-
Neurochemical Research 10/2011; · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has still not been clearly established whether the cognitive deficits of idiopathic normal pressure hydrocephalus (iNPH) are caused by a disturbance in cerebrospinal fluid (CSF) dynamics or an underlying metabolic disturbance.
To identify the possible associations between biochemical markers, the neuroimaging characteristics, and cognitive deficits of patients undergoing investigations for possible iNPH.
A CSF sample obtained during a lumbar puncture from 10 patients with iNPH was analyzed for several biochemical markers (lactate, 8-isoprostane, vascular endothelial growth factor [VEGF], neurofilament heavy protein, glial fibrillary acidic protein, amyloid beta 1-42, and total tau). All patients underwent a battery of neuropsychological testing and imaging as part of their selection process for their suitability for CSF diversion surgical procedure. Volumetric analysis of imaging was carried out measuring the ventricular volume (VV), intracranial volume (ICV), periventricular lucencies, deep white matter hyperintensities, and white matter (WM) volume, as well as their ratios.
A significant negative correlation of preoperative symptom duration and total tau levels (R = -0.841, P = .002) was found. There was a significant positive correlation (R = 0.648, P = .043) between the levels of VEGF and the VV/ICV ratio. There was a significant positive correlation of the levels of glial fibrillary acidic protein and the VV/deep white matter hyperintensities ratio (R = 0.828, P = .006). A significant negative correlation was observed between the levels of neurofilament heavy protein and the VV/ICV ratio (R = -0.657, P = .039) and the WM volume (R = -0.778, P = .023). Lactate levels were lower for patients performing in the normal range on the Recognition Memory Test for faces. Patients who performed better in the Recognition Memory Test words test had higher ICV volumes. All the patients in this study showed below normal performance when the subcortical function was assessed.
The positive correlation of VEGF with the severity of ventriculomegaly may indicate that this is because of the transmantle pressure gradient; this response may not be because of hypoxia but represents an attempt at neuroregeneration. The degree of reactive gliosis correlates inversely with the severity of WM lesions. Neuronal degeneration is negatively correlated with the volume of the WM in these patients. The small association of volumetry and the cognitive profile of these patients may be consistent with a direct biochemical disturbance being responsible for the cognitive deficit observed. Ongoing studies with set protocols for neuropsychological assessment and volumetric analysis are warranted to further elucidate on the preliminary results of the current study.
Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2011; 7(5):501-8. · 5.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values.
Neurochemical Research 03/2011; 36(3):528-32. · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The prognostic value of CSF biomarkers in patients with idiopathic normal pressure hydrocephalus (iNPH) has not been adequately studied to date. The aim of this study was to identify CSF markers of favorable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt.
Ventricular CSF was collected intraoperatively from 22 patients with iNPH and enzyme-linked immunosorbent assay was used to analyze the levels of amyloid-β 1-42 (Aβ(1-42)) and total tau protein. The Black grading scale was used to assess outcomes at 6 months. Receiver operating characteristic (ROC) curves were obtained and discriminant function analysis was undertaken to provide sensitivity and specificity figures for each marker as well as their combination.
The mean age of the patients was 71.45 years (± 9.5 years [SD]). Follow-up was achieved in 21 patients. Seventeen patients had a favorable outcome and 4 patients had unfavorable outcome at 6 months. An Aβ(1-42) level of 180 pg/ml had a sensitivity of 35% and a specificity of 20% for predicting a favorable outcome at 6 months. A total tau level of 767 pg/ml will have a sensitivity of 17% and a specificity of 20% for predicting a favorable outcome at 6 months. A combination of Aβ(1-42) and total tau levels predicted favorable outcomes with a sensitivity of 80% and specificity of 82.4%.
In this pilot study a combination of Aβ(1-42) levels and total tau protein levels predicted favorable surgical outcomes at 6 months with adequate accuracy to be of clinical use. Further study in a larger group with longer follow-up is warranted.
Journal of Neurosurgery 03/2011; 115(1):145-50. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: External lumbar drainage (ELD) is known as a good predictor of favourable outcome in shunting patients suffering from idiopathic normal pressure hydrocephalus (iNPH).
Eleven patients suffering from iNPH had a lumbar drain (LD) inserted for 72 h and participated in a research study to quantify any improvement in their clinical symptoms. The lumbar cerebrospinal fluid (CSF) levels of lactate, 8-isoprostane, vascular endothelial growth factor (VEGF), glial fibrillar acidic protein (GFAP), neurofilament (heavy chain) protein (NF (h)), Abeta(1-42) (beta-amyloid) and total tau were assayed samples from all three time points.
The concentrations of lactate, VEGF, GFAP and tau increased significantly during the 72 h of drainage. There were also increases in 8-isoprostane and Abeta(1-42) (non significant). The concentration of NF (h) was reduced significantly following 72 h of drainage. There was a significant positive correlation between Abeta(1-42) and total tau in the first sample. GFAP was negatively correlated in a significant fashion with both Abeta(1-42) and total tau. NF (h) was negatively correlated with VEGF.
Evidence is provided that ELD is producing measurable changes in the CSF composition of patients with iNPH. The present paper discusses how such changes may be implicated in the pathophysiology of the condition.
Journal of neurology, neurosurgery, and psychiatry 07/2009; 80(10):1130-3. · 4.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Three paired serial samples of CSF and serum (from days 8, 13 and 22) were taken from a patient referred to the National Hospital for Neurology and Neurosurgery with what was duly confirmed as having herpes simplex encephalitis using PCR. The samples were investigated using affinity-mediated immunoblotting followed by incubation with sodium thiocyanate. Digitisation of the blots enabled further analysis. We showed that the clones of antigen-specific IgG, which were produced intrathecally, were of higher relative affinity than polyclonal antigen-specific IgG.
Journal of Neuroimmunology 05/2007; 185(1-2):130-5. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Affinity maturation has previously been shown with assays for total IgG for specific antigens using the technique of competition by chaotropic ions. We have extended this technique to individual clones and followed the maturation of clones during the course of herpes encephalitis. This has important implications for our understanding of the pathogenesis of multiple sclerosis.
Journal of Neuroimmunology 12/2006; 180(1-2):29-32. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We describe a semi-quantitative method for measuring the relative affinity of antigen-specific oligoclonal IgG bands separated by isoelectric focusing followed by blotting onto antigen-coated membrane and incubation with sodium thiocyanate. When the developed blot is digitised in greyscale, densitograms can be made and peak areas calculated using ImageJ freeware. By expressing peak area as a percentage of the total area under the curve we have shown that there is a statistically significant rise in percentage of peak area for a given band which persists with increasing molarities of sodium thiocyanate.
Journal of Immunological Methods 04/2006; 310(1-2):62-6. · 2.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The production of oligoclonal, polyspecific immunoglobulin G is characteristic of multiple sclerosis (MS), yet no pathogen has been identified as an infectious agent. Recent studies have proposed Acinetobactercalcoaceticus and Pseudomonas aeruginosa as candidate organisms, on the basis of a sequence homology between a bacterial enzyme and bovine myelin basic protein. To investigate this, we looked for specific, high-affinity immunoglobulin G against these pathogensin paired serum and cerebrospinal fluid from MS patients compared to other neurological diseases. We found no greater incidence of high-affinity antibodies against the organisms studied in MS vs. other neurological diseases, and so conclude that A. calcoaceticus and P. aeruginosa are unlikely to be implicated in the pathogenesis of MS.
European Neurology 02/2005; 53(1):27-31. · 1.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous investigations have suggested that Sydenham's chorea (SC) may be an autoantibody mediated disorder. We examined this autoimmune hypothesis by measuring Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-10) cytokines, oligoclonal bands (OCB) and anti-basal ganglia antibodies (ABGA). CSF IL-4 was elevated in 31% of acute SC and 50% of persistent SC. CSF IL-10 was also elevated in 31% of acute SC but 0% of persistent SC. CSF IFN-gamma was undetectable in all patients. Serums IL-4, IL-10 and IL-12 were elevated in acute compared to persistent SC. OCB were found in 46% of acute SC, ABGA were in 93% of acute SC and 50% of persistent SC was of IgG(1) and IgG(3) subclass. These findings support an autoantibody pathogenesis.
Journal of Neuroimmunology 04/2003; 136(1-2):149-53. · 2.96 Impact Factor
