Aylin Y. Reid

How accurate is ICD coding for epilepsy

Purpose:  Assess the validity of ICD‐9‐CM and ICD‐10 epilepsy coding from an emergency visit (ER) and a hospital discharge abstract database (DAD).

Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation

Peripheral inflammatory diseases are often associated with behavioral comorbidities including anxiety, depression, and cognitive dysfunction, but the mechanism for these is not well understood. Changes in the neuronal and synaptic functions associated with neuroinflammation may underlie these behavioral abnormalities. We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA- and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor α in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.

Febrile seizures: current views and investigations.

Febrile seizures (FSs) are seizures that occur during fever, usually at the time of a cold or flu, and represent the most common cause of seizures in the pediatric population. Up to 5% of children between the ages of six months and five years-of-age will experience a FS. Clinically these seizures are categorized as benign events with little impact on the growth and development of the child. However, studies have linked the occurrence of FSs to an increased risk of developing adult epileptic disorders. There are many unanswered questions about FSs, such as the mechanism of their generation, the long-term effects of these seizures, and their role in epileptogenesis. Answers are beginning to emerge based on results from animal studies. This review summarizes the current literature on animal models of FSs, mechanisms underlying the seizures, and functional, structural, and molecular changes that may result from them.

Epilepsy is associated with unmet health care needs compared to the general population despite higher health resource utilization—A Canadian population-based study

Purpose:  (1) To determine whether health resource utilization (HRU) and unmet health care needs differ for individuals with epilepsy compared to the general population or to those with another chronic condition (asthma, diabetes, migraine); and (2) to assess the association among epilepsy status, sociodemographic variables and HRU.

Increased excitability and molecular changes in adult rats after a febrile seizure

Both early life inflammation and prolonged febrile seizures have been associated with increased excitation in the adult brain. We hypothesized this may be due in part to changes in the cation‐chloride cotransporter system. Rat pups received saline or lipopolysaccharide/kainic acid (LPS/KA) resulting in inflammation, followed by a behavioral febrile seizure (FS) in approximately 50% of rats. Adult animals from the saline, inflammation, or inflammation + FS groups underwent the following: (1) in vitro electrophysiologic studies; (2) Western blotting or polymerase chain reaction; or (3) application of the Na‐K‐Cl cotransporter 1 (NKCC1) blocker bumetanide to determine its effect on reversing increased excitability in vitro. The inflammation and inflammation + FS groups demonstrated increased excitability in vitro and increased hippocampal protein expression of NR2B and GABAA α5 receptor subunits and mRNA expression of NKCC1. The inflammation + FS group also had decreased protein expression of GluR2 and GABAA α1 receptor subunits and mRNA and protein expression of KCC2. Bumetanide decreased in vitro 4‐aminopyridine‐induced inter‐ictal activity in the inflammation and inflammation + FS groups. The results demonstrate early‐life inflammation with or without a behavioral FS can lead to long‐lasting molecular changes and increased excitability in the adult rat hippocampus, although some changes are more extensive when inflammation is accompanied by behavioral seizure activity. Bumetanide is effective in reversing increased excitability in vitro, providing evidence for a causal role for cation‐chloride cotransporters and suggesting this drug may prove useful for treating epilepsy that develops after a FS.

A prolonged experimental febrile seizure results in motor map reorganization in adulthood

INTRODUCTION Clinical studies have suggested that children experiencing a febrile seizure (FS) before the age of 1year have persistent deficits, but it is unknown whether these seizures lead to permanent cortical reorganization and alterations in function. A FS on the background of increased genetic seizure susceptibility may also lead to negative long-term consequences. Alterations in neocortical motor map expression provide a measure of neocortical reorganization and have been reported in both adults with frontal lobe epilepsy and following seizure induction in experimental models. The objectives of the present study were to determine whether (1) an infantile FS leads to changes to motor map expression in adulthood; (2) long-term cortical reorganization is a function of the age at FS or genetic seizure susceptibility; and (3) different levels of GABA(A) or glutamate receptor subunits or cation-chloride-co-transporters (CCCs) at the time of FS correlate with alterations to motor map expression. MATERIALS AND METHODS FSs were induced in postnatal day 10 (P10) or P14 Long-Evans (LE) rats or in P14 seizure-prone FAST rats by the administration of the bacterial endotoxin lipopolysaccharide (LPS) and a subconvulsant dose of kainic acid. Ten weeks later intracortical microstimulation was performed to generate motor maps of forelimb movement representations. Sensorimotor neocortex samples were also dissected from naïve P10 FAST and P10 and P14 LE pups for western blotting with antibodies against various GABA(A), NMDA, and AMPA receptor subunits and for CCCs. RESULTS Adult FAST rats had larger motor maps with lower stimulation thresholds after a FS at P14, while adult LE rats had significantly lower map stimulation thresholds but similar sized maps after a FS at P10 compared to controls. There were no differences in neocortical motor map size or stimulation thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had significantly lower levels of the GABA(A) receptor α1 subunit, higher levels of the α2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the P14 LE rats. CONCLUSIONS A single infantile FS can have long-term effects on neocortical reorganization in younger individuals and those with underlying seizure susceptibility. These changes may be related to an increased level of excitability in the neocortex of younger or genetically seizure-prone rats, as suggested by immaturity of their GABAergic and CCC systems. Given the high incidence of FSs in children, it will be important to gain a better understanding of how age and genetic seizure predisposition may contribute to the long-term sequelae of these events.

Pathologic electrographic changes after experimental traumatic brain injury

To investigate possible electroencephalography (EEG) correlates of epileptogenesis after traumatic brain injury (TBI) using the fluid percussion model.

Motor maps, seizures, and behaviour.

Atypically organised motor maps have been described in some people with epilepsy and we have modelled this in rats. Our goal is to more fully understand the mechanisms responsible for seizure-induced functional brain reorganisation and to reverse their effects. Here we present an overview of the relationship between neocortical motor maps, seizures, and interictal behaviour. To begin we summarise the observations of atypical motor maps with epilepsy and in animal models following experimentally induced seizures. Our novel experiments have established that motor map expansion is linked to a functional alteration of motor behaviour. Evidence for some of the putative brain mechanisms responsible for motor map size is discussed. Our successes reversing seizure-induced map expansion by two different methods are also briefly reviewed. Lastly, unanswered questions for possible future experimentation are posed.

The progression of electrophysiologic abnormalities during epileptogenesis after experimental traumatic brain injury.

Posttraumatic epilepsy (PTE) accounts for 20% of acquired epilepsies. Experimental models are important for studying epileptogenesis. We previously reported that repetitive high‐frequency oscillations with spikes (rHFOSs) occur early after lateral fluid percussion injury (FPI) and may be a biomarker for PTE. The objective of this study was to use multiple electrodes in rat hippocampal and neocortical regions to describe the long‐term electroencephalographic and behavioral evolution of rHFOSs and epileptic seizures after traumatic brain injury (TBI).

Surgical management of epilepsy

See related commentary on page [973][1] and at [www.cmaj.ca/lookup/doi/10.1503/cmaj.140427][2] Epilepsy is the second most commonly reported neurologic condition worldwide and affects people of both sexes and of all ages and socioeconomic statuses.[1][3] It is a frequent reason for consultation in