Infections in Neurosurgery and Their Management

Surgical site and postoperative infections are common problems in surgical wards and treating them can be challenging and very complicated. It is important to understand different types of postoperative infections and their best management. In this chapter we try to emphasis on infections which are occurring in neurosurgical units and how to approach them. Foreign body infection is another challenge that happens in neurosurgical units, and it is vital to recognize these infections in time and start the treatment as soon as possible. Atypical infections occurrence is low therefore this problem is not addressed often in textbooks or in the literature, therefore atypical infections will be discussed in this chapter too. By discussing the most common postoperative complications and their best management profile, the authors here will try to widen the perspective of readers on infections in neurosurgical units in order to understand this problem better. Untreated infections or poorly treated infections can lead to sepsis and catastrophic results

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Observations of Changes of Blood Pressure Before and after Neurosurgical Decompression in Hypertensive Patients with Different Types of Neurovascular Compression of Brain Stem

Aims: The neurovascular pulsatile compression of the rostral ventrolateral medulla can be divided into different subtypes. The posterior inferior cerebellar artery and/or vertebral artery can compress either the rostral ventrolateral medulla or the cranial nerves IX and X or both and on left, right or both sides. Methods: It was retrospectively investigated whether the types of neurovascular compression can influence blood pressure values. Data from 13 resistant hypertensive patients after decompression were investigated. Results: Six patients had 2 compressions, two had only medulla compression, four had only nerve compression on the left side and one had 2 compressions on both sides. There was no correlation between the types of compression and the levels of blood pressure, either before or after the decompression. Both, systolic and diastolic blood pressures and pulse pressure also decreased in all cases after the decompression but the change was significant only in the group with 2 compressions on the left side. Conclusion: According to our data, in a severe hypertension not responding to conventional antihypertensive therapy, the surgical decompression of the brain stem independently of the types of neurovascular compression could guarantee a decrease of blood pressure and improved sensitivity to antihypertensive medication

Automatic deep learning-driven label-free image-guided patch clamp system

Patch clamp recording of neurons is a labor-intensive and time-consuming procedure. Here, we demonstrate a tool that fully automatically performs electrophysiological recordings in label-free tissue slices. The automation covers the detection of cells in label-free images, calibration of the micropipette movement, approach to the cell with the pipette, formation of the whole-cell configuration, and recording. The cell detection is based on deep learning. The model is trained on a new image database of neurons in unlabeled brain tissue slices. The pipette tip detection and approaching phase use image analysis techniques for precise movements. High-quality measurements are performed on hundreds of human and rodent neurons. We also demonstrate that further molecular and anatomical analysis can be performed on the recorded cells. The software has a diary module that automatically logs patch clamp events. Our tool can multiply the number of daily measurements to help brain research. Patch clamp recording of neurons is slow and labor-intensive. Here the authors present a method for automated deep learning driven label-free image guided patch clamp physiology to perform measurements on hundreds of human and rodent neurons.Peer reviewe

LTD fails in weak single-fiber PC-FSIN connections, but is generated by coactivity of multiple glutamatergic fibers.

<p>(A) LTD fails in PC–FSIN pairs with small EPSP. (A1) Schematic shows experimental design. A presynaptic PC spike (red) with postsynaptic EPSCs (blue, average of 5 at −60 mV) in one recording and confocal micrographs of the FSIN axon (nb, neurobiotin) with pv+ boutons (scale 5 μm, arrows point colabeling in merged image). (A2) One PC–FSIN pair with the EPSPs in baseline and after the afferent cell 40 Hz bursts (arrow). Averaged EPSPs (5) at Em −72 mV on top at different time points and a 40 Hz burst. Postsynaptic cell is at Em (current clamp) during the recording and the bursts. (A3) Mean ± s.e.m. (30 s bin, baseline-normalized) of similar experiment in five PC–FSIN pairs with small amplitude EPSPs (1.89 ± 0.43 mV in baseline with failures). (A4) Failure of the LTD in weak PC–FSIN connections is not due to insufficient postsynaptic depolarization. Plot shows EPSP in one PC–FSIN pair before and following the presynaptic bursts, now paired with FSIN depolarization beyond the firing threshold (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#sec009" target="_blank">Methods</a>). Averages of EPSPs (5 at Em −66 mV) and a 40 Hz burst with simultaneous depolarization (30 mV, 250 ms) in voltage clamp shown on top. (A5) Mean ± s.e.m. of five similar experiments with small EPSP (1.44 ± 0.22 mV in baseline with failures) PC–FSIN pairs (baseline-normalized, 30 s bin). The underlying data are shown in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s010" target="_blank">S4 Data</a>. (B) Connections between PCs exhibit small amplitude EPSPs with no long-term plasticity when PC1 bursts, while PC2 is at resting membrane potential. (B1) EPSP amplitude in one experiment before and after the 40 Hz presynaptic cell bursts (arrow, postsynaptic cell at Em −78 mV). Averaged EPSPs (five at Em) shown on top with a 40 Hz burst, and a schematic showing the experimental design. (B2) Mean ± s.e.m. of baseline-normalized EPSPs (1.40 ± 0.30 mV in baseline with failures) in four PC–PC pairs as in <i>B1</i> (30 s bin) (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s010" target="_blank">S4 Data</a>). (C) Activation of multiple afferent pathways to FSINs using extracellular stimulation reveals group I mGluR-dependent LTD in weak PC–FSIN synapses (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s011" target="_blank">S5 Data</a>). (C1) One experiment with monosynaptic EPSC in FSIN (voltage clamped at −60 mV) at baseline and following the 40 Hz bursts applied to the stimulation pathway (arrow at 0 time point). Inset traces (averages of 5) show evoked EPSCs in baseline and in LTD. The monosynaptic component is indicated by dotted vertical line. Schematic shows experimental design. (C2) Mean ± s.e.m. of seven baseline-normalized experiments as in <i>C1</i> showing the LTD in control conditions (open symbols, <i>p</i> < 0.001, paired <i>t</i>-test) and blockade of the LTD in experiments with LY367385 (100 μM) and MPEP (25 μM) (solid symbols, <i>n</i> = 7, paired <i>t</i>-test). (C3) Generation of group I mGluR-dependent LTD by 40 Hz stimulation is conserved in mammalian neocortex occurring also in rat FSINs. Multiple fiber extracellular stimulation with LTD in rat L2–3 somatosensory cortex FSINs. Open symbols show experiments in control conditions (<i>n</i> = 5, <i>p</i> < 0.01) and solid symbols in the presence of LY367385 (100 μM) and MPEP (25 μM) (<i>n</i> = 5) (Wilcoxon test). Blockers for glutamate <i>N</i>-methyl-D-aspartatereceptors (NMDARs) (DL-2-Amino-5-phosphonopentanoic acid; DL-APV, 100 μM) and GABA_ARs (PiTX, 100 μM) were present in <i>C1–C3</i>. (C4-C5) Likewise, LTD of the EPSCs in both species is associated with an increased amplitude SD versus the mean. Data shows decreased CV⁻² (baseline-normalized at 20 min after 40 Hz) in LTD in control conditions, but not when LTD is blocked in the presence of group I mGluR blockers (<i>p</i> < 0.05 between groups, Mann-Whitney test).</p

The LTD depresses discharge of FSINs in complex events.

<p>(A) Large EPSPs and APs in FSIN (blue) with short 3 to 5 ms delay elicited by single PC spike (red, peak indicated by vertical line). The figure shows four consecutive cycles with 10 s interval in one vgat+ and pv+ FSIN at Em (−69 mV) (note short AP duration, the positive peaks are indicated in the abscissa). Schematic shows experimental setting. (B) Single PC spike triggers disynaptic GABAergic currents in the layers 2–3. Dual whole-cell PC recordings (voltage-clamp) show that single PC1 APs trigger dIPSCs in PC2 with high probability and short delay. Schematic shows experimental design. (B1) Traces show consecutive events (4) in one experiment. The dIPSC onsets are marked in abscissa. (B2) Histograms (ordinates normalized and show from 0 to 1) illustrate delay distribution of the first dIPSC onset in four experiments (each 6–9 min, indicated as pairs 1–4) in control conditions. Most evoked dIPSCs are phase-locked to the presynaptic PC spike with <10 ms delay with obvious moderate variability of the mode of delay between experiments (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s012" target="_blank">S6 Data</a>). (C) The dIPSCs are generated by glutamatergic excitation. Sample traces show five consecutive dIPSCs between PC1 and PC2 in baseline conditions and the blockade with AMPAR blocker GYKI53655 (25 μM) (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s004" target="_blank">S4 Fig</a>). (D–E) The single AP-evoked dIPSCs between PCs are stable over a long period (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s012" target="_blank">S6 Data</a>). (D) Raster plot illustrates timing of dIPSC onset (in PC2) evoked by an AP in the presynaptic PC (PC1) in one 30 min experiment. Consecutive (6) presynaptic spikes and dIPSCs at different time points shown on top. (E) Three experiments (pairs 1, 2, and 3) as in <i>D</i> (pair 1), illustrated with histograms showing the dIPSC onset delay in different time windows (0–5 min, 10–15 min, and 20–25 min). The dIPSC probability and delay are stable for at least 30 min (Chi-square test). (F–G) dIPSCs show LTD after presynaptic PC 40 Hz burst firing (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s012" target="_blank">S6 Data</a>). (F) 40 Hz spike bursts in the presynaptic PC (similar to the LTD experiments in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.g002" target="_blank">Fig 2</a>) induce LTD of the dIPSCs. Raster plot shows dIPSCs in one paired PC recording. After baseline, the 40 Hz spike bursts in PC1 (at 0 time point, dotted horizontal line) induce permanent depression of the dIPSC occurrence. Traces illustrate the presynaptic cell spike and the dIPSCs (6) at baseline and the absence of dIPSCs after 20 min. (G) Three similar experiments (pairs 1, 2, and 3) as in <i>F</i> (pair 1), showing the LTD of dIPSCs after the 40 Hz presynaptic bursts (BL −5 to 0 min) (<i>p</i> < 0.01, Chi-square test). (H–I) The LTD of dIPSCs is blocked with group I mGluR antagonists (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s012" target="_blank">S6 Data</a>). (H) Similar experiment as in <i>F</i>, but in the presence of LY367385 (100 μM) and MPEP (25 μM). Traces on top show the pre- and disynaptic currents at baseline and 20 min after the 40 Hz bursts. (I) Three experiments as in <i>H</i> (pair 1) illustrated with dIPSC onset delay histograms at the baseline (−5 to 0 min) and at two time windows after the 40 Hz presynaptic bursts.</p

A subset of human neocortical PCs innervate FSINs with VLEs.

<p>(A) Triple whole-cell recording demonstrating the rich glutamatergic connectivity in the human neocortex layers 2–3 (L2–3). Two PCs (PC1 red and PC2 green) in L2–3 synaptically excite the same FSIN (blue). (A1) Partial reconstruction of the cells with color-coding presented in the schematic inset. Scale 25 μm. Confocal images illustrate positive immunoreactions of the neurobiotin (nb, Cy3)-filled interneuron axon boutons for vgat (Cy5, arrows in merged image) and pv (Alexa488, arrow). Scales 5 μm. (A2–3) Sample traces show presynaptic spikes (superimposed) and postsynaptic currents in the synaptic connections (cells voltage clamped at −60 mV). PC1 generates large monosynaptic EPSC in the interneuron (A2), whereas PC2 evokes small EPSC in the same cell (A3). In addition, PC2 is synaptically connected to PC1. The EPSCs from the PCs show fast kinetics in the interneuron, whereas EPSC in the PC–PC connection is slow. (A4) The two glutamatergic inputs to the FSIN show very different amplitude EPSPs and distinct paired-pulse ratios in current clamp (at Em –69 mV). (B) Histograms show the distribution of average EPSP amplitude (1 mV bin, failures excluded) in 16 identified L2–3 PC–PC pairs (B1) and in 22 PC–FSIN pairs (B2). (B3) The very large and the small amplitude EPSCs from PCs to FSINs show similarly fast time-to-peak time. Values are average EPSCs (of at least five) from individual pairs. The underlying data are shown in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s007" target="_blank">S1 Data</a>.</p

Single fiber connections to FSINs with large EPSP show group I mGluR-dependent LTD.

<p>(A) Paired recordings from synaptically connected layer 2–3 PCs and FSINs with large amplitude EPSCs/EPSPs show LTD. The LTD is generated by the presynaptic PC firing 40 Hz bursts (5 pulses, 40 times), while the postsynaptic cell is at Em. (A1) Partial reconstruction of one recorded PC (red, axon orange)–FSIN (blue, axon light blue) pair with large EPSCs/EPSPs. Scale 50 μm. L2–3 indicates layer 2–3. Schematic shows experimental design and color-coding for the cells and traces. Confocal micrographs illustrate vgat+ and pv+ axon bouton of the FSIN filled with neurobiotin (nb, scale 2 μm). A PC spike and averaged EPSC (5 at −60 mV) in the cell pair below. Scales 1 nA and 100 pA/5 ms. (A2) Single AP-evoked EPSP amplitude (interval 10 s) in the same experiment at baseline and following the PC 40 Hz burst firing (arrow at 0 time point). The afferent single fiber burst firing induced LTD (at 20−25 min <i>p</i> < 0.001, paired <i>t</i>-test). The EPSPs (blue, average of 5 at Em –62 mV) and presynaptic cell spikes (red) at different time points and one 40 Hz burst illustrated on top. The FSIN is at Em during the recording. (A3) Mean ± standard error of the mean (s.e.m.) in five PC–FSIN pairs with large EPSP (5.85 ± 0.59 mV at baseline, showing no failures) show prominent LTD (30 s bin, baseline-normalized, <i>n</i> = 5 pairs, <i>p</i> < 0.01, Wilcoxon test). (A4) The LTD requires group I mGluRs. A PC–FSIN pair with large EPSP in the presence of group I mGluR blockers LY367385 (100 μM) and 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP, 25 μM) (applied 5 min before the bursts indicated by arrow). The EPSPs (blue, at Em −67 mV) and presynaptic cell spikes (red) shown on top. The FSIN is at Em during recording. (A5) Mean ± s.e.m. of similar PC–FSIN pairs with large EPSPs (8.42 ± 2.83 mV in baseline, showing no failures) in four experiments (30 s bin, baseline-normalized). The underlying data are shown in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s008" target="_blank">S2 Data</a>. (B) EPSP analyses indicate presynaptic LTD. (B1) LTD (<i>n</i> = 5) is associated with an increased ratio of the EPSP amplitude SD/mean illustrated here as decreased baseline-normalized CV⁻² (mean ± s.e.m. black asterisk, <i>p</i> < 0.05, Mann-Whitney test). Red asterisk compared with the non-LTD experiments (<i>n</i> = 4) (<i>p</i> < 0.05, Mann-Whitney test). (B2) Likewise, the EPSP amplitude PPR (1^st versus 2^nd EPSP) is reduced in the LTD experiments (black asterisk, <i>p</i> < 0.05, Mann-Whitney test), but not in the presence of group I mGluR blockers. Red asterisk indicates significance between the groups (<i>p</i> < 0.05, Mann-Whitney test). Baseline-normalized time window is 20–25 min after afferent bursts. The data are available in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2000237#pbio.2000237.s009" target="_blank">S3 Data</a>. (B3) Sample traces from one experiment above showing the PC firing (paired-pulse 50 ms)-evoked EPSPs in the FSIN during baseline and in LTD.</p