Outcome prediction in traumatic brain injury: comparison of neurological status, CT findings, and blood levels of S100B and GFAP.

OBJECTIVE: To investigate the predictive value of early serum levels of S100B and glial fibrillary acidic protein (GFAP) in traumatic brain injury. METHODS: Sixty patients admitted within 24 h of trauma were included. Neurological status on admission (Glasgow Coma Scale), initial cranial computed tomography (CCT) studies (Marshall Computed Tomographic Classification), and outcome after 6 months (Glasgow Outcome Scale) were evaluated. S100B and GFAP levels were determined on admission and 24 h after trauma. RESULTS: Blood levels of S100B and GFAP were elevated following head trauma and quantitatively reflected the severity of trauma. S100B levels after 24 h and on admission were of higher predictive value than CCT findings or clinical examination. GFAP, but not S100B levels rapidly declined after trauma. CONCLUSIONS: Blood levels of S100B and GFAP indicate the severity of brain damage and are correlated with neurological prognosis after trauma. Both methods can yield additional prognostic information if combined with clinical and CCT findings.

Dose reduction in dynamic perfusion CT of the brain: effects of the scan frequency on measurements of cerebral blood flow, cerebral blood volume, and mean transit time.

The influence of the frequency of computed tomography (CT) image acquisition on the diagnostic quality of dynamic perfusion CT (PCT) studies of the brain was investigated. Eight patients with clinically suspected acute ischemia of one hemisphere underwent PCT, performed on average 3.4 h after the onset of symptoms. Sixty consecutive images per slice were obtained with individual CT images obtained at a temporal resolution of two images per second. Eight additional data sets were reconstructed with temporal resolutions ranging from one image per second to one image per 5 s. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) measurements were performed in identical regions of interest. Two neuroradiologists evaluated the PCT images visually to identify areas of abnormal perfusion. Perfusion images created up to a temporal resolution of one image per 3 s were rated to be diagnostically equal to the original data. Even at one image per 4 s, all areas of infarction were identified. Quantitative differences of CBF, CBV and MTT measurements were < or = 10% up to one image per 3 s. For PCT of the brain, temporal resolution can be reduced to one image per 3 s without significant compromise in image quality. This significantly reduces the radiation dose of the patient.

Elevated plasma levels of S-100b protein in schizophrenic patients.

BACKGROUND: In this study, we examined the possibility that structural damage to the brain may play a role in the pathogenesis of schizophrenia. METHODS: We compared plasma levels of S-100b protein in 20 patients with schizophrenic psychosis and 20 age- and gender-matched healthy blood donors. Concentrations of S-100 protein were determined by microtiter-based immunofluorometric assay detecting predominantly S-100b. RESULTS: Mean concentrations of S-100b protein in blood were significantly (p < or = .001) higher in schizophrenic patients (0.165 +/- 0.138 microgram/L) compared to control subjects (0.054 +/- 0.031 microgram/L). Levels did not correlate with age of onset or duration of psychosis. CONCLUSIONS: Our findings indicate that patients with schizophrenia may suffer ongoing structural damage to cells of the central nervous system, and that the concentration of S-100b protein in plasma may help to identify clinical subgroups in schizophrenia.

Dynamic CT perfusion imaging of acute stroke.

BACKGROUND AND PURPOSE: Because cerebral perfusion imaging for acute stroke is unavailable in most hospitals, we investigated the feasibility of a method of perfusion scanning that can be performed rapidly during standard cranial CT. Our aim was to identify the scanning parameters best suited to indicate tissue at risk and to measure a perfusion limit to predict infarction. METHODS: Seventy patients who had suffered stroke and had undergone cranial CT 0.5 to 12 hours (median, 3.75 hr) after the onset of symptoms participated in the study. While undergoing conventional CT, each patient received a bolus of iodinated contrast medium. Maps of time to peak (TTP), cerebral blood volume (CBV), and CBF were calculated from the resulting dynamically enhanced scans. These perfusion images were compared with follow-up CT scans or MR images showing the final infarctions. RESULTS: CBF maps predicted the extent of cerebral infarction with a sensitivity of 93% and a specificity of 98%. In contrast, CBV maps were less sensitive and TTP maps were less specific and also showed areas of collateral flow. Infarction occurred in all of the patients with CBF reduction of more than 70% and in half of the patients with CBF reduction of 40% to 70%. CONCLUSION: Dynamic CT perfusion imaging safely detects tissue at risk in cases of acute stroke and is a feasible method for any clinic with a third-generation CT scanner.

S-100B is increased in melancholic but not in non-melancholic major depression.

BACKGROUND: Recent evidence suggests that neurodegeneration may be involved in the pathophysiology of major depression. The astroglial peptide S-100B was shown to be increased in many diseases causing neuronal cell damage or degeneration. METHOD: S-100B plasma levels were determined in 28 patients with major depression and 28 matched healthy controls using an immunofluorometric sandwich assay. RESULTS: Patients suffering from melancholic depression showed significantly increased S-100B levels compared to healthy controls while non-melancholic patients demonstrated normal levels. LIMITATIONS: Medication of patients varied. The differentiation between melancholic and non-melancholic patients was performed clinically without using a standardized instrument. CONCLUSIONS: Neurodegeneration or axonal remodeling may be involved in the pathogenesis of melancholic depression.

Dislocation of the third ventricle due to space-occupying stroke evaluated by transcranial duplex sonography.

Transcranial color-coded duplex sonography is a recently introduced method for visualizing (1) the blood flow velocity of the basal cerebral arteries and (2) the brain parenchyma as an acoustic impedance image. Dislocation of the third ventricle due to space-occupying stroke is an important clinical marker. This study evaluated the dislocation of the third ventricle from the brain midline by transcranial duplex sonography in 10 healthy volunteers. The mean dislocation was 0.2 +/- 0.3 mm. Eighteen stroke patients were investigated within 12 hours by both duplex sonography and computed tomography (CT) and the dislocation of the third ventricle was measured. Correlation between the two methods was high (r = 0.87, N = 27). Twelve stroke patients divided into three subgroups according to the extent of the space-occupying effects of the lesion were followed for 3 weeks. The increase and decrease of the dislocation of the third ventricle over the time were monitored. In conclusion, transcranial duplex sonography is a reliable tool to monitor dislocation of the third ventricle due to space-occupying stroke.

Contralateral cerebral blood flow velocity changes after intracarotid amobarbital injection.

BACKGROUND AND PURPOSE: The intracarotid amobarbital procedure (IAP) leads to a prompt decrease in ipsilateral middle cerebral artery (MCA) mean blood flow velocity (MFV). Little is known about contralateral MFV changes. METHODS: The authors investigated bilateral MCA MFV using transcranial Doppler sonography (TCD) in 8 patients with epilepsy undergoing IAP. Measurements were excluded from analysis if angiography revealed any signs of interhemispheric cross-flow. RESULTS: With in 64 seconds after amobarbital injection, ipsilateral MFV decreased to a mean of 44.4% +/- 7.5% of baseline value (P < .01). In the absence of interhemispheric cross-flow and within 68 seconds, contralateral MFV decreased to 83.1% +/- 7.9% (P < .01). CONCLUSIONS: The observed decrease of contralateral MFV was not caused by amobarbital cross-perfusion. A possible underlying mechanism may be interhemispheric deafferentation.

[Contrast-enhanced intracranial 3 D MR angiography (CE-MRA) in assessing arterial stenoses and aneurysms]. / Kontrastmittelgestützte 3D-MR-Angiographie (CE-MRA) bei intrakraniellen Stenosen und Aneurysmen.

PURPOSE: The aim of this study was to evaluate the diagnostic potential of CE-MR angiography in intracranial arterial stenoses and aneurysms. MATERIAL AND METHODS: Thirteen patients with intracranial arterial stenoses and ten patients with aneurysms, including 6 cases with GDC coil-occluded aneurysms, were examined by both 3 D TOF-MR angiography and CE-MR angiography. In cases of stenoocclusive diseases colour-coded duplex sonography and in cases of aneurysms arterial digital subtraction angiography served as reference method. RESULTS: Both TOF-MRA and CE-MRA could well depict filiform stenosis. In contrast to TOF-MRA, CE-MRA did not show any false positive stenosis or occlusion in regions of turbulent or slow blood flow. Stenoses of the medial cerebral artery could not be graded sufficiently by CE-MRA. In aneurysms the parent vessel was better shown by TOF-MRA. CE-MRA, however, more sensitively detected reperfusion in GDC coil-occluded aneurysms. CONCLUSION: Stenoses of small vessels were graded less exactly by CE-MRA than by TOF-MRA due to lower spatial resolution. CE-MRA, however, seems to be superior in regions of turbulent or slow blood flow. CE-MRA also offers advantages in follow-up examinations of coil-occluded aneurysms.

Glial and neuronal serum markers after controlled cortical impact injury in the rat.

The aim of this study was to investigate the time course and the correlation of glial fibrillary acidic protein (GFAP), protein S-100B, and neuron specific enolase (NSE) serum levels to the severity of traumatic brain injury in rats. Male Wistar rats (n = 65 S-100B, NSE group and n = 55 GFAP group) underwent a severe cortical impact injury (100PSI, 2 mm deformation). Blood samples were drawn directly after trauma, 1 h, 6 h, 12 h, 24 h, and 48 h post trauma as well as in sham operated animals directly after craniotomy, after 6 h and 48 h. Serum levels at different severities were estimated in 20 rats (45PSI, 75PSI, 2 mm deformation). We found a time-dependent release of NSE and GFAP into serum after trauma. The highest NSE values were detected six hours after trauma (31.5 micrograms/l, mean, p < 0.0001), the highest GFAP levels were measured one hour after trauma (0.079 microgram/l, mean, p < 0.0014). Additionally we found a close relationship between NSE serum levels and the severity of traumatic brain injury (45PSI = 12.7 micrograms/l, 75PSI = 16.17 micrograms/l, 100PSI = 28.45 micrograms/l, p < 0.05). S-100B serum levels showed an increase (0.92 microgram/l, p < 0.005) but no time-dependent release. S-100B and GFAP showed no relationship to trauma severity. Serum levels of GFAP, S-100B and NSE are significantly elevated in the early phase after experimental traumatic brain injury. In this experimental model of cortical impact injury only NSE, but not GFAP and S-100B serum levels are time-dependently correlated with the severity of cortical impact.

Cavernous angioma as a rare neuroradiologic finding in the cavernous sinus.

We report the case of a 56-year-old female with a pathologically confirmed cavernous angioma of the cavernous sinus. There are only a few reports on cavernous sinus angiomas in the literature. In contrast to typical intracerebral cavernous angiomas, these lesions are characterized by strong contrast enhancement on computed tomography and magnetic resonance imaging. In spite of the problematic location within the cavernous sinus, these angiomas can be completely resected without additional neurologic deficits. The clinical course of the patient and the unusual neuroradiologic imaging findings, as well as the cases from the literature are discussed.

Measurement of S-100 protein in human blood and cerebrospinal fluid: analytical method and preliminary clinical results.

An immunofluorometric sandwich assay for determination of S-100 protein in cerebrospinal fluid (CSF) and blood is described. The lower detection limit was 0.015 micrograms/l of S-100 protein. Intra-assay and inter-assay imprecision (coefficients of variation, CVs) were 2.1 to 3.2% and 7.8 to 11.6%, respectively. S-100 protein recovery in cerebrospinal fluid was 94 to 103%. In blood the recovery varied from 67 to 96%, depending on blood samples used and the concentration of S-100 protein. The best recovery in blood was found using heparinized plasma. In healthy subjects 0.098 +/- 0.11 micrograms/l (mean +/- SD) of S-100 protein was detected (n = 30). In the CSF of otherwise healthy patients undergoing a myelography for lumbar pain 1.43 +/- 0.49 micrograms/l (mean +/- SD) of S-100 protein was found. Preliminary results from longitudinal studies on S-100 protein in neurosurgical patients indicate a positive correlation between S-100 protein blood levels and clinical course. Thus, the determination of S-100 protein in blood appears to be helpful in the monitoring of patients with neuronal damage.

Chronic spondylogenic cervical myelopathy. A critical evaluation of surgical treatment after early and long-term follow-up.

In the past, chronic spondylogenic cervical myelopathy has been thought of being a disease often resistant to neurosurgical therapy. 56 out of 70 patient treated by laminectomy or different ventral fusion procedures improved immediately following operation. Only 36, however, continued to be improved at follow-up 5 to 8 years later, whereas additional 8 had worsened again, and another 5 mean-while had died due to myelopathy. Laminectomy turned out to be the least successful procedure of treatment. Nevertheless, early diagnosis, early operation, appropriate and individual surgical procedures, careful re-evaluation at follow-up, and -- if needed -- an early decision for a second-step operation can impressively improve the prognosis.

Time-resolved immunofluorometric assay for the quantification of lipoprotein(a) in serum.

Although two recent studies have failed to reveal lipoprotein(a) (LP(a)) serum concentrations > 300 mg/l to be an independent risk factor for early onset of atherosclerosis, Lp(a) serum concentrations are frequently measured to evaluate the additional risk of coronary heart disease. We describe a time-resolved immunofluorometric assay (TRIFMA) for quantifying Lp(a) levels in humans serum using commercially available reagents, which is rapid, robust and simple to perform. The two-site immunometric assay was based on microtitre plates as solid phase coated with a polycloncal anti Lp(a) antibody. The liquid-phase antibody was labelled with biotin and detected by europium labelled streptavidin in the DELFIA 1232 fluorometer. The measuring range was 2-1600 mg/l. The intra-assay imprecision was < 7% (CV), the inter-assay imprecision < 12% (CV). No interference was detected with plasminogen concentration up to 2.2 g/l. There was an acceptable correlation with a commercially available enzyme immunoassay (r = 0.95) and with electroimmunodiffusion (r = 0.85) on 100 routine serum samples measured. The assay appeared to detect different Lp(a) isoforms as dilution curves were parallel for B/F, S2 and S4 isoforms.

[A new immunoluminometric solid phase sandwich assay for antibodies to hepatitis B surface antigen]. / Ein neuer immunoluminometrischer Festphasen-Sandwich-Assay zum quantitativen Nachweis von Antikörpern gegen das Hepatitis B-Oberflächen (HBs)-antigen.

A solid phase quantitative immunoluminometric assay for antibodies to hepatitis B surface antigen (Anti-HBsAg) is described. This solid phase assay uses polystyrene balls of 6.4 mm diameter, coated with pure hepatitis B surface antigen (HBsAg) obtained from the plasma of chronic HBsAg carriers. After incubation with patient serum (90 min), HBsAg labelled with 7-(4-aminobutyl-N-ethyl)naphthalene 1,2-dicarboxylic acid hydrazide hemisuccinamide (ABEN-H) was used as the signal carrier. Dilutions of samples and standards were made with sera previously shown to be negative for anti HBsAg. The lower detection limit was about 1.3 U/l the upper limit for undiluted serum about 1000 U/l. The mean coefficient of variation was 5%. The dynamic range (expressed as the signal ratio of the highest standard: zero standard) was 182:1 and covered the range 23-4200 relative light units. The assay was tested for specificity and gave no false-positive reactions in the presence of other hepatitis B antigens and antibodies.

A sensitive and rapid luminescence sandwich assay for antibodies to hepatitis-B surface antigen (anti-HBsAg).

A chemiluminescent assay for hepatitis-B surface antigen is described which used an isoluminol derivative as the label. The assay is precise intra-assay CV, 1.96-2.45%; inter-assay CV, 5.26-8.11% and has a lower detection limit for hepatitis-B surface antigen of 1.3 U/l.

Development and evaluation of a time-resolved immunofluorimetric assay for thyrotropin.

The assay described in this article is based on microtitre plate technology; it employs an europium label. The streptavidin-biotin system has been used and all components are commercially available. The lower detection limit of the assay is below 0.003 mU/l; the standards are made up in newborn calf serum. Correlation with a commercially available immunoluminometric assay (Berilux--Behringwerke) was excellent (r = 0.92, n = 201 data pairs, range covered 0-10 mU/l). The regression line using a double logarithmic transformation was: (log y) = 0.91 (log x)-0.08. The assay precision at the clinical limits of decision--i.e. between hyper- and euthyroidism (0.2 mU/l) and eu- and hypothyroidism (4 mU/l)--was acceptable. The median coefficient of variation was 1.93% in the range 0.02-1 mU/l and 2.11% in the range 1.0-3.5 mU/l, with both values being determined from precision profiles using 214 and 188 data pairs respectively. Inter-assay coefficients of variation determined in over 30 consecutive assays were under 6% in the range 1.3-20 mU/l. From 201 sera measured in both assays, 194 sera gave clinically identical values; 8 sera gave clinically discrepant values. The assay has a large dynamic range covering a concentration range of above 5 decades, with the count ratio between the 100 mU/l standard and the zero standard being in excess of 4150:1. A high dose hook effect was first seen in excess of 500 mU/l. The maximum signal was achieved around 150 mU/l, which registered around 8 x 10(6) counts per second, a figure more than 8000 times higher than that in the zero standard.

Thyroglobulin is a more sensitive indicator of iodine deficiency than thyrotropin: development and evaluation of dry blood spot assays for thyrotropin and thyroglobulin in iodine-deficient geographical areas.

Immunometric assays were developed for thyrotropin and thyroglobulin using time-resolved fluorescence as the measurement signal. The assays were suitable for measurements in serum/plasma or in dry blood spots (3 mm diameter). Both assays have acceptable coefficients of variation for dry blood spots (intra-assay median CV < 10%, interassay CV < 15%) in the concentration range of interest (thyrotropin 3-250 mU/l, thyroglobulin 10-500 micrograms/l). The relatively high CV values are not only due to the assay design but also the inhomogeneity of the samples used. For serum samples the median intra-assay CV was < 3% for thyrotropin in the range 0.1-50 mU/l and for thyroglobulin between 2 and 500 micrograms/l. The corresponding inter-assay CV were less than 5%. The assays were evaluated in field studies carried out under auspices of International Council for Control of Iodine Deficiency Disorders (ICCIDD) with the support of UNICEF in Algeria, Peru, India and Zimbabwe, and were found to be practical inasmuch as dry blood spot samples could be transported without special precautions for up to 5-6 weeks without significant loss in immunoreactivity. This agrees with other findings. The results showed that serum thyroglobulin levels are a more sensitive indicator of iodine deficiency than thyrotropin; elevated thyroglobulin levels were found in 182/304 children in Zimbabwe compared with elevated thyrotropin level in 28/304 cases. 213/304 children had enlarged thyroid glands. The cut-off levels used here were 4.5 mU/l thyrotropin and 20 micrograms/l for thyroglobulin, both in whole blood. The assays proved useful for assessing the efficacy of iodine therapy, either by oral dosage or intramuscularly (iodised oil).(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary apoplexy after cardiac surgery presenting as deep coma with dilated pupils.

Acute clinical deterioration due to infarction or haemorrhage of an existing, often previously unrecognized, pituitary tumour is a rare but well-described complication. It can occur spontaneously or may be caused e.g. by mechanical ventilation, infection or surgical procedures. We report on a case of pituitary apoplexy occurring in a 64-year-old patient 3 weeks after cardiac surgery. The patient presented with deep coma and dilated pupils. Magnetic resonance imaging revealed a haemorrhagic pituitary tumour. After prompt endocrinologic replacement therapy with levothyroxine and hydrocortisone the patient regained consciousness. Neurological examination revealed right oculomotor nerve palsy and bilateral cranial nerve VI palsy. Subsequent trans-sphenoidal removal of a nonfunctional macroadenoma with large necrotic areas was performed. The patient recovered completely. To our knowledge, pituitary tumours presenting with a combination of deep coma and dilated pupils must be considered exceedingly rare. Possible pathophysiologic mechanisms are discussed. As our case illustrates, even in severe cases complete recovery is possible if the diagnosis is suspected, and diagnostic and therapeutic measures are initiated in time.