Variation of barrier permeability for albumin and immunoglobulin G influx into cerebrospinal fluid.

BACKGROUND: The aim of the present study was to analyze variations in permeability of albumin and immunoglobulin G (IgG) influx into cerebrospinal fluid (CSF) in a clinical setting. METHODS: In a retrospective intra-individual comparison of CSF samples, we used the IgGIndex and its constituents to indicate alterations in IgG/albumin permeability. RESULTS: We found altered IgGIndices in 25/64 patients (range -25% to +44%), with differently altered QAlb and QIgG values (-69% to +549%), unaltered IgG-Indices in a further 25/64 patients with equally altered QAlb and QIgG values (-46% to +107%), and no parameter alteration in 14/64 patients. Parameter alterations in 25/64 patients indicated that permeability of albumin was changed to different extents than for IgG. It changed in the same direction in 20/25 patients, and the opposite in five patients. In further 25/64 patients, equal QAlb and QIgG alterations indicated equally altered permeabilities and/or altered efflux of the proteins. In 14/64 patients, no alteration in permeability or efflux was seen. CONCLUSIONS: Results revealed surprisingly variable intra-individual changes in permeabilities for albumin and IgG in pathologic as well as normal CSF. Differing changes in permeability indicate that the diffusion paths of the two proteins may react to disturbances independently of each other. The details of the influx permeability for albumin and IgG into CSF illustrate the prospect of a more comprehensive insight into the protein exchange between blood and CSF.

Increased prevalence of microangiopathic brain lesions among siblings of patients with lacunar stroke. A prospective multicenter study.

BACKGROUND: Family and twin studies suggest predisposing genetic factors in stroke. Lacunar infarcts represent a homogeneous phenotype, which is a prerequisite for genetic analyses. Applying an affected sib -pair analysis, we prospectively assessed the prevalence of microangiopathic brain lesions (MBL) and associated risk factors among siblings of patients with lacunar stroke. METHODS: Index patients fulfilled clinical criteria of a lacunar stroke in combination with a corresponding MBL on CT or MRI. Siblings were characterized as affected if MBL demonstrated on MRI. The prevalence of MBL was compared with population prevalence data extracted from other studies. RESULTS: From 784 patients screened, 81 index patients with lacunar stroke and 97 siblings were recruited, of which 42% were identified as affected. Compared with data from unselected historical controls and stratified by age groups, prevalence was between 2 and 5 times higher. CONCLUSIONS: Our results indicate that genetic stroke studies are feasible even in subtypes of ischemic stroke. The high prevalence of MBL among siblings of patients with lacunar infarct might suggest a familial aggregation. However, due to the small sample size these results need to be interpreted with caution and require confirmation by planned genetic analyses.

What determines the CSF concentrations of albumin and plasma-derived IgG?

OBJECTIVES: To estimate the mean influence of the main determinants of the cerebrospinal fluid (CSF) concentration of albumin and plasma-derived immunoglobulin G (IgG). METHODS: Correlations of serum and CSF concentrations of albumin and IgG and assumptions of the mode of action of the determinants (plasma concentration, barrier permeability, and CSF flow) are used to quantify the determinants' influences in a sample of 1700 patients. RESULTS: We estimated in patients with normal CSF albumin that the serum concentrations of albumin and IgG explained 3.3% and 23% of the variation of the respective CSF concentrations, whereas the barrier permeability accounted for 41.9% and 22.2%, and CSF flow for 54.8%. In patients with pathologic CSF albumin concentration, the serum concentrations were estimated to explain 0.2% and 8.2% of the variation of the respective CSF concentrations, the barrier permeability 19.7% and 11.7%, and CSF flow 80.1%. CONCLUSIONS: CSF flow had the strongest mean influence, especially at elevated CSF albumin levels. The serum concentrations and barrier permeabilities of albumin and IgG influenced the respective CSF concentrations quite differently, which should be due to the different physicochemical properties of the two molecules. Mean influences from large patient samples, as explored here, can give only an overview. Understanding the determinants in individuals will need further specific measurements, especially of CSF flow.

Determinants of lumbar CSF protein concentration.

OBJECTIVE: To determine factors influencing the wide variation of protein concentration in lumbar cerebrospinal fluid (CSF). METHODS: Patient variables with potential influence on spinal CSF flow and resorption were measured in different patient settings and compared with albumin and IgG CSF/serum quotients. RESULTS: In patients whose diagnostic lumbar puncture produces normal CSF the albumin quotient increased with body mass index (r = 0.408), abdominal circumference (r = 0.399), and body weight (r = 0.317), age-corrected with partial correlation. Body motion before lumbar puncture showed only marginal influence on albumin quotient. In patients with radiculography the albumin quotient decreased with iodine contrast medium elimination from spinal subarachnoid space (r = -0.598) and increased with narrowing of lumbosacral spinal canal (r = 0.515). CONCLUSION: Correlation of albumin quotient with body mass index and related variables may be mediated by spinal CSF resorption, which should be impaired in overweight patients with elevated venous pressure. Negative correlation of albumin quotient with iodine resorption from spinal CSF supports this assumption. Correlation of albumin quotient with narrowing of lumbosacral canal should be due to slowed spinal CSF flow which does increase protein concentration. Tested variables explain part of variation of CSF protein concentration. Other variables like blood-CSF barrier permeability and pulsatile spinal CSF flow should have additional influence.