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Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG BOLD ) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age-matched controls (median 63y; 73% females) were scanned for MREG BOLD signal during 2018-2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREG BOLD signal was calculated to examine the stability of physiological brain pulsations. Group-level differences in CV were examined using nonparametric covariate-adjusted tests. Subject-level CV alterations were examined against control population Z-score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast-enhanced, diffusion-weighted, fluid-attenuated inversion recovery (FLAIR) data]. Whole-brain mean CV was linked to short-term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10 5 mm 3 ) extended spatially beyond FLAIR lesions (median 0.62 × 10 5 mm 3 ) with differences in volumes (p = .0055)., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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., (© 2022. The Author(s).)

Purpose: Anesthesiologists have increasingly started to use EEG-based indexes to estimate the level and type of unconsciousness. However, the physiology and biophysics are poorly understood in anesthesiological literature., Methods: EEG was recorded from electrodes on the surface of head, including scalp, as well as DBS (deep brain stimulation) electrodes implanted deep in the brain. Mathematical modeling with a realistic head model was performed to create illustrative images of the sensitivity of electrode montages., Results: EEG pattern of anesthesia, burst-suppression, is recordable outside of scalp area as well in the depth of brain because the EEG current loops produce recordable voltage gradients in the whole head. The typical electrodes used in anesthesia monitoring are most sensitive to basal surface of frontal lobes as well as frontal and mesial parts of temporal lobes., Conclusions: EEG currents create closed-loops, which flow from the surface of the cortex and then return to the inside of the hemispheres. In the case of widespread synchronous activity like physiological sleep or anesthesia, the currents recorded with surface and depth electrodes return through the base of brain and skull.

Objectives: The aim of the study was to compare the EEG findings and haemodynamic parameters of adult male patients while undergoing mask induction with sevoflurane anaesthesia with either controlled hyperventilation (CH) or spontaneous breathing (SB)., Methods: Twenty male patients, aged 23-52 (mean 42) years were anaesthetized randomly with either spontaneous breathing or mild controlled hyperventilation via mask. EEG was recorded using a full 10-20 electrode set., Results: Anaesthesia induction with high inhaled concentrations of sevoflurane produced several epileptiform and periodic EEG patterns. CH doubled the amount of these EEG patterns compared to SB. Higher heart rate was recorded in the CH group., Conclusions: We describe a high incidence of paroxysmal EEG activity: epileptiform and generalized periodic discharges (GPDs) during rapid sevoflurane in nitrous oxide-oxygen mask induction in hyperventilated male patients. However these activities have no effect to the heart rate or the mean arterial pressure., Significance: The monitoring of GPDs and burst suppression patterns during rapid anaesthesia induction with sevoflurane provides possibility to study the effects of volatile anaesthetics in the healthy brain. In order to analyse the different sources of EEG patterns a wide-band multichannel EEG recording is necessary., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation. We analysed 25 patients (age range: 40-71 years) who were treated in first or second line with BBBD therapy. When we started BBBD treatment, patients had relapsed or refractory PCNSL or they did not tolerate Bonn-like therapy. In recent years, some of the patients were treated in first line. We found promising response rates. Altogether 19 (76 %) of the patients achieved a complete response (CR). Two-year progression-free survival (PFS) and overall survival (OS) rates were 61 and 57 % respectively and the five-year OS was 47 %. Patients who were treated with a five-drug therapy had a very promising prognosis. The CR rate was 100 % in first-line therapy and 60 % in relapsed cases. These findings suggest that BBBD is a promising therapy for PCNSL, especially for patients in first line, but also for patients with relapsed or refractory disease after conventional chemotherapy, who commonly have a very poor prognosis. Treatment-related toxicity was generally manageable. Thus, BBBD followed by ASCT could be a treatment of choice in transplant-eligible patients with PCNSL.

Primary central nervous system lymphoma (PCNSL) is sensitive to both chemotherapy and radiation, but the blood-brain barrier limits the usefulness of the most effective chemotherapeutic agents. On the other hand radiation therapy carries along serious long term adverse events. In BBBD-therapy the blood-brain barrier is opened with intra-arterial mannitol infusion thus permitting both the chemotherapeutics and antibodies to enter through blood-brain barrier. So far 17 patients have started the therapy in our clinics. Ten patients have reached a complete response and 8 of these responses are ongoing with follow-up times of 6-62 months.

Background: Several measures have been developed to quantify the change in EEG from wakefulness to deep anaesthesia. Measures of signal complexity or entropy have been popular and even applied in commercial monitors. These measures quantify different features of the signal, however, and may therefore behave in an incomparable way when calculated for standardized EEG patterns., Methods: Two measures widely studied for anaesthesia EEG analysis were considered: spectral entropy and approximate entropy. First, we generated surrogate signals which had the same spectral entropy as a prototype signal, the sawtooth wave. Secondly, EEG samples where rhythmic pattern caused a peak in the power spectrum in the α-frequency band were modified by enhancing or suppressing the corresponding rhythm., Results: We found that the value of spectral entropy does not, in general, correlate with the visual impression of signal regularity. Also, the two entropy measures interpret a standardized artificially modified EEG signal in opposite directions: spectral peak of increasing amplitude in the α-frequency band causes spectral entropy to increase but decreases approximate entropy when low frequencies are present in the signal., Conclusions: Spectral entropy and approximate entropy of EEG are two totally different measures. They change similarly in deepening anaesthesia due to an increase in slow activity. In some cases, however, they may change in opposite directions when the EEG signal properties change during anaesthesia. Failure to understand the behaviour of these measures can lead to misinterpretation of the monitor readings or study results if no reference to the raw EEG signal is taken.

Penicillin-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., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Our aim was to explore time-varying coherence values versus spacing and referencing of electrode contacts in thalamic level from human encephalographic (EEG) data. Data has been acquired during induction of propofol anesthesia until burst-suppression level in scalp EEG. Results are shown from coherence analysis applied to EEG signals from selected depth electrode contacts pair-wise of three subjects. Alpha coherence is the most prominent behavior in all channel pairs. It is persistent throughout the time period followed and in coherence calculated between bipolar derivations in depth electrodes.

Background: Epileptiform patterns, spikes, polyspikes and periodic epileptiform discharges (PED) have been reported in electroencephalograms (EEGs) during anaesthesia induction with sevoflurane in healthy adults and children. Published recordings have been performed with a limited number of channels, and therefore the topographic distributions of these patterns are not known., Methods: Twenty ASA I children aged 4-10 years undergoing routine operations were anaesthetized with 8% sevoflurane in 50%/50% oxygen and nitrous oxide using mask induction with controlled normoventilation. An EEG was recorded with a full 10-20 electrode system including orbitofrontal and ear electrodes, and a recording band of 0.016-70 Hz. Beat-to-beat heart rate (HR) was calculated off-line., Results: Nineteen out of 20 children developed multifocal spikes and polyspikes with a maximum over the frontal lobes. Four patients developed suppression, which was almost continuous and lasted several minutes, and thereafter a continuous EEG resumed, a few spikes were seen and then a nonepileptiform pattern. In three children a couple of PED waves were seen at the onset of a continuous EEG. HR increased maximally before the onset of spikes. No motor phenomena were seen., Conclusion: These recordings confirm the epileptogenic property of sevoflurane in mask induction. The spikes and polyspikes had frontal multifocal maxima and may be missed in recordings from frontopolar electrodes used by depth-of-anaesthesia monitors. PED and burst suppression were synchronous over the whole cortex. Epileptiform activity was indiscernible from epileptiform waveforms without anaesthesia, such as the patterns seen in status epilepticus.

Background: Measurement of slow EEG activity and burst suppression are the main tasks in monitoring the effects of anaesthestics with EEG, which is often done with commercial univariate indexes such as BIS. The aim of this study was to describe the characteristics of burst suppression EEG during propofol anaesthesia using scalp electrodes and depth electrodes in the subthalamic nucleus. Specifically, we describe the electrical fields of the three EEG patterns we have previously described: the sharp wave, the burst and the spindle., Methods: We recorded the EEG of three Parkinson patients during propofol anaesthesia from the scalp electrodes and the depth electrode implanted in the subthalamic nucleus for treating parkinsonism., Results: (1) The slow waves of bursts recorded from all surface electrodes on scalp or neck with depth electrode reference are positive and have the highest amplitude in frontal electrodes, suggesting synchronous generation in the whole cerebral cortex. (2) The sharp wave and spindles have the highest amplitude at vertex. They are opposite in polarity in vertex and depth electrodes when referred to the neck electrode, suggesting generation in the sensorimotor cortex., Conclusions: Recording simultaneously EEG from the depth and scalp electrodes shows that bursts and their slow wave oscillations are synchronous in the whole cortex while spindles and sharp waves are produced by the sensorimotor cortex. The amplitude of slow waves recorded with surface electrodes is equal to the difference of the wave at two electrodes and therefore only a small part of that generated by the cortex.

In 40-60% of cases with interictal activity in EEG, fMRI cannot locate any focus or foci with simultaneous EEG/fMRI. In experimental focal epilepsy, a priori knowledge exists of the location of the epileptogenic area. This study aimed to develop and to test an experimental focal epilepsy model, which includes dynamic induction of epileptic activity, simultaneous EEG/fMRI, and deep anesthesia. Reported results are from seven pigs (23 +/- 2 kg) studied under isoflurane anesthesia (1.2-1.6 MAC, burst-suppression EEG) and muscle relaxant. Hypo- and hypercapnia were tested in one pig. Penicillin (6000 IU) was injected via a plastic catheter (inserted into the somatosensory cortex) during fMRI (GRE-EPI, TE = 40 ms, 300 ms/two slices, acquisition delay 1700 ms) in 1.5 T (N = 6). Epileptic spikes between acquisition artifacts were reviewed and EEG total power calculated. Cross-correlation between voxel time series and three model functions resembling induced spike activity were tested. Activation map averages were calculated. Development of penicillin induced focal epileptic activity was associated with linear increase and saturation up to approximately 10-20%, in BOLD activation map average. Its initial linear increase reached 2.5-10% at the appearance of the first distinguished spike in ipsilateral EEG in all six animals. Correlated voxels were located mainly in the vicinity of the penicillin injection site and midline, but few in the thalamus. In conclusion, development of focal epileptic activity can be detected as a BOLD signal change, even preceding the spike activity in scalp EEG. This experimental model contains potential for development and testing different localization methods and revealing the characteristic time sequence of epileptic activity with fMRI during deep anesthesia.

Differences in the blood oxygen level dependent (BOLD) signal changes were studied during voluntary hyperventilation (HV) between young healthy volunteer groups, (1) with intermittent rhythmic delta activity (IRDA) (N = 4) and (2) controls (N = 4) with only diffuse arrhythmic slowing in EEG (normal response). Subjects hyperventilated (3 min) during an 8-min functional MRI in a 1.5-T scanner, with simultaneous recording of EEG (successful with N = 3 in both groups) and physiological parameters. IRDA power and average BOLD signal intensities (of selected brain regions) were calculated. Hypocapnia showed a tendency to be slightly lighter in the controls than in the IRDA group. IRDA power increased during the last minute of HV and ended 10-15 s after HV. The BOLD signal decreased in white and gray matter after the onset of HV and returned to the baseline within 2 min after HV. The BOLD signal in gray matter decreased approximately 30% more in subjects with IRDA than in controls, during the first 2 min of HV. This difference disappeared (in three subjects out of four) during IRDA in EEG. BOLD signal changes seem to depict changes, which precede IRDA. IRDA due to HV in healthy volunteers represent a model with a clearly defined EEG pattern and an observable BOLD signal change.

Cortical evoked responses to median nerve stimulation were recorded from 21 subjects during sevoflurane anaesthesia at the level of burst suppression in EEG. The N20/P22 wave had the typical form of a negative wave postcentrally, and positive precentrally. The amplitude exceeded 4 microV in all patients, making it easily visible without averaging on the low-amplitude suppression. These results show that two kinds of somatosensory evoked potential can be studied without averaging during EEG suppression in deep anaesthesia. One is the localised N20/P22 wave, which is seen regularly during suppression after stimuli with intervals exceeding 1 s. The other is the burst, involving the whole cortex, which is not evoked by every stimulus. We suggest that somatosensory evoked potentials can be monitored during sevoflurane-induced EEG suppression, and often can be evaluated reliably from a couple of single sweeps with stimulation interval exceeding 1 s. The enhancement of early cortical components of SEP, their adaptation to repeated stimuli, and the disappearance of later polysynaptic components during EEG suppression, give new possibilities to study the generators of SEP and the different effects of anaesthetics.