The Na,K,2Cl Cotransporter, Not Aquaporin 1, Sustains Cerebrospinal Fluid Secretion While Controlling Brain K Homeostasis.

Disturbances in the brain fluid balance can lead to life-threatening elevation in intracranial pressure (ICP), which represents a vast clinical challenge. Targeted and efficient pharmaceutical therapy of elevated ICP is not currently available, as the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved. To resolve the quantitative contribution of key choroid plexus transport proteins, this study employs mice with genetic knockout and/or viral choroid plexus-specific knockdown of aquaporin 1 (AQP1) and the Na, K, 2Cl cotransporter 1 (NKCC1) for in vivo determinations of CSF dynamics, ex vivo choroid plexus for transporter-mediated clearance of a CSF K load, and patient CSF for [K] quantification.

Proteomic profile and predictive markers of outcome in patients with subarachnoid hemorrhage.

Background: The molecular mechanisms underlying development of posthemorrhagic hydrocephalus (PHH) following subarachnoid hemorrhage (SAH) remain incompletely understood. Consequently, treatment strategies tailored towards the individual patient remain limited. This study aimed to identify proteomic cerebrospinal fluid (CSF) biomarkers capable of predicting shunt dependency and functional outcome in patients with SAH in order to improve informed clinical decision making.

Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial.

Background: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

Background: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC.

Critical ICP thresholds in relation to outcome: Is 22 mmHg really the answer?

Purpose: Intensive care for patients with traumatic brain injury (TBI) aims, among other tasks, at avoiding high intracranial pressure (ICP), which is perceived to worsen motor and cognitive deficits and increase mortality. International recommendations for threshold values for ICP were increased from 20 to 22 mmHg in 2016 following the findings in a study by Sorrentino et al., which were based on an observational study of patients with TBI of averaged ICP values.

Predictors of shunt insertion in patients with aneurysmal subarachnoid haemorrhage-a single-centre retrospective analysis.

Background: No standard has been established regarding timing and choice of strategy for discontinuation of external ventricular drainage (EVD) in patients with aneurysmal subarachnoid haemorrhage (aSAH), and little is known about the importance of clinical variables. A proportion of the patients who initially pass their discontinuation attempt return with delayed hydrocephalus and the need of a permanent shunt. Early differentiation between patients who need a shunt and those who do not would facilitate care.

Distinct Cerebrospinal Fluid Lipid Signature in Patients with Subarachnoid Hemorrhage-Induced Hydrocephalus.

Patients with subarachnoid hemorrhage (SAH) may develop posthemorrhagic hydrocephalus (PHH), which is treated with surgical cerebrospinal fluid (CSF) diversion. This diversion is associated with risk of infection and shunt failure. Biomarkers for PHH etiology, CSF dynamics disturbances, and potentially subsequent shunt dependency are therefore in demand.

Posthemorrhagic Hydrocephalus in Patients with Subarachnoid Hemorrhage Occurs Independently of CSF Osmolality.

The molecular mechanisms underlying the development of posthemorrhagic hydrocephalus (PHH) remain incompletely understood. As the disease pathogenesis often cannot be attributed to visible cerebrospinal fluid (CSF) drainage obstructions, we here aimed to elucidate whether elevated CSF osmolality following subarachnoid hemorrhage (SAH) could potentiate the formation of ventricular fluid, and thereby contribute to the pathological CSF accumulation observed in PHH. The CSF osmolality was determined in 32 patients with acute SAH after external ventricular drainage (EVD) placement and again upon EVD removal and compared with the CSF osmolality from 14 healthy control subjects undergoing vascular clipping of an unruptured aneurism.

Effect of controlled blood pressure increase on cerebral blood flow velocity and oxygenation in patients with subarachnoid haemorrhage.

Background: Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF - and thereby oxygen delivery - passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred.

Methods: The study was carried out within 5 days after ictus.

Inflammatory Markers as Predictors of Shunt Dependency and Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

The mechanisms underlying post-hemorrhagic hydrocephalus (PHH) development following subarachnoid hemorrhage (SAH) are not fully understood, which complicates informed clinical decisions regarding the duration of external ventricular drain (EVD) treatment and prevents the prediction of shunt-dependency in the individual patient. The aim of this study was to identify potential inflammatory cerebrospinal fluid (CSF) biomarkers of PHH and, thus, shunt-dependency and functional outcome in patients with SAH. This study was a prospective observational study designed to evaluate inflammatory markers in ventricular CSF.

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt.

Lysophosphatidic acid as a CSF lipid in posthemorrhagic hydrocephalus that drives CSF accumulation via TRPV4-induced hyperactivation of NKCC1.

Background: A range of neurological pathologies may lead to secondary hydrocephalus. Treatment has largely been limited to surgical cerebrospinal fluid (CSF) diversion, as specific and efficient pharmacological options are lacking, partly due to the elusive molecular nature of the CSF secretion apparatus and its regulatory properties in physiology and pathophysiology.

Methods: CSF obtained from patients with subarachnoid hemorrhage (SAH) and rats with experimentally inflicted intraventricular hemorrhage (IVH) was analyzed for lysophosphatidic acid (LPA) by alpha-LISA.

Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters.

Introduction: Posthemorrhagic hydrocephalus (PHH) often develops following hemorrhagic events such as intraventricular hemorrhage (IVH) and subarachnoid hemorrhage (SAH). Treatment is limited to surgical diversion of the cerebrospinal fluid (CSF) since no efficient pharmacological therapies are available. This limitation follows from our incomplete knowledge of the molecular mechanisms underlying the ventriculomegaly characteristic of PHH.

Reliability of non-invasive arterial blood pressure measurement in patients with aneurysmal subarachnoid haemorrhage.

. Invasively measured arterial blood pressure (ABP) is associated with complications, while non-invasively measured ABP is generally considered risk-free. This study aimed to investigate the reliability of non-invasive ABP measured using finger-cuff volume-clamp device compared to invasive ABP measured by an arterial catheter in patients with aneurysmal subarachnoid haemorrhage (SAH).

Reliability of cerebral autoregulation using different measures of perfusion pressure in patients with subarachnoid hemorrhage.

Dynamic cerebral autoregulation to spontaneous fluctuations in cerebral perfusion pressure (CPP) is often assessed by transcranial Doppler (TCD) in the time domain, yielding primarily the mean flow index (Mx), or in the frequency domain using transfer function analysis (TFA), yielding gain and phase. For both domains, the measurement of blood pressure is critical. This study assessed the inter-method reliability of dynamic cerebral autoregulation using three different methods of pressure measurement.

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus in adult patients with aneurysmal subarachnoid haemorrhage: a systematic review.

Objectives: To summarise the evidence on benefits and harms of prompt closure versus gradual weaning of external ventricular drainage (EVD) in patients with hydrocephalus following aneurysmal subarachnoid haemorrhage (aSAH) based on randomised clinical trials (RCTs) in humans.

Setting: RCTs comparing prompt closure versus gradual weaning of EVD in adult patients with hydrocephalus following aSAH were included.

Participants: Patients aged equal to or greater than 18 years with an EVD due to hydrocephalus following aSAH were eligible for inclusion.

Discontinuation of External Ventricular Drainage in Patients with Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage - a Scandinavian Multi-institutional Survey.

Background: Hydrocephalus requiring external ventricular drainage is common following aneurysmal subarachnoid hemorrhage (aSAH). Timing and strategy for the discontinuation of the external ventricular drain (EVD) are, however, controversial as guidelines are based on limited scientific evidence. A recent similar survey showed that guidelines and recommendations are not being followed.

Prompt closure versus gradual weaning of extraventricular drainage for hydrocephalus in adult patients with aneurysmal subarachnoid haemorrhage: a systematic review protocol with meta-analysis and trial sequential analysis.

Introduction: In Neuro Intensive Care Units (NICU) and neurosurgical units, patients with an external ventricular drain (EVD) due to hydrocephalus following aneurysmal subarachnoid haemorrhage (SAH) are commonly seen. Cessation of the EVD involves the dilemma of either closing the EVD directly, or gradually weaning it before removal. Development of increased intracranial pressure (ICP) and acute hydrocephalus with subsequent need of a permanent shunt has been associated with prompt closure of theEVD, whereas increased risk of infection with possible spreading to the brain and subsequent patient fatality is suspected in connection to a longer treatment as seen in gradual weaning.

Multiple Extracranial Metastases from Primary Gliosarcoma in a Patient with Two Previous Different Primary Cancers.

Gliosarcoma (GS) constitutes a minor fraction of primary glioblastoma (GBM), which is the most frequent malignant brain tumor in adults. Despite the fact that malignant gliomas are highly invasive, extracranial metastases are very rarely seen, and the mechanisms behind extracranial dissemination are still unclarified. We report a case of a 55-year-old male with a prior history of two distinct primary cancer types who, as a third independent type, developed GS with penetrating tumor growth to the skull and subcutaneous soft tissue via explosive spreading through a titanium net as well as extracranial metastases to the lumbar spine, paravertebral musculature, and most likely the right lung.

[Rapid resolution of acute subdural haematoma with significant impact on clinical outcome].

A 73-year-old woman was admitted to hospital due to anaemia. She suffered a minor head trauma and deteriorated to deep unconsciousness. A CT revealed an acute subdural haematoma (ASDH).