Recent Advances In Epilepsy Research In 2018

- Mar 21, 2019-

In 2018, research in the field of epilepsy has made some progress in the direction of disease mechanism, drug therapy, epilepsy surgery and sudden death of epilepsy (SUDEP). Professor Zhou Dong of West China Hospital of Sichuan University wrote a review of the progress of epilepsy research in 2018 in Nature Reviews Neurology and explained the significance of international and multidisciplinary cooperation in epilepsy research.5,5-Dimethyl-2,4-oxazolidinedione


    Although a new generation of anti-epileptic drugs (AEDs) that have been on the market for the past two decades have expanded the choice of drugs for epilepsy treatment, an observational cohort study conducted in Scotland by a team of researchers from the UK, Australia and China shows: new The long-term prognosis of patients with epilepsy has not been significantly improved. The study tracked the prognosis of 1795 patients with epilepsy between 1982 and 2012. By the end of the study, 1144 (63.7%) patients had at least 1 year epilepsy without seizures, of which 993 (86.8%) achieved monotherapy. There was no seizures in one year, and 1028 patients (89.9%) were achieved in the first or second AED treatment regimen. Each attempt to achieve an AED treatment regimen then significantly reduces the probability of epileptic seizures. These results suggest that in order to improve the prognosis of epilepsy, epilepsy treatment and research strategies need to be transformed.

 

    Another longitudinal observational cohort study in China showed differences in efficacy between different treatment strategies after the failure of the first antiepileptic drug treatment. The study included 502 patients who failed treatment at the first standard dose of AED, and received three follow-up treatments after randomization: combination therapy, replacement therapy, or an increase in the first AED dose. The results showed that patients who received combination therapy had a significantly higher likelihood of achieving epileptic seizures than the other two groups, indicating that the first combination of AED treatment failure was more likely to have epileptic seizures than other treatment strategies.DMO CAS 695-53-4


    The new study further demonstrates the efficacy and tolerability of the addition of cannabidiol in the treatment of refractory epilepsy in children. A multicenter, randomized, double-blind, placebo-controlled phase III trial validated the drug's ability to reduce the frequency of falls in patients with Lennox-Gastaut syndrome.


    Congenital malformations associated with AEDs are a hot topic in the treatment of female epilepsy. A large cohort study based on the International Anti-Epilepsy Pregnancy Register (EURAP) included 7355 pregnancies and assessed the teratogenic risk of eight commonly used antiepileptic drugs. Studies have shown that different AEDs have different teratogenic risks, with valproic acid having the highest risk of teratogenicity (10.3%) and levetiracetam having the lowest risk of teratogenicity (2.8%). These results help to select the right drug based on relative risk.Dimethadione


    The latest basic research on epilepsy shows the potential of mossy cells as a new target for the treatment of epilepsy. Mossy cells are key neurons in the hippocampus excitatory circuit, and partial loss of these cells is a characteristic phenomenon of temporal lobe epilepsy. In a recent study, the researchers used a mouse model of temporal lobe epilepsy to study how bryophytes participate in spontaneous episodes of electrical activity and spatial scene memory in combination with optogenetics, electrophysiology, and behavioral methods. The results suggest that reducing moss cell loss or stimulating surviving cells is a potential therapeutic strategy for the treatment of temporal lobe seizures and cognitive dysfunction.


    Despite the availability of many new AEDs, 30%-40% of epileptic seizures remain uncontrolled. Surgery may have a good effect on selected patients with refractory focal epilepsy. However, the risk of surgical complications, including stroke, postoperative bleeding, and infection, limits the widespread use of craniotomy. In a randomized, single-blind, controlled trial in 2018, 58 patients in 14 centers in the United States, Britain, and India were preoperatively evaluated for adult patients with medial temporal lobe epilepsy (MTLE). The aim of the study was to evaluate the efficacy and safety of stereotactic radiosurgery in patients with MTLE versus anterior temporal lobectomy. The results show that both regimens are effective in MTLE and have reasonable safety, indicating that stereotactic radiosurgery is feasible for some patients and is a minimally invasive or alternative treatment for craniotomy.


    For many patients with intractable epilepsy who are not suitable for surgery, neuromodulation has gradually become one of their treatment options. In particular, deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) has shown encouraging results. Recently, the Yu research team reported that high-frequency ANT-DBS can de-synchronize the background local potential and reduce the epileptic activity in the initial episode. These findings suggest that desynchronization is the primary mechanism by which ANT-DBS inhibits seizures.


    Epilepsy genetics is another focus of attention in 2018. A study published in the New England Journal of Medicine included 120 families with epilepsy encephalopathy caused by "de novo mutations" (de novo) to assess the risk of epileptic encephalopathy in their offspring. . The geneticist calculated the risk by theory to be about 1%, but the results of the study showed that the actual risk was as high as 50%. Using single-molecule inversion probe technology, the researchers found chimeric mutations (ie, part of the disease-causing mutations in their offspring) in 10 parents in 120 subjects, and 4 of the 10 families gave birth. Another child with the same mutation. This study suggests that the hereditary nature of "new hair" epilepsy encephalopathy was previously underestimated. For families with offspring of epileptic encephalopathy caused by “new disease-causing mutations”, high-coverage genetic testing can provide a more accurate risk assessment for recurrence, thus helping genetic counseling.


    The genetic basis of juvenile myoclonic epilepsy (JME) has been speculated, and its underlying network mechanisms remain unclear. A new study found mutations in intestinal cell kinase (ICK) in a JME family. Further sequencing in 310 JME patients revealed 22 patients carrying 21 possible disease-causing mutations. . Brain slice data from ICK model mice also support the conclusion that pathogenic mutations in ICK mediate JME by interfering with mitosis, neuroblast migration, and apoptosis.


    In 2018, we also have a new understanding of childhood epilepsy. The risk of sudden seizures (SUDEP) is a frequently overlooked problem in children with epilepsy, and clinicians generally do not mention the problem until the patient has been a child. According to previous studies, the incidence of SUDEP in children is only 1/5 to 1/4 of that of adults. However, a recent large population study of children's SUDEP in Canada pointed out that this may not be the case. The study identified and validated SUDEP events through three independent data sources (National Pediatric Surveillance Program, Child Neurologist Report, Provincial Forensic Autopsy Report). The results of the analysis showed that the incidence of SUDEP identified or likely in children with epilepsy was 1.45 person/1000 person-years, which was comparable to that of adults. Therefore, clinicians should not underestimate the risk of SADEP in children, and should also communicate with the family members of the child in time. The child population is similar to that of adults. Drug-refractory epilepsy, secondary generalized tonic-clonic seizures, and nighttime generalized episodes increase the risk of SUDEP. And for relatively specific populations such as children, severe epileptic encephalopathy can also increase this risk.


    In the past 2018, a series of heavyweight research results were born in the basic and clinical areas of epilepsy. In the future, with the common goal of improving the management level of patients with epilepsy, international and multidisciplinary cooperation will continue to provide strong support and help to solve new problems in the field of epilepsy.5,5-Dimethyloxazolidine-2,4-dione CAS 695-53-4 is the main material for epilepsy drugs.


A longitudinal observation cohort of patients with newly diagnosed epilepsy showed that the use of new antiepileptic drugs in recent years did not improve the long-term prognosis of patients with epilepsy.

Mossy cells, neurons that play an important role in the hippocampal excitatory network, may be a new target for future treatments for epilepsy.

A randomized controlled trial of stereotactic radiosurgery and anterior temporal lobe resection for patients with medial temporal lobe epilepsy has shown that stereotactic radiosurgery is a viable alternative in certain patients.

Emerging gene sequencing methods that detect parental chimerism allow parents with children with epilepsy encephalopathy to obtain more precise genetic counseling.

An epidemiological study found that the risk of sudden death from epilepsy (SUDEP) in children is comparable to that in adults, suggesting that children with epilepsy have a higher risk of sudden death than previous data.