Discussion

Differential diagnosis of vertigo is essential, because the cerebellar and brainstem ischaemic diseases that may cause dizziness can be serious and potentially deadly. Vertigo can be classified as central or peripheral. The causes of central vertigo may be life-threatening; because of this, it is vital to establish a differential diagnosis for peripheral and central vertigo in patients with dizziness (Table 5).^{Reference Derin and Yaprak5}

Table 5. Causes of vertigo

It has been reported that between 0.7 and 3.2 per cent of patients who presented to the emergency department in the USA with dizziness had ischaemic disease (central vertigo). The cost of diagnosing dizziness in the USA was, in 2013, estimated to exceed $10 million. Emergency service medics try to diagnose the diseases as quickly as possible and with the lowest cost. However, in some cases, it is difficult to diagnose them based on anamnesis and physical examination, and, because of this, further examination and imaging findings are needed. This leads to prolonged hospital stays and overcrowding in the emergency department.^{Reference Spiegel, Kirsch, Rosin, Rust, Baumann and Sutter2,Reference Edlow, Gurley and Newman-Toker3,Reference Halmagyi and Akdal6}

It is essential that differential diagnosis of life-threatening vertigo be performed rapidly and safely, which should also prevent emergency department overcrowding. Furthermore, the quality of life of vertigo patients can be significantly increased with appropriate treatment. The most important thing is the differential diagnosis of peripheral and central vertigo. A differential diagnosis can be made with good anamnesis and physical examination, but computed tomography (CT) and MRI of the brain are required in some clinical situations.^{Reference Lawhn-Heath, Buckle, Christoforidis and Straus7,Reference Lee8} Magnetic resonance imaging is not available in many emergency departments; CT imaging is more common. In a study by Pavlović et al., CT imaging was not helpful in vertigo patients without focal neurological signs.^{Reference Pavlović, Milošević, Trtica and Budinčević9} In patients who cannot be differentially diagnosed, MRI imaging is required, leading to extended length of stay in the emergency department and increased cost of diagnosis.

S100B is a calcium-binding protein released from brain astroglial cells, and is detectable in cerebrospinal fluid and blood. High levels of S100B can be found in patients with infectious diseases, ischaemic conditions and traumatic brain injuries. It is also effective in detecting cerebral injury after stroke, successful cardiac resuscitation or cardiac surgery. There is a consistent correlation between the severity of ischaemic lesions and S100B level.^{Reference Akoglu, Denizbasi, Guneysel, Onur, Eroğlu and Sarıtemur10,Reference Rezaei, Pakdaman, Gharehgozli, Simani, Vahedian-Azimi and Asaadi11}

Copeptin is a biomarker released as a precursor of arginine vasopressin from the posterior pituitary gland. It is easily detectable because of its stability in plasma and serum. It is estimated that copeptin could be widely used in emergency departments to ensure the diagnosis of life-threatening ischaemic diseases.^{Reference Perovic, Mrdjen, Harapin, Tesija Kuna and Simundic12,Reference Duman, Ozkan, Durukan, Avsaroglu, Muhtaroglu and Ipekci13}

Emergency departments in Turkey are quite crowded. Emergency physicians are not only trying to make a safe and rapid diagnosis; they are also trying to reduce the duration of stay in the emergency department. For this reason, a rapid, inexpensive and accurate diagnostic method is needed for patients who cannot be differentially diagnosed with central or peripheral vertigo. New biomarkers are also being analysed, and various algorithms are being created.

Vanni et al. evaluated the effectiveness of the ‘STANDING’ algorithm (i.e. (1) discrimination between spontaneous and positional nystagmus, (2) evaluation of nystagmus direction, (3) head impulse test and (4) evaluation of equilibrium) for a safe and effective diagnosis of the cause of vertigo in emergency department patients. The mean age of the patients was 58 ± 18 years, and 59.7 per cent of these patients were female. Patients with central vertigo were found to be older.^{Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe14} In a study by Perovic et al., 46 of the 109 stroke patients were male. In addition, the mean age of the stroke patients was higher than in the control group.^{Reference Perovic, Mrdjen, Harapin, Tesija Kuna and Simundic12}

In a study by Kartal et al., there were more male patients in the MRI-positive acute ischaemic group.^{Reference Kartal, Yılmaz, Yaka, Pekdemir, Sarısoy and Çekmen15} In contrast, the number of female patients was higher in the MRI-negative group without ischaemia. The mean age of patients with central vertigo was significantly higher than that of patients with peripheral vertigo. Regarding the difference between central and peripheral vertigo, gender was not found to be significant.

In the current study, the time between symptom onset and presentation to the emergency department was significantly greater in the central vertigo group than the peripheral vertigo group. Patients with peripheral vertigo were more likely to have a severe clinical presentation and to present to the emergency department earlier.

Akoglu et al. found that the probability of cardiac or hypovolaemic syncope in patients increased with high S100B levels, and adverse events were seen more often in patients who presented to the emergency department with syncope.^{Reference Akoglu, Denizbasi, Guneysel, Onur, Eroğlu and Sarıtemur10} In addition, patients with high S100B levels had more hypoperfusion in the brain, showing that adverse events of cerebral damage were more frequent. In light of these findings, they reported that the S100B level could be used to predict the prognosis of patients with syncope.^{Reference Akoglu, Denizbasi, Guneysel, Onur, Eroğlu and Sarıtemur10}

Rezaei et al. found that serum S100B level showed high sensitivity (94.4 per cent) but weak specificity (31.8 per cent) in the diagnosis of central vertigo.^{Reference Rezaei, Pakdaman, Gharehgozli, Simani, Vahedian-Azimi and Asaadi11} Therefore, they concluded that serum S100B level is advantageous in diagnosis and follow up, and for estimating the likelihood of developing the complication of ischaemic stroke. Still, it should be noted that serum S100B level may give false positive and false negative results in the diagnosis of central vertigo.

Kartal et al. compared the MRI and S100B levels in the differentiation of peripheral and central vertigo, and concluded that the S100B level alone could not replace MRI sensitivity.^{Reference Kartal, Yılmaz, Yaka, Pekdemir, Sarısoy and Çekmen15} Still, it could be sufficient for differential diagnosis if the clinical symptoms and S100B levels were evaluated together.

In the current study, the S100B value was significant in the differential diagnosis of central and peripheral vertigo (area under the curve, 0.981 μg/l (95 per cent CI, 0.960–1.000 μg/l)). A cut-off value of 17 for S100B was found to be significant (area under the curve, 0.933 μg/l (95 per cent CI, 0.873–0.993 μg/l)). The accuracy was 86.7 per cent, positive predictive value was 100 per cent, specificity was 100 per cent and negative predictive value was 88.2 per cent in the differential diagnosis of central and peripheral vertigo. The S100B levels were significantly higher in patients with central vertigo than in those with peripheral vertigo (p < 0.05). This is consistent with other studies. S100B is a useful biomarker in the differential diagnosis of central and peripheral vertigo (Figure 1).

Katan et al. found that the level of copeptin is a better option compared with blood laboratory parameters such as blood glucose, C-reactive protein and white blood cells, as well as clinical measurements such as blood pressure and body temperature.^{Reference Katan and Christ-Crain16} Copeptin is useful for the diagnosis and prognosis of patients with ischaemic stroke when it is evaluated with the National Institutes of Health Stroke Scale score.

Perovic et al. showed that ischaemic stroke patients had high copeptin levels, irrespective of age and sex. Their findings indicated that high copeptin level shows a poor prognosis.^{Reference Perovic, Mrdjen, Harapin, Tesija Kuna and Simundic12}

Dobša et al. studied copeptin's role in various diseases, and stated that C-peptide is a highly reliable biomarker in the diagnosis and follow up of cerebrovascular cases.^{Reference Dobša and Cullen Edozien17} They concluded that other biomarkers (D-dimer, glutamate, matrix metalloproteinases and S100B) are also useful in early diagnosis and mortality estimation of intracerebral cases. Still, C-peptide is directly released into the systemic circulation, unlike the other biomarkers, so measuring it would be more meaningful.

Copeptin level was found to be significant regarding its efficacy in the differential diagnosis of central and peripheral vertigo (area under curve, 0.792 pmol/l (95 per cent CI, 0.702–0.882 pmol/l)). The cut-off value for copeptin was determined as 1.65 pmol/l (area under curve, 0.722 pmol/l (95 per cent CI, 0.615–0.830 pmol/l)). For copeptin in the differential diagnosis of peripheral vertigo and central vertigo, the accuracy was determined as 95.6 per cent, positive predictive value was 65.2 per cent, specificity was 91.7 per cent and negative predictive value was 48.9 per cent. Patients with central vertigo were found to have higher copeptin levels than those with peripheral vertigo (p < 0.05). The results obtained from this study are consistent with other studies. They indicate that copeptin is another biomarker that can be used to differentiate central and peripheral vertigo (Figure 2).