Children with myoclonic astatic epilepsy (MAE; Doose syndrome) whose seizures do not respond immediately to standard antiepileptic drugs (AEDs) are at high risk of developing an epileptic encephalopathy with cognitive decline. A classic ketogenic diet (KD) is a highly effective alternative to AEDs. To date, there are only limited data on the effectiveness of the modified Atkins diet (MAD), which is less restrictive and more compatible with daily life. We report findings from a retrospective study on 30 MAE patients treated with MAD.Methods
Four participating centers retrospectively identified all patients with MAE in whom a MAD had been started before June 2015. Seven children were recruited from a cohort included in an open prospective controlled trial. A retrospective review of all available charts was performed in the other patients.Results
Thirty patients (24 boys) were included. Mean age at epilepsy onset was 3.1 years (range 1.5–5.6). MAD was started at a mean age of 4.5 years (range 2.2–9.1) after the children had received an average of six different AEDs (range 2–15). Mean MAD observation time was 18.7 months (range 1.5–61.5). Twenty of 30 patients were still on MAD at the end of study (duration range 1.5–61.5, mean 18.5 months). MAD was stopped without relapse in three patients after sustained seizure freedom for >2 years. For the other seven cases, ineffectiveness (three patients), loss of efficacy (two), or noncompliance (two) led to termination. No severe adverse effects were noted. By the end of the observation period, 25 (83%) of 30 patients experienced a seizure reduction by ≥50% and 14 (47%) of 30 were seizure-free. None of the evaluated factors differed significantly between the groups of seizure-free and non–seizure-free children.Significance
MAD is an effective treatment for MAE. It should be considered as an alternative to AEDs or the more restrictive classic ketogenic diet.
Presurgical language localization with visual naming associated ECoG high- gamma modulation in pediatric drug-resistant epilepsy
This prospective study compared presurgical language localization with visual naming–associated high-γ modulation (HGM) and conventional electrical cortical stimulation (ECS) in children with intracranial electrodes.Methods
Patients with drug-resistant epilepsy who were undergoing intracranial monitoring were included if able to name pictures. Electrocorticography (ECoG) signals were recorded during picture naming (overt and covert) and quiet baseline. For each electrode the likelihood of high-γ (70–116 Hz) power modulation during naming task relative to the baseline was estimated. Electrodes with significant HGM were plotted on a three-dimensional (3D) cortical surface model. Sensitivity, specificity, and accuracy were calculated compared to clinical ECS.Results
Seventeen patients with mean age of 11.3 years (range 4–19) were included. In patients with left hemisphere electrodes (n = 10), HGM during overt naming showed high specificity (0.81, 95% confidence interval [CI] 0.78–0.85), and accuracy (0.71, 95% CI 0.66–0.75, p < 0.001), but modest sensitivity (0.47) when ECS interference with naming (aphasia or paraphasic errors) and/or oral motor function was regarded as the gold standard. Similar results were reproduced by comparing covert naming-associated HGM with ECS naming sites. With right hemisphere electrodes (n = 7), no ECS-naming deficits were seen without interference with oral-motor function. HGM mapping showed a high specificity (0.81, 95% CI 0.78–0.84), and accuracy (0.76, 95% CI 0.71–0.81, p = 0.006), but modest sensitivity (0.44) compared to ECS interference with oral-motor function. Naming-associated ECoG HGM was consistently observed over Broca's area (left posterior inferior-frontal gyrus), bilateral oral/facial motor cortex, and sometimes over the temporal pole.Significance
This study supports the use of ECoG HGM mapping in children in whom adverse events preclude ECS, or as a screening method to prioritize electrodes for ECS testing.
During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAARs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAARs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAARs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE. High doses of diazepam failed to stop electrographic SE, showing that benzodiazepine pharmacoresistance had developed. The diazepam-ketamine-valproate combination was far more effective in stopping SE than triple-dose monotherapy using the same individual drugs. Isobolograms showed that this drug combination's therapeutic actions were synergistic, with positive cooperativity between drugs, whereas drug toxicity was simply additive, without positive or negative cooperativity. As a result, the therapeutic index was improved by this drug combination compared to monotherapy. These results suggest that synergistic drug combinations that target receptor changes can control benzodiazepine-refractory SE.
Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy
Brain hypothermia controls epileptic discharge and reduces extracellular concentrations of glutamate (Glu), an excitatory neurotransmitter. We aimed to determine the effects of focal brain cooling (FBC) on levels of γ-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. The relationship between Glu or GABA concentrations and the severity of epileptic symptoms was also analyzed.Methods
Patients with intractable epilepsy underwent FBC at lesionectomized (n = 11) or hippocampectomized (n = 8) regions at 15°C for 30 min using custom-made cooling devices. Concentrations of Glu (n = 18) and GABA (n = 12) were measured in extracellular fluid obtained through microdialysis using high-performance liquid chromatography (HPLC). The reduction rate of neurotransmitter levels and its relationship with electrocorticography (ECoG) signal changes in response to FBC were measured.Results
We found no relationship between the concentrations of Glu or GABA and seizure severity. There was a significant decrease in the concentration of Glu to 66.3% of control levels during the cooling period (p = 0.001). This rate of reduction correlated with ECoG power (r2 = 0.68). Cortical and hippocampal GABA levels significantly (p = 0.02) and nonsignificantly decreased to 47.7% and 32.4% of control levels, respectively. However, the rate of this reduction did not correlate with ECoG (r2 = 0.11).Significance
Although the decrease in hippocampal GABA levels was not significant due to wide variations in its concentration, the levels of cortical GABA and Glu were decreased following FBC. FBC suppresses epileptic discharge and the release of both excitatory and inhibitory neurotransmitters. The reduction in Glu levels further contributes to the reduction in epileptic discharge. However, the reduction in the levels of GABA has no impact on ECoG.
This study aimed to determine the role C5aR1 plays in mediating immune responses acutely after pilocarpine-induced status epilepticus (SE), specifically those of brain-infiltrating leukocytes. Three days following pilocarpine SE, we determined by flow cytometry the brain immune cell phenotypes and measured key proinflammatory and antiinflammatory cytokine expression by infiltrating leukocytes and microglia in C5aR1-deficient and wild-type mice. Absence of C5aR1 reduced by 47% the numbers of Ly6G+ neutrophils in the brains of No-SE mice and decreased neutrophil entry after SE to levels found in wild-type brains that did not undergo SE (No-SE). Moreover, C5aR1-deficient mice showed increased interleukin (IL)-4 expression in infiltrating leukocytes, but not in microglia. Increases in IL-4 expression in infiltrating leukocytes coupled with decreased neutrophil invasion in C5aR1-deficient mice after SE is likely to contribute to the reduced neuronal loss previously found in these mice compared to their wild-type littermates. Although other SE models need to be investigated to substantiate our findings, this study provides further evidence that C5aR1 is an inflammatory mediator and may play a role in epileptogenesis.
Researchers in the U.S. developed a new scoring system that can help doctors prioritise which patients should receive long-term video-EEG monitoring to evaluate whether staring spells are epileptic seizures.
Staring spells are episodes where children appear to stare into space and do not respond if spoken to or touched. These spells are the main symptom in patients with absence seizures and account for 10-17% of childhood-onset epilepsy. They are a common reason for a child to be referred to neurology services for overnight epilepsy monitoring. However overnight monitoring is time-consuming, expensive, and can cause distress to both children and their families.
Researchers led by Dr Jack Stevens at Nationwide Children’s Hospital and Ohio State University in Columbus performed a four-year chart review of all children who received long-term monitoring in one centre to characterise staring.
“The two goals were a) assess how often [a long-term monitoring] admission captured a staring spell that was diagnosed as a seizure and b) determine if any baseline factors predicted this particular positive result,” the researchers wrote.
Long-term monitoring was able to capture only 29 staring spells in all 276 patients who were referred for monitoring, and diagnose it as seizures. This is just a little more than 10% of all cases. Importantly, the researchers were able to predict whether or not staring spells would be diagnosed as seizures before the long-term monitoring. This was thanks to the scoring system they developed based on the following criteria: most recent EEG results, parental reports of the duration, frequency, and breakability of the staring events. Factors such as the mental status of the children following seizures, the presence or absence of automatisms, previous neurological and psychiatric diagnoses and medications, and family history of epilepsy were also considered.
The score of a child was calculated as follows: − 3 points if the previous EEG was normal, − 1 point if the child took any drugs for a psychiatric condition, + 1 point if the child took an antiepileptic drug (AED) for epilepsy, and + 1 point if the spells lasted less than one minute. If the total score was zero or less, staring spells were rarely diagnosed (in less than 5% of cases) during long-term monitoring.
“Our scoring system shows how consideration of prior EEG findings, medication history, and staring spell duration can help prioritise patients for [long-term monitoring admission] to evaluate if staring spells are epileptic seizures,” the authors concluded.
They added that the scoring system can only be an addition to clinical judgment on when children should be referred for long-term monitoring, and cannot replace it. It is important to note that factors predicting the outcome of the prediction may be different from one patient group to the other and across different centres. Therefore a comprehensive approach should be adopted when evaluating patients before admission to long-term monitoring. Further research in more than one centre is needed to evaluate the validity of the scoring system proposed in the present study.
The study was published in the journal Epilepsy and Behavior.
Author: Dr Özge Özkaya
To compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)–resistant status epilepticus (SE).Methods
Patients with LOR-resistant SE were randomized to intravenous LCM 400 mg at a rate of 60 mg/kg/min or SVA 30 mg/kg at a rate of 100 mg/min. The SE severity score (STESS), duration of SE and its etiology, and magnetic resonance imaging (MRI) findings were noted. Primary outcome was seizure cessation for 1 h, and secondary outcomes were 24 h seizure remission, in hospital death and severe adverse events (SAEs).Results
Sixty-six patients were included, and their median age was 40 (range 18–90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs. 69.7%; p = 0.79). Twenty-four hour seizure freedom was higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%), but this difference was not statistically significant. Death (10 vs. 12) and composite side effects (4 vs. 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (one patient), and SVA with liver dysfunction (six patients).Significance
In LOR-resistant SE patients, both LCM and SVA have comparable efficacy and safety. SVA resulted in slightly better 24 h seizure remission.
Some Forms of Epilepsy Could Be Autoimmune in Nature, Suggests Study Linking Parasitic Infection and Nodding Syndrome
Some forms of epilepsy such as nodding syndrome, could be autoimmune in nature according to a study published in the journal Science Translational Medicine.
“The findings … suggest that therapies targeting the immune system may be effective treatments against this disorder and possibly other forms of epilepsy,” said the senior author of the study Dr Avindra Nath who is also the clinical director of the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), in a press release.
Nodding syndrome is a form of childhood epilepsy seen in certain areas of East Africa. It is characterised by head nodding, seizures, severe impairment in thinking ability and restricted growth.
The cause of the condition remained a mystery until now. The present study suggests that the condition might be caused by an immune response triggered by a parasitic worm called Onchocerca volvulus, which then attacks the body’s own nervous system.
For the study, Dr Nath and colleagues compared blood samples from children with nodding syndrome and children without, who all lived in the same village in Uganda. They found antibodies in the blood of children with nodding syndrome, which recognised proteins from the parasitic worm as well as a protein called leiomodin-1. Leiomodin-1 antibodies were also present in the fluid covering the brain and the spinal chord of the children with nodding syndrome.
Leiomodin-1 is highly expressed in human nerve cells grown in the laboratory and is also found in certain areas of the mouse brain. These areas of the brains are the counterparts of the areas in the children’s brain that were affected by nodding syndrome.
When the researchers treated normal nerve cells grown in the laboratory with serum from nodding syndrome patients, they saw that the nerve cells died suggesting that the serum of the children contains a factor that was toxic for nerve cells. In order to test whether this factor could be leiomodin-1 antibodies, the researchers treated the nerve cells with the antibody directly and obtained the same results: the nerve cells died. And when they treated the nerve cells with serum from which the leiomodin-1 antibodies had been removed, the nerve cells survived
The researchers concluded that nodding syndrome may be an auto-immune epileptic disorders triggered by infection with a parasitic worm. The antibodies that the body produces to fight off the parasite wrongly recognise a protein found in the nerve cells and attacks them.
According to the authors, more research is needed to better understand the role of leiomodin-1 in healthy people and people with epilepsy.
Author: Dr Özge Özkaya
What is Nodding Syndrome? This information is from the WHO website
Nodding syndrome (NS) is a neurological condition with unknown etiology. It was first documented in the United Republic of Tanzania (URT) in the 1960s, then later in the Republic of South Sudan in the 1990s and in northern Uganda in 2007. Typically, NS affects children between the ages of 5 and 15 years old, causing progressive cognitive dysfunction, neurological deterioration, stunted growth and a characteristic nodding of the head. Despite numerous and extensive investigations in all three countries, very little is known about the cause of the disease.
To date, Nodding Syndrome is known to occur in the southern region of the United Republic of Tanzania (URT) (Mahenge mountains, Ulanga District), South Sudan (Western Equatoria State, Eastern Equatoria State, Central Equatoria State, and Lakes State) and northern Uganda (Pader, Kitgum and Lamwo districts, with new cases starting to present in Gulu, Amuru, Oyam and Lira districts).
Jilek et al (1962) first described several children with attacks of “head nodding” in Mahenge, a region in URT. The current burden of NS in URT is unknown but observations during case control studies in 2005 and 2009 in the Mahenge region do not suggest a notable increase in the number of cases relative to those detected in the late 1950s and early 1960s.
Samaritan Purse, a local NGO, described observations of head nodding among several children in southern Sudan in the Lui and Amadi villages of East Mundri County in the mid-1990s. A physician from Samaritan Purse reported the outbreak to WHO in 1997. The 2001-2002 investigations by WHO and partners estimated the prevalence of NS at 4.6% among a small population in Western Equatoria State, which appeared to have the highest burden of the illness. By 2003, an estimated 300 cases had been reported from this region. The Ministry of Health of South Sudan estimates the current burden of NS at between six and seven thousand cases, but no systematic large-scale prevalence study has been conducted. The Mundri region in the northeast of Western Equatoria is the presumed epicentre for the disease.
In 2008 and 2009, an illness consistent with NS was reported from Kitgum and Pader Districts in northern Uganda. As of February 2012, Uganda has reported over 3 000 cases of NS from the three districts of Kitgum, Lamwo and Pader. A community survey is underway in Uganda to determine the real burden of NS in the affected districts. Kaiser et al (2009) referred to a phenomenon of head nodding observed in the Kabarole District in Western Uganda as possibly constituting a feature of an epileptic syndrome caused by Onchocerca volvulus (O. volvulus).
The prevalence of both onchocerciasis and epilepsy in the areas affected by NS is high. The affected populations are impoverished and experience regular and prolonged periods of severe food shortages. In South Sudan and in northern Uganda, affected populations have a history of internal displacement and living in internally displaced persons (IDPs) camps.
Familial clustering has been observed in some families with NS patients, with more than one sibling with NS and/or siblings or relatives with other forms of epilepsy.
The age of onset in the vast majority of cases ranges between 5 and 15 years old, but cases have been reported in children as young as 2 years old and in adults up to 32 years old. There is no observed significant difference in the proportion of males to females among the affected, nor is there an observed seasonal variation.
Characterization of focal cortical dysplasia with balloon cells by layer-specific markers: Evidence for differential vulnerability of interneurons
Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b).Methods
Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer-specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region.Results
We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer-specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32-positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin- and Calretinin-positive interneurons in layers II and III were not different from controls, whereas Parvalbumin-expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4-positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b.Significance
The application of a broad panel of markers defining layer-specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin-positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition.
The formation of a specific type of brain cell during the progression of brain tumours is also linked to the development of epileptic seizures, according to a study conducted on mice and published in the leading scientific journal Nature Neuroscience. This knowledge can help scientists better understand how brain tumours cause epilepsy and potentially help them develop new approaches that can prevent or even treat the condition.
“We do not understand exactly how malignant cells cause seizures, or why seizures persist after tumor surgery,” said one of the senior authors of the study, Dr Jeffrey Noebels, professor of neurology, neuroscience, and molecular and human genetics at Baylor College of Medicine in Texas, in a press release.
Dr Noebels and colleagues were studying normal brain cells and in particular a type of brain cell called astrocytes. These are start-shaped cells that fulfil a broad range of roles including biochemically supporting other cell types in the brain cells, providing nutrients to the brain, and repairing the nervous tissue following injury. They are also crucial for the formation of synapses or connections between neurons.
Astrocytes are often considered to be just one type of cell, but researchers identified five distinct sub-types of astrocytes based on the molecules found on their surface. They thought that the different sub-types may be responsible of fulfilling different roles in the brain.
They then looked at the brain of a mouse model of glioma, or brain cancer. They saw that as the tumor grew, neighbouring cells became more excitable, and eventually the mice started to have seizures. This correlated with the emergence of one of the five sub-populations of astrocytes. Strikingly, this sub-population expressed a significant number of genes linked to epilepsy.
Dr Benjamin Deneen, associate professor at Baylor explained: “[A]s the tumor evolves, different subpopulations of astrocyte-like cells develop within the tumor and execute distinct functions that are related to two important tumor characteristics, synaptic imbalance that can lead to seizures, and tumor migration that can lead to tumor invasion of other tissues”.
Dr Noebels added he is excited that for the first time, it is possible to study the earliest effects of tumours on the brain before seizures even start. “These studies would be a major advance in patient care, allowing clinicians to bypass precious months spent searching for effective therapy to stop seizures. Because seizures themselves damage brain tissue, timely effective therapy is of the essence,” he concluded.
Author: Dr Özge Özkaya
What is an Astrocyte
The video below from the Khan Academy gives a good and accessible overview of astrocytes.
Overexpression of pregnane X and glucocorticoid receptors and the regulation of cytochrome P450 in human epileptic brain endothelial cells
Recent evidence suggests a metabolic contribution of cytochrome P450 enzymes (CYPs) to the drug-resistant phenotype in human epilepsy. However, the upstream molecular regulators of CYP in the epileptic brain remain understudied. We therefore investigated the expression and function of pregnane xenobiotic (PXR) and glucocorticoid (GR) nuclear receptors in endothelial cells established from post-epilepsy surgery brain samples.Methods
PXR/GR localization was evaluated by immunohistochemistry in specimens from subjects who underwent temporal lobe resections to relieve drug-resistant seizures. We used primary cultures of endothelial cells obtained from epileptic brain tissues (EPI-ECs; n = 8), commercially available human brain microvascular endothelial cells (HBMECs; n = 8), and human hepatocytes (n = 3). PXR/GR messenger RNA (mRNA) levels in brain ECs was initially determined by complementary DNA (cDNA) microarrays. The expression of PXR/GR proteins was quantified by Western blot. PXR and GR silencing was performed in EPI-ECs (n = 4), and the impact on downstream CYP expression was determined.Results
PXR/GR expression was detected by immunofluorescence in ECs and neurons in the human temporal lobe samples analyzed. Elevated mRNA and protein levels of PXR and GR were found in EPI-ECs versus control HBMECs. Hepatocytes, used as a positive control, displayed the highest levels of PXR/GR expression. We confirmed expression of PXR/GR in cytoplasmic-nuclear subcellular fractions, with a significant increase of PXR/GR in EPI-ECs versus controls. CYP3A4, CYP2C9, and CYP2E1 were overexpressed in EPI-ECs versus control, whereas CYP2D6 and CYP2C19 were downregulated or absent in EPI-ECs. GR silencing in EPI-ECs led to decreased CYP3A4, CYP2C9, and PXR expression. PXR silencing in EPI-ECs resulted in the specific downregulation of CYP3A4 expression.Significance
Our results indicate increased PXR and GR in primary ECs derived from human epileptic brains. PXR or GR may be responsible for a local drug brain metabolism sustained by abnormal CYP regulation.
Validating the shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) in a sample of children with drug-resistant epilepsy
The aim of this study was to validate the newly developed shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) in a sample of children with drug-resistant epilepsy.Methods
Data came from 136 children enrolled in the Impact of Pediatric Epilepsy Surgery on Health-Related Quality of Life Study (PEPSQOL), a multicenter prospective cohort study. Confirmatory factor analysis was used to assess the higher-order factor structure of the QOLCE-55. Convergent and divergent validity was assessed by correlating subscales of the KIDSCREEN-27 with the QOLCE-55. Measurement equivalence of the QOLCE-55 was evaluated using multiple-group confirmatory factor analysis of children with drug-resistant epilepsy from PEPSQOL versus children with new-onset epilepsy from HERQULES (Health-Related Quality of Life in Children with Epilepsy Study).Results
The higher-order factor structure of the QOLCE-55 demonstrated adequate fit: Comparative Fit Index (CFI) = 0.948; Tucker-Lewis Index (TLI) = 0.946; Root Mean Square of Approximation (RMSEA) = 0.060 (90% confidence interval [CI] 0.054–0.065); Weighted Root Mean Square Residuals (WRMR) = 1.247. Higher-order factor loadings were strong, ranging from λ = 0.74 to 0.81. Internal consistency reliability was excellent (α = 0.97, subscales α > 0.82). QOLCE-55 subscales demonstrated moderate to strong correlations with similar subscales of the KIDSCREEN-27 (ρ = 0.43–0.75) and weak to moderate correlations with dissimilar subscales (ρ = 0.25–0.42). The QOLCE-55 demonstrated partial measurement equivalence at the level of strict invariance – χ2 (2,823) = 3,727.9, CFI = 0.961, TLI = 0.962, RMSEA = 0.049 (0.044, 0.053), WRMR = 1.834.Significance
The findings provide support for the factor structure of the QOLCE-55 and contribute to its robust psychometric profile as a reliable and valid measure. Researchers and health practitioners should consider the QOLCE-55 as a viable option for reducing respondent burden when assessing health-related quality of life in children with epilepsy.
Accuracy of claims-based algorithms for epilepsy research: Revealing the unseen performance of claims-based studies
To evaluate published algorithms for the identification of epilepsy cases in medical claims data using a unique linked dataset with both clinical and claims data.Methods
Using data from a large, regional health delivery system, we identified all patients contributing biologic samples to the health system's Biobank (n = 36K). We identified all subjects with at least one diagnosis potentially consistent with epilepsy, for example, epilepsy, convulsions, syncope, or collapse, between 2014 and 2015, or who were seen at the epilepsy clinic (n = 1,217), plus a random sample of subjects with neither claims nor clinic visits (n = 435); we then performed a medical chart review in a random subsample of 1,377 to assess the epilepsy diagnosis status. Using the chart review as the reference standard, we evaluated the test characteristics of six published algorithms.Results
The best-performing algorithm used diagnostic and prescription drug data (sensitivity = 70%, 95% confidence interval [CI] 66–73%; specificity = 77%, 95% CI 73–81%; and area under the curve [AUC] = 0.73, 95%CI 0.71–0.76) when applied to patients age 18 years or older. Restricting the sample to adults aged 18–64 years resulted in a mild improvement in accuracy (AUC = 0.75,95%CI 0.73–0.78). Adding information about current antiepileptic drug use to the algorithm increased test performance (AUC = 0.78, 95%CI 0.76–0.80). Other algorithms varied in their included data types and performed worse.Significance
Current approaches for identifying patients with epilepsy in insurance claims have important limitations when applied to the general population. Approaches incorporating a range of information, for example, diagnoses, treatments, and site of care/specialty of physician, improve the performance of identification and could be useful in epilepsy studies using large datasets.