A characteristic time sequence of epileptic activity in EEG during dynamic penicillin-induced focal epilepsy—A preliminary study

AbstractPenicillin-induced focal epilepsy is a well-known model in experimental epilepsy. However, the dynamic evolution of waveforms, DC-level changes, spectral content and coherence are rarely reported. Stimulated by earlier fMRI findings, we also seek for the early signs preceding spiking activity from frequency domain of EEG signal. In this study, EEG data is taken from previous EEG/fMRI series (six pigs, 20–24kg) of an experimental focal epilepsy model, which includes dynamic induction of epileptic activity with penicillin (6000IU) injection into the somatosensory cortex during deep isoflurane anaesthesia. No ictal discharges were recorded with this dose. Spike waveforms, DC-level, time–frequency content and coherence of EEG were analysed. Development of penicillin induced focal epileptic activity was not preceded with specific spectral changes. The beginning of interictal spiking was related to power increase in the frequencies below 6Hz or 20Hz, and continued to a widespread spectral increase. DC-level and coherence changes were clear in one animal. Morphological evolution of epileptic activity was a collection of the low-amplitude monophasic, bipolar, triple or double spike-wave forms, with an increase in amplitude, up to large monophasic spiking. In conclusion, in the time sequence of induced epileptic activity, immediate shifts in DC-level EEG are plausible, followed by the spike activity-related widespread increase in spectral content. Morphological evolution does not appear to follow a clear continuum; rather, intermingled and variable spike or multispike waveforms generally lead to stabilised activity of high-amplitude monophasic spikes

The brain's electrical activity in deep anaesthesia:with special reference to EEG burst-suppression

Abstract Several anaesthetics are able to induce a burst-suppression (B-S) pattern in the electroencephalogram (EEG) during deep levels of anaesthesia. A burst-suppression pattern consists of alternating high amplitude bursts and periods of suppressed background activity. All monitors measuring the adequacy of anaesthesia recognize the EEG B-S as one criterion. A better understanding of EEG burst-suppression is important in understanding the mechanisms of anaesthesia. The aim of the study was to acquire a more comprehensive understanding of the function of neural pathways during deep anaesthesia. The thesis is comprised of four prospective clinical studies with EEG recordings from 64 patients, and of one experimental study of a porcine model of epilepsy with EEG registrations together with BOLD fMRI during isoflurane anaesthesia (II). In study I, somatosensory cortical evoked responses to median nerve stimulation were studied under sevoflurane anaesthesia at EEG B-S levels. In study III, The EEGs of three Parkinson`s patients were observed to describe the characteristics of B-S during propofol anaesthesia using scalp electrodes and depth electrodes in the subthalamic nucleus. In study IV, EEG topography was observed in 20 healthy children under anaesthesia mask induction with sevoflurane. Twenty male patients were randomized to either controlled hyperventilation or spontaneous breathing groups for anaesthesia mask induction with sevoflurane in study V. EEG alterations in relation to haemodynamic responses were examined in studies IV and V. Somatosensory information reached the cortex even during deep anaesthesia at EEG burst-suppression level. Further processing of these impulses in the cortex was suppressed. The EEG slow wave oscillations were synchronous over the entire cerebral cortex, while spindles and sharp waves were produced by the sensorimotor cortex. The development of focal epileptic activity could be detected as a BOLD signal increase, which preceded the EEG spike activity. The epileptogenic property of sevoflurane used at high concentrations especially during hyperventilation but also during spontaneous breathing together with heart rate increase, was confirmed in healthy children and male. Spike- and polyspike waveforms concentrated in a multifocal manner frontocentrally.Tiivistelmä Useat anestesia-aineet pystyvät aiheuttamaan aivosähkökäyrän (EEG) purskevaimentuman syvän anestesian aikana. Purskevaimentuma koostuu EEG:n suuriamplitudisten purskeiden sekä vaimentuneen taustatoiminnan vaihtelusta. Kaikkien anestesian syvyyttä mittaavien valvontalaitteiden toiminta perustuu osaltaan EEG:n purskevaimentuman tunnistamiseen. Tämän ilmiön parempi tunteminen on tärkeää anestesiamekanismien ymmärtämiseksi. Tutkimuksen päämääränä oli saada kattavampi käsitys hermoratojen toiminnasta syvässä anestesiassa. Väitöskirjatyö koostuu neljästä prospektiivisesta yhteensä 64 potilaan EEG-rekisteröinnit sisältävästä tutkimuksesta sekä yhdestä kokeellisen epilepsiatutkimuksen koe-eläintyöstä, jossa porsailla käytettiin isofluraanianestesiassa sekä EEG-rekisteröintejä sekä että magneettikuvantamista (fMRI) samanaikaisesti (II). Ensimmäisessä osatyössä tutkittiin keskihermon stimulaation aiheuttamia somatosensorisia herätepotentiaaleja aivokuorella EEG:n purskevaimentumatasolla sevofluraanianestesian aikana. Kolmannessa osatyössä selvitettiin propofolianestesian aiheuttamaa EEG:n purskevaimentumaa kolmelta Parkinsonin tautia sairastavalta potilaalta käyttäen sekä pintaelektrodien että subtalamisen aivotumakkeen syväelektrodien rekisteröintejä. Neljännessä osatyössä tutkittiin EEG:n topografiaa 20:llä terveeellä lapsella indusoimalla anestesia sevofluraanilla. Kaksikymmentä miespotilasta nukutettiin sevofluraanilla ja heidät satunnaistettiin joko kontrolloidun hyperventilaation tai spontaanin hengityksen ryhmiin osatyössä V. EEG-muutoksia sekä niiden yhteyttä verenkiertovasteisiin selviteltiin molemmissa osatöissä IV ja V. Omasta kehosta tuleviin tuntoärsykkeisiin liittyvä somatosensorinen informaatio saavutti aivokuoren myös syvässä EEG:n purskevaimentumatasoisessa anestesiassa. Impulssien jatkokäsittely aivokuorella oli kuitenkin estynyt. EEG:n hidasaaltotoiminta oli synkronista koko aivokuoren alueella, sen sijaan unisukkulat ja terävät aallot paikantuivat sensorimotoriselle aivokuorelle. Paikallisen epileptisen toiminnan kehittyminen oli mahdollista havaita jo ennen piikikkäiden EEG:n aaltomuotojen ilmaantumista edeltävänä BOLD-ilmiöön liittyvänä aivoverenkierron lisääntymisenä. Sevofluraanin epileptogeenisyys varmistui erityisesti hyperventilaation, mutta myös spontaanin hengityksen yhteydessä ja näihin liittyi sykkeen nousu sekä terveillä lapsilla että miehillä. Piikkejä ja monipiikkejä käsittävien aaltomuotojen keskittymistä esiintyi otsalohkon keskialueilla

Case report: chemotherapy in conjunction with blood–brain barrier disruption for a patient with germ cell tumor with multiple brain metastases

Clinical practice points Testicular cancer with brain metastases is related to poor prognosis because the penetration of chemotherapeutic agents is decreased by the blood–brain barrier. The standard treatment of brain metastases—whole brain radiation therapy combined with chemotherapy—is related to a limited increase in survival and considerable deleterious cognitive effects. The blood–brain barrier can be transiently disrupted using hyperosmolar intra-arterial mannitol injection. When combined with intra-arterial chemotherapy, therapeutic intratumoral concentrations can be attained. In experienced centers, blood–brain barrier disruption therapy is relatively safe with a low incidence of catheter-related complications. Blood–brain barrier disruption therapy is a promising treatment modality for brain metastases as an alternative to whole brain radiation therapy

Primary central nervous system lymphoma high incidence and poor survival in Finnish population-based analysis

Abstract Background: We report here the first population-based incidence rates and prognosis of primary central nervous system lymphoma (PCNSL) in Finland. Methods: Finnish Cancer Registry data by histological diagnosis and tumor location (2007–2017) for cases with diffuse large B-cell lymphoma. Results: During 2007–2017, 392 new cases of PCNSL were reported (195 males, 197 females). The average age-adjusted incidence was 0.68/100,000 person-years. Incidence for males was 0.74/100,000 and for females 0.63/100,000, respectively. The incidence was highest, 2.93/100,000, among people aged 75–79 years. Concerning all cases in 2007–2017 the 2-year age-adjusted relative survival rate was 33% and the corresponding 5-year survival rate was 26%. Among patients under the age of 70, the age-adjusted 5-year relative survival rate increased from 36% in 2007–2012 to 43% for 2013–2017. Among patients aged 70+ the corresponding survival rates were poor, 7 and 9%. Conclusions: PCNSL incidence in Finland is among the highest reported in the world. The annual increase in incidence was 2.4%. The prognosis is still dismal, especially in elderly patients

Typical spatial distribution of the DC-EEG responses.

<p>Specimen traces recorded during the BBBD procedure with left (a), right (b) and vertebral (c, d) artery infusion of mannitol. On average, carotid artery infusion evoked responses of the kind shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0174072#pone.0174072.g001" target="_blank">Fig 1</a> in electrodes of the 10-10 system located anterior to vertex on the side of the infusion, whereas posterior electrodes on the opposite side showed rather similar responses with opposite polarity (common average reference montage). Therefore, the four subsets of five electrodes shown here were chosen for further characterization of the signals. When using the common average montage, responses evoked by vertebral artery mannitol infusion (c) were strikingly small in amplitude compared to those seen upon carotid artery infusion, suggesting in the former case the presence of a uniformly distributed signal component that cancels out in a differential recording against the common average reference. A reference point distant to the electrodes of the 10-10 system was provided by the ECG reference electrode, and indeed, re-referencing to the low-pass filtered ECG reference electrode signal revealed a prolonged negative shift (d).</p

Grand average DC-EEG and average NIRS traces illustrating characteristic responses evoked by intra-arterial mannitol infusion.

<p>Each DC-EEG trace (upper panels; shaded area indicates values within ±1 SD) was generated by first calculating the mean of five electrode signals and then calculating the grand average of each recording. Mannitol infusion starts at time = 0 and lasts 30 s. DC-EEG responses upon carotid or vertebral artery mannitol infusion are shown using the common average montage (CA), however the responses to vertebral artery infusion are shown also after re-referencing to the distant ECG reference electrode (ECG; upper panel on the right). Bottom graphs show corresponding average oxy- and deoxyhemoglobin NIRS traces in arbitrary units (a.u.; ±1 SD). The number of NIRS recordings is less than that of DC-EEG, but all NIRS recordings are paralleled by simultaneously recorded DC-EEG data included in the upper graphs. Left (n = 13) and right (n = 16) carotid artery infusions induce a negative DC-EEG shift in electrodes above the treated arterial territory, which outlasts the infusion and is followed by a slower shift of opposite polarity. Contralateral posterior electrodes record a response that is qualitatively similar but reversed in polarity. A clear fall in the NIRS signals is seen during left (n = 8) and right (n = 8) carotid artery infusions, followed by a pronounced rise in HbO and a transient partial recovery of Hb after which Hb settles down on a level below the original baseline and HbO decreases slowly but does not fully recover. Vertebral artery infusions show a fronto-occipital DC-EEG potential shift (n = 18) without a lateralized effect, as expected. Re-referencing to the distant ECG reference electrode reveals that there is a negative shift throughout the entire scalp. The early transient shifts in the NIRS signals shown for vertebral artery infusions (n = 7) are more delayed and have much smaller amplitudes because NIRS was always measured on the forehead, i.e. they show responses generated in a non-infused brain area.</p

Characteristic EEG and NIRS responses seen during the BBBD procedure.

<p>Specimen traces illustrating simultaneous changes in raw EEG (upper graph) and NIRS signals (lower graph) during right carotid intra-arterial (i.a.) mannitol infusion. Deepening anesthesia with intravenous (i.v.) thiopental bolus (marked with an arrow) induces a baseline shift and suppresses activity at conventional EEG frequencies (insets a to d show 15 s sample traces on a 6 times expanded vertical scale) prior to mannitol infusion. Mannitol infusion (2nd arrow) then induces a multi-phasic potential response that begins with a pronounced negative shift reaching nearly -2000 μV in less than 1 min. The negative peak is followed by a slow potential descent below the pre-bolus level. Note the emerging burst-suppression (c) and subsequent faster EEG activity (d) similar to baseline state (a) as the thiopental effect slowly dissipates over 15 minutes. The simultaneously recorded NIRS graph shows first how the i.v. thiopental bolus produces a minor elevation to both NIRS HbO and Hb signals (red solid line and blue dashed line, respectively). When the 30 s i.a. mannitol infusion starts both NIRS signals plummet due to dilution of blood and they start to increase towards the original levels after the infusion. Subsequently, HbO rises above the baseline and stays there over the 15 minutes. On the other hand, Hb approaches the baseline level but soon starts to fall again obtaining a steady level clearly below the original baseline.</p

Spatiotemporal analysis of the DC-EEG data illustrated using heat maps.

<p>(a) Thiopental given at time 0 min generates a weak response in 3 min with slightly positive values along the midline and negative values at lateral electrode locations. Re-referencing the common average (CA) referenced data to the ECG reference renders the entire response slightly more negative. Data from all recordings (47 infusions) were pooled because thiopental was applied intravenously. (b) Temporal evolvement of the spatial distribution of DC-EEG responses to mannitol infusion shown using logarithmically increasing time intervals. The signal level preceding mannitol infusion (0 min) defines the zero level for the average responses calculated for 13 left carotid artery, 16 right carotid artery and 18 vertebral artery infusions. All data are shown using the CA reference montage. In addition, the bottom row of heat plots shows vertebral artery infusion data after re-referencing to the ECG reference.</p

Region of interest analysis of the cbCT following i.a. multi-chemotherapy.

<p>Selected major territories are described using white ellipses marked by numbers 1-5 bilaterally (a). HU-values calculated from these areas and mean of them (named as ‘all’) are illustrated by treated artery; right carotis (b), left carotis (c) and vertebralis (d). In every case right (blue) and left (red) side are separated and also SD bars are represented.</p