The significance of endoplasmic reticulum (ER) store calcium in modulating transmitter release is slowly gaining recognition. One transmitter system that might play an important role in store calcium modulation of transmitter release in the CNS is acetylcholine (ACh). The main olfactory bulb (OB) receives rich cholinergic innervation from the horizontal limb of the diagonal band of Broca and blocking cholinergic signaling in the bulb inhibits the ability of animals to discriminate between closely related odors. Here we show that exposing OB slices to carbamylcholine (CCh), a hydrolysis-resistant analog of Ach, increases gamma-aminobutyric acid (GABA) release at dendrodendritic synapses onto the mitral cells. This increase in transmitter release is mediated by the activation of the M1 class of muscarinic receptors and requires the mobilization of calcium from the ER. The site of action of CCh for this effect is developmentally regulated. In animals younger than postnatal day 10, the major action of CCh appears to be on mitral cells, enhancing GABA release by reciprocal signaling resulting from increased glutamate release from mitral cells. In animals older than postnatal day 10, CCh appears to modulate transmitter release from dendrites of the interneurons themselves. Our results point to modulation of inhibition as an important role for cholinergic signaling in the OB. Our data also strengthen the emerging idea of a role for store calcium in modulating transmitter release at CNS synapses.

Purpose of review Epilepsy and anticonvulsant medications may substantially alter endocrine homeostasis, including the male reproductive hormonal system. Recent findingsSeizures in medial temporal lobe structures, through their connectivity to the hypothalamus, alter the secretion of gonadotropins. Levels of circulating bioavailable testosterone are affected by changes in the level of binding proteins, which in turn may be affected by seizure medications. The use of older generation medications which induce the cytochrome P450 system is associated with an increase in sex hormone binding globulin and lower bioactive testosterone. Sexual dysfunction, including decreased libido and decreased potency, and infertility, is seen commonly in men with epilepsy., However, its relation to sex hormone levels remains unclear. Co-morbid depression and anxiety may be important confounding factors. Testosterone and sexual function appear not to be affected by the newer generation (non-inducing) anticonvulsants. SummaryEpilepsy and its drug treatments are associated with alterations in hormonal and sexual function in men. Further study is needed to clarify the precise mechanisms behind these alterations, as some of the data conflict. More attention should be paid to this issue in male patients with seizures; when appropriate, treatment for psychiatric co-morbidity and switches in anticonvulsant therapy may be worth consideration.

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To investigate the performance of seizure detection methods and nursing staff response in our epilepsy monitoring unit (EMU). Methods: We retrospectively reviewed 38 EMU patient admissions over a 1-year period capturing 133 epileptic and non-epileptic seizures with associated video-EEG data. We recorded detailed seizure event characteristics for further analysis. Results: Rates of seizure detection, alarm usage, and time to nursing response varied by seizure type. Patients self-activated the push button (PB) alarm for 31.1% of all seizures, but only 8.9% of focal impaired awareness (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS). In comparison, the Persyst automated seizure alarm reliably detected both electrographic seizures (76.2% of electrographic seizures) and FIAS/FBTCS (87.2% of FIAS/FBTCS), with a false positive alarm rate (FAR) of 0.14/hour, or every 7.3 h.11.4% of all seizures went unrecognized by nursing staff, of which the majority (80.0%) were FIAS. The PB alarm was of higher yield for alerting nurses to focal aware seizures (FAS) and psychogenic non-epileptic seizures (PNES) versus FIAS and FBTCS (p < 0.001). In contrast, nurses relied more on the automated Persyst software alarm to detect FIAS (p < 0.001). Time to nursing response was no different following audible alarm onset for the PB compared to the Persyst alarms (p = 0.14). Conclusion: Automated seizure detection software plays an important role in our EMU in seizure recognition, particularly for alerting nurses to FIAS. More rigorous studies are needed to determine the best utilization of various monitoring techniques and to promote high quality standards and patient safety in the EMU.

BackgroundOptimal anti-epileptic drug (AED) treatment maximises therapeutic response and minimises adverse effects (AEs). Key to therapeutic AED treatment is adherence. Non-adherence is often related to severity of AEs. Frequently, patients do not spontaneously report, and clinicians do not specifically query, critical AEs that lead to non-adherence, including sexual dysfunction. Sexual dysfunction prevalence in patients with epilepsy ranges from 40 to 70%, often related to AEDs, epilepsy or mood states. This case reports lamotrigine-induced sexual dysfunction leading to periodic non-adherence.AimsTo report lamotrigine-induced sexual dysfunction leading to periodic lamotrigine non-adherence in the context of multiple comorbidities and concurrent antidepressant and antihypertensive pharmacotherapy.MethodCase analysis with PubMed literature review.ResultsA 56-year-old male patient with major depression, panic disorder without agoraphobia and post-traumatic stress disorder was well-controlled with escitalopram 20 mg bid, mirtazapine 22.5 mg qhs and alprazolam 1 mg tid prn. Comorbid conditions included complex partial seizures, psychogenic non-epileptic seizures (PNES), hypertension, gastroesophageal reflux disease and hydrocephalus with patent ventriculoperitoneal shunt that were effectively treated with lamotrigine 100 mg tid, enalapril 20 mg qam and lansoprazole 30 mg qam. He acknowledged non-adherence with lamotrigine secondary to sexual dysfunction. With lamotrigine 300 mg total daily dose, he described no libido with impotence/anejaculation/anorgasmia. When off lamotrigine for 48 h, he described becoming libidinous with decreased erectile dysfunction but persistent anejaculation/anorgasmia. When off lamotrigine for 72 h to maximise sexual functioning, he developed auras. Family confirmed patient’s consistent monthly non-adherence for 2–3 days during the past year.ConclusionsSexual dysfunction is a key AE leading to AED non-adherence. This case describes dose-dependent lamotrigine-induced sexual dysfunction with episodic non-adherence for 12 months. Patient/clinician education regarding AED-induced sexual dysfunction is warranted as are routine sexual histories to ensure adherence.Declaration of interestNo financial interests. K.R.K. is Editor of BJPsych Open; he took no part in the peer-review of this work.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

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Topiramate (TPM) is effective for multiple seizure types and epilepsy syndromes in children and adults. Topiramate has adverse effects (including cognitive, depression, renal stones), but many of these are low incidence when started at a low dose and slowly titrated to 100 to 200 mg/day. Also, TPM has proven benefit for migraine, obesity, eating disorders, and alcohol use disorders, which can be comorbid in patients with epilepsy and may also be effective in subpopulations within specific psychiatric diagnoses. Recently approved extended-release formulations of TPM (Trokendi and Qudexy in the United States) have reliable data supporting their safety and efficacy for patients with epilepsy. They have potential for more rapid titration within 1 month to 200 mg/day and have better patient retention than TPM immediate-release, but there are no robust double-blind randomized controlled trials comparing the different formulations. We expect the once per day extendedrelease formulations to improve medication adherence compared with the twice per day formulations. This has significant potential to improve outcomes in epilepsy and the other TPM-responsive disorders.

Dementia, especially Alzheimer's disease, is an important cause of seizures and epilepsy midst the elderly. With the increasing life span, the incidence of dementia and epilepsy is expected to increase exponentially. Care of patients with advanced dementia can be demanding and seizures add to this burden. Though recognition of seizures in these patients can be difficult, seizures in these patients tend to be highly responsive to pharmacological therapy. However, choosing the right antiepileptic drug can be a challenge and complicated by altered kinetics and polypharmacy. While ongoing seizures can worsen the cognitive status in these patients, antiepileptic drugs could also add to the cognitive burden. The newer generation drugs show promise in terms of their side effect profile without compromising on the efficacy.