Prognostic factors for glioblastoma patients--a clinical population-based study.

OBJECTIVES: To address in a retrospective and population-based study prognostic factors for survival time after diagnosis and surgery for glioblastoma multiforme (GBM). MATERIAL AND METHODS: During the study period, 430 patients were identified at the multidisciplinary team conferences as newly diagnosed GBM, 201 of these were considered not to benefit from surgery, and thus, a total of 229 consecutive adult patients with GBM were operated between January 2004 and December 2008 at Sahlgrenska University Hospital and were retrospectively analyzed. Potential predictors of survival were statistically analyzed using Poisson regression models. RESULTS: Median survival was 0.73 years. Multivariable analysis showed the following factors to positively influence survival: younger age at surgery, secondary tumor genesis, unifocal tumor location (vs multifocal), resection (vs biopsy only), radiotherapy, and combination of radiotherapy and chemotherapy. CONCLUSION: This population-based study supports the importance of surgery instead of biopsy only, followed by radiotherapy and chemotherapy, a finding which has also been stated in earlier non-population-based reports. However, it is obvious that the solution is not just surgical radicality followed by optimal oncological treatment. It is of great importance to seek further subclassifications, biomarkers, and new treatment modalities to make a significant change in survival for individuals.

High-Sensitive Troponin T and N-Terminal Pro B-Type Natriuretic Peptide for Early Detection of Stress-Induced Cardiomyopathy in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Patients developing stress-induced cardiomyopathy (SIC) after subarachnoid hemorrhage (SAH) have increased risk of vasospasm, delayed cerebral ischemia and death. We evaluated whether high-sensitive troponin T (hsTnT) and N-terminal pro B-type natriuretic peptide (NTproBNP) are useful biomarkers for early detection of SIC after SAH. METHODS: Medical records of all patients admitted to our NICU with suspected or verified SAH from January 2010 to August 2014 were reviewed. Patients in whom echocardiography was performed and blood samples for measurements of hsTnT and/or NTproBNP were obtained, within 72 and 48 h, respectively, after onset of symptoms, were included. SIC was defined as reversible left ventricular segmental hypokinesia diagnosed by echocardiography. RESULTS: A total of 502 SAH patients were admitted during the study period, 112 patients fulfilled inclusion criteria and 25 patients fulfilled SIC criteria. Peak levels of hsTnT and NTproBNP were higher in patients with SIC (p < 0.001). hsTnT had its peak on admission, while NTproBNP peaked at days 2-4 after onset of symptoms. A hsTnT > 89 ng/l or a NTproBNP > 2,615 ng/l obtained within 48 h after onset of symptoms had a sensitivity of 100% and a specificity of 79% in detecting SIC. CONCLUSIONS: The cardiac biomarkers, hsTnT and NTproBNP, are increased early after SAH and levels are considerably higher in patients with SIC. These biomarkers are useful for screening of SIC, which could make earlier diagnosis and treatment of SIC in SAH patients possible.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Background: Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. Methods: We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Results: Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. Conclusion: The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

Health status and life satisfaction after decompressive craniectomy for malignant middle cerebral artery infarction.

OBJECTIVES: To study the long-term outcome in patients with malignant middle cerebral artery (MCA) infarction treated with decompressive craniectomy. The outcome is described in terms of survival, impairment, disabilities and life satisfaction. MATERIALS AND METHODS: Patients were examined at a minimum of 1 year (mean 2.9, range 1-6) after the surgery and classified according to the Glasgow Outcome Scale (GOS), the National Institutes of Health Stroke scale (NIHSS), the Barthel Index (BI), the short-form health survey (SF-36) and the life satisfaction checklist (LiSat-11). RESULTS: Eighteen patients were included. The long-term survival was 78%. The mean NIHSS score was 13.8 (range 6-20). No patient was left in a vegetative state. The mean BI was 63.9 (5-100). The SF-36 scores showed that the patients' view of their health was significantly lower in most items compared with that of a reference group. According to the LiSat checklist, 83% found their life satisfying/rather satisfying and 17% found their life rather dissatisfying/dissatisfying. CONCLUSION: We conclude that the patients remained in an impaired neurological condition, but had fairly good insight into their limitations. Although their life satisfaction was lower compared with that of the controls, the majority felt that life in general could still be satisfying.

Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging.

This case report describes a patient who sustained severe head trauma with diffuse axonal injury (DAI). Examination with magnetic resonance diffusion tensor imaging (MRDTI), 6 days post-injury, showed a severe reduction in fractional anisotropy (FA) in the rostral pons containing the corticospinal tract, which correlated to the patient's severe hemiparesis. By 18 months post-accident, the patient had recovered completely and conventional MRI showed no pathology. However, although her FA values in the rostral pons had increased, they were still not normalized. It seems that a complete normalization of the FA values is not required to achieve clinical recovery, and that MR-DTI seems to be more sensitive to DAI compared to conventional MRI.

Activity in cortical cells after stimulation of tooth pulp afferents in the cat. Intracellular analysis.

The projection of tooth pulp afferents to cortical cells was studied in intracellular recordings. In a small region of the coronal gyrus, cells in lamina IV were responding at stimulation of contralateral tooth pulp afferents with short latency, steeply rising EPSPs, and one or two action potentials followed by an IPSP. These cells received convergence from skin afferents. In a large cortical area in the coronal, anterior suprasylvian and anterior ectosylvian gyri, tooth pulp stimulation elicited long latency, long lasting EPSPs not succeeded by hyperpolarization mainly in superficial cortical cells. These EPSPs could elicit trains of spikes. A complex type of responses consisted of a short latency EPSP with one or two spikes followed by hyperpolarization which in part was counteracted by a second, long latency EPSP of long duration. Stimulation of low threshold contralateral skin afferents usually gave short latency EPSPs with spikes followed by long lasting hyperpolarization. A common feature of many cells was a high convergence from tooth pulp afferents and bilateral low threshold skin afferents. The response characteristics at tooth pulp stimulation compared to low threshold input are discussed in relation to cortical mechanisms of pain.

Activity in cortical cells after stimulation of tooth pulp afferents in the cat. Extracellular analysis.

The cortical projection of tooth pulp afferents has been investigated by extracellular recordings in lightly chloralose anaesthetized cats. The results indicate two different projection systems from the tooth pulp afferents terminating on the cortical cells. One system appears to be specific with topographical distribution and activates cells mainly in lamina IV in a restricted region of the coronal gyrus. The cells in this area receive excitation also from restricted cutaneous fields. At stimulation of the tooth pulps with single electrical pulses cells are activated with high discharge probability and with a stable latency. The other system projects mainly to cells in the superficial cortical laminae in a much larger area. These cells receive input from large bilateral cutaneous fields but show less discharge probability and require often temporal summation to discharge at tooth pulp stimulation.

Cortical responses evoked by tooth pulp stimulation in the cat. Surface and intracortical responses.

In lightly chloralose-anaesthetized cats selective stimulation of tooth pulp afferents elicited responses in coronal, anterior suprasylvian and adjacent cortical gyri. In the lateral part of coronal gyrus the potentials evoked from the contralateral canine tooth pulps were initially positive. Such responses from the upper and lower teeth had different cortical distribution suggesting a topographical organization. In the regions adjacent to those with initially positive responses stimulation of the same tooth pulp evoked initially negative potentials. Stimulation of ipsilateral tooth pulp afferents elicited almost exclusively initially negative potentials with a similar distribution as the responses of contralateral teeth but with longer latency. Laminar analysis showed that the region with initial positivity in the response to stimulation of the tooth pulp coincided with an intracortical negative focal potential of maximum amplitude mainly in lamina IV. In areas with initially negative responses the maximum of the focal potential following tooth pulp stimulation was obtained in superficial cortical layers. It is postulated that the projection system underlying the initially positive cortical responses has a topographically arranged cortical projection terminating mainly in lamina IV. The projection system eliciting the initially negative potentials, has a widespread cortical distribution and produces excitation predominantly in the superficial laminae.

A standardized neurosurgical neurointensive therapy directed toward vasogenic edema after severe traumatic brain injury: clinical results.

OBJECTIVE: Analysis of a standardized therapy focusing on prevention and treatment of vasogenic edema in patients suffering severe traumatic brain injury (TBI). DESIGN: A retrospective analysis. SETTING: Neurointensive care unit at Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: 38 patients with severe TBI were included. The median Glasgow Coma Score was 5 (range 3-8) and median age 27 years (range 5-70 years). INTERVENTIONS: Measurement of intracranial pressure (ICP). Surgical evacuation of hematomas and contusions. Volume expansion aiming at normovolemia. Sedation with continuous intravenous infusion of low-dose thiopentone and reduction of stress response by clonidine. Normalization of capillary hydrostatic pressure by metoprolol and clonidine. If ICP and cerebral perfusion pressure (CPP) were not stabilized (ICP < 20 mmHg and CPP > 60 mm Hg), a continuous infusion of dihydroergotamine was added. In 4 patients a craniectomy was performed. RESULTS: Of the 38 patients, 27 (71%) survived with good recovery or moderate disability, 5 (13%) survived with severe disability, 1 (3%) remained in a vegetative state, and 5 (13%) died. The mortality due to intracranial hypertension was 11% (4 patients). CONCLUSION: A therapy focusing on treatment of the assumed vasogenic edema in combination with aggressive neurosurgery resulted in an outcome as good as the best previously reported.

Effect of DLF lesions at different spinal levels on morphine induced analgesia.

The effect of morphine on tail flick latency was tested in 3 groups of rats. It is shown that in normal rats and in rats with a bilateral DLF lesion at Th10 or lower spinal root segments, morphine increased the tail flick latency. After a bilateral DLF lesion at Th9 or higher segments, morphine did not change the tail flick latency.

Influence of changes of tooth temperature on reflex and central activity evoked by stimulation of tooth pulp afferents.

The importance of the temperature of the dentine was studied in teeth prepared for electrical stimulation. During experiments with the mouth open, the temperature of teeth covered by cement was normal. The digastric EMG and the brainstem--evoked response following electrical stimulation of the tooth pulp as well as the threshold for eliciting a jaw-opening response remained constant throughout prolonged experiments. However, heat produced by the cement used to fixate the tooth electrodes could have damaged the tooth if the dentine temperature had exceeded 45 degrees C. A careful preparation of the tooth pulp by repeated application of thin layers of cement allowed an adequate preparation without damage to tooth pulp afferents.

Expression of Ca(2+)-ion permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in Xenopus oocytes injected with total RNA from human epileptic temporal lobe.

By using the Xenopus oocyte as an expression system, we have performed a series of experiments in order to examine the divalent cation-permeability of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors from the human epileptic temporal lobe. Xenopus oocytes, injected with total RNA from the epileptic temporal lobe, were tested for expression of receptors by a conventional two electrode voltage-clamp technique. Administration of glutamate and AMPA gave small or no clear current responses, whereas kainate produced large inward non-desensitizing currents. The current responses evoked by kainate were concentration dependent. Experimental data gave a Hill coefficient of 1.06 and an EC50 value of 87 microM. The current to voltage relationship showed an inward rectification and when the concentration of divalent cations were enhanced, there was a shift in the reversal potential from -11 mV (2 mM Ca2+) to 12 mV (60 mM Ba2+). This yielded a pBa2+/pK+ permeability ratio of 1.6 when the constant field equation was used. The amplitude of the currents evoked by 600 microM kainate in solutions containing higher Ba(2+)-ion concentrations was markedly diminished (46% in 10 mM Ba(2+)- and 75% in 60 mM Ba(2+)-solution), when compared to those obtained in normal Ringer's solution, suggesting interactions between different cation species and/or screening of surface charges.

Complications of epilepsy surgery after 654 procedures in Sweden, September 1990-1995: a multicenter study based on the Swedish National Epilepsy Surgery Register.

OBJECTIVE: To present the first national multicenter study on complications after epilepsy surgery procedures to include all epilepsy surgery centers in Sweden: Göteborg, Linköping, Lund, Stockholm, Umeå, and Uppsala. METHODS: Every epilepsy surgery procedure in Sweden is reported to the Swedish National Epilepsy Surgery Register. The report includes relevant social and medical items and complications. A complication is defined as minor if it resolves within 3 months and major if it affects activities of daily living and lasts longer than 3 months. Follow-up data are recorded for 2 years after the operation. Intrinsic checkpoints and external revision validate the register data. RESULTS: During the inclusion period (September 1990-December 1995), 654 surgical procedures were performed (age range, 6 mo-67 yr). Of these, 205 were invasive electrode procedures (182 first investigations and 23 reinvestigations), and 449 were therapeutic procedures (375 first operations and 74 reoperations). After invasive electrode procedures, only minor complications were reported (6.3%). For all 449 therapeutic procedures (including reoperations), minor complications were reported in 8.9% and major complications in 3.1 %. Only one major complication was reported in a patient under the age of 35 years. CONCLUSION: This is the first national multicenter study on complications after epilepsy surgery. It demonstrates that these procedures as performed at six different centers in Sweden are safe, but also that risk is related to age. In patients younger than age 35 years, the risk for a major complication after invasive subdural strip electrode investigation and epilepsy surgery is low.

Cortical reorganisation of sensory, motor and language functions due to early cortical damage.

During evaluation of a 22-year-old man for epilepsy surgery it was demonstrated that reorganisation of sensory, motor and language functions had occurred. Restricted perinatal lesions in the left frontal opercular region and in the hand primary sensory area had resulted in severe partial epilepsy and minor neuropsychological deficits, but no neurological deficits. The dominance for language and handedness was shifted to the right hemisphere but some language representation was still found in the left hemisphere. Threshold electrical stimulation via subdurally placed cortical electrodes revealed reorganisation of the hand sensory area in the left hemisphere. Hand sensory responses were electrically evoked close to the opercular region where also face sensory responses were recorded. Some of the sensory responses were located in the frontal lobe in the premotor cortex. The locations of the sensory representation areas differed from those expected neuroanatomically. The cortical motor responses were located around the presumed location of the precentral gyrus. These findings are considered to represent a functional intra- and interhemispherical reorganisation of cortical areas as a result of early cortical lesions, anatomically close to the somatosensory and language areas. A possible mechanism discussed is reorganisation of the thalamocortical projections.

Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy.

Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.

A new operant discrimination test procedure for resident rats.

An automated method for testing visual discrimination with water reinforcement using a modified residential Y-maze is described. The visual stimulus is presented above one of two water holes. Rats have been tested with different lengths of water periods and different intervals between the periods. During the 10 days of testing, overall activity decreased. Activity on the initial days was low during daytime, with few drinking attempts. Discrimination learning acquisition was measured as the increase in the percentage of water periods with drinking attempts in which the first attempt occurred on the correct side, and/or as the increase in the number of correct drinking attempts as a percentage of all drinking attempts. Acquisition was observed both when light indicated water and when it indicated no water. This test model may offer a useful method for standardized measurement of left/right, light on/off discriminations.

Effects of prenatal alcohol exposure on activity and learning in Sprague-Dawley rats.

Nulliparous pregnant Sprague-Dawley rats were exposed to ethanol via a liquid diet technique (FAE, fetal alcohol exposure) or administered a fixed amount of control diet from gestational day 11 to day 21. The offspring, at 2-3 months of age, were studied in tests of mechanically monitored motor activity and learning acquisition in an automatized testing cage requiring an instrumental discriminative response, where the ability to learn and relearn correlations of a light signal to water presentation was monitored. A significantly reduced activity (i.e. ramp mounting behaviour) in a novel situation was obtained in the FAE group compared to controls. The initial disruption of ramp mounting behaviour could reflect alterations in either habituation to a novel test situation, altered neophobia, or some retardation in associating these responses with the outcome of water-availability. Adult FAE rats (six months of age) showed a tendency towards a lowered acquisition performance (p = 0.06) when tested in a circular Morris-type swim maze, but no detectable differences were shown in a motor activity test chamber situation.

[Well-integrated chain of care results in better prognosis in severe brain injury]. / Sammanhållen vårdkedja ger bättre prognos vid svår hjärnskada.

The result of a project in the western region of Sweden regarding a multi- and interdisciplinary approach to patients with severe traumatic brain injury/subarachnoid bleeding is reported. The importance of early structured intervention and long-range follow-up by a rehabilitation team is stressed. The goal is to afford patients and their families/caregivers optimal care and support from the time of injury through rehabilitation. The project has resulted in an established clinical routine. Results indicate that patients treated in this manner attain a higher level of performance in a shorter period of time. Furthermore, results from one-year post-injury evaluation demonstrate a high degree of Life Satisfaction (Fugl-Meyer questionnaire) for most patients. This is a long-range study which will monitor patients for at least four years.

Plateau waves and baroreflex sensitivity in patients with head injury: a case study.

The study aimed to investigate baroreceptor reflex sensitivity in a patient with head injury for whom plateau waves of intracranial pressure (ICP) were recorded. Baroreflex sensitivity index was separately estimated on top of plateau waves and during intermediate intervals between two consecutive waves. The EuroBaVar data set was utilized to verify and validate the results. A very high baroreflex sensitivity associated with dominant parasympathetic activity was observed spontaneous to the acute elevations of ICP. The high vagal afferent discharge was found to be suggestive for the high firing rate of carotid baroreceptors and probably an active Cushing reflex mechanism during plateau waves.

Pulse wave velocity in patients with severe head injury a pilot study.

The study aimed to determine the potential of pulse wave velocity measurements to reflect changes in compliant cerebral arteries/arterioles in head injured patients. The approach utilizes the electrocardiogram and intracranial pressure signals to measure the wave transit time between heart and cranial cavity. Thirty five clinical records of nineteen head injured patients, with different levels of cerebrovascular pressure-reactivity response, were investigated through the study. Results were compared with magnitude of normalized transfer function at the fundamental cardiac frequency. In patients with intact cerebrovascular pressure-reactivity, magnitude of normalized transfer function at the fundamental cardiac component was found to be highly correlated with pulse wave transit time.