Dizziness in older patients in general practice: away from diagnostic nihilism Dros, J.

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1 UvA-DARE (Digital Academic Repository) Dizziness in older patients in general practice: away from diagnostic nihilism Dros, J. Link to publication Citation for published version (APA): Dros, J. (2013). Dizziness in older patients in general practice: away from diagnostic nihilism General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 08 Mar 2017

2 Chapter 2 Tests used to evaluate dizziness in primary care Jacquelien Dros Otto R. Maarsingh Henriëtte E. van der Horst Patrick J. Bindels Gerben ter Riet Henk C.P.M. van Weert CMAJ 2010 Sep 21;182(13):E621-31

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4 ABSTRACT Background Although dizziness is a common symptom, the diagnostic approach to a dizzy patient is not straightforward, especially not in primary care. Purpose: To assess and summarize evidence about the accuracy of diagnostic tests which can be used in primary care to establish a diagnosis in dizzy patients or to select dizzy patients that need further testing or treatment. Methods We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Gerolit from database inception to February Two reviewers independently selected studies in dizzy patients comparing an index test feasible in primary care with an appropriate reference standard. Two pairs of two independent reviewers assessed the methodology of included studies using QUADAS and abstracted data. Results Of articles, 128 were eligible, and 26 were finally selected for data synthesis. These 26 studies evaluated 11 different diagnostic tests and 5 questionnaires. We found only tests for neuro-otological and psychiatric conditions. Data on head shaking nystagmus test (HSN) and head impulse test (HIT), diagnosing vestibular dysfunction, were considered appropriate for pooled analysis. From eight studies on HSN (4059 patients) pooled sensitivity was 45% (95% CI, 30-62%), pooled specificity 82% (95% CI, 68-90%), and pooled LR (95% CI, ). From six studies evaluating the HIT (869 patients) pooled sensitivity was 63% (95% CI, 40-81%), pooled specificity 93% (95% CI, 83-98%), and pooled LR (95% CI, 4.28 to 20.16). Limitations No accuracy studies were found in other relevant medical fields than otoneurology and psychiatry and no diagnostic accuracy studies were found for commonly used diagnostic tests in the domain dizziness. Data on HSN and HIT should be interpreted with caution in primary care. The other, single test studies, were not useful for conclusions on test accuracy. Conclusions There are many diagnostic tests on aspects of dizziness, but few have been validated in unselected patients. The accuracy of diagnostic tests on dizziness is poor, with possible exception of the HIT. 23

5 INTRODUCTION Dizziness is a nonspecific term that refers to various abnormal sensations of body orientation in space; patients often find these sensations difficult to describe. The prevalence of dizziness in the community ranges from 1.8% among young adults to over 30% in the elderly. Yearly consultation rates because of dizziness in primary care range from 2.5% among patients aged 25 to 44 years, to 8.3% among patients aged 65 years and older, and to 18.2% among patients aged 85 years and older. 1-5 Dizziness can be classified into four subtypes: vertigo, disequilibrium, presyncope and atypical dizziness. This classification is based on the study by Drachman and Hart. 6 There are few studies of the distribution of the specific diseases that can cause dizziness. The following data should, therefore, be interpreted with caution (Appendix 1). 5, 7-11 In primary care patients, vertigo (prevalence 38%) is mainly caused by otolaryngical conditions; disequilibrium (prevalence 10%) is mainly caused by orthopedic, neurologic or sensory problems; presyncope (prevalence 10%) is mainly caused by cardiac or vasomotor conditions; and atypical dizziness (prevalence 17%) is mainly caused by psychiatric problems. In about 25% of patients, the type cannot be classified or the problem has multiple causes. The prevalence of these diagnostic categories differs according to age. In younger patients, atypical dizziness and presyncope are most common. In middle-aged patients, vertigo is the most prominent. Presyncope and disequilibrium are more prevalent in elderly patients. 5, 12, 13 However, elderly 5, 12, 13 patients symptoms often have multiple causes. Practice guidelines advocate the use of several diagnostic tests in the evaluation of dizziness, including history-taking, pulse measurement, carotid sinus massage, nystagmus tests and the Dix-Hallpike manoeuvre. However, these recommendations are based more on opinion than on evidence. Many tests can often only be performed in secondary and tertiary care settings, although most patients are first seen in primary care. The main problem for primary care physicians is to decide which patients need additional testing, which should be referred to secondary care, which require immediate therapy, and which should receive an explanation, reassurance, advice and a wait and see approach. 24

6 Life-threatening conditions requiring immediate treatment are rare in patients with dizziness, a diagnostic workup should have the power to rule out such conditions (Appendix 2). 3, 6, 8, 17 In these mainly acute conditions (mastoiditis, pacemaker failure, myocardial or brainstem/cerebellar infarction, haemorrhage and serious electrolyte disturbances), dizziness is almost never the only presenting symptom, and obtaining a careful patient history and performing a targeted physical examination is usually sufficient for triage. Further diagnostic testing should be done in a secondary care setting. Primary care physicians need to know the characteristics of the diagnostic tests that can be used as point-of-care tests for the diagnosis of the more common conditions. We performed a systematic review of diagnostic tests that can be used to diagnose dizziness in patients in primary care. Because prevalence is important in the discriminative power of such tests, we provide epidemiologic information about target conditions in patients who present with dizziness. We have limited our review to the evaluation of these tests in patients with dizziness. METHODS Literature search We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Gerolit, from database inception to May 2009 to identify studies on diagnostic tests for dizziness in primary care. The complete strategy is shown in Appendix 3. 18, 19 We used the search filters reported by Bachmann and collegues. Study selection Two reviewers (JD, OM) independently selected potentially relevant studies on titles and abstracts. If disagreement occurred, consensus was reached with a third reviewer (HvW or HvdH). We excluded studies if the title did not include dizziness, disequilibrium, (pre)syncope or vertigo or a word with the same meaning or if it did not involve a disease that can cause dizziness (Appendix 3). We excluded articles if the abstract did not mention any diagnostic procedure, if the study population did not include patients with dizziness or if the test studied was too complex, time consuming or expensive to be feasible in primary care (e.g., carotid sinus massage, tilt table testing, posturography and specialized imaging techniques). We included only studies published in English, French, German or Dutch. 25

7 Data extraction and quality assessment The methodological quality of the studies was assessed by two pairs of reviewers (OM/HvdH and JD/HvW) with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. 20 Within each pair both reviewers independently scored all studies with the QUADAS checklist, extracted data and constructed 2 x 2 tables. Consensus was reached for any discrepancies. If an article reported the accuracy of more than one index test, target condition or cut-off point, we report the data for these tests, target conditions and cut-off points separately. Data synthesis and analysis We calculated sensitivity and specificity from the 2 2 tables and plotted the results in forest plots and receiver operating characteristics plots. We pooled the results from studies involving the same tests and conditions by use of a bivariate regression model that takes into account the correlation between sensitivity and specificity. This method was recently recommended for meta-analysis of diagnostic tests. 21, 22 If we could only extract the sensitivity of the test from the original data, we calculated the mean sensitivity and weighted it for the number of patients in the study. To assess clinical usefulness, we derived likelihood ratios and pre- and post-test probabilities of the target condition in the study population. Because we were interested in the accuracy of the diagnostic tests in primary care but most of the studies were done in secondary or tertiary care settings, we calculated pre- and post-test probabilities for a hypothetical primary care situation, assuming that the sensitivity and specificity would not be different in primary care. We estimated and retrieved the pretest probabilities of the target conditions in primary care from pertinent prevalence studies in primary care (Appendix 1). We used STATA/SE 10.1 (StataCorp, College Station, TX, USA) to perform the bivariate analyses. 26

8 RESULTS The study selection process is shown in Figure 1. We identified 290 primary articles that studied diagnostic tests that can be used in the primary care of patients with dizziness. Figure 1. Flow chart of the study selection process The kappa statistic was 0.81 for agreement on study selection by the two reviewers (J.D., O.M.). Based on a review of the full text, we excluded 162 articles. We assessed 128 articles using QUADAS. 20 After this review, we excluded 102 articles (Figure 1). Thus, we included 26 articles in this review (Table 1). 27

9 Table 1. Characteristics of 26 studies of diagnostic tests on dizziness feasible in primary care Study No. of participants, (women, %) Age, yr, mean (range) PSYCHIATRY, Psychogenic dizziness Persoons et al., (66) 48 (18 75) Study entry and inclusion criteria Random sample of dizzy patients referred to otorhino-laryngologist NEURO-OTOLOGY Questionnaires Kentala and Rauch, (74) 47 (20 78) Consecutive patients with dizziness López-Escámez 100 (65) NR Non-selected patients et al., with dizziness or vertigo von Brevern et al., 61 (51) NR (18-60+) Consecutive patients with dizziness Whitney et al., (64) 61 (15-95) Non-selec ted patients with balance and/or vestibular disorder Symptoms and signs Chan, (52) 79 (median) (33-90) : instrument for triage, not diagnostic NR: not reported Dix-Hallpike manoeuvre Cohen, (NR) NR (NR) Norré, (61) 54 (14-87) Consecutive patients with dizziness not fulfilling exclusion criteria Selected patients with vertigo on head move ment and referred for vestibular testing Selected patients with vertigo on head movement Side-lying manoeuvre Cohen, (NR) NR (NR) Selected patients with vertigo on head movement and referred for vestibular testing 28

10 Setting Target condition Index test Reference standard tertiary academic clinic, Belgium Major depressive disorder; panic disorder Depression and panic disorder part of the patient health questionnaire MINI interview tertiary clinic, USA Vertigo Dizziness questionnaire Diagnosis after clinical evaluation clinic, Spain Ménière s disease Structured questionnaire of vertigo Ménière s disease criteria of the American Academy of Otolaryngology, Head and Neck Surgery; 10 months follow-up tertiary clinics, Germany academic (physical therapy) clinic, USA Benign Paroxysmal Positional Vertigo (BPPV) Vestibular vertigo questionnaire BPPV DHI BPPV subscore, 5 items or 2 items Dix-Hallpike manoeuvre and/or diagnosis after clinical evaluation Dix-Hallpike manoeuvre tertiary clinic, China BPPV Spinning; episodic; Positional; nausea/ vomiting Dix-Hallpike and side-lying manoeuvre tertiairy academic clinic, USA BPPV Dix-Hallpike manoeuvre Battery of vestibular tests academic clinic, Belgium BPPV Dix-Hallpike manoeuvre Battery of vestibular tests tertiairy academic clinic, USA BPPV Side-lying manoeuvre Battery of vestibular tests 29

11 Table 1, continued Study No. of participants, (women, %) Head-shaking nystagmus Burgio et al., (NR) NR (NR) Age, yr, mean (range) Study entry and inclusion criteria Non-selec ted referred dizzy patients Fujimoto et al., Goebel and Garcia, Guidetti et al., Harvey et al., (58) 48 (8 91) 214 (NR) 55 (median) (9 83) 661 (65) 55 (14-80) 105 (67) 52 (13 87) Consecutive patients during routine ENG testing Randomly selected dizzy patients Non-selec ted patients with and without vertigo Consecutive dizzy patients Jacobson et al., 116 (NR) NR (NR) Consecutive dizzy patients referred for balancae testing Mandala et al., 65 (37) (13-84) Selected patients with vestibular neuritis Tseng and Chao, 258 (62) NR (14 79) Vicini et al., 277 (53) (6-83) Head impulse test Beynon et al., 150 (NR) (13-76) Cnyrim et al, 83 (53) (NR) Consecutive patients with dizziness or vertigo NR; referred patients with vestibular and/or neu ro logical complaints NR; patients with balance disorder Selected patients with vertigo, nystagmus and postural imbalance Harvey et al., (65) (224 ears) 53 (13 87) NR; dizzy patients Harvey et al., 105 (67) (13 87) Mandala et al., 65 (37) (13-84) Consecutive dizzy patients Selected patients with vestibular neuritis 30

12 Setting Target condition Index test Reference standard academic clinic, USA academic clinic, Canada tertiary clinic, USA tertiary academic clinic, Italy tertiary academic clinic, USA clinic, USA academic clinic, Italy academic clinic, Taiwan (academic) clinics, Italy Peripheral vestibular dysfunction Peripheral vestibular dysfunction Peripheral vestibular dysfunction Peripheral vestibular dysfunction Peripheral vestibular dysfunction Peripheral vestibular dysfunction Periphera vestibular dysfunction (vestibular neuritis) Peripheral vestibular dysfunction Peripheral and central vestibular dysfunction Head-shaking nystagmus Caloric tests and ENG Head-shaking nystagmus >20% difference in right/ left caloric testing Head-shaking nystagmus Caloric tests Head-shaking nystagmus Caloric tests Head-shaking nystagmus Caloric tests Head-shaking nystagmus Battery of vestibular tests Head-shaking nystagmus Caloric tests Head-shaking nystagmus Caloric tests with ENG Head-shaking nystagmus Battery of vestibular tests clinics, UK academic clinics, Germany and USA academic clinic, USA tertiary academic clinic, USA academic clinic, Italy Peripheral vestibular dysfunction Peripheral (vestibular neuritis) and central vestibular dysfunction Peripheral vestibular dysfunction Peripheral vestibular dysfunction Peripheral vesti bular dysfunction (vestibular neuritis) Head impulse test Head impulse test Head impulse test Head impulse test Head impulse test Caloric tests Caloric tests with ENG and cranial MRI Caloric tests Caloric tests Caloric tests 31

13 Table 1, continued Study No. of participants, (women, %) Age, yr, mean (range) Newman-Toker 42 (35) 64 et al., (26-92) Study entry and inclusion criteria Consecutive referred patients with acute vertigo and high risk for stroke Perez and Rama- 265 (50) 50 Lopez, (NR) Non-selec ted referred patients with vertigo Vibration induced nystagmus Mandala et al., (37) 54 (13-84) Selected patients with vestibular neuritis Michel et al., 399 (NR) NR (NR) NR; patients with and without vertigo Cold mini caloric test Weinberg and Sadé, (NR) NR (NR) NR; patients with ves ti bu lar neuroni tis, Menière disease, acoustic tumor or dizziness Head heave test Mandala et al., 65 (37) (13-84) Selected patients with vestibular neuritis High-frequency oscillopsia test Burgio et al., (NR) NR (NR) Non-selec ted referred dizzy patients Hyperventilation-induced nystagmus Robichaud et al., (66) 53 (25-72) Robichaud et al., 24 (54) (39-78) Selected referred dizzy patients with >25% difference in right/left caloric testing Patients with acoustic neurinoma Positional nystagmus test Guidetti et al., (65) 55 (14-80) Non-selected patients with and without vertigo NR: not reported 32

14 Setting Target condition Index test Reference standard () tertiary academic clinic, USA academic clinic, Spain Peripheral (vesti bular neuritis) and cen tral vestibular dysfunction (brainstem or cere bel lar stroke) Peripheral vestibular dysfunction Head impulse test Head impulse test ENG or videonystagmography and cranial MRI Caloric tests academic clinic, Italy clinics, France Peripheral vesti bular dysfunction (vestibular neuritis) Peripheral vestibular dysfunction Vibration-induced nystagmus Vibration-induced nystagmus Caloric tests Caloric tests clinic, Israel Peripheral vesti bular dysfunction Cold mini caloric test Clinical diagnosis academic clinic, Italy Peripheral vesti bular dysfunction (vestibular neuritis) Head heave test Caloric tests academic clinic, USA Peripheral vesti bular dysfunction Oscillopsia test Caloric tests and ENG tertiairy academic clinic, Canada tertiairy academic clinic, Canada Peripheral vestibu lar dysfunction Central vestibular dysfunction Hyperventilation - induced nystagmus Caloric tests Cranial MRI tertiary academic clinic, Italy Peripheral vestibu lar dysfunction Positional nystagmus by direct observation Caloric tests 33

15 We included one study of a psychiatric test (subtype atypical), and 25 studies of neuro-otologic tests (subtype vertigo). No studies about disequilibrium and presyncope were available. Five studies involved two or more tests, five studies reported on target conditions, and two studies evaluated two cut-off points of the same test (Table 2). Methodological quality Quality assessment with the QUADAS tool is presented in Appendix 4. Each study had Table 2. Data from 26 studies that tested the accuracy of diagnostic tests for diagnosing dizziness in primary care Study Truepositive results PSYCHIATRY, Psychogenic dizziness Target condition = major depressive disorder Patient Health Questionnaire Falsepositive results Falsenegative results Persoons et al., Target condition = panic disorder Patient Health Quetionnaire Persoons et al, Truenegative results NEURO-OTOLOGY Target condition = Benign Paroxysmal Positional Vertigo Questionnaires von Brevern et al., Whitney et al., ; DHI BPPV subscore, 5 items Whitney et al., ; DHI BPPV subscore, 2 items Symptoms and signs Chan, Spinning sensation Chan, Episodic attacks of dizziness Chan, Rapid head movements provoking dizziness Chan, Nausea and/or vomitting as associated symptoms Dix-Hallpike maneuver Cohen, Norré,

16 at least two methodologic limitations that could introduce bias. In almost all studies, the spectrum of included patients was not representative of primary care patients. Sensitivity, specificity, and likelihood ratios Table 2 shows the sensitivity, specificity and positive and negative likelihood ratios of the included studies. The pre- and post-test probabilities of the target condition in the study population and in a theoretical primary care population are shown in Appendix 5. Sensitivity (95% CI) Specificity (95% CI) LR of posi tive result (95% CI) LR of nega tive re sult (95% CI) 72.7 ( ) 94.2 ( ) ( ) 0.29 ( ) 94.1 ( ) 96.3 ( ) 25.1 ( ) 0.06 ( ) 88.0 ( ) 91.7 ( ) ( ) 0.13 ( ) 73.8 ( ) 38.1 ( ) 1.19 ( ) 0.69 ( ) 40.5 ( ) 75.4 ( ) 1.65 ( ) 0.79 ( ) 60.0 ( ) 63.9 ( ) 1.66 ( ) 0.63 ( ) 80.0 ( ) 26.5 ( ) 1.09 ( ) 0.76 ( ) 80.0 ( ) 36.1 ( ) 1.25 ( ) 0.55 ( ) 20.0 ( ) 63.9 ( ) 0.55 ( ) 1.25 ( ) 58.6 ( ) 87.1 ( ) 35

17 Table 2, continued Study Truepositive results Falsepositive results Side-lying maneuver Cohen, Falsenegative results Truenegative results Target condition = vertigo Questionnaire Kentala and Rauch, Target condition = Ménière s disease Questionnaire López-Escámez et al., Target condition = peripheral vestibular dysfunction Head shaking nystagmus Burgio et al., Fujimoto et al., Goebel and Garcia, Guidetti et al., Harvey et al., Jacobson et al., Mandala et al., Tseng and Chao, Vicini et al., Head impulse test Beynon et al., Cnyrim et al, Harvey et al., Harvey et al.,

18 Sensitivity (95% CI) Specificity (95% CI) LR of posi tive result (95% CI) LR of nega tive re sult (95% CI) 65.5 ( ) 60.0 ( ) 63.6 ( ) 1.65 ( ) 0.63 ( ) 83.3 ( ) 97.9 ( ) ( ) 0.17 ( ) 42.9 ( ) 51.2 ( ) 0.88 ( ) 1.11 ( ) 50.2 ( ) 72.7 ( ) 1.84 ( ) 0.69 ( ) 41.9 ( ) 84.8 ( ) 2.75 ( ) 0.69 ( ) 20.1 ( ) 90.2 ( ) 2.05 ( ) 0.89 ( ) 35.0 ( ) 91.8 ( ) 4.25 ( ) 0.71 ( ) 45.1 ( ) 98.5 ( ) ( ) 0.56 ( ) 95.4 ( ) 90.2 ( ) 53.4 ( ) 1.94 ( ) 0.18 ( ) 34.1 ( ) 77.4 ( ) 1.51 ( ) 0.85 ( ) 49.0 ( ) 100 ( ) ( ) 0.51 ( ) 92.5 ( ) 60.5 ( ) 2.34 ( ) 0.12 ( ) 39.4 ( ) 96.9 ( ) ( ) 0.63 ( ) 35.0 ( ) 95.3 ( ) 7.44 ( ) 0.68 ( ) 37

19 Table 2, continued Study Truepositive results Falsepositive results Mandala et al., Falsenegative results Truenegative results Newman-Toker et al., Perez and Rama-Lopez, Asymmetry caloric test >22% Perez and Rama-Lopez, Asymmetry caloric test >42.5% Vibration induced nystagmus Mandala et al., Michel et al., Cold mini caloric test Weinberg and Sadé, Head heave test Mandala et al., High-frequency oscillopsia test Burgio et al., Hyperventilation-induced nystagmus Robichaud et al., Positional nystagmus test Guidetti et al., Target condition = central vestibular dysfunction Head shaking nystagmus Vicini et al., Head impulse test Cnyrim et al, Newman-Toker et al., Hyperventilation-induced nystagmus Robichaud et al.,

20 Sensitivity (95% CI) 83.1 ( ) ( ) 56.8 ( ) 77.2 ( ) Specificity (95% CI) 91.2 ( ) 90.5 ( ) 88.4 ( ) LR of posi tive result (95% CI) 9.44 ( ) 5.97 ( ) 6.68 ( ) LR of nega tive re sult (95% CI) 0.06 ( ) 0.48 ( ) 0.26 ( ) 81.3 ( ) 88.2 ( ) 90.8 ( ) 9.6 ( ) 0.13 ( ) 94.4 ( ) 88.6 ( ) 8.26 ( ) 0.06 ( ) 66.2 ( ) 40.0 ( ) 75.0 ( ) 1.60 ( ) 0.80 ( ) 18.4 ( ) 6.4 ( ) 100 ( ) ( ) 0.94 ( ) 22.6 ( ) 65.9 ( ) 0.66 ( ) 1.17 ( ) 60.5 ( ) 91.2 ( ) 92.5 ( ) 100 ( ) 8.06 ( ) 16.2 ( ) 0.43 ( ) 0.11 ( ) 58.3 ( ) 39

21 Tests The performance of all studied tests and the analyses of tests described in a single study are presented in Appendix 6. Accurate evaluation of diagnostic tests should be based on the results of more than one study. Therefore, we describe four tests, all targeted for neuro-otologic conditions, that were evaluated in more than one study. Dix-Hallpike manoeuvre Both studies of the use of the Dix-Hallpike manoeuvre to diagnose benign paroxysmal positional vertigo used multiple vestibular tests as reference standards. Data from 114 patients were available, and we calculated a mean sensitivity of 80% (95% confidence interval [CI] 71% 87%). Head-shaking nystagmus test All nine studies of the use of the head-shaking nystagmus test used caloric measurement as part of the reference standard. Data from 4059 patients (eight studies) were available for pooled analysis (Figure 2 and Appendix 7). The pooled sensitivity was 45% (95% CI 30% 62%), the pooled specificity was 82% (95% CI 68% 90%), the pooled positive likelihood ratio (LR) was 2.47 (95% CI ) and the pooled negative LR was 0.67 (95% CI ). In these studies, the pooled probability of peripheral vestibular dysfunction after a positive headshaking nystagmus test result increased from 27% to 48%, and the probability after a negative result decreased from 27% to 25%. Using an estimated prevalence of 33% for peripheral vestibular dysfunction in primary care patients with dizziness, 7, 9-11 the post-test probability of a positive head-shaking nystagmus test result was 55% and the post-test probability of a negative result was 25%. 40

22 Figure 2. Sensitivity and specificity of the head-shaking nystagmus test for diagnosing unilateral vestibular dysfunction Head impulse test The seven studies that evaluated the head impulse test for peripheral vestibular dysfunction used caloric measurement as a reference standard. Data were available from 869 patients (six studies) for pooled analysis (Figure 3 and Appendix 8). The pooled sensitivity was 63% (95% CI 40% 81%), and the pooled specificity was 93% (95% CI 83% 98%). The pooled positive LR was 9.29 (95% CI ), and the pooled negative LR was 0.40 (95% CI ). In these studies, the probability of peripheral vestibular dysfunction after a positive test result increased from 33% to 82%, and the probability after a negative result decreased from 33% to 17%. Because the estimated prevalence in primary care 7, 9-11 matched the prevalence in the studied population (both 33%), the posttest probabilities were the same. 41

23 Figure 3. Sensitivity and specificity of the head impulse test for diagnosing unilateral vestibular dysfunction Two studies 28, 40 evaluated the accuracy of the head impulse test for central vestibular dysfunction in patients with vertigo. These studies used cranial magnetic resonance imaging as a reference standard. Data from 125 patients were available for pooled analysis. A negative result of this test suggests a central lesion. The pooled sensitivity was 74% (95% CI 63% 83%), and the pooled specificity was 94% (95% CI 83% 99%). The probability of central vestibular dysfunction after a positive head impulse test result decreased from 62% to 31%, and the probability after a negative result increased from 62% to 95%. Vibration-induced nystagmus test In the two studies that evaluated vibration-induced nystagmus, data were available from 463 patients, giving a calculated sensitivity of 84% (95% CI 81% 88%). We calculated specificity based only on one study, with a positive result of the vibration-induced nystagmus test increasing the probability of peripheral vestibular dysfunction from 13% to 59%. Using the estimated prevalence of 33% 7, 9-11 for peripheral vestibular dysfunction in primary care patients with dizziness, we estimated the post-test probability of a positive vibrationinduced nystagmus test result to be 83%. 42

24 DISCUSSION The results of our review show that the empirical validation of commonly used diagnostic tests for dizziness in primary care is poor. We found few studies that focused on dizziness. It was only possible to perform a meta-analysis of two tests in the neuro-otological field. Although many studies were performed for tests used in diagnosing dizziness, most were not diagnostic studies, were methodologically inadequate or did not include patients with dizziness. All of the included studies used some type of preselection of patients and were intended to diagnose specific conditions, such as Ménière disease, peripheral vestibular dysfunction, major depressive disorder or panic disorder. The main interest in primary care, however, is the differentiation between selflimiting conditions, those for which adequate treatment is available and those that are dangerous or progressive or both and require referral or immediate treatment. Although many tests are used to diagnose dizziness in primary care, we could not find any studies that included consecutive patients with dizziness. Studies about the use of patient history, pulse measurement, heart auscultation and balance in the diagnosis of dizziness are lacking. Although we looked for studies of tests that are feasible in primary care, all of the included studies were, at least, partially conducted in secondary or tertiary settings. As a result, the high prevalence of the target conditions in the included populations (6% for Ménière disease and 80% for vertigo) inflates the positive predictive values and decreases the negative predictive values. Furthermore, symptoms are probably more severe or pronounced in patients referred for secondary or tertiary care, which may inflate both the sensitivity and specificity. Although we used prevalence in a hypothetical primary care population to estimate likelihood ratios, we could not correct for this phenomenon. This limits the generalizability of our results to patients in primary care. An exception may be the head-shaking nystagmus test and the head impulse test. The prevalence of peripheral vestibular dysfunction in primary care patients with dizziness was similar to that in the studied populations. Although the prevalence of dizziness increases with age and the need for valid diagnostic tests or protocols is evident, especially for use in elderly patients, none of the studies in our review included an elderly population. As age increases, both the prevalence of dizziness and the risk of more serious causes of dizziness (stroke or cardiovascular diseases) increase. Comorbid conditions causing dizziness (e.g., diabetes, Parkinson disease) also become more prevalent. Most tests for the diagnosis of dizziness were analyzed in a single study. The exceptions were the head-shaking nystagmus test, the head impulse test, the vibration-induced nystagmus test and the Dix-Hallpike manoeuvre. Promising 43

25 tests within single test studies were the Vestibular Vertigo Questionnaire for the diagnosis of BPPV (positive LR 10.56, 95% CI ), the depression part of the Patient Health Questionnaire for the diagnosis of major depressive disorder (positive LR 12.51, 95% CI ) and the panic disorder part of the Patient Health Questionnaire for the diagnosis of panic disorder (positive LR 25.1, 95% CI ). Both the head-shaking nystagmus test and the head impulse test seem to be better suited for ruling in than for ruling out peripheral vestibular dysfunction. However, for conditions that are most often self-limiting (e.g., peripheral vestibular dysfunction), an increased probability from 27% to 48% after a positive test result is of limited value. The head impulse test performs better for the diagnosis of peripheral vestibular dysfunction, with an increased probability from 33% to 82% after a positive result and, based on two studies, an increased probability of central vestibular dysfunction from 62% to 95% after a negative result. Many tests have been evaluated in patients without dizziness (e.g., peripheral neuropathy tests, visual acuity) or are included in the definition of the condition (e.g., hypoglycaemia or orthostatic hypotension tests). Before the results of these studies can be used in the assessment of a certain diagnosis in a patient with dizziness, these tests must be validated in the appropriate domain. This is especially true for dizziness, because the cause is often not sufficiently supported by scientific evidence. In elderly patients, who often have more than one condition that can cause dizziness, physicians must be cautious in not treating these patients on the basis of test results that are not consistent with the patient s symptoms. The appropriate patients to be included in studies of diagnostic tests for dizziness are those who present with dizziness as an isolated symptom and who are not at risk for the acutely life-threatening illnesses mentioned earlier. Prior selection of patients may affect test characteristics. The signs and symptoms must be described precisely, and the study design must comply with accepted 49, 50 methodologic criteria. Additional research into the tests that can be used in primary care to diagnose dizziness or to determine which patients need further testing or treatment is highly warranted. 44

26 Appendix 1. Prevalence of dizziness in primary care 7, 9-11 Prevalence of dizziness in primary care according to the classification in four subtypes Subtype (%) Madlon-Kay 1985 (n = 121) Kroenke 1992 (n = 100) Sloane 1994 (n = 144) Hanley 2002 (n = 170) Total* (n = ) Vertigo Disequilibrium Presyncope Atypical No diagnosis Multicausal * Total n depends on studies reporting specific categories. If a study did not report a certain category (- in table) the study population is left out in the total. 45

27 Appendix 2. 7, 9, 11 Reported frequency of causes of dizziness in primary care studies Diagnoses (%) Madlon- Kay 1985 (n=121) Kroenke 1992 (n=100) Sloane 1994 (n=144) Hanley 2002 (n=170) Total* (n= ) Peripheral vestibular dysfunction Labyrinthitis or vestibular neuronitis Benign paroxysmal positional vertigo Ménière s disease Other recurrent vestibulopathy Neurologic conditions (excluding cerebrovascular conditions) Central neurologic conditions Disequilibrium Cardiovascular conditions (inclu ding cerebrovascular conditions) Cardiac disease Cerebrovascular conditions Vasovagal conditions Migraine Presyncope Psychiatric conditions Major depression # Panic disorder # Hyperventilation Infection 15 ± Viral syndrome Otitis media, otitis externa or sinusitis Other infection Adverse effects of drugs, including alcohol Metabolic or endocrine conditions 9 ~ Anemia, including gastrointestinal Bleeding Diabetes Other conditions Multiple conditions None * Total n depends on studies reporting specific categories. If a study did not report a certain category (- in table) the study population is left out in the total. Peripheral vestibular dysfunction = labyrinthitis + BPPV + Ménière s disease + other vestibulopathy. Neurologic conditions, excluding cerebrovascular conditions = central neurologic conditions (e.g. cerebral tumors) + disequilibrium + other neurologic conditions (not reported in studies). Cardiovascular conditions = cerebrovascular conditions + migraine + cardiac disease + vasovagal conditions + presyncope. # Diagnoses mentioned separately because used in systematic review. ± Infection = viral syndrome + otitis media, otitis externa or sinusitis + other infection. ~ Metabolic or endocrine conditions = anemia, including gastrointestinal bleeding + diabetes + other metabolic or endocrine conditions (not reported in studies) 46

28 Appendix 3. Search strategy Our search strategy in MEDLINE was built up with the following components: 1.MeSH: -disequilibrium #1 Search Dizziness [MeSH] OR Musculoskeletal Equilibrium [MeSH] OR Parkinsonian Disorders [MeSH] OR Brain Concussion [MeSH] OR Brain Ischemia [MeSH] OR Carotid Artery Diseases [MeSH] OR Cerebrovascular Accident [MeSH] OR Cerebrovascular Trauma [MeSH] OR Hypoxia-Ischemia, Brain [MeSH] OR Cerebral Arterial Diseases [MeSH] OR Intracranial Embolism and Thrombosis [MeSH] OR Intracranial Hemorrhages [MeSH] OR Somatosensory Disorders [MeSH] OR Gait Disorders, Neurologic [MeSH] OR Polyneuropathies [MeSH] OR Diabetic Neuropathies [MeSH] OR Peripheral Nervous System Neoplasms [MeSH] OR Muscular Diseases [MeSH] -presyncope #2 Search Dizziness [MeSH] OR Syncope [MeSH] OR Hypotension [MeSH] OR Anxiety Disorders [MeSH] OR Depression [MeSH] OR Heart Diseases [MeSH] OR Hypertension [MeSH] OR Brain Ischemia [MeSH] OR Carotid Artery Diseases [MeSH] OR Cerebrovascular Accident [MeSH] OR Cerebrovascular Trauma [MeSH] OR Hypoxia- Ischemia, Brain [MeSH] OR Cerebral Arterial Diseases [MeSH] OR Intracranial Embolism and Thrombosis [MeSH] OR Intracranial Hemorrhages [MeSH] -vertigo #3 Search Labyrinth Diseases [MeSH] OR Vestibulocochlear Nerve Diseases [MeSH] OR Cholesteatoma, Middle Ear [MeSH] OR Ear Neoplasms [MeSH] OR Ear Deformities, Acquired [MeSH] OR Tinnitus [MeSH] OR Herpes Zoster Oticus [MeSH] OR Otitis Media [MeSH] OR Tympanic Membrane Perforation [MeSH] OR Brain Ischemia [MeSH] OR Carotid Artery Diseases [MeSH] OR Cerebrovascular Accident [MeSH] OR Cerebrovascular Trauma [MeSH] OR Hypoxia-Ischemia, Brain [MeSH] OR Cerebral Arterial Diseases [MeSH] OR Intracranial Embolism and Thrombosis [MeSH] OR Intracranial Hemorrhages [MeSH] OR Brain Neoplasms [MeSH] 2.Textwords: #4 Search balance[tw] OR disorientat*[tw] OR dizz*[tw] OR faint*[tw] OR falli*[tw] OR float*[tw] OR gidd*[tw] OR imbalance[tw] OR impaired postural control[tw] OR instab*[tw] OR (light[tw] AND head[tw]) OR lighthead*[tw] OR lighthead*[tw] OR orthostat*[tw] OR (postur*[tw] AND hypotens*[tw]) OR rotat*[tw] OR spinn*[tw] OR stagger*[tw] OR sway*[tw] OR swing*[tw] OR unstab*[tw] OR unstead*[tw] OR vertig*[tw] OR whirl*[tw] OR wobb*[tw] 47

29 Appendix 3, continued 3.Filters: -adult #5 Search child[mesh] NOT adult[mesh] -human #6 Search animal[mh] NOT human[mh] -publication type (pt) #7 Search addresses [pt] OR bibliography [pt] OR biography [pt] OR case reports [pt] OR clinical conference [pt] OR congresses [pt] OR consensus development conference [pt] OR consensus development conference, nih [pt] OR dictionary [pt] OR directory [pt] OR duplicate publication [pt] OR evaluation studies [pt] OR festschrift [pt] OR government publications [pt] OR guideline [pt] OR interview [pt] OR lectures [pt] OR legal cases [pt] OR legislation [pt] OR meta analysis OR news [pt] OR newspaper article [pt] OR patient education handout [pt] OR periodical index [pt] OR practice guideline [pt] OR review [pt] OR review, multicase [pt] OR review, tutorial [pt] OR review of reported cases OR scientific integrity review [pt] OR technical report [pt] OR twin study [pt]) -Bachmann #8 Search Sensitivity and Specificity [MeSH] OR predict*[tw] OR diagnos*[tw] OR accura*[tw] #9 Search #1 OR #2 OR #3 #10 Search #9 AND #4 #11 Search 10 NOT (#5 OR #6 OR #7) #12 Search #11 AND #8 Our search strategy in EMBASE was built up with the following components: 1.Keywords: -disequilibrium: #1 Search Balance Disorder/ or Body Equilibrium/ or Brain Degeneration/ or Brain Embolism/ or Brain Hypoxia/ or Brain Injury/ or Brain Tumor/ or Cerebellum Disease/ or Cerebrovascular Disease/ or Diabetic Neuropathy/ or Dizziness/ or Falling/ or Gait Disorder/ or Hypertension Encephalopathy/ or Motor Dysfunction/ or Motor Neuropathy/ or Muscle Disease/ or Parkinson Disease/ or Parkinsonism/ or Peripheral Neuropathy/ or Polyneuropathy/ or Proprioception/ or Senile Plaque/ or Sensorimotor Neuropathy/ 48

30 -presyncope #2 Search Anxiety/ or Anxiety Disorder/ or Cerebrovascular Disease/ or Collapse/ or Depression/ or Faintness/ or Heart Arrhythmia/ or Hyperventilation/ or Hypotension/ or Orthostatic Hypertension/ or Syncope/ -vertigo #3 Search Ear infection/ or Ear injury/ or Ear tumor/ or Inner ear disease/ or Inner ear malformation/ or Middle ear disease/ or Middle ear malformation/ or Otalgia/ or Otorrhea/ or Vertigo/ 2. Textwords: #4 Search (balance or disorientat$ or dizz$ or faint$ or falli$ or float$ or gidd$ or imbalance or (impaired and postural and control) or instab$ or (light and head) or lighthead$ or orthostat$ or (postur$ and hypotens$) or rotat$ or spinn$ or stagger$ or sway$ or swing$ or unstab$ or unstead$ or vertigo$ or whirl$ or wobb$).mp 3. Filters: -human #5 Search animal/ not human/ #6 Search animal experiment/ or animal model/ -adult #7 Search child/ not adult/ -Publication type #8 Search Letter/ or Editorial/ or Note/ or Review/ or Short Survey/ or Case report/ or In vitro study/ -Bachmann #9 Search (sensitiv$ or detect$ or accura$ or specific$ or reliab$ or positive or negative or diagnos$).mp #10: 1 or 2 or 3 #11: 10 and 4 #12: 11 not 5 not 6 not 7 not 8 #13: 12 and 9) We identified studies in PsycINFO, CINAHL, and Gerolit using the search terms dizz* or dizziness and, if possible, diagnosis or diagnostic. More advanced searches on the subject of dizziness were not possible in these databases. 49

31 Appendix 4. The QUADAS Tool 20 Qualification of the 26 studies with the QUADAS tool Study, year PSYCHIATRY, Psychogenic dizziness Persoons, 2003??? yes yes yes yes yes yes? yes yes yes yes NEURO-OTOLOGY Questionnaires Kentala & no no? yes yes yes yes yes no yes yes yes yes n.a. Rauch, 2003 López- Escámez, 2000 von Brevern, 2006? yes? yes yes yes yes yes yes yes? yes no no yes yes yes yes yes yes yes? yes yes? yes?? Whitney, 2005 yes no yes yes yes yes yes yes yes n.a. yes yes?? Symptoms and signs Chan, 2008 no yes yes yes yes yes yes? yes yes yes yes yes yes Dix-Hallpike maneuver Cohen, 2004 yes no? yes yes yes yes yes yes?? yes yes yes Norré, 1994 no no yes yes yes yes yes yes yes yes? yes no n.a. Side-lying maneuver Cohen, 2004 yes no? yes yes yes yes yes yes?? yes yes yes Head shaking nystagmus (HSN) Burgio, 1991 no no? yes yes yes yes yes no??? no n.a. Fujimoto, 1993? no yes? yes yes yes? no?? no? yes Goebel & Garcia, 1992 no no?? yes yes yes yes yes no no yes? yes Guidetti, 2006 no? yes? yes yes yes yes yes yes yes yes?? Harvey, 1997 no? yes? yes yes yes yes yes yes yes? yes yes Jacobson, 1990? no yes? yes yes yes yes???? yes? Mandala, 2008 no yes yes yes yes yes yes yes yes?? yes yes yes Tseng & Chao, 1997? no yes? yes yes yes yes yes??? yes yes Vicini, 1980 no no? yes yes no no yes no?? yes no yes 50

32 Study, year Head impulse test (HIT) Beynon, 1998 no no yes? yes yes yes yes????? yes Cnyrim., 2008 no yes yes yes yes yes yes yes yes? no yes?? Harvey, 1996? no yes yes yes yes yes yes yes yes yes yes?? Harvey, 1997 no? yes? yes yes yes yes yes yes yes? yes yes Mandala, 2008 no yes yes yes yes yes yes yes yes?? yes yes yes Newman- Toker, 2008 no yes yes yes yes yes yes yes yes yes no yes yes yes Perez Rama- Lopez, 2003 no yes yes yes yes yes yes yes yes??? n.a. n.a. Vibration induced nystagmus (VIN) Mandala, 2008 no yes yes yes yes yes yes yes yes?? yes yes yes Michel, 2001 no no? yes yes yes yes yes no?? no no no Cold mini caloric test Weinberg & Sadé, 1984 no no? yes yes yes? no??? no yes? Head heave test Mandala, 2008 no yes yes yes yes yes yes yes yes?? yes yes yes High-frequency oscillopsia test Burgio, 1992 no no yes? yes yes yes yes yes?? no no n.a. Hyperventilation induced nystagmus Robichaud, 2002 no no yes? yes? yes no?? yes no? yes Positional nystagmus test Guidetti, 2006 no? yes? yes yes yes yes yes yes yes yes?? 51

33 Appendix 4, continued The QUADAS tool has been developed in 2003 by Whiting et al. 20 They combined empirical evidence and expert opinion in a formal consensus method to develop a tool to be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. The tool does not incorporate a quality score. Instead, it is structured as a list of 14 questions that should each be answered yes, no or unclear. The 14 items cover patient spectrum, reference standard, disease progression bias, verification bias, review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and indeterminate results. The QUADAS tool* Item Yes No Unclear 1. Was the spectrum of patients representative ( ) ( ) ( ) of the patients who will receive the test in practice? 2. Were selection criteria clearly described? ( ) ( ) ( ) 3. Is the reference standard likely to correctly ( ) ( ) ( ) classify the target condition? 4. Is the time period between reference standard ( ) ( ) ( ) and index test short enough to be reasonably sure that the target condition did not change between the two tests? 5. Did the whole sample or a random selection ( ) ( ) ( ) of the sample, receive verification using a reference standard of diagnosis? 6. Did patients receive the same reference ( ) ( ) ( standard regardless of the index test result? 7. Was the reference standard independent of ( ) ( ) ( ) the index test (i.e. the index test did not form part of the reference standard)? 8. Was the execution of the index test described in ( ) ( ) ( ) sufficient detail to permit replication of the test? 9. Was the execution of the reference standard ( ) ( ) ( ) described in sufficient detail to permit its replication? 10. Were the index test results interpreted without ( ) ( ) ( ) knowledge of the results of the reference standard? 11. Were the reference standard results ( ) ( ) ( ) interpreted without knowledge of the results of the index test? 12. Were the same clinical data available when ( ) ( ) ( ) test results were interpreted as would be available when the test is used in practice? 13. Were uninterpretable/ intermediate test results ( ) ( ) ( ) reported? 14. Were withdrawals from the study explained? ( ) ( ) ( ) *Reproduced with permission from Health Technology Assessment

34 Appendix 5. Data from 26 studies that tested the accuracy of diagnostic tests Study, Year (Reference) for dizziness in primary care in relation to primary care prevalences Systematic review Prevalence (pre-test probability)*, % Post-test probability, % Positive test Negative test Dizzy patients in primary care Prevalence (pre-test probablity)**, % Post-test probability, % Positive test Negative test PSYCHIATRY, Psychogenic dizziness Target condition = major depressive disorder Patient Health Questionnaire Persoons et al., Target condition = panic disorder Patient Health Questionnaire Persoons et al, NEURO-OTOLOGY Target condition = BPPV Questionnaires von Brevern 41 et al., Whitney et al., ; DHI BPPV subscore, 5 items Whitney et al., ; DHI BPPV subscore, 2 items Symptoms and signs Chan, , Spinning sensation Chan, , Episodic attacks of dizziness Chan, , Rapid head movements provoking dizziness Chan, , Nausea and/or vomitting associated symptoms

35 Appendix 5, continued Study, Year (Reference) Systematic review Prevalence (pre-test probability)*, % Post-test probability, % Positive test Negative test Dizzy patients in primary care Prevalence (pre-test probablity)**, % Post-test probability, % Positive test Negative test Target condition = vertigo Questionnaire Kentala and Rauch, Target condition = Ménière s disease Questionnaire López-Escámez et al., Target condition = peripheral vestibular dysfunction Head shaking nystagmus Burgio et al., Fujimoto et al., Goebel and Garcia, Guidetti et al., Harvey et al., Jacobson et al., Tseng and Chao, Vicini et al.,

36 Study, Year (Reference) Systematic review Prevalence (pre-test probability)*, % Post-test probability, % Positive test Negative test Dizzy patients in primary care Prevalence (pre-test probablity)**, % Post-test probability, % Positive test Negative test Head impulse test Beynon et al., Cnyrim et al., Harvey et al., Harvey et al., Newman-Toker et al., Perez and Rama-Lopez, , Asymmetry caloric test >22% Vibration induced nystagmus Michel et al., Cold mini caloric test Weinberg and Sadé, High-frequency oscillopsia test Burgio et al., Positional nystagmus Guidetti et al., Target condition = centrall vestibular dysfunction Head impulse test Cnyrim et al., Newman-Toker et al., *Pooled if possible and rounded off; **Estimated (see Appendix 1) 55

37 Appendix 6. Performance of all studied tests and results of single test studies Psychiatric Patient Health Questionnaire (PHQ) The PHQ is a self-administered instrument to assess categorical psychiatric disorders according to the diagnostic criteria of DSM-IV. It has been validated in primary care patients. The PHQ consists of 5 modules (Somatoform Disorder, Mood Disorder, Anxiety Disorder, Eating Disorder and Alcohol Disorder) and concludes with a single question which quantifies the impact of the reported problems on work and social activities. Each module can be used separately. Algorithms are used to diagnose major depressive disorder (MDD)and panic disorder. We found one study in the psychiatric field that met our criteria and although Persoons et al. studied 4 target conditions, we included only MDD and panic disorder, because original data were lacking for the 2 other conditions (other depressive disorder and other anxiety disorder). In this study, assessing the Mood Disorder module of the PHQ increased the probability of MDD from 11% to 61%. Using the estimated prevalence of 8% for MDD in dizzy primary care patients 3, 8-11, the post-test probability of a positive depression part of the PHQ was 52%. Assessing the Anxiety Disorder module of the PHQ in this study increased the probability of panic disorder from 17% to 84%. Using the estimated prevalence of 11% for panic disorder in dizzy primary care patients 3, 5, 9, the post-test probability of a positive panic disorder part of the PHQ was 76%. Neuro-otologic Questionnaires Both questionnaire studies on benign paroxysmal positional vertigo (BPPV) used the Dix-Hallpike maneuver as (part of) the reference standard. Because they used different index tests, pooled analysis was not possible. In the study of von Brevern et al. the prevalence of BPPV increased from 41% to 88% after a positive test result on the Vestibular Vertigo Questionnaire (VVQ). Based on an estimated prevalence of BPPV in dizzy primary care patients of 11% 3, 9, 10, the probability after a positive score on the VVQ was 57%. In diagnosing BPPV, Whitney et al. tested the 5- and 2-items BPPV sub-scale of the Dizziness Handicap Inventory. The Dizziness Handicap Inventory is one of the most commonly used standardized questionnaires to quantify symptoms in dizzy patients. The 5-items BPPV sub-scale is positive if the score is 10 (out of 18), the 2-items BPPV sub-scale is positive if the score is 6 (out of 8). In this study the prevalence of BPPV increased from 23% to 26% after a positive test-result on the 5-items BPPV sub-scale and to 32% after a positive test-result on the 2-items BPPV sub-scale of the DHI. Using the estimated prevalence of BPPV in dizzy primary care patients of 11% 3, 9, 10 the probability after a positive score on the 5-items BPPV sub-scale was 13% and 17% after a positive score on the 2-items BPPV sub-scale. 56

38 The study of Kentala and Rauch is not a true diagnostic accuracy study on a test but a study based on history taking to triage dizzy patients into diagnostic groups for further management. The target condition was true vertigo with a thorough medical evaluation as a reference standard. In this study the prevalence of true vertigo increased from 61% to 72% after a positive test result. Using the estimated prevalence of vertigo in dizzy primary care patients of 38% 3,7-11 the probability after a positive score on the Dizziness Questionnaire was 50%. In the questionnaire study of López-Escámez et al., a positive Structured Questionnaire of Vertigo increased the probability of Ménière s disease from 6% to 71%. Estimating the prevalence of Ménière s disease in dizzy primary care patients at 4% 7, 9 the post-test probability would be 62%. Symptoms and signs Patients with benign paroxysmal positional vertigo (BPPV) usually have episodic attacks of a spinning sensation which are precipitated by a rapid change in head position. In the study of Chan four pathognomonic physical findings for BPPV were studied: (1) spinning sensation, (2) episodic attacks of dizziness, (3) rapid head movements provoking dizziness, and (4) nausea and/or vomitting as associated symptoms. The presence of a spinning sensation in dizzy patients increased the probability of BPPV from 6% to 9%. When dizzy patients had no spinning sensation the probability of BPPV decreased from 6% to 4%. When patients had episodic attacks of dizziness the probability of BPPV was 6%. In dizzy patients without episodic attacks of dizziness the probability of BPPV decreased from 6% to 4%. When rapid head movements provoked dizziness the probability of BPPV increased from 6% to 7%. When in dizzy patients rapid head movements did not provoke their dizziness the probability of BPPV decreased from 6% to 3%. When dizzy patients were nauseous or vomitting the probability of BPPV decreased from 6% to 3%, and when dizzy patients were not nauseous or vomitting the probability increased from 6% to 7%. Dix-Hallpike maneuver The Dix-Hallpike maneuver is the classic test for BPPV of the posterior semicircular canal. In patients with BPPV this maneuver provokes a nystagmus that persists for several seconds and is accompanied with complaints of vertigo. Dix-Hallpike is performed by turning the patient s head 45 toward the side to be tested and then moving the patient briskly to supine-lying, with the neck hyperextended approximately

39 Appendix 6, continued Side-lying maneuver The side-lying maneuver is an alternative for the Dix-Hallpike maneuver, also testing BPPV, and adapted from Nylen. The Dix-Hallpike maneuver has some disadvantages: many patients have difficulty relaxing enough to allow brisk passive movement of the head backward for fear of eliciting vertigo. Also, many (elderly) patients are difficult to test as a result of musculoskeletal limitations or obesity. The side-lying maneuver also stimulates the posterior semicircular canal. Side-lying is performed by turning the patient s head 45 away from the side to be tested. The neck is hyperextended in 20 and the arms are crossed to prevent the patient from inadvertently stopping the motion. The examiner supports the head and lays the patient briskly on the side being tested while eye movements are observed for 1 minute. Cohen, studying the side lying maneuver to diagnose BPPV, used a battery of vestibular tests as reference standard. Only the sensitivity could be calculated from the data and this was 66% (95% CI, 46% to 82%). Head shaking nystagmus test The head shaking nystagmus test is listed as a helpful bedside test for detection of unilateral vestibular dysfunction. Several methods of performing the head shaking nystagmus test are described. They have in common the passive rotation of the head back and forth in the horizontal plane 30 to either side with eyes closed for 25 cycles at a frequency of 2 Hz. Roughly speaking, they differ in the following aspects: (1) active versus passive, (2) darkened room yes/no, (3) use of Frenzel glasses yes/no, and (4) shaking horizontally versus sinusoidally. Immediately after an abrupt halt of the head shake the patient opens the eyes and the investigator decides on the presence or absence of nystagmus. At least three beats of well-defined nystagmus are required to consider the test positive. Head impulse test The head impulse test is a simple bedside test that also aims to identify the presence of unilateral vestibular dysfunction. It comprises a rapid horizontal passive head turn by the examiner while the patient is instructed to fixate on a target (e.g. the nose of the examiner). The test is negative when the patient is able to maintain visual fixation. The head impulse test is positive when the eyes initially drift in the direction of the head turn followed by a compensatory saccadic refixation of the eyes to the stationary target. 58

40 Vibration induced nystagmus test For the vibration induced nystagmus test a handheld electromagnetic vibration stimulator (100 Hz) is applied to both mastoids, the vertex and the right and left dorsal neck. The test is considered to be positive if a nystagmus appears, beating in the same direction in at least 3 positions out of 5. Cold mini caloric test The cold mini caloric test is a simple and time-saving caloric test with a piece of cotton wool soaked in ice water and applied to the tympanic membrane. The other ear is tested after 2 minutes. The test is positive when nystagmus is determined visually. In the study of Weinberg and Sadé, performing the CMC test increased the probability of peripheral vestibular dysfunction after a positive test result on one side from 44% to 86%. Using the estimated prevalence of 33% for peripheral vestibular dysfunction in dizzy primary care patients, 3, 7-11 the post-test probability of a positive cold mini caloric test was 81%. Head heave test The head heave test is a simple bedside test that also aims to identify the presence of unilateral vestibular dysfunction. The test is performed by heaving the head of the patient with abrupt, high-acceleration interaural translations (heaves) of about 5-10 cm in excursion. The examiner stands in front of the patient, who is instructed to fixate on a target (e.g. the examiner s nose). The test is negative when the patient is able to maintain visual fixation. The head heave test is positive when the eyes initially drift in the direction of the head movement followed by a compensatory saccadic refixation of the eyes to the stationary target. In the study of Mandala et al. testing the head heave test in diagnosing peripheral vestibular dysfunction, caloric tests were used as reference standard. Only the sensitivity could be calculated from the data and this was 66% (95% CI, 53% to 77%). High-frequency oscillopsia test The high-frequency oscillopsia test is a bedside test of the vestibulo-ocular reflex and aims to identify unilateral vestibular dysfunction by measuring visual acuity with and without head movements. These head movements are randomly high frequency horizontal movements within a frequency range of 2 to 7 Hz. The test is positive if a patient lose more than 2 lines, including the line initially read, on a Snellen eye chart. In the study of Burgio et al., performing the high-frequency oscillopsia test increased the probability of peripheral vestibular dysfunction after a positive test result from 30% to 41%. Using the estimated prevalence of 33% for peripheral vestibular dysfunction in dizzy primary care patients, 3,7-11 the post-test probability of a positive high-frequency oscillopsia test was 44%. 59

41 Appendix 6, continued Hyperventilation-induced nystagmus test The hyperventilation-induced nystagmus test aims to identify central vestibular dysfunction. Hyperventilation testing is carried out for 90 seconds. The test is positive if nystagmus occur and last longer than 5 seconds. Robichaud et al. studied this test for the target conditions peripheral and central vestibular dysfunction. Only the sensitivity could be calculated from the data. The sensitivity of the hyperventilation-induced nystagmus for peripheral vestibular dysfunction was 18% (95% CI, 8% to 34%), and for central vestibular dysfunction 58% (95% CI, 37% to 78%). Positional nystagmus test The positional nystagmus test also aims to identify unilateral vestibular dysfunction and in this test the supine patient is lying in four different positions: lying supine on the back (primary position), with the head hanging downward, lying on the right side, lying on the left side and turning back to the primary position. In the last three positions the head lies on a pillow in order to have the head, neck and trunk in the same horizontal plane. The test is positive if in one or more positions nystagmus is observed. The study of Guidetti et al. used caloric tests as the reference standard and performing the positional nystagmus test increased the probability of peripheral vestibular dysfunction, after a positive test result, from 80% to 98%. Using the estimated prevalence of 33% for peripheral vestibular dysfunction in dizzy primary care patients 3, 7-11 the post probability of a positive positional nystagmus test was 90%. 60

42 Appendix 7. Summary receiver-operating characteristic curve for the head-shaking nystagmus test for the diagnosis peripheral vestibular dysfunction Each circle corresponds to a study estimate of sensitivity and specificity; the area of each circle is proportional to the study size. The solid line indicates the receiver-operating curve of the weighted analysis, with the square indicating the summary point. The inner dashed line indicates the 95% confidence region; the outer the 95% prediction region. 61

43 Appendix 8. Summary receiver-operating characteristic curve for the head impulse test for the diagnosis peripheral vestibular dysfunction Each circle corresponds to a study estimate of sensitivity and specificity; the area of each circle is proportional to the study size. The solid line indicates the receiver-operating curve of the weighted analysis, with the square indicating the summary point. The inner dashed line indicates the 95% confidence region; the outer the 95% prediction region. 62