Paediatric sudden unexpected death in epilepsy: A parental report cohort.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) accounts for a large percentage of deaths in children with epilepsy. Contributing factors to paediatric SUDEP are incompletely understood. AIMS OF STUDY: The Epilepsy Deaths Register (EDR) is an anonymized register that compiles information on deaths related to epilepsy, across all ages and epilepsy classifications. Using the EDR, we sought to identify key risk factors for SUDEP in children to assist the development of preventive measures. METHODS: All registrations between the ages of 1 and 16 years were reviewed to identify definite or probable SUDEP. These cases were analysed to identify common demographics, comorbidities, monitoring, treatments and circumstances near to the deaths. RESULTS: We identified forty-six cases (27 males) of definite or probable SUDEP. Paediatric SUDEP is more common in a 12- to 16-year age group and in those with neuro-disability. Most paediatric SUDEP occurs during apparent sleep. There were four cases with a vagus nerve stimulator. SUDEP can occur early after the onset of seizures. CONCLUSIONS: This is the largest single cohort of SUDEP reported in children. Reports from caregivers can augment population data. Surveillance in sleep is a priority area of development.

The view of the clinician and the scientist on the family experience of sudden epilepsy deaths.

A sudden epilepsy-associated death is a tragedy for the bereaved, a failure for the clinician and a challenge for a research scientist. Sudden death in epilepsy cannot be truly anticipated or prepared for by the bereaved, or the clinical team. Communications and provision of pastoral care following sudden unexpected death in epilepsy (SUDEP) is an important part of an epilepsy service where interaction with the family and specialist services for the bereaved can be rewarding. Sudden death and SUDEP are valid targets for research attention, but families may be less aware of opportunities to assist in life science research or conversely feel coerced at a vulnerable time. We have a responsibility to ensure that the SUDEP risk is minimized and that we maximize the learning potential from each death. Out of such tragedies some good must come, but this will take combined efforts from doctors, families, and the voluntary sector acting in league with scientific and academic funders. In this review, we set out to consider the dual viewpoints of the clinician and the scientist and how they consider the family experience of sudden deaths to provide advice for all parties. "This paper is for the Special Issue: Prevent 21: SUDEP Summit - Time to Listen".

(3R,4S,5S,8S,10R,13R)-3-Hy-droxy-kaura-9(11),16-dien-18-oic acid.

The title compound, C(20)H(28)O(3), was isolated during our investigation into the chemical composition and pharmacological activity of Centipeda cunninghamii (DC.) A. Braun & Asch. (Asteraceae). The enanti-opure compound, a diterpene with a carbon skeleton, is composed of three six- and one five-membered rings in chair, twist-boat, half-chair and envelope conformations, respectively. Each mol-ecule makes one intra- and one inter-molecular O-H⋯O hydrogen bond in the crystal lattice, forming hydrogen-bonded chains along [010]. The absolute configuration of the compound was assigned on the basis of optical rotation measurements.

Decarboxylative Claisen rearrangement reactions: synthesis and reactivity of alkylidene-substituted indolines.

Microwave-assisted decarboxylative Claisen rearrangement (dCr) reactions of substituted acetate derivatives of 3-(hydroxyalkyl)indoles give de-aromatised products. The reactivity of the resultant compounds was evaluated.

Transannular Claisen rearrangement reactions for the synthesis of vinylcyclobutanes: formal synthesis of (±)-grandisol.

Unsaturated eight-membered lactones undergo decarboxylative and non-decarboxylative transannular Ireland-Claisen rearrangement reactions, to give substituted vinylcyclobutanes. A formal synthesis of (±)-grandisol is described.

Claisen rearrangements of equilibrating allylic azides.

Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen rearrangement reactions to give unsaturated γ-azidoesters and -acids, respectively. Decarboxylation of the acids under basic conditions gives azidosulfones, with moderate to high diastereoselectivity.

Risk of seizures with antidepressants: what is the evidence?

Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.

A tiered strategy for investigating status epilepticus.

In status epilepticus the imperative to start anti-seizure therapy, initially subjugates the need to investigate the cause. Once treatment is initiated this balance shifts in favour of identifying: the causes and consequences of the seizure; the factors that predetermined the occurrence of status epilepticus; and finally the prognosis of this acute episode. Just as there are multiple causes of seizures and epilepsy, there are a vast number of causes of status epilepticus. We discuss the more common and the more important to identify as they may dictate a change in therapy or a certain prognosis. Acknowledging that the burden of epilepsy and status epilepticus is preferentially felt in lower and middle income countries, we have tried to rationalise the investigation of status epilepticus. Basic laboratory studies are necessary in all patients with status epilepticus as systemic complications can occur early and can involve every organ system. Aetiology is important, however the morbidity from treatment does not discriminate when treatment resistant status epilepticus is due to dissociative seizures. Seven percent of epilepsy hospitalisations are for status epilepticus and epilepsy is a prior diagnosis half the time; awareness of prior history is invaluable. EEG is critical for diagnosis in the anaesthetised patient or those in non-convulsive status epilepticus. There is poor correlation of EEG with aetiology except in rare circumstances. Currently quantitative EEG methods should best be viewed as screening tool to reduce EEG reviewing time. MRI is clearly superior for identifying cytotoxic change and the networks that are or were involved in the episode of status epilepticus. Sequential imaging changes may give an estimate of recovery but there is insufficient detail to use MRI as a prognostication tool. We suggest the following model: 1) immediate investigations; 2) investigations targeted by the clinical scenario; 3) investigations targeted following results from bloods, imaging or EEG; 4) investigations targeted for rarer causes and super-refractory status epilepticus.

Synthesis and hetero-Diels-Alder reactions of enantiomerically pure dihydro-1H-azepines.

Thermolysis of enantiomerically pure 3-substituted 7,7-dihalo-2-azabicyclo[4.1.0]heptanes in the presence of K2CO3 gives in good yields 2-alkyl-6-halo-1-tosyl-2,3-dihydro-1H-azepines. These undergo highly stereoselective [4+2] cycloaddition reactions with heterodienophiles and arylation/alkenylation under Suzuki conditions.

Highly regioselective ring-opening of trisubstituted aziridines by sulfur-stabilised carbanions.

The highly regioselective, stereospecific ring-opening of trisubstituted N-tosylaziridines possessing vinyl and hydroxymethyl groups by sulfone- and sulfide-stablised carbanions is reported.

Fluxionality in a paramagnetic seven-coordinate iron(II) complex: a variable-temperature, two-dimensional NMR and DFT study.

The preparation and detailed characterizations of the high-spin seven-coordinate complexes [M(kappa(7)N-L)](ClO(4))(2) (M = Mn(II), Fe(II); L = N,N,N',N'-tetrakis(2-pyridylmethyl)-2,6-bis(aminomethyl)pyridine) are described. The X-ray crystal structures reveal seven-coordinate metal complex ions. Consideration of continuous shape measures reveals that the coordination environments about the metal ions are better described as having (C(s)) face-capped trigonal prismatic symmetry than (C(2)) pentagonal bipyramidal symmetry. The (S = (5)/(2)) Mn(II) species shows complicated X-band electron paramagnetic resonance (EPR) spectra and broad, unrevealing (1)H NMR spectra. In contrast, the (S = 2) Fe(II) complex is EPR-silent and shows completely interpretable (1)H NMR spectra containing the requisite number of paramagnetically shifted peaks in the range delta +150 to -60. The (13)C NMR spectra are likewise informative. Variable-temperature (1)H NMR spectra show coalescences and decoalescences indicative of an intramolecular process that pairwise-exchanges the nonequivalent pyridylmethyl "arms" of the two bis(pyridylmethyl)amine (bpa) domains. A suite of NMR techniques, including T(1) relaxation measurements and variable-temperature (1)H-(1)H correlation spectroscopy, (1)H-(1)H total correlation spectroscopy, (1)H-(1)H nuclear Overhauser effect spectroscopy/exchange spectroscopy, and (1)H-(13)C heteronuclear multiple-quantum coherence experiments, has been used to assign the NMR spectra and characterize the exchange process. Analysis of the data from these experiments yields the following thermodynamic parameters for the exchange: DeltaH++ = 53.6 +/- 2.8 kJ mol(-1), DeltaS++ = -10.0 +/- 9.8 J K(-1) mol(-1), and DeltaG++ (298 K) = 50.6 kJ mol(-1). Density functional theory (B3LYP) calculations have been used to explore the energetics of possible mechanistic pathways for the underlying fluxional process. The most plausible mechanism found involves dissociation of a pyridylmethyl arm to afford a strained six-coordinate species followed by rebinding of the arm in a different position to afford a new seven-coordinate transition state in which the pyridylmethyl arms within each bpa domain are essentially equivalent; the calculated energy barrier for this process is 53.5 kJ mol(-1), in good agreement with the observations.

2,8-Dimethyl-tricyclo-[5.3.1.1]dodecane-syn-2,syn-8-diol-propanoic acid (1/1).

The racemic title compound, C(14)H(24)O(2)·C(3)H(6)O(2), crystallizes in the monoclinic space group P2(1)/c as a 1:1 diol/carboxylic acid cocrystal, A-B. The lattice incorporates infinite chains of the alcohol-carboxylic acid-alcohol supra-molecular synthon, (⋯O-H⋯O=C(R)-O-H⋯O-H⋯), in which the hydrogen-bonded mol-ecules (A-B-A)(n) surround a pseudo-threefold screw axis. The carboxylic acid group functions like an extended alcohol hydr-oxy group. Each diol, A, takes part in two such threefold screw arrangements, leading to a hydrogen-bonded layer structure, with adjacent layers containing diol mol-ecules of opposite handedness. The central C atom of the propano bridge is disordered over two sites of occupancies 0.75 (1) and 0.25 (1). The methyl group of the propanoic acid molecule is disordered over two sites of occupancies 0.68 (1) and 0.32 (1).

1,4-Dichloro-naphthalene-2,3-diol.

The achiral planar (maximum deviation 0.014 Å) title compound, C(10)H(6)Cl(2)O(2), crystallizes in the chiral space group P2(1)2(1)2(1) in an arrangement incorporating conventional O-H⋯O hydrogen bonding leading to a supra-molecular chain.

(1R*,2R*,4S*,5R*,6R*,8S*)-4,8-Dimethyl-2,6-diphenyl-bicyclo-[3.3.1]nonane-2,6-diol.

The racemic title compound, C(23)H(28)O(2), crystallizes in the space group C2/c as a layered structure in which a centrosymmetric three hydrogen bond sequence links four molecules. Both hydroxy groups are involved in this arrangement, but they differ in that one participates in two hydrogen bonds while the other takes part in only one. Between layers, the aromatic rings take part in edge-face interactions [shortest C-H⋯C distances 3.04, 3.10 and 3.12 Šand angle between normal to planes 86.7(2)°], forming a centrosymmetric dimer. The lattice is further stabilized by C-H⋯π interactions involving both methyl (shortest C⋯C 3.82 and 3.97 Å) and methylene (shortest C⋯C 3.60 Å) groups.

2,3-Dichloro-benzene-1,4-diol.

The achiral title compound, C(6)H(4)Cl(2)O(2), crystallizes with O-H⋯O hydrogen bonding linking mol-ecules into layers. Between layers there are chains of Cl⋯Cl⋯Cl inter-actions with alternating distances of 3.274 (2) and 3.742 (2) Å. Augmenting this arrangement there are also C-H⋯Cl (2.97 and 3.17 Å) and Cl⋯π (shortest distances 3.40 and 3.54 Å) inter-actions.

7α,15α-Dibromo-8,16-diphenyl-6,7,14,15-tetra-hydro-6α,14α-epithio-cyclo-octa-[1,2-b:5,6-b']diquinoline deuterochloro-form solvate.

In the racemic title compound, C(34)H(22)Br(2)N(2)S·CDCl(3), pairs of diquinoline host mol-ecules form centrosymmetric brick-like dimers utilizing three different aryl edge-to-face inter-actions (EF(1-3)). The dimeric (EF)(6) (i.e. 2 × EF(1-3)) building blocks pack with the deuterochloro-form guest mol-ecules positioned near each of their corners. The Cl atoms of the latter are disordered over two sets of sites in a 0.53 (2):0.47 (2) ratio.

The synthesis of azadirachtin: a potent insect antifeedant.

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.

A quantitative structure-reactivity relationship in decarboxylative Claisen rearrangement reactions of allylic tosylmalonate esters.

First-order rate constants have been determined for the decarboxylative Claisen rearrangement reactions at 293 K of substituted methyl (E)-3-phenyl-2-propenyl 2-tosylmalonate esters, which show a linear free-energy relationship indicative of the development of positive charge on the benzylic position in the sigmatropic rearrangement transition-state.

Double decarboxylative Claisen rearrangement reactions: microwave-assisted de novo synthesis of pyridines.

Microwave-assisted double decarboxylative Claisen rearrangement of bis(allyl) 2-tosylmalonates provides substituted 1,6-heptadienes, which may be alkylated, and then converted into pyridines by ozonolysis followed by reaction with ammonia generated in situ under microwave conditions.

2,8-Dibromo-4,10-dichloro-6H,12H-5,11-methano-dibenzo[b,f][1,5]diazo-cine.

The title compound, C(15)H(10)Br(2)Cl(2)N(2), a 2,8-dibromo-4,10-dichloro Tröger's base analogue derived from 4-bromo-2-chloro-aniline, has a dihedral angle of 110.9 (10)° between the two aryl rings, the largest yet measured for a simple dibenzo analogue.