http://www.cerebrospinalfluidresearch.com The latest research articles published by Cerebrospinal Fluid Research 2009-07-02T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Cerebrospinal fluid (CSF)/serum quotient graphs have been used previously to determine local synthesis in brain of immunoglobulins and C3 complement component. The aim of this study was to use the same technique to construct quotient graphs, or Reibergrams, for the beta globulin C 4 and to evaluate the method for assessing intrathecal synthesis in neurological disease. Methods: The constants in the previously-defined Reibergram for immunoglobulin IgA were used to calculate the CSF/serum quotient for C 4. CSF and serum were analyzed for C 4, IgA and albumin from a total of 12 patients with meningoencephalitis caused by encapsulated microorganisms and 10 subjects without infections or inflammatory neurological disease, some of which had dysfunction of the blood-CSF barrier, Results: The formula and C 4 Reibergram with the constants previously found for IgA, determined the intrathecal C 4 synthesis in CSF. The intrathecal C 4 fraction in CSF (C 4 loc in mg/l) was compared to the C 4-Index (fraction of CSF: serum for C 4 / fraction of CSF: serum for albumin). There was a significant correlation between the two formulae. The CSF/Serum quotient graph was superior for detecting intrathecal synthesis of C 4 under variable conditions of blood-CSF barrier permeability. Conclusions: The C 4 Reibergram can be used to quantify the intrathecal synthesis of this component of the complement system in different infectious diseases of the central nervous system and is especially useful for patients with blood-brain barrier dysfunction. http://www.cerebrospinalfluidresearch.com/content/6/1/8 Barbara Padilla-Docal Alberto Dorta-Contreras Raisa Bu-Coifiu-Fanego Alexis Rodriguez-Rey Cerebrospinal Fluid Research 2009, 6:8 2009-07-02T00:00:00Z doi:10.1186/1743-8454-6-8 Cerebrospinal Fluid Research 1743-8454 6 8 2009-07-02T00:00:00Z PDF Background: Treatment modalities in Chiari malformation type 1(CMI) accompanied by syringomyelia have not yet been standardized. Pathologies like a small posterior fossa and thickened dura mater have already been discussed. Various techniques have been explored to enlarge foramen magnum and to expand the dura. The aim of this clinical study was to explore a new technique of excision of the external dura accompanied by widening the cisterna magna and making longitudinal incisions in the internal dura without disturbing the arachnoid. Methods: A prospective series of 10 cases with CMI and syringomyelia, operated between 2004 and 2006 were included in this study. All cases underwent foramen magnum decompression of 3x3 cm area with C1-C2 (partial) laminectomy, resection of foramen magnum fibrous band, excision of external dura, delamination and widening of internal dura with longitudinal incisions. Results: Patients were aged between 25 and 58 years and occipital headache was the most common complaint. The mean duration of preoperative symptoms was 4 years and the mean follow-up time was 25 months. Clinical progression was halted for all patients; eight patients completely recovered and two reported no change. In one patient, there was a transient CSF fistula that was treated with tissue adhesive. While syringomyelia persisted radiologically with radiological stability in five patients; for three patients the syringomyelic cavity decreased in size, and for the remaining two it regressed completely. Conclusion: Removal of the fibrous band and the outer dural layer, at level of foramen magnum, together with the incision of inner dural layer seems to be good technique in adult CMI patients. Advantages are short operation time, no need for duraplasty, sufficient posterior fossa decompression, absence of CSF fistulas as a result of extraarachnoidal working, and short duration of hospitalization. Hence this surgical technique has advantages compared to other techniques. http://www.cerebrospinalfluidresearch.com/content/6/1/7 Kadir Kotil Rabia Tari Tugrul Ton Yildiray Savas Cerebrospinal Fluid Research 2009, 6:7 2009-06-22T00:00:00Z doi:10.1186/1743-8454-6-7 Cerebrospinal Fluid Research 1743-8454 6 7 2009-06-22T00:00:00Z PDF Background: Children with the severe form of spina bifida (SBM: spina bifida with myelomeningocele with accompanying hydrocephalus) may manifest attention deficits, and have a similar psychological profile to children with hydrocephalus due to other etiologies. It is unclear to what extent tests to assess attention in SBM are confounded by the accompanying cognitive or visual-motor impairments. The aim of this study was to analyse attention functions by administering two different types of attention tests, one with high and the other with low cognitive and motor requirements. This enabled the possible interaction between attention and cognitive and motor impairment to be assessed. Methods: The study group comprised 31 children with SBM with shunted hydrocephalus. Twenty children with SB-only formed a closely matched comparison group. Of these, 19 children with SBM and 18 with SB had a full-scale IQ (FSIQ) higher than 70. All had undergone spinal surgery and all children with SBM had been shunted within the first months of life. Between 6 and 15 years of age, the children were assessed on focused and sustained attention, encoding, and distractibility/impulsivity, using both traditional tests and computerized attention tests. Results: Compared to the SB group, attention scores of children with SBM were lower on the traditional tests, but when interfering cognitive and visual-motor requirements were eliminated using the computerised tasks, most differences disappeared. Furthermore, in contrast to traditional attention tasks, computerized tests showed no significant correlations with IQ-scores and visual-motor skills. Conclusion: Assessment of attention functions in children with SBM by traditional tests may be misleading, because this paediatric population with complex cerebral malformations has difficulty with the cognitive and visual-motor requirements. To control for these interactions, the use of both traditional and computerized attention tests is recommended. http://www.cerebrospinalfluidresearch.com/content/6/1/6 Anja Vinck Reinier Mullaart Jan Rotteveel Ben Maassen Cerebrospinal Fluid Research 2009, 6:6 2009-05-28T00:00:00Z doi:10.1186/1743-8454-6-6 Cerebrospinal Fluid Research 1743-8454 6 6 2009-05-28T00:00:00Z XML Background: Radioisotope (RI) cisternography is considered to be the most important examination for the final diagnosis of intracranial hypotension, typically indicating cerebrospinal fluid (CSF) leakage as RI parathecal activity. Early bladder filling (EBF) of RI is another important finding. However, whether EBF without parathecal activity represents real CSF leakage due to intracranial hypotension or only an epiphenomenon of lumbar puncture causing CSF leak through a needle hole has been questioned. Methods: To address this issue, we performed quantitative analysis of RI cisternography on 171 patients with suspected intracranial hypotension using different needle sizes (22 G, 23 G and 25 G) and compared RI residual activity in the CSF at different time points after injection. We also analyzed occurrence of early bladder filling and post-lumbar puncture headache. Results: No significant difference in RI residual activity was identified between the 22 G, 23 G and 25 G groups. The incidence of parathecal activity and early bladder filling was not significantly different between groups. The 22 G and 23 G groups had a higher but non-significant incidence of post lumbar headache. Conclusion: The results suggest that needle size, at least for 22–25 G, does not affect the results of RI cisternographic diagnostic tests for CSF leakage and bladder filling in intracranial hypotension. http://www.cerebrospinalfluidresearch.com/content/6/1/5 Koichi Takahashi Tatsuo Mima Cerebrospinal Fluid Research 2009, 6:5 2009-05-27T00:00:00Z doi:10.1186/1743-8454-6-5 Cerebrospinal Fluid Research 1743-8454 6 5 2009-05-27T00:00:00Z XML Background: Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus. Methods: Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP. Results: When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP. Conclusion: Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals. http://www.cerebrospinalfluidresearch.com/content/6/1/4 Kelley Deren Jennifer Forsyth Osama Abdullah Edward Hsu Petra Klinge Gerald Silverberg Conrad Johanson James McAllister Cerebrospinal Fluid Research 2009, 6:4 2009-05-26T00:00:00Z doi:10.1186/1743-8454-6-4 Cerebrospinal Fluid Research 1743-8454 6 4 2009-05-26T00:00:00Z XML Background: It has been shown that distal cerebrospinal fluid-contacting neurons (dCSF-CNs) exist near the ventral midline of the midbrain aqueduct and also in the grey matter of the inferior third ventricle and the fourth ventricle floor in the superior segment of the pons. The dCSF-CNs communicate between the cerebrospinal fluid (CSF) and the brain parenchyma and may participate in the transduction and regulation of pain signals. The cold sensation receptor channel, TRPM8 is involved in analgesia for neuropathic pain, but whether the TRPM8 receptor exists on dCSF-CNs remains unknown. However, there is preliminary evidence that TRPM8 is expressed in dCSF-CNs and may participate in the transmission and regulation of sensory information between brain parenchyma and cerebrospinal fluid (CSF) in rats. Methods: Retrograde tracing of the cholera toxin subunit B labeled with horseradish peroxidase (CB-HRP) injected into the lateral ventricle was used to identify dCSF-CNs. A double-labeled immunofluorescent technique and laser scanning confocal microscopy were used to identify the expression of TRPM8 in dCSF-CNs. Software Image-Pro Plus was used to count the number of neurons in three sections where CB-HRP positive neurons were located in the mesencephalon of six rats. Results: The cell bodies of CB-HRP-positive dCSF-CNs were found in the brain parenchyma near the midline of the ventral Aq, also in the grey of the 3V, and the 4V floor in the superior segment of the pons. In the mesencephalon their processes extended into the CSF. TRPM8 labeled neurons were also found in the same area as were CB-HRP/TRPM8 double-labeled neurons. CB-HRP/TRPM8 double-labeled neurons were found in 42.9 ± 2.3% of neurons labeled by TRPM8, and all CB-HRP-labeled neurons were also labeled with TPRM8. Conclusion: This study has demonstrated that the cold sensation receptor channel, TRPM8, is localised within the dCSF-CNs of the mesencephalon. TRPM8 acts as receptor of dCSF-CNs for sensation transmission and pain regulation. http://www.cerebrospinalfluidresearch.com/content/6/1/3 Jing Du Xinwei Yang Licai Zhang Yinming Zeng Cerebrospinal Fluid Research 2009, 6:3 2009-03-17T00:00:00Z doi:10.1186/1743-8454-6-3 Cerebrospinal Fluid Research 1743-8454 6 3 2009-03-17T00:00:00Z XML Background: Toxoplasmic encephalitis (TE) is one of the most common opportunistic infections in immunocompromised patients. In Cuba, despite the highly active antiretroviral therapy, TE is still the most important cause of cerebral mass lesions in patients infected with the human immunodeficiency virus (HIV). The detection of Toxoplasma gondii by PCR may facilitate the diagnosis and follow-up of TE in acquired immunodeficiency syndrome (AIDS) patients by direct identification of parasite DNA in clinical samples. The aim of the present study was to evaluate a rapid PCR method using the B1 gene to detect T. gondii in cerebrospinal fluid (CSF) samples from patients with suspected TE. Methods: CSF samples from AIDS and HIV-negative patients were analyzed. Patients were divided into two groups according to the Centre for Disease Control and Prevention (CDC) criteria for AIDS-related TE: AIDS patients with suspected neurotoxoplasmosis and AIDS and HIV-negative patients with other confirmed neurological diseases but no suspicions of TE. Predictive values, diagnostic accuracy, sensitivity and specificity of the PCR B1 method were calculated. Results: The results obtained from 190 patients showed that this assay has a good sensitivity and specificity (83.3% and 95.7%, respectively) for the diagnosis of TE in AIDS patients. Conclusion: PCR using the B1 gene and B22/B23 set of primers is a single, rapid and reliable method that may be valuable for discrimination between toxoplasmosis and other central nervous system (CNS) diseases. http://www.cerebrospinalfluidresearch.com/content/6/1/2 Yenisey Alfonso Jorge Fraga Carlos Fonseca Narciso Jimenez Taimy Pinillos Alberto Dorta-Contreras Raymundo Cox Virginia Capo Olga Pomier Francisco Bandera Dora Ginorio Cerebrospinal Fluid Research 2009, 6:2 2009-03-06T00:00:00Z doi:10.1186/1743-8454-6-2 Cerebrospinal Fluid Research 1743-8454 6 2 2009-03-06T00:00:00Z XML Posthaemorrhagic hydrocephalus (PHH) is a major problem for premature infants, generally requiring lifelong care. It results from small blood clots inducing scarring within CSF channels impeding CSF circulation. Transforming growth factor – beta is released into CSF and cytokines stimulate deposition of extracellular matrix proteins which potentially obstruct CSF pathways. Prolonged raised pressures and free radical damage incur poor neurodevelopmental outcomes. The most common treatment involves permanent ventricular shunting with all its risks and consequences.This is a review of the current evidence for the treatment and prevention of PHH and shunt dependency. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) and PubMed (from 1966 to August 2008) were searched. Trials using random or quasi-random patient allocation for any intervention were considered in infants less than 12 months old with PHH. Thirteen trials were identified although speculative interventions were also evaluated.The literature confirms that lumbar punctures, diuretic drugs and intraventricular fibrinolytic therapy can have significant adverse effects and fail to prevent shunt dependence, death or disability. There is no evidence that postnatal phenobarbital administration prevents intraventricular haemorrhage (IVH). Subcutaneous reservoirs and external drains have not been tested in randomized controlled trials, but can be useful as a temporising measure. Drainage, irrigation and fibrinolytic therapy as a way of removing blood to inhibit progressive deposition of matrix proteins, permanent hydrocephalus and shunt dependency, are invasive and experimental. Studies of ventriculo-subgaleal shunts show potential as a temporary method of CSF diversion, but have high infection rates.At present no clinical intervention has been shown to reduce shunt surgery in these infants. A ventricular shunt is not advisable in the early phase after PHH. Evidence exists that pre-delivery corticosteroid therapy reduces mortality and IVH and there may be trends towards reduced disability in the short term. There is also evidence that postnatal indomethacin reduces IVH but with no effect on mortality or disability. Overall, there is still no definitive algorithm for the treatment of PHH or prevention of shunt dependence. New therapeutic approaches in neonatal care, including those aimed at pre-empting PHH, offer the best hope of improving neurodevelopmental outcomes. http://www.cerebrospinalfluidresearch.com/content/6/1/1 David Shooman Howard Portess Owen Sparrow Cerebrospinal Fluid Research 2009, 6:1 2009-01-30T00:00:00Z doi:10.1186/1743-8454-6-1 Cerebrospinal Fluid Research 1743-8454 6 1 2009-01-30T00:00:00Z XML Background: In human neonatal high pressure hydrocephalus (HPHC), diffuse white matter injury and gliosis predispose to poor neuro-developmental outcome. The underlying mechanism for diffuse white matter damage in neonatal HPHC is still unclear. Analogous to inflammatory white matter damage after neonatal hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be involved in neonatal HPHC. If so, early anti-inflammatory therapy could ameliorate white matter damage in HPHC, before irreversible apoptosis has occurred. In HPHC and control neonates, we therefore aimed to compare cerebrospinal fluid (CSF) concentrations of IL18, IFNγ and sFasL (interleukin 18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively). Methods: In neonatal HPHC (n = 30) and controls (n = 15), we compared CSF concentrations of IL18, IFNγ and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20), aqueduct stenosis (n = 4), and fetal intra-cerebral haemorrhage (n = 6). Neonatal control CSF was derived from otherwise healthy neonates (n = 15), who underwent lumbar puncture for exclusion of meningitis. Results: In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNγ concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values. Conclusion: Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNγ) in the CSF, whereas CSF apoptosis biomarkers (sFasL) were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting) could be helpful to preserve cerebral white matter. http://www.cerebrospinalfluidresearch.com/content/5/1/21 Deborah Sival Ursula Felderhoff-Muser Thomas Schmitz Eelco Hoving Carlo Schaller Axel Heep Cerebrospinal Fluid Research 2008, 5:21 2008-12-31T00:00:00Z doi:10.1186/1743-8454-5-21 Cerebrospinal Fluid Research 1743-8454 5 21 2008-12-31T00:00:00Z XML Background: Although fibroblast growth factor (Fgf) signalling plays crucial roles in several developing and mature tissues, little information is currently available on expression of Fgf2 during early choroid plexus development and whether Fgf2 directly affects the behaviour of the choroid plexus epithelium (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent and human developing CPe and possible function of Fgf2, using in vitro models. The application of Fgf2 to brain in vivo can affect the whole tissue, making it difficult to assess specific responses of the CPe. Methods: Expression of Fgf2 was studied by immunohistochemistry in rodent and human embryonic choroid plexus. Effects of Fgf2 on growth, secretion, aggregation and gene expression was investigated using rodent CPe vesicles, a three-dimensional polarized culture model that closely mimics CPe properties in vivo, and rodent CPe monolayer cultures. Results: Fgf2 was present early in development of the choroid plexus both in mouse and human, suggesting the importance of this ligand in Fgf signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression and cell proliferation during CP development suggests that Fgf2 is not involved in CPe proliferation in vivo. Consistent with this observation is the failure of Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is significantly increased by treatment with this growth factor. We show that this is due to an increase in cell aggregation during vesicle formation rather than increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of the CPe-associated transcription factors, Foxj1 and E2f5, whereas transthyretin, a marker of secretory activity, is not affected by Fgf2 treatment. Conclusion: Fgf2 expression early in the development of both human and rodent choroid plexus, and its ability to modulate behaviour and gene expression in CPe, supports the view that Fgf signalling plays a role in the maintenance of integrity and function of this specialized epithelium, and that this role is conserved between rodents and humans. http://www.cerebrospinalfluidresearch.com/content/5/1/20 Sarah Greenwood Adam Swetloff Angela Wade Tetsuya Terasaki Patrizia Ferretti Cerebrospinal Fluid Research 2008, 5:20 2008-12-29T00:00:00Z doi:10.1186/1743-8454-5-20 Cerebrospinal Fluid Research 1743-8454 5 20 2008-12-29T00:00:00Z XML