS, and, possibly rarely, in less benign eating disorders such as anorexia and obesity.

Isolated absence of optic chiasm revealed by congenital nystagmus, MRI and VEPs.

Congenital nystagmus is a rare condition mainly characterised by rhythmic, conjugate, and horizontal oscillations of both eyes that persist in the vertical gaze. This disorder is usually noticed in the neonatal period and persists throughout life. It can be of sensory origin, associated with low visual acuity of various causes, or of motor origin, caused by a defect in the slow eye movement system. The former can be genetically determined. It can also be associated with several conditions, the most frequent being albinism. The achiasma syndrome has recently been recognized in two patients as an autosomal recessive inherited cause of congenital nystagmus. We report the case of the so far youngest reported baby having been diagnosed with the isolated achiasmatic condition, which presented with congenital nystagmus and see-saw nystagmus, and discuss its clinical findings and 18 months follow-up. The achiasmatic syndrome should be included in the differential diagnosis of congenital nystagmus, as all the described cases presented like that. Complete investigations should be performed to allow the best evolution and follow-up of these children.