Examples of delayed or missed NCSE diagnosis; from Kaplan [48].
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3820",leadTitle:null,fullTitle:"Tumors of the Central Nervous System - Primary and Secondary",title:"Tumors of the Central Nervous System",subtitle:"Primary and Secondary",reviewType:"peer-reviewed",abstract:"A novel concept that is reviewed and discussed in several chapters in the book alludes to the transport of drugs bound to red blood cells into the highly vascular CNS tumors - both primary and metastatic. Such a transport mechanism is unique and of significant therapeutic potential. It is hopeful that the novel information presented in this book will result in new approaches to the treatment CNS tumors.",isbn:null,printIsbn:"978-953-51-1576-2",pdfIsbn:"978-953-51-7211-6",doi:"10.5772/57014",price:119,priceEur:129,priceUsd:155,slug:"tumors-of-the-central-nervous-system-primary-and-secondary",numberOfPages:272,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"b7d48165285bf02f0ea063d2610993d3",bookSignature:"Lee Roy Morgan",publishedDate:"June 11th 2014",coverURL:"https://cdn.intechopen.com/books/images_new/3820.jpg",numberOfDownloads:14616,numberOfWosCitations:7,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:10,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:20,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 29th 2013",dateEndSecondStepPublish:"June 19th 2013",dateEndThirdStepPublish:"September 15th 2013",dateEndFourthStepPublish:"October 15th 2013",dateEndFifthStepPublish:"March 26th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"158053",title:"Dr.",name:"Lee Roy",middleName:null,surname:"Morgan",slug:"lee-roy-morgan",fullName:"Lee Roy Morgan",profilePictureURL:"https://mts.intechopen.com/storage/users/158053/images/system/158053.png",biography:"Dr. Lee Roy Morgan, MD, PhD, is a clinical pharmacologist and oncologist whose research interests are focused on the development of new and novel agents that penetrate the CNS and are effective against both primary and metastatic malignancies involving the CNS. \r\nDr. Lee Roy Morgan received his PhD degree in organic chemistry from Tulane University, New Orleans, Louisiana, in 1960. He completed his postdoctoral studies at Imperial College, University of London, in 1961. In 1971, he received his MD degree from Louisiana State University Medical School. From 1961 to 1986, he was a professor and the chairman of the Department of Pharmacology and Experimental Therapies, Louisiana State University Medical School, New Orleans, Louisiana, USA. He founded Dekk-Tec, Inc., in New Orleans, Louisiana in 1983 and is the CEO and director of research. In addition, he is an adjunct professor of Medicine in Tulane University School of Medicine and adjunct professor of Chemistry in the University of New Orleans, Louisiana. He has published over 200 research articles and book chapters. Dr. Morgan is married with four children and seven grandchildren.",institutionString:"DEKK-TEC Inc.",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1085",title:"Neuro-Oncology",slug:"neuro-oncology"}],chapters:[{id:"46786",title:"High Grade Glioma — Standard Approach, Obstacles and Future Directions",doi:"10.5772/58548",slug:"high-grade-glioma-standard-approach-obstacles-and-future-directions",totalDownloads:2224,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Siddharth K. 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Silicon Carbide (SiC) is regarded as a promising candidate for electronic devices used in harsh radiation environments (Rad-hard devices) such as in space, accelerator facilities and nuclear power plants [1-5]. In order to apply SiC to such rad-hard devices, we have to know the radiation response of the characteristics of SiC devices, because semiconductor devices show destructive and non-destructive malfunctions and/or degradation their characteristics due to irradiation. For radiation effects on semiconductor devices, three major effects, Single Event Effects (SEEs), Total Ionizing Dose (TID) effect, and Displacement Damage Dose (DDD) effects are known.
\n\t\t\tWhen charged particles such as heavy ions are irradiated into semiconductors, dense charge (electron-hole pairs) is generated in semiconductors along to the ion track. The malfunctions of electronic devices such as LSIs and power devices caused by charge generated by charged particles are called SEEs. The SEEs occur even by only one particle incidence, and there are both nondestructive (soft errors) and destructive (hard errors) SEE failures [6-8]. The soft errors arise if the amount of charge collected by devices is large enough to reverse or flip the data state of a memory cell, register, latch, or flip-flop. Since the soft errors are not destructive, the function of semiconductor devices can be recovered by writing new data to the bit and/or resetting of devices. For example, the Single Event Upset (SEU) and the Multiple Bit Upset (MBU) in a Static Random Access Memory (SRAM) and a Dynamic Random Access Memory (DRAM), the Single Event Functional Interrupt (SEFI) in Field Programmable Gate Array (FPGA) or DRAM control circuitry are known as the soft errors. Recently, the Single Event Transient (SET) arises as a serious issue for analog electronics and digital logic cells. In general, the SETs in analog electronics are referred to as ASETs, and those in digital combinatorial logic are referred to as DSETs. In contrast, the Single Event Latch-up (SEL), the Single Event Burnout (SEB), and the Single Event Gate Rupture (SEGR) in power electronic devices are known as the hard errors.
\n\t\t\tElectron-hole pairs are induced in insulator layers of Metal-Insulator-Semiconductor (MIS) structure devices, such as Metal-Oxide-Semiconductor (MOS) devices by irradiation, and as a result, charge trapped in insulator (oxide) and/or traps near the interface between oxide and semiconductor (interface traps) are generated. Since such charge trapped in insulator and interface traps act give harmful influence to transport properties of semiconductors, the electrical characteristics of MIS devices are degraded by their generation [9, 10]. For example, the shift of threshold voltage (
When energetic particles are irradiated into semiconductor crystals, atoms at lattice sites are scattered into non-lattice sites (knock-on effects). As a result, vacancies and interstitials are created in semiconductor crystals. This is the origin of the DDD effect. However, in reality, the structure of residual defects is not so simple and a wide variety of defects such as divacancies, vacancy clusters, and vacancy-impurity complexes exists in crystals because generated vacancies and interstitials thermally diffuse and finally they become stable defects. In general, such defects act as scattering/recombination centers to free carriers, and as a result, the electrical characteristics of semiconductors devices are degraded. In the case of the DDD effect, similar to the TID effect, the degradation of the characteristics of semiconductor devices becomes larger with increasing fluence of radiation. The degradation of the electrical performance of solar cells installed in space satellites is known as one of the examples of the DDD effect [11-14].
\n\t\t\tIn this chapter, the effects of radiation on the electrical characteristics of SiC devices are described from the point of view of the TID effect and the SEEs.
\n\t\tFigure 1 shows the change in the subthreshold region of drain current (
Change in the subthreshold region of
According to Mcwhorter and Winokur [9], the density of charge trapped in gate oxide (Δ
where Δ
Since the subthreshold curve between
where „post“ and „pre“ mean after and before irradiation, respectively.
\n\t\t\tIn order to obtain the value of
where
The value of Δ
where
Figure 2 (a) shows the Δ
Δ
These behaviors indicate that both positively and negatively charges are generated in gate oxide for the H2 SiC MOSFETs by gamma-ray irradiation. It was reported from the change in capacitance – voltage characteristics of 6H-SiC MOS capacitors due to gamma-ray irradiation that negative and positive trapped charges were generated near SiO2/SiC interface and in oxide at 40 nm from the interface, respectively [18]. Although the mechanism of H2-anneling effect on the gate oxide and the interface between oxide and SiC has not yet been clarified, since the initial value of
(a) Δ
The values of Δ
For Δ
a) Δ
The μch for Si MOSFETs is known to decrease with increasing absorbed dose [10]. In order to confirm this for SiC MOSFETs, μch for the H2 SiC MOSFETs were plotted as a function of absorbed dose (Fig. 5). For comparison, the result reported for Si MOSFETs are also plotted in the figure [9]. The μch for the H2 SiC MOSFETs does not change up to 20 kGy and the value decreases with increasing absorbed dose above 60 kGy. Then, the value of μch reduces to be 50 % of the initial value at 530 kGy. On the other hand, μch for the Si MOSFETs decreases with increasing absorbed dose and becomes 50 % of the initial value by irradiation at 10 kGy. Although the initial value of μch for Si MOSFETs (600 cm2/Vs) is much higher than the initial value of μch for the H2 SiC MOSFET (~ 50 cm2/Vs), the value for Si MOSFETs is assumed to be almost zero after irradiation at 100 kGy whereas the H2 SiC MOSFETs still keep 25 cm2/Vs of μch even after irradiation at 530 kGy. In addition, it is mentioned that the stability of their electrical performance against irradiation is also important for Rad-hard devices. Therefore, it can be concluded that SiC MOSFETs are quite tolerant against radiation in comparison with Si MOSFETs. For the degradation mechanism of μch, Ohshima et al. reported [17] that the relationship between the decrease of μch and Δ
μch for H2 SiC MOSFETs as a function of absorbed dose. For comparison, the result reported for Si MOSFETs are also plotted in the figure [
Next, the effects of the surface morphology on μch of SiC MOSFETs irradiated with gamma-rays will be discussed. In this study, MOSFETs were fabricated on n-type 6H-SiC epitaxial layers using the same fabrication process except the procedures of high temperature annealing after implantation [23]. Thus, although all samples were annealed at 1650°C for 3 min in an Ar atmosphere, the surface of one series of samples was covered with carbon films (C-coating) during the annealing to avoid the degradation of the surface morphology [24], and the other series of samples were annealed without the carbon coating (non-coating). After the annealing, the carbon films were removed by the oxidation at 800°C for 30 min in O2 gas. Gate oxide of both series of the MOSFETs were formed by pyrogenic oxidation (H2:O2 = 1:1) at 1100°C for 30 min. For the details of the fabrication process, please see Ref. [23]. The initial values of μch for C-coating and non-coating SiC MOSFETs are 41 and 44 cm2/Vs, respectively. For the surface morphology, the values of root mean square (RMS) for the C-coating and non-coating SiC are obtained to be 0.67 and 1.36 nm, respectively, from AFM measurements, whereas the RMS was 0.25 nm before annealing.
\n\t\t\tFigures 6 (a) and (b) show μch and Δ
a) μch and (b) Δ
In this section, the change in the electrical characteristics of SiC transistors such as Static Induction Transistors (SITs), Metal-Semiconductor (MES) FETs and MOSFETs due to gamma-ray irradiation will be compared to Si MOS FETs from the point of view of the radiation hardness. Figure 7 shows Δ
Next, the change in the electrical characteristics of the SiC SITs by gamma-ray irradiation is expressed. The SiC SITs have an on-resistance of 0.15 Ω and a blocking voltage of 900 V at
Change in ΔVT for SiC SITs (squares), SiC MESFETs (diamonds), C-coating+Dry SiC MOSFETs (triangles) and C-coating+Pyro SiC MOSFETs (circles) as a function of absorbed dose. All transistors were irradiated with gamma-rays at RT. During gamma-ray irradiation, no bias was applied to any electrodes of the transistors. For comparison, the results reported for Si MOSFETs (upside-down triangles) are also plotted in the figure [
Shift of the breakdown voltage from the initial value for SiC SITs (squares), Si MOSFETs (triangles) and Si IGBT (upside-down triangles) as a function of absorbed dose. The blocking characteristics for SiC SITs and Si ones (IGBTs and MOSFETs) were measured under
The on-state characteristics were measured under
Shift of the on-voltage from the initial value for SiC SITs (squares), Si MOSFETs (triangles) and Si IGBT (upside-down triangles) as a function of absorbed dose.
Since destructive or/and non-destructive malfunctions called SEEs occurs in electronic devices by charge (electron-hole pairs) generated by charged particle incidence, especially heavy ions. The SEEs on semiconductor devices are one of the most major issues for space applications. On the other hand, for high energy physics using accelerators with high luminosity, such as J-PARC and Super-LHC, Rad-hard particle detectors are expected to be developed. For the development of Rad-hard particle detectors as well as Rad-hard devices for space applications, it is important to clarify the behavior of charge generated in devices by charged particle incidence. In a previous study [30], Nava et al. reported that the Charge Collection Efficiency (CCE) obtained from 4H-SiC Schottky diodes by alpha particle incidence was estimated to be 100 %. It was also reported that 4H-SiC Schottky diodes could detect X-rays from radio isotopes [31,32]. Besides, the neutron detection by SiC diodes was investigated previously [33, 34]. As for light ions and X-rays irradiation into SiC, relatively large number of studies has been already reported. On the other hand, from the point of view of SEEs, study of ion irradiation on electronic devices using heavy ions is important. In this section, charge induced in SiC diodes by heavy ion incidence is reviewed on the basis of our previous studies [35-40].
\n\t\t\tSchematic set-up of the TIBIC system installed at JAEA Takasaki and photo of the TIBIC system.
In order to obtain the information on charge induced in electronic devices, Ion Beam Induced Charge (IBIC) measurements is thought to be one of the useful methods. However, the decrease in collected charge during IBIC measurements should be considered for the accurate evaluation of charge induced by ion beams, since the device characteristics are degraded by radiation damage created in samples by ion incidence [41]. Therefore, single-ion hit Transient Ion Beam Induced Current (TIBIC) was developed at JAERI Takasaki in order to realize the evaluation of ion-induced current with minimizing the influence of damage [42]. Figure 10 shows the schematic set-up of the TIBIC system installed at JAEA Takasaki and the photo of the TIBIC system. The TIBIC collection system connects with a heavy ion microbeam line from the 3MV Tandem accelerator, and consists of a single event triggering system and a fast switch beam shutter system. The transient current signals induced by ions can be detected using a digital sampling oscilloscope (Tektronix 3 GHz TDS694C or 15 GHz TDS6154C). The details of the single ion hit TIBIC collection system are described in Ref. [43]. Since the TIBIC system connects with a beam scanning system, spatial images of transient current signals can be obtained.
\n\t\t\t\n\t\t\t\tFigure 11 shows TIBIC signals obtained from 6H-SiC n+p diodes with applied bias of 30, 90 or 150 V. Si ions with 12 MeV were used as probe beams. In this study, the 6H-SiC n+p diodes with 100 - 300 μm diameters were fabricated on p-type substrates with p-type epitaxial layers (Al doping concentration between 8x1014 and 3.5x1015 /cm3). The n+ region was formed by three-fold implantation (60, 90, 140 keV) of phosphorus (P) ions at 800°C and subsequent annealing at 1650°C for 3 min in argon (Ar) atmosphere. The thickness and a mean P concentration of the implanted layer are ~100 nm and 5x1019 /cm3, respectively. During the annealing, the sample surface was covered with a carbon film to avoid the degradation of the surface morphology [24]. The details of the diode fabrication process are described elsewhere [40]. The peak height of the TIBIC signals increases with increasing applied bias, and the value becomes to 0.50 from 0.19 mA when applied bias increases to 150 from 30 V. The fall-time, which is defined as the time from 90 % to 10 % of the current transient, shorten with increasing applied reverse bias, and the value decreases to 0.48 from 0.98 ns when applied bias increases to 150 from 30 V. These results can be interpreted in terms of an increase of the electric field in the depletion layer due to increasing applied bias. It is also mentioned the leakage currents of the diodes were in order of 10-11 A at an applied reverse bias of 150 V, and no significant differences in
TIBIC signals obtained from 6H-SiC n+p diodes with applied bias of 30, 90 or 150 V. Si ions with 12 MeV were used as probe beams.
By the integration of a TIBIC signal, charge collected by a diode can be estimated. Charge collected by the 6H-SiC n+p diodes as a function of applied bias is shown in Fig. 12. In this study, Si ions with different energies were applied as probe beams, and the value of energy of Si ions are described in the figure. Charge collected by the diodes increases with increasing applied bias, and the value of collected charge saturates in a higher bias region. For example, the saturation is observed above 40 and 60 V for 15 and 18 MeV, respectively. Charge generated in the depletion region of a diode can be collected by its electric field (Drift component). On the other hand, charge generated in deeper than the depletion region diffuses, and only charge reaching the repletion region can be collected by a diode (Diffusion component) whereas some generated carriers recombine during diffusion. Thus, if the depletion region is shorter than the projection range of ions, the decrease in collected charge is observed due to the recombination of generated carriers during diffusion. Since ions with higher energy have a longer projection range, the results obtained in Fig. 12 can be qualitatively interpreted in terms of the drift and the diffusion components. However, in reality, since an extended drift region is temporarily created in a deeper region than the depletion region, the saturation of collected charge occurs even in the case that the depletion region is shorter than the ion projection range [44].
\n\t\t\tAt a bias of 150V, the depletion region is estimated to be 7 μm, and this is longer than the ion projection range of Si ions at 18 MeV which is estimated to be 4.8 μm by a Monte Carlo simulation code, SRIM [45]. Thus, at a bias of 150 V, all charge generated in the 6H-SiC diodes by Si ion incidence can be collected by the electric field in the depletion layer. The CCE for the 6H-SiC diodes is estimated from the value of charge collected at a bias of 150 V. Here, the value of CCE is defined as
\n\t\t\twhere Qexp and Qideal are the value of charge experimentally obtained at 150 V and the ideal value of charge generated in SiC, respectively. The value of Qideal is obtained by the equation
\n\t\t\twhere
Charge collected by 6H-SiC n+p diodes as a function of applied bias. Si ions with different energies were applied as probe beams, and the value of energy of Si ions are described in the figure.
In order to understand the degradation of the CCE due to not energy loss near the surface regions, the effect of ion species on the CCE was investigated. Figure 13 shows the relationship between ions species with the same energy (12 MeV) and the value of the CCE. The value of the CCE is obtained from the integration of TIBIC signals for the 6H-SiC n+p diodes at a bias of 150 V. The CCE for the diodes probed by O ions is estimated to be 90 %, and this value is the highest of all ion species in Fig. 13. With increasing atomic number, the value of the CCE decreases. The CCE of 42 % is observed by Au ion incidence. The degradation of the CCE for SiC diodes by Au ion incidence was also reported [36]. Zajic et al. suggested that high density of e-h pairs is generated by heavy ions, and generated e-h pairs are easy to recombine in such dense plasma [46].
\n\t\t\tRelationship between ions species with the same energy (12 MeV) and the value of CCE. The value of CCE is obtained from the integration of TIBIC signals for 6H-SiC n+p diodes at a bias of 150 V.
The carrier density generated in SiC, and the distributions of e-h pairs are calculated on the basis of Kobetich and Katz (KK) theorem [47]. In this calculation, the KK model improved using empirical equations reported by Fageeha et al. [48] was applied since the KK model overestimates the density of e-h pairs at the core of the ion track. The calculated results of the density of e-h pairs generated in SiC by (Left) 12 MeV-O and (Right) -Au ion irradiation are shown in Fig. 14. In the case of 12 MeV-O ion incidence, the radius of the ion track at the sample surface and projection range of ions are estimated to be ≈ 40 nm and 5.2 μm, respectively. On the other hand, the ion track radius at the surface and the ion range for 12 MeV-Au ions are estimated to be ≈ 2 nm and 1.9 μm, respectively. Since the energy (12 MeV) is the same for both O and Au ions, the total number of e-h pairs generated in the ion track region is the same between O and Au ions. Thus, the density of e-h pairs in SiC irradiated with Au ions is much higher than that irradiated with O ions, and the estimated density of e-h pairs in SiC irradiated with 12 MeV-Au ions is a several orders of magnitude higher than that in SiC irradiated with 12 MeV-O ions. In such a high density of e-h pairs, the ambipolar effect occurs easily and the electric field temporarily weakens. As a result, the amount of the recombination between electrons and holes increases. For the dynamics of carriers generated in SiC by heavy ion incidence, please see Ref. [44]. The result obtained in this study indicates that it is important to consider the decrease in the CCE for SiC particle detectors when heavy ions are detected. From the point of view of SEEs in SiC, the decrease in collected charge is thought to be one of the advantages for the development of Rad-Hard devices. The similar charge collection behaviours have been also obtained for SiC p+n diodes, although only results obtained from SiC n+p diodes were introduced in this article [39].
\n\t\t\tCalculated results of the e-h density generated in SiC by (Left) 12 MeV-O and (Right) -Au ion irradiation.
For the effects of ion incidence on MOS capacitors fabricated on SiC, it was reported that the peak amplitude of TIBIC signals decreased and the fall time increased with increasing number of incident ions [49-51]. Furthermore, the peak of TIBIC signals can be refreshed to its original value by applying a forward bias of + 1V to the gate electrode. From the measurement of the capacitance of SiC MOS capacitors during O ion irradiation, the value of capacitance was found to increase with increasing number of incident ions. This indicates that the depletion length of the MOS capacitors becomes shorten with increasing number of incident ions. Since large amounts of charge are induced by heavy ion incidence and some of them might flow to the interface between SiO2 and SiC, the degradation of TIBIC signals can be explained by a change in the net bias applied to the gate oxide due to the creation of the inversion region or/and charging up deep traps. The refreshment of TIBIC signals by applying a forward bias can be also interpreted in terms of releasing charge from the interface or/and deep traps. For the effects of heavy ion irradiation on 6H-SiC MOSFETs, Onoda et al. Reported from experimental results and their simulation using the Technology Computer Aided Design (TCAD) [52] that the charge collection behaviours were affected by drift, funnelling, diffusion, and recombination, and especially, the enhancement of transient currents was observed due to the parasitic bipolar action. It was also reported that the enhanced charge collection was observed for 4H-SiC MESFETs by heavy ion incidence [26]. According to device simulations using the TCAD, it was concluded that the enhanced charge collection effect can be interpreted in terms of not only the bipolar action but also the channel modulation effects. For the DDD effect in SiC devices, it was reported that the value of the CCE for SiC n+p diodes and the majority carrier concentration in them decreased with increasing gamma-rays, electrons or protons and the damage factor of the CCE and the carrier removal rate can be scaled by Non Ionizing Energy Loss (NIEL) [53-55].
\n\t\tIn order to develop Rad-hard devices based on SiC, the radiation response of SiC devices have to be understood. In this chapter, effects of gamma-rays and swift heavy ions on SiC devices were reviewed. Firstly, the gamma-ray irradiation effects on SiC MOSFETs were introduced, and the degradation of their characteristics was discussed on the basis of charge generated in gate oxide and interface traps by irradiation. Then, the radiation resistance of SiC transistors, MOSFETs, MESFETs and SITs was compared to Si transistors. SiC transistors showed higher radiation resistance than Si transistors, and SiC SITs could be operated up to 10 MGy. This indicates that SiC SITs have extremely high radiation tolerance from the point of view of TID effects. Charge generated in 6H-SiC n+p diodes by heavy ion incidence was evaluated using TIBIC. The signal peak of the transient current increased, and the fall-time decreased with increasing applied reverse bias. The high CCE values were observed when ions with relatively light mass such as O and Si ions were applied as probe ions. However, the CCE decreased with increasing atomic number, and the value reduced to approximately 40 % when 12 MeV-Au ions were applied as probe ions. From the calculation based on the modified KK model, it was found that the density of e-h pairs in SiC irradiated with heavy ions, such as Ni and Au, is much higher than that in SiC irradiated with O and Si ions. Therefore, the decrease in the CCE by the irradiation of ions with heavy mass was interpreted in terms of the recombination of e-h pairs in plasma.
\n\t\tThis study of gamma-ray irradiation effects on SiC SIT was supported by the Strategic Promotion Program for Basic Nuclear Research by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Also, the study of charge induced in SiC pn diodes and MOS capacitors by heavy ion incidence was partially supported by the Ministry and Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (B), 2006, 18360458 and (B), 2009, 21360471, respectively.
\n\t\tNonconvulsive status epilepticus (NCSE) is accompanied with an altered mental status (AMS) without convulsive motor activity [1]. Because of the paucity of clinical symptoms, EEG is mandatory for the diagnosis of NCSE. In the intensive care unit (ICU), where the patient is often obtunded/comatose, cEEG monitoring is required to reveal NCSE. cEEG monitoring is important because of the difficulty distinguishing when AMS and coma are ictal and differentiating them from non-ictal symptoms associated with underlying pathology such as posthypoxic, metabolic or septic encephalopathies, and the effects of sedative drugs. Furthermore, the diagnosis of NCSE is frequently delayed, with patients in the ICU having often other serious medical conditions. To diagnose NCSE a high degree of suspicion is required [2], and consequently NCSE remains unrecognized. Table 1 shows how frequently the diagnosis of NCSE could be missed in the emergency room.
Lethargy and confusion attributed to a postictal state |
Ictal confusion mistaken for metabolic encephalopathy |
Unresponsiveness and catalepsy presumed to be psychogenic |
Obtundation thought to be due to alcohol or drug intoxication |
Hallucinations and agitation mistaken for psychosis or delirium |
Lethargy presumed secondary to hypoglycemia |
Mutism attributed to aphasia |
Laughing and crying ascribed to emotional lability |
Examples of delayed or missed NCSE diagnosis; from Kaplan [48].
In the United States, the estimated incidence of status epilepticus (SE) is 15–20/100,000 cases per year [3], and NCSE is representing 63% of all SE [4]. Both nonconvulsive seizures (NCS) and NCSE occur very frequently in the ICU and emergency department (ED): NCSs/NCSE is recorded in 8% to 48% in ICU patients [5, 6, 7, 8], many of which are fatal [9, 10, 11].
Prevalence of NCSE is reported from different geographical areas of the world in patients with AMS [12, 13, 14, 15, 16]; However, to our knowledge, there is no study reporting the frequency of NCSE in the Middle East and North Africa (MENA) region; in this vast geographic area, the only NCSE incidence/prevalence is described from the MENA’s neighboring countries like Pakistan, India, Turkey, and Israel [17, 18, 19, 20, 21]. There is a need for studies regarding the prevalence and morbidity of NCSE in MENA countries [22].
There is also a lack of consensus regarding the EEG monitoring duration when looking for NCSE in ICU patients with AMS; the authors dealing with this issue report a considerable variation in the duration of cEEG monitoring [23, 24, 25, 26].
The aims of this chapter are multiple:
Know the rate of occurrence of NCSE in patients with AMS admitted to Hamad General Hospital (HGH) Doha, Qatar, using cEEG monitoring.
Describe the clinical and EEG findings, causes, head CT/MRI, as well as the treatment and outcomes of NCSE in patients with AMS, and compare the results to a matched control group with similar clinical presentations of AMS.
Highlight and discuss the lack of consensus in the literature regarding the duration of cEEG monitoring while looking for NCSs/NCSE in patients with AMS.
This clinical study was performed according to the Good Clinical Practice (GCP) guidelines. Approval was obtained from Hamad Medical Corporation Ethical Committee and Institutional Review Board (IRB). All subjects/relative(s) (caregivers) provided consent before participating.
NCSE was defined as an AMS with diminished responsiveness, a positive EEG. and a response to anti-seizure drug (ASD) therapy; as a status, NCSE should be present for a minimum of 30 minutes of continuous nonconvulsive seizure activity or after repeated seizures without recovery of consciousness between events [1]; recently shorter durations have been reported.
Young’s criteria [27] of electrographic SE and modified criteria of Chong and Hirsch [28] were used to diagnose NCSE; In addition, the International League against Epilepsy (ILAE) definition and classification of Status Epilepticus [29] and EEG Salzburg Consensus Criteria for NCSE [30] were used to recognize NCSE; NCSE was diagnosed in the presence of continuous generalized spike wave discharges with changes in intensity or frequency, epileptiform activity with ictal patterns that wax and wane, rhythmic and periodic discharges, and subtle and discrete electrographic seizures, when lasting for 30 minutes [10, 13, 15]. In comatose patients, epileptiform discharges faster than 2.5 Hz or generalized periodic discharges (GPDs), lateralized periodic discharges (LPDs) and continuous 2/s GPDs with triphasic morphology [31] of less than 2.5 Hz, as well as rhythmic discharges (RDs) faster than 0.5 Hz were also taken into consideration as NCSE if they responded to benzodiazepine treatment with improvement in the EEG or in patient mental status [13, 15, 29, 32].
Two EEG specialists agreed independently that the patient condition and EEG findings represent NCSE particularly when an EEG pattern did not meet above criteria; finally NCSE was considered if the EEG/or level of consciousness responded to an ASD trial.
Unexplained confusional state, change in behavior, mild to moderate obtundation, alteration in cognition and behavior from baseline, and unexplained decrease in level of consciousness including after convulsive status epilepticus treatment [2, 33] were considered AMS; in elderly patients, delirium (altered level of consciousness, with a fluctuating course, disorganized thinking, and inattention) was also included [15].
All patients with AMS, from the Emergency Department and from ICUs, aged 12 years or above, had a cEEG monitoring [2, 33]. Not included were patients with open head injury, those whose relatives did not sign the consent form and patients with suspected brain death and an isoelectric EEG. In addition, patients treated for convulsive status epilepticus (CSE) who did not develop later NCSs/NCSE on cEEG monitoring were excluded.
Patients with AMS and those whose EEG was not compatible with NCSE during 3 days of cEEG monitoring recording were taken as controls. The NCSE and control groups were compared: this included the clinical presentation and medical condition, AMS etiology, neuroimaging, laboratory findings, length of stay, recovery, and outcome
The following EEG recording system was used: international 10/20 system with 21 silver/silver chloride cup electrodes. Digital EEG signal stored electronically was filtered for display. High-pass filter and low-pass filter were 0.5–1 and 70 Hz. For extraneous electrical artifact, 50 Hz notch filter was used; impedance was 100 and 5000 ohms. cEEG was done by EEG technologists and monitored at least twice a day by an EEG specialist.
The duration of cEEG monitoring was determined by the response to treatment of NCSs/NCSE, the presence of other EEG features like rhythmic and periodic discharges, and their responses to treatment.
The following investigations were performed in most NCSE cases and controls: complete blood count, electrolytes, liver and renal functions, brain MRI, and/or CT head; imaging was performed either before or after cEEG monitoring
Benzodiazepines (lorazepam or diazepam) were used when NCSs/NCSE was suspected. If seizures persisted, European Federation of Neurological Sciences (EFNS) Guidelines and Glauser et al. report on NCSE treatment were followed: IV diazepam or lorazepam first and then second-line ASDs were initiated—valproic acid, phenytoin, or levetiracetam. If no results, continuous infusions of propofol, midazolam, and barbiturates were used [34, 35].
Many patients received more than one ASD. refractory NCSE was treated with anesthetic agents; same treatment protocol was followed in comatose NCSE. ASDs were not used in control group.
Seizure control and survival/death were considered as primary outcome parameters, while complete recovery and length of stay were secondary outcome parameters.
Descriptive statistics (mean with standard deviation) for continuous variables, frequency, and percentages for categorical variables was used; differences between mean levels of NCSE and controls, outcome and morbidity, and Student’s t-test were calculated; to detect associations between categorical variables and NCSE vs controls, outcome, and morbidity, chi-square tests or Fisher’s exact tests were used. For independent variables at univariate analysis, NCSE logistic regressions were performed using a significance level of 0.05. A P value of 0.05 (two tailed) was considered a statistically significant level. For statistical analysis, an SPSS 22.0 statistical software was used.
Six patients suffered from CSE; only one of them who showed later NCSE EEG features and was included in the study. Twenty patients presented NCSs; 30% of them (n = 6) responded to ASDs and did not develop NCSE on cEEG monitoring; they were also excluded from the study; the rest (70%, n=14) developed later NCSE during cEEG monitoring. These patients were included in the study.
NCSE group: 250 patients with AMS or coma underwent cEEG monitoring. Sixty-two patients were excluded (see reasons above and patient selection). In total, 65 patient responded to the criteria of NCSE (Table 2). The occurrence rate of NCSE was 65/250 (26%).
Variable | NCSE (n 65) | Controls (n 185) | P value |
---|---|---|---|
Age | 45.7 ± 19 | 52.3 ± 15.8 | 0.001 |
Gender | M = 37/F = 28 | M = 101/F = 84 | 0.75 |
Unresponsive/somnolent | 11 (17%) | 46 (25%) | 0.19 |
Acute confusion | 7 (11%) | 18 (10%) | 0.81 |
Severely decreased level of consciousness | 20 (31%) | 61 (33%) | 0.74 |
Stupor/coma | 27 (42%) | 60 (32%) | 0.23 |
Subtle motor phenomena | 12 (18%) | 8 (4%) | 0.001 |
Characteristics of patients with NCSE and controls.
Note: P values are calculated using Chi-square tests and student t tests wherever appropriate.
The control group consisted of 185 patients with AMS or coma in which cEEG monitoring did not show any features of NCSE. Table 2 shows the demographic and clinical features of NCSE and control subjects. Only age and presence of subtle motor phenomena differed between the two groups; the NCSE patients were relatively younger and displayed subtle motor phenomena more often. As for etiology and comorbid states, a history of previous seizures and presence of cortical dysplasia were significantly more common in the NCSE group (Table 3). Other etiologies were not informative. Head injury, stroke, and status postcardiac arrest were frequently encountered in accident and emergency patients with NCSE; CT head done in 52 NCSE cases and in 101 of controls and MRI head done in 41 NCSE cases and in 97 of controls showed hippocampal sclerosis, malformations of cortical development, and encephalomalacia, which were more commonly seen in the NCSE group (Table 4).
Variable | NCSE (n 65) | Controls (n 185) | P value |
---|---|---|---|
Stroke (hemorrhagic, ischemic, subarachnoid hemorrhage) | 16 (25%) | 67 (36%) | 0.09 |
Status post cardiac arrest | 15 (23%) | 35 (19%) | 0.59 |
Head injury | 8 (12%) | 34 (18%) | 0.34 |
Previous seizures (uncontrolled) | 12 (18.4%) | 4 (2%) | 0.001 |
Cortical dysplasia | 3 (4.6%) | 0 | 0.02 |
Sepsis | 3 (4.6%) | 7 (3.8%) | 1.00 |
Hepatic encephalopathy | 1 (1.5%) | 3 (1.6%) | 1.00 |
End stage renal disease, post renal transplant | 2 (3%) | 11 (6%) | 0.37 |
Intoxications | 0 | 8 (4.3%) | 0.12 |
Hypertensive encephalopathy | 1 (1.5%) | 6 (3.2%) | 0.68 |
Personality disorder | 1 (1.5%) | 3 (1.6%) | 1.0 |
Unknown | 3 (4.6%) | 7 (3.8%) | 1.0 |
Etiology of patients with NCSE and controls.
Note: P values are calculated using Chi-square tests or Fisher’s exact test wherever appropriate.
Variable | CT (n pts) | MRI (n pts) | ||||
---|---|---|---|---|---|---|
NCSE (n 52) | Controls (n 101) | P value | NCSE (n 41) | Controls (n 97) | P value | |
Abnormal | 32 (62%) | 49 (49%) | 0.17 | 33 (80%) | 53 (55%) | 0.01 |
Ischemia, intracerebral hemorrhage, subarachnoid & subdural hemorrhage | 14 (27%) | 18 (18%) | 0.21 | 16 (39%) | 32 (33%) | 0.56 |
Cortical atrophy | 5 (10%) | 10 (10%) | 1.0 | 3 (7%) | 6 (6%) | 1.0 |
Polymicrogyria, cortical dysplasia, heterotopia | 3 (7%) | 0 | 0.02 | |||
Hippocampal sclerosis | 3 (6%) | 0 | 0.04 | 3 (7%) | 1 (1%) | 0.08 |
Encephalomalacia | 3 (7%) | 10 (10%) | 0.04 | |||
Meningeal/cortical enhancement | 1 (2%) | 2 (2%) | 1.0 | 1 (2%) | 2 (2%) | 1.0 |
Head CT and MRI findings (some patients had both CT and MRI).
Note: P values are calculated using Chi-square tests or Fisher’s exact test wherever appropriate.
Abnormal cholesterol and liver enzymes were more often abnormal in the NCSE group than controls (NCSE 15%, controls 4%, p 0.004).
Twenty patients showed NCSs; 65% of them (n = 13) had NCSs during the first 40 minutes of recording, whereas 35% (n = 7) had their seizures later but within the first 48 hours of cEEG monitoring.
In the NCSE group (n = 65), NCSE EEG patterns were recorded during the first 3 hours in 66% (n = 43), later but within the first 48 hours in 22% (n = 14), and in the third day in 12% (n = 8). Among the 22 patients with late NCSE, 17 (77%) were comatose.
The NCSE group was further subdivided into two: NCSE proper without coma (n = 39) and comatose NCSE (n = 26) [32, 36]; NCSE proper is defined as clinical symptoms suggestive of SE with mild impairment of consciousness (absence status or complex focal SE); NCSE with coma-lateralized epileptiform discharges, NCSE with coma-generalized epileptiform discharges is defined as deep coma of various etiology with characteristic epileptiform EEG pattern but with no clinical motor signs of SE; NCSE proper patients are significantly younger than the comatose NCSE ones (Table 5). NCSE in comatose patients was often recorded after the first day of cEEG monitoring: during the first 24 hours in only 54% (n = 14/26), later but within 48 hours in 35% (n = 9/26), and in the third day in 11% (n = 3/26) of the patients; comparatively, NCSE proper was recorded during the first day in 77% (n = 30/39), later but within 48 hours in 10% (n = 4/39), and during the third day in 13% (n = 5/39) of patients.
Variable | NCSE (n 65) | NCSE proper (=without coma) (n 39) | NCSE with coma (n 26) | Control (n 185) | P value |
---|---|---|---|---|---|
Deaths | 20 (31%) | 8 (21%)* | 12 (46%)*§ | 35 (19%) | * 0.05, § 0.0007 |
Gender male | 37 (57%) | 23 (59%) | 14 (54%) | 101 (55%) | |
Age (years) | 45.7 ± 19§ | 36.9 ± 24& | 51.3 ± 16.9& | 52.3 ± 15.8 § | § 0.001, & 0.006 |
Hospital stay (days) | 15.2 ± 7.7# | 14.6 ± 7.8 | 16.4 ± 7.7^ | 12.7 ± 5.5#^ | # 0.02, ^0.03 |
Complete recovery | 26 (40%) | 18 (46%) | 8 (31%)a | 98 (53%)a | a 0.04 |
Occurrence and comparison of the listed variables in the NCSE groups and control group.
Note: P values are calculated using Chi-square tests, Fisher exact tests and Student t tests wherever appropriate.
* and § compare Death occuring respectively in NCSE without coma to NCSE with coma and also Death occurring in NCSE with coma to controls (respectively 0.05 and 0.0007).
§ and & compare patients and controls ‘s age respectively in NCSE group to controls and also in NCSE without coma to NCSE with coma (respectively 0.001 and 0.006).
# and ^ compare hospital stay respectively in NCSE group to controls and also in NCSE with coma to controls (respectively 0.02 and 0.03); symbol a compares complete recovery in NCSE with coma to controls (0.04)
The 14 patients with early comatose NCSE (first 24 hs) suffered from head injury (n = 4), stroke (n = 4), and cardiac arrest (n = 3); and no etiology was found in three patients; comparatively, in the NCSE proper group (n = 30), 18 patients suffered from previous seizures, 5 from stroke, 3 from sepsis, 2 from head injury, and 2 from cardiac arrest.
Patients with NCSs (n = 20) were treated as follows: 18 with benzodiazepines, 10 with valproate IV, and 8 with levetiracetam plus valproate IV. The 65 NCSE patients received the following: lorazepam 4–8 mg IV or diazepam 10 mg IV (n = 45), levetiracetam IV or PO (n = 22), phenytoin IV (n = 21), valproate IV or PO (n = 18), topiramate PO (n = 5), phenobarbitone IV (n = 7), midazolam IV (n = 15), propofol (n = 5), fentanyl (n = 2), and thiopental (n = 3).
NCSE group (n = 65): 69% (n = 45, m 25, f 20) responded to treatment within 48 hours, whereas 31% (n = 20, m 12, f 8) died.
Control group (n = 185): 19% (n = 35, m 20, f 15) died. Thus, compared to the control group, death was more frequent in the NCSE group; there was additional statistical significance when NCSE proper was compared to comatose NCSE and when comatose NCSE was compared to controls (Table 5), with comatose patients exhibiting a more ominous outcome. The majority of patients with early occurrence of NCSs/NCSE = 65% (40 minutes to 3 hours) died (n = 13/20). Causes of death in NCSE (n = 20) group were distributed as follows: cardiac arrest (n = 6), hemorrhagic and ischemic strokes (n = 5), sepsis (n = 3), head injury (n = 4), subarachnoid hemorrhage (n = 1), and cerebral abscess (n = 1).
Compared to controls, NCSE achieved complete recovery in 40% (n = 26, m 15, f 11) compared to controls 53% (n = 98, m 55, f 43); Table 5 shows that this achieved statistical significance when comatose NCSE was compared to controls; NCSE group (NCSE proper plus comatose NCSE) had a longer hospital stay than the controls.
Thirty-two percent of patients with NCSE (n = 21, m 13, f 8) suffered from refractory NCSE, defined as seizures lasting more than 60 minutes with failure of two ASDs [37]; they received the following treatment: midazolam IV (n = 10), propofol (n = 5), thiopental (n = 4), and fentanyl (n = 2). Fifty-seven percent (n = 12, m 8, f 4) survived; forty-three percent (n = 9, m 5, f 4) died with the following reasons: cardiac arrest (3), sepsis (3), ischemia (1), subarachnoid hemorrhage (1), and cerebral abscess (1). Only 33% (n = 7, m 4, f 3) recovered completely.
EEG patterns recorded in the NCSE patients (n = 65): focal spike/sharp and wave >3/s in 43% (n = 28), generalized spike/sharp and wave >3/s in 28% (n = 18), GDPs, LPDs, continuous 2/s GPDs with triphasic morphology in 25% (n = 16), and multifocal spikes in 4% (n = 3); Figures 1–5 show NCSE EEGs cases before and after ASD treatment.
(a) EEG shows left LPDs; patient received 4mg lorazepam IV and (b) EEG and clinical improvement following lorazepam IV.
(a) EEG shows left LPDs in a comatose patient following cardiac arrest; patient receives 10 mg Diazepam IV and (b) EEG shows dramatic improvement following Diazepam IV; however the patient remains comatose (possible NCSE ?).
(a) EEG shows evolving GPDs with triphasic morphology and (b) EEG demonstrates some improvement following Diazepam; however the patient remained comatose.
(a) EEG shows predominantly left sided LPDs with triphasic morphology; 32 years old male given baclofen 30 mg for spasticity the first day of admission; 2 days later he presented an altered mental status with “akinetic mutism”; patient was given 6 mg lorazepam IV bolus. (b) Dramatic improvement in EEG and clinical status following IV lorazepam ; patient recovered completely, started talking and moving around normally; he was found to have a moderate to severe renal impairment (responsible for baclofen intoxication ?).
(a) (Comatose focal NCSE) 67 years old male comatose, following head injury. EEG shows abnormal fast activity starting in right fronto-temporal leads accompanied by abnormal eye movements and facial twitching. (b) The ictal fast activity spreads to the contralateral fronto-temporal leads; patient shows same clinical manifestations (discrete twitching of the left face); the abnormal electrical activity was continuous for more than 30 mn. (c) 1 minute following 2 mg of lorazepam IV; patient remains comatose; EEG shows diffuse generalized slowing; no epileptiform activity; no clinical manifestations; survived with memory impairment and left hemiplegia.
EEG in NCSE patients who ultimately died (n = 20): 40% periodic patterns (n = 8), 30% continuous generalized spike/sharp and waves (n = 6), and 30% with focal spike/sharp and waves (n = 6). Fifty-two percent (n = 34) showed a continuous ictal pattern, and forty-three percent (n = 28) an intermittent/recurrent ictal pattern; five percent (n = 3) were not classified; forty-six percent (n = 30) showed a focal onset and 29% (n = 19) a generalized onset; twenty-five percent (n = 16) showed a periodic pattern; focal seizures originated from the temporal areas (55%) and from the frontal areas (31%). In the control group (n = 185), focal/generalized slowing was seen in 43% (n = 80) and slowing with some spike/sharp wave activity in 2% (n = 4).
In the current longitudinal prospective hospital-based study, we investigated the frequency of NCSE in patients with AMS admitted to Hamad Hospital, Doha, Qatar. The prevalence of NCSE among patients with AMS was 26% at our center that is compatible with previous similar studies (prevalence = 16–37%) (Table 6); these researchers used a similar design, with a parallel control group; however, most were retrospective, the cEEG recording duration often shorter or not mentioned. Five other authors from MENA’ s neighboring countries (mentioned in Section 1) also reported the prevalence of NCSE in patients with AMS; however, they used different study designs, and therefore, those studies cannot be compared with our study.
Author (year) | Methods | Duration of EEG recording | Patients with AMS (n) | Patients with NCSE (n) (%) | Outcome |
---|---|---|---|---|---|
Mesraoua et al. (2017) Current study | Prospective | 72 hs | (250) | 65 (26) | Response to ASDs: NCSE 45/65 (69%); death: NCSE 20/65 (31%); death in controls: 35/185 (19%); complete recovery: NCSE 26/65 (40%); controls 98/185 (53%); NCSE longer hospital stay than controls p < 0.02 (Table 5) |
Laccheo et al. [38] (2015) | Prospective | >24hs | (170) | 36 (21) | Mortality 31% NCSE vs 14% in controls |
Kurtz et al. [12] (2014) | Retrospective | ? | (154) | NCSE/NCSs 24 (16), PEDs 45(29) | NCSs/NCSE independently associated with poor outcome 20% vs 3% controls, p = 0.039 |
Bottaro et al. [13] (2007) | Retrospective | 20mn | (124) | 22 (18) | NCSE significant association with mortality, longer hospitalization and poor outcome |
Privitera et al. [9] (1994) | Prospective | 30mn | (198) | 74 (37) | Death was more common in NCSE (37%) compared to controls (23%) |
Current and previous studies on NCSE prevalence and outcome.
NCSE is often associated with a poor outcome and a high mortality rate [9, 12, 13, 38]. In the current study, the mortality rate among patients with AMS and NCSE was 31%, while the mortality rate among those with AMS and without NCSE was only 19%; NCSE carried a poor prognosis. Only one author reported similar outcome in NCSE and controls [9]; however death was more common in NCSE (37%) than in controls (23%). As previously reported by Young et al. [27], the length of stay and age were statistically significantly associated with mortality in the NCSE group (Table 7). In addition, in the current study, among patients with AMS and NCSE, head injury and stroke were associated with bad clinical outcomes with regard to recovery (Table 8). Also, we observed a longer hospitalization for NCSE group than that in the controls that is compatible with previous reports [13, 15].
Variable | OR | 95% CI | P value |
---|---|---|---|
Age | 1.16 | 1.0–1.34 | 0.05 |
Length of stay | 2.03 | 1.29–3.20 | 0.002 |
Cardiac arrest | 3.27 | 0.07–153 | 0.55 |
Stroke | 35.0 | 0.33–3629 | 0.14 |
Head injury | 30.1 | 0.02–56,392 | 0.38 |
Multivariate logistic regression for mortality in NSCE.
Note: Variables significant at univariate analysis and having adequate numbers were used for multivariate analysis.
Variable | OR | 95% C.I. | P value |
---|---|---|---|
Age | 1.0 | 0.96–1.05 | 0.74 |
Length of stay | 1.10 | 0.90–1.34 | 0.36 |
Cardiac arrest | 4.22 | 0.64–27.9 | 0.14 |
Stroke | 26.30 | 3.24–213 | 0.03 |
Head injury | 19.5 | 1.30–293 | 0.002 |
Multivariate logistic regression for morbidity in NSCE.
Note: Variables significant at univariate analysis and having adequate numbers were used for multivariate analysis.
We agree with Claassen [14] that most patients showing early NCSE EEG features (n = 13, =65%) did not achieve good outcome; we did not find any association between acute symptomatology and outcome as highlighted by Kang [39].
Patients with “periodic discharges” did not completely meet the EEG criteria for NCSE. In ICUs and cEEG monitoring units, these periodic EEG patterns are described as lying along an ictal–interictal continuum. There are convincing studies that these PDs, especially GPDs and LPDs, are strongly associated with NCSE and may be ictal [13, 15, 32, 40, 41, 42, 43, 44, 45]; in fact, these EEG patterns have been found in patients with AMS, some were evolving and some responded to benzodiazepines, as shown in Figures 1–4. Many studies reported that PDs carry a bad prognosis, and the final outcome depends mainly on the etiology of AMS [8, 18, 19, 20, 39]; in our study, 50% of patients with PDs died; they suffered from stroke, cardiac arrest, sepsis, or head injury. However, in multivariate logistic regression analysis, we did not find a correlation between these etiologies and mortality in patients with AMS and NCSE (Table 7). It seems that prognosis in NCSE depends on several factors (e.g., age, etiology, level of consciousness, etc.) and cannot be based on EEG or any one factor alone [20, 42].
Finally, the outcome of refractory NCSE was very poor in our study; 9 out of 21 patients (43%) with refractory NCSE died; this is much higher than that reported in a previous study (25%) [46]. However, in that study, 17% of refractory NCSE patients were in a vegetative state.
As reported previously, history of epilepsy/seizures could be a risk factor for NCSs/NCSE [12, 13, 38].
The optimal length of cEEG monitoring in critically ill ICU patients with AMS is a controversial issue in the literature. In our study, majority (66%) of NCSE cases were detected during the first 3 hours of cEEG monitoring; this detection rate reached to 90% by 48 hours of monitoring. Various required cEEG monitoring durations have been suggested in the literature; 12–24 hours [8, 12, 19, 22], 72 hours [16, 18, 47], and finally 7–10 days [23]. A recent study reported that 1/5 of patients without early EEG epileptiform features develop them during 72 hours of cEEG monitoring [25]; Claassen et al. concluded that seizures are detected only in 87% of comatose patients compared to non-comatose patients (98%) in the first 48 hours of cEEG monitoring [14].
Based on the results from our study and review of the literature, and also considering the challenges and costs associated with cEEG monitoring, we suggest that 3 days of cEEG monitoring is optimal in ICUs and in patients with AMS to detect the majority of cases of NCSs/NCSE [14, 25].
To our knowledge, this is the first prospective study reporting the prevalence of NCSE in Qatar, a small country in the MENA region. This figure (26%) was in the middle range. Patients with NCSE did not do better than the controls, the result being disappointing regarding comatose NCSE. NCSE is an emerging condition requiring rapid diagnosis and rapid treatment. Regarding the duration of cEGG monitoring to diagnose the majority of NCSE cases, 3 days of cEEG monitoring could accomplish this task.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\\n\\nPeer Review Policies
\\n\\nAll scientific works are Peer Reviewed prior to publishing. Read more
\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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