Acta Neurochirurgica

, Volume 99, Issue 3–4, pp 135–144

S-100 Protein in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Relation to functional outcome, late CT and SPECT changes, and signs of higher cortical dysfunction
  • H. -G. Hårdemark
  • O. Almqvist
  • T. Johansson
  • S. Påhlman
  • L. Persson


The concentration of S-100 protein measured in ventricular cerebrospinal fluid (CSF) from 32 patients with subarachnoid haemorrhage (SAH) during the acute phase was related to features on admission such as the Hunt and Hess neurological scale and the amount of blood at the first computed tomography (CT). The S-100 values were also related to functional outcome assessed by the Glasgow outcome scale (GOS) at 12 months. Twenty-two patients were re-examined more than 2 years after the SAH, and the initial S-100 values were related to signs of structural brain damage at CT and single photon emission computed tomography (SPECT) and to the results of neuropsychological evaluation (NPE). NPE included standardized tests for memory functions, intellectual functions, visuo-spatial abilities, sensory-motor functions, and concept formation. Life-adjustment was assessed by two separate questionnaires. Tests for agnostic dysfunction and the Western aphasia battery test (WABT) were also performed.

Patients who were functionally disabled or ultimately died had significantly higher initial CSF concentrations of S-100 protein than patients showing good recovery. Patients with low-attenuated regions and/or increased ventricular size at CT and/or regionally decreased tracer uptake on SPECT had higher S-100 levels during days 2–8 than had patients showing no such changes. Logistic and multiple regression analysis of all characteristics assessed during the acute phase after SAH showed that the CSF S-100 concentration during days 2–8 was the factor best correlated to GOS and findings on CT and/or SPECT.

All patients showed varying degrees of cognitive impairment at follow-up. The results of NPE and the WABT were related to outcome assessed by GOS and to increased ventricular size on CT. Women had a stronger feeling of maladjustment, but the scores for life adjustment were otherwise not related to other outcome criteria.

It is concluded that the ventricular CSF S-100 concentration during the acute phase after SAH is related not only to the functional outcome as assessed by GOS but also to signs of brain damage seen on late CT and SPECT.


Subarachnoid haemorrhage brain damage S-100 protein CSF CT SPECT neuropsychological evaluation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alexander M, Freedman M (1984) Amnesia after anterior communicating artery aneurysm rupture. Neurology 34: 752–757PubMedGoogle Scholar
  2. 2.
    Almqvist O. Unpublished dataGoogle Scholar
  3. 3.
    Almqvist O, Thorén M, Sääf M, Eriksson O (1986) Effects of growth hormone substitution on mental performance in adults with growth hormone deficiency: A pilot study. Psychoneuroendocrinology 11: 347–352PubMedGoogle Scholar
  4. 4.
    Bach F, Kruse A, Melgaard B, Børgesen S (1988) Creatine kinase BB release into cerebrospinal fluid after lateral ventricle cannulation. Br J Neurosurg 2: 339–342PubMedGoogle Scholar
  5. 5.
    Baddeley A (1968) A 3-minute reasoning test based on grammatical transformation. Psychonomic Science 10: 341–342Google Scholar
  6. 6.
    Baker E, Letz R, Fidler A (1985) A computer-administered neurobehavioural evaluation system for occupational and environmental epidemiology: Rationale, methodology and pilot study results. J Occup Med 27: 206–212PubMedGoogle Scholar
  7. 7.
    Benton A, Hamsher K (1976) Multilingual aphasia examination. University of Iowa, Iowa CityGoogle Scholar
  8. 8.
    Berg E (1948) A simple objective technique for measuring for flexibility in thinking. J Gen Psychol 39: 15–22Google Scholar
  9. 9.
    Bergman H, Bergman I, Engelbrektsson K, Holm L, Johannesson K, Lindberg S (1983) Psykologhandboken (in Swedish). Magnus Huss klinik-Karolinska sjukhuset, StockholmGoogle Scholar
  10. 10.
    Broadbent D, Cooper P, Fitzgerald P, Parkes KR (1982) The Cognitive Failures Questionnaire and its correlates. Br J Clin Psychol 21: 1–16PubMedGoogle Scholar
  11. 11.
    Crompton M (1964) The pathogenesis of cerebral infarction following the rupture of cerebral berry aneurysms. Brain 87: 491–510PubMedGoogle Scholar
  12. 12.
    Derogatis L, Spencer P (1982) Administration and procedures: BSI manual-I. Johns Hopkins University, BaltimoreGoogle Scholar
  13. 13.
    Dureman I, Kebbon L, Österberg E (1971) Manual to the DS battery (in Swedish). Psykologiförlaget AB, StockholmGoogle Scholar
  14. 14.
    Endo E, Tanaka T, Kasai H, Okuyama T, Hidaka H (1981) Calcium dependent affinity chromatography of S-100 and calmodulin antagonist coupled sepharose. J Biol Chem 256: 12485–12489PubMedGoogle Scholar
  15. 15.
    Fisher C, Kistler J, Davis J (1980) Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6: 1–9PubMedGoogle Scholar
  16. 16.
    Gerhardt W, Keller H (1986) Evaluation of test data from clinical studies. Scand J Clin Lab Invest 46 [Suppl] 181Google Scholar
  17. 17.
    Grote E, Hassler W (1988) The critical first minutes after subarachnoid hemorrhage. Neurosurgery 22: 654–661PubMedGoogle Scholar
  18. 18.
    Gyldensted C (1977) Measurements of the normal ventricular system and hemispheric sulci of 100 adults with computed tomography. Neuroradiology 14: 183–192PubMedGoogle Scholar
  19. 19.
    Hart R, Kwentus J, Wade J, Hamer R (1987) Digit symbol performance in mild dementia and depression. J Consult Clin Psychol 55: 236–238PubMedGoogle Scholar
  20. 20.
    Hay E, Royds J, Davies-Jones G, Timperley W, Lewtas N, Taylor C (1984) Cerebrospinal fluid enolase in stroke. J Neurol Neurosurg Psychiatry 47: 724–729PubMedGoogle Scholar
  21. 21.
    Hunt W, Hess R (1968) Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28: 14–20PubMedGoogle Scholar
  22. 22.
    Hårdemark H-G, Persson L, Bolander H, Hillered L, Olsson Y, Påhlman S (1988) Neuron-specific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid. Stroke 19: 1140–1144PubMedGoogle Scholar
  23. 23.
    Jennet B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet ii: 480–484Google Scholar
  24. 24.
    Johansson T, Söderborg B, Virgin J (1988) Cerebral infarctions studied by I-123-iodoamphetamine. Eur Neurol 28: 18–23PubMedGoogle Scholar
  25. 25.
    Kertesz A (1982) The Western Aphasia Battery. Grune & Stratton, New YorkGoogle Scholar
  26. 26.
    Langworth S, Almqvist O, Elinder C-G (1987) Inverkan av metalliskt kvicksilver på centrala nervsystemet och njurarna (in Swedish). Arbetsmilöfonden, StockholmGoogle Scholar
  27. 27.
    Luria A (1986) Higher cortical functions in man. Basic Books, New YorkGoogle Scholar
  28. 28.
    Marangos P, Schmechel D, Parma A, Clark R, Goodwin F (1979) Measurement of neuron-specific (NSE) and non-neuronal (NNE) isoenzymes of enolase in rat, monkey and human nervous tissue. J Neurochem 33: 319–329PubMedGoogle Scholar
  29. 29.
    Milner B (1971) Interhemispheric differences in the location of psychological processes in man. Br Med Bull 27: 272–277PubMedGoogle Scholar
  30. 30.
    Moretti J, Cinotti L, Cesaro P, Defer G, Joulin Y, Sergent A, Vigneron N, Rapin J, Raynaud C (1987) Amines for brain tomoscintigraphy. Nucl Med Comm 8: 581–595Google Scholar
  31. 31.
    Persson L, Hårdemark H-G, Edner G, Ronne E, Mendel-Hartvig I, Påhlman S (1988) S-100 protein in cerebrospinal fluid of patients with subarachnoid hemorrhage: A potential marker of brain damage. Acta Neurochir (Wien) 93: 116–122Google Scholar
  32. 32.
    Persson L, Hårdemark H-G, Gustafsson J, Rundström G, Mendel-Hartvig I, Esscher T, Påhlman S (1987) S-100 protein and neuron specific enolase in cerebrospinal fluid and serum: Markers of cell damage in the human central nervous system. Stroke 18: 911–918PubMedGoogle Scholar
  33. 33.
    Raynaud C, Rancurel G, Samson J, Baron J, Soucy J, Kieffer E, Cabanis E, Majdalani A, Ricard S, Bardy A, Bourguignon M, Syrota A, Lassen N (1987) Pathophysiologic study of chronic infarcts with I-123-Isopropyl iodo-amphetamine: The importance of periinfarct area. Stroke 18: 21–29PubMedGoogle Scholar
  34. 34.
    Reitan R (1966) Diagnostic inferences of brain lesions based on psychological test results. Can Psychologist 7: 368–383Google Scholar
  35. 35.
    Rey A (1964) L'examen clinique en psychologie. Presses universitaires de France, ParisGoogle Scholar
  36. 36.
    Rey A (1941) L'examen psychologique dans les cas d'encephalopathie traumatique. Archives de psychologie 28: 286–340Google Scholar
  37. 37.
    Royds J, Davies-Jones G, Lewtas N, Timperley W, Taylor C (1983) Enolase isoenzymes in the cerebrospinal fluid of patients with diseases of the nervous system. J Neurol Neurosurg Psychiatry 46: 1031–1036PubMedGoogle Scholar
  38. 38.
    Royds J, Timperley W, Taylor C (1981) Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological change. J Neurol Neurosurg Psychiatry 44: 1129–1135PubMedGoogle Scholar
  39. 39.
    Schenkenberg T, Bradford D, Ajax E (1980) Line bisection and unilateral visual neglect in patients with neurological impairment. Neurology 30: 509–517PubMedGoogle Scholar
  40. 40.
    Seashore C, Lewis D, Seatveit D (1960) Seashore measures of musical talent. Psychological Corporation, New YorkGoogle Scholar
  41. 41.
    Sindic C, Chalon M, Cambiaso C, Laterre E, Masson P (1982) Assessment of damage to the central nervous system by determination of S-100 protein in the cerebrospinal fluid. J Neurol Neurosurg Psychiatry 45: 1130–1135PubMedGoogle Scholar
  42. 42.
    Smith B (1963) Cerebral pathology in subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 26: 535–539PubMedGoogle Scholar
  43. 43.
    Smith P, Langolf G, Goldberg J (1983) Effects of occupational exposure to elemental mercury on short term memory. Br J Ind Med 40: 413–419PubMedGoogle Scholar
  44. 44.
    Säveland H, Sonesson B, Ljunggren B, Brandt L, Uski T, Zygmunt S, Hindfelt B (1986) Outcome evaluation following subarachnoid hemorrhage. J Neurosurg 64: 191–196PubMedGoogle Scholar
  45. 45.
    Takayasu M, Shibuya M, Kanamori M, Suzuki Y, Ogura K, Kageyama N, Umekawa H, Hidaka H (1985) S-100 protein and calmodulin levels in cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 63: 417–420PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • H. -G. Hårdemark
    • 1
    • 2
  • O. Almqvist
    • 3
  • T. Johansson
    • 1
  • S. Påhlman
    • 4
  • L. Persson
    • 2
  1. 1.Department of Neurology, SödersjukhusetKarolinska InstituteStockholmSweden
  2. 2.Department of NeurosurgeryUniversity HospitalUppsalaSweden
  3. 3.Department of Psychiatry, S:t Görans sjukhusKarolinska InstituteStockholmSweden
  4. 4.Department of PathologyUniversity HospitalUppsalaSweden

Personalised recommendations