Presence Of Cerebrospinal Fluid Research Articles

Dural-Pleural Fistula as a Complication of Spinal Instrumentation

SESSION TITLE: Disorders of the Pleura SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pleural effusions are usually caused by increased pleural fluid production or decreased absorption. Common causes are heart failure and pneumonia. However, other less common causes of pleural effusion have been recognized. We report here a case of a dural-pleural fistula as a complication of spinal instrumentation. CASE PRESENTATION: A 68 year old female with past medical history significant for six previous surgeries for spinal herniation. She presented with bilateral lower extremity weakness and pain. She had fallen multiple times in the prior two months from weakness. She was admitted to the hospital with T9-T10 disc herniation. She underwent a thoracotomy with T9-T10 discectomy followed by staged posterior T11 to T4 fusion and posterior decompression laminectomy of T8-T11. Shortly after the surgery she started to complain of shortness of breath; and a chest x-ray showed a right-sided pleural effusion. A contrasted CT study showed the effusion was loculated. The effusion worsened so a thoracentesis was done; this confirmed an exudative fluid. Studies included: fluid LDH of 326, protein of 1.7, WBC of 476, RBC 1703. Due to clinical suspicion, B2-transferrin was also tested. When this returned positive, a thoracic CT Myelogram was done and showed extension of intrathecal contrast into the right pleural space immediately adjacent to the T9-T10 bone graft, consistent with CSF leak. DISCUSSION: The presence of cerebrospinal fluid in the pleural fluid is rare. It is sometimes seen as a consequence of trauma, malignancy and rarely a complication of thoracic or spinal surgery. Our case is a result of a complication during spinal surgery. The pathogenesis here is a tear in the dura that caused a fistula between the pleural space and the dural space. A pressure gradient formed between the negative pressure of the pleural space and the positive pressure of the dural space. This resulted in fluid shift and rapid accumulation of cerebrospinal fluid in the pleural space. The symptoms can range from none to severe respiratory compromise due to massive effusion. Headache, nausea and vomiting could result as a consequence of decreased CSF fluid. The diagnosis is made by testing for B2-transferrin in the pleural fluid, as B2-transferrin is produced exclusively in the cerebrospinal fluid. It has been reported as 100% sensitive and 95% specific. Confirmation is made by myelography, as was done with this patient. CONCLUSIONS: We present a case of a dural-pleural fistula as a complication of spinal instrumentation. Dural-pleural fistula is a complication of spinal surgery and should be considered when evaluating a patient with post-operative pleural effusions. High clinical suspicion paired with B2-transferrin testing is necessary to make the diagnosis, followed by CT-myelography to confirm the location of the fistula. Reference #1: Bhatnagar, R., & Maskell, N. (January 01, 2015). The modern diagnosis and management of pleural effusions. British Medical Journal, 8024, 28-28. DISCLOSURE: The following authors have nothing to disclose: Ali Khalofa, Kyle Chapman, John Parker No Product/Research Disclosure Information

Comparison of the hanging-drop technique and running-drip method for identifying the epidural space in dogs

ObjectiveTo compare the running-drip and hanging-drop techniques for locating the epidural space in dogs. Study designProspective, randomized, clinical trial. AnimalsForty-five healthy dogs requiring epidural anaesthesia. MethodsDogs were randomized into four groups and administered epidural anaesthesia in sternal (S) or lateral (L) recumbency. All blocks were performed by the same person using Tuohy needles with either a fluid-prefilled hub (HDo) or connected to a drip set attached to a fluid bag elevated 60 cm (RDi). The number of attempts, ‘pop’ sensation, clear drop aspiration or fluid dripping, time to locate the epidural space (TTLES) and presence of cerebrospinal fluid (CSF) were recorded. A morphine–bupivacaine combination was injected after positive identification. The success of the block was assessed by experienced observers based on perioperative usage of rescue analgesia. Data were checked for normality. Binomial variables were analysed with the chi-squared or Fisher’s exact test as appropriate. Non-parametric data were analysed using Kruskal–Wallis and Mann–Whitney tests. Normal data were studied with an anova followed by a Tukey's means comparison for groups of the same size. A p-value of < 0.05 was considered to indicate statistical significance. ResultsLateral recumbency HDo required more attempts (six of 11 dogs required more than one attempt) than SRDi (none of 11 dogs) (p = 0.0062). Drop aspiration was observed more often in SHDo (nine of 11 dogs) than in LHDo (two of 11 dogs) (p = 0.045). Mean (range) TTLES was longer in LHDo [47 (18–82) seconds] than in SHDo [20 (14–79) seconds] (p = 0.006) and SRDi [(34 (17–53) seconds] (p = 0.038). There were no differences in ‘pop’ sensation, presence of CSF, rescue analgesia or pain scores between the groups. Conclusion and clinical relevanceThe running-drip method is a useful and fast alternative technique for identifying the epidural space in dogs. The hanging-drop technique in lateral recumbency was more difficult to perform than the other methods, requiring more time and attempts.

Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS.

Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and 13C-NMR to investigate metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles of citrate in physiological and pathophysiological processes in the CNS. An interesting feature of citrate is its ability to chelate Ca2+, Mg2+ and Zn2+and thereby playing a pivotal role as an endogenous modulator of glutamate receptors and in particular the NMDA subtypes of these receptors in the CNS. Besides its presence in cerebrospinal fluid (CSF) citrate is also found in high amounts in prostate fluid reaching concentrations as high as 180mM and here Zn2+ seems also to play an important role, which makes prostate cells interesting for comparison of features of citrate and Zn2+ between these cells and cells in the CNS.

Cerebrospinal fluid-induced retardation of amyloid β aggregation correlates with Alzheimer's disease and the APOE ε4 allele

Misfolding and aggregation of amyloid β (Aβ) are key features of Alzheimer's disease (AD) pathogenesis, but the molecular events controlling this process are not known in detail. In vivo, Aβ aggregation and plaque formation occur in the interstitial fluid of the brain extracellular matrix. This fluid communicates freely with cerebrospinal fluid (CSF). Here, we examined the effect of human CSF on Aβ aggregation kinetics in relation to AD diagnosis and carrier status of the apolipoprotein E (APOE) ε4 allele, the main genetic risk factor for sporadic AD. The aggregation of Aβ was inhibited in the presence of CSF and, surprisingly, the effect was more pronounced in APOE ε4 carriers. However, by fractionation of CSF using size exclusion chromatography, it became evident that it was not the ApoE protein itself that conveyed the inhibition, since the retarding species eluted at lower volume, corresponding to a much higher molecular weight, than ApoE monomers. Cholesterol quantification and immunoblotting identified high-density lipoprotein particles in the retarding fractions, indicating that such particles may be responsible for the inhibition. These results add information to the yet unresolved puzzle on how the risk factor of APOE ε4 functions in AD pathogenesis.

Retrospective validation of a β-trace protein interpretation algorithm for the diagnosis of cerebrospinal fluid leakage.

Cerebrospinal fluid (CSF) leakage is a rare condition that can potentially lead to the development of serious complications. In the last decade, β-trace protein (β-TP) has been shown to be a valuable immunological biomarker that allows prompt and non-invasive identification of CSF leakage. At our institution, the measurement of β-TP has been included in the diagnostic work-up of CSF leakage for more than 10 years. According to our diagnostic algorithm, the presence of CSF in secretion is excluded when β-TP values are <0.7 mg/L, whereas β-TP values ≥1.3 mg/L indicate the presence of CSF in secretion. β-TP values between 0.7 and 1.29 mg/L indicate the presence of CSF if the β-TP ratio (β-TP secretion/β-TP serum) is ≥2. This study aimed to validate this diagnostic algorithm using clinically defined nasal/ear secretions. We performed a retrospective statistical analysis of three β-TP interpretation strategies using data of 236 samples originating from 121 patients with suspect CSF leakage received at our laboratory between 2004 and 2012. The highest odds ratio was obtained when the proposed algorithm has been used for the interpretation of β-TP results, showing a sensitivity of 98.3% and a specificity of 96%. Positive and negative predictive values were 89.2% and 99.4%, respectively. Our data suggest that the proposed β-TP interpretation algorithm is a valuable tool for the diagnosis of CSF leakage in the clinical practice.

Primary ventriculoperitoneal shunting outcomes: a multicentre clinical audit for shunt infection and its risk factors.

To determine the frequency of primary ventriculoperitoneal shunt infection among patients treated at neurosurgical centres of the Hospital Authority and to identify underlying risk factors. This multicentre historical cohort study included consecutive patients who underwent primary ventriculoperitoneal shunting at a Hospital Authority neurosurgery centre from 1 January 2009 to 31 December 2011. The primary endpoint was shunt infection, defined as: (1) the presence of cerebrospinal fluid or shunt hardware culture that yielded the pathogenic micro-organism with associated compatible symptoms and signs of central nervous system infection or shunt malfunction; or (2) surgical incision site infection requiring shunt reinsertion (even in the absence of positive culture); or (3) intraperitoneal pseudocyst formation (even in the absence of positive culture). Secondary endpoints were shunt malfunction, defined as unsatisfactory cerebrospinal fluid drainage that required shunt reinsertion, and 30-day mortality. A primary ventriculoperitoneal shunt was inserted in 538 patients during the study period. The mean age of patients was 48 years (range, 13-88 years) with a male-to-female ratio of 1:1. Aneurysmal subarachnoid haemorrhage was the most common aetiology (n=169, 31%) followed by intracranial tumour (n=164, 30%), central nervous system infection (n=42, 8%), and traumatic brain injury (n=27, 5%). The mean operating time was 75 (standard deviation, 29) minutes. Shunt reinsertion and infection rates were 16% (n=87) and 7% (n=36), respectively. The most common cause for shunt reinsertion was malfunction followed by shunt infection. Independent predictors for shunt infection were: traumatic brain injury (adjusted odds ratio=6.2; 95% confidence interval, 2.3-16.8), emergency shunting (2.3; 1.0-5.1), and prophylactic vancomycin as the sole antibiotic (3.4; 1.1-11.0). The 30-day all-cause mortality was 6% and none were directly procedure-related. This is the first Hong Kong territory-wide review of infection in primary ventriculoperitoneal shunts. Although the ventriculoperitoneal shunt infection rate met international standards, there are areas of improvement such as vancomycin administration and the avoidance of scheduling the procedure as an emergency.

Uric Acid Amplifies Aβ Amyloid Effects Involved in the Cognitive Dysfunction/Dementia: Evidences From an Experimental Model In Vitro.

There is still a considerable debate concerning whether uric acid is neuroprotective or neurotoxic agent. To clarify this topic, we tested the effects of uric acid on neuronal cells biology by using differentiated SHSY5Y neuroblastoma cells incubated with amyloid β to reproduce an in vitro model of Alzheimer's disease. The incubation of cells with uric acid at the dose of 40 µM or higher significantly reduced cell viability and potentiated the proapoptotic effect of amyloid β. Finally, uric acid enhanced the generation of 4-hydroxynonenal and the expression of PPARβ/δ promoted by amyloid β, indicating a prooxidant effects. In conclusion, uric acid could exert a detrimental influence on neuronal biology being this influence further potentiated by the concomitant exposure to neurotoxic stimuli. This effect is evident for uric acid concentrations close to those achievable in cerebrospinal fluid in presence of mild hyperuricemia thus suggesting a potential role of uric acid in pathophysiology of cognitive dysfunction. These effects are influenced by the concentrations of uric acid and by the presence of favoring conditions that commonly occur in neurodegenerative disorders and well as in the aging brain, including increased oxidative stress and exposure to amyloid β. J. Cell. Physiol. 232: 1069-1078, 2017. © 2016 Wiley Periodicals, Inc.

Klotho: a humeral mediator in CSF and plasma that influences longevity and susceptibility to multiple complex disorders, including depression

Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan. The Klotho-deficient mouse dies prematurely at 8–9 weeks of age. At 4–5 weeks of age, a syndrome resembling human ageing emerges consisting of atherosclerosis, osteoporosis, cognitive disturbances and alterations of hippocampal architecture. Several deficits in Klotho-deficient mice are likely to contribute to these phenomena. These include an inability to defend against oxidative stress in the central nervous system and periphery, decreased capacity to generate nitric oxide to sustain normal endothelial reactivity, defective Klotho-related mediation of glycosylation and ion channel regulation, increased insulin/insulin-like growth factor signaling and a disturbed calcium and phosphate homeostasis accompanied by altered vitamin D levels and ectopic calcification. Identifying the mechanisms by which Klotho influences multiple important pathways is an emerging field in human biology that will contribute significantly to understanding basic physiologic processes and targets for the treatment of complex diseases. Because many of the phenomena seen in Klotho-deficient mice occur in depressive illness, major depression and bipolar disorder represent illnesses potentially associated with Klotho dysregulation. Klotho's presence in CSF, blood and urine should facilitate its study in clinical populations.

Sodium Bicarbonate Facilitates Hemostasis in the Presence of Cerebrospinal Fluid Through Amplification of Platelet Aggregation.

Appropriate hemostasis is essential for clear visualization of the neural structures and cleavage planes. It is also essential for avoiding heat-induced injury, minimizing blood loss, and reducing operative time. To determine the role of cerebrospinal fluid (CSF) in platelet-dependent hemostasis during neurosurgery. The amplification of aggregation, activation of integrin αIIbβ3, intrinsic and extrinsic coagulation pathways, and activation of signaling cascades in platelets were evaluated. For comparison, various concentrations of a commercially available artificial CSF solution (aCSF), an artificial CSF solution prepared by the authors, and normal saline (NS) were used. Differences between aCSF and NS in obtaining in vivo hemostasis were assessed by measuring the tail vein bleeding time in C57BL/6N mice. Platelet aggregation was directly amplified by the addition of aCSF through increased activation of integrin αIIbβ3, phosphatidylserine exposure, and P-selectin expression. However, the prothrombin time and activated partial thromboplastin time were not primarily related to coagulation activity with the addition of aCSF. Activation of Src kinase was related to platelet activation by aCSF. The elimination of sodium bicarbonate from aCSF and the addition of the selective inhibitor of the HCO3/Cl exchanger, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt, significantly inhibited platelet aggregation. The bleeding time in aCSF-treated mice was significantly shorter than that in NS-treated mice. Sodium bicarbonate facilitates hemostasis through the amplification of platelet aggregation function. The existence of CSF and irrigation with aCSF provide better conditions for physiological hemostasis and they have the potential of improving hemostasis by bipolar coagulation or with irrigation during neuroendoscopic procedures.

Autoantibodies Profile in Matching CSF and Serum from AD and aMCI patients: Potential Pathogenic Role and Link to Oxidative Damage.

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Amyloid-ß-peptide (Aß) forms senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles, are the hallmarks of AD neuropathology. Evidence support the involvement of immune system in AD progression and current concepts regarding its pathogenesis include the participation of inflammatory and autoimmune components in the neurodegenerative process. Pathologically, immune system components have been detected in the brain, cerebrospinal fluid (CSF) and in serum of AD subjects and their trend of variation correlates with disease progression. However, patients with AD present significantly lower levels of antibody immunoreactivity against Aß in serum and CSF than healthy controls suggesting that a depletion of such patrolling system is involved in the deposition of toxic aggregates in AD. Within this frame, incomplete and often controversial results are reported about CNS immune/ autoimmune responses during AD, and a better comprehension of such processes is needed. Our research will aim to shed light on the nature and potential role of autoantibodies in CSF and serum from AD and amnestic mild cognitive impairment (aMCI) patients compared to healthy subjects by using an immunoproteomics approach. Our method allows recognition of natural occurring antibodies by the identification of brain antigen targeted by human IgGs. Overall our data reveal that the alterations of autoantibodies profile both in CSF and serum follow disease staging and progression. However, we demonstrate a fair overlap between CSF and serum suggesting the existence of different immunogenic events. Interestingly, CSF autoantibodies recognized, among others, key players of energy metabolic pathway, including glycolysis and TCA cycle, found oxidatively modified in AD brain studies. These data suggest a potential casual sequence between oxidative damage at brain level, autoantibodies presence in CSF and reduced energy metabolism of AD patients.

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases.

SummaryHere, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600‐mutant metastatic melanoma for organ‐specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression.Based on this, we tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell death in response to both BRAF inhibitors. Effective cell killing was restored by co‐administration of a PI‐3 kinase inhibitor.We conclude that the efficacy of vemurafenib is variable in different organs with CNS being particularly prone to resistance. Extrinsic factors, such as ERK‐ and PI3K‐activating factors in CSF, may mediate BRAF inhibitor resistance in the CNS.

Monomeric ß-amyloid interacts with type-1 insulin-like growth factor receptors to provide energy supply to neurons.

ß-amyloid (Aß1−42) is produced by proteolytic cleavage of the transmembrane type-1 protein, amyloid precursor protein. Under pathological conditions, Aß1−42self-aggregates into oligomers, which cause synaptic dysfunction and neuronal loss, and are considered the culprit of Alzheimer's disease (AD). However, Aß1−42 is mainly monomeric at physiological concentrations, and the precise role of monomeric Aß1−42 in neuronal function is largely unknown. We report that the monomer of Aß1−42 activates type-1 insulin-like growth factor receptors and enhances glucose uptake in neurons and peripheral cells by promoting the translocation of the Glut3 glucose transporter from the cytosol to the plasma membrane. In neurons, activity-dependent glucose uptake was blunted after blocking endogenous Aß production, and re-established in the presence of cerebrospinal fluid Aß. APP-null neurons failed to enhance depolarization-stimulated glucose uptake unless exogenous monomeric Aß1−42 was added. These data suggest that Aß1−42 monomers were critical for maintaining neuronal glucose homeostasis. Accordingly, exogenous Aß1−42 monomers were able to rescue the low levels of glucose consumption observed in brain slices from AD mutant mice.

Percutaneous Minimally Invasive Treatment for the Trigeminal Neuralgia: A Review

Aim of review: The objective of this review is to evaluate the effect of percutaneous minimally invasive treatment for the trigeminal neuralgia (TN).Method: We systematically searched for clinical studies on the TN. We searched the MEDLINE (PubMed) and EMBASE database, using the free text terms: minimally invasive treatment, TN and combination of these. Date of last electronic search was 30 December 2012.Recent findings: From the available evidence, we can concluded that：1) Percutaneous glycerol gangliolysis is very effective and applicable to a wide variety of patients with TN. The presence of cerebrospinal fluid (CSF) outflow during puncture predicts better immediate and long-term outcomes; 2) It may be quite obvious that the high-speed real-time CT fluoroscopic method enables better imaging compared to X-ray fluoroscopy; 3) Computed tomography (CT) images are by far superior, when combined with neuronavigation, which allows trajectory visualization in three dimensions and multiple planes at the surgeon's choosing, and use of real-time annulations. Three dimensional (3D)-CT and electrophysiology Gasser's ganglion locations can raise the success rate of puncture, enhance the safety and reduce the incidence of complication, showing high academic value and its promising future; 4) Balloon Compression causes only a mild sensory loss with immediate pain relief in practically all patients; 5) Ultrasound-guided technique for the blockade of trigeminal nerve peripheral branches is very rational.Summary: For both treatment methods, the fused CT and magnetic resonance imaging (MRI) scans are used for improved treatment planning in the treatment for the TN. While the MRI scans provides better details on the anatomical situation, CT scans are required for dissymmetric assessment. In the future, other imaging methods like spectroscopy and evoked-potential imaging will become available to better shape the target volume and spare critical normal tissue structures. Citation: Xiang-Fei Guo, Jun Ma. Percutaneous minimally invasive treatment for the trigeminal neuralgia: a review. J Anesth Perioper Med 2015; 2: 167-74. doi: 10.24015/JAPM.2015.0023This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Combat-related intradural gunshot wound to the thoracic spine: significant improvement and neurologic recovery following bullet removal.

The vast majority of combat-related penetrating spinal injuries from gunshot wounds result in severe or complete neurological deficit. Treatment is based on neurological status, the presence of cerebrospinal fluid (CSF) fistulas, and local effects of any retained fragment(s). We present a case of a 46-year-old male who sustained a spinal gunshot injury from a 7.62-mm AK-47 round that became lodged within the subarachnoid space at T9-T10. He immediately suffered complete motor and sensory loss. By 24-48 hours post-injury, he had recovered lower extremity motor function fully but continued to have severe sensory loss (posterior cord syndrome). On post-injury day 2, he was evacuated from the combat theater and underwent a T9 laminectomy, extraction of the bullet, and dural laceration repair. At surgery, the traumatic durotomy was widened and the bullet, which was laying on the dorsal surface of the spinal cord, was removed. The dura was closed in a water-tight fashion and fibrin glue was applied. Postoperatively, the patient made a significant but incomplete neurological recovery. His stocking-pattern numbness and sub-umbilical searing dysthesia improved. The spinal canal was clear of the foreign body and he had no persistent CSF leak. Postoperative magnetic resonance imaging of the spine revealed contusion of the spinal cord at the T9 level. Early removal of an intra-canicular bullet in the setting of an incomplete spinal cord injury can lead to significant neurological recovery following even high-velocity and/or high-caliber gunshot wounds. However, this case does not speak to, and prior experience does not demonstrate, significant neurological benefit in the setting of a complete injury.

Exosomes in neurological disease, neuroprotection, repair and therapeutics: problems and perspectives.

Exosomes: Exosomes are a sub-population of micro-vesicles ranging from 40–100 nm that were earlier thought as artefacts under electron microscope. They recently came into attention for their storage of biological information, cell-to-cell communication, serving as biomarkers and potential use in neural protection and regeneration (Kalani et al., 2013, 2014a). Exosomes are secreted by different brain cells including neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells and their presence in cerebro-spinal fluid has also been confirmed. Exosomes represent cup-shaped morphology with a buoyant density of 1.13–1.19 g/cm2. They originate through the endocytic pathway after the fusion of multivesicular bodies (MVBs) with the plasma membrane and then release into the extracellular environment. Exosomes contain different proteins (membrane transport and fusion proteins, tetraspannins, heat-shock proteins, MVB biogenesis proteins), lipids, saccharides, and genetic materials (miRNA and other non-coding RNAs) which are collectively termed as ‘cargo’ contents (Kalani et al., 2014a). Recent findings suggest that exosomes contain unique molecular conservatories and therefore represent pathophysiological state of the cellular source from where they originate. On functional aspects, exosomes have been confirmed to perform roles as transporters, bridging the communication gap between cells and shuttling material from their cells of origin to the other distantly located cells. Because of their nano-size and non-complexed structure, exosomes efficiently cross blood-brain barrier (BBB) and therefore present novel ways to design therapeutic strategies against different cerebral diseases.

Insulin and IGF receptor signalling in neural-stem-cell homeostasis.

Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Similarly to other somatic stem cells, adult NSCs are found within specialized niches that are organized to facilitate NSC self-renewal. Alterations in stem-cell homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. Insulin and the insulin-like growth factors (IGFs) function in stem-cell homeostasis across species. Studies in the mammalian central nervous system support essential roles for IGF and/or insulin signalling in NSC self-renewal, neurogenesis, cognition and sensory function through distinct ligand-receptor interactions. IGF-II is of particular interest as a result of its production by the choroid plexus and presence in cerebrospinal fluid (CSF). CSF regulates and supports the development, division and migration of cells in the adult brain and is required for NSC maintenance. In this Review, we discuss emerging data on the functions of IGF-II and IGF and/or insulin receptor signalling in the context of NSC regulation in the SVZ and SGZ. We also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.

Unilateral massive transudative pleural effusion due to a duropleural fistula

Twenty three-year-old man had thoracal spinal cord surgery for gunshot injury three months ago. He had right hemiplegia and paraplegia for the past two months. He was admitted with poor performance status and progressive, severe dyspnea. Chest X-ray showed massive pleural effusion on the right side. Thoracentesis showed transudative pleural fluid. Duropleural fistula was considered due to the history of spinal injury and surgery. The presence of cerebrospinal fluid in the pleural fluid was demonstrated by beta-2 transferrin test. After the demonstration of the presence of duropleural fistula on intrathecal contrast-enhanced computed tomography scan surgical management of the duropleural fistula was successfully repaired by duroplasty. This case was presented as a complication of spinal cord injury and neurosurgery duropleural fistula is a very rare reason of massive transudative pleural effusions and the use of the cerebrospinal fluid by beta-2 transferrin in pleural effusion is reported very rare in the literature.

The natural course of clinically isolated syndrome in pediatric patients.

The first episode of central nervous system (CNS) symptoms with a presumed inflammatory demyelinating cause is defined as clinically isolated syndrome (CIS) according to the 2007 consensus of the International Pediatric Multiple Sclerosis Study Group, which developed diagnostic criteria for CNS demyelination disease in children. Using this definition of CIS, we attempted to identify the natural course of pediatric patients with CIS in a single Korean institution and to determine the factors affecting their prognosis. We retrospectively reviewed the medical records of all pediatric patients (age <18 years old) who presented with clinical symptoms of CNS events between 1997 and 2008. We identified 32 patients with CIS. Their mean age with standard deviation was 10.0±4.1 years. The most common type of presentation of CIS was optic neuritis (ON). Sixteen (16/32, 50%) patients experienced a second demyelinating event. The mean interval between the first event and the recurrent episode was 21±20 months. The mean follow-up was 6.1±1.6 years. Eleven (34%) patients developed childhood onset multiple sclerosis (MS). In contrast to previous studies, asymptomatic brain lesions on magnetic resonance imaging (MRI) and the presence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs) were not predictors of conversion to MS. In our study, a second relapse and initial presentation with brain stem, cerebellar, cerebral dysfunction, or multifocal CIS were strongly associated with the development of MS (p=0.002). Despite clinical definitions and increased understanding of CIS in children, challenges remain in predicting its progression to a chronic demyelinating disease.

Cystatin C in Cerebrospinal Fluid is Upregulated in Elderly Patients With Chronic Osteoarthritis Pain and Modulated Through Matrix Metalloproteinase 9–Specific Pathway

Although high abundant cystatin c (CysC) in cerebrospinal fluid (CSF) is well known, its ambiguous role associated with pain still remains unclear. This study evaluated the effects of intrathecal CysC content from chronic pain caused by osteoarthritis (OA) and the novel relationship with matrix metalloproteinases 2 and 9 (MMP2 and MMP9) in CSF. Samples of CSF were obtained from 8 elderly patients (65 y and above) with OA with lower limb pain for at least 6 months (OA group) and 8 sex-matched and age-matched relatively healthy elderly individuals without any pain problems (control group). The intrathecal CysC, MMP2, and MMP9 were examined by Western blotting. The analysis of CysC cleavage under different conditions was performed through silver staining and using mass-spectroscopy (SELDI-TOF) on 2 groups. Expression of full-length CysC and pro-MMP2 proteins showed statistically significant upregulation (P=0.0004 vs. 0.03), and expression of MMP9 protein showed downregulation (P=0.007) in the OA group. Both MMP9 and MMP2 initiated the mechanism for full-length CysC cleavage only in the presence of CSF. However, MMP9 showed greater ability than MMP2 for CysC cleavage in control and OA groups in sliver staining. Incubation of CSF with the MMP9 inhibitor led to the suppression of CysC cleavage in SELDI-TOF. These findings provide the first in vivo evidence on a relationship between CysC and gelatinases (MMP2 and MMP9), and could facilitate further investigation of novel interactions among these proteins within the proteomics field, especially protein-protein interactions involved in pain.

A Review of Non-Invasive Methods of Monitoring Intracranial Pressure

Intracranial p ressure (ICP) monitoring is an important aspect of neuro-medicine. ICP is the pressure created by the presence of cerebrospinal fluid. ICP monitoring techniques consist of invasive ( in vivo ) and non-invasive methods ( in vitro ). Modern research aims to eliminate invasive monitoring of ICP and promote non-invasive methods of monitoring ICP. This review aims to assess the current methods and research related to non-invasive monitoring of ICP. Invasive methods of monitoring ICP remain the most accurate methods of measuring ICP but are associated with many complications. This review discusses the current approaches, advantages and disadvantages of these approaches in ICP monitoring. A critical study of the literature review demonstrates that for accuracy and precision, an innovative non-invasive method for ICP monitoring is needed. There is more room for further research and development in ICP monitoring. A universal method of ICP monitoring is needed and not for a class or group of patients. J Neurol Res. 2014;4(1):1-6 doi: http://dx.doi.org/10.14740/jnr269w