Microgyria

In the era after World War II, Francis (Frank) Forster (1912-2006) became a preeminent American neurologist and epileptologist, with international prominence in the study of reflex epilepsy. Forster's interest in reflex epilepsy began with a chance observation of the condition, in 1946, in a four-year-old girl. When medical measures failed to control her somatosensory-evoked seizures, Forster recommended surgery, and then facilitated transfer to Canadian neurosurgeon Wilder Penfield (1891-1976) at the Montreal Neurological Institute...

Desmosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis resulting in multiple congenital abnormalities and syndromic intellectual disability. It is caused by defects in DHCR24, the gene encoding 3-β-hydroxysterol-24-reductase (24-dehydrocholesterol reductase), which acts in conversion of cholesterol precursor desmosterol, hence resulting in elevated plasma desmosterol levels. To date, desmosterolosis has been reported in 10 patients. Here we report an eleventh patient with desmosterolosis, and the first one to be diagnosed antenatally...

Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). An approach to increment epileptogenesis and SES is to use a second insult to be added to the genetic background. Here, we used adult naïve WARs with microgyria induced by neonatal cortical freeze-lesion (FL) to evaluate the occurrence of SES and the modification in cortical oscillation patterns and behavior...

OBJECTIVE: Malformations of the polymicrogyria spectrum can be mimicked in rodents through neonatal transcranial focal cortical freeze lesions. The animals presenting the malformations present both altered synaptic events and epileptiform activity in the vicinity of the microgyrus, but the comprehension of their contribution to increased predisposition or severity of seizures require further studies. METHODS: In order to investigate these issues, we induced both microgyria and schizencephaly in 57 mice and evaluated: their convulsive susceptibility and severity after pentyleneterazol (PTZ) treatment, the quantification of their symmetric and asymmetric synapses, the morphology of their dendritic arbors, and the content of modulators of synaptogenesis, such as SPARC, gephyrin and GAP-43 within the adjacent visual cortex...

GPR56 gene is best known for its pivotal role in cerebral cortical development. Mutations inGPR56give rise to cobblestone-like brain malformation, white matter changes and cerebellar dysplasia. This study aimed to identify causative variant in a consanguineous family having five individuals affected with developmental delay, mild to severe intellectual disability, speech impairment, strabismus and seizures. Whole exome sequencing was performed to identify mutation in affected individuals. Variants were filtered and further validated by Sanger sequencing and segregation analysis...

Abnormal migration of subventricular zone (SVZ)-derived neural progenitor cells (SDNPs) is involved in the pathological and epileptic processes of focal cortical dysplasias (FCDs), but the underlying mechanisms are not clear. Recent studies indicated that high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) are widely expressed in epileptic specimens of FCDs, which suggests that the HMGB1-RAGE pathway is involved in the pathological and/or epileptic processes of FCDs. The present study used Nestin-GFPtg/+ transgenic mice, and we established a model of freezing lesion (FL), as described in our previous report...

Cortical dysplasia (CD) is a common cause of drug-resistant epilepsy. Increasing studies have implicated innate immunity in CD with epilepsy. However, it is unclear whether innate immune factors induce epileptogenic CD. Here, we injected recombinant human high mobility group box 1 (rHMGB1) into embryonic rat ventricles to determine whether rHMGB1 can induce epileptogenic CD with pathophysiological characteristics similar to those of human CD. Compared with controls and 0.1 μg rHMGB1-treated rats, the cortical organization was severely disrupted in the 0...

Wilder Penfield (1891-1976) is widely regarded as a dominant figure in 20th century neurobiology for his singular contributions to the structure-function relationship of the brain, his discovery of the language function of the supplementary motor area, the discovery (with Herbert Jasper and Brenda Milner) of the anatomy of recall, and his pioneering work in the surgical treatment of focal epilepsy. But another of his significant discoveries has escaped notice: the recognition that focal microgyria can generate epileptic seizures, and that these can be treated surgically...

Developmental cortical malformations (DCM) are one of the main causes of refractory epilepsy. Many are the mechanisms underlying the hyperexcitability in DCM, including the important contribution of N-methyl-D-aspartate receptors (NMDAR). NMDAR blockers are shown to abolish seizures and epileptiform activity. Memantine, a NMDAR antagonist used to treat Alzheimeŕs disease, has been recently investigated as a possible treatment for other neurological disorders. However, the effects on preventing or diminishing seizures are controversial...

Introduction: Splenogonadal fusion is a rare congenital anomaly, defined by the presence of ectopic splenic tissue caused by an abnormal connection between the spleen and the gonad or mesonephrotic derivatives during the embryonic period. Materials and Methods: By reporting an observational case and performing a review of the literature according to the CARE guidelines (using the PubMed database and guidelines from urology, general surgery, and pediatric learned societies), we present the embryological genesis of the splenogonadal fusion, the associated anatomical anomalies, and the diagnostic procedure...

We analyzed our two new cases of infantile-onset epilepsy with developmental delay with de novo variant in TUBB2A and review the related literatures. Our two probands were both girls with infantile-onset epilepsy and global developmental delay. Case 1 had a novel de novo heterozygous missense variant: c.728C>T [p.Pro243Leu] (NM_001069.2). Her brain magnetic resonance imaging (MRI) showed nonspecific white matter myelination delay and slightly enlarged anterior horn of lateral ventricle. Her epilepsy had been controlled by TPM monotherapy...

Intractable epilepsy is commonly associated with developmental cortical malformations. Using the rodent freeze lesion model, we have sought the underlying circuit abnormalities contributing to the epileptiform activity that occurs in association with the structural pathology of four-layered microgyria. We showed previously that within the epileptogenic paramicrogyral region (PMR) surrounding the malformation, non-fast-spiking neurons commonly containing somatostatin (SSt) exhibit alterations, including having a greater maximum firing rate...

BACKGROUND: The direct oral anticoagulant (DOAC) rivaroxaban, an oral Factor Xa inhibitor, is increasingly used as an alternative to vitamin-K-antagonists (VKAs). Absorption and elimination of DOACs are dependent on the permeability glycoprotein (P-gp) efflux transporter protein system, and DOACs are substrates of the hepatic cytochrome P 450 3A4 (CYP3A4) enzymes. Therefore, drug-interactions may occur when DOACs are administered with drugs affecting the activity of P-gp or CYP3A4 systems...

Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5-75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels...

BACKGROUND: Corpus callosotomy is a palliative procedure especially for Lennox-Gastaut semiology without localization with drop attacks. OBJECTIVE: To describe endoscopic-assisted complete corpus callosotomy combined with anterior, hippocampal, and posterior commissurotomy. METHODS: Patients with drug refractory epilepsy having drop attacks as the predominant seizure type, bilateral abnormalities on imaging, and moderate to severe mental retardation were included...

BACKGROUND: The use of minimally invasive endoscopic surgery is fast emerging in many subspecialties of neurosurgery as an effective alternative to the open procedures. OBJECTIVE: The author describe a novel technique of using an endoscope for performing a corpus callosotomy and hemispherotomy. A description of endoscopic disconnection for a hypothalamic hamartoma (HH) and a review of the literature is also presented. MATERIALS AND METHODS: Thirty four patients underwent endoscopic procedures between January 2010 and March 2015...

Pharmaco-resistant epilepsies, and also some neuropsychiatric disorders, are often associated with malformations in hippocampal and neocortical structures. The mechanisms leading to these cortical malformations causing an imbalance between the excitatory and inhibitory system are largely unknown. Animal models using chemical or physical manipulations reproduce different human pathologies by interfering with cell generation and neuronal migration. The model of in utero injection of methylazoxymethanol (MAM) acetate mimics periventricular nodular heterotopia...

A variety of major developmental cortical malformations are closely associated with clinically intractable epilepsy. Pathophysiological aspects of one such disorder, human polymicrogyria, can be modeled by making neocortical freeze lesions (FL) in neonatal rodents, resulting in the formation of microgyri. Previous studies showed enhanced excitatory and inhibitory synaptic transmission and connectivity in cortical layer V pyramidal neurons in the paramicrogyral cortex. In young adult transgenic mice that express green fluorescent protein (GFP) specifically in parvalbumin positive fast-spiking (FS) interneurons, we used laser scanning photostimulation (LSPS) of caged glutamate to map excitatory and inhibitory synaptic connectivity onto FS interneurons in layer V of paramicrogyral cortex in control and FL groups...

SESSION TITLE: Pediatric PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: Neonatal respiratory distress is any difficulty in breathing during the first 28 days of life. Clinical manifestations include a wide range depending on gestational age and its triggering causes. METHODS: we present the case of a newborn who manifested respiratory disorders due to intermittent intracranial hypertension, a case involving difficulties in establishing an accurate diagnosis and prognosis...

Despite early disruption of developmental processes, hyperexcitability is often delayed after the induction of cortical malformations. In the freeze-lesion model of microgyria, interictal activity cannot be evoked in vitro until postnatal day (P)12, despite the increased excitatory afferent input to the epileptogenic region by P10. In order to determine the most critical time period for assessment of epileptogenic mechanisms, here we have used low-Mg(2+) aCSF as a second hit after the neonatal freeze lesion to examine whether there is an increased susceptibility prior to the overt expression of epileptiform activity...