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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 (MREGBOLD) 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 MREGBOLD signal during 2018–2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREGBOLD 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 × 10₅mm₃) extended spatially beyond FLAIR lesions (median 0.62 × 10₅mm₃) with differences in volumes (p = .0055).

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.

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.

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.

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, 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 paikantui