GFAP and S100B in the acute phase of mild traumatic brain injury.

OBJECTIVE: The biomarkers glial fibrillary acid protein (GFAP) and S100B are increasingly used as prognostic tools in severe traumatic brain injury (TBI). Data for mild TBI are scarce. This study aims to analyze the predictive value of GFAP and S100B for outcome in mild TBI and the relation with imaging. METHODS: In 94 patients biomarkers were determined directly after admission. Collected data included injury severity, patient characteristics, admission CT, and MRI 3 months postinjury. Six months postinjury outcome was determined with Glasgow Outcome Scale Extended (GOSE) and return to work (RTW). RESULTS: Mean GFAP was 0.25 µg/L (SD 1.08) and S100B 0.54 µg/L (SD 1.18). In 63% GFAP was not discernible. GFAP was increased in patients with an abnormal CT (1.20 µg/L, SD 2.65) compared to normal CT (0.05 µg/L, SD 0.17, p < 0.05). Also in patients with axonal injury on MRI GFAP was higher (0.65 µg/L, SD 0.91 vs 0.07 µg/L, SD 0.2, p < 0.05). GFAP was increased in patients with incomplete RTW compared to complete RTW (0.69 µg/L, SD 2.11 vs 0.12 µg/L, SD 0.38, p < 0.05). S100B was not related to outcome or imaging studies. In multivariate analysis GFAP was not predictive for outcome determined by GOSE and RTW. CONCLUSIONS: A relation between GFAP with imaging studies and outcome (determined by RTW) was found in contrast to S100B. As the positive predictive value of GFAP is limited in this category of TBI patients, this biomarker is not suitable for prediction of individual patient outcome.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES: Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS: The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS: We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS: Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

Strategies for patients with newly diagnosed oral squamous cell carcinoma and a positive chest CT. A cohort study on the effects on treatment planning and incidence.

The purpose of this study was to establish how often routine CT scan of the chest yields positive findings in patients suffering from oral SCC and how it influences the treatment in terms of extra diagnostic procedures, treatment planning and treatment delay. Costs of this additional diagnostic approach for pulmonary tumors in a selected group were also calculated. A retrospective study was conducted of a group of 196 patients who were newly diagnosed with a squamous cell carcinoma of the oral cavity between January 2004 and July 2006; 142 hospital files were eligible for reviewing. In 20 (13%) patients chest abnormalities were observed on CT scan of the chest and in 6 (4%) patients malignancy was pathologically confirmed. Both pulmonary second primary tumors and pulmonary metastases were independent of stage of oral malignancy. We found that additional diagnostic procedures did not significantly lengthen the time interval between first consult and start of treatment. The cost of the screening for pulmonary malignancies in the group was € 8.214 per observed pulmonary malignancy. We advocate that CT imaging of the chest should be routinely performed in the diagnostic work up of all patients with a newly discovered SCC of the oral cavity, irrespective of the tumor stage of the oral malignancy.

Hyperdense middle cerebral artery sign and outcome after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: The presence of a hyperdense middle cerebral artery sign (HMCAS) on baseline brain CT is associated with poor clinical outcome in stroke patients treated with intravenous recombinant tissue plasminogen activator (tPA). It remains uncertain whether the presence of HMCAS is associated with acute neurological deterioration after tPA treatment. OBJECTIVE: To evaluate the effect of HMCAS in routinely intravenous tPA-treated patients with anterior circulation stroke on acute neurological deterioration, the 3-month functional outcome and the occurrence of symptomatic ICH. METHODS: We analyzed data from a single stroke unit registry of 384 consecutive patients with anterior circulation infarction, treated with intravenous tPA. Logistic regression models were used to assess if HMCAS was independently associated with predefined outcome definitions. RESULTS: We found a HMCAS in 104 patients (27%). The HMCAS was related to the risk of early neurological deterioration (p=0.04) and poor functional outcome (p<0.001) on univariate analysis. The incidence of symptomatic ICH was not significantly different between patients with and without HMCAS (7% versus 6%, p=0.81). In the multivariable analysis, the presence of HMCAS was significantly associated with a poor outcome (p=0.004). CONCLUSIONS: The HMCAS is associated with early neurological deterioration and poor functional outcome, but not with symptomatic ICH.

Differentiation between Supratentorial Single Brain Metastases and High Grade Astrocytic Tumors: an Evaluation of Different DSC MRI Measurements.

This study evaluated the role of different perfusion MRI measurements in the pre-operative differentiation between single brain metastases and high grade astrocytic tumors. 24 high-grade astrocytic tumors and 29 single metastases were studied. A gradient echo-planar sequence was used for DSC MRI. Relative cerebral blood volume, cerebral blood flow and mean transit time in both tumor parenchyma (T rCBV, T rCBF and T rMTT) and peritumoral edema (P rCBV, P rCBF and P rMTT) were measured. Mann-Whitney tests were used to assess differences between single brain metastases and high grade astrocytic tumors. Receiver operating characteristic analyses were performed to determine optimum thresholds for tumor differentiation. Sensitivity, specificity and accuracy for identifying brain metastases were calculated. Mean T rCBV, T rCBF, P rCBV and P CBF of brain metastases (2.75±1.72, 2.51±2.09, 1.05±0.53, 0.87±0.40) differed statistically (P <0.05) from those of high grade astrocytic tumors (6.00±2.17, 5.68±2.35, 1.77±1.19 and 1.58±0.99). No statistical difference was found between mean rMTTs of these two entities (P >0.05). Based on the area under the ROC curves (AUC), the efficiency of T rCBV and T rCBF for correct diagnosis of brain metastases is almost identical (AUC: 0.899, 0.890 respectively) and superior to other measurements. A threshold value of 3.50 for T rCBF provided the same specificity (86.7) as that of T rCBV but higher sensitivity (86.2) and accuracy (86.3). Different perfusion measurements can be used to differentiate single metastases from high-grade astrocytic tumors. T rCBF showed the highest diagnostic efficiency among these measurements.

FDG-PET and detection of distant metastases and simultaneous tumors in head and neck squamous cell carcinoma: a comparison with chest radiography and chest CT.

Detection of distant metastases and second primary tumors in patients with head and neck squamous cell carcinoma (HNSCC) is of importance because of the impact on treatment and prognosis. The aim of this study was to assess the value of whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) in detecting distant metastases and second primary tumors below clavicular level in HNSCC compared to chest CT and chest radiography (CXR). Patient records of 149 consecutive patients with a primary HNSCC in whom a whole-body FDG-PET for initial staging was performed were reviewed. FDG-PET showed a sensitivity and specificity for detecting distant disease of 92% and 93%, respectively. Chest CT (n=82) showed a sensitivity and a specificity of 74% and 61% respectively. CXR (n=106) showed a sensitivity and a specificity of 41% and 91%, respectively. FDG-PET was shown to be able to detect distant metastases and second primary tumors in HNSCC with a high sensitivity and specificity. The higher sensitivity of PET compared to chest CT is mainly due to the detection of extrapulmonary malignancy. Sensitivity of PET and CT were similar in detecting intrapulmonary malignancy, but PET specificity was significantly higher. FDG-PET helps to determine the nature of pulmonary lesions and might be considered as a first diagnostic modality for detecting distant disease in advanced HNSCC.

MR spectroscopy of the brain in Leigh syndrome.

Brain magnetic resonance spectroscopy in two patients with Leigh syndrome revealed the presence of lactate in gray and white matter brain tissue and relatively high choline levels in the white matter. The latter observation, most probably related to an ongoing demyelination process, underlines specific involvement of white matter metabolism in Leigh syndrome even in cases without involvement of the white matter as visualized on MRI. Magnetic resonance spectroscopy might thus be of help in differentiating Leigh syndrome from a range of other mitochondrial diseases, such as ophthalmoplegia and Kearns-Sayre syndrome, showing lack of lactate in brain tissues appearing normal on MRI.