Clinical considerations in transitioning patients with epilepsy from clonazepam to clobazam: a case series.

IntroductionIn treating refractory epilepsy, many clinicians are interested in methods used to transition patients receiving clonazepam to clobazam to maintain or increase seizure control, improve tolerability of patients' overall drug therapy regimens, and to enhance quality of life for patients and their families. However, no published guidelines assist clinicians in successfully accomplishing this change safely.Case presentationsThe following three case reports provide insight into the transition from clonazepam to clobazam. First, an 8-year-old Caucasian boy with cryptogenic Lennox-Gastaut syndrome beginning at 3.5 years of age, who was experiencing multiple daily generalized tonic-clonic, absence, myoclonic, and tonic seizures at presentation. Second, a 25-year-old, left-handed, White Hispanic man with moderate mental retardation and medically refractory seizures that he began experiencing at 1 year of age, secondary to tuberous sclerosis. When first presented to an epilepsy center, he had been receiving levetiracetam, valproate, and clonazepam, but reported having ongoing and frequent seizures. Third, a 69-year-old Korean woman who had been healthy until she had a stroke in 2009 with subsequent right hemiparesis; as a result, she became less physically and socially active, and had her first convulsive seizure approximately 4 months after the stroke.ConclusionsFrom these cases, we observe that a rough estimate of final clobazam dosage for each mg of clonazepam under substitution is likely to be at least 10-fold, probably closer to 15-fold for many patients, and as high as 20-fold for a few. Consideration and discussion of the pharmacokinetic, pharmacologic, and clinical properties of 1,4- and 1,5-benzodiazepine action provide a rationale on why and how these transitions were successful

A developmental and genetic classification for malformations of cortical development: update 2012.

Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development

Epilepsy-related cytoarchitectonic abnormalities along white matter pathways

Objective Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. Unfortunately, the clinical outcomes of TLE cannot be determined based only on current diagnostic modalities. A better understanding of white matter (WM) connectivity changes in TLE may aid the identification of network abnormalities associated with TLE and the phenotypic characterisation of the disease. Methods We implemented a novel approach for characterising microstructural changes along WM pathways using diffusional kurtosis imaging (DKI). Along-the-tract measures were compared for 32 subjects with left TLE and 36 age-matched and gender-matched controls along the left and right fimbria-fornix (FF), parahippocampal WM bundle (PWMB), arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF) and cingulum bundle (CB). Limbic pathways were investigated in relation to seizure burden and control with antiepileptic drugs. Results By evaluating measures along each tract, it was possible to identify abnormalities localised to specific tract subregions. Compared with healthy controls, subjects with TLE demonstrated pathological changes in circumscribed regions of the FF, PWMB, UF, AF and ILF. Several of these abnormalities were detected only by kurtosis-based and not by diffusivity-based measures. Structural WM changes correlated with seizure burden in the bilateral PWMB and cingulum. Conclusions DKI improves the characterisation of network abnormalities associated with TLE by revealing connectivity abnormalities that are not disclosed by other modalities. Since TLE is a neuronal network disorder, DKI may be well suited to fully assess structural network abnormalities related to epilepsy and thus serve as a tool for phenotypic characterisation of epilepsy

Multimodal neuroimaging in presurgical evaluation of childhood epilepsy

In pre-surgical evaluation of pediatric epilepsy, the combined use of multiple imaging modalities for precise localization of the epileptogenic focus is a worthwhile endeavor. Advanced neuroimaging by high field Magnetic resonance imaging (MRI), diffusion tensor images, and MR spectroscopy have the potential to identify subtle lesions. 18F-FDG positron emission tomography and single photon emission tomography provide visualization of metabolic alterations of the brain in the ictal and interictal states. These techniques may have localizing value for patients which exhibit normal MRI scans. Functional MRI is helpful for non-invasively identifying areas of eloquent cortex. These advances are improving our ability to noninvasively detect epileptogenic foci which have gone undetected in the past and whose accurate localization is crucial for a favorable outcome following surgical resection

Dissociable contributions of the prefrontal cortex in group-based cooperation

© The Author(s) (2018). Published by Oxford University Press. The success of our political institutions, environmental stewardship and evolutionary fitness all hinge on our ability to prioritize collective-interest over self-interest. Despite considerable interest in the neuro-cognitive processes that underlie group cooperation, the evidence to date is inconsistent. Several papers support models of prosocial restraint, while more recent work supports models of prosocial intuition.We evaluate these competing models using a sample of lesion patients with damage to brain regions previously implicated in intuition and deliberation. Compared to matched control participants (brain damaged and healthy controls), we found that patients with dorsolateral prefrontal cortex (dlPFC) damage were less likely to cooperate in a modified public goods game, whereas patients with ventromedial prefrontal cortex (vmPFC) damage were more likely to cooperate. In contrast, we observed no association between cooperation and amygdala damage relative to controls. These findings suggest that the dlPFC, rather than the vmPFC or amygdala, plays a necessary role in groupbased cooperation. These findings suggest cooperation does not solely rely on intuitive processes. Implications for models of group cooperation are discussed