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Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011 and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia, and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. The current study involves a total of 58 distinct participants; of these, 43 caregivers were interviewed using the Vineland-3 and answered a survey regarding therapy and other questions, 10 of whom completed the Vineland-3 but did not answer the survey, and 5 participants who answered the survey but have not yet performed the Vineland-3 due to language constraints. The average age at the time of the most recent assessment was 12.4 years, with individuals ranging in age from 11 months to 40.2 years. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome (n = 53). Sub-domain analysis found the decline to be present across all modalities. In addition, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. A therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy, with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status, and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Aims: In this study, the anticonvulsant action of closed-loop, low-frequency deep brain stimulation (DBS) was investigated. In addition, the changes in brain rhythms and functional connectivity of the hippocampus and prefrontal cortex were evaluated., Methods: Epilepsy was induced by pilocarpine in male Wistar rats. After the chronic phase, a tripolar electrode was implanted in the right ventral hippocampus and a monopolar electrode in medial prefrontal cortex (mPFC). Subjects' spontaneous seizure behaviors were observed in continuous video recording, while the local field potentials (LFPs) were recorded simultaneously. In addition, spatial memory was evaluated by the Barnes maze test., Results: Applying hippocampal DBS, immediately after seizure detection in epileptic animals, reduced their seizure severity and duration, and improved their performance in Barnes maze test. DBS reduced the increment in power of delta, theta, and gamma waves in pre-ictal, ictal, and post-ictal periods. Meanwhile, DBS increased the post-ictal-to-pre-ictal ratio of theta band. DBS decreased delta and increased theta coherences, and also increased the post-ictal-to-pre-ictal ratio of coherence. In addition, DBS increased the hippocampal-mPFC coupling in pre-ictal period and decreased the coupling in the ictal and post-ictal periods., Conclusion: Applying closed-loop, low-frequency DBS at seizure onset reduced seizure severity and improved memory. In addition, the changes in power, coherence, and coupling of the LFP oscillations in the hippocampus and mPFC demonstrate low-frequency DBS efficacy as an antiepileptic treatment, returning LFPs to a seemingly non-seizure state in subjects that received DBS., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug-resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A 1 Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms., Methods: Control group, SE (status epilepticus) group, SE-DBS group, and SE-sham-DBS group were included in this study. One week after a pilocarpine-induced status epilepticus, rats in the SE-DBS group were treated with DBS for 4 weeks. The rats were monitored by video-EEG. ADK and A 1 Rs were tested with histochemistry and western blot, respectively., Results: Compared with the SE group and SE-sham-DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A 1 R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A 1 Rs., Conclusion: The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A 1 Rs. A 1 Rs might be a potential target of DBS for the treatment of epilepsy., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Deep brain stimulation (DBS) and electromagnetic induction are new techniques that are increasingly used in modern epilepsy treatments; however, the mechanism of action remains unclear. In this study, we constructed a bidirectional-coupled cortico-thalamic model, based on which we proposed three regulation schemes: isolated regulation of DBS, isolated regulation of electromagnetic induction and combined regulation of the previous two. In particular, we introduced DBS with a lower amplitude and considered the influence of electromagnetic induction caused by the transmembrane current on the membrane potential. The most striking finding of this study is that the three therapeutic schemes could effectively control abnormal discharge, and combined regulation could reduce the occurrence of epileptic seizures more effectively. The present study bridges the gap between the bidirectional coupling model and combined control. In this way, the damage induced by electrical stimulation of the patient's brain tissue could be reduced, and the abnormal physiological discharge pattern of the cerebral cortex was simultaneously regulated by different techniques. This work opens new avenues for improving brain dysfunction in patients with epilepsy, expands ideas for promoting the development of neuroscience and is meaningful for improving the health of modern society and developing the field of science., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Aims: Deep brain electrical stimulation (DBS), as a potential therapy for drug resistive epileptic patients, has inhibitory action on epileptogenesis. In the present investigation, the role of dopamine D 2 -like receptors in the antiepileptogenic action of DBS was studied., Methods: Seizures were induced in adult rats by stimulating the perforant path in a semi-rapid kindling method. Five minutes after the last kindling stimulation, daily DBS was applied to the perforant path at the pattern of low frequency stimulation (LFS; 1 Hz; pulse duration: 0.1 ms; intensity: 50-150 μA; 4 trains of 200 pulses at 5 min intervals). Sulpiride (10 μg/1 μl, i.c.v.), a selective dopamine D 2 -like receptor antagonist, was administered prior to the daily LFS application., Results: Kindling stimulations increased cumulative daily behavioral seizure stages, daily afterdischarge duration (dADD), and population spike amplitude (PS) in dentate gyrus following perforant path stimulation, while applying LFS decreased the kindled seizures' parameters. In addition, kindling potentiated the early (at 10-50 ms inter-pulse interval) and late (at 150-1000 ms inter-pulse interval) paired-pulse inhibition and decreased the paired-pulse facilitation (at 70-100 ms inter-pulse interval). These effects were also inhibited by applying LFS. All inhibitory effects of LFS on kindling procedure were prevented by sulpiride administration., Conclusion: These data may suggest that LFS exerts its preventive effect on kindling development, at least partly, through the receptors on which sulpiride acts which are mainly dopamine D 2 -like (including D 2 , D 3 , and D 4 ) receptors., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Ictal hypoxaemia is a feature seen in epileptic seizures, characterized by low oxygen saturations, increasing seizure prolongation risk and possibly contributing to sudden unexpected death in epilepsy (SUDEP). High flow oxygen is recommended in the management of seizures by UK's National Institute of Health and Care excellence (NICE); however, the evidence supporting this recommendation is unclear., Aims: To identify the efficacy of oxygen in the seizure treatment., Method: A scoping review was conducted using PRISMA-ScR guidance. PsycINFO, EMBASE and MEDLINE were searched along with the references section of identified literature. Articles were critically appraised for study, patient, seizure, oxygen therapy and outcome characteristics, summarized and quality-assessed using Sackett's criteria., Results: Literature search identified 623 articles of which five met the pre-criteria for full review. One animal study demonstrated favourable effects of oxygen administration. Three human studies also reported favourable effects of oxygen administration, while one reported outcomes that were not statistically significant. Study design concerns in all identified literature confounded the ability to assess efficacy. All five publications were assigned Sackett's score of 2b., Conclusion: There is a significant lack of evidence to support the efficacy of oxygen administration in epileptic seizures. Future research is needed., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Epilepsy, frequently comorbid with depression, easily develops drug resistance. Here, we investigated how dorsal raphe (DR) and its 5-HTergic neurons are implicated in epilepsy., Methods: In mouse hippocampal kindling model, using immunochemistry, calcium fiber photometry, and optogenetics, we investigated the causal role of DR 5-HTergic neurons in seizure of temporal lobe epilepsy (TLE). Further, deep brain stimulation (DBS) of the DR with different frequencies was applied to test its effect on hippocampal seizure and depressive-like behavior., Results: Number of c-fos + neurons in the DR and calcium activities of DR 5-HTergic neurons were both increased during kindling-induced hippocampal seizures. Optogenetic inhibition, but not activation, of DR 5-HTergic neurons conspicuously retarded seizure acquisition specially during the late period. For clinical translation, 1-Hz-specific, but not 20-Hz or 100-Hz, DBS of the DR retarded the acquisition of hippocampal seizure. This therapeutic effect may be mediated by the inhibition of DR 5-HTergic neurons, as optogenetic activation of DR 5-HTergic neurons reversed the anti-seizure effects of 1-Hz DR DBS. However, DBS treatment had no effect on depressive-like behavior., Conclusion: Inhibition of hyperactivity of DR 5-HTergic neuron may present promising anti-seizure effect and the DR may be a potential DBS target for the therapy of TLE., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Implantation of a vagus nerve stimulator (VNS) can be an effective treatment for medically refractory seizures. Laryngeal side effects from a VNS can include hoarseness, cough, and shortness of breath. This report highlights a 5-year-old female who presented with stridor in the setting of acquired laryngomalacia, global developmental delay, and a VNS device. The case demonstrates that a VNS can exacerbate the symptoms of acquired laryngomalacia and that close monitoring of laryngeal side effects is crucial to optimizing care in this population. Laryngoscope, 131:E1733-E1734, 2021., (©2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives: To determine what proportion of our First Seizure referrals reflected true unprovoked first seizures or epilepsy, and to assess the long-term diagnostic accuracy of our First Seizure Clinic (FSC) by quantifying the risk of subsequent seizures in our FSC cohort., Methods: We prospectively collected data of 200 adult patients referred to the FSC between May 2014 and December 2015. We reviewed clinical notes, electroencephalography (EEG) data and performed telephone follow-up at 28-month post-diagnosis., Results: Of the 200 patients referred to the FSC, 181 attended. At the initial assessment, 39 of these patients were diagnosed with epilepsy, with most of these patients (59%) found to have a history of previous seizures. Fifty patients were diagnosed with a first seizure, of which 28% were labelled as provoked seizures. Sixty nine of the patients received another diagnosis and 23 were labelled as indeterminable. At 28 months follow-up, 11 (22%) of patients who received a diagnosis of first seizure subsequently received a diagnosis of epilepsy. In the remaining groups, only 5 (5%) patients were diagnosed with epilepsy (of these three were in the indeterminable group)., Conclusions: Our study shows that 50% of the patients referred to a FSC had not experienced a seizure but were given an alternative diagnosis. Secondly, our study indicates that the risk of seizure recurrence following a first seizure is quite low (22%). This is because a substantial proportion of the patients were diagnosed with epilepsy already at the first assessment. The high proportion of patients being diagnosed with epilepsy was mainly due to a history of previous seizures. Thirdly, patients who were given an alternative diagnosis at the first assessment had a low probability (5%) for seizure recurrence., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Seizure freedom is recognized as the goal of epilepsy treatment by patients, families, and in treatment guidelines and is associated with notably improved quality of life. However, many studies of epilepsy treatments (including antiseizure medications/antiepileptic drugs, neurostimulation, and dietary therapies) fail to report data on seizure freedom. Even among studies that include this outcome, methods for defining and analyzing seizure freedom vary considerably. Thus, the available data are often difficult to interpret and comparisons between studies are particularly challenging. Although these issues had been identified over a decade ago, there remains a lack of clarity and standardized methods used in analyzing and reporting seizure freedom outcomes in studies of epilepsy treatments. In addition, it remains unclear whether short-term seizure freedom outcomes from pivotal clinical trials are predictive of longer-term seizure freedom outcomes for patients with treatment-refractory epilepsy. Ultimately, the limitations of the available data lead to the potential for misinterpretation and misunderstanding of seizure freedom outcomes associated with the spectrum of available treatments when examining treatment options for patients. Clearly defined outcome analyses of seizure freedom attainment and duration are essential in future clinical studies of treatment for seizures to guide treatment selection and modification for patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To develop recommendations for the management of patients with primary or secondary generalized tonic-clonic seizures (GTCS) based on best evidence and experience., Methods: The Delphi methodology was followed. A multidisciplinary panel of 10 experts was established, who defined the scope, users and preliminary recommendations. Systematic and narrative reviews of the current literature were performed to assess data on the risk of sudden unexpected death in epilepsy and the efficacy and safety of add-on therapy in patients with GTCS. Twenty-five definitive recommendations were generated which were then graded on a scale of 1 (totally disagree) to 10 (totally agree) by the experts and 45 neurologists. Consensus was reached if at least 70% of the participants applied a score of ≥7. Each recommendation was then assigned a level of evidence, a grade of agreement and a grade of recommendation. The entire process was supervised by an expert methodologist., Results: Overall, 24 out of 25 recommendations achieved consensus. These included specific recommendations on diagnosis, evaluation and treatment. The recommendations also emphasized the importance of proper psychological evaluation and effective communication between patients and health professionals, and the importance of patient and family education and support., Significance: The recommendations generated by this consensus can be used as a guide for the diagnosis and management of patients with GTCS., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Holoprosencephaly (HPE) consists of a spectrum of malformations related to incomplete separation of the prosencephalon. There is a wide clinical variability depending on the HPE subtype seen on imaging. Early postnatal lethality is common, however a significant fraction of newborns diagnosed with HPE will survive into childhood and even adulthood. Here we will review the clinical management of HPE during different ages from the prenatal period to adulthood., (© 2018 Wiley Periodicals, Inc.)

The antiepileptic effects of the electrical stimulation therapies developed for patients with intractable epilepsies depend critically on the stimulation parameters, including the pulse duration, current, and frequency. Consequently, optimization of such therapies requires many animals for testing each of the stimulation parameters alone or in combination, which is costly and time consuming. This drawback could be reduced by testing several stimulation paradigms in each animal, but this requires an animal model of long-lasting seizures allowing such repetitive tests. This study was performed to validate such a model of long-lasting seizures. The present analysis was performed on electrocorticogram and intracortical signals collected from the somatosensory cortex of 11 Sprague Dawley rats. A protocol of controlled intravenous infusion of pentylenetetrazol (PTZ) was developed to induce spike-and-wave (SW) seizures and maintain stable those seizures for the whole experimental time. SW discharges were induced and maintained stable for 2 h in all rats through a two-stage infusion of PTZ. During the first stage, the SW discharges were induced by 2.5 min infusion of 10 mg/kg/min PTZ. During the second stage, the SW discharges were maintained at a stable level of frequency and power for 2 h via a 0.21 mg/kg/min PTZ infusion rate. The proposed animal model of seizures is characterized by SW discharges which remain stable for 2 h. This 2-h long time interval allows repetitive tests with different stimulation parameters in each animal, which may lead to a significant reduction of the number of animals necessary for optimizing electrical stimulation therapies developed to inhibit seizures., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: A transient decrease in seizure frequency has been identified during therapeutic brain stimulation trials with stimulator in patients in the inactive sham group. This study was performed to examine whether the implantation of intracranial electrodes decreases seizure occurrence and explores factors that may be associated., Methods: A retrospective review of 193 patients was performed, all evaluated with both scalp video EEG monitoring and intracranial EEG (iEEG) monitoring. Data about the number of seizures per day during the monitoring period, the number of days until the first seizure, anti-epileptic drugs (AEDs), pain medications, types of implanted electrodes, and anesthetic agents were reviewed. We conducted a repeated measure analysis for counted data using generalized estimating equations with a log-link function and adjustment for number of days and anti-epileptic medication load on the previous day to compare seizure frequencies between scalp and iEEG monitoring., Results: The time to the first seizure was significantly prolonged during iEEG monitoring as compared to scalp monitoring after correction for AED withdrawal (hazard ratio: 0.81, CI 0.69-0.96). During scalp video EEG monitoring, patients experienced an average of 1.09 seizures/day vs 1.27 seizures/day during iEEG monitoring (P=.066). There was no significant difference in seizure frequency in patients that received craniotomy vs burr holes only for intracranial implantation. An increasing number of electrodes implanted increased the delay to seizures (P=.01). Of all anesthetic agents used, desflurane seemed to have an anticonvulsive effect compared to other anesthetics (P=.006). Pain medication did not influence delay to seizures., Significance: Seizures are delayed during iEEG as opposed to scalp monitoring illustrating the "implantation effect" previously observed. Surgical planning should account for longer monitoring periods, particularly when using larger intracranial arrays., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Previous reports summarized the seizure types occurring in patients with idic(15) syndrome. To better define this issue, we retrospectively analyzed the evolution of electroencephalogram findings and seizures in 35 patients with confirmed idic(15). Epilepsy occurred in 28 patients (80%), with a median age of onset of 3 years 3 months. The initial seizures were infantile spasms associated with a hypsarrhythmic electroencephalogram (nine patients), focal/generalized tonic (seven patients), or atypical absences (eight patients). High doses of oral steroids were given in all nine children with infantile spasms, with remission of seizures and resolution of electroencephalogram abnormalities. Among them, three were seizure free at the time of evaluation, but six later developed Lennox-Gastaut syndrome or Lennox-Gastaut-like syndrome. The eight patients with atypical absences developed Lennox-Gastaut syndrome or Lennox-Gastaut-like syndrome. Epilepsy was well controlled in 32% of the patients; satisfactorily controlled (seizures reduced >75%) in 21.4%; partially controlled (seizures reduced <50%) in 10.7%; and uncontrolled in 32%. One patient was not taking any anti-epileptic drugs by his parents' choice. Fourteen percent were on monotherapy; whereas the other 82% were on polytherapy. Seizures stopped at a median age of 5 years 5 months. The interictal electroencephalogram showed slow/sharp waves, and/or biphasic spikes-polyspikes, spike/wave complexes, and an excess of fast activity mainly over the fronto-temporal areas. Epilepsy is a major clinical challenge in patients with idic(15), associated with a poor prognosis in 55%. Frontal lobe seizures are a novel finding. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Vagus nerve stimulation (VNS) is used as an adjunctive therapy for drug-resistant epilepsy and results in a 50% seizure reduction in up to 50% of treated patients. The VNS frequency used in the clinic today is in the range of 10-30 Hz. The evidence for choosing the stimulation frequency is limited, and little knowledge is available on the effect of other VNS frequencies. Deep brain, trigeminal nerve, or spinal cord stimulation studies have suggested the use of stimulation frequencies above 80 Hz for seizure control. Therefore, our objective for the present study was to investigate if VNS using frequencies higher than those currently used in the clinic could be more effective in attenuating seizures. Spike-and-wave (SW) discharges were induced in 11 rats, which then were subjected to VNS sessions applied at the frequencies of 10, 30, 80, 130, and 180 Hz combined with control intervals without stimulation. The anticonvulsive effect of VNS was evaluated by comparing the normalized mean power (nMP) and frequency (nMSF) of the SW discharges derived from intracortical recordings collected during the stimulation and control intervals. Compared with the control intervals, all the tested VNS frequencies significantly reduced the nMP (in the range of 9-21%). However, we found that 130 and 180 Hz VNS induced a 50% larger attenuation of seizures than that achieved by 30 Hz VNS. In addition, we found that 80, 130, and 180 Hz VNS induced a significant reduction of the nMSF, that is by 5, 7, and 8%, respectively. These results suggest that a VNS stimulation frequency in the range of 130-180 Hz may be more effective in inhibiting seizures than the 30 Hz VNS applied in the clinic today., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Unlabelled: There is a lack of scientific evidence to support the best management of neonatal seizures. Current strategies for neonatal seizure management were investigated by analysis of all surveys published during the time period 2000-2012. Methods for seizure diagnosis and availability of electroencephalogram (EEG), including monitoring, varied. Phenobarbital was the drug of first choice, and the use of off-label drugs and treatment times varied., Conclusion: We conclude that there is an urgent need for more evidence-based studies to guide neonatal seizure management., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Injury of the CA1 subregion induced by a single injection of kainic acid (1 × KA) in juvenile animals (P20) is attenuated in animals with two prior sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early-life conditioning seizures we profiled and compared the transcriptomes of CA1 subregions from control, 1 × KA- and 3 × KA-treated animals. More genes were regulated following 3 × KA (9.6%) than after 1 × KA (7.1%). Following 1 × KA, genes supporting oxidative stress, growth, development, inflammation and neurotransmission were upregulated (e.g. Cacng1, Nadsyn1, Kcng1, Aven, S100a4, GFAP, Vim, Hrsp12 and Grik1). After 3 × KA, protective genes were differentially over-expressed [e.g. Cat, Gpx7, Gad1, Hspa12A, Foxn1, adenosine A1 receptor, Ca(2+) adaptor and homeostasis proteins, Cacnb4, Atp2b2, anti-apoptotic Bcl-2 gene members, intracellular trafficking protein, Grasp and suppressor of cytokine signaling (Socs3)]. Distinct anti-inflammatory interleukins (ILs) not observed in adult tissues [e.g. IL-6 transducer, IL-23 and IL-33 or their receptors (IL-F2 )] were also over-expressed. Several transcripts were validated by real-time polymerase chain reaction (QPCR) and immunohistochemistry. QPCR showed that casp 6 was increased after 1 × KA but reduced after 3 × KA; the pro-inflammatory gene Cox1 was either upregulated or unchanged after 1 × KA but reduced by ~70% after 3 × KA. Enhanced GFAP immunostaining following 1 × KA was selectively attenuated in the CA1 subregion after 3 × KA. The observed differential transcriptional responses may contribute to early-life seizure-induced pre-conditioning and neuroprotection by reducing glutamate receptor-mediated Ca(2+) permeability of the hippocampus and redirecting inflammatory and apoptotic pathways. These changes could lead to new genetic therapies for epilepsy., (© 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Objectives: Hospital admission in otherwise healthy patients following a first unprovoked seizure is controversial. We aimed to evaluate the influence of admission in a neurology department on the identification of risk factors for seizure recurrence in patients with a first unprovoked seizure., Materials and Methods: We retrospectively reviewed the medical records of patients with a first unprovoked seizure, who were admitted to the neurology departments at two medical centers between 2007 and 2009. Risk factors for seizure recurrence included the following: abnormal neurological examination, abnormal brain CT scan, and epileptiform discharges on the EEG., Results: The study group included 97 patients (52 men) aged 18-85 years (mean 42). Eighty-seven (90%) patients were admitted following a generalized tonic-clonic seizure. Risk factors were identified in the emergency room (ER) in 36 (37%) patients, mainly including abnormalities of the neurological examination and brain CT scan. Nineteen (20%) patients had a risk factor which was not apparent during ER evaluation, consisting of epileptiform activity on the EEG. Five (5%) patients had recurrent seizures during admission, three of them without risk factors during the ER evaluation., Conclusions: Risk factors for seizure recurrence were detected during admission in nearly a quarter of the patients who presented to the emergency room with a first unprovoked seizure. Because the main advantage of admission is the EEG recording, we suggest that an early EEG should be obtained in these patients either during admission or through a special accelerated outpatient arrangement., (© 2013 John Wiley & Sons A/S.)

Lung ultrasonography is a standard tool in the intensive care unit and in emergency medicine, but has not been described in the particular setting of the labour ward. During pregnancy, acute respiratory failure and pulmonary oedema are not uncommon life-threatening events. We present two case reports outlining the potential of lung ultrasonography in parturients. In case 1, lung ultrasonography allowed early diagnosis and treatment of acute dyspnoea in a parturient admitted for suspected asthma exacerbation. Lung ultrasonography revealed a 'B-pattern' of vertical lines radiating into the lung tissue, indicating severe pulmonary oedema complicating previously undiagnosed pre-eclampsia. In case 2, a pre-eclamptic patient was managed with combined transthoracic echocardiography and lung ultrasonography. The accuracy of lung ultrasonography in detecting interstitial oedema at a pre-clinical stage allowed adequate fluid resuscitation in this patient who had a high risk of alveolar pulmonary oedema. We believe that these cases strongly support the prospective validation of lung ultrasound for management of lung disorders in pregnant women., (Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.)

Many studies have shown that patients with Alzheimer's disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome, and progression vary widely between studies. We performed a literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG) studies, and treatment responses. Finally, we consider limitations and methodological issues. There is considerable variability in the reported prevalence and incidence of seizures in patients with AD-with reported lifetime prevalence rates of 1.5-64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps., (© 2011 Blackwell Publishing Ltd.)

Aims: It is unknown whether hypothermia can disrupt the progress of epileptogenesis. The present study aimed to determine the effect of hypothermia on brain edema and epileptogenesis and to establish whether brain edema is associated with epileptogenesis after severe status epilepticus (SE)., Methodology: Rats were injected with a single dose of Kainic acid (KA) to produce either chronic epileptic rats (rats with spontaneous recurrent seizure, SRS) or rats without spontaneous recurrent seizure (no-SRS rats). A second KA injection was used to induce SE in SRS rats and in no-SRS rats. The number of SRS was counted and the brain edema induced by SE was assessed by brain water content measurement. The cognitive function was assessed by the radial-arm maze (RAM) test., Results: A second KA injection resulted in brain edema that was more severe in SRS rats than in no-SRS rats. After second injection of KA, hypothermia treatment attenuated the KA induced brain edema and reduced the SRS attack in SRS rats. Additionally cognitive function was better in hypothermia-treated SRS rats than in nomothermia treated SRS rats 1 month after the second KA injection., Conclusions: Hypothermia treatment immediately after SE not only exhibited protective effects against the chronic spontaneous recurrent convulsant seizures but also improved cognitive function. These antiepileptogenic properties of hypothermia may be related to its attenuating effect on brain edema induced by SE. They therefore suggest that brain edema may be involved in the progress of epileptogenesis., (© 2010 Blackwell Publishing Ltd.)

The main objective of this study was to evaluate the prevalence of emergencies in dental practices and the prepared-ness and the training experience in cardiopulmonary resuscitation (CPR) of Brazilian dentists in dealing with emergencies. The volunteer participants in the study were 498 Brazilian dentists who were present at the 27th International Congress of Dentistry in São Paulo. The most prevalent emergency was presyncope (reported by 54.20 percent of respondents), followed by orthostatic hypotension (44.37 percent), moderate allergic reactions (16.86 percent), hypertensive crisis (15.06 percent), asthma (15.06 percent), syncope (12.65 percent), angina (6.82 percent), convulsion (6.22 percent), hypoglycemia (5.62 percent), hyperventilation crisis (5.22 percent), choking (2.20 percent), and cerebrovascular accident (0.8 percent). Anaphylaxis, myocardial infarction, and cardiac arrest were the rarest emergencies, reported by only 0.4, 0.2, and 0.2 percent of dentists, respectively. Only 41 percent of the dentists judged themselves capable to diagnose the cause of an emergency during a dental visit. The majority responded that they would be capable of performing initial treatment of presyncope, syncope, orthostatic hypotension, convulsion, and choking. However, most of them felt unable to treat anaphylaxis, myocardial infarction, or cardiac arrest. Further, the majority felt unable to perform CPR or undertake an intravenous injection. It was concluded that the most prevalent medical emergencies in dental practice of Brazilian dentists are presyncope and orthostatic hypotension. The occurrence of life-threatening medical emergencies like anaphylaxis, myocardial infarction, cardiac arrest, and cerebrovascular accident is rare. Brazilian dentists are not fully prepared to manage medical emergencies and have insufficient experience training in CPR.

Objective: The precise mechanism of action of vagus nerve stimulation (VNS) in suppressing epileptic seizures remains to be elucidated. This study investigates whether VNS modulates cortical excitability by determining the threshold for provoking focal motor seizures by cortical electrical stimulation before and after VNS., Material and Methods: Male Wistar rats (n = 8) were implanted with a cuff-electrode around the left vagus nerve and with stimulation electrodes placed bilaterally on the rat motor cortex. Motor seizure threshold (MST) was assessed for each rat before and immediately after 1 h of VNS with standard stimulation parameters, during two to three sessions on different days., Results: An overall significant increase of the MST was observed following 1 h of VNS compared to the baseline value (1420 microA and 1072 microA, respectively; P < 0.01). The effect was reproducible over time with an increase in MST in each experimental session., Conclusions: VNS significantly increases the MST in a cortical stimulation model for motor seizures. These data indicate that VNS is capable of modulating cortical excitability.

Holoprosencephaly (HPE) is the most common malformation of the embryonic forebrain in humans. Although HPE occurs along a continuous spectrum, it has been categorized into four types from most severe to least severe: alobar, semilobar, lobar, and middle interhemispheric (MIH) variant. Facial malformations are often associated with HPE and usually correlate with the severity of brain malformation. With the most severely affected newborns, there is a high mortality rate in the first month of life, however, with milder forms of HPE, the majority survive beyond infancy. The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations have enrolled 182 living children in a prospective research study. Based on previously published reports using this database, reports from other investigators, as well as our experience and personal observations, the range of developmental, neurological, and medical problems found in children with HPE is described in this article. Virtually all children with HPE have some developmental disability and the severity correlates with the severity of the brain malformation on neuroimaging. Common medical problems include hydrocephalus, seizures, motor impairment, oromotor dysfunction with risk of poor nutrition and aspiration, chronic lung disease, gastroesophageal reflux, constipation, hypothalamic dysfunction with disturbed sleep-wake cycles and temperature dysregulation, as well as endocrine dysfunction. Diabetes insipidus in particular is found in about 70% of children with classic HPE. Recommendations for management of these problems are given based on experiences of the authors and familiarity with the literature., (2010 Wiley-Liss, Inc.)

Hyponatremia is not uncommon, serious cases can cause dangerous complications as seizures, brain damage and even death. We present a case of a young mother with post partum hemorrhage and some of the serious complications.

An endotoxin-like reaction is a host response to an agent that induces the release of endogenous pyrogens, including cytokines. The typical reaction that is associated with gentamicin is fever and chills, rigor, shivering, tachycardia with hypertension or hypotension, respiratory symptoms and muscle cramps. We report a case of a 92-year-old patient who developed an endotoxin-like reaction in the post-operative recovery unit following 200 mg of gentamicin. The reported side effect is not included in the drug sheet or in the British National Formulary. No similar incidents were reported in the UK. We discuss the clinical picture of this rare event, along with a review of the literature and recommendations.

Objectives: To evaluate the feasibility and safety of head-neck cooling in conscious normal volunteers (10) and patients with medically refractory epilepsy (5) without causing shivering., Patients and Methods: We used a non-invasive head-neck cooling system (CoolSystems Inc., Lincoln, CA, USA). The tympanic temperature (TT) and intestinal temperature (IT) were measured as two measurements of 'core temperature' (CT), and multi-site external temperatures, several physiologic variables and EEG were monitored. Seizure counts over 4-week precooling, treatment and follow-up phases were compared., Results: All 15 participants completed all the cooling sessions without significant complaints. At the end of 60 min of cooling, scalp temperature fell on average by 12.2 degrees C (P < 0.001), TT by 1.67 degrees C (P < 0.001), and IT by 0.12 degrees C (P = NS). Average weekly seizure frequency decreased from 2.7 to 1.7 events per patient per week (MANOVA: P < 0.05)., Conclusions: Non-invasive head-neck cooling is safe and well-tolerated. Initial pilot data in patients suggest that additional therapeutic studies are warranted.

We report a case of intentional overdose in a 29-year-old male with two of the newer anti-epileptic agents, lamotrigine and pregabalin. To our knowledge, this case report details the highest plasma levels of lamotrigine ever recorded in the literature. The patient presented with seizures and a reduced level of consciousness. Management of these and subsequent complications centres on supportive care in the high dependency and intensive therapy units.

Lipid emulsion has been used in the successful treatment of local anaesthetic-induced cardiovascular collapse in animals and in two cases of cardiac arrest in humans. Previous reports of levobupivacaine toxicity in humans have been characterised by neurological signs and symptoms, without serious cardiovascular events. We present a case in which presumed intravenous injection of levobupivacaine led to neurological and cardiovascular consequences. This was treated successfully by resuscitation that included intravenous Intralipid infusion.

A 17-month-old toddler became critically ill after an accidental overdose with 'Ecstasy'. A single tablet was quickly retrieved intact from under her tongue, but within 5 min the child developed generalised tonic-clonic seizures requiring immediate transfer to hospital. She also had hyperthermia (38.5 degrees C), tachycardia (150 beats.min(-1)) and hypertension. Treatment to terminate the seizures necessitated intubation and ventilation, and cooling measures brought the temperature within normal limits. The child was admitted to the intensive care unit and made a rapid recovery. She was discharged to the ward 12 h later, and had no long-term sequelae.

An 84-year-old Asian woman with hypertension and chronic renal failure was evaluated for incoherent speech, followed by intermittent interruptions of consciousness, and then status epilepticus after ingesting one star fruit (Averrhoa carambola) each day for 3 days. Conventional first-line anticonvulsants and hemodialysis were administered without significant control of the patient's seizures. Treatment was started with propofol, an intravenous agent that induces anesthesia with rapid onset and elimination from the central nervous system; this resulted in complete control of the seizures. Propofol may be an effective alternative when dialysis and conventional first-line anticonvulsants are unsuccessful in treating the symptoms of neurotoxicity.

Galanin, a 29- or 30-amino acid neuropeptide, has been implicated in the modulation of seizures. In this study, we constructed a recombinant adeno-associated viral (AAV) vector to constitutively over-express galanin (AAV-GAL). The vector mediated efficient transduction of HEK 293 cells in vitro and robust galanin expression in vivo when injected into the rat dorsal hippocampus. Rats were administered kainic acid intrahippocampally 2.5 months following AAV-GAL or empty vector (AAV-Empty) injection to study the effect of vector-mediated galanin over-expression on seizures. AAV-GAL-injected rats showed a decreased number of seizure episodes and total time spent in seizures compared to AAV-Empty rats, despite similar latencies to development of the first EEG seizure and similar levels of neuronal damage in the CA3 region for both groups. These data show that recombinant AAV mediates strong and stable over-expression of galanin when injected into the rat hippocampus resulting in a significant anticonvulsive effect. The seizure suppression effect of galanin expression in the hippocampus by viral vectors may lead to novel therapeutic strategies for the treatment and management of intractable seizures with focal onset such as temporal lobe epilepsy.

Aim: To document the incidence and early evolution of hyponatraemia (serum sodium < 136 mmol l(-1)) associated with respiratory syncytial virus (RSV) bronchiolitis in infants requiring intensive care., Methods: In a retrospective review over two winter seasons, 130 infants were admitted with confirmed RSV infection, of whom 39 were excluded because of either pre-existing risk factors for hyponatraemia: diuretic therapy (n = 14), cardiac disease (n = 10), renal disease (n = 2) or lack of admission sodium data (n = 13)., Results: The incidence of admission hyponatraemia in the remaining infants (median age 6 wk) was 33% (30/91), with 11% (10/91) exhibiting a serum sodium less than 130 mmol l(-1) . Hyponatraemic and normonatraemic infants were of a similar age (median 6 vs 7 wk, p = 0.82). With fluid restriction and diuretic therapy, the incidence of hyponatraemia at 48 h had decreased to 3.3%, odds ratio 0.07 (95% confidence interval 0.02-0.24, p < 0.001). Four infants (4%) suffered hyponatraemic seizures at admission (sodium 114-123 mmol l(-1)); three had received hypotonic intravenous fluids at 100-150 ml kg(-1) d(-1) before referral to intensive care. All four were managed successfully with hypertonic (3%) saline, followed by fluid restriction, resulting in immediate termination of seizure activity and normalization of serum sodium values over 48 h., Conclusion: Hyponatraemia is common among infants with RSV bronchiolitis presenting to intensive care. Neurological complications may occur and fluid therapy in vulnerable infants should be tailored to reduce this risk.

Objective: Over recent years transcranial magnetic stimulation (TMS) has become widely applied in the study of neuropsychiatric disorders. The aim of this article is to review the application of TMS as an investigative tool and as a potential therapeutic modality in psychiatric disorders., Method: A comprehensive literature review., Results: When applied as an investigative tool, TMS provides innovative ways to directly study the excitability of the cortex, cortical regional connectivity, the plasticity of brain responses and cognitive functioning in illness and disease states. A number of studies suggest the potential of treatment with TMS in disease states, especially in patients with depression, although difficulties exist with the interpretation of the published literature., Conclusion: TMS has a considerable role in neuropsychiatric research. It appears to have considerable potential as a therapeutic tool in depression, and perhaps a role in several other disorders, although widespread application requires larger trials and establishment of sustained response.

Aims: To carry out a retrospective pharmacoeconomic analysis of the impact of therapeutic drug monitoring (TDM) in adult patients with generalized tonic-clonic epilepsy in an academic, non profit making organization., Methods: Twenty-five patients who had undergone TDM were compared with 25 age, disease and duration of drug therapy matched controls who had not undergone TDM. Only direct costs were calculated. These included cost to the hospital of providing the TDM service, cost to the hospital per seizure saved, and cost to the patient per seizure saved., Results: Patients undergoing TDM had much more effective seizure control (P = 0.00032, OR 4.846, 95% confidence interval 1.29,18.3), fewer adverse events, better earning and were more likely to be married than the control group., Conclusions: In patients with adult onset epilepsy, a minimum of two drug estimations per year offers significant benefit in terms of better seizure control, fewer adverse events and greater chances of remission.

A peer training program, in which experienced staff trained new staff, was evaluated as a method for teaching and maintaining safety-related caregiver skills in an institutional setting for the developmentally disabled. Three sets of safety-type skills were assessed in simulated emergency situations: responding to facility fires, managing aggressive attacks by residents, and assisting residents during convulsive seizures. Using a multiple-baseline research design, results indicated that the peer training program was an effective method of training the three types of emergency skills to new direct care staff. The program also appeared effective in improving the skills of the peer trainers. Perhaps most importantly, results indicated that if experienced staff functioned as peer trainers for particular emergency skills, then their proficiency in those skills maintained over time whereas their proficiency declined in emergency skills for which they did not act as peer trainers. Social validity information collected from available staff 23 months after the program was completed supported the utility of the training in terms of staff responses during actual emergencies. Also, acceptability measures indicated that staff liked participating in the program. However, some inconsistencies between staff verbal reports and performance-based measures of acceptability were noted. Results are discussed regarding the overall effectiveness of the peer training program, the importance of maintenance strategies for safety-related skills, and the need for multidimensional analyses of staff acceptability in staff training/management research.