Lower Seizure Threshold Research Articles

Low concentration dimethyl sulfoxide (DMSO) modulates epileptiform synchronization in the 4-aminopyridine in vitro model

Dimethyl sulfoxide (DMSO) is commonly used to dissolve water-insoluble drugs due to its dipolar and aprotic properties. It also serves as a vehicle in many pharmacological studies. However, it has been reported that DMSO can induce seizures in human patients, lower seizure threshold in vivo, and modulate ion receptors activities in vitro. Therefore, we investigated here the effect of 0.03 % and 0.06 % DMSO, which are 10–50 times lower than what usually employed in previous studies, in the 4-aminopyridine (4AP) model of epileptiform synchronization in male mouse brain slices. We found that 0.03 % and 0.06 % DMSO increase 4AP-induced ictal discharge rate, while 0.06 % DMSO decreases ictal discharge duration. Our results suggest that the effects of DMSO on neuronal excitability deserve further analysis and that investigators need to be aware of its confounding effect as a solvent, even at very low concentrations.

Levetiracetam Prevents Neurophysiological Changes and Preserves Cognitive Function in the Human Immunodeficiency Virus (HIV)-1 Transactivator of Transcription Transgenic Mouse Model of HIV-Associated Neurocognitive Disorder.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects nearly half of the 39 million people living with HIV. HAND symptoms range from subclinical cognitive impairment to dementia; the mechanisms that underlie HAND remain unclear and there is no treatment. The HIV protein transactivator of transcription (TAT) is thought to contribute to HAND because it persists in the central nervous system and elicits neurotoxicity in animal models. Network hyperexcitability is associated with accelerated cognitive decline in neurodegenerative disorders. Here we show that the antiepileptic drug levetiracetam (LEV) attenuated aberrant excitatory synaptic transmission, protected synaptic plasticity, reduced seizure susceptibility, and preserved cognition in inducible TAT (iTAT) transgenic male mice. iTAT mice had an increased frequency of spontaneous excitatory postsynaptic currents in hippocampal slice recordings and impaired long-term potentiation, a form of synaptic plasticity that underlies learning and memory. Two-week administration of LEV by osmotic minipump prevented both impairments. Kainic acid administered to iTAT mice induced a higher maximum behavioral seizure score, longer seizure duration, and shorter latency to first seizure, consistent with a lower seizure threshold. LEV treatment prevented these in vivo signs of hyperexcitability. Lastly, in the Barnes maze, iTAT mice required more time to reach the goal, committed more errors, and received lower cognitive scores relative to iTAT mice treated with LEV. Thus, TAT expression drives functional deficits, suggesting a causative role in HAND. As LEV not only prevented aberrant synaptic activity in iTAT mice but also prevented cognitive dysfunction, it may provide a promising pharmacological approach to the treatment of HAND. SIGNIFICANCE STATEMENT: Approximately half of people living with human immunodeficiency virus (HIV) also suffer from HIV-associated neurocognitive disorder (HAND), for which there is no treatment. The HIV protein transactivator of transcription (TAT) causes toxicity that is thought to contribute to HAND. Here, the antiepileptic drug levetiracetam (LEV) prevented synaptic and cognitive impairments in a TAT-expressing mouse. LEV is widely used to treat seizures and is well-tolerated in humans, including those with HIV. This study supports further investigation of LEV-mediated neuroprotection in HAND.

Hyperandrogenism Decreases Seizure Threshold in a Rat Model of Polycystic Ovary Syndrome

Plain Language SummaryThis study looked at how a condition called polycystic ovary syndrome (PCOS), which involves higher levels of testosterone, is related to a comorbidity with epilepsy in women. They used female rats to mimic PCOS and raised their hormone levels using a drug called letrozole. Then we tested how easy these rats were kindled to seizures compared to normal rats and recorded their brain activity using electroencephalograms. We also used a common medication in PCOS, called Diane-35, to see if it could change the effects of the high testosterone levels on seizures. The results showed that the rats with PCOS-like symptoms had lower seizure thresholds and higher levels of certain hormones in their brains and blood. When they used Diane-35, the reduced testosterone in the brain affects neuronal signaling receptors, which could be linked to antiepileptic effect. Overall, this research suggests a connection between high hormone levels seen in PCOS and decreased threshold to seizures. Understanding this link could be important in developing specific treatments for people who have both epilepsy and PCOS.

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

Characterization of soticlestat, a novel cholesterol 24-hydroxylase inhibitor, in acute and chronic neurodegeneration models

We investigated whether soticlestat (TAK-935), a newly discovered cholesterol 24-hydroxylase (CH24H) inhibitor now in phase 3 clinical trials for Dravet and Lennox-Gastaut syndromes, has effects on neurodegeneration in both chronic and acute animal models associated with glutamate hyperexcitation. Soticlestat was administered at doses that approximately halve 24S-hydroxycholesterol in both experiments. In the kainic acid (KA)-induced acute hippocampal degeneration model, soticlestat ameliorated inflammatory cytokine expression, hippocampal degeneration, and memory impairment. We ruled out the possibility that soticlestat directly interferes with KA binding to the KA receptor, or that 24S-hydroxycholesterol modulates KA receptor signaling, by conducting receptor binding and cell death assays. In the PS19 chronic degeneration model of tauopathy, treatment effects were observed in neurodegeneration markers. Notably, there was a significant correlation between the levels of brain 24S-hydroxycholesterol and a proinflammatory cytokine, tumor necrosis factor-α, which is implicated in cognitive decline and lowering of seizure threshold. This is the first study demonstrating that CH24H inhibition can alleviate neurodegeneration concomitant with neuroinflammation. Herein, we discuss the interplay among 24S-hydroxycholesterol production, neuroinflammation, and excitotoxicity. Effects on neurodegeneration and neuroinflammation demonstrated in two preclinical models suggest that soticlestat is effective in ameliorating seizures and addressing cognitive dysfunction in seizure disorders.

Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.

Epilepsy is a chronic and debilitating neurological disorder, known for the occurrence of spontaneous and recurrent seizures. Despite the availability of antiseizure drugs, 30% of people with epilepsy experience uncontrolled seizures and drug resistance, evidencing that new therapeutic options are required. The process of epileptogenesis involves the development and expansion of tissue capable of generating spontaneous recurrent seizures, during which numerous events take place, namely blood-brain barrier (BBB) dysfunction, and neuroinflammation. The consequent cerebrovascular dysfunction results in a lower seizure threshold, seizure recurrence, and chronic epilepsy. This suggests that improving cerebrovascular health may interrupt the pathological cycle responsible for disease development and progression. Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors, encountered in brain endothelial cells, glial cells, and neurons. KLFs are known to regulate vascular function and changes in their expression are associated with neuroinflammation and human diseases, including epilepsy. Hence, KLFs have demonstrated various roles in cerebrovascular dysfunction and epileptogenesis. This review critically discusses the purpose of KLFs in epileptogenic mechanisms and BBB dysfunction, as well as the potential of their pharmacological modulation as therapeutic approach for epilepsy treatment.

Effectiveness and Safety of Flumazenil Augmentation During Electroconvulsive Therapy.

Benzodiazepines are considered to negatively affect seizure quality and duration during electroconvulsive therapy (ECT). Several researchers have advocated the use of flumazenil, a competitive benzodiazepine receptor antagonist, for patients treated with benzodiazepines during ECT. However, clinical evidence regarding flumazenil use in ECT remains sparse. The aim of this study is to investigate the effects of flumazenil on seizure duration and adverse effects. All patients with depressive disorders, treated with flumazenil during a course of ECT in 2019 in a tertiary hospital, were identified through a retrospective chart review. Seizure duration was recorded before and after flumazenil administration. Effectiveness of ECT was assessed using the Inventory of Depressive Symptomatology and the Bush-Francis Catatonia Rating Scale. Postictal agitation was ascertained by identifying patients who received additional sedatives immediately after ECT or who needed physical restraint. Twenty-six patients were included, receiving a total of 363 treatments, of which 263 were augmented with flumazenil. Flumazenil administration increased electroencephalogram seizure duration on average with 10.5 seconds comparing ECT with or without flumazenil (P = 0.003). In 21.8% of the cases, no increase in seizure duration was observed. Postictal agitation occurred at least once in 34.6% of the patients receiving flumazenil during their course of ECT. Our results show that flumazenil increases seizure duration, albeit with limited clinical implications. Noteworthy, the prevalence of postictal agitation is high. When confronted with short seizures, clinicians should therefore deploy other available techniques to lower seizure threshold before considering flumazenil.

Case Report: Pediatric Thyroid Storm Presenting to the Emergency Department with Afebrile Seizure.

Seizures are a common presenting complaint and account for approximately 1% of total emergency department (ED) visits. Seizures are especially common in children less than fiveyears old as they have a lower seizure threshold as compared to adults. One potentially dangerous etiology that is far less common, especially in children, is thyroid storm, the extreme manifestation of hyperthyroidism. We describe the case of a 3-year-old girl who presented to the ED with an afebrile seizure but was found to be in thyroid storm. This case should serve as a reminder for emergency physicians to consider thyroid disease when evaluating patients presenting with seizures. Although most pediatric seizures are self-limited and frequently benign, it is imperative that the emergency physician evaluate for and rule out any potentially associated dangerous conditions such as thyroid storm.

White Matter Hyperintensities as a Predictor of Aphasia Recovery

ObjectiveTo examine the relation between baseline white matter hyperintensities (WMH) and change in naming, content production, and efficiency after treatment in subacute aphasia. We hypothesized that more severe baseline WMH would result in less improvement with treatment. DesignRetrospective analysis of a cohort from a double-blind randomized controlled trial (RCT). SettingOutpatient clinical setting or participant home. ParticipantsWe retrospectively reviewed imaging and behavioral data for 52 participants with subacute aphasia due to left-hemisphere ischemic stroke enrolled in the RCT. RCT inclusion criteria: English proficiency, normal/corrected-to-normal hearing/vision, and no history of neurologic conditions other than the stroke resulting aphasia. One participant with a chronic right-hemisphere lesion was retained as she presented with no residual deficits on neurologic examination. Individuals with scalp sensitivities or on medications that lower seizure threshold or any N-methyl-D-aspartate (NMDA) antagonists were excluded. Of the 52 participants, for this analysis, 2 were excluded for not having a magnetic resonance imaging, and 7 were excluded for not participating in treatment or pre/post assessment for at least 1 outcome, resulting in final sample of 43 participants (20 women sex, M [SD] age=64.4 [11.9] and M [SD] education=14.9 [3.1] years). InterventionsParticipants received 15 sessions (2-3 times/week) of computerized lexical-semantic (ie, verification) treatment with [sham/active] transcranial direct current stimulation (tDCS). Sessions were approximately 45 minutes each (tDCS for first 20 minutes). Main Outcome MeasuresNaming accuracy, content units (CUs, a measure of semantically accurate production), and efficiency (ie, syllables/CU) on a picture description task. ResultsPeriventricular WMH severity was independently associated with recovery in picture naming for the active tDCS group. Deep WMH severity was associated with recovery for CU production for the sham tDCS group. ConclusionBaseline periventricular and deep WMH, among other factors, may be an important consideration for prognosis and treatment planning, especially when considered in conjunction with tDCS treatment.

Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats.

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy (TLE). We postulated that kainic acid (KA)-Induced status epilepticus triggers microglia-dependent inflammation, leading to neuronal damage, a lowered seizure threshold, and the emergence of spontaneous recurrent seizures (SRS). Extensive evidence from our laboratory suggests that dextromethorphan (DM), even in ultra-low doses, has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease. Our results showed that administration of DM (10 ng/kg per day; subcutaneously via osmotic minipump for 4 weeks) significantly mitigated the residual effects of KA, including the frequency of SRS and seizure susceptibility. In addition, DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss. We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91phox and p47phox proteins in KA-induced chronic TLE rats. Notably, even after discontinuation of DM treatment, ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects, which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

NCMP-23. EVALUATION OF IMMUNOTHERAPY EFFECTS IN CANCER PATIENTS ON EPILEPTIFORM ACTIVITY

Abstract BACKGROUND/OBJECTIVE Immune checkpoint inhibitors are associated with increased risk of autoimmune neurologic conditions, both in the peripheral and central nervous system. Increased activation of the immune system can lower seizure threshold, potentially increasing a patient’s risk of seizures. We hypothesize that patients treated with immune checkpoint inhibitors have a higher rate of seizures. METHODS We retrospectively reviewed 465 cancer patients undergoing electroencephalography (EEG) monitoring performed at Memorial Sloan Kettering Cancer Center from January 2022 to March 2023. Data was gathered from an EEG RedCap database containing patient demographic and seizure data. Patients were separated based on whether they had received immune checkpoint inhibitors (+ICI) prior to seizure occurrence or were never exposed to immune checkpoint inhibitors (-ICI) and had a seizure. Patient cancer type and presence of brain lesions (primary or metastases) were also reviewed. RESULTS Out of 465 patients, 109 received immune checkpoint inhibitors (+ICI) during their treatment. Seven of those patients were reported to have had at least one seizure (7/109, 6.42%) following treatment with ICI. The remaining 356 patients did not undergo immune checkpoint inhibitor treatment (-ICI), of which 30 were reported to have had at least one seizure (30/356, 8.43%). Of the +ICI patients who were experiencing seizures, 5 of them had brain lesions; 4 had primary brain tumors and 1 had brain metastases. Of –ICI patients, 21 patients had brain lesions; 15 had primary brain tumors and 6 had brain metastases. DISCUSSION Although immune checkpoint therapy may lead to increased activation of the immune system, our data did not reveal a higher incidence of seizures. Limitations to our study include its retrospective design, low number of patients, and low overall number of seizures captured on EEG.

Antiepileptic Drugs and the Relationship with the Intestinal Microbiota

This review of the literature examines the use of antiepileptic medications and how they relate to gut microbiota. Relationships exist between the makeup of the intestinal microbiota and the development and execution of the most fundamental physiological processes. Additionally, it affects the functioning of the central nervous system (CNS) by interacting with the microbiota-intestine-brain axis. The use of pharmaceutical medication is one of the factors that can alter the composition of the gut microbiota. When treating epilepsy, various drug types are used, each with a different mechanism of action. Among the medications in question are to piramate, primidone, phenytoin, carbamazepine, and phenobarbital. The similarity in structure and function between enteric and nerve cells establishes the connection between the brain and the gut. Valproic acid significantly reduced intestinal inflammation in research involving rats with colitis. Its limited ability to treat seizures in these circumstances may be due to the enterocytes limited ability to absorb this medicine. The study came to the conclusion that colitis patients and people with healthy gut, brain, and microbiota interactions typically respond better to antiepileptics and anticonvulsants than people with imbalances in this axis. These imbalances can result in a lower seizure threshold and an increased frequency of epileptic seizures.

Insight into Genetic Mutations of SZT2: Is It a Syndrome?

The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene could result in hyperactive mTORC1 signaling, which can lead to several neurological disorders. To review every reported case and present two novel cases to expand the current knowledge and understanding of the mutation. Whole exome sequencing (WES) was used to identify the novel cases and present their clinical and radiological findings. A detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data were extracted. The study included 16 female patients and 13 male patients in addition to the 2 novel male cases. Eighteen patients had heterozygous mutations; others were homozygous. The majority presented with facial dysmorphism (n = 22). Seizures were noted as the predominant hallmark (n = 26). Developmental delay and hypotonia were reported in 27 and 15 patients, respectively. The majority of patients had multifocal epileptiform discharges on the electroencephalogram (EEG) and short and thick corpus callosum on the magnetic resonance imaging (MRI). Several promising features are becoming strongly linked to patients with SZT2 mutations. High variability among the cases was observed. Developmental delay and facial dysmorphism can be investigated as potential hallmarks; aiding clinicians in diagnosing the condition and optimizing management plans.

Exploring the concept and management of post ictal psychosis through a clinical case and review

IntroductionPostictal Psychosis of Epilepsy (PIPE), part of the group collectively known as Psychosis of Epilepsy, is characterized by an onset of confusion or psychotic symptoms within one week of apparent normal mental function. PIPE has been argued to be underdiagnosed in the clinical population, perhaps due to a failure to recognize the temporal relation between the seizure and the psychotic episode.ObjectivesTo explore the concept and management of post ictal psychosis.MethodsWe present a clinical case and a review of the literature concerning post ictal psychosis.Results We report the case of a 36 year old woman with focal refractory epilepsy after a likely episode of limbic encephalitis in 2015. Cognitive and psychiatric sequelae in the form of depressive symptoms, in treatment with neurology and psychiatry since 2021. One previous episode of psychotic symptoms during seizures. Worsening of seizure frequency since march of 2022 with apparent normalization (absence of seizures after dose reduction of eslicarbamazepine and introduction oflamotrigine) for about four days before being hospitalized in the neurology unit due tobehavioral abnormalities. During psychiatric exploration, the patient showed signs of partial clouding of consciousness with manierisms, ecopraxias and ecolalias; verbigerance in the form of the neurologist’s name and bizarre movements like looking behind suggestive of sensoroperceptive disturbances. The symptomatology resolved itself during the following week after treatment with diazepam.Finally, a narrative review concerning the case was also performed; with particular emphasis on antipsychotic drugs with low risk of lowering seizure threshold (such as risperidone or aripiprazole) as the recommended treatment.ConclusionsOur findings point to the relevance of Postictal Psychosis of Epilepsy as a clinical entity. Further studies on pathogenic mechanisms and therapeutic management are required.Disclosure of InterestNone Declared

KIF4 regulates neuronal morphology and seizure susceptibility via the PARP1 signaling pathway.

Epilepsy is a common neurological disease worldwide, and one of its causes is genetic abnormalities. Here, we identified a point mutation in KIF4A, a member of kinesin superfamily molecular motors, in patients with neurological disorders such as epilepsy, developmental delay, and intellectual disability. KIF4 is involved in the poly (ADP-ribose) polymerase (PARP) signaling pathway, and the mutation (R728Q) strengthened its affinity with PARP1 through elongation of the KIF4 coiled-coil domain. Behavioral tests showed that KIF4-mutant mice exhibited mild developmental delay with lower seizure threshold. Further experiments revealed that the KIF4 mutation caused aberrant morphology in dendrites and spines of hippocampal pyramidal neurons through PARP1-TrkB-KCC2 pathway. Furthermore, supplementing NAD, which activates PARP1, could modulate the TrkB-KCC2 pathway and rescue the seizure susceptibility phenotype of the mutant mice. Therefore, these findings indicate that KIF4 is engaged in a fundamental mechanism regulating seizure susceptibility and could be a potential target for epilepsy treatment.

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development. We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD). Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice. We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.

Erector spinae plane block for thoracoscopy in a paediatric patient

We present the case of a 9 year old patient with a clinical history of epilepsy and various hospitalizations due to aspirative broncopneumonia among others, who was admitted to our hospital because of septic shock secondary to pneumonia of the lower left lobule associated with a parapneumonic pleural effusion and a complicated clinical course. During her stay, the patient undergoes surgical debridement using video assisted thoracoscopic surgery (VATS) under general anaesthesia and the hydropneumothorax is drained. For the procedure an ecoguided erector spinae plane block is performed and combined with general anaesthesia. On one hand this block permitted reduction of perioperative opioid administration and improved the patient's respiration, on the other hand it permitted avoiding the use of drugs, which can lower seizure threshold and increase the risk of convulsions. This case illustrates the importance of locoregional anaesthesia, a technique on the rise in the field of paediatric anaesthesia.

Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats.

Caffeine is a psychoactive substance used worldwide. The present study analyzes the seizure-related behavior and electrocorticographic (ECoG) patterns observed in rats following of a toxic dose of caffeine (150mg/kg; intraperitoneal). Sixty-three rats were divided into three experiments: 1-Behavior's Description associated with caffeine-induced convulsion; 2- Comparison of the electrocorticographic patterns induced by caffeine and pentylenetetrazole, and 3- Assessment of the electrocorticographic response to antiepileptic drugs (diazepam, phenytoin, and phenobarbital). The behavioral analysis demonstrated tonic-clonic seizures with a loss of postural reflex and a latency of 365.8s after the caffeine's administration. Caffeine-induced changes in the ECoG were consistent with the development of seizures with rapid evolution and burst potential consistent with the behavioral patterns observed during the caffeine-induced seizure. The ECoG of the brainwaves varied significantly between the seizures caused by caffeine and pentylenetetrazole. The predominant brain forces observed during the seizures were beta-band oscillations. The caffeine-induced seizures were resistant to attempted control with phenytoin and phenobarbital, but responded well to diazepam, which is consistent with a study of Pilocarpine, which showed that diazepam has anticonvulsant effects. These findings are important for the development of effective treatments for caffeine intoxication, in particular for individuals with a low seizure threshold.

ODP194 EPC (Epilepsia Partialis Continue)- as a presenting symptom of HHS (Hyperglycemic Hyperosmolar Syndrome)

Abstract Case presentation A 51 year old female with history of type 2 DM and hypertension presented with elevated blood glucose levels (>500 mg/dL) and a two day history of multiple episodes of numbness, tremors and weakness affecting the right upper extremity. These episodes lasted ∼10 seconds and resolved spontaneously. She had no history of seizures or prior similar symptoms. Extensive review of systems was negative. Neurological exam was normal except for decreased sensation and dysmetria affecting the right upper extremity. Labs included: serum glucose 616 (70-99 mg/dL), serum osmolarity 302 mOsm/kg (285-295 mOsm/kg), serum bicarbonate 19 (21-31 mmol/L), anion gap 18 (6-14 mmol/L), serum ketones 0.2 (normal <0.6 mmol/L), Stroke work up including CT head, MRI brain, CTA/MRA head and neck, and TTE were negative. EEG showed no epileptiform changes likely due to the episodic nature of symptoms. Endocrinology started basal-bolus insulin regimen with IVF therapy for hyperosmolar hyperglycemia without diabetic ketoacidosis. However, she continued to have multiple documented episodes of twitching of right thumb with tingling, numbness and cramping lasting 10-15 seconds while fully awake and followed by full return of function. These episodes coincided characteristically with periods of hyperglycemia (in range of 122-440 mg/dL). Neurology attributed her symptoms to partial focal seizures in the setting of non ketotic hyperglycemia. Seizures decreased in frequency with improved glycemic control. She was discharged on basal-bolus insulin regimen and showed continued improvement with tight regulation of glycemic control. Discussion EPC is a rare variant of simple focal motor status epilepticus characterized by recurrent focal epileptic seizures involving distal extremities lasting seconds to hours and occurring over prolonged periods of time. It may be preceded by aura continua, non-motor manifestations such as tingling and numbness, and followed by Todd's phenomenon, transient unilateral weakness. Etiologically, it is attributed to structural (stroke, trauma), infectious (encephalitis, prion disease), autoimmune (Sjorgen syndrome), neoplastic (gliomas) and metabolic (HHS) pathologies. HHS is a rare yet known cause of EPC. Glucose plays a crucial role in synaptic transmission, and hyperglycemia increases the metabolism of inhibitory neurotransmitters such as gamma-aminobutyric-acid (GABA) thus lowering seizure threshold. Diagnosis is clinical; EEG is supportive only. Management primarily entails correction of underlying cause, hyperglycemia. Review of literature suggests that HHS induced EPC can often be resistant to anti-epileptic agents and medications such as phenytoin and valproic acid may actually exacerbate this condition due to their hyperglycemic effect. Through this case, we wish to highlight the importance of recognizing HHS as a cause of EPC in clinical practice and also emphasize that the first line treatment is the correction of underlying hyperglycemia. Presentation: No date and time listed

Allergic rhinitis in BALB/c mice is associated with behavioral and hippocampus changes and neuroinflammation via the TLR4/ NF-κB signaling pathway

BackgroundAllergic rhinitis is a systemic disease with high prevalence, which some of its neuropsychological problems have been reported. The primary pathophysiology and mechanism of the neuropsychological dysfunction of AR patients have not been described yet, so here we subjected an animal model of AR to identify any behavioral or seizure threshold changes and to assess the pathophysiology of the disease. MethodsEighty male BALB/C mice were randomly divided into the allergic rhinitis group and controls. Allergic rhinitis was induced in the first group by administering OVA and aluminum hydroxide intraperitoneally and then nasal injection of OVA for 14 consecutive days. Both groups were subjected to different tests for assessing depressive-like behavior, anxiety, spatial and contextual memory, and learning and seizure threshold. Hippocampus and plasma samples of mice were subjected for analyzing cytokines and immune modulators and for pathology and immunohistochemistry evaluation. ResultsThe depressive and anxiety-like behavior were increased in AR, and the spatial learning and memory were disturbed in the AR group. Also, AR mice had lower seizure thresholds compared to controls. Lab data suggested that TLR4, NF-κB, IL-1β, and TNFα expressions were increased in the AR hippocampus as well as their plasma proinflammatory cytokines. Likewise, demyelination, cell death, and M1 macrophage aggregation were increased in the AR hippocampus. ConclusionBehavioral and cognitive problems should be taken seriously in patients with AR or other atopic diseases, and more investigating is required to clear the pathophysiology behind it and its treatment.