Spatiotemporal dynamics of high-K^+-induced epileptiform discharges in hippocampal slice and the effects of valproate

The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K ＋ concentration （8.5 mmol/L） in the bath, and the effects of the anti-epileptic drug valproate （VPA） on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration （100 μmol/L） suppressed the propagation speed but not the rate or duration of high-K＋-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.

Development of localized interictal epileptiform discharges following vagus nerve stimulation for lennox-gastaut syndrome: a case report

Background Lennox-gastaut syndrome(LGS)is an epileptic encephalopathy often associated with behavioral and psychiatric disorders.Vagus nerve stimulation(VNS)has been approved effective for LGS treatment.Surgical resection is also an option for LGS patients with focal pathology,offering a high probability of seizure control.However,it is challenging to accurately localize the seizure focus.Case presentation The case presented here is a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders.He was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types.He was treated with VNS in 2017 at the age of 15.After that,the frequency of the short tonic seizures decreased from 4–5 times per day to 2–5 times per year,and the generalized tonic–clonic seizure pattern did not recur,which had a frequency of 2–4 times per month before the surgery.In 2019,the generalized abnormal interictal epileptiform discharges changed to be localized in the right frontal–temporal lobe at the age of 17 years(2019).Conclusions This case report suggested that the generalized epileptiform discharges evolve into localized discharges after VNS treatment,which may help reveal the primary seizure focus for resection surgery in patients with LGS.

GABA_A Receptor Activity Suppresses the Transition from Interictal to Ictal Epileptiform Discharges in Juvenile Mouse Hippocampus

Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We used Mg2+-free artificial cerebrospinal fluid(ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizurelike events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges(IIDs) to pre-ictal epileptiform discharges(PIDs), and then to IDs.During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 lmol/L of the GABAAreceptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 lmol/L muscimol abolished all the epileptiform discharges. When the GABAAreceptor antagonist bicuculline was applied at 10 lmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAAreceptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.

Promising medical treatment for childhood psycho-cognitive problems

Subclinical electroencephalogram discharges in children with psycho-cognitiVe problems are not uncommon. However, the clinical importance and relationship to cognitive deficits, as well as indications for medical treatment, are not well understood. Transient cognitive impairment, which accompanies electroencephalogram discharges, could negatively influence cognitive abilities over time. Studies have suggested that treatment with antiepileptic drugs normalizes electroencephalogram results, thereby preventing electrical paroxysmal discharges that could be harmful to the developing brain. Physicians should attempt to differentiate between corresponding factors, such as subtle seizures, nature of underlying etiology, stable cognitive deficits, seizure-inducing effects, and potential side effects of antiepileptic drugs prior to initiation of medical treatment for definitive diagnosis of transient cognitive impairment and its consequences. Therefore appropriate criteria for patient selection and proper guidelines for medical therapy, should be addressed in future studies.

Integration of multiscale entropy and BASED scale of electroencephalography after adrenocorticotropic hormone therapy predict relapse of infantile spasms

Background Even though adrenocorticotropic hormone(ACTH)demonstrated powerful efficacy in the initially successful treatment of infantile spasms(IS),nearly half of patients have experienced a relapse.We sought to investigate whether features of electroencephalogram(EEG)predict relapse in those IS patients without structural brain abnormalities.Methods We retrospectively reviewed data from children with IS who achieved initial response after ACTH treatment,along with EEG recorded within the last two days of treatment.The recurrence of epileptic spasms following treatment was tracked for 12 months.Subjects were categorized as either non-relapse or relapse groups.General clinical and EEG recordings were collected,burden of amplitudes and epileptiform discharges(BASED)score and multiscale entropy(MSE)were carefully explored for cross-group comparisons.Results Forty-one patients were enrolled in the study,of which 26(63.4%)experienced a relapse.The BASED score was significantly higher in the relapse group.MSE in the non-relapse group was significantly lower than the relapse group in theγband but higher in the lower frequency range(δ,θ,α).Sensitivity and specificity were 85.71%and 92.31%,respectively,when combining MSE in theδ/γfrequency of the occipital region,plus BASED score were used to distinguish relapse from non-relapse groups.Conclusions BASED score and MSE of EEG after ACTH treatment could be used to predict relapse for IS patients without brain structural abnormalities.Patients with BASED score≥3,MSE increased in higher frequency,and decreased in lower frequency had a high risk of relapse.

Continuous video electroencephalogram for herpes simplex encephalitis:a case report and literature review

Background:Electroencephalogram(EEG)is an important tool for the diagnosis of herpes simplex virus encephalitis(HSE).However,the diagnosis of non-convulsive status epilepticus(NCSE)in HSE is challenging without the help of continuous video EEG(CVEEG),and whether EEG is a predictor of outcome remains controversial.Case presentation:A 63-year-old woman presented with a 5 day history of fever,coma and seizures.Results of EEG,magnetic resonance imaging and polymerase chain reaction(PCR)in cerebrospinal fluid(CSF)were suggestive of herpes simplex encephalitis-1(HSE-1).Preliminary EEG showed periodic discharges at the prefrontal and temporal lobes,which were particularly synchronized with intermittent lip smacking movements,and the discharges were terminated by diazepam.After 2-week treatment with acyclovir,high-dose hormone pulse therapy and high-dose immunoglobulin therapy,the CSF was improved,but the patient’s consciousness became worsen,consistent with the diffuse slow waves in the delta range and low voltage of EEG activity.In the following 1 month,the patient had non-responsiveness to pain and sound as shown by CVEEG with diffuse slow waves.Sometimes paroxysmal very slow waves(0.5–1 Hz)were synchronized with intermittent paroxysmal eye movements,pupil abnormality,and sweating in the frontal area.After 2 months of treatment,the EEG abnormalities improved to have alpha rhythm.Conclusion:The CVEEG not only helps identify NCSE but can also be used to monitor HSE progression.