[Oral anticoagulant-associated intracerebral haemorrhage]. / Intrazerebrale Blutungen unter oraler Antikoagulation.

Intracerebral haemorrhage during treatment with oral anticoagulants is associated with high rates of morbidity and mortality. Impaired haemostasis can lead to progressive haematomas and, therefore, it should be identified early in order to initiate measures to reverse anticoagulation. Substitution of coagulation factors is essential in the treatment of these patients, but other intensive care measures such as blood pressure control are mandatory as well.

[Traumatic brain injury in anticoagulated patients : Hemostatic therapy for the treatment of intracranial hemorrhage]. / Schädel-Hirn-Trauma unter antithrombotischer Medikation : Hämostaseologische Therapie bei intrakraniellen Blutungen.

Impaired hemostasis represents a major risk factor for increased morbidity and mortality in patients with traumatic intracranial hemorrhage. In cases of polytrauma with major bleeding, hyperfibrinolysis may develop and this may result in excessive coagulopathy. Patients receiving antithrombotic medication and suffering from intracranial hemorrhage are at particular risk for the development of neurological sequelae due to the increased tendency to bleeding. This article outlines the principles of hemostatic therapy of traumatic intracranial hemorrhage during antithrombotic treatment. The basic principles of the pathophysiology and effects of coagulation impairment in this patient population are reviewed. Furthermore, the use of specific coagulation tests and the administration of hemostatic substances are discussed.

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI.

The role of spreading depolarization in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating disease associated with death and poor functional outcome. Despite decades of intense research and improvements in clinical management, delayed cerebral ischaemia (DCI) remains the most important cause of morbidity and mortality after SAH. The key role of angiographic cerebral vasospasm, thought to be the main cause of DCI, has been questioned. Emerging evidence suggests that DCI is likely to have a multifactorial etiology. Over the last few years, spreading depolarization (SD) has been identified as a potential pathophysiological mechanism contributing to DCI. The presence of cortical spreading ischaemia, due to an inverse hemodynamic response to SD, offers a possible explanation for DCI and requires more intensive research. Understanding the role of SD as another mechanism inducing DCI and its relationship with other pathological factors could instigate the development of new approaches to the diagnosis and treatment of DCI in order to improve the clinical outcome.

[Severe traumatic brain injury]. / Schweres Schädel-Hirn-Trauma.

Traumatic brain injury is a leading cause of morbidity and mortality, especially under 45 years of age. The primary brain injury occurs at the moment of trauma and is defined by the direct damage to tissue. In contrast, secondary brain injury develops over time and is accessible to therapeutic interventions. Patients with severe traumatic brain injury have to be transferred to a specialized trauma centre in order to perform appropriate diagnostic and therapeutic procedures. These include surgical management of lesions (e.g. haematoma evacuation) as well as specific neurointensive care. Neurointensive care medicine principles such as treatment of increased intracranial pressure and advanced invasive neuromonitoring of brain tissue have to be followed.

Diagnostic markers for glioblastoma.

Glioblastoma (GBM) is the most malignant form of cerebral gliomas, and despite distinct progress in surgical resection, radiation and chemotherapy, the prognosis of patients with GBM is still very poor. In the past decades knowledge of genomics and proteomics and of diagnostic, prognostic, predictive and pharmakodynamic markers measured in cerebrospinal-fluid (CSF), serum, or tumor tissue biomarkers has improved. This review briefly compiles our concepts on diagnostic markers for GBM, focusing on the latest developments.

Effects of lisuride hydrogen maleate on pericontusional tissue metabolism, brain edema formation, and contusion volume development after experimental traumatic brain injury in rats.

After traumatic brain injury (TBI), the primary insult is followed by a cascade of secondary events which lead to enlargement of the primary lesion and are potentially amenable to therapeutic intervention. Lisuride is a dopaminergic agonist with additional serotoninergic, adrenergic, and glutamate antagonistic properties. In lack of previous data on lisuride in TBI, and based on well documented changes of dopamine metabolism after TBI, we speculated that lisuride could provide neuroprotection in the acute and post-acute stage of controlled cortical impact (CCI) injury in rats. The effect of varying dosages of lisuride on physiological parameter was investigated. Cerebral microdialysis (CMD) was employed to provide a temporal profile of lactate, pyruvate, glucose and glutamate in the pericontusional brain tissue. Additionally, brain edema formation and the development of contusion volume were assessed. In this study, no effect of treatment was seen on physiological parameters or microdialysis profiling of tissue metabolites. Whereas posttraumatic increase in brain water content and an increase in contusion volume could be observed, there was no significant effect of treatment. Taken together, our results suggest that lisuride does not provide neuroprotection in the CCI model at the acute and subacute stages. Based on the available literature, however, it might be possible that dopamine agonists such as lisuride, respectively, improve outcome in terms of cognitive function in a chronic setting.

Cerebral microdialysis in acutely brain-injured patients with spreading depolarizations.

Multimodal cerebral monitoring was utilized to examine the relationship between pathological changes in microdialysis parameters and the occurrence of spreading depolarizations (SD) in brain-injured patients. SD are a relatively newly discovered phenomenon in man found to be linked to secondary insults and infarct growth and they can be detected via electrocorticography (ECoG). A total of 24 brain-injured patients (mean age: 52±11 years) requiring craniotomy took part in this prospective observational study. Each patient was monitored with a linear strip electrode for ECoG data and a cerebral microdialysis probe. SD were detected in 13 of the 24 patients. Pathological concentrations of glucose and lactate in brain parenchyma were significantly correlated with various time points prior to and/or immediately following the SD. Severe systemic hyperglycemia and systemic hypoglycemia were also found to be correlated with the occurrence of SD. The present study shows a clear relationship between SD and pathological changes in cerebral metabolism; further studies are needed to elucidate these complex interactions with the ultimate goal of developing therapeutic strategies for improving outcome in brain-injured patients.

Hemangiopericytomas grade II are not benign tumors.

BACKGROUND: Hemangiopericytomas (HPs) of the central nervous system are rare tumors and afflicted with a high propensity of recurrences and metastases. Histopathologically, HPs correspond to differentiated (WHO grade II) and anaplastic (WHO grade III) tumors. With respect to the available literature and our own experiences, the aggressiveness, especially of differentiated grade II HPs, seems to be underestimated. METHODS: Thus, in this retrospective study, we describe tumor behavior and examined the effect of radio- and chemotherapy on tumor control with respect to the WHO classification of grade II and III neoplasms. This study consists of 15 patients with cerebral (n = 10) and spinal (n = 5) HPs. RESULTS: Seven HPs were histopathologically classified as grade II and eight as anaplastic grade III tumors. Complete surgical resection could be achieved in 60% of cerebral and in 25% of spinal HPs. In total, local recurrences occurred in 20% of patients within 17.3 months after the primary operation. Recurrences occurred both from differentiated (n = 1) and anaplastic (n = 2) neoplasms. Treatment comprised re-operation followed by radio- and chemotherapy. Pointing out the importance of the extent of surgical resection, in this study, we could not detect a single patient showing any recurrences or systemic metastases after complete surgical resection of grade II HPs. During primary diagnostics, four patients showed systemic metastases. Although these tumors could be controlled via surgery, systemic metastases appeared in further four patients within 60.4 months. Interestingly, two of them were classified as differentiated tumors (WHO grade II). To control tumor progress, radiotherapy seemed to be partially effective. On the other hand, however, chemotherapy did not show any effect on tumor control. With respect to these results, screening investigations seem to be indispensable and are highly recommended during primary diagnostics and after the appearance of recurrences or metastases, independent of the histopathological staging of the tumor. CONCLUSION: With respect to our results, radical surgical resection offers the best treatment option to control tumor progress. In case of subtotal resection or histopathologically diagnosed anaplasia (WHO III), radiotherapy seems to be indicated; however, chemotherapy did not show effectiveness to control tumor progress.

Stereotactic brainstem biopsy in a patient with coagulopathy of unclear etiology: case report.

BACKGROUND: Parenchymal hemorrhage is one of the most feared risks of stereotactic brain biopsies potentially resulting in neurological deficits or even a fatal outcome. Patients with disorders of the coagulation system are at particular risk, so identifying these is one of the main tasks prior to surgery. Some patients may have a bleeding tendency despite normal laboratory values of the hemostatic system. CASE REPORT: We report the case of a patient with coagulopathy of unclear etiology undergoing a stereotactic brainstem biopsy. CONCLUSION: A medication scheme with tranexamic acid and desmopressin effectively decreased the patient's bleeding time in vivo and the procedure was carried out without complications.

[Intracranial pressure-volume relationship. Physiology and pathophysiology]. / Intrakranielle Druck-Volumen-Beziehung. Physiologie und Pathophysiologie.

Posttraumatic increase of intracranial pressure (ICP) is a strong prognostic factor for the outcome of patients after traumatic brain injury. After exhausting all compensatory mechanisms ICP increases exponentially, where ICP(norm)=(CSF production*CSF flow resistance)+venous pressure((sinus sagittalis))=10-15 mmHg. The ICP curve is influenced by the compliance (DeltaV/DeltaP) and elasticity (DeltaP/DeltaV) of the brain. Marmarou could demonstrate that the non-linear cranio-spinal pressure-volume relationship describes a logarithmic, mono-exponential, strongly linear relationship between pressure and volume and named this the pressure volume index (PVI=log ICP/DeltaV). The pressure volume index describes the volume necessary to increase ICP by a factor of 10. Additionally to PVI the measurement of volume-pressure response (VPR) was introduced. The continuous intracranial compliance could be determined on the principle of pulsatile volume increases as an equivalent of very small intra-cranial volume increases. However, to ascertain functional status of the injured brain a combination of measurements of different parameters, such as tissue oxygen partial pressure (p(ti)O2), cerebral blood flow (CBF), microdialysis and electrocorticography (ECoG) is recommended.

Transorbital penetrating head injury by a toilet brush handle.

BACKGROUND: Transorbital penetrating brain injuries are rare lesions without defined therapy standards. CLINICAL PRESENTATION AND INTERVENTION: A male patient presented at our institution with a toilet brush handle in the right cerebral hemisphere. CT imaging identified the object entering the right orbit and having crossed the right hemisphere in the ventricular plane. After performing a medium-sized craniotomy, the object was removed step-by-step under monitoring with an intraoperative CT scan to ensure no involving major hemorrhage. CONCLUSION: Transorbital penetrating brain injuries are treated best by utilizing all up-to-date technical developments such as intraoperative CT-scanning to increase the safety in the management of such exceptional lesions with increased risk of immediate life-threatening intracranial bleeding.

[Classification and therapy of craniocerebral injury (CCI)]. / Einteilung und therapie des schädel-hirn-traumas (SHT).

In spite of great success in research severe traumatic brain injury (TBI) remains the most frequent cause for morbidity and mortality in the age < 45 years. The primary lesion emerges at the moment of trauma. Due to several pathophysiological mechanisms secondary lesions occur that enlarge size of contusions significantly. As a consequence of intracranial bleedings and brain edema intracranial pressure (ICP) increases and threaten the patient. Extent of severity (declared in Glasgow Coma Scale Score [GCS]), expansion and type of bleedings (acute and chronic subdural hemorrhage, epidural bleeding, contusion bleedings and intracerebral hemorrhage) determinate operative and conservative therapy as well as intensive care medicine. A specific feature represents frontobasal lesions that, apart of penetrating injuries, are treated interdisciplinary not before ICP is stable, brain edema declining and coagulation sufficient several days after trauma. A persisting rhinoliquorrhoe cause meningitis up to 85 % within 10 years. Patient with GCS < 8 have to be intubated and controlled ventilated. Basic monitoring does not differ from those of other patients treated at the intensive care ward (sufficient breathing [pO (2), pCO (2)], arterial blood pressure, CBC and coagulation parameters, fluid monitoring and nutrition). Additionally, ICP have to be measured and be treated corresponding to the algorithm of ICP treatment. Complementary, oxygen saturation of brain tissue (ptiO (2)), local cerebral blood flow (r-CBF) and cerebral metabolism (micro dialysis) can be measured. Just the combination of the single monitoring parameters gives evidence of the functional condition of the injured brain and relieved planning and performing of the appropriate therapy.

Granulocyte colony-stimulating factor does not affect contusion size, brain edema or cerebrospinal fluid glutamate concentrations in rats following controlled cortical impact.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is an established treatment in the neutropenic host. Usage in head-injured patients at risk for infection may aggravate brain damage. In contrast, evidence of G-CSF neuroprotective effects has been reported in rodent models of focal cerebral ischemia. We investigated effects of G-CSF in acute focal traumatic brain injury (TBI) in rats. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with 1.2%) to 2.0% isoflurane and subjected to controlled cortical impact injury (CCII). Thirty minutes following CCII, either vehicle or G-CSF was administered intravenously. Animals were sacrificed 24 hours following CCII. Glutamate concentrations were determined in cisternal cerebrospinal fluid (CSF). Brain edema was assessed gravimetrically. Contusion size was estimated by 2,3,5-triphenyltetrazolium chloride staining and volumetric analysis. RESULTS: Dose-dependent leukocytosis was induced by infusion of G-CSF. Physiological variables were unaffected. Water content of the traumatized hemisphere and CSF glutamate concentrations were unchanged by treatment. Contusion volume was similar in all groups. CONCLUSIONS: A single injection of G-CSF did not influence cortical contusion volume, brain edema, or glutamate concentrations in CSF determined 24 hours following CCII in rats. G-CSF, administered 30 minutes following experimental TBI, failed to exert neuroprotective effects.

The use of neuronavigation in transnasal transsphenoidal pituitary surgery.

BACKGROUND: Recurrent pituitary adenomas and localisation of microadenomas potentially cause difficulties during transsphenoidal pituitary surgery. Neuronavigation might improve tumour removal in such cases. METHODS: Between 12/98 and 04/01 transnasal transsphenoidal adenomectomies were performed in 152 patients at our department. In 16 of these patients neuronavigation was chosen as a means of safely approaching the tumour and improving the efficacy of tumour localisation and removal. Mean age of the 7 female and 9 male patients was 51.8 +/- 13.7 years. Patients were subdivided according to the underlying pathology, i. e. microadenomas (n = 8, mean diameter: 5.75 +/- 2.1 mm), and recurrent adenomas (n = 8). The imaging of adenomas was achieved in preoperatively obtained 1 mm transversely reconstructed magnetic resonance sections from a dynamic enhanced 3D-FFE sequence (Gyroscan 1.5 Tesla, Philips). Contour-guided surgery via a transnasal transsphenoidal approach to the sella region was performed using the MKM navigation microscope (Zeiss). RESULTS: Endocrinologic studies revealed secretion of growth hormone (GH), ACTH, and follicle stimulating hormone (FSH) in 5, 4, and 1 patient, respectively. The remaining 7 adenomas did not secrete any hormones. All pituitary tumours were accurately localised by neuronavigation. In all recurrent macroadenomas, the tumours were rapidly and safely approached through the scarred tissue and the tumour volume was significantly reduced. Neither intraoperative nor postoperative complications occurred in these patients. In hormone-secreting pituitary tumours with far lateral localisation, endocrinologic abnormalities were corrected in 5 patients, while hormone secretion was significantly decreased in 3 patients. In 1 patient with histologically verified adenoma, hormone secretion did not significantly change following surgical removal. CONCLUSIONS: Neuronavigation in pituitary surgery is of use in only a small number of cases. Nevertheless, we suggest that contour-guided, transsphenoidal adenomectomy may prove helpful in approaching recurrent adenomas and localising lateral microadenomas.

Cerebral metabolism and intracranial hypertension in high grade aneurysmal subarachnoid haemorrhage patients.

We evaluated the effect of intracranial hypertension on cerebral metabolism in patients with high grade aneurysmal subarachnoid hemorrhage (SAH) using bedside cerebral microdialysis (MD). Thirty-six patients with SAH were studied and classified into two groups (intracranial pressure, ICP > 20 mmHg, n = 25) and (ICP < 20 mmHg, n = 11). ICP was monitored hourly using an intraventricular drainage (n = 36). The MD catheter was placed after aneurysm clipping into the vascular territory of interest and was perfused with Ringer's solution (0.3 microl/min). The MD samples were collected hourly for measurements of glucose, lactate, and glutamate (CMA 600, Sweden). Lactate/pyruvate ratio was also calculated. To calculate group specific differences, the 24 hours median values of the first 7 days after SAH were compared. Differences were considered statistically significant at P < 0.05. Patient groups were comparable for age, severity of SAH, Fisher's grade and duration of MD sampling. In patients with ICP > 20 mmHg from day 1 to 7 after SAH, extracellular concentrations of glucose were significantly lower, while the lactate/ pyruvate ratio was higher compared to SAH patients with normal ICP values. The differences between groups in glutamate levels was only significant on day 1 after SAH due to high inter-individual differences. We concluded that intracranial hypertension in associated with an anaerobic cerebral metabolism indicated cerebral ischemia in high grade SAH patients.

Assessment of the relationship between age and continuous intracranial compliance.

The aim of this open, descriptive and prospective study was to determine if the new monitoring parameter "continuous intracranial compliance (cICC)" decreases with age in patients with traumatic brain injury (TBI). 30 patients with severe and moderate TBI (Glasgow Coma Scale score < or = 10) contributing to a European multicenter study, organized by the Brain-IT group, underwent computerized monitoring of blood pressure, intracranial pressure (ICP), cerebral perfusion pressure and cICC. Regression analyses of individual median ICP and median cICC versus patients' age revealed no significant dependency. Median cICC declined significantly with increasing ICP (when median ICP = 10, 20 and 30 mmHg, cICC = 0.64, 0.56 and 0.42 ml/mmHg respectively, p < 0.05). These three ICP groups were then subdivided according to age (0-20, 21-40, 41-60 and 61-80 years). Median cICC declined with age in both high ICP groups (median ICP = 20,30 mmHg). Percentage cICC values below a set pathological threshold of lower than 0.05 ml/mmHg across the four age groups were 28% (0-20 yrs), 59% (21-40 yrs), 60% (41-60 yrs) and 70% (61-80 yrs) respectively. The observed phenomenon of decreased intracranial volume challenge compensation with advancing age may contribute to the well-known fact of a worse outcome in elderly patients after TBI.

The antioxidant effect of N-acethylcysteine on experimental contusion in rats.

N-acethylcysteine (NAC) is known to have direct and indirect antioxidant abilities. We investigated the potential protective effect of NAC on ICP, brain edema and contusion volume after Controlled Cortical Impact (CCI) injury. A moderate CCI injury was induced on the left hemisphere in 48 Sprague Dawley rats. The animals were treated with intraperitoneal injection of NAC (163 mg/kg/KG) or physiological saline. Measurements of intracranial pressure (ICP) were performed and brains were removed at 24 hours. Gravimetric analysis of post-traumatic edema and morphometric measurements (TTC staining) of contusion volume were carried out in 24 animals, respectively. ICP measurements increased significantly over time with no significant differences between both groups. The relative difference in water content in NAC treated animals (1.45 +/- 0.1%) did not differ significantly versus placebo (1.47 +/- 0.2%). The contusion volume was diminished by 19% in the NAC group (53.52 +/- 5.3 mm3) versus placebo (66.28 +/- 4.7 mm3) without showing statistical significance. The antioxidant properties of NAC did not affect intracranial pressure or posttraumatic brain edema formation, although the moderate reduction of contusion volume might reveal beneficial effects on focal contusion.

Acute haemorrhage into a microcystic meningioma leading to cerebral herniation.

Low-grade (WHO level I) meningiomas are slow-growing, benign tumours typically presenting with unspecific symptoms (e.g. headache), seizures, cranial nerve compression and neuropsychological symptoms determined by location and size of the lesion. Haemorrhagic onset and sequelae are rare, and have been described infrequently. This is a case of a 50-year-old male presenting with signs of tentorial herniation secondary to hyperacute intratumoural haemorrhage (ITH) into a previously undiagnosed meningioma. Emergency surgical decompression and exstirpation of the lesion helped to achieve a favourable outcome. ITH has been described in all including benign intracranial neoplasms. Factors associated with a higher risk for haemorrhage in meningiomas are discussed. Though haemorrhages associated with meningiomas have been reported, ITH into low-grade meningiomas leading to herniation remains a rarity. Bearers of known lesions and their treating physicians who opt for conservative or delayed treatment should be aware of this remote complication.

Edema and brain trauma.

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury (TBI) as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" due to blood-brain barrier (BBB) disruption resulting in extracellular water accumulation and "cytotoxic/cellular" due to sustained intracellular water collection. A third type, "osmotic" brain edema is caused by osmotic imbalances between blood and tissue. Rarely after TBI do we encounter a "hydrocephalic edema/interstitial" brain edema related to an obstruction of cerebrospinal fluid outflow. Following TBI, various mediators are released which enhance vasogenic and/or cytotoxic brain edema. These include glutamate, lactate, H(+), K(+), Ca(2+), nitric oxide, arachidonic acid and its metabolites, free oxygen radicals, histamine, and kinins. Thus, avoiding cerebral anaerobic metabolism and acidosis is beneficial to control lactate and H(+), but no compound inhibiting mediators/mediator channels showed beneficial results in conducted clinical trials, despite successful experimental studies. Hence, anti-edematous therapy in TBI patients is still symptomatic and rather non-specific (e.g. mannitol infusion, controlled hyperventilation). For many years, vasogenic brain edema was accepted as the prevalent edema type following TBI. The development of mechanical TBI models ("weight drop," "fluid percussion injury," and "controlled cortical impact injury") and the use of magnetic resonance imaging, however, revealed that "cytotoxic" edema is of decisive pathophysiological importance following TBI as it develops early and persists while BBB integrity is gradually restored. These findings suggest that cytotoxic and vasogenic brain edema are two entities which can be targeted simultaneously or according to their temporal prevalence.