Surgical management of acute subdural haematomas: current practice patterns in the United Kingdom and the Republic of Ireland.

INTRODUCTION: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of acute subdural haematomas (ASDH). In 2011, a collaborative group was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of decompressive craniectomy, in comparison with craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multicentre, pragmatic, parallel group randomised trial of DC versus craniotomy for adult head-injured patients with an ASDH. In this study, we used an online questionnaire to assess the current practice patterns in the management of ASDH in the UK and the Republic of Ireland, and to gauge neurosurgical opinion regarding the proposed RESCUE-ASDH trial. MATERIALS AND METHODS: A questionnaire survey of full members of the Society of British Neurological Surgeons and members of the British Neurosurgical Trainees Association was undertaken between the beginning of May and the end of July 2012. RESULTS: The online questionnaire was answered by 95 neurosurgeons representing 31 of the 32 neurosurgical units managing adult head-injured patients in the UK and the Republic of Ireland. Forty-five percent of the respondents use primary DC in at least 25% of patients with ASDH. In addition, of the 22 neurosurgical units with at least two Consultant respondents, only three units (14%) showed intradepartmental agreement regarding the proportion of their patients receiving a primary DC for ASDH. CONCLUSION: The survey results demonstrate that there is significant uncertainty as to the optimal surgical technique for primary evacuation of ASDH. The fact that the majority of the respondents are willing to become collaborators in the planned RESCUE-ASDH trial highlights the relevance of this important subject to the neurosurgical community in the UK and Ireland.

Chordoma of the anterior skull base presenting as a swelling of the medial canthus of the eye.

Intracranial chordomas are locally infiltrative tumours that usually present with deficits of the cranial nerves. Because of their location in the skull base they are difficult to cure and pose complex problems in management. We report an unusual case of a chordoma that presented as a swelling of the medial canthus. Diagnosis of chordoma might not be considered in this site, which is unfortunate because its superficial location offers the possibility of complete excision and cure.

Activation of Ih is necessary for patterning of mGluR and mAChR induced network activity in the hippocampal CA3 region.

Neuronal networks of the hippocampal CA3 region generate stereotyped patterns of electrical activity in response to activation of metabotropic glutamate receptors (mGluRs) or muscarinic acetylcholine receptors (mAChRs) that consist of intermittent episodes of prolonged oscillatory activity. In light of the slow kinetics of such network responses, we investigated the possible contribution of the hyperpolarisation-activated inward current (I(h)) in the generation and maintenance of hippocampal oscillatory states. Hippocampal 'mini-slice' experiments in which the main subfields of the hippocampus were isolated by transection of the connecting afferents revealed that the CA3 region was the primary generator of both mGluR and mAChR-mediated network responses. Subsequent patch-clamp experiments confirmed the presence of a prominent hyperpolarisation-activated inward current in the principal cells of the CA3 region that was sensitive to caesium chloride and the selective I(h) blocker ZD-7288.Furthermore, in the presence of mAChR or mGluR agonists these cells exhibited a slow membrane potential oscillation that was independent of AMPA receptor-mediated synaptic transmission. Blockade of I(h) suppressed this oscillation as well as mGluR and mAChR-induced theta based intermittent network oscillatory behaviour. These data support the idea that the I(h) pacemaker current is important in the generation of patterned neuronal activities in the hippocampus.

Opioid receptor regulation of muscarinic acetylcholine receptor-mediated synaptic responses in the hippocampus.

A common feature of many synapses is their regulation by neurotransmitters other than those released from the presynaptic terminal. This aspect of synaptic transmission is often mediated by activation of G protein coupled receptors (GPCRs) and has been most extensively studied at amino acid-mediated synapses where ligand gated receptors mediate the postsynaptic signal. Here we have investigated how opioid receptors modulate synaptic transmission mediated by muscarinic acetylcholine receptors (mAChRs) in hippocampal CA1 pyramidal neurones. Using a cocktail of glutamate and gamma-amino-butyric acid (GABA) receptor antagonists a slow pirenzepine-sensitive excitatory postsynaptic potential (EPSP(M)) that was associated with a small increase in cell input resistance could be evoked in isolation. This response was enhanced by the acetylcholine (ACh) esterase inhibitor physostigmine (1 microM) and depressed by the vesicular ACh transport inhibitor vesamicol (50 microM). The mu-opioid receptor agonists DAMGO (1-5 microM) and etonitazene (100 nM), but not the delta- and kappa-opioid receptor selective agonists DTLET (1 microM) and U-50488 (1 microM), potentiated this EPSP(M) (up to 327%) without affecting cell membrane potential or input resistance; an effect that was totally reversed by naloxone (5 microM). In contrast, postsynaptic depolarizations and increases in cell input resistance evoked by carbachol (3 microM) were unaffected by DAMGO (1-5 microM) but were abolished by atropine (1 microM). Taken together these data provide good evidence for a mu-opioid receptor-mediated presynaptic enhancement of mAChR-mediated EPSPs in hippocampal CA1 pyramidal neurones.

Regulation of muscarinic acetylcholine receptor-mediated synaptic responses by GABA(B) receptors in the rat hippocampus.

1. Both GABA(B) and muscarinic acetylcholine receptors (mAChRs) influence hippocampal-dependent mnemonic processing. Here the possibility of a direct interaction between GABA(B) receptors and mAChR-mediated synaptic responses has been studied using intracellular recording in rat hippocampal slices. 2. The GABA(B) receptor agonist (-)-baclofen (5-10 microM) depressed an atropine-sensitive slow EPSP (EPSP(M)) and occluded the GABA(B)-receptor-mediated IPSP (IPSP(B)) which preceded it. These inhibitory effects were accompanied by postsynaptic hyperpolarization (9 +/- 2 mV) and a reduction in cell input resistance (12 +/- 3 %). 3. The selective GABA(B) receptor antagonist CGP 55845A (1 microM) fully reversed the depressant effects of (-)-baclofen (5-10 microM) such that in the combined presence of (-)-baclofen and CGP 55845A the EPSP(M) was 134 +/- 21 % of control. 4. (-)-Baclofen (5-10 microM) caused a small (28 +/- 11 %) inhibition of carbachol-induced (3.0 microM) postsynaptic depolarizations and increases in input resistance. 5. CGP 55845A (1 microM) alone caused an increase in the amplitude of the EPSP(M) (253 +/- 74 % of control) and blocked the IPSP(B) that preceded it. 6. In contrast, the selective GABA uptake inhibitor NNC 05-0711 (10 microM) increased the amplitude of the IPSP(B) by 141 +/- 38 % and depressed the amplitude of the EPSP(M) by 58 +/- 10 %. This inhibition was abolished by CGP 55845A (1 microM). 7. Taken together these data provide good evidence that synaptically released GABA activates GABA(B) receptors that inhibit mAChR-mediated EPSPs in hippocampal CA1 pyramidal neurones. The mechanism of inhibition may involve both pre- and postsynaptic elements.

Coincident activation of mGluRs and mAChRs imposes theta frequency patterning on synchronised network activity in the hippocampal CA3 region.

Activation of metabotropic glutamate receptors (mGluRs) with the broad spectrum mGluR agonist 1S,3R ACPD (10-50 microM) induced spontaneous field potentials at low frequencies ('burst-mode' activity; <1 Hz) in the CA3 region of rat hippocampal slices. At higher concentrations (100-400 microM) ACPD switched this form of activity to a second, more complex pattern of activity in which intermittent episodes of theta frequency oscillations predominated ('theta-mode' activity; 4-14 Hz). Both patterns of activity were evoked by selective activation of group I mGluRs and, in particular, could be induced by activation of mGluR5 alone using the subtype selective agonist CHPG (0.5-5 mM). In contrast, activation of group II mGluRs (DCG IV; 100 microM) produced only burst-mode behaviour whilst activation of group III mGluRs (L-AP4; 100 microM) did not result in synchronised network activity. Concurrent extra- and intracellular recordings demonstrated that this mGluR-induced theta-mode activity represented the synchronous firing of CA3 pyramidal cells and that it shared a similar temporal signature to that generated by activation of muscarinic acetylcholine receptors (mAChRs). Furthermore, application of mGluR and mAChR agonists at concentrations sufficient to produce only burst-mode activity when applied individually, produced theta-mode activity when co-applied. These data suggest that the level of activation of different mGluRs and mAChRs crucially determine the pattern of rhythmical network activity generated in the hippocampal CA3 network. These results also indicate that individual receptor subtypes (i.e. mGluR5) can initiate patterns of coherent network activity but that interactions between the cholinergic and glutamatergic transmitter systems may also be important factors in governing the temporal patterning of hippocampal network activity.

Activation of nicotinic acetylcholine receptors patterns network activity in the rodent hippocampus.

1. Intracellular and extracellular recordings from area CA3 of rat and mouse hippocampal slices revealed two distinct modes of synchronous network activity in response to continuous application of muscarinic acetylcholine receptor (mAChR) agonists. At low concentrations (e.g. 0.1-1 microM oxotremorine-M), 'burst-mode' activity comprised regular individual AMPA receptor-mediated depolarizing events, each generating several action potentials. At higher concentrations (5-50 microM), 'theta-mode' prevailed in which ordered clusters of depolarizing theta-frequency oscillations occurred. 2. Whilst theta-mode activity was abolished by the mAChR antagonist atropine (5 microM), the nicotinic acetylcholine receptor (nAChR) antagonists tubocurarine (100 microM), mecamylamine (100-500 microM) and dihydro-beta-erythroidine (250 microM) converted this mode of activity to burst-mode. 3. Likewise, disruption of synaptically available ACh using inhibitors of choline uptake (hemicholinium-3; 20-50 microM) or vesicular ACh transport (vesamicol; 50 microM) converted theta-mode into burst-mode activity. 4. Hippocampal slices prepared 2-3 weeks after transection of the primary cholinergic efferent pathway from the medial septum exhibited reduced vesicular ACh transporter immunoreactivity but still supported nAChR-dependent theta-mode activity suggesting that ACh released from this pathway was not critical for the activation of these receptors. 5. In summary, ACh-mediated activation of nAChRs tailors the pattern of network activity into theta-frequency depolarizing episodes as opposed to synchronized individual events at much lower frequencies.