RESILIENCE (Retrospective Linkage Study of Autoimmune Encephalitis): protocol for an Australian retrospective cohort study of outcomes in autoimmune encephalitis using data linkage techniques.

Introduction: The autoimmune encephalitides (AE) are a heterogeneous group of neurological disorders with significant morbidity and healthcare costs. Despite advancements in understanding their pathophysiology, uncertainties persist regarding long-term prognosis and optimal management. This study aims to address these gaps, focusing on immunotherapeutic strategies, neoplastic associations and functional outcomes.

Neuropsychological Outcomes After Stereo-EEG Radiofrequency Thermocoagulation.

Background And Objectives: Stereo-EEG-guided radiofrequency thermocoagulation (RFTHC) has been proposed as relatively safe from a cognitive perspective; however, there is a lack of evidence based on neuropsychological assessments supporting this. This study is the first prospective evaluation of neuropsychological outcomes associated with stereo-EEG-guided RFTHC in patients with focal drug-resistant epilepsy.

Methods: This cohort study involved prospective recruitment of consecutive patients undergoing stereo-EEG from 2 Australian centers.

The efficacy and tolerability of adjunctive brivaracetam for the treatment of adult epilepsy: An Australian multi-center retrospective real-world observational cohort study.

Objective: Assess the efficacy and tolerability of add-on therapy brivaracetam (BRV) in adult patients with epilepsy in a real-world setting.

Methods: This multi-center retrospective observational cohort study examined all adult patients who commenced on BRV at 11 Australian epilepsy centers between 2017 and 2020. Primary outcomes were seizure response (≥50% reduction in frequency) and seizure freedom 12 months post BRV commencement, and tolerability.

Second-line immunotherapy and functional outcomes in autoimmune encephalitis: A systematic review and individual patient data meta-analysis.

Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic management, with first-line immunotherapy followed by second-line immunotherapy if response to first-line therapy is inadequate. Meta-analysis of the evidence base may provide higher quality evidence to support this recommendation.

Pre-hospital benzodiazepines associated with improved outcomes in out-of-hospital status epilepticus: A 10-year retrospective cohort study.

Unlabelled: Outcomes of status epilepticus have not substantially changed over the last decade. Given onset is most often in the community, early termination strategies that are implementable outside of hospitals are of public health importance. This 10-year retrospective single-centre cohort study aimed to determine whether pre-hospital benzodiazepine administration is associated with improved health outcomes in patients with out-of-hospital onset status epilepticus.

Multiday cycles of heart rate are associated with seizure likelihood: An observational cohort study.

Background: Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly, and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles.

Evaluation of the Biocompatibility of Polypyrrole Implanted Subdurally in GAERS.

This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side.

Injectable phenytoin loaded polymeric microspheres for the control of temporal lobe epilepsy in rats.

Purpose: Epilepsy is a prevalent neurological disorder with a high frequency of drug resistance. While significant advancements have been made in drug delivery systems to overcome anti-epileptic drug resistance, efficacies of materials in biological systems have been poorly studied. The purpose of the study was to evaluate the anti-epileptic effects of injectable poly(epsilon-caprolactone) (PCL) microspheres for controlled release of an anticonvulsant, phenytoin (PHT), in an animal model of epilepsy.

A safe lithium mimetic for bipolar disorder.

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, therapeutic target of lithium remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist.

Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats.

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week.

Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens.

Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method.

Novel methods of antiepileptic drug delivery -- polymer-based implants.

Epilepsy is a neurological disorder characterised by spontaneous seizures. Over one third of patients receive insufficient benefit from oral anti-epileptic drug (AED) therapy, and continue to experience seizures whilst on medication. Epilepsy researchers are consequently seeking new ways to deliver AEDs directly to the seizure focus in the brain in order to deliver higher, more effective doses to the seizure focus whilst bypassing the remainder of the brain and body to prevent side effects.

In vivo biocompatibility and in vitro characterization of poly-lactide-co-glycolide structures containing levetiracetam, for the treatment of epilepsy.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier.

From protein to peptides: a spectrum of non-hydrolytic functions of acetylcholinesterase.

Acetylcholinesterase (AChE), a member of the α/β-hydrolase fold superfamily of proteins, is a serine hydrolase responsible for the hydrolysis of the well studied neurotransmitter acetylcholine (ACh). However, it is becoming clear that AChE has a range of actions other than this 'classical' role. Non-classical AChE functions have been identified in apoptosis, stress-responses, neuritogenesis, and neurodegeneration.

Exploring the tolerability of spatiotemporally complex electrical stimulation paradigms.

A modified cortical stimulation model was used to investigate the effects of varying the synchronicity and periodicity of electrical stimuli delivered to multiple pairs of electrodes on seizure initiation. In this model, electrical stimulation of the motor cortex of rats, along four pairs of a microwire electrode array, results in an observable seizure with quantifiable electrographic duration and behavioural severity. Periodic stimuli had a constant inter-stimulus intervals across the two-second stimulus duration, whilst synchronous stimuli consisted of singular biphasic, bipolar pulses delivered to the four pairs of electrodes at precisely the same time for the entire two second stimulation period.

Closed-loop seizure control with very high frequency electrical stimulation at seizure onset in the GAERS model of absence epilepsy.

A closed-loop system for the automated detection and control of epileptic seizures was created and tested in three Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats. In this preliminary study, a set of four EEG features were used to detect seizures and three different electrical stimulation strategies (standard (130 Hz), very high (500 Hz) and ultra high (1000 Hz)) were delivered to terminate seizures. Seizure durations were significantly shorter with all three stimulation strategies when compared to non-stimulated (control) seizures.

Teaching medical students basic neurotransmitter pharmacology using primary research resources.

Teaching pharmacology to medical students has long been seen as a challenge, and one to which a number of innovative approaches have been taken. In this article, we describe and evaluate the use of primary research articles in teaching second-year medical students both in terms of the information learned and the use of the papers themselves. We designed a seminar where small groups of students worked on different neurotransmitters before contributing information to a plenary session.

Evaluation of a technique to identify acetylcholinesterase C-terminal peptides in human serum samples.

A novel theory for neurodegeneration is that non-cholinergic functions of acetylcholinesterase (AChE) are responsible for the progressive death of global neurons. The C-terminal region of AChE has been shown to be responsible for non-cholinergic actions of AChE by binding to an allosteric site on the alpha 7-nicotinic acetylcholine receptor, thereby causing calcium influx; the resultant signal has trophic effects in immature neurons, but toxic effects in mature neurons. Although there is strong in vitro and in vivo evidence for the involvement of this C-terminal region of AChE in neurodegeneration, a cleaved C-terminal peptide has not yet been identified in human brains.

Seizure severity and duration in the cortical stimulation model of experimental epilepsy in rats: a longitudinal study.

The aim of this study was to determine the current intensities necessary to elicit three levels of varying EEG and behavioural phenomena with electrical stimulation, and also to determine the consistency of the EEG and behavioural components of the triggered seizures over time. Electrical stimulation of the primary motor/somatosensory cortex was performed in 16 adult rats with multichannel microwire electrode arrays. Stimulation was delivered at a frequency of 60 Hz (1 ms pulse width), for 2 s duration, as biphasic rectangular pulses over four of the eight available electrode pairs.

The thalamocortical circuit and the generation of epileptic spikes in rat models of focal epilepsy.

We investigate thalamocortical interactions in the tetanus toxin and the cortical stimulation rat models of epilepsy. Using local field potential recordings from the cortex and the thalamus of the rat, the nonlinear regression index is calculated to create the direction index in order to study neurodynamics during seizures. Coarse time-scale analysis reveals that the cortex drives the thalamus for the majority of the time during seizures.