Andrea Kleindienst

• MD, PhD
• Professor at Friedrich-Alexander-University Erlangen-Nürnberg

Background/Objectives: S100B is a well-established neuromarker for cerebral damage, with renal elimination playing a key role in interpreting its serum levels. The aim of this study was to assess whether the renal S100B elimination is different in neurotrauma and control patients.

S100B is a 21-kDa protein that is produced and secreted by astrocytes and widely used as a marker of brain injury in clinical and experimental studies. The majority of these studies are based on measurements in blood serum, assuming an associated increase in cerebrospinal fluid and a rupture of the blood–brain barrier (BBB). Moreover, extracerebral...

The utilization of vasopressin receptor antagonists, known as vaptans, in the management of hyponatremia among patients afflicted with the syndrome of inappropriate antidiuretic hormone (SIADH) remains a contentious subject. This meta-analysis aimed to evaluate the safety and efficacy of vaptans for treating chronic hyponatremia in adult SIADH pati...

(1) The neurotrophic protein S100B is a marker of brain injury and has been associated with neuroregeneration. In S100Btg mice rendering 12 copies of the murine S100B gene we evaluated whether S100B may serve as a treatment option. (2) In juvenile, adult, and one-year-old S100Btg mice (female and male; n = 8 per group), progenitor cell proliferatio...

Background: 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 fir...

(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) mice with 12 copie...

(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 pro...

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...

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 therapeut...

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 rest...

Release of neurotrophic and growth factors like S100B yields an endogenous repair mechanism following traumatic brain injury (TBI). While nanomolar S100B concentrations enhance hippocampal progenitor cell proliferation, neuronal differentiation and cognitive recovery, micromolar concentrations may foster inflammatory effects counteracting neuroplas...

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...

Purpose Glioblastoma (GB) is one of the most vascularized of all solid tumors and, therefore, represents an attractive target for antiangiogenic therapies. Many lesions, however, quickly develop escape mechanisms associated with changes in the tumor microenvironment (TME) resulting in rapid treatment failure. To prevent patients from adverse effect...

Despite progress in surgery and radiochemotherapy, the prognosis of glioblastoma (GB) remains poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Treatment strategies utilizing oxygen (O2) or ozone (O3) and generating reactive oxygen species induce cell growth inhibition and apoptosis. The anti-tumorigenic prop...

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 monit...

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 prospectivel...

Objectives: 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),...

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 <125 mmol/L. The pathophysiology of hyponatremia in neurotrauma is not completely understood, but in large part is explained by the syndrome...

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 prospectivel...

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 y...

Background Little information is available on the rostro-caudal concentration gradient of Alzheimer’s disease (AD) biomarkers. Objective 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. Methods The sampl...

One of the major concerns in transsphenoidal surgery are infections because the approach to the pituitary includes a route of microbial colonization. To minimize the associated morbidity and mortality, a surveillance program is crucial to monitor for perioperative infections. For 1 year, we analysed body temperature (BT), erythrocyte sedimentation...

Objective: The measurement of neuromarker/neuroproteins in the cerebrospinal fluid (CSF) is gaining increased popularity. However, insufficient information is available on the rostrocaudal distribution of neuroproteins in the CSF to guarantee an appropriate interpretation of ventricular versus lumbar concentrations. Methods: In 10 patients treat...

Background: Neurogenesis is documented in adult mammals including humans, is promoted by neurotrophic factors, and constitutes an innate repair mechanism following brain injury. The glial neurotrophic protein S100B is released following various types of brain injuries, enhances hippocampal neurogenesis and improves cognitive function following bra...

Background: The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10-100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could...

In recent years, the measurement of biomarkers following neurotrauma assisted in improving outcome prediction and guiding therapy. The use of neuroproteins as diagnostic parameters requires a detailed knowledge of their dynamics in biological fluids for an appropriate interpretation. S100B is the most widely studied neuromarker, and its concentrati...

Background: The hormone and neuropeptide arginine-vasopressin is designated to the maintenance of osmotic homoeostasis and blood pressure regulation. While experimental data show vasopressin V(1A) receptors to regulate aquaporin (AQP)4 water channel dependent brain water movement, the specific role in vasogenic and cytotoxic edema formation remain...

Craniopharyngiomas are rare benign sellar region tumors, which are diagnosed either in childhood or adolescence due to local mass effects on visual pathways, pituitary and hypothalamus, or because of an increased intracranial pressure resulting from obstructive hydrocephalus. The neurosurgeons challenge is to achieve tumor control without aggravati...

Hyponatremia is frequent following cranial -neurosurgery or acute brain injury like subarachnoid hemorrhage (SAH), and increases mortality by 30%. The patho-physiology is not understood nor does a causal therapy exist. Since clinical trials are potentially dangerous in this very ill population, we examined whether an established rat model allows st...

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...

Posthemorrhagic hydrocephalus requiring permanent ventriculoperitoneal shunt placement is a major complication of aneurysmal subarachnoid hemorrhage (SAH). High S100B serum and cerebrospinal fluid (CSF) levels are considered to reflect the severity of brain injury. We prospectively assessed whether S100B levels in serum and CSF were predictive para...

The Wnt/ß-catenin signalling pathway is involved in tumorigenesis including endocrine tumors. We investigated the Wnt/ß-catenin pathway's modulation by corticotropin-releasing hormone (CRH) and somatostatin or somatotropin release-inhibiting factor (SRIF) in mouse pituitary AtT-20 corticotroph cells. The Wnt/β-catenin signalling pathway was activat...

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 h...

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 immun...

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...

The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) is known to interact with aquaporin 4 (AQP 4), a water-selective transporting protein that is abundant in astrocytes, and has experimentally been found to decrease osmotically-induced cell swelling. The purpose of this study was to examine whether PMA reduces brain edema following...

Neuroendocrine dysfunction following traumatic brain injury (TBI) has been described extensively. However, few studies are longitudinal and most lack subtle radiological, clinical, and repetitive endocrine assessment in the acute phase. Accordingly, we prospectively assessed neuroendocrine function in 71 patients after TBI. Injury was documented by...

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...

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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. Alternativ...

Several studies documented metabolic and psychological benefits of GH substitution in deficient adults, most of them suffering from benign pituitary adenomas. Since GH substitution is considered to promote tumour regrowth, adequate treatment is performed with some reservation. Therefore, we aimed to elucidate the effect of GH replacement therapy on...

Posthemorrhagic hydrocephalus requiring permanent ventriculoperitoneal shunt placement is a major complication of aneurysmal subarachnoid hemorrhage (SAH). High S100B serum and cerebrospinal fl uid (CSF) levels are considered to refl ect the severity of brain injury. We prospectively assessed whether S100B levels in serum and CSF were predic-tive p...

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...

We provide a critical analysis of the relevance of S100B in acute brain injury emphazising the beneficial effect of its biological properties. S100B is a calcium-binding protein, primarily produced by glial cells, and exerts auto- and paracrine functions. Numerous reports indicate, that S100B is released after brain insults and serum levels are pos...

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 r...

The protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), is known to interact with aquaporin-4 (AQP4), a waterselective transporting protein abundant in astrocytes and ependymal cells, that has been found to decrease osmotically-induced swelling. The purpose of this study was to examine whether PMA given at different time points follo...

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 r...

Dimethyl sulfoxide (DMSO) is widely used as a solvent for other drugs, i.e., for the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) and the V1a receptor-antagonist SR49059, to reduce brain edema. We studied the effect of DMSO on blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO) and the consequen...

The protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), is known to interact with aquaporin-4 (AQP4), a waterselective transporting protein abundant in astrocytes and ependymal cells, that has been found to decrease osmotically-induced swelling. The purpose of this study was to examine whether PMA given at different time points follo...

Dementia is a heterogenous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathological changes. As such, there lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes. The authors present therefore the cu...

Evidence of injury-induced neurogenesis in the adult hippocampus suggests that an endogenous repair mechanism exists for cognitive dysfunction following traumatic brain injury (TBI). One factor that may be associated with this restoration is S100B, a neurotrophic/mitogenic protein produced by astrocytes, which has been shown to improve memory funct...

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 res...

S100B protein in brain is produced primarily by astrocytes, has been used as a marker for brain injury and has also been shown to be neurotrophic and neuroprotective. Using a well characterized in vitro model of brain cell trauma, we examined the potential role of exogenous S100B in preventing delayed neuronal injury. Neuronal plus glial cultures w...

Elevated serum S100B levels have been shown to be a predictor of poor outcome after traumatic brain injury (TBI). Experimental data, on the other hand, demonstrate a neuroprotective and neurotrophic effect of this calcium-binding protein. The purpose of this study was to examine the role of increased S100B levels on functional outcome after TBI. Fo...

As evidence exists about independent regulation of peripheral and central release of the vasoactive and natriuretic neuropeptides arginine-vasopressin (AVP) and oxytocin (OXT), we investigated their release patterns following subarachnoid hemorrhage (SAH). After injection of 0.1 ml arterial blood or saline into the great cistern of 33 Wistar rats,...

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. Over a 3 year...

Despite the moderate to high risk of venous thromboembolic events in neurosurgical intensive care patients, prophylaxis with heparin has not been established routinely due to the deleterious effects of bleeding complications. After initiating early low molecular weight heparin (LMWH) prophylaxis, we reviewed our patients in order to examine this pr...

A prospective study was undertaken to determine the number of potential organ donors in a neurosurgical intensive care unit and to record the actual number of organ donations. The reasons for refusal of organ donations were analysed with respect to the controversial public discussion of the brain death concept and the transplantation law in Germany...

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 neona...

The purpose of this prospective study was to determine the potential of MR imaging to depict morphologic alterations of the median nerve correlating with the stage of carpal tunnel syndrome (CTS). Eighteen wrists of normal subjects and 81 wrists of patients with CTS were examined. MR imaging was performed with proton-density- and T2-weighted spin-e...

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...

In order to determine the reliability of magnetic resonance imaging (MRI) in the diagnosis and staging of carpal tunnel syndrome (CTS), the most common entrapment neuropathy, the following prospective study has been performed. We compared clinical and electrophysiological studies in 58 cases of CTS with MRI investigations and confirmed the reliabil...

We examined 62 patients (72 hands) with carpal tunnel syndrome (CTS) by magnetic resonance imaging (MRI) of the carpal tunnel and latency measurements of the median nerve. In 32 of 72 hands a probable causative lesion of the CTS was identified by MRI, for example tenosynovitis, a cyst-like structure, or an aberrant muscle. The MRI findings were con...

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 pra...