Skip to main content

Advertisement

Log in

Isolated blood–cerebrospinal fluid barrier dysfunction: prevalence and associated diseases

  • ORIGINAL COMMUNICATION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Objective

An isolated dysfunction of the blood–CSF barrier is characterised by an abnormal elevation of the albumin CSF/serum concentration ratio (Qalb) without any other pathological CSF findings. Although common in routine CSF analysis, the clinical significance of an isolated barrier dysfunction frequently remains unclear. We examined neurological disorders associated with an isolated elevation of Qalb to identify possible determinants of blood–CSF barrier dysfunction.

Methods

367 patients (124 women, 243 men, median age 60. 0 years) out of 3873 patients receiving diagnostic lumbar puncture at the University Hospital of Ulm (Germany) showed an isolated dysfunction of the blood–CSF barrier. Clinical data as well as MRI findings of these patients were analysed.

Results

Isolated barrier dysfunction occurred most frequently (> 30%) in Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), normal pressure hydrocephalus (NPH), lumbar spinal stenosis, and polyneuropathy (PNP). In patients who showed no other evidence of neurological disease, isolated barrier dysfunction was found in 14. 9% of cases. The extent of barrier dysfunction was most prominent in brain tumours, GBS, and CIDP. There was a significant correlation of Qalb with both weight and body mass index (BMI).

Conclusions

Although isolated barrier dysfunction may be found in a variety of neurological diseases, it is especially frequent in GBS, CIDP, NPH, spinal canal stenosis, and PNP. In these patients, disease–related mechanisms contributing to barrier dysfunction are likely. Moreover, barrier function seems to be influenced by disease–independent determinants like weight and BMI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alafuzoff I, Adolfsson R, Bucht G, Winblad B (1983) Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia. J Neurol Sci 60:465–472

    Article  PubMed  Google Scholar 

  2. Baethmann A (1990) Pathophysiology of acute brain damage following epilepsy. Acta Neurochir (Suppl) 50:14–18

    Google Scholar 

  3. Chandra V, Bellur SN, Anderson RJ (1986) Low CSF protein concentration in idiopathic pseudotumor cerebri. Ann Neurol 19:80–82

    Article  PubMed  Google Scholar 

  4. Felgenhauer K, Schliep G, Rapic N (1976) Evaluation of the blood-CSF barrier by protein gradients and the humoral immune response within the central nervous system. J Neurol Sci 30:113–128

    Article  PubMed  Google Scholar 

  5. Folstein MF, Robins LN, Helzer JE (1983) The Mini-Mental State Examination. Arch Gen Psychiatry 40:812

    PubMed  Google Scholar 

  6. Fuchs A, Rosenthal R (1904) Physikalisch-chemische, zytologische und anderweitige Untersuchungen der Cerebrospinalflüssigkeit. Wien Med Presse 45:2081–2087

    Google Scholar 

  7. Garton MJ, Keir G, Lakshmi VM, Thompson EJ (1991) Age-related changes in cerebrospinal fluid protein concentrations. J Neurol Sci 104:74–80

    Article  PubMed  Google Scholar 

  8. Hampel H, Muller-Spahn F, Berger C, Haberl A, Ackenheil M, Hock C (1995) Evidence of blood-cerebrospinal fluidbarrier impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation. Dementia 6:348–354

    PubMed  Google Scholar 

  9. Hogan QH, Prost R, Kulier A, Taylor ML, Liu S, Mark L (1996) Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and abdominal pressure. Anesthesiology 84:1341–1349

    Article  PubMed  Google Scholar 

  10. Hornig CR, Busse O, DorndorfW, Kaps M (1983) Changes in CSF blood-brain barrier parameters in ischaemic cerebral infarction. J Neurol 229:11–16

    Article  PubMed  Google Scholar 

  11. Johnson G, Brane D, van Kammen DP, Gurklis J, Peters JL, Perel JM, Ghanbari HA, Merril CR (1992) Haloperidol induced CSF protein variations in schizophrenic patients: as studied by two-dimensional electrophoresis. Appl Theor Electrophor 3:21–26

    PubMed  Google Scholar 

  12. Keir G, Luxton RW, Thompson EJ (1990) Isoelectric focusing of cerebrospinal fluid immunoglobulin G: an annotated update. Ann Clin Biochem 27:436–443

    PubMed  Google Scholar 

  13. Kirch DG, Alexander RC, Suddath RL, Papadopoulos NM, Kaufmann CA, Daniel DG, Wyatt RG (1992) Blood- CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia. J Neural Transm Gen Sect 89:219–232

    Article  PubMed  Google Scholar 

  14. Leonardi A, Abbruzzese G, Arata L, Cocito L, Vische M (1984) Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis. J Neurol 231:75–78

    Article  PubMed  Google Scholar 

  15. May C, Kaye JA, Atack JR, Schapiro MB, Friedland RP, Rapoport SI (1990) Cerebrospinal fluid production is reduced in healthy aging. Neurology 40:500–503

    PubMed  Google Scholar 

  16. Muller N, Ackenheil M (1995) Immunoglobulin and albumin content of cerebrospinal fluid in schizophrenic patients: relationship to negative symptomatology. Schizophr Res 14:223–228

    Article  PubMed  Google Scholar 

  17. Olsson Y (1971) Studies on vascular permeability in peripheral nerves. Acta Neuropath (Berl) 17:114–126

    Article  PubMed  Google Scholar 

  18. Rao ML, Boker DK (1987) Cerebrospinal fluid and serum levels of albumin, IgG, IgA and IgM in patients with intracranial tumors and lumbar disc herniation. Eur Neurol 26:241–245

    PubMed  Google Scholar 

  19. Reiber H (1995) External quality assessment in clinical neurochemistry: survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/ serum quotients. Clin Chem 41: 256–263

    PubMed  Google Scholar 

  20. Reiber H, Otto M, Trendelenburg C, Wormek A (2001) Reporting cerebrospinal fluid data: knowledge base and interpretation software. Clin Chem Lab Med 39:324–332

    Article  PubMed  Google Scholar 

  21. Rosenberg GA (1999) Ischemic brain edema. Prog Cardiovasc Dis 42: 209–216

    PubMed  Google Scholar 

  22. Segurado OG, Kruger H, Mertens HG (1986) Clinical significance of serum and CSF findings in the Guillain-Barré syndrome and related disorders. J Neurol 233:202–208

    Article  PubMed  Google Scholar 

  23. Seyfert S, Kunzmann V, Schwertfeger N, Koch HC, Faulstich A (2002) Determinants of lumbar CSF protein concentration. J Neurol 249:1021–1026

    Article  PubMed  Google Scholar 

  24. Silverberg GD, Mayo M, Saul T, Rubenstein E, McGuire D (2003) Alzheimer’s disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis. Lancet Neurol 2:506–511

    Article  PubMed  Google Scholar 

  25. Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I, Gottfries CG, Blennow K (1998) A population study on blood-brain barrier function in 85- year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology 50:966–971

    PubMed  Google Scholar 

  26. Skouen JS, Larsen JL, Vollset SE (1993) Cerebrospinal fluid proteins as indicators of nerve root compression in patients with sciatica caused by disc herniation. Spine 18:72–79

    PubMed  Google Scholar 

  27. Sugerman HJ, DeMaria EJ, Felton WL, III, Nakatsuka M, Sismanis A (1997) Increased intra-abdominal pressure and cardiac filling pressures in obesity- associated pseudotumor cerebri. Neurology 49:507–511

    PubMed  Google Scholar 

  28. Tibbling G, Link H, Öhman S (1977) Principles of albumin and IgG analysis in neurological disorders. 1. Establishment of reference values. Scand J Clin Lan Invest 37:385–390

    Google Scholar 

  29. Tumani H, Nau R, Felgenhauer K (1998) Beta-trace protein in cerebrospinal fluid: a blood-CSF barrierrelated evaluation in neurological diseases. Ann Neurol 44:882–889

    Article  PubMed  Google Scholar 

  30. Upton ML, Weller RO (1985) The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations. J Neurosurg 63:867–875

    PubMed  Google Scholar 

  31. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P; European Task Force on Age-Related White Matter Changes (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. Tumani MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brettschneider, J., Claus, A., Kassubek, J. et al. Isolated blood–cerebrospinal fluid barrier dysfunction: prevalence and associated diseases. J Neurol 252, 1067–1073 (2005). https://doi.org/10.1007/s00415-005-0817-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-0817-9

Key words

Navigation