Search

Objective We aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques. Methods Seventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks. Results Ictal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain. Conclusions In this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient. Significance Cortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.

Objective: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. Material and Methods: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. Results: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. Conclusions: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Introduction: Pontocerebellar hypoplasia (PCH) involves a diverse range of etiologies including a group of single gene disorders. Mutations in the tRNA splicing endonuclease complex (TSEN) 54 gene can be responsible for PCH type 2, 4 and 5. The more common and less severe PCH 2 phenotype is caused by homozygosity for the common missense mutation A307S, while the severe phenotype seen in type 4 and 5 is caused by compound heterozygosity of the A307S mutation along with a nonsense or splice site mutation. Report: We report a 4- month-old girl who presented with epileptic spasms that remained intractable to several antiepileptic medications. Magnetic Resonance Imaging (MRI) brain showed fairly severe hypoplasia with superimposed atrophy of the cerebellum and brainstem with prominent extra-axial fluid spaces. Extensive metabolic testing was negative. Commercial testing for PCH via TSEN54 gene revealed missense mutation of Ala307Ser. A novel sequence variant, designated c.17_40 del, was also found and was predictive of an in-frame deletion of eight amino acids. Follow-up over 2 years revealed intractable epileptic spasms, progressive microcephaly and development of prominent choreoathetosis. Conclusion: This case report describes a rare case of PCH with overlapping features of the less severe PCH2 and the more severe PCH4/5 phenotype. It also adds another new entity in the list of genetic conditions where West syndrome and pontocerebellar hypoplasia can be seen together, emphasizing the need for further investigations of the genotype-phenotype correlation of mutations in order to advance our understanding of the pathophysiologic mechanism in these rare conditions.