Andrea Kleindienst

To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension (P < 0.00001), 2) increasing age (P = 0.00005), 3) surgical treatment (P = 0.00010), 4) localization in basal ganglia (P = 0.0108) and 5) hypertension as only etiology (P = 0.01471). A lower case fatality was found in patients with cerebrovascular malformations (P = 0.00006) and when the hemorrhage was localized to the cerebral lobes (P = 0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.

To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension (P&lt;0.00001), 2) increasing age (P=0.00005), 3) surgical treatment (P=0.00010), 4) localization in basal ganglia (P=0.0108) and 5) hypertension as only etiology (P=0.01471). A lower case fatality was found in patients with cerebrovascular malformations (P=0.00006) and when the hemorrhage was localized to the cerebral lobes (P=0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.

Early diagnosis of acromegaly prevents irreversible comorbidities and facilitates surgical cure. Carpal tunnel syndrome (CTS) is common in acromegaly and patients have often undergone surgery for CTS prior to the diagnosis of acromegaly. We hypothesized that screening CTS-patients for acromegaly could facilitate active case-finding. We prospectively enrolled 196 patients [135 women, 56.9 (range 23-103) years] who presented with CTS for surgery. Patients were asked about 6 symptoms suggestive of acromegaly using a questionnaire calculating a symptom score (0-6 points), and insulin-like-growth factor 1 (IGF-1) was measured. If IGF-1 was increased, IGF-1 measurement was repeated, and random growth hormone (GH) and/or an oral glucose tolerance test (OGTT) with assessment of GH-suppression were performed. The mean symptom score was 1.7±1.3 points. Three patients reported the maximal symptom score of 6 points, but none of them had an increased IGF-1. There was no correlation between the symptom score and IGF-1-SDS (standard deviation score) (r=0.026; p=0.71). Four patients had an IGF-1&gt;2 SDS. In 2 patients acromegaly was ruled out using random GH and OGTT. One patient had normal IGF-1 and random GH at follow-up. One patient refused further diagnostics. In this prospective cohort of patients with CTS, the observed frequency of acromegaly was at most 0.51% (95% CI 0.03 to 2.83%). In this prospective study, none of the 196 patients with CTS had proven acromegaly. Thus, we see no evidence to justify general screening of patients with CTS for acromegaly.

Summary Background. Despite the high risk of venous thromboembolic events (VTE) in neuro-surgical patients, heparin prophylaxis has not been routinely established due to concern about bleeding complications. After initiating early low molecular weight heparin (LMWH) prophylaxis, we reviewed our patients in order to examine the viability of this practice. Method. Over a 3 year period, the records of patients admitted

There exists no pharmacological treatment for fulminating brain edema. Since evidence indicates that brain aquaporin-4 (AQP4) water channels are modulated by vasopressin V1a receptors, we examined the edema-reducing properties of the selective V1a receptor antagonist, SR49059, following middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or SR49059 infusion at different dosages (each n = 6,480 microL/hr, 640 microL/hr, 720 microL/hr) and starting 60 minutes before or after MCAO. After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. Statistics were performed using an ANOVA followed by a Tukey post hoc analysis. SR049059 treatment reduced brain water content in the infarcted area given at 640 microL/hr (p = 0.036), 720 microL/hr 60 minutes before (p = 0.002) or 60 minutes after (p = 0.005) MCAO. The consecutive sodium shift into the brain was prevented (p = 0.001), while the potassium loss was inhibited only by pre-treatment (p = 0.003). These findings imply that in ischemia-induced brain edema, the selective V1a receptor-antagonist SR49059 inhibits brain edema and the subsequent sodium shift into brain. This substance offers a new avenue in brain edema treatment and prompts further study into AQP4 modulation.

S100 calcium-binding protein B (S100B) is a member of the S100 family, mainly expressed and secreted by astrocytes in the Central Nervous System. Extracellular levels of this protein have been used as a general marker of brain injury, particularly in blood serum and cerebrospinal fluid (CSF). Mice overexpressing S100B (S100BTg) was firstly developed to better understand the Down Syndrome and Alzheimer&#39;s Disease, once both S100B and amyloid precursor protein (APP) genes are located in chromosome 21. Also, it was previously demonstrated the exacerbation of amyloidogenesis in transgenic mice for both human APP and S100B, but the influence of this protein on APP processing had not yet been investigated in the S100BTg itself. Considering the interaction between the S100B protein and the amyloid beta processing, as well as the S100B&#39;s neuroinflammatory signalling, we investigated S100B and amyloid beta 42 peptide levels by Elisa in the hippocampus (Hp), frontal cortex (FC), hypothalamus (Ht), CSF, serum and also the possible amyloid deposition by Thioflavin-T and immunofluorescence in 1-year-old transgenic mice overexpressing S100B as Reeves&#39; procedure, in female and male S100BTg and respective wild type (Wt) mice. Our results showed a higher S100B content in the three examined brain regions of S100BTg (Hp, FC and Ht) and Hp showed higher levels of this protein than other two regions, even in Wt. Moreover, for the first time we found elevated CSF S100B in these old transgenic mice, which supports the idea that S100B released by astrocytes could affect the neural neighborhood. In addition, we found more plaque-like deposits in males S100Tg than females in comparison with Wt. Ultimately, our data reinforces the importance and potential of this model for experimental studies and the role of S100B in the pathogenesis of AD, points out specific brain changes of S100B (in brain tissue and CSF) and indicates that changes in S100B and amyloid plaques in this mice seems to be dependent on sex.

Objective: Hyponatremia is frequently encountered in patients with intracranial processes, and contributes substantially to the related morbidity and mortality. The pathophysiology of hyponatremia is not completely understood, and may in part be explained by the syndrome of inappropriate secretion of[for full text, please go to the a.m. URL]

Object. After traumatic brain injury (TBI), S100B protein is released by astrocytes. Furthermore, cerebrospinal fluid (CSF) and serum S100B levels have been correlated to outcome. Given that no data exist about the temporal profile of cerebral S100B levels following TBI and their correlation to serum levels, the authors examined whether proton magnetic resonance (MR) spectroscopy is capable of measuring S100B. Methods. Results of in vitro proton MR spectroscopy experiments (2.35-tesla magnet, 25 G/cm, point-resolved spatially localized spectroscopy) revealed an S100B-specific peak at 4.5 ppm and confirmed a positive correlation between different S100B concentrations (10 nM–1 µM) and the area under the curve (AUC) for the S100B peak (r = 0.991, p &lt; 0.001). Thereafter, proton MR spectroscopy was performed in male Sprague—Dawley rats (7 × 5 × 5—mm voxel in each hemisphere, TR 3000 msec, TE 30 msec, 256 acquisitions). Exogenously increased CSF S100B levels (∼ 200 ng/ml) through the i...

Delayed cerebral vasospasm has long been recognized as an important cause of poor outcome after an otherwise successful treatment of a ruptured intracranial aneurysm, but it remains a pathophysiological enigma despite intensive research for more than half a century.

A terapia hemodinâmica, mais conhecida como “três-H”, é usada rotineiramente no manejo dos pacientes com vasoespasmo secundário à HSA. A razão de se induzir hipertensão relativa, hipervolemia e hemodiluição nestes doentes é melhorar o fluxo sanguíneo cerebral e evitar a isquemia tardia. Atualmente, apenas o bloqueador de canal de cálcio Nimodipina tem benefício comprovado no tratamento do vasoespasmo na HSA. Várias outras alternativas estão sendo estudadas. O Tirilazad não é efetivo, e vários outros têm resultados controversos, tais como: sulfato de magnésio, estatinas, antagonistas de endotelina, esteróides, antiagregantes plaquetários, e fibrinolíticos intratecais. O objetivo deste trabalho é promover uma revisão sistemática da literatura existente acerca do tratamento do vasoespasmo cerebral.

(1) Background: Despite progress in surgery and radio-chemotherapy of glioblastoma (GB), the prognosis remains very poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Enhancing oxidative phosphorylation—known as the anti-Warburg effect—with cyclic AMP activators has been demonstrated to drive GB cells from proliferation to differentiation thereby reducing tumor growth in a cell culture approach. Here we re-evaluate this treatment in a more clinically relevant model. (2) Methods: The effect of treatment with dibutyryl cyclic AMP (dbcAMP, 1 mM) and the cAMP activator forskolin (50µM) was assessed in a GB cell line (U87GFP+, 104 cells) co-cultured with mouse organotypic brain slices providing architecture and biochemical properties of normal brain tissue. Cell viability was determined by propidium-iodide, and gross metabolic effects were excluded in the extracellular medium. Tumor growth was quantified in terms of area, volume, and invasion at the start of culture, 48 h, 7 days, and 14 days after treatment. (3) Results: The tumor area was significantly reduced following dbcAMP or forskolin treatment (F2,249 = 5.968, p = 0.0029). 3D volumetric quantification utilizing two-photon fluorescence microscopy revealed that the treated tumors maintained a spheric shape while the untreated controls exhibited the GB typical invasive growth pattern. (4) Conclusions: Our data demonstrate that treatment with a cAMP analog/activator reduces GB growth and invasion.

As a result of demographic change, traumatic brain injury (TBI) in the elderly population is a difficulty which will occur increasingly. A report on the epidemiology of TBI and its pathophysiology (e.g., diffuse axonal injury) will give insight in the development of brain damage following head trauma. Initial evaluation of trauma severity and monitoring of process can be performed via imaging (computed tomography, magnetic resonance imaging) and biomarker profiles (S100B). An association between TBI and neurodegenerative illness exists. Of importance here are the biomarkers amyloid beta (Aβ) and tau as well as the existence of the apolipoprotein E e4 allele.

Context The relevance of hyponatremia has been acknowledged by guidelines from the United States (2013) and Europe (2014). However, treatment recommendations differ due to limited evidence. Objective In hyponatremia following pituitary surgery—caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion—we compared fluid restriction with the pharmacological increase of water excretion by blocking the vasopressin 2 receptors with tolvaptan at a low and a moderate dose. Design Prospective observational study. Setting Neurosurgical Department of a University hospital with more than 200 surgical pituitary procedures per year. Patients Patients undergoing pituitary surgery and developing serum sodium below 136 mmol/L. The diagnosis of SIADH was established by euvolemia (daily measurement of body weight and fluid balance), inappropriately concentrated urine (specific gravity), and exclusion of adrenocorticotropic and thyroid-stimulating hormone deficiency. Intervention P...

Background Following spinal cord injury (SCI), the routine use of magnetic resonance imaging (MRI) resulted in an incremental diagnosis of posttraumatic syringomyelia (PTS). However, facing four decades of preferred surgical treatment of PTS, no clear consensus on the recommended treatment exists. We review the literature on PTS regarding therapeutic strategies, outcomes, and complications. Methods We performed a systematic bibliographic search on (“spinal cord injuries” [Mesh] AND “syringomyelia” [Mesh]). English language literature published between 1980 and 2020 was gathered, and case reports and articles examining syrinx due to other causes were excluded. The type of study, interval injury to symptoms, severity and level of injury, therapeutic procedure, duration of follow-up, complications, and outcome were recorded. Results Forty-three observational studies including 1803 individuals met the eligibility criteria. The time interval from SCI to the diagnosis of PTS varied betwee...

Background A generally accepted rule is that posttraumatic syringomyelia (PTS) results from spinal cord injury (SCI). Case presentation Here, we report the development of syringomyelia without SCI in a 54-year-old Caucasian man following a mild motor vehicle accident. The computed tomography on admission excluded an injury of the spine. Because of neck and back pain, magnetic resonance imaging was performed on day 3 post-injury and demonstrated minimal changes from a ligamentous strain at the cervicothoracic transition. Any traumatic affection of the bone, vertebral discs, intraspinal compartment, or spinal cord were excluded. Some limb weakness and neurogenic bladder dysfunction started manifesting within the following weeks. Repeated MRIs following the accident demonstrated arachnoid adhesions at the C1–2 level and spinal cord edema equivalent to a pre-syrinx state at 12 months and syrinx formation at 24 months. Because of further deterioration, decompression was performed at 36 m...

1002 www.ccmjournal.org July 2019 • Volume 47 • Number 7 MSCs. Although it is not powered for efficacy endpoints and precludes any substantial considerations, patient-specific and dose-dependent response seen in this cohort of septic shock patients ultimately merits the compulsion of bigger sample size. For, a major advantage of MSC therapy is deterrence from any immune allogeneic reactions due to the absence of Major Histocompatibility Complex Class-II surface expression. Additionally, MSCs have the ability to suppress “graft vs host” reaction, elevating their suitability for potential MSC transplantation in septic shock patients. Multiple sources of MSCs (bone marrow, umbilical cord, the adipose, the placenta, and the pancreas) make it even more attractive for therapeutic use, except that it demands caution to scrutinize any discrepancies in their properties with more detailed mechanistic studies.

Treating recurrent glioblastoma (GB) is one of the challenges in modern neurooncology. Hypoxia, neovascularization, and energy metabolism are of crucial importance for therapy failure and recurrence. Twenty-one patients with initially untreated GB who developed recurrence were examined with a novel MRI approach for noninvasive visualization of the tumor microenvironment (TME). Imaging biomarker information about oxygen metabolism (mitochondrial oxygen tension) and neovascularization (microvascular density and type) were fused for classification of five different TME compartments: necrosis, hypoxia with/without neovascularization, oxidative phosphorylation, and glycolysis. Volume percentages of these TME compartments were compared between untreated and recurrent GB. At initial diagnosis, all 21 GB showed either the features of a glycolytic dominant phenotype with a high percentage of functional neovasculature (N = 12) or those of a necrotic/hypoxic dominant phenotype with a high perc...

S100B has been proposed as a putative biochemical marker in determining the extent of brain injury and corresponding prognosis in neurotrauma. The aim of this study was to evaluate the prognostic value of S100B early concentrations in serum and cerebrospinal fluid (CSF) in traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH), to determine prognostically relevant threshold values and to evaluate fluctuation following EVD placement. In 102 patients (45 SAH and 57 TBI) under intensive care unit (ICU) treated between January 2011 and December 2012 with external ventricular drain (EVD) S100B measurements were performed simultaneously in serum and CSF during the first 5 days and before and after EVD exchange. Glasgow coma scale (GCS) was assessed on admission and Glasgow outcome scale (GOS) 6 months later. Peak S100B levels in CSF and serum were measured on the first day after admission and concentrations decreased during the ensuing days post injury gradually. CSF and serum S10...

The high morbidity and mortality associated with the management of vein of Galen aneurysmal malformations (VGAM) continues to pose a tremendous challenge to the neurosurgeon as well as to the attending interventional radiologist. Since 1985, five patients with VGAM have been referred to the neurosurgical unit of the University of Cologne, two neonates, one infant and two adults. Four patients underwent direct operation and two patients received a shunt. The treatment was performed without mortality. A review of the literature reflects no substantial difference between neurosurgical treatment during the last 15 years (mortality 10%) and endovascular treatment (best series mortality 6%).

Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. 2042 www.ccmjournal.org September 2015 • Volume 43 • Number 9 Medical benefits and applications of hypothermia are expanding rapidly, and a temperature-targeted therapy holds promise in the treatment of patients with various forms of neurologic injury. Understanding the mechanisms by which hypothermia affects body systems, particularly the brain, is paramount to the advancement of its application. The brain is particularly vulnerable to ischemia and a complete interruption of cerebral blood flow (CBF) for only 5 minutes triggers the death of neurons, while cardiac myocytes or kidney cells survive 20–40 minutes of ischemia. The vulnerability of brain tissue to ischemia results from its high metabolic rate. Although the human brain represents only about 2.5% of body weight, it accounts for 20% of basal metabolism. Neurons are almost exclusively dependent on glucose as an energy substrate, and brain stores of glucose or glycogen are limited. Furthermore, the brain’s intrinsic signaling system, normally responsible for information processing, becomes harmful under ischemic conditions, accelerating energy failure and enhancing final pathways underlying cell death in all tissues. Within seconds of cerebral ischemia, the local cortical activity ceases. The shutdown of neural activity is induced by K efflux from neurons, mediated initially by the opening of voltage-dependent K channels and later by adenosine triphosphate (ATP)-dependent K channels, leading to transient membrane hyperpolarization. A few minutes later, despite this energy sparing response, an abrupt and dramatic redistribution of ions occurs across the plasma membrane, associated with membrane depolarization (efflux of K and influx of Na, Cl, and Ca). This “anoxic depolarization” results in the excessive release of neurotransmitters, in particular glutamate, promoting further spatial spread of cellular depolarization, depletion of energy stores, and advancement of injury cascades. Experimental evidence indicates that hypothermia protects neurons by reducing CBF and oxygen consumption (1), decreasing the cerebral metabolic rate by about 6–7% for every 1°C drop in body temperature (2), improving brain glucose utilization (3), and preserving cerebral autoregulation (4). Optimum conditions for hypothermic neuroprotection seem mostly affected by the duration and timing of cooling, rather than the depth of cooling. Experimental research suggests that small decreases in temperature (34°C) are as neuroprotective as larger decreases (25°C) (5), while clinical reports indicate that the body temperature is inversely correlated to infarct volume and clinical outcome (6). In 2011, five international critical care societies issued a joint report regarding evidence-based recommendations for the use of therapeutic hypothermia and recommended replacing the term “therapeutic hypothermia” with “targeted temperature management” (TTM) to emphasize the importance of defining a complete temperature profile (7). TTM was strongly recommended for out-of-hospital cardiac arrest survivors with electrocardiogram rhythm of ventricular tachycardia or fibrillation, who remain unconscious following the return of spontaneous circulation and was weakly recommended in newborns following sustained asphyxia with acidosis and/or encephalopathy. The jury did not recommend either for or against the use of TTM in other cardiac rhythms or in-hospital cardiac arrest as well as in the management of traumatic brain injury, increased intracranial pressure, acute ischemic stroke, subarachnoid hemorrhage, spinal cord injury, and acute liver failure encephalopathy due to insufficient evidence of its benefit. In this issue of Critical Care Medicine, Mizoue et al (8) provide insight into the cellular mechanisms of hypothermia in cerebroprotection during global ischemia. They determine prospectively the effect of hypothermia on CBF thresholds critical for membrane repolarization following restoration of blood flow. Specifically, they subject adult, male Sprague-Dawley rats (n = 40) to bilateral occlusion of the common carotid arteries plus hypovolemia, which results in transient global brain ischemia. CBF, membrane depolarization, brain temperature, and neuronal repolarization in the cerebral cortex were measured simultaneously. Ischemia duration was maintained for 5 or 10 minutes at either normothermic brain temperature (37°C) or Hypothermia Reduces the Cerebral Blood Flow Threshold Critical to Reestablish Neuronal Membrane Potential*

Hyponatremia is frequent in patients suffering from traumatic brain injury, subarachnoid hemorrhage or following intracranial procedures, with approximately 20% having a decreased serum sodium concentration to &lt;125 mmol/L. The pathophysiology of hyponatremia in neurotrauma is not completely understood, but in large part is explained by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The abnormal water and/or sodium handling creates an osmotic gradient promoting the shift of water into brain cells, thereby worsening cerebral edema and precipitating neurological deterioration. Unless hyponatremia is corrected promptly and effectively, morbidity and mortality increases through seizures, elevations in intracranial pressure, and/or herniation. The excess mortality in patients with severe hyponatremia (&lt;125 mmol/L) extends beyond the time frame of hospital admission, with a reported mortality of 20% in hospital and 45% within 6 months of follow-up. Current o...

There exists no pharmacological treatment for fulminating brain edema. Since evidence indicates that brain aquaporin-4 (AQP4) water channels are modulated by vasopressin V1a receptors, we examined the edema-reducing properties of the selective V1a receptor antagonist, SR49059, following middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or SR49059 infusion at different dosages (each n = 6,480 microL/hr, 640 microL/hr, 720 microL/hr) and starting 60 minutes before or after MCAO. After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. Statistics were performed using an ANOVA followed by a Tukey post hoc analysis. SR049059 treatment reduced brain water content in the infarcted area given at 640 microL/hr (p = 0.036), 720 microL/hr 60 minutes before (p = 0.002) or 60 minutes after (p = 0.005) MCAO. The consecutive...

We provide a critical analysis of the value of S100B as a marker of brain damage and possible therapeutic implications. The early assessment of the injury severity and the consequent prognosis are of major concern for physicians treating patients suffering from traumatic brain injury (TBI). A reliable indicator to accurately determine the extent of the brain damage has to meet certain requirements: (i) to originate in the central nervous system (CNS) with no contribution from extracerebral sources; (ii) a passive release from damaged neurons and/or glial cells without any stimulated active release; (iii) a lack of specific effects on neurons and/or glial cells interfering with the initial injury; (iv) an unlimited passage through the blood-brain barrier (BBB). The measurement of putative biochemical markers, such as the S100B protein, has been proposed in this role. Over the past decade, numerous studies have reported a positive correlation of S100B serum levels with a poor outcome ...

Little information is available on the rostro-caudal concentration gradient of Alzheimer&#39;s disease (AD) biomarkers. We studied the concentrations of amyloid-β (Aβ) peptides 1-42 and 1-40 as well as the Tau and pTau proteins in simultaneously collected ventricular and lumbar cerebrospinal fluid (CSF) samples. The samples were simultaneously collected from the ventricle and the lumbar spinal canal in two groups of patients: 10 subjects being treated for normal pressure hydrocephalus (NPH) by the placement of a ventriculo-peritoneal shunt and 5 patients treated simultaneously with an external ventricular drain and a lumbar CSF drain due to posttraumatic hydrocephalus (PTH). The ventricular-lumbar (V/L) concentration ratio for Aβ1-40 was 0.81 in NPH patients and 0.71 in PTH patients. The V/L-ratio for Aβ1-42 was 0.84 in NPH, reflecting significantly higher concentrations in lumbar CSF than in ventricular CSF, and 1.02 in PTH patients. The V/L-ratios for Tau and pTau differed signifi...

Atrial natriuretic peptide (ANP) plays an important role in body fluid homeostasis. ANP has been established as a marker of cardiac dysfunction and may play a role in brain edema development after traumatic brain injury (TBI). In order to identify its specific assignment following TBI, we related clinical data and treatment variables in 63 patients to longitudinal midregional (MR) proatrail natriuretic peptide (ANP) measurements. ANP correlated significantly to age (p &lt; 0.0001) and vasopressin release (p &lt; 0.001). Following TBI, ANP was increased initially and on day 3 (cut-off 100 pg/L) in 22% of the patients, in 31% on day 7, and was normalized at follow-up examination. The group comparison revealed that ANP levels did not significantly differ with regard to injury severity, but that high ANP levels predicted a worse Glasgow Outcome Score at 6 months (p &lt; 0.05). While the initially intact osmoregulation - a correlation of urine volume and high serum sodium (r = 0.536, p =...

The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, reflects AVP activity. In 71 TBI patients we measured copeptin in serum by a sandwich immunoassay. Injury severity was assessed by Glasgow Coma Score (GCS) and computed tomography, and recovery by Glasgow Outcome Score (GOS). Neuroendocrine and osmoregulation regulation were examined on day 0, 3 and 7, and 24 months post-injury. Copeptin was highest on admission (40.0 +/- 72.3 pmol/l), stabilized on day 3 and 7 (21.2 +/- 18.3 resp. 20.3 +/- 17.1 pmol/l), and normalized at follow-up (4.2 +/- 1.7 pmol/l). On admission, there was a correlation between serum sodium and urine excretion (p = 0.003), but the correlation got lost on day 3 and 7. Copeptin did not reflect the individual 24 h urine excretion or serum sodium levels indicati...

We have pursued the concept that traumatic brain edema is predominantly cellular and that water entry is modulated in part by aquaporins. Aquaporin-4 (AQP4) has been shown to play a significant role in cellular edema formation. Phorbol myristate acetate (PMA) is a potent PKC activator; purportedly involved in modulation of AQP4 activity. Alternatively, AQP4 may be regulated by arginine-vasopressin. Administration of the vasopressin antagonist (SR49059) reduced brain water content and sodium shift following MCAo. To investigate if edema formation is affected by the reduction of AQP4 expression, we utilized PMA and SR49059 following middle cerebral artery occlusion model (MCAo), and measured AQP4 expression by Western-Blot (WB) techniques. Male Sprague Dawley rats were randomly assigned to sham (n=4) or MCAo groups (vehicle, PMA or SR49059 infusion; n=6 each). Each solution was infused for 5 hours, starting 1 hour before injury. After a two-hour period of ischemia and two-hour reperfu...

Following brain injury, S100B is released from damaged astrocytes but also yields repair mechanisms. We measured S100B in the cerebrospinal fluid (CSF) and serum (Cobas e411 electrochemiluminescence assay, Roche) longitudinally in a large cohort of patients treated with a ventricular drainage following traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). Statistical analysis was performed with SPSS software applying the Mann-Whitney rank sum test or chi-test where appropriate. S100B in CSF and serum was significantly increased following TBI (n = 71) and SAH (n = 185) for at least one week following injury. High S100B levels in CSF and serum were inconsistent associated with outcome. The passage of S100B from CSF to blood (100( *)serum(S100B)/CSF(S100B)) was significantly decreased although the albumin quotient suggested an &quot;open&quot; blood-CSF barrier. Events possibly interfering with the BBB did not affect the S100B passage (P = .591). In conclusion, we could not co...

oth traumatic brain injury (TBI) and ischemic/hem-orrhagic stroke render a substantial burden of mor-bidity and mortality to the society. While around 1.4 million persons suffer from TBI each year, causing about 50,000 deaths from TBI-related injuries, almost a million adults are affected by stroke annually, with around 150,000 related deaths per year in the United States (1). Thus, acute brain injury resulting from either the mechanical type of TBI or the ischemic or hemorrhagic type of stroke represents an enormous challenge requiring continuing improvement of therapeutic approaches.Research over the past decades has elucidated the patho-physiology of neurotrauma after brain injury. Beside the “primary” damage, numerous “secondary” events evolve after-ward, including activation of neuroinflammatory cascades, toxic neurotransmitter release, or production of free radicals, which have a crucial impact on the subsequent neurological damage and the final outcome (2, 3). Current management protocols have established the importance of maintaining adequate physiological variables, that is, cerebral perfusion and oxygenation and avoiding subsequent complications (2, 4) and thereby bisected the mortality following brain injury. However, any neuroprotective strategy—as promising in the experimental setting—including the inhibition of inflamma-tory cascades or of the generation of free radicals, has failed in clinical studies (5, 6).One lesson we learned over the past decades of brain research is that nothing is exactly as it appears to be. The French poet and Nobel Prize laureate Anatole France coined the phrase “Nature has no principles. She makes no distinction between good and evil.” This is especially true for inflamma-tion and has to be kept in mind interpreting the results of Stoc-chetti’s group. As much as the attenuation of the inflammatory response may be neuroprotective as many reports focus on the participation of inflammation in neuroregeneration (7).In this issue of

High S100B serum levels are considered to reflect brain injury severity. However, the dynamics of S100B passage from the cerebral compartment into the blood remain unclear. We examined the temporal profile of S100B release into the cerebrospinal fluid (CSF) and blood in acute brain injury.In patients treated with ventricular drainage (subarachnoid hemorrhage, SAH, n = 23; traumatic brain injury, TBI, n = 19), we measured S100B levels in the serum and CSF. The Glasgow Coma Score (GCS) was assessed daily. Statistical analysis was performed by the Mann-Whitney rank sum test for group differences and by the Pearson correlation.In normal controls (n = 6), S100B levels in the serum (0.05 +/- 0.01 microg/L) comprised around 10% of the CSF concentration (0.66 +/- 0.08 microg/L). Following brain injury, S100B levels were significantly increased in the serum (p &amp;lt; 0.05 in SAH day 2-5, TBI day 1-8) and excessively increased in the CSF (p &amp;lt; 0.05 in SAH and TBI day 1-10). For the individual patient, there was no consistent correlation between S100B levels in serum or CSF and GCS. We therefore calculated the ratio of S100B serum/CSF. Following brain injury, the S100B passage from the CSF to the blood was significantly impaired. Further, higher ratios were correlated with better neurological function (p = 0.002).Because stimulated active S100B release may serve as a repair mechanism, a higher S100B serum/CSF ratio may contribute to neurological recovery.