Exploring the Experiences of Self-Determination of Individuals with Mild Intellectual Disabilities and Epilepsy

Abstract found on PubMed

Background: While epilepsy can decrease quality of life and self-determination in individuals without intellectual disabilities, the impact of epilepsy on experienced self-determination in people with intellectual disabilities remains unclear.

Method: We conducted semi-structured interviews with six adults (four men, two women) aged 30-61 with mild intellectual disabilities and drug-resistant epilepsy to investigate their experiences of self-determination. The data were analysed using Interpretative Phenomenological Analysis.

Results: Three main themes were identified: (A) I am a competent person with epilepsy; (B) My social needs: being accepted as I am and stability in relationships; and (C) Being in control.

Conclusions: In this study, the impact of epilepsy on experienced self-determination of people with mild intellectual disabilities outweighs the influence of intellectual disabilities. Identity formation, friendships with peers, and autonomy support in risk management are identified as important topics in supporting this group.

Identification of Drug Resistance in a Validated Cohort of Incident Epilepsy Patients in the Danish National Patient Register

Abstract found on PubMed


Objective: The main purposes of this study were to validate the epilepsy diagnosis in incident epilepsy cases in the Danish National Patient Registry (DNPR), containing information on nearly 9,000,000 individuals; and identify persons in the validated cohort who fulfilled the International League Against Epilepsy (ILAE) criteria for drug resistant epilepsy (DRE).


Methods: We reviewed a random sample of medical records from all individuals registered with a first diagnosis of epilepsy (ICD-10: G40) or seizures (ICD-10: G41, R56, or F445) in Central Denmark Region from 2010-2019. In persons with a validated incident epilepsy diagnosis, we determined the proportion with DRE at the latest contact. We performed logistic regression analyses to identify clinical factors that correlated with risk of DRE.


Results: Of 20,723 persons with a first diagnosis of epilepsy (n=11,812) or seizures (n=8,911), we reviewed the medical records of n=1,067 with incident epilepsy and n=610 with incident seizures. Among those with a register diagnosis of epilepsy, the diagnosis was confirmed in 838 cases (45% females, mean age at onset = 42.4 years), providing a positive predictive value (PPV) of 79% (95% CI: 76-81%). The PPV of focal epilepsy was 86% (95% CI: 82-89%), and the PPV of generalized epilepsy was 71% (95% CI: 61-80%). Of 740 patients with confirmed incident epilepsy and ? 1 year of follow-up, 103 (14%) fulfilled the definition of DRE, 476 (64%) were drug responsive, and 161 (22%) had undefined responsiveness. In multivariable logistic regression analysis, early age at epilepsy onset, cognitive impairment, and a history of status epilepticus were associated with DRE.


Significance: In the Danish National Patient Registry, we found a positive predictive value of the epilepsy diagnosis of 79%. Among persons with confirmed epilepsy, 14% fulfilled ILAE criteria of drug resistant epilepsy. Early age at epilepsy onset, cognitive impairment, and a history of status epilepticus were independently associated with drug resistance.

Single Target, Multiple Possibilities: MicroRNA Holds Promise for Epilepsy Treatment 

Article published by News Medical Life Sciences

Featuring the work of former CURE Epilepsy grantee Dr. David Henshall


In a recent study published in the PNAS Journal, a group of researchers investigated the role of micro-ribonucleic acid (miRNA) miR-335-5p as a potential therapeutic target for epilepsy by regulating neuronal excitability through the modulation of voltage-gated sodium channels (VGSCs). 


Epilepsy affects millions of individuals worldwide, and current antiseizure medications (ASMs) target VGSCs. However, some forms of epilepsy, like Dravet syndrome, are treatment-resistant due to loss of VGSC function. To develop better therapies, researchers are exploring miRNAs that regulate gene expression. 


MiRNAs can control VGSC expression, making them attractive therapeutic targets. Triangulating miRNA datasets and studying miRNA alterations caused by effective ASMs could reveal potential therapeutic miRNAs for epilepsy. 


Cannabidiol (CBD), approved for treatment-resistant epilepsy, is an example of an effective ASM with an unknown mechanism of action, arising the need for further investigation. 


The study focused on investigating epilepsy using animal models. Animals were kept in controlled conditions with a 12-hour light-dark cycle, proper temperature, and humidity, with food and water freely available. 


The researchers used two epilepsy models: the PPS model of temporal lobe epilepsy (TLE) in rats and the pentylenetetrazol (PTZ) model in mice. For the perforant path stimulation (PPS) model, electrodes were implanted, and seizures were induced using paired-pulse stimuli. For the PTZ model, mice received a convulsant dose of PTZ to trigger seizures. 


Various treatments were administered to investigate their effects on epilepsy. They modulated miRNA through antisense oligonucleotide “antimir” injections and viral particles expressing specific miRNAs. Additionally, they administered CBD, a compound derived from cannabis, to study its potential effects on epilepsy. 


The researchers analyzed miRNA and mRNA expression in the brain tissues of the animals. They also identified miRNA-target interactions and performed pathway enrichment analyses to understand the molecular mechanisms involved in epilepsy. 

Epilepsy Research News: July 2023

This issue of Epilepsy Research News includes summaries of articles on:


Beating Seizures by Jamming the Cellular Circuitry

Researchers have shown for the first time how the commonly prescribed antiseizure and pain medication gabapentin (Neurontin®) acts to affect cell function, potentially opening the door to new, more effective treatments for diseases like epilepsy. This research shows how gabapentin interacts with proteins called voltage-gated calcium channels, which are critical to the function of the brain. Voltage-gated calcium channels control the flow of calcium in and out of the cell and regulate brain excitation. By utilizing a technique called cryo-electron microscopy, the researchers confirmed the site where gabapentin binds to the channel to affect its function. The researchers also discovered that gabapentin interferes with the actions of a protein known as EMC. This interference could inhibit the actions of the ion channel, possibly decreasing the amount of calcium that gets into brain cells, in turn reducing brain activity and seizures. The study authors noted that by showing how gabapentin binds to calcium channels, there may be the opportunity to design a new generation of therapies.

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Identifying Seizures that Occur While Driving, Before Epilepsy Diagnosis

Five percent of people with focal epilepsy had a seizure while driving prior to being diagnosed with epilepsy, according to a new study. Researchers looked at clinical descriptions from study participants’ seizure diaries and medical records to classify types of seizures, seizure occurrence, and information about seizures while driving. They found 23 out of 447 participants, or 5% of participants, experienced one or more seizures while driving, for a total of 32 seizures while driving prior to diagnosis. Of these 23 people, seven people, or 30%, had more than one seizure while driving prior to diagnosis. The consequences of these seizures while driving included 19 motor vehicle accidents and 11 hospitalizations for injuries ranging from a tongue bite and a dislocated thumb to a near drowning. “From our study, we estimate nearly 6,500 people per year may experience pre-diagnosis seizures while driving in the United States alone, leading to nearly 4,000 possible motor vehicle accidents and over 2,200 hospitalizations,” stated the study authors. “Much of this may be preventable by earlier diagnosis.”

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Understanding Autism and Epilepsy

A study has increased our understanding and identified a possible treatment target for people with autism and epilepsy due to a lack of the ANK2 gene. This study showed that mice lacking the ANK2 gene in certain brain cells that contribute to brain excitation have autism spectrum disorder-like behaviors and juvenile seizure-related death. The researchers identified increased excitability of cortical neurons in these ANK2-deficient mice. These changes were accompanied by decreases in the function of a particular type of potassium channel in the brain. When the researchers used retigabine, an antiseizure medication, to enhance potassium channel function in the mice, they were able to restore neuronal excitability to normal levels and reduce seizure-induced deaths, suggesting that activation of potassium channels may be effective in treating epilepsy caused by ANK2 defects.

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Brain Inflammation and Drug-Resistant Epilepsy

New research investigated how inflammation contributes to the development of drug-resistant epilepsy. To study this, researchers examined brain tissue obtained during resective epileptic brain surgery. The researchers used a genetic sequencing technique called cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), which gathers information on RNA and surface proteins in single cells. They uncovered a proinflammatory microenvironment in drug-resistant epilepsy lesions that resembles brain autoimmune diseases, such as multiple sclerosis. They found that the drug-resistant epilepsy microenvironment includes activated microglia and other proinflammatory immune cells, and they captured cellular interactions with additional molecular analyses. The researchers noted that these results provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.

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Reducing Seizures After Brain Tumor Treatment

According to a recent study, inhibiting a mutated gene can reduce seizure activity in adult-type diffuse gliomas, which are the most common type of malignant tumors arising in the central nervous system and which commonly cause seizures that are difficult to control with medication. Previous research has shown that gliomas with mutations in the IDH (IDHMut) gene are more likely to cause seizures because the mutated gene produces D-2-hydroxyglutarate (D2HG), a chemical which excites neurons and leads to an increase in seizure activity. In the recent study, scientists found that AG881, a newly discovered small molecule inhibitor that can cross the blood-brain barrier, can reduce seizure activity in mice with IDHmut gliomas by more than 50 percent. IDHmut inhibition also inhibited the production of D2HG by IDHmut glioma cells. The researchers stated that these findings provide a potential basis for treating seizures in human glioma patients.

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