Search

Background A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses. Furthermore, the outcomes currently being measured may not reflect what is important to people with epilepsy. Therefore, we aim to develop a COS specific to clinical effectiveness research for adults with epilepsy using Delphi consensus methodology. Methods The EPSET Study will comprise of three phases and follow the core methodological principles as outlined by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Phase 1 will include two focused literature reviews to identify candidate outcomes from the qualitative literature and current outcome measurement practice in phase III and phase IV clinical trials. Phase 2 aims to achieve international consensus to define which outcomes should be measured as a minimum in future trials, using a Delphi process including an online consensus meeting involving key stakeholders. Phase 3 will involve dissemination of the ratified COS to facilitate uptake in future trials and the planning of further research to identify the most appropriate measurement instruments to use to capture the COS in research practice. Discussion Harmonising outcome measurement across future clinical trials should ensure that the outcomes measured are relevant to patients and health services, and allow for more meaningful results to be obtained. Core Outcome Set registration COMET Initiative as study 118.

Sound waves are all around us resonating at audible and inaudible frequencies. Our ability to hear is crucial in providing information and enabling interaction with our environment. The human brain generates neural oscillations or brainwaves through synchronised electrical impulses. In epilepsy these brainwaves can change and form rhythmic bursts of abnormal activity outwardly appearing as seizures. When two waveforms meet, they can superimpose onto one another forming constructive, destructive or mixed interference. The effects of audible soundwaves on epileptic brainwaves has been largely explored with music. The Mozart Sonata for Two Pianos in D major, K. 448 has been examined in a number of studies where significant clinical and methodological heterogeneity exists. These studies report variable reductions in seizures and interictal epileptiform discharges. Treatment effects of Mozart Piano Sonata in C Major, K.545 and other composer interventions have been examined with some musical exposures, for example Hayden's Symphony No. 94 appearing pro-epileptic. The underlying anti-epileptic mechanism of Mozart music is currently unknown, but interesting research is moving away from dopamine reward system theories to computational analysis of specific auditory parameters. In the last decade several studies have examined inaudible low intensity focused ultrasound as a neuro-modulatory intervention in focal epilepsy. Whilst acute and chronic epilepsy rodent model studies have consistently demonstrated an anti-epileptic treatment effect this is yet to be reported within large scale human trials. Inaudible infrasound is of concern since at present there are no reported studies on the effects of exposure to infrasound on epilepsy. Understanding the impact of infrasound on epilepsy is critical in an era where sustainable energies are likely to increase exposure.

INTRODUCTION We present our 12-year experience of the surgical management of lower-grade gliomas (LGGs) by a multidisciplinary team in a large tertiary UK brain tumour centre. METHODS Retrospective analysis of all adult patients who underwent surgery in the Leeds Low Grade Glioma Service between January 2010 and January 2022. Data collected included demographics, procedure type, extent of resection, histological diagnosis, morbidity, mortality, tumour location, seizure control, adjuvant therapy, cognitive outcomes, progression-free survival (PFS) and overall survival (OS). Results were statistically analysed by Kaplan-Meier and Log Rank (Cox Proportional Regression Hazard) Testing (p< 0.05). RESULTS 254 patients underwent surgery between 2010-2022. Of these, 77 patients underwent a second resection surgery, 9 a third, and 1 patient had a total of 4 resections. 184 operations were carried out awake, 115 asleep and 42 patients underwent biopsy only. The most common histology at initial surgery was astrocytoma, IDH1m, WHO Grade 2 (41.7%) with oligodendroglioma, IDH1m, WHO Grade 2 being the second most common. The majority of tumors were located in the right frontal lobe (24%) followed by the left frontal lobe (18%). 32% of tumors were on the left side. The median time between diagnosis and first surgery was 36.5 months. 8 patients died during this time frame, 7 who had resection, 1 had biopsy. CONCLUSION Our experience of the surgical management of LGG over the last 12 years shows that maximal safe surgical resection remains important as first-line treatment. Greater extent of resection (EOR) can delay transformation, control seizures and improve survival. Awake surgery is well tolerated and can preserve eloquent function. A multidisciplinary team approach achieves the best outcomes, and is appreciated by our patients

AIMS The prevalence of epilepsy in WHO grade 2 glioma is high, with seizures often being the presenting symptom. We explore the epidemiology of seizures in this patient population in a regional neurosurgical centre. METHOD Electronic health records of patients with histologically-proven WHO grade 2 glioma (n=227) were reviewed with data collected including patient demographics, epilepsy prevalence and seizure semiology. Relationships between epilepsy and overall survival were calculated using a Cox proportional hazards model in the statistical software “R,” controlling for all other variables – including histological diagnosis. RESULTS Overall, 196/227 (86.3%) patients were diagnosed with epilepsy - either at presentation (179/196, 91.3%), or during the course of their disease (17/196, 8.7%) . Mean follow-up was 7.0 years. Diffuse astrocytoma histology was associated with reduced overall 10-year survival (HR 4.68, p CONCLUSION Most WHO Grade 2 glioma patients experience focal seizures, though generalised tonic-clonic seizures are common. Motor seizure activity is a frequent feature in WHO Grade 2 glioma and may confer a survival benefit, when compared to patients that have primarily non-motor seizure activity.

Background Novel psychoactive substances (NPS) are a growing public health concern. We aimed to identify the acute neurological consequences of NPS. Method We performed a retrospective case-note review of patients who presented to the emergency department after taking NPS. Results We identified 237 admissions from 190 patients, mostly young men. There were high rates of psychiatric comorbidity (43%), unemployment (39%), homelessness (24%) and incarceration (17%). Most reported use of synthetic cannabinoids (SC; 91%). Some took synthetic cathinones (SCath; 7%) or nitrous oxide (NOS; 2%). SC caused impaired consciousness (61%) and seizures (16%). SCath users presented with psychiatric disturbance or seizures (55%). Most patients were managed conservatively (67%) and a small proportion (14%) were referred to drug or psychology services. Conclusions NPS users represent a vulnerable group in society. Certain clinical features may suggest the type of NPS used. Most patients require supportive management and onward referral to drug addiction services is recommended.

We report a case of changing semiology of intractable right temporal lobe epilepsy. The patient’s semiology of ictal spitting, altered awareness, automatisms and occasional secondary generalization remained stable for many years. 3T MRI head was normal, and subsequent advanced imaging and neu- rophysiology localised the seizure focus to the right temporal lobe and surrounding regions. He received a right temporal lobectomy, with subsequent redo surgery due to incomplete margins. These did not confer seizure freedom. Subsequently his seizure semiology changed to episodic fluent dysphasia with preserved awareness. This was correlated with scalp EEG changes now showing lateralisation to the bilateral temporal lobes.This case demonstrates that seemingly unilateral temporal lobe epilepsy may arise from bilateral networks, which can manifest for years from one hemisphere. It is also possible that extra-temporal origin seizures (for example from perisylvian, fronto-basal or parietal locations) can manifest with temporal-like semiology and can spread to either temporal lobe, and thus can be a cause of epilepsy surgery failure.nchlasim@doctors.org.uk35

The dibenzazepines particularly carbamazepine are associated with known adverse effects (AEs) and drug to drug interactions. Eslicarbazepine acetate (ESL) is structurally distinct from other members of the dibenzazepine family and has the advantage of once daily dosing. Observational and trial data report successful switching from older dibenzazepines to ESL. The evidence base for doing so is unclear and not standardized. This is a literature review following the PRISMA scoping guidelines identifying the evidence of switching dibenzazepines. Transition methods, ratios, tolerance to change, adverse effects and retention post-change were evaluated. Study quality was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. Seven studies investigated the outcome of transition between carbamazepine and or oxcarbazepine to ESL, with specific data on the transition dose ratio and scheduling. The available data suggest that the overnight transition between oxcarbazepine and ESL in a 1:1 ratio (most common) is generally well tolerated with high retention rates. The transition showed improvement in adverse events associated with oxcarbazepine across a variety of domains. Almost 60% transitioned because of adverse events experienced no further symptoms at 12 months. There is less data on the transition from carbamazepine to ESL. The evidence available suggests an overnight transition in the ratio of 1:1.3-1.5. The retention rate following transition from carbamazepine to ESL was 69% (follow-up of 4 months) with almost half of those transitioned because of adverse events experiencing no further symptoms. There is Grade C evidence available to help guide clinicians in the transition.

Highlights • Lacosamide response in Intellectual Disability (ID) is alike to general population. • Efficacy is comparable to similar studies from the UK, Germany & the Netherlands. • Higher retention & lower behavioural side-effects noted to Dutch & German studies. • Titration differs significantly in first three months between ID and non-ID group. • Findings of the UK Ep-ID Register support the safe use of LCM in the ID population., Purpose Epilepsy prevalence is significantly higher in people with Intellectual Disability (ID) compared to people with epilepsy (PWE) from the general population. Increased psychological and behavioural problems, healthcare costs, morbidity, mortality and treatment resistance to antiepileptic drugs (AEDs) is associated with epilepsy in ID populations. Prescribing AEDs for PWE and ID is challenging and influenced heavily by studies conducted with the general population. Our study compares Lacosamide (LCM) response for the ID population to those from the general population; using data from an UK based epilepsy database register (EP ID/PDD AED Register). Methods Pooled retrospective case notes data for PWE prescribed LCM at 11 UK NHS Trusts were analysed. Participants were classified as per WHO guidance into groups of moderate-profound ID, mild ID and General population. Demographics, concomitant AEDs, starting and maximum dosage, exposure length, adverse effects, dropout rates, seizure frequency were collected. Group differences were reported as odds ratios estimated from univariable logistic regression models. Results Of 232 consented participants, 156 were from the general population and 76 had ID (24 mild, 52 moderate-profound). Twelve month withdrawal rates and reasons, efficacy, side-effects, start and maximum doses were similar between the groups. Dose titration between baseline and three months was significantly slower in the ID group (p = 0.02). Conclusion There were no differences for LCM outcomes between general and ID groups. Slower LCM titration in ID populations in the first 3 months was associated with higher retention and lower behavioural side effects as compared to similar European studies.

Background Presurgical evaluation for temporal lobe epilepsy routinely assesses speech and memory lateralization and anatomic localization of the motor and visual areas but not baseline musical processing. This is paramount in a musician. Although validated tools exist to assess musical ability, there are no reported functional magnetic resonance imaging (fMRI) paradigms to assess musical processing. We examined the utility of a novel fMRI paradigm in an 18-year-old left-handed pianist who underwent surgery for a left temporal low-grade ganglioglioma. Methods Preoperative evaluation consisted of neuropsychological evaluation, T1-weighted and T2-weighted magnetic resonance imaging, and fMRI. Auditory blood oxygen level–dependent fMRI was performed using a dedicated auditory scanning sequence. Three separate auditory investigations were conducted: listening to, humming, and thinking about a musical piece. Results All auditory fMRI paradigms activated the primary auditory cortex with varying degrees of auditory lateralization. Thinking about the piece additionally activated the primary visual cortices (bilaterally) and right dorsolateral prefrontal cortex. Humming demonstrated left-sided predominance of auditory cortex activation with activity observed in close proximity to the tumor. Conclusions This study demonstrated an fMRI paradigm for evaluating musical processing that could form part of preoperative assessment for patients undergoing temporal lobe surgery for epilepsy.

This study resulted in the isolation of new alkali metal complexes of (R,R)-bis(α-methylbenzyl)amine (B-α-mba) characterized by NMR spectroscopy and single-crystal X-ray diffraction where possible. The reaction outcome was found to be dependent on metal and Lewis donor choice to afford species [{PhCH(CH3)}2NLi·Dioxane]2 2, [{PhCH(CH3)}2NLi·HMPA]2 3, [{PhCH(CH3)}2NLi·TMEDA] 4, and [{PhCH(CH3)}2NNa·(THF)k]n 5 as simple amido species. Complex [{PhC(═CH2)}{PhCH(CH3)}NNa·TMEDA]∞ 6 was isolated as a result of a β-hydride elimination. A complex mixture of species was isolated when B-α-mba was reacted with potassium in the presence of TMEDA and PMDETA to give species [{PhCH(CH3)}2NK·(TMEDA)k]n 7a, [{PhC(═CH2)}{PhCH(CH3)}NK·(TMEDA)k]n 7b, [{PhC(═CH2)NH}K·(TMEDA)k]n 7c, [{PhCH(CH3)}2NK·(PMDETA)k]n 8a, [{PhC(═CH2)}{PhCH(CH3)}NK·(PMDETA)k]n 8b, and [{PhC(═CH2)NH}K·(PMDETA)k]n 8c. In both cases, the decomposition to form the potassium enamide species 7c and 8c was the more favorable process. The decomposition reaction...

Epilepsy affects 1% of the world's population and is defined as two or more unprovoked seizures. Psychiatric conditions (depression, psychosis, anxiety, and attention deficit hyperactivity disorder (ADHD)) may coexist and are linked to negative seizure outcomes and poorer quality of life. There is an increasing body of evidence to suggest a bidirectional relationship between epilepsy and psychiatric disorders, which may imply shared pathophysiologic mechanisms. Extensive research has examined neurobiologic and neuroanatomic substrates for this association revealing some interesting similarities. Psychiatric disorders in people with epilepsy often go underdiagnosed and undertreated, due to fears of exacerbating psychiatric symptoms or provoking seizures, which may cause delays in optimal management. This chapter covers psychiatric conditions in epilepsy largely focusing on depressive disorders and psychotic disorders. Anxiety and ADHD in association with epilepsy are also discussed. Epidemiology, pathophysiologic mechanisms, and pharmacotherapies used to treat epilepsy and psychiatric disorders are also covered.

Clinical studies suggest that the antiepileptic drug (AED) brivaracetam (BRV) is associated with fewer behavioral and psychiatric adverse events (AEs) compared with levetiracetam (LEV) in treating epilepsy. There are, however, few comparative studies of treatment-emergent AEs between patients on BRV with preexisting psychiatric or behavioral comorbidities to those without. Our study compared longer-term tolerability over a 26-month period between these patient groups and assessed the overall efficacy of BRV as add-on therapy. Patients with intellectual disabilities in whom the prevalence of epilepsy is higher, are often excluded from randomized controlled trials, and our study further assessed comparative effectiveness between this patient group and those with normal range intellect. We collected prospective data on 134 patients prescribed add-on BRV for epilepsy at a tertiary UK center over a 26-month period. All patients had previously received LEV. Sixty-three patients were on LEV at the start of the data collection period. Levetiracetam was withdrawn and switched to BRV in 39 patients because of inefficacy and 24 patients because of behavioral or psychiatric side effects. Seventy-three patients (54%) had a preexisting psychiatric or behavioral disorder compared with 64 patients (46%) without. The retention rate at last follow-up [mean: 11 months (0.5–26 months)] was 60% in the psychiatric/behavioral disorders group versus 67% in those without (p = 0.68). Forty-one patients had diagnosed intellectual disabilities. The retention rate was 66% in this group versus 62% in patients without intellectual disabilities (p = 0.36). The commonest treatment-emergent AEs were somnolence (26%), aggression (23%), and depression (9%). There were similar frequencies reported for these specific events across the groups. The proportion with a 50% responder rate was 29% in patients with focal epilepsy and 47% in patients with generalized and combined focal and generalized epilepsies. However, fifteen patients (11%) reported increased seizure activity leading to withdrawal of treatment. This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no significant differences in tolerability between patients with preexisting psychiatric or behavioral comorbidities, or intellectual disability to those without.

INTRODUCTION: Brain tumours are the leading cause of cancer death in the under 40 year olds in the United Kingdom. Over the last 15–20 years there has been a significant shift in the management of Low Grade Glioma (LGG), with increasing evidence that upfront resection can improve outcome. Despite this, there remains a variation between clinical teams in their understanding and attitude regarding treatment options. Through this survey we sought to obtain information about how LGG Neurosurgery & Oncology practice is shaped throughout the UK, about the involvement of Allied Health Professionals (AHPs) and how care is structured and delivered. METHODS: Neurosurgical units in the UK were distributed a Society of British Neurological Surgeons approved questionnaire asking about LGG practices in their area. Paediatric hospitals were excluded. RESULTS: Completed forms were returned by 17 out of 32 units (53.1% response rate). In 41%, the patients are seen in a specialised LGG clinic, 35% use neuro-oncology clinics, while 24% review their patients in general neurosurgery clinics. On average, specialised LGG clinics will have 4 specialties present, as opposed to 2 in neuro-oncology clinics and only a neurosurgeon in general clinics. An average of 11 different specialties will be involved during some stage of care. In 76% of the units, the strategy is to aim for primary resection where possible. Only 12% (two units) will start by observing the tumour even if it is focal and deemed resectable. Units seeing patients in general neurosurgery clinics have more tendency to biopsy routinely at presentation compared to those with neuro-oncology or specialist clinics (p=0.027). Most centres (88%) offer surgery via awake craniotomy – with a variety of testing methods used. There was a positive correlation between operative numbers and the ability to offer awake surgery (rs(13)=0.623, p=0.013). Following surgery for Grade 2 glioma, the majority of centres (65%) initially follow their patients with serial scans. The remainder (35%) may refer patients for consideration of adjuvant therapy (chemo- and/or radiotherapy) immediately following surgery. CONCLUSIONS: Five years after guidelines were published by the European Association for Neuro-Oncology, a large proportion of respondents confirmed that they provide specialist LGG services in established multidisciplinary environments. Whilst there is heterogeneity in the approaches to the management of these tumours, the majority of centres (but not all) recognise the value of upfront surgery with the aim of achieving significant bulk resection. The methodology surrounding awake craniotomy varies markedly across the UK centres that offer this service. A unit-to-unit variation in the post-operative care of grade 2 glioma patients was also noted, with disparity in which patients are referred for adjuvant therapy. This survey supports the establishment of a UK National LGG Working Group who can setup a regular National outcome audit & establish a National LGG Database.

BackgroundNew psychoactive substances (NPS) are of global concern accounting for increasing deaths in the UK. We conducted a retrospective analysis of patients attending Leeds Teaching Hospitals NHS Trust with NPS abuse during 2016–2017 and report neurological presentations and outcomes.MethodsWe identified 227 records of NPS attendances through electronic searches using Symphony electronic software. Demographic and clinical data were obtained from case-note review.ResultsAverage age was 34, 82% were male. Two thirds were unemployed, 17% prisoners, 9% students and 4% prison workers. ‘Spice’ accounted for the majority of presentations (90%). 4-methyl methcathinone (‘MCAT’) accounted for 8% of presentations. The remainder reported nitrous oxide (NOS) use. In the spice subgroup, 52% had low GCS, 20% had seizures. Ventilatory support was required in two cases (1%). In the MCAT subgroup, average GCS was 14 and 20% of patients presented with seizure. Psychiatric disturbance was higher in MCAT group (30%). Most patients (62%) were observed in the emergency department and then discharged. Only 3% were referred to the drug and alcohol team.ConclusionsSpice accounted for the majority of NPS presentations. Unemployed single men were particularly at risk. Low GCS and seizures were the commonest presentations, with most requiring observation only.

Purpose Accurate patient assessment and screening for pressure ulcer (PU) is difficult in the clinical setting, and evaluation of nutritional status is especially problematic. The aim of this retrospective study was to determine the extent to which Braden Scale scores and other nutrition screening parameters (body mass index, poor intake, and weight loss) predict PU development in general and heel and sacral ulcers specifically. Methods Records of 230 hospitalized patients who developed PU were compared to a matched control group without PU. Logistic regression was used to determine the association of total Braden scores, Braden nutrition subscale scores, and nutrition factors with PU development at any time, within week 1, or within week 2 of hospitalization; and development of sacral and heel ulcers at these same periods. Results Braden Scale scores on hospital admission were predictive of hospital-acquired pressure ulcer development at some point during the hospital stay; and more specifically Braden scores on day 7 were predictive of PU development within week 2 of hospitalization. Among nutrition screening factors and PU development, a low body mass index showed a statistically significant relationship with sacral ulcer development. Conclusions Findings indicate that the overall Braden score is a valid predictor of PU development. Implications for clinical practice to decrease the risk for PU development include appropriate use of reliable and valid scales by nurses along with careful evaluation of nutrition parameters.

Purpose. The development and implementation of an electronically based, nurse-driven pneumococcal vaccination protocol for hospitalized patients are described. Summary. A multidisciplinary team was formed to address the development, implementation, and management of an automatic pneumococcal vaccination program. Screening of patients was performed by the nursing staff on admission to the hospital; the screening process was streamlined using computer-generated assessment forms. The electronic program enabled systematic identification of patients eligible for vaccination, standardization of vaccine order instructions, documentation of vaccinations in a centralized electronic database, automatic documentation of vaccinations on patients’ discharge instructions, and collection of vaccination data for future analysis. If vaccination was indicated, an electronic order was automatically generated for the vaccine to be administered within 24 hours. The electronic order appeared on the electronic medication administration record like any other medication. Given the prominent role of nursing in the protocol, the largest training effort was in the nursing department, with education targeting 1200 nurses. Precautions were taken to minimize unintended duplicate vaccine administration. Patients were excluded from the vaccination protocol if they were younger than age 65 years, had a fever, were still in an intensive care unit, had an acute neurologic disorder, or had any condition for which there was doubt about the safety or appropriateness of the vaccination. Multidisciplinary resources are used to further reevaluate and refine the vaccine protocol. Conclusion. A multidisciplinary team successfully developed and implemented an electronically based, nurse-driven pneumococcal vaccination protocol for hospitalized patients in a teaching hospital.

The association between music and epileptic seizures is complex and intriguing. Musical processing within the human brain recruits a network which involves many cortical areas that could activate as part of a temporal lobe seizure or become hyperexcitable on musical exposure as in the case of musicogenic epilepsy. The dichotomous effect of music on seizures may be explained by modification of dopaminergic circuitry or counteractive cognitive and sensory input in ictogenesis. Research has explored the utility of music as a therapy in epilepsy and while limited studies show some evidence of an effect on seizure activity; further work is required to ascertain its clinical potential. Sodium channel-blocking antiepileptic drugs, e.g., carbamazepine and oxcarbazepine, appear to effect pitch perception particularly in native-born Japanese, a rare but important adverse effect, particularly if a professional musician. Temporal lobe surgery for right lateralizing epilepsy has the capacity to effect all facets of musical processing, although risk and correlation to resection area need further research. There is a need for the development of investigative tools of musical processing that could be utilized along the surgical pathway. Similarly, work is also required in devising a musical paradigm as part of electroencephalography to improve surveillance of musicogenic seizures. These clinical applications could aid the management of epilepsy and preservation of musical ability.

In the Multi-Centre Study of Early Epilepsy and Single Seizures (MESS), patients were randomly allocated to immediate or delayed antiepileptic drug treatment. For time to first seizure recurrence, MESS provides strong evidence of an effect for carbamazepine as monotherapy but mixed evidence of an effect for valproate.

The highly air sensitive reaction of trimethylaluminium and trimethylgallium with a series of commonly utilised chiral secondary amines ((S)-Ph(Me)CH)(PhCH2)NH, (R,R)-Ph(Me)CH2NH and (S)-Ph(Me)CH(CH2CH CH2)NH afforded the corresponding datively bonded chiral Lewis acid/base adducts. The molecular structures of (S,R)-[Me3Al · HN(CHMePh)(CH2Ph)] (1), [(S,R)-Me3Ga · HN(CHMePh)(CH2Ph)] (2), Me3Al · HN(CHMePh)2 (3), Me3Ga · HN(CHMePh)2 (4), (S,S)-]Me3Al · HN(CHMePh)(CH2CH CH2)] (5) and (S,S)-[Me3Ga · HN(CHMePh)(CH2CH CH2)] (6) have been determined by single-crystal X-ray diffraction and found to be isostructural, crystallising in the same space group, P212121. NMR studies established that complexes 1, 2, 5 and 6 form as a diasteriomeric mixture however, in contrast to the other complexes, 1 appears to display two distinct structural isomers at low temperature.

Reaction of the chiral amine (S)-N-(α-methylbenzyl)allylamine with n-BuLi in hexane and the subsequent addition of the thus formed lithium amide to n-BuK followed by thf results in the formation and crystallisation of the cyclic heterobimetallic tetramer, {[(S)-α-(PhC(H)Me)(CH2CH CHK)N]Li · (thf)}4 (1), containing the C-metallated and N-metallated dianion of the chiral amine. The structure reveals a degree of asymmetry derived from competitive binding of K+ cations to available thf molecules, π(arene) electrons, and deprotonated allylamine moieties. Solution studies indicate very strong agostic interactions with C–H bonds in the allylamine group and retention of the terminal vinylic anion rather than delocalisation.

Crystals of a monomeric lithium dialkylaluminium amide containing two different chiral amide moieties have been isolated from the reaction of lithiated Schollkopf’s bis-lactim ether complexed by pmdta with the diethylaluminium amide of (S)-α-(methylbenzyl)benzylamine, with single crystal X-ray diffraction revealing a migration of the Li cation in the aluminate from its initial position on the pyrazine ring of the lactim ether precursor. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The thermally induced solvent-free reactions of Ph3Bi with a series of thiols and carboxylic acids (2-mercaptobenzothiazole, 2-mercaptobenzoxazole, 2-ethoxybenzoic acid, 1-mercapto-2-propanol and salicylic acid) in the ratio 1 ∶ 3 have been investigated and shown to produce the fully substituted bismuth thiolates and benzoates in good yields and purity. Thermogravimetric analysis and differential scanning calorimetry have been used to study the profiles of those reactions involving two solid components and indicate that the reactions occur with the onset of the melting of Ph3Bi. The two products from the reactions with 2-ethoxybenzoic acid and 1-mercapto-2-propanol have been characterised by single crystal X-ray diffraction and shown to be dimeric, [(2-EtOC6H5CO2)3Bi]2, 1, and polymeric, [{(CH3CH(OH)CH2S)(CH3CH(O)CH2S)}Bi]∞, 2, respectively. Compound 1 crystallises as centrosymmetric dimers with the two Bi centres bridged by carboxylate O atoms with possible polymerisation prevented by the further interaction of one of the ethoxy groups with each metal centre. In contrast compound 2 is made up of monomeric units, containing both a mono-anion and a dianion with quasi polymeric linkages arising from bridging S atoms accompanying OH⋯O hydrogen bonding interactions between the two ligand species.

Addition of the respective Lewis base donors PMDTA and HMPA to lithiated Schollkopf's bis[lactim ether] (=3,6-diethoxy-2,5-dihydro-2-isopropylpyrazine) results in the formation of the monomeric PMDTA complex (R)-(4) (P212121, orthorhombic) and the dimeric HMPA complex (R,S)-3 (P, triclinic), as determined by single-crystal X-ray crystallography. Complex 3 was always found in racemic form, while complex 4 was enantiomerically pure. The racemization process that leads to the HMPA complex (R,S)-3 was investigated and found to be independent of the temperature at which either lithiation or addition of the Lewis base occurs.

The reaction of nBuNa with (S)-N-(α-methylbenzyl)allylamine, followed by the addition of tmeda, gives a chiral sodium 1-azaallyl complex, {[(S)-α-[PhC(H)MeN−··C(H)−··CHCH3)]Na·tmeda}2, as confirmed by single crystal X-ray diffraction and solution NMR spectroscopy, and is most likely the result of a 1,3-sigmatropic rearrangement and subsequent delocalisation within the resulting enamide. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Dilithiation of the chiral amine (S)-N-(α-methylbenzyl)allylamine in the absence of a coordinating Lewis donor results in formation of crystals of a cyclic hexamer, {[(S)-α-(PhC(H)Me)(CH2CHCHLi)N]Li}6, 1, (rhombohedral, R3) while the addition of tmeda (N,N,N′,N′-tetramethylethylenediamine) leads to deaggregation and formation of the dimer, {[(S)-α-(PhC(H)Me)(CH2CHCHLi)N]Li·(tmeda)2}2, 2 (monoclinic, P21). Reaction with nBuLi followed by nBuNa leads to crystals of a cyclic mixed metal tetramer coordinated with thf, {[(S)-α-(PhC(H)Me)(CH2CHCHNa)N]Li·(thf)}4, 3 (orthorhombic, P212121). The three bimetallic complexes have been characterised by single crystal X-ray diffraction, NMR and elemental analysis. The allyl moieties in all three complexes retain the bonding pattern expected in an N-allylamine (–N(M)—CH2–C(H)C(H)M′, M = Li, M′ = Li or Na) rather than forming a delocalised dianion or an enamide. The anionic amido N and the terminal vinylic C centres form multiple short bonds to all metal centres which in turn form short interactions with all atoms in the allyl groups, and in 1 with the closest Ph carbons.

About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission.We conducted a systematic review and aimed to answer the following clinical questions: What are the benefits and risks of starting anti-epileptic drug treatment following a single seizure? What are the effects of monotherapy in newly diagnosed partial epilepsy, and in newly diagnosed generalised epilepsy (tonic clonic type)? What are the effects of additional treatments in people with drug-resistant partial epilepsy? Which people in remission from seizures are at risk of relapse on withdrawal of drug treatment? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of second-line drugs (gabapentin, levetiracetam, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin, or zonisamide), amygdalohippocampectomy, anti-epileptic drug withdrawal for people in remission, anti-epileptic drugs after a single seizure, biofeedback, carbamazepine, cognitive behavioural therapy (CBT), educational programmes, family counselling, hemispherectomy, lesionectomy, phenobarbital, phenytoin, relaxation therapy (alone or plus behavioural modification therapy), sodium valproate, temporal lobectomy, topiramate, vagus nerve stimulation as adjunctive therapy for partial seizures, and yoga.

Background: Surgical site infections (SSIs) are the third most common nosocomial infection. An antimicrobial suture was approved recently by the FDA and its use to control SSIs is supported by the high incidence of SSIs localized to the incision, the juxtaposition of sutures with incisional wounds and efficacy in preclinical models of SSIs. However, the active agent in the suture, triclosan, has associated liabilities including limited coverage for certain SSI pathogens, ubiquitous use in consumer products and the potential for resistance. Therefore, substitution of more appropriate active agents in antimicrobial sutures is highly warranted. We have developed small nonpeptidic mimics of host defense proteins (HDP) as antimicrobial agents and examined their suitability versus triclosan as active agents for antimicrobial sutures.

Broca's aphasia may manifest as mutism in some patients. Mutism may be misinterpreted as part of a depressive illness in patients with a psychiatric history. We report on a patient presenting with acute mutism who had a history of amphetamine and cannabis abuse and was later found to have sustained an infarct of the dorsolateral frontal cortex. Recognition of this mode of presentation will aid early diagnosis and treatment.

The reaction of BunM (M = Li, Na) with [(R,R)]-bis(α-methylbenzyl)amine in the presence of pmdeta results in the formation of the chiral lithium amide complex (R,R)-{[Ph(Me)CH]2NLi·pmdeta} and, remarkably, the sodium enamide, {[PhC(CH2)NH]Na·pmdeta}2; both compounds have been authenticated by single crystal X-ray diffraction.