CDKL5 Deficiency Disorder Without Epilepsy.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) has epilepsy as a cardinal feature. Here we report two new female patients and review six previously published patients, one male and five females, with features of CDD but who never developed epilepsy. In contrast with the classical and severe CDD phenotype, they presented with milder gross motor delays, autism spectrum disorder, and no visual cortical impairment. Prolonged video electroencephalography was normal in adult cases but showed interictal frontal-temporal bilateral spikes and sharp waves in sleep in the three-year-old girl. Causative CDKL5 variants included two likely gene damaging (nonsense and frameshift) and six missense variants, being de novo or maternally inherited from asymptomatic females with skewed X-chromosome inactivation (two missense variants). Our data indicate that a milder form of CDD without epilepsy can occur in some cases without clear correlation with specific variants in the CDKL5 gene.

Tailored resections in occipital lobe epilepsy surgery guided by monitoring with subdural electrodes: characteristics and outcome.

PURPOSE: Occipital lobe epilepsy is uncommon in epilepsy surgery series and often difficult to assess due to rapid seizure propagation, misleading seizure semiology and confounding interictal epileptiform activity. Ictal recordings with surface electrodes may not define properly the seizure onset zone in surgical evaluation for intractable occipital epilepsy. Specially in dysplastic lesions, the extension of the epileptogenic zone is not well defined by neuroimaging techniques, therefore, implantation of intracranial electrodes is often indicated. In this study we present our experience with individually tailored resections of occipital lobe epileptic foci guided by monitoring with subdural electrodes. METHODS: Data from interictal and ictal surface and intracranial recordings, neuroimaging, surgical treatment, pathology and outcome of seven patients are presented. RESULTS: The most common seizure type (6/7 patients) was complex partial with temporal lobe semiology, five patients experienced visual auras as part of their complex partial seizures or as separate simple partial seizures. Two patients had seizures suggesting supplementary motor area involvement. One patient had temporal as well as frontal seizure propagation. Neuroimaging showed lesions in 6/7 patients. Pathological studies revealed cortical dysplasia and tumors as the most common causes. Intracranial recordings (6/7 patients) revealed focal onset in 2 patients, regional onset in 2, and diffuse onset in 2. Surgery was performed according to intracranial recordings restricting resections in cases with focal seizure onset (even in large dysplastic lesions) and performing wider resections in patients with regional or diffuse onset. Five of seven patients are seizure free after 12-55 months (mean 24.3). The two remaining patients may be classified as Engel 2b and 3a. CONCLUSIONS: This series of occipital lobe epilepsy surgery shows that, even in patients with cortical dysplasias, restricted resections may have a good outcome and that intracranial monitoring is usually necessary in order to design an individually tailored resection.

Postictal behaviour in temporal lobe epilepsy.

Postictal phenomena such as nose-wiping, coughing and hypersalivation are believed to reflect a purposeful reaction to hypersecretion after regaining consciousness following a complex partial seizure, and are very common in patients with temporal lobe epilepsy, particularly in mesial temporal lobe epilepsy. Nose-wiping is usually performed with the hand ipsilateral to the side of seizure onset. Our patient illustrates an unusual, exaggerated postictal behaviour consisting of long-lasting nose-wiping, coughing and guttural sounds following a complex partial seizure due to right mesial temporal lobe epilepsy. [Published with video sequences].

Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors.

S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety.