Cerebral venous sinus thrombosis (CVST) is a rare clinicopathological entity. The incidence of CVST in children and neonates has been reported to be as high as 7 cases per million people, whereas in adults the incidence is 3–4 cases per million. The predisposing factors to this condition are mainly genetic and acquired prothrombotic states and infection. The clinical picture of CVST is nonspecific, highly variable, and can mimic several other clinical conditions. Diagnosis of CVST is established with the implementation of neuroimaging studies, especially MR imaging and venography. Identification and elimination of the underlying cause, anticoagulation, proper management of intracranial hypertension, and anticonvulsant prophylaxis constitute cornerstones of CVST treatment. Newer treatment strategies such as endovascular thrombolysis and decompressive craniectomy have been recently used in the treatment of patients with CVST with variable success rates. Further clinical research must be performed to delineate the exact role of these newer treatments in the management of severe cases of CVST. The recent advances in the diagnosis and treatment of patients with CVST have significantly lowered the associated mortality and morbidity and have improved the outcome of these patients.

The aquaporin (AQP) family of water channels are a group of small, membrane-spanning proteins that are vital for the rapid transport of water across the plasma membrane. These proteins are widely expressed, from tissues such as the renal epithelium and erythrocytes to the various cells of the central nervous system. This review will elucidate the basic structure and distribution of aquaporins and discuss the role of aquaporins in various neuropathologies. AQP1 and AQP4, the two primary aquaporin molecules of the central nervous system, regulate brain water and CSF movement and contribute to cytotoxic and vasogenic edema, where they control the size of the intracellular and extracellular fluid volumes, respectively. AQP4 expression is vital to the cellular migration and angiogenesis at the heart of tumor growth; AQP4 is central to dysfunctions in glutamate metabolism, synaptogenesis, and memory consolidation; and AQP1 and AQP4 adaptations have been seen in obstructive and non-obstructive hydrocephalus and may be therapeutic targets.

A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5 h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm2) versus sham groups (78.3±0.1%; 9.5±0.9 µm2), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8 µm2). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03± 0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema.

Negative-pressure or low-pressure hydrocephalus associated with CSF leaks, especially after cranial base approaches, is difficult to treat. The solution often requires the utilization of subatmospheric external ventricular drains to establish a lower ventricular drainage pressure than the drainage pressure created in the subarachnoid space, where the pressure is artificially lowered by the CSF leak. Treatment involves correction of the CSF leak, neck wrapping to increase brain turgor and allow the pressure in the ventricles to rise to the level of the opening pressure of the valve, and reestablishing the CSF route.

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Object The definition of tethered cord syndrome (TCS) relies mainly on radiological criteria and clinical picture. The presence of a thickened filum terminale and a low-lying conus medullaris in symptomatic patients is indicative of TCS. The radiological definition of TCS does not take into account cases that involve a normal-lying conus medullaris exhibiting symptoms of the disease. Methods The authors performed a MEDLINE search using the terms “tethered cord” and “pathophysiology.” The search returned a total of 134 studies. The studies were further filtered to identify mostly basic research studies in animal models or studies related to the biomechanics of the filum terminale and spinal cord. Results Spinal cord traction and the loss of filum terminale elasticity are the triggers that start a cascade of events occurring at the metabolic and vascular levels leading to symptoms of the disease. Traction on the caudal cord results in decreased blood flow causing metabolic derangements that culminate in motor, sensory, and urinary neurological deficits. The untethering operation restores blood flow and reverses the clinical picture in most symptomatic cases. Conclusions Although classically defined as a disease of a low-lying conus medullaris, the pathophysiology of TCS is much more complex and is dependent on a structural abnormality, with concomitant altered metabolic and vascular sequelae. Given the complex mechanisms underlying TCS, it is not surprising that the radiological criteria do not adequately address all presentations of the disease.

Object The aim of this study was to provide a systematic update of the current literature regarding the clinical role of the S100B serum biomarker in the initial evaluation of children who have sustained a mild traumatic brain injury (TBI). Methods Searches in MEDLINE were defined with the keywords “mild TBI children S100,” “mild TBI pediatric S100,” and “children S100 brain injury.” From the pool of obtained studies, those that had the inclusion criteria of mild TBI only or mixed types of TBI but including detailed information about groups of children with mild TBI were used. Results Few studies were identified and fewer included more than 100 cases. The prospective studies showed that the S100B biomarker levels could be influenced by patient age and the time frame between head injury and blood sampling. Moreover, extracranial sources of S100B or additional injuries could influence the measured levels of this biomarker. A normal value of S100B in children with mild TBI could rule out injury-associated abnormalities on CT scans in the majority of reported cases. Conclusions The vulnerability of S100B serum levels to the influences of patient age, blood sampling time, and extracranial S100B release limits the biomarker's role in the initial evaluation of children with mild TBI. The application of S100B in pediatric mild TBI cases has an elusive role, although it could help in selected cases to avoid unnecessary head CT scans.

Aquaporin-1 is highly expressed at the choroid plexus and is related to CSF production. Aquaporin-4 is expressed at the ependyma, glia limitans, and at the perivascular end feet processes of astrocytes of the BBB, facilitating the water movement across these tissue interfaces. The observations obtained from animal studies and few cases in humans indicate an adaptive and protective role of AQPs in hydrocephalus by decreasing CSF production and increasing edema clearance. Aquaporins are attractive targets for the pharmaceutical treatment of hydrocephalus.