ORIGINAL CONTRIBUTION

Diagnostic Value of S100B Protein in the Differential Diagnosis of Acute Vertigo in the Emergency Department € lfer Kartal, MD, Serkan Yılmaz, MD, Elif Yaka, MD, Murat Pekdemir, MD, Hasan Tahsin Aslı Gu € ksel, MD Sarısoy, MD, Mustafa Baki C ß ekmen, MD, and Melih Yu

Abstract Objectives: Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining the nature of the vertigo is crucial in the emergency department (ED). With a broad range of potential etiologies, distinguishing central causes from benign peripheral causes is a diagnostic challenge. Cranial magnetic resonance imaging (MRI) is the recommended neuroimaging method when clinical findings are ambiguous. However, MRI scanning for every patient with an uncertain diagnosis may not be efficient or possible. Therefore, to improve ED resource utilization for patients with vertigo, there is a need to identify the subset most likely to have MRI abnormalities. It has previously been shown that S100B protein provides a useful serum marker of stroke, subarachnoid hemorrhage, and traumatic brain injury. This study evaluated whether S100B levels could predict central causes of vertigo as identified by cranial MRI in the ED. Methods: This prospective, observational study was conducted with adult patients with acute-onset vertigo (within 6 hours) in the ED of a teaching hospital in Kocaeli, Turkey. Patients with nausea or dizziness complaints without previously known vertigo or cranial pathology, and who agreed to participate in the study, were included. Patients with trauma or with neurologic findings that developed concurrent with their symptoms were excluded. Serum levels of S100B were measured with an electrochemiluminescence immunoassay kit. All subjects underwent cranial MRI. The predictors of positive MRI results were evaluated using logistic regression analysis. Sensitivity and specificity of S100B levels for identifying subjects with central causes of vertigo on MRI were calculated with receiver operating characteristic (ROC) curve. Results: Of the 82 subjects included in the study, 48 (58.5%) were female, and the mean (SD) age was 51 (16) years. Thirty-one (37.8%) subjects had positive MRI results. Median (with interquartile range [IQR]) serum S100B levels were significantly different between MRI-negative and MRI-positive groups (median = 27.00 pg/mL, IQR = 10.00 to 44.60 vs. median = 60.94 pg/mL, IQR = 38.25 to 77.95, respectively; p = 0.04). In logistic regression analysis, subjective “he or she is spinning” (p = 0.030, odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.38 to 2.49), systolic blood pressure (sBP; p = 0.045, OR = 1.044, 95% CI = 1.021 to 1.080), and serum S100B level (p = 0.042, OR = 1.22, 95% CI = 1.018 to 1.445) were found to be independent predictors of MRI abnormalities. In the ROC analysis, S100B > 30 pg/mL predicted the clinical outcome with 83.9% sensitivity (95% CI = 66.3% to 94.5%) and 51.0% specificity (95% CI = 36.6% to 65.2%). The area under the ROC curve was 0.774 (95% CI = 0.666 to 0.881). Conclusions: To the best of our knowledge this is the first study assessing the utility of serum S100B levels for diagnosis of acute-onset vertigo. Serum S100B levels are associated with the presence of central causes of vertigo on cranial MRI. However, serum S100B levels are not sufficiently sensitive to exclude candidates from cranial MRI. ACADEMIC EMERGENCY MEDICINE 2014;21:736–741 © 2014 by the Society for Academic Emergency Medicine

From the Department of Emergency Medicine (AGK, SY, EY, MP, MY), the Department of Radiology (HTS), and the Department of Biochemistry (MBC ß ), Faculty of Medicine, Kocaeli University, Kocaeli, Turkey. Received November 6, 2013; revision received January 14, 2014; accepted March 10, 2014. Presented at the Seventh Mediterranean Emergency Medicine Congress, Marseille, France, September 2011. The authors have no relevant financial information or potential conflicts of interest to disclose. Supervising Editor: Clifton Callaway, PhD, MD. Address for correspondence and reprints: Serkan Yılmaz, MD; e-mail: [email protected].

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ISSN 1069-6563 736 PII ISSN 1069-6563583

© 2014 by the Society for Academic Emergency Medicine doi: 10.1111/acem.12420

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ertigo is a common presenting complaint in emergency departments (EDs), resulting from either peripheral vestibular pathologies or central causes. Ascertaining the nature of acute vertigo symptoms is crucial in the ED, because central causes of vertigo have the potential to cause disability and death. Appropriate management of vertigo in the ED is frequently precluded by difficulties with a constellation of signs and symptoms, low diagnostic value of computed tomography (CT), limited access to magnetic resonance imaging (MRI), and costs of MRI. Cranial MRI is the recommended “usually appropriate” neuroimaging modality to differentiate central from peripheral vertigo for suspected posterior fossa disorders or in patients where clinical findings are uncertain.1–3 However, it is not readily available in many EDs. Further, in busy EDs, ordering neuroimaging for every patient with an uncertain diagnosis may not be efficient. The context of limited neuroimaging availability underscores the value of selecting appropriate candidates for MRI. The challenge of managing a vertiginous patient in the ED lies in appropriately identifying candidates for MRI in terms of safety and cost-effectiveness. Biomarkers provide one strategy to identify a subset of patients for MRI. The calcium binding protein S100B has previously shown its utility in guiding neuroimaging decisions in patients with stroke, subarachnoid hemorrhage, and minor head trauma.4–6 S100 is a multigenic family of calcium-modulated proteins of the EF-hand type expressed in vertebrates. S100B is a member of the S100 family, is an acidic protein with a molecular weight of 21 kDa, and exists as a homodimer composed of two beta subunits.7 S100B is an important factor in neurodevelopment, differentiation, and brain construction, and extracellular concentration of S100B increases following brain damage. S100B easily penetrates into cerebrospinal fluid in brain damage and then into the blood.8,9 During traumatic brain damage, S100B increases in human blood and cerebrospinal fluid. Levels of S100B also increase in various ischemic conditions.5 S100B levels have not been examined as adjuncts for determining vertigo etiology in the ED. S100B may be a promising adjunct for emergency physicians to support neuroimaging decisions. The aim of this study was to evaluate the potential utility of S100B protein as a predictor of brain MRI abnormalities in patients with acute vertigo in the ED. METHODS Study Design This single-center, prospective, observational study was conducted between January 1, 2011, and December 30, 2011. Institutional review board approval (review number 2010/37) and written informed consent from each participant were obtained. Study Setting and Population The setting was an academic tertiary care hospital ED with an annual census of 40,000 visits. According to the institutional protocols, emergency physicians can order all types of imaging modalities and have the results

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within 1 hour. Adult patients with the chief complaint of vertigo presenting within 6 hours of symptom onset were eligible for the current study. Patients with previously diagnosed vertigo and known cranial structural disease and cranial pathology from recent trauma were excluded. Patients with obvious neurologic findings (aside from the nystagmus and disequilibrium of vertigo) concurrent with their symptoms and those who had contraindications for MRI were also excluded. Study Protocol Eligible subjects were monitored at their arrival and vital signs were obtained electronically. The electrocardiograms of each patient were obtained and interpreted within 10 minutes of arrival. Blood samples for S100B levels were obtained at the same venipuncture as for hemoglobin and electrolyte measurements. All included patients underwent MRI unless they had contraindications such as cardiac pacemaker or prosthesis. Clinically relevant MRI findings were defined as acute ischemia on diffusion-weighted imaging, hematoma on T2weighted imaging, and intracranial mass on axial T1-weighted imaging. The patients who had MRI abnormalities relevant to vertigo were assigned MRI-positive group, and the others were MRI-negative group. Emergency care was not modified according to the current study. Study patient flow is provided in Figure 1. Blood samples of 10 mL were obtained in gel tubes and allowed to clot for 30 minutes. They were centrifuged at 800 to 1,000 rpm for 10 minutes at the emergency laboratory. Serum samples were transferred to test tubes after diluting with 1 mL distilled water as standard and control. The dilutions were kept at –20°C to preserve their stability and were analyzed up to 3 months from the day of collection. Lipemic samples were not used. Samples were defrosted at room temperature for processing. Repeated freezing and defrosting were avoided. The analysis was performed at the central laboratory of the hospital. S100B levels in the serum were measured with an electrochemiluminescence immunoassay S100B protein kit (Elecsys, Roche Diagnostics, Mannheim, Germany). Results are expressed as picogram per milliliter (pg/mL). Data Analysis Statistical analyses were performed with SPSS version 16.0 for Windows. Results were expressed as mean  standard deviation ( SD), median, interquartile range (IQR), and percentage where appropriate. The Kolmogorov-Smirnov test was used to test the distributions of variables. In the univariate analysis, the Student’s t-test or chi-square tests were used according to the types of variables. S100B levels were not normally distributed; therefore, the relationship between MRI results and S100B levels was evaluated with Mann-Whitney U-test. For a multivariate analysis, the possible factors identified with univariate analyses (p ≤ 0.25) were further entered into a logistic regression model to determine independent predictors of patient outcome. Hosmer-Lemeshow goodness-of-fit statistics were used to assess model fit. A receiver operating characteristic (ROC) curve was constructed to determine test characteristics (sensitivity and specificity) of S100B. The Younden’s index was used to

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Kartal et al. • S100B PROTEIN IN ACUTE VERTIGO

Figure 1. Patient selection. MR = magnetic resonance.

select best cutoff values of the S100B level. The area under the curve (AUC) was calculated for S100B’s ability to predict MRI abnormalities relevant to vertigo. Positive and negative likelihood ratios were also calculated. Statistical significance was set at p < 0.05. All results were reported along with their associated 95% confidence intervals (CIs) and p-values. RESULTS Among the MRIs performed, 42 (51.2%) revealed normal results, and nine subjects had chronic ischemic disease. Patient characteristics are given in Table 1. A central cause of vertigo was evident on MRI for 31 subjects (37.8%). The most common pathology identified in the current study was acute ischemia of posterior circulation (n = 26) on diffusion-weighted MRI. Four patients had cerebellar hematomas on T2-weighted imaging, and one patient had a cerebellar mass on axial T1weighted imaging. Median S100B levels were significantly different between MRI-negative (median = 27.00 pg/mL, IQR = 10.00 to 44.60 pg/mL) and MRI-positive (median = 60.94 pg/mL, IQR = 38.25 to 77.95 pg/mL) groups (p = 0.04). In multivariate analysis, a subjective complaint of “he/ she is spinning,” systolic blood pressure (sBP), and S100B level were found to be independent predictors of positive MRI results (Table 2). The fit of the developed model was acceptable (Hosmer-Lemeshow p = 0.54) A one-unit increase in the S100B level is associated with a 1.2-fold increased odds of positive MRI results. The ROC analysis demonstrated an AUC of 0.774 (95% CI = 0.668 to 0.859) for S100B to predict abnormal MRI findings (Figure 2). At a cutoff value of S100B set at 30 pg/mL based on the highest sensitivity, the sensitivity, specificity, positive predictive value, and negative predictive value for S100B were 83.89% (95% CI = 66.3% to 94.5%), 51.0% (95% CI = 36.6% to 65.2%), 51.0% (95% CI = 36.6% to 65.2%), and 83.9% (95%

CI = 65.9% to 94.7%), respectively. The positive likelihood ratio of the test was 1.71 (95% CI = 1.2 to 2.4), and negative likelihood ratio was 0.32 (95% CI = 0.1 to 0.7). DISCUSSION This study evaluated the potential of serum S100B levels for identifying central etiologies of acute vertigo in patients with indefinite clinical findings in the ED. Results suggest that S100B is not sufficiently sensitive for emergency physicians to exclude MRI for patients with acute-onset vertigo in the ED. S100B levels have previously been reported to increase during the acute phases of minor head trauma and stroke, whereas, to the best of our knowledge, this is the first study assessing whether serum S100B levels increase in presentations with central vertigo. The S100B levels in patients whose MRI scans revealed central etiologies of their vertigo were on average significantly higher than in those with peripheral vertigo. However, based on the sensitivity, specificity, and AUC, serum S100B levels only modestly discriminated between central and peripheral causes of vertigo in presentations with indefinite clinical findings. To identify patients with vertigo of central origin, MRI has become the preferred diagnostic tool.1–3 It has been reported that the use of brain CT and MRI in the differential diagnosis of patients with dizziness has increased by 160%, even though the frequency of diagnosed central etiologies did not increase during the same period.10 Newman-Toker et al.11 also reported that the use of MRI in the diagnosis of patients with dizziness increased by 140% between 1993 and 2005. Considering the fact that identified central etiologies did not increase, the importance of patient selection for MRI use in patients with acute vertigo is obvious in terms of cost-effectiveness. Studies evaluating the utility of serum biomarkers in the differential diagnosis of central and peripheral

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Table 1 Patients Characteristics MRI-negative (n = 51)

Characteristics Demographics Age Sex (female) Complaint As if everywhere is spinning As if he/she is spinning Positional vertigo Tinnitus Infection in ear Plugged ear Experienced URTI Nausea/vomiting Comorbidities Physical examination sBP (mm Hg) dBP (mm Hg) Fever (°C) Pulse (beats/min) sPO2 (%) Horizontal nystagmus Vertical nystagmus Laboratory Glucose (mg/dl) WBCs (cell/mm³) Hemoglobin (g/dL) Platelet (cell/mm³) Urea (mg/dl) Creatinine (mg/dL) Sodium (mEq/L) Potassium (mEq/L) Calcium (mg/dL) S100B (pg/L)

MRI-positive (n = 31)

p-value

51 (16) 27 (56.2)

51 (17) 21 (43.8)

0.260 0.220

36 7 35 17 3 16 10 43 31

13 14 13 9 3 10 9 21 17

(41.9) (45.2) (41.9) (29) (9.7) (32.3) (29) (67.7) (54.8)

0.019 0.003 0.022 0.808 0.608 0.998 0.420 0.101 0.630

152.7 (29.3) 81.5 (20.3) 36.1 (0.3) 77.1 (14) 98.6 (1.7) 5 (16.1) 1 (3.1)

0.204 0.980 0.773 0.282 0.726 0.228 0.213

(70.5) (13.7) (68.6) (33.3) (5.9) (31.4) (19.6) (84.3) (60.8)

144.6 (26.5) 81.4 (15.1) 36.1 (0.4) 80.5 (13) 98.5 (1.7) 15 (29.4) 4 (7.8) 123.6 (43) 7.9 (2.5) 12.9 (1.5) 257,058 (72,000) 35 (23.2) 0.80 (0.4) 138 (2.1) 4.3 (0.4) 9.1 (0.5) 27.00 (18.07–37.4)

133.1 (73.5) 8.6 (3.9) 13.3 (2.1) 262,935 (85,000) 41.5 (24.1) 1.08 (0.9) 138.6 (2.8) 4.3 (0.4) 9.1 (0.6) 60.94 (43.34–70.20)

0.456 0.317 0.272 0.685 0.230 0.076 0.298 0.953 0.716 0.004

All values are n (%), except continuous values, which are reported as mean (SD) if normally distributed, or reported as median (IQR) if nonnormal distribution. dBP = diastolic blood pressure; IQR = interquartile range; sBP = systolic blood pressure; RR = respiratory rate; URTI = upper respiratory tract infection; WBC = white blood cell.

Table 2 Independent Predictors of Positive MRI Results Predictors Age Sex (female) As if everywhere is spinning As if he/she is spinning Positional vertigo Nausea/vomiting sBP (mm Hg) Horizontal nystagmus Vertical nystagmus Urea (mg/dL) Creatinine (mg/dL) S100B (pg/L)

OR

95% CI

p-value

0.975 0.476 0.606 1.634 0.593 1.877 1.044 0.277 1.807 1.005 1.888 1.220

0.932–1.020 0.150–1.511 0.108–3.387 1.375–2.490 0.164–2.147 0.470–7.501 1.021–1.080 0.088–9.953 0.395–8.279 0.958–1.055 0.396–8.996 1.018–1.445

0.277 0.208 0.569 0.030 0.426 0.373 0.045 0.446 0.482 0.832 0.425 0.042

MRI = magnetic resonance imaging; sBP = systolic blood pressure.

Figure 2. ROC curve analysis of serum S100B levels results in patients with acute vertigo. AUC = area under the curve; ROC = receiver operating characteristic.

vertigo are also available in the literature. In a study by Akinci et al.,12 it was reported that serum D-dimer, fibrinogen, and C-reactive protein levels were not useful in the differential diagnosis of central and peripheral vertigo. However, we found no other studies concerning cerebral biomarkers. In this regard, our study is original

in showing that serum S100B levels are associated with a diagnosis of central versus peripheral vertigo and may aid in the selection of patients for MRI. Serum S100B levels increase in various disorders of the central nervous system, including elevated intracranial pressure due to disrupted blood/brain barrier and cerebral edema, ischemia, and injury.13 In some cases,

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high serum levels can be detected even in very early stages. Persson et al.4 were the first to report that S100B protein increased in blood in patients with stroke. Abraha et al.5 found that serum S100B protein was elevated in cerebral infarction and intracerebral hemorrhage, with levels depending on the size of infarction. They concluded, therefore, that serum S100B levels reveal the volume of brain damage in patients with stroke. In another study, Wunderlich et al.6 noted a strong correlation between S100B serum concentrations and neurologic status. S100B levels increased significantly when the neurologic status deteriorated, suggesting that S100B levels could be used not only to predict the amount of ischemic brain damage in brain tomography, but as a monitoring parameter during acute ischemic stroke. Various cutoff values have been proposed for identifying brain injury with serum S100B levels. S100B > 30 pg/mL had the highest sensitivity for detecting stroke.6 Yardan et al.13 reported serum S100B > 0.10 lg/L identified patients with loss of consciousness due to carbon monoxide poisoning, and Zongo et al.14 reported that serum S100B > 0.12 lg/L identified patients with minor head trauma. These cutoff values were close to the 50 pg/mL value recommended by the manufacturer of the test kits. Even though our electrochemiluminescence immunoassay kit was the same as that of Zongo et al.,14 the cutoff value determined in our study was significantly lower. It is not surprising that the cutoff value of the current study of conscious subjects without large neurologic deficits is lower than those reported in patients with loss of consciousness and brain injury.13,14 In this study, 38% of all subjects had acute intracranial pathology on MRI. The central vertigo rate is quite variable in epidemiologic studies on vertigo and dizziness. Norrving et al.15 reported a 25% stroke rate in an elderly population presenting with isolated dizziness. Kerber et al.10 studied patients presenting to the ED with complaints of vertigo and dizziness during a 10-year period by referring to data from the American National Hospital Ambulatory Medical Care Survey (NHAMCS), and they determined the rate of cerebrovascular disease in this patient group as 3.9%. Newman-Toker et al.11 determined this rate as 11.2%, whereas Herr et al.16 reported it as 15%. The 38% rate of central vertigo in this study is higher than all of these reported rates. However, the difference originates from patient selection. Patients with recurrent vertigo and near-syncope, as well as those with possible causes of dizziness such as cardiovascular or metabolic problems, were excluded from our study. As a result, among 240 total patients with vertigo and dizziness, only 82 subjects were included in the study group. Of all patients presenting to the ED with acute vertigo and dizziness, 12.9% (31 of 240) had central causes of vertigo. This rate is consistent with that of previous studies. Dizziness or isolated vertigo in the ED is usually benign, although a substantial fraction of patients harbor serious neurologic disease. Clinical suspicion should be heightened for patients with advanced age, imbalance, or focal deficits.17 The risk factors for cerebrovascular disease such as hypertension, heart disease, and diabetes

Kartal et al. • S100B PROTEIN IN ACUTE VERTIGO

were also the risk factors for central vertigo.18 However, Cloutier and Saliba19 reported that 52% of patients with isolated vertigo of unclear etiology have posterior circulation anomalies. Distinguishing central causes from benign peripheral causes is a diagnostic challenge for the emergency physician. Clinical symptoms are still the mainstay of evaluating the patients with vertigo. The current study suggests that a subjective description of “he/she is spinning,” sBP, and serum S100B levels are independent predictors of positive MRI results. This study indicates that sensitivity of serum S100B levels are not sufficient to discriminate peripheral from central vertigo etiologies, but serum biomarkers in combination with clinical findings may be helpful for diagnosis in patients with indefinite signs and symptoms. LIMITATIONS This study was carried out with a limited number of patients, because of the limited funding for the S100B kits. We also applied restrictive selection criteria for patient inclusion. As the study aimed to determine the central etiologies of vertigo when there was a diagnostic challenge, only isolated real vertigo patients without obvious neurologic deficits, and without previously known central and vestibular disorders, were included in the study. This inevitably led to enrollment of patients who had relatively good clinical status. Because the study was conducted with patients with relatively good clinical status, no exploratory information about the prognostic value of serum S100B was acquired. S100B protein has a very short half-life, and serum levels should be assessed within the first 6 hours following the acute event. Timeliness of sampling and processing may have had an effect on the resulting heterogeneity of obtained S100B levels. Future studies should confirm these associations in broader patient populations and determine if a combination of serum markers and clinical symptoms can provide a more efficient selection of vertigo patients for MRI. CONCLUSIONS To the best of our knowledge this is the first study assessing the utility of serum S100B levels for diagnosis of acute-onset vertigo of central origin. The importance of patient selection for magnetic resonance imaging scanning in the workup of vertigo is obvious in terms of cost-effectiveness and efficiency. This study finds that serum S100B levels are not sufficiently sensitive to exclude candidates from cranial magnetic resonance imaging when determining vertigo etiologies. However, there are associations between serum S100B levels, clinical signs, and magnetic resonance imaging abnormalities in patients with indefinite presentations. References 1. Bruzzone MG, Grisoli M, De Simone T, RegnaGladin C. Neuroradiological features of vertigo. Neurol Sci 2004;1:20–3.

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2. Marzo SJ, Leonetti JP. The importance of magnetic resonance imaging in the evaluation of vertigo and imbalance. Skull Base Surg 2000;10:171–2. 3. Heath CL, Buckle C, Christofiridis G, Straus C. Utility of head CT in the evaluation of the vertigo/dizziness in the emergency department. Emerg Radiol 2013;20:45–9. 4. Persson L, Hardemark HG, Gustafsson J, et al. S100 protein and neuron-specific enolase in cerebrospinal fluid and serum markers of cell damage in human central nervous system. Stroke 1987;18:911–8. 5. Abraha HD, Butterworth J, Bath PM, Wassif WS, Garthwaite J, Sherwood RA. Serum S100 protein, relationship to clinical outcome in acute stroke. Ann Clin Biochem 1997;34:546–50. 6. Wunderlich MT, Wallesch CW, Goertler M. Release of neurobiochemical markers of brain damage is related to the neurovascular status on admission and the site of arterial occlusion in acute ischemic stroke. J Neurol Sci 2004;227:49–53. 7. Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 2003;60:540–51. 8. Rothermundt M, Peters M, Preehn JH, Arolt V. S100B in brain damage and neurodegenaration. Microsc Res. Tech 2003;60:614–32. 9. Heinzmann CW, Fritz G, Schafer BW. S100 Proteins: structure, functions and pathology. Front Biosci (Zurich) 2002;7:1356–8. 10. Kerber KA, Meurer WJ, West BT, Fendrick AM. Dizziness presentations in U.S. emergency departments, 1995-2004. Acad Emerg Med 2008;15:744–50.

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11. Newman-Toker DE, Hsieh YH, Camargo CA Jr, Pelletier AJ, Butchy GT, Edlow JA. Spectrum of dizziness visits to US emergency departments: cross-sectional analysis from a nationally representative sample. Mayo Clin Proc 2008;83:765–75. 12. Akinci E, Aygencel G, Keles A, Demircan A, Bildik F. Role of C-reactive protein, D-dimer and fibrinogen levels in the differential diagnosis of central and peripheral vertigo. Adv Ther 2007;24:1068–77. 13. Yardan T, Cevik Y, Donderici O, et al. Elevated Serum S100B protein and neuron-specific enolase level in carbon monoxide poisoning. Am J Emerg Med 2009;27:838–42. reau-Gayon R, Laborey M, et al. 14. Zongo D, Ribe S100B protein as a screening tool for the early assessment of minor head injury. Ann Emerg Med 2012;59:209–18. 15. Norrving B, Magnusson M, Holtas S. Isolated acute vertigo in the elderly; vestibular or vascular disease? Acta Neurol Scand 1995;91:43–8. 16. Herr D, Zun L, Mattehews JJ. A directed approach to the dizzy patient. Ann Emerg Med 1989;18:664–72. 17. Navi BB, Kamel H, Shah MP, et al. Rate and predictors of serious neurologic causes of dizziness in the emergency department. Mayo Clin Proc 2012;87:1080–8. 18. Ozono Y, Kitahara T, Fukushima M, et al. Differential diagnosis of vertigo and dizziness in the emergency department. Acta Otolaryngol 2014;134:140–5. 19. Cloutier JF, Saliba I. Isolated vertigo and dizziness of vascular origin. J Otolaryngol Head Neck Surg 2008;37:331–9.

Diagnostic value of S100B protein in the differential diagnosis of acute vertigo in the emergency department.

Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining...
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