Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14.

AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.

The role of ICP overnight monitoring (ONM) in children with suspected craniostenosis.

PURPOSE: Secondary craniostenosis is a relevant problem pediatric neurosurgeons are confronted with and poses challenges regarding reliable diagnosis of raised ICP, especially in case of absent or questionable papilledema. How to identify children with elevated ICP is still controversial and diagnostics vary. We report on our experience with computerized ICP ONM in relation to imaging derived parameters. METHODS: Thirty-four children with primary or secondary craniostenosis and clinical suspicion of raised ICP were investigated. We compared clinical signs, history, and radiographic assessment with the results of computerized ICP ONM. Differences were significant at a p < 0.05. RESULTS: Baseline ICP was significantly higher in patients with combined suture synostosis, who also had a higher rate of questionable papilledema. Children with narrowed external CSF spaces in MRI had significantly higher ICP levels during REM sleep. Mean RAP was significantly elevated in patients with multi-suture synostosis, indicating poor intracranial compensatory reserve. Syndromal craniostenosis was associated with elevated ICP, RAP was significantly lower, and skull X-rays showed more impressions (copper beaten skull). RAP increased with more severe impressions only to decline in most severe abnormalities, indicating exhaustion of cerebrovascular reserve at an upper ICP breakpoint of 23.9 mmHg. Headaches correlated to lower ICP and were not associated with more severe X-ray abnormalities. CONCLUSION: Narrowed external CSF spaces in MRI seem to be associated to elevated ICP. Skull X-rays can help to identify patients at risk for chronically elevated ICP. Severe X-ray changes correlate with exhausted cerebrovascular reserve as indicated by RAP decline. Only ICP monitoring clearly identifies raised ICP and low brain compliance. Thus, in cases with ambiguous imaging, ONM constitutes an effective tool to acquire objective data for identification of surgical candidates.

[Recommendation on temperature management after cardiopulmonary arrest and severe traumatic brain injury in childhood beyond the neonatal period : Statement of the German Society for Neonatology and Pediatric Intensive Care Medicine (GNPI) and the scientific Working Group for Paediatric Anaesthesia (WAKKA) of the German Society of Anaesthesiology and Intensive Care (DGAI)]. / Empfehlung zum Temperaturmanagement nach Atem-Kreislauf-Stillstand und schwerem Schädel-Hirn-Trauma im Kindesalter jenseits der Neonatalperiode : Stellungnahme der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI) und der AG Kinderintensivmedizin des Wissenschaftlichen Arbeitskreises Kinderanästhesie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (WAKKA).

The available data on the effectiveness of therapeutic hypothermia in different patient groups are heterogeneous. Although the benefits have been proven for some collectives, recommendations for the use of hypothermia treatment in other groups are based on less robust data and conclusions by analogy. This article gives a review of the current evidence of temperature management in all age groups and based on this state of knowledge, recommends active temperature management with the primary aim of strict normothermia (36-36.5 °C) for 72 hours after cardiopulmonary arrest or severe traumatic brain injury for children beyond the neonatal period.

Effect of leukotriene inhibitors on evolution of experimental brain contusions.

AIMS: Leukotriene levels increase in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) injury in rats. We investigated the impact of two different leukotriene inhibitors in the CCI model on CSF leukotriene levels, brain water content (BWC), brain swelling (BS) contusion size and cellular response. METHODS: 134 male Sprague Dawley rats were investigated at 4, 24 and 72 h after CCI for CSF leukotriene levels and BWC/BS, lesion size in T2-weighted magnetic resonance imaging and immunohistochemistry. Animals received vehicle, MK-886, an inhibitor of 5-lipoxygenase activating protein, or Boscari(®) , a mixture of boswellic acids, acting as competitive nonredox 5-lipoxygenase inhibitors before trauma and then every 8 h until sacrifice. RESULTS: The intracranial pressure (ICP) was unaffected by treatment. Boscari treatment reduced CSF leukotriene C4 increase by -45% at 4 h (P < 0.03) and increase of BWC and BS by 49% (P < 0.05) and -58% at 24 h. Treatment with both substances showed a reduction of lesion volume at 72 h by -21% (P < 0.01) in T(2) -weighted magnetic resonance imaging, which was reflected in a smaller lesion area determined from a NeuN labelled section (-17% to -20%, P < 0.05). Triple immunofluorescence and Fluoro-Jade B staining showed rarefaction of neurones, glia and vasculature in the contusion core, whereas in the pericontusional zone astro- and microglia were upregulated in the presence of dying neurones. Treatment resulted in an improved survival of NeuN labelled neurones in the pericontusional cortex (+15% to +20%, P < 0.05). CONCLUSIONS: Leukotriene inhibition should be further investigated as therapeutic option to counteract secondary growth of traumatic brain contusions and to possibly improve pericontusional neuronal survival.

MR Imaging and Clinical Characteristics of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters.

BACKGROUND AND PURPOSE: Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of the present study was to describe MR imaging and clinical characteristics of patients with DGONC. MATERIALS AND METHODS: Preoperative MR images of 9 patients with DGONC (median age at diagnosis, 9.9 years; range, 4.2-21.8 years) were reviewed. RESULTS: All tumors were located superficially in the frontal/temporal lobes and sharply delineated, displaying little mass effect. Near the circle of Willis, the tumors encompassed the arteries. All except one demonstrated characteristics of low-to-intermediate aggressiveness with high-to-intermediate T2WI and ADC signals and bone remodeling. Most tumors (n = 7) showed a homogeneous ground-glass aspect on T2-weighted and FLAIR images. On the basis of the original histopathologic diagnosis, 6 patients received postsurgical chemo-/radiotherapy, 2 were irradiated after surgery, and 1 patient underwent tumor resection only. At a median follow-up of 61 months (range, 10-154 months), 6 patients were alive in a first complete remission and 2 with stable disease 10 and 21 months after diagnosis. The only patient with progressive disease was lost to follow-up. Five-year overall and event-free survival was 100% and 86±13%, respectively. CONCLUSIONS: This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

OBJECTIVES: The term hydrocephalus encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are often encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. In this study we aimed to update our knowledge of how key quantitative parameters describing CSF dynamics may be used in diagnosis of shunt-responsive hydrocephalus and in the assessment of shunt function. METHODS: A number of quantitative parameters [including resistance to CSF outflow (Rcsf), pulse amplitude of intracranial pressure waveform (AMP), RAP index and slow vasogenic waves] were studies in 1423 patients with 2665 CSF infusion tests and 305 overnight intracranial pressure (ICP)-monitoring sessions over a 17 year period. OBSERVATIONS: We demonstrate our observations for typical values of Pb, Rcsf, AMP, slow vasogenic waves derived from infusion studies or overnight ICP monitoring in differentiating atrophy from shunt-responsive normal pressure hydrocephalus or acute hydrocephalus. From the same variables tested on shunted patients we demonstrate a standardised approach to help differentiate a properly-functioning shunt from underdrainage or overdrainage. CONCLUSIONS: Quantitative variables derived from CSF dynamics allow differentiation between clinically overlapping entities such as shunt-responsive normal pressure hydrocephalus and brain atrophy (not shunt responsive) as well as allowing the detection of shunt malfunction (partial or complete blockage) or overdrainage. This observational study is intended to serve as an update for our understanding of quantitative testing of CSF dynamics.

Prenatal evaluation of the position of the fetal conus medullaris.

OBJECTIVES: To determine the position of the fetal conus medullaris during pregnancy in relation to the last vertebral body and to examine its use in detecting skin-covered spinal dysraphism. METHODS: This was a retrospective study involving 300 consecutive ultrasound examinations between 15 weeks of gestation and term. Two operators independently assessed images of the spine to determine whether the conus medullaris and the last vertebral body could be visualized in a single image in a midsagittal plane. The distance between these two landmarks (the conus distance) was measured twice by both operators who were not aware of any previous measurements. Intra- and interobserver variability was assessed by 95% limits of agreement. Linear regression analysis was used to determine the relevant contributors to the conus distance and a normal range was computed based on the best-fit model. The normal results were compared with five cases of prenatally detected skin-covered spinal dysraphism. RESULTS: In 84.7% of the 300 cases, both operators were able to visualize the conus medullaris and the last vertebral body. Ninety-five percent limits of agreement for the intraobserver variability in measurement of conus distance were ± 1.9 mm. For the interobserver variability, they were - 3.7 and 2.5 mm. We found a linear relationship between conus distance and gestational age, biparietal diameter and abdominal circumference. The strongest relationship was observed for femur length (conus distance = - 8.2 + femur length (mm)). In the five abnormal cases, conus distance was well below the 5(th) percentile. CONCLUSIONS: Determination of conus distance allows for an objective and feasible assessment of the conus medullaris position. This parameter promises to be useful in the prenatal detection of skin-covered spinal dysraphism.

Paradigm-shift: radiological changes in the asymptomatic iNPH-patient to be: an observational study.

BACKGROUND: Many radiological signs are known for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH). However, there is little information about these signs in the pre-symptomatic phase. For pathophysiological investigative purposes we conducted a descriptive image analysis study on pre-symptomatic patients. METHODS: Patients that had contact with either the neurological or neurosurgical department of the university hospital Tuebingen from 2010 through 2016 with magnetic resonance images > 3 years before onset of symptoms, were included. The date of onset and severity of symptoms, date of first imaging and birth date were recorded. Evan's index (EI), width of the third ventricle (3VW), tight high convexity (THC), Sylvian fissure, extent of white matter hyperintensities and aqueductal flow were assessed in images before and around symptom onset. RESULTS: Ten patients were included. In all ten patients the first symptom was gait disturbance. Nine of ten pre-symptomatic images showed classic signs for iNPH. EI showed a significant increase between the pre-symptomatic and symptomatic phase. 3VW showed a trend for increase without significance. THC changed back and forth over time within some patients. CONCLUSIONS: In accordance with the scarce literature available, radiological changes are present at least 3 years before onset of iNPH-symptoms. EI seems to be a robust measure for pre-symptomatic radiological changes. Extrapolating the data, the development of iNPH typical changes might be an insidious process and the development of THC might be a variable and non-linear process. Further studies with larger sample sizes are necessary to put these findings into the pathophysiological perspective for the development of iNPH.

Pulsatile flow in ventricular catheters for hydrocephalus.

The obstruction of ventricular catheters (VCs) is a major problem in the standard treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF) being one important factor thereof. As a first approach to this problem, some of the authors studied previously the CSF flow through VCs under time-independent boundary conditions by means of computational fluid dynamics in three-dimensional models. This allowed us to derive a few basic principles which led to designs with improved flow patterns regarding the obstruction problem. However, the flow of the CSF has actually a pulsatile nature because of the heart beating and blood flow. To address this fact, here we extend our previous computational study to models with oscillatory boundary conditions. The new results will be compared with the results for constant flows and discussed. It turns out that the corrections due to the pulsatility of the CSF are quantitatively small, which reinforces our previous findings and conclusions.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Parental perception of treatment and medical care in children with craniosynostosis.

Surgery for craniosynostosis implies a relevant strain on the child and the parents. The development of the child's self-perception and self-confidence is mainly influenced by parental attitudes. The outcomes of 46 patients were analysed, taking into consideration parental perceptions. Parents were asked to indicate their satisfaction with the medical care and treatment provided using a questionnaire. Aesthetics were evaluated by the parents and doctors using a score (1=perfect, 5=deficient). Major surgical complications (2.2%) were reported only in the case of complex synostosis. Reoperation was necessary in 2.9% of isolated cases and 45.5% of complex cases. In general, parents were satisfied with the medical (1.3) and nursing (1.6) inpatient care. Aesthetic assessments differed between parents and surgeons, although not significantly (P=0.27). The surgeons perceived the results to be better than the parents, especially for complex synostosis (1.3 vs. 2.7). Alopecia and persistent asymmetry led to a worse perception of aesthetics. Persistent bone defects did not influence parental satisfaction. All participating parents would opt for surgery again. Surgery led to satisfactory results with a low risk of severe complications. Nevertheless, the outcomes and limits of the surgical procedure must be communicated effectively to parents, especially in complex cases, to avoid a mismatch in expectations. It would be desirable to implement structured interviews with parents during regular treatment management.

Brain injury and proteomics/peptidomics: is it relevant? an overview.

Proteomics and peptidomics are different and supplemental to genomics, since in contrast to the basically constant genome - the proteome and peptidome are dynamic, constantly changing, and complex networks. Proteomics is traditionally linked to 2D-gel electrophoresis techniques. Concerning peptidomics, three different approaches are currently available, all using mass spectrometry as a key element. The use of proteomics or peptidomics in traumatic brain injury (TBI) research is demanding. From the technical point of view there are high-level requirements concerning the preanalytical phase, specific machinery, sophisticated software and skilled manpower/intellectual input. There are currently no bedside techniques and most methods are suitable for experimental TBI research in specialized laboratories. In screening experiments of CSF following controlled cortical impact in rats we identified several peptides, which, although previously known, were so far not reported in the TBI context or in CSF. Peptidomics and proteomics, as highly complex screening technologies, thus seem to carry a large potential to lead TBI science. Newly "discovered" peptide targets have to be validated with different methodology to establish a real diagnostic or therapeutic value.

Brain tissue biomechanics in cortical contusion injury: a finite element analysis.

The controlled cortical impact model has been used extensively to study focal traumatic brain injury. Although the impact variables can be well defined, little is known about the biomechanical trauma as delivered to different brain regions. This knowledge however could be valuable for interpretation of experiment (immunohistochemistry etc.), especially regarding the comparison of the regional biomechanical severity level to the regional magnitude of the trauma sequel under investigation. We used finite element (FE) analysis, based on high resolution T2-weighted MRI images of rat brain, to simulate displacement, mean stress, and shear stress of brain during impact. Young's Modulus E, to describe tissue elasticity, was assigned to each FE in three scenarios: in a constant fashion (E = 50 kPa), or according to the MRI intensity in a linear (E = [10, 100] kPa) and inverse-linear fashion (E = [100, 10] kPa). Simulated tissue displacement did not vary between the 3 scenarios, however mean stress and shear stress were largely different. The linear scenario showed the most likely distribution of stresses. In summary, FE analysis seems to be a suitable tool for biomechanical simulation, however, to be closest to reality tissue elasticity needs to be determined with a more specific approach, e.g. by means of MRI elastography.

Direct magnification technique for cerebral angiography in the rat.

RATIONALE AND OBJECTIVES: The authors evaluated the performance of direct magnification radiography (DIMA) with digital image processing for cerebral angiography in the rat. METHODS: A microfocal x-ray unit with a focal spot of 5 microns was used for cerebral angiography in 10 rats. The animals were examined form x 4 up to x 20 magnification after injection of 0.2 mL x-ray contrast medium into the common carotid artery. RESULTS: Direct magnification radiography technology provides high resolution images and enables the visualization of very small vessels with high quality. It allows the peripheral branches of the middle cerebral artery or the ophthalmic artery to be visualized. Superimposition and noise effects can be excluded with digital subtraction and image processing. CONCLUSIONS: The experiments show that DIMA radiography is a suitable technique for cerebral angiography in the rat.

Local brain surface temperature compared to temperatures measured at standard extracranial monitoring sites during posterior fossa surgery.

Mild hypothermia is assumed to protect against secondary brain injury. However, the accuracy of brain temperature estimation remains debatable if direct measurement in the target area is to be avoided or is impossible. Furthermore, intracerebral temperature gradients exist, especially under intraoperative conditions. We aimed to establish how brain surface temperatures (TBrain) relate to temperatures taken at standard sites in posterior fossa surgery. Ten patients undergoing cerebellopontine angle tumor removal were monitored for TBrain, esophageal temperature (TEso), bladder temperature (TBlad), ipsi- and contralateral tympanic membrane (TTymp-I, TTymp-C), and scalp temperatures (TScalp). During monitoring, TEso increased from 35.3+/-0.2 degrees C to 36.0+/-0.3 degrees C. After dura opening, TBrain was -0.14+/-0.1 degrees C below TEso. At the end of tumor removal, this difference increased to -0.43+/-0.31 degrees C (P < 0.05). TTymp-C was -0.29+/-0.18 degrees C below TBrain at dura opening. TTymp-C reflected the behavior of TEso adequately (r = 0.938), however, with a mean difference of -0.39+/-0.04 degrees C. In contrast, TTymp-I readings closely followed temperature changes in the area of surgery. TBlad reflected TEso except in periods of rapid temperature changes. In posterior fossa (PF) surgery, local TBrain is most accurately reflected by TEso. For clinical use TBlad and TTymp-C are also sufficient to assess brain surface temperature in the PF. Intraoperative surface cooling of the brainstem is less than the previously described cooling rate of exposed cerebral cortex.

Arachnoid cysts of the posterior fossa.

BACKGROUND: The surgical indications and management of posterior fossa arachnoid cysts (AC) are still controversial. Different surgical techniques and management have already been suggested for arachnoid cysts of the posterior fossa. AC involving the posterior fossa and especially the cerebellopontine angle may carry a high surgical morbidity because of the involvement of important neurovascular structures (e.g., brain stem and cranial nerves). Only long-term follow-up will determine the best surgical technique for such lesions. METHODS: Between 1990 and 1996 a total of 12 patients underwent surgery for arachnoid cysts involving the posterior fossa. In seven cases AC were located within the cerebellopontine angle (CPA), in three cases in the CPA with major extension dorsal to the brainstem, and in two cases at the CPA extending into the internal auditory canal. RESULTS: A suboccipital retrosigmoid approach was performed in all patients. Radical resection of the cyst could be accomplished in all but one case. There was no mortality. Major postoperative morbidity was present in one case because of an intraoperative air embolism in the semisitting position and strong adherence of the cyst wall to the surrounding neurovascular structures. Long-term follow-up (mean, 3.3 years) revealed improvement of most preoperative symptoms. CONCLUSION: Open surgery and radical removal of the AC located at the posterior fossa, based on our retrospective analysis, provide very good long-term postoperative results. The suboccipital approach provides a good and safe exposure of vascular structures and cranial nerves in the CPA and allows radical resection of the cyst, reducing the chance of recurrence.

1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled cortical impact injury: pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in experimental traumatic brain injury for characterisation of posttraumatic metabolic dysfunction. Following human brain injury pathological findings correlated with outcome measures. Combined with conventional T2-weighted MR imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue following trauma. Studies have been restricted so far to diffuse axonal injury models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI combined with 1H-MRS was applied in a pilot study to the controlled cortical impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley rats were investigated, of which two served as controls. Four animals were injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI indicated a transient brain oedema development and metabolic changes induced by the craniotomy itself. Following CCII MRI demonstrated that the area of contusion as well as the surrounding brain oedema increased twofold in size within 24 h (p < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and glutamate ipsilateral to the contusion and a drop of NAA on the contralateral side. MRS/MRI investigations in the CCII model demonstrated a potential to further elucidate the pathophysiology following traumatic brain contusion.

Influences of secondary injury following traumatic brain injury in developing versus adult rats.

Hypoxia and hypotension are both common findings following traumatic brain injury occurring with a frequency of up to 46% according to data of the Traumatic Coma Data Bank. In the present study the influence of secondary injury on intracranial pressure and the cardiovascular response is investigated in developing rats. Differences from adult rats are determined. Diffuse brain injury was produced in intubated and ventilated 17-20 days old Sprague-Dawley rats (N = 16) using a modification of the Marmarou-model. Hypoxia was induced by reducing O2-concentration to 8% lasting for 15/30 min. Mean arterial blood pressure recordings and intracranial pressure recordings were performed continuously. Animals were divided into two groups, sustaining hypoxia alone (N = 9) and trauma/hypoxia (N = 7). The results were compared to readings in adult animals subjected to hypoxia (N = 5) and trauma/hypoxia (N = 5) (450 gm/150 cm). Immediately following the onset of hypoxia in the developing rat, MABP decreased from 76.5 +/- 13 mm Hg to 35.8 +/- 7 mm Hg. In the adult rat the decrease was more marked (from 93.3 +/- 8 mm Hg to 33.5 +/- 5.7 mm Hg) (p < 0.05). Mortality rate in developing rats with trauma/hypoxia was 43% with no significant change of ICP (from 13 +/- 5.2 to 22.3 +/- 11). All adult animals recovered following trauma/hypoxia with no relevant ICP-increase within one hour post-trauma. Hypoxia induces hypotension in adult and developing rats. However, developing rats appear to be more vulnerable to hypoxia associated with trauma.

ICP and MABP following traumatic subarachnoid hemorrhage in the rat.

Traumatic subarachnoidal hemorrhage (t-SAH) is a common finding in head-injured patients occurring with a frequency of 39% according to data of the Traumatic Coma Data Bank. The present study is the first description of a t-SAH-model with particular emphasis on patterns of intracranial pressure (ICP) changes and mean arterial blood pressure (MABP) response. Diffuse brain injury was produced in intubated and ventilated adult Sprague-Dawley rats (N = 24) using a brass weight (500 gm) free falling from a predetermined height (1.5 m) on a steel disc glued to the skull of the rat. Before induction of the injury, heparin was administered intra-arterially (i.a.) and antagonised after injury by protamine. MABP-recordings and ICP-recordings were performed continuously. Histopathology was undertaken. Following injury MABP decreased from 138 +/- 14 mmHg to 89 +/- 22 mmHg. During 5 to 15 min ICP increased up to 89.4 +/- 50.4 mmHg, decreasing slowly within 60 min in surviving animals. The mortality rate was 41.6%. All brains showed a severe subarachnoid hemorrhage in the basal cisterns and cell-loss within the brainstem. Experimental t-SAH is possible. Following t-SAH there is a subacute increase of ICP due to the actual bleeding. The model may provide deeper understanding in the basic physiological patterns of t-SAH.

Brain-stem auditory evoked potential monitoring in experimental diffuse brain injury.

The time course of brain-stem auditory evoked potential (BAEP) changes was investigated using an impact-acceleration trauma model in 23 spontaneously breathing rats. Intracranial pressure (ICP), arterial blood pressure and respiratory rate were monitored. The experiments were terminated at four hours after trauma. No significant changes in intracranial pressure (ICP) occurred following the impact. After a short increase, blood pressure returned to baseline values within 5 min. Transient apnea was not followed by prolonged respiratory depression. Diffuse closed head injury (CHI) did not result in general, unidirectional changes of peak latencies or amplitudes of auditory evoked responses. Most BAEP changes developed slowly reaching a maximum at 1 to 4 hours after the injury. In the absence of ICP changes, this pattern reflects secondary ischemia in sensitive brain-stem areas rather than direct traumatic lesions or hypoxia due to respiratory depression.

Traumatic brain injury in the developing rat pup: studies of ICP, PVI and neurological response.

Diffuse brain swelling is a common complication in young victims of a seven head injury but, there is a lack of data on relevant models of injury. We produced diffuse brain injury in 21 day old Lewis rat pups (N = 33) by modifying a recently established weight-drop-model. The trauma threshold, neurological response, histological changes, intracranial pressure (ICP), and arterial blood pressure (ABP) were determined. In addition, the pressure-volume-index (PVI) was measured 15 min before, 2 min, and 1 h after brain injury. In the 1 m/100 g group 4 of 5 rats died, whereas in the 0.5 m/100 g only 4 of 28 died. The PVI increased at 2 min after traumatic brain injury (TBI) but ICP was unchanged, except for a minor increase immediately after injury. Histological studies revealed diffuse neuronal death, predominantly involving the cortex and hippocampus. The results of the present study indicate that determination of ICP in the developing rat pup during and after diffuse brain injury is possible. A 0.5 m/100 g weight-drop-trauma results in a morphologically severe injury but with low mortality. The increase in PVI can be attributed to a decrease of cerebral perfusion pressure (CPP) after injury. However, the absence of a further increase of ICP after injury in the developing rat indicates that this may not be a primary consequence of injury in paediatric patients.