A new study has found that hypertension may double an adult’s risk of developing epilepsy, according to a new study published in Epilepsia.
The study recruited 2986 US participants with an average age of 58 years, 55 new cases of epilepsy were identified during an average follow-up of 19 years. Hypertension, defined as presence of elevated blood pressure or use of antihypertensive medications, was linked to a nearly 2-fold higher risk of epilepsy. After excluding participants with normal blood pressure who were taking antihypertensive medications, hypertension was linked to a 2.44-times higher risk of epilepsy.
“Our study shows that hypertension, a common, modifiable, vascular risk factor, is an independent predictor of epilepsy in older age,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University School of Medicine. “Even though epidemiological studies can only show association and not causation, this observation may help identify subgroups of patients who will benefit from targeted, aggressive hypertension management and encourage performance of dedicated clinical studies that will focus on early interventions to reduce the burden of epilepsy in older age.”
A pioneering new study from Taiwan showed that focused ultrasound, which can be used to non-invasively target circuits in the brain, may benefit some patients with epilepsy who experience seizures which remain unresponsive to standard anti-seizure medications.
The results showed that of six patients with drug-resistant seizures, two patients had fewer seizures within three days of receiving focused ultrasound; however, one patient showed signs of more frequent subclinical seizures (which are not felt by the individual). The findings from the study were published in the journal Epilepsia.
Imaging tests performed after the treatment show that there were no negative effects on the brain. One patient reported a sensation of heat on the scalp during the treatment, and another patient experienced temporary memory impairment that resolved within three weeks.
“Neuromodulation is an alternative treatment for drug-resistant epilepsy. Compared with the present modalities used in neuromodulation for epilepsy, focused ultrasound can access deeper brain regions and focus on the main target of the epileptic network in a relatively less invasive approach,” explained senior author Hsiang-Yu Yu, MD, of Taipei Veterans General Hospital, in Taiwan. “It gives new hope and sheds new light for patients with drug-resistant epilepsy.”
A review published in Developmental Medicine & Child Neurology investigates the knowledge base of cannabis-based medicinal products in paediatric epilepsies, highlighting areas in need of additional research.
Following reports in the media of children with epilepsies apparently deriving benefits from medical marijuana (or cannabis-based medicinal products) accessed abroad, the UK government allowed clinicians to prescribe these products. A previous review found that there was some benefit in certain drug-resistant epilepsies in children.
In the review, the authors also looked at the prescribing environment surrounding these products. They found that the major obstacle to prescribing is a lack of quality evidence for efficacy and safety. The authors stress that unlicensed cannabis-based medicinal products should not circumvent the usual regulatory requirements before being prescribed. They are also concerned that children with epilepsy are at risk of being exploited as a “Trojan horse” for the cannabis industry, with widespread acceptance of medicinal cannabis accelerating the wider legalisation of marijuana and opening up a highly lucrative commercial market.
Researchers have found that neuron connectivity patterns within brain regions can better indicate disease progression and treatment outcomes for people with brain disorders such as epilepsy.
Many brain diseases lead to cell death and the removal of connections within the brain. A team led by Dr Marcus Kaiser from the School of Medicine at the University of Nottingham looked at epilepsy patients undergoing surgery. Their findings were published in Human Brain Mapping.
They found that changes in the local network within brain regions can predict disease progression, and also whether surgery will be successful or not.
The team found that looking at connectivity within regions of the brain, showed superior results compared to only observing fibre tract connectivity between brain regions, which is the current method. Dividing the surface of the brain into 50 000 network nodes of comparable size, each brain region could be studied as a local network with 100-500 nodes. There were distinct changes seen in these local networks in patients suffering from epileptic seizures.
Employing diffusion tensor imaging, a special measurement protocol for MRI scanners, the team of scientists showed that fibres within and between brain regions are removed for patients.
However, they found that connectivity within regions better predicted whether surgical removal of brain tissue was successful in preventing future seizures.
Dr Kaiser, Professor of Neuroinformatics at the University of Nottingham, explained: “When someone has an epileptic seizure, it ‘spreads’ through the brain. We found that local network changes occurred for regions along the main spreading pathways for seizures. Importantly, regions far away from the starting point of the seizure, for example in the opposite brain hemisphere, were involved.
“This indicates that the increased brain activity during seizures leads to changes in a wide range of brain regions. Furthermore, the longer patients suffered, the more regions showed local changes and the more severe were these changes.”
The researchers from the involved universities, along with the company Biomax, evaluated the scans of 33 temporal lobe epilepsy patients and 36 control subjects.
Project partners used the NeuroXM™ knowledge management platform to develop a knowledge model for high-resolution connectivity with more than 50 000 cortical nodes and several millions of connections and corresponding automated processing pipelines accessible through Biomax’s neuroimaging product NICARA™.
Project manager Dr Markus Butz-Ostendorf from Biomax said: “Our software can be easily employed at hospitals and can also be combined with other kinds of data from genetics or from other imaging approaches such as PET, CT, or EEG.”
Professor Yanjiang Wang, who is one of the corresponding authors, and Ms Xue Chen, both from China University of Petroleum (East China), commented: “Local connectivity was not only better in overall predictions but particularly successful in identifying patients where surgery did not lead to any improvement, identifying 95% of such cases compared to 90% when used connectivity between regions”.
Researchers from the Icahn School of Medicine at Mount Sinai Hospital have repurposed a drug to treat depression by using an ion channel that is a completely different mechanism than regular antidepressants.
A study demonstrated that a drug called ezogabine, which opens KCNQ2/3 type of potassium channels in the brain, is linked to significant improvements in depressive symptoms and anhedonia (a lack of ability to feel pleasure) in patients with depression. Anhedonia is a complex, core symptom of depression and is associated with poor outcomes such as increased risk of suicide and reduced responsiveness to antidepressants. Ezogabine is an anticonvulsant for epilepsy treatment; this novel application in treating depression opens up the investigation of the KCNQ2/3 channel as a potential drug target.
“Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients. Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment,” said Professor James Murrough, MD, PhD, at the Icahn School of Medicine at Mount Sinai, and senior author of the paper.
The KCNQ2/3 channel belongs to the KCNQ (or Kv7) family of ion channels which are important controllers of brain cell excitability and function in the central nervous system, affecting brain cell function by controlling electrical charge flow across the cell membrane in the form of potassium (K+) ions. Previous research in mice also showed involvement of KCNQ2/3 in depression. Mice that were more resilient to stress had increased KCNQ2/3 channels in their brains.
“We viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression,” said Ming-Hu-Han, PhD, who also discovered that by increasing the activity of this channel, such as by administering ezogabine, to depressed mice, the drug acted as an antidepressant.
A trial with adult human patients showed that, compared to placebo, those treated with ezogabine showed a large reduction in a number of key measures of depression severity, anhedonia, and overall illness severity. “The fundamental insight by Dr Han’s group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us,” said Dr Murrough.
In collaboration with Dr Han, Dr Murrough carried out a series of human studies, with an initial open-label (no placebo) study in patients with depression providing initial evidence that ezogabine could improve symptoms of depression and anhedonia.
“I think it’s fair to say that most of us on the study team were quite surprised at the large size of the beneficial effect of ezogabine on clinical symptoms across multiple measures related to depression. We are greatly encouraged by these findings and the hope they offer for the prospect of developing novel, effective treatments for depression and related disorders. New treatments are urgently needed given that more than one-third of people suffering from depression are inadequately treated with currently approved therapeutics.”
