Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo Davor Pavlin-Premrl a, John Waterston a,b, Sean McGuigan a,c, Bernard Infeld d, Ron Sultana e, Richard O’Sullivan a,f, Richard P. Gerraty a,b,d,g,⇑ a
Department of Medicine, Monash University, Clayton, VIC, Australia Neurology Department, Alfred Hospital, Melbourne, VIC, Australia Clinical Trials and Research Centre, Epworth HealthCare, Richmond, VIC, Australia d Neurosciences Institute, Epworth HealthCare, Richmond, VIC, Australia e Emergency Department, Epworth HealthCare, Richmond, VIC, Australia f Healthcare Imaging Services, Epworth HealthCare, Richmond, VIC, Australia g Victor Smorgon Epworth Education and Research Institute, Epworth HealthCare, Richmond, VIC, Australia b c
a r t i c l e
i n f o
Article history: Received 7 July 2014 Accepted 3 September 2014 Available online xxxx Keywords: Acute vestibular neuritis Spontaneous ocular nystagmus Vestibular diseases
a b s t r a c t Vertigo is a common cause of emergency department attendance. Detection of spontaneous nystagmus may be a useful sign in distinguishing vestibular neuritis from other vestibular diagnoses. We aimed to assess the contribution of spontaneous nystagmus in the diagnosis of acute vertigo. We enrolled consecutive consenting patients arriving at a single emergency department with acute vertigo. There was no declared protocol for the emergency department staff. A standardized history and examination was conducted by the investigators. Observation for spontaneous nystagmus, its response to visual fixation, and testing the vestibulo-ocular reflex with the horizontal head impulse test were the chief examination components. MRI was obtained within 24 hours. Clinical criteria and MRI were used to reach the final diagnosis. The investigators’ physical findings and final neurological diagnosis were compared with the initial emergency department examination findings and the referral diagnosis. There were 28 patients, 15 with vestibular neuritis, six with benign paroxysmal positional vertigo, one with stroke, suspected clinically, and three with migraine. In three the diagnosis remained uncertain. Spontaneous nystagmus was seen in all 15 patients with vestibular neuritis, fixation-suppressed in eight of 11 tested for this. The head impulse test was positive in 12 of 15 with vestibular neuritis. The emergency department referral diagnosis was correct in six of 23 patients. The ability to detect spontaneous nystagmus is useful in vestibular diagnosis, both in support of a diagnosis of vestibular neuritis and in avoiding false positive diagnoses of benign paroxysmal positional vertigo. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction Vertigo accounts for 1% of emergency department (ED) visits [1] and differentiation of peripheral from central lesions such as stroke is the main object of diagnosis [2–4]. Spontaneous nystagmus in the primary position, non-direction changing and suppressible by fixation, is a feature of vestibular neuritis (VN) [5], one of the most common causes of vertigo, but this sign is often missed. An abnormal head impulse test, which has high specificity for VN, is often difficult for a non-expert to detect and its absence may be indicative of a ⇑ Corresponding author. Address: Suite 8.5 Epworth Centre, 32 Erin Street, Richmond, VIC 3121, Australia. Tel.: +61 3 9428 8440; fax: +61 3 9428 8220. E-mail address: [email protected] (R.P. Gerraty).
stroke [6]. A subtle spontaneous torsional-horizontal nystagmus may also be amplified during the Dix–Hallpike test due to deprivation of the patient’s familiar fixation cues, and may be wrongly construed as the nystagmus of benign positional vertigo. In this situation the absence of latency and fatigability of the nystagmus may not be appreciated by the non-expert. More accurate diagnosis of vertigo in the ED would help in deciding which patients need admission, treatment or investigation [1]. With randomized trial evidence suggesting benefit of corticosteroids in VN [7] it is now important to differentiate VN reliably from other peripheral disorders, as well as from central disorders. We aimed to assess the benefit of being able to observe spontaneous nystagmus in the diagnosis of patients presenting to the ED with vertigo. We compared ED physician notes of physical signs
http://dx.doi.org/10.1016/j.jocn.2014.09.011 0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
2
D. Pavlin-Premrl et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
and/or diagnosis with those of neurologists with an interest in vestibular disorders. 2. Methods Consecutive patients with acute vertigo were recruited from our ED and examined by the authors following referral by the ED physician. Epworth Hospital Richmond is a 520 bed private hospital with a busy neuroscience unit and its own ED in the centre of a city of 4 million people. Potential participants were enrolled on the day of admission and within 48 hours of symptom onset, and were identified by ED physicians, neurologists and by the study team regularly reviewing the ED electronic census during weekdays. Patients who could be treated and discharged from the ED without hospital admission were also included. Written informed consent was obtained from all participants and the study was approved by the Human Research Ethics Committees of Epworth HealthCare and Monash University. Patients with chronic vertigo were excluded, as were patients unable to give first person consent. Patients with any of the following conditions were excluded: previous cerebellar or brainstem stroke; acoustic neuroma or other posterior fossa lesion; previous VN with incomplete recovery; previous diagnosis of vestibular migraine; and bilateral or unilateral vestibular failure from prescription drugs, autoimmune diseases or other causes. Participants underwent a structured history and examination by the investigators, following the assessment by the ED physician. ED diagnosis was not governed by this study protocol, but according to routine practice. In the investigators’ examination, spontaneous nystagmus was diagnosed on direct inspection. If not present, ophthalmoscopy, with and without visual fixation, was undertaken to look for more subtle spontaneous nystagmus [8]. Nystagmus was confirmed to be non-direction changing. Next, the horizontal head impulse test (hHIT) was performed,
and finally the Dix–Hallpike test was performed in those in whom there was no spontaneous nystagmus or hHIT abnormality. Close attention was paid to fixation suppression of spontaneous nystagmus. This was performed macroscopically with a large white piece of linen, or ophthalmoscopically by occluding the other eye. Patients were tested for head-shaking nystagmus, abnormal smooth pursuit, skew deviation and other eye movement abnormalities, pupillary abnormalities and facial sensory loss [3]. A general neurological examination was performed including assessment of gait, when feasible. The ED physician diagnosis and examination findings were recorded. The clinical presentation, examination findings and previous history were used to determine whether the patient had migraine. Patients were reexamined at least once daily during their admission. Patients were diagnosed according to the following criteria. VN = spontaneous non-direction changing nystagmus in torsionalhorizontal pattern or positive hHIT or both; negative examination for signs of central lesion location. Benign paroxysmal positional vertigo (BPPV) = positive Dix–Hallpike test, characterized by torsional-upbeat nystagmus with latency and fatigability. Migraine = history of migraine, associated headache and absence of physical signs. Stroke = physical signs consistent with a central lesion and/ or positive MRI. Where patients did not fit any of the above criteria, they were assigned to the uncertain diagnosis category. Brain MRI was sought for research purposes if not considered clinically indicated by the managing neurologist. MRI was performed using a 3 Tesla scanner (Siemens, Verio, Erlangen, Germany) including a diffusion weighted sequence with a B value of 0 and 1000. Apparent diffusion coefficient maps were reviewed. Non-contrast CT scans were performed on a multislice CT scanner with multiplanar reconstruction. The sensitivity, specificity, likelihood ratios and post-test probabilities of spontaneous nystagmus for a diagnosis of VN were calculated, along with the same measures for the hHIT.
Table 1 Vestibular diagnosis and examination findings Patient
Neurologist diagnosis
ED diagnosis
Neurologist spontaneous nystagmus
ED spontaneous nystagmus
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Uncertain BPPV Stroke VN VN VN VN Migraine BPPV VN Uncertain Migraine VN VN BPPV Migraine VN Uncertain VN VN BPPV BPPV VN VN VN VN VN BPPV
BPPV VN BPPV VN VN ?BPPV ?VN ?BPPV BPPV BPPV No diagnosis BPPV Migraine BPPV BPPV No diagnosis ?VN BPPV BPPV BPPV Peripheral vestibular No diagnosis BPPV No diagnosis No diagnosis Peripheral vestibular disease or stroke BPPV Referred ?VN BPPV
No No Yes Yes Yes Yes Yes No No Yes No No Yes Yes No No Yes Uncertain Yes Yes No No Yes Yes Yes Yes Yes No
NR NR NR NR NR No NR No NR Yes NR NR Yes No No Yes Yes No Yes No No No No No No No Yes No
Dix-Hallpike test (neurologist)
Horizontal head impulse test (neurologist)
+ ND ND ND
+ +
ND + ND ND
+ +
+
+ + ND ND ND ND ND +
+ + + + +
BPPV = benign paroxysmal positional vertigo, ED = emergency department, ND = not done, NR = not recorded, VN = vestibular neuritis, + = present/positive, negative.
= absent/
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
D. Pavlin-Premrl et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
3. Results We recruited 28 patients, 17 women (61%) and 11 men. The mean age was 62.7 years (range 38–91). Twelve patients (43%) were examined within 24 hours of onset and the remainder within 48 hours. VN was the final diagnosis in 15 (54%), six (21%) had BPPV and three (11%) had migraine (Table 1). There was one stroke and in three patients the diagnosis was uncertain. No patient was on medication that could cause nystagmus. Sixteen of the 28 patients had spontaneous nystagmus. All patients with VN had spontaneous nystagmus. An 82-year-old woman, extremely nauseated and unable to walk, had spontaneous nystagmus detectable only on ophthalmoscopy, not suppressible with fixation. She had a negative hHIT and no other signs. She was deemed likely to have a stroke. Brain MRI confirmed a right cerebellar nodular infarct. Some patients declined MRI. Fourteen of the 28 had MRI of the brain, and eight others had brain CT scans. All other brain MRI were normal. Spontaneous nystagmus had a sensitivity for VN of 100% (95% confidence interval [CI]: 79.6% to 100%), specificity of 92.3% (95% CI: 66.7% to 98.6%), positive likelihood ratio of 9 (95% CI: 2 to 41.1), negative likelihood ratio of 0.04 (95% CI: 0.002 to 0.54), positive predictive value of 93.8% (95% CI: 71.7% to 98.9%) and negative predictive value of 100% (95% CI: 75.8% to 100%). Four out of the 16 patients (25%) with spontaneous nystagmus required an ophthalmoscope to detect this. Fixation suppression of spontaneous nystagmus was found in eight of the 11 patients (73%) where fixation-suppression was tested. In three the nystagmus was subtle and the effect of fixation suppression was difficult to determine. The hHIT had a sensitivity of 80% for VN (95% CI: 54.8% to 93.0%), specificity of 100% (95% CI: 77.2% to 100%), positive likelihood ratio of 21.9 (95% CI: 1.42 to 336.8), negative likelihood ratio of 0.23 (95% CI: 0.1 to 0.58), positive predictive value of 100% (95% CI: 75.7% to 100%) and negative predictive value of 81.3% (95% CI: 57.0% to 93.4%). For VN diagnosis, spontaneous nystagmus was 20% (95% CI: 4.2% to +45.2%) more sensitive than the hHIT. The hHIT was 7.7% (95% CI: 6% to +33.3%) more specific than spontaneous nystagmus. Out of the 12 patients for whom data on detection of spontaneous nystagmus was available, ED physicians correctly identified five patients (36%). Ten of these 12 patients had spontaneous nystagmus detectable macroscopically. In those where a specific diagnosis from the ED was recorded, the ED diagnosis accorded with the neurologist’s diagnosis in six of 23 (26.1%). Had the rate of detection of spontaneous nystagmus, correctly interpreted, been 100%, the correct diagnosis might have been made in 16 of 23 (70%) patients. This would have included improvement in the rate of VN diagnosis, and a reduction in the false positive rate of BPPV diagnosis in true VN. 4. Discussion We found that spontaneous nystagmus, sometimes detectable only by ophthalmoscopy, is always present in VN, and could potentially be used to differentiate VN from the other causes of vertigo. We found that the majority of vertigo cases presenting to our ED had VN, and that the rate of successful observation and interpretation of spontaneous nystagmus in the ED is low. A number of patients classified by us as having VN early after the onset of symptoms had complete resolution of all signs inside 24 hours. This is a very quick recovery for VN, and it raises the possibility of an alternative pathology, such as vestibular migraine. One of the limitations of this study is the diagnostic criteria for VN: spontaneous nystagmus, the physical sign we studied, is one of
3
the criteria for the diagnosis, along with a positive head impulse test and the absence of focal signs referable to the cerebellum or brain stem. The lack of acute MRI in some patients might be considered a deficiency, but a detailed clinical examination can be more sensitive than MRI for small brainstem infarcts [3]. In our one patient with stroke the diagnosis was made clinically before the MRI. The HINTS paper [3] reported on those signs most useful for indicating a central rather than peripheral cause of the acute vestibular syndrome. These were direction changing nystagmus, a normal head impulse test, and skew deviation of the eyes detected by cover/uncover testing. Because we saw only the one stroke our study could not replicate those findings. Training of ED personnel regarding subtle fixation suppressible spontaneous nystagmus might lead to more accurate diagnosis of vestibular disorders in the ED. Technological aids to amplify nystagmus, such as the direct ophthalmoscope, PanOptic ophthalmoscope (Welch Allyn, Skaneateles Falls, NY, USA) [9], Fresnel lenses or automated devices such as portable vestibular testing goggles [10] might aid diagnosis, but these are either expensive, not made available or are ubiquitous but not well used in the ED [11]. More accurate diagnosis will allow earlier decisions on patients for discharge, with BPPV for instance, or admission with VN or stroke. There is evidence that ED physicians are skilled in differentiating serious from less serious causes of vertigo [12], but more accurate diagnosis of peripheral disorders will allow earlier treatment with steroids for VN, if indicated, and may help limit the number of investigations such as CT scans and MRI. Spontaneous nystagmus which does not change direction and is fixation-suppressible is a useful but often missed physical sign in the examination of patients with acute vertigo, and was present in all patients with VN. It should be easier to detect than subtle abnormalities of the bedside hHIT which we found to be less sensitive, but more specific. Careful inspection for spontaneous nystagmus would increase the accuracy of ED diagnosis of patients with acute vertigo. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgements Funded by a grant from the Epworth Research Institute. Presented at the Combined Asian and Oceanian Congress of Neurology and Australian and New Zealand Association of Neurologists Annual Scientific Meeting, Melbourne, Australia, June 2012; and in part at the Annual Scientific Meeting of the Neuro-Otology Society of Australia, Newcastle, October 2011. References [1] Newman-Toker DE, Hsieh YH, Camargo Jr CA, et al. Spectrum of dizziness visits to US emergency departments: cross-sectional analysis from a nationally representative sample. Mayo Clin Proc 2008;83:765–75. [2] Cnyrim CD, Newman-Toker D, Karch C, et al. Bedside differentiation of vestibular neuritis from central ‘‘vestibular pseudoneuritis’’. J Neurol Neurosurg Psychiatr 2008;79:458–60. [3] Kattah JC, Talkad AV, Wang DZ, et al. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke 2009;40:3504–10. [4] Chen L, Lee W, Chambers BR, et al. Diagnostic accuracy of acute vestibular syndrome at the bedside in a stroke unit. J Neurol 2011;258:855–61. [5] Hotson JR, Baloh RW. Acute vestibular syndrome. N Engl J Med 1998;339:680–5. [6] Newman-Toker DE, Kattah JC, Alvernia JE, et al. Normal head impulse test differentiates acute cerebellar strokes from vestibular neuritis. Neurology 2008;70:2378–85. [7] Fishman JM, Burgess C, Waddell A. Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane Database Syst Rev 2011;5:CD008607.
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
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D. Pavlin-Premrl et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
[8] Zee DS. Ophthalmoscopy in examination of patients with vestibular disorders. Ann Neurol 1978;3:373–4. [9] Petrushkin H, Barsam A, Mavrakakis M, et al. Optic disc assessment in the emergency department: a comparative study between the PanOptic and direct ophthalmoscopes. Emerg Med J 2012;29:1007–8. [10] Manzari L, Burgess AM, MacDougall HG, et al. Objective verification of full recovery of dynamic vestibular function after superior vestibular neuritis. Laryngoscope 2011;121:2496–500.
[11] Bruce BB, Lamirel C, Wright DW, et al. Nonmydriatic ocular fundus photography in the emergency department. N Engl J Med 2011;364:387–9. [12] Hansen CK, Fisher J, Joyce N, et al. Emergency department consultations for patients with neurological emergencies. Eur J Neurol 2011;18:1317–22.
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo Davor Pavlin-Premrl a, John Waterston a,b, Sean McGuigan a,c, Bernard Infeld d, Ron Sultana e, Richard O’Sullivan a,f, Richard P. Gerraty a,b,d,g,⇑ a
Department of Medicine, Monash University, Clayton, VIC, Australia Neurology Department, Alfred Hospital, Melbourne, VIC, Australia Clinical Trials and Research Centre, Epworth HealthCare, Richmond, VIC, Australia d Neurosciences Institute, Epworth HealthCare, Richmond, VIC, Australia e Emergency Department, Epworth HealthCare, Richmond, VIC, Australia f Healthcare Imaging Services, Epworth HealthCare, Richmond, VIC, Australia g Victor Smorgon Epworth Education and Research Institute, Epworth HealthCare, Richmond, VIC, Australia b c
a r t i c l e
i n f o
Article history: Received 7 July 2014 Accepted 3 September 2014 Available online xxxx Keywords: Acute vestibular neuritis Spontaneous ocular nystagmus Vestibular diseases
a b s t r a c t Vertigo is a common cause of emergency department attendance. Detection of spontaneous nystagmus may be a useful sign in distinguishing vestibular neuritis from other vestibular diagnoses. We aimed to assess the contribution of spontaneous nystagmus in the diagnosis of acute vertigo. We enrolled consecutive consenting patients arriving at a single emergency department with acute vertigo. There was no declared protocol for the emergency department staff. A standardized history and examination was conducted by the investigators. Observation for spontaneous nystagmus, its response to visual fixation, and testing the vestibulo-ocular reflex with the horizontal head impulse test were the chief examination components. MRI was obtained within 24 hours. Clinical criteria and MRI were used to reach the final diagnosis. The investigators’ physical findings and final neurological diagnosis were compared with the initial emergency department examination findings and the referral diagnosis. There were 28 patients, 15 with vestibular neuritis, six with benign paroxysmal positional vertigo, one with stroke, suspected clinically, and three with migraine. In three the diagnosis remained uncertain. Spontaneous nystagmus was seen in all 15 patients with vestibular neuritis, fixation-suppressed in eight of 11 tested for this. The head impulse test was positive in 12 of 15 with vestibular neuritis. The emergency department referral diagnosis was correct in six of 23 patients. The ability to detect spontaneous nystagmus is useful in vestibular diagnosis, both in support of a diagnosis of vestibular neuritis and in avoiding false positive diagnoses of benign paroxysmal positional vertigo. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction Vertigo accounts for 1% of emergency department (ED) visits [1] and differentiation of peripheral from central lesions such as stroke is the main object of diagnosis [2–4]. Spontaneous nystagmus in the primary position, non-direction changing and suppressible by fixation, is a feature of vestibular neuritis (VN) [5], one of the most common causes of vertigo, but this sign is often missed. An abnormal head impulse test, which has high specificity for VN, is often difficult for a non-expert to detect and its absence may be indicative of a ⇑ Corresponding author. Address: Suite 8.5 Epworth Centre, 32 Erin Street, Richmond, VIC 3121, Australia. Tel.: +61 3 9428 8440; fax: +61 3 9428 8220. E-mail address: [email protected] (R.P. Gerraty).
stroke [6]. A subtle spontaneous torsional-horizontal nystagmus may also be amplified during the Dix–Hallpike test due to deprivation of the patient’s familiar fixation cues, and may be wrongly construed as the nystagmus of benign positional vertigo. In this situation the absence of latency and fatigability of the nystagmus may not be appreciated by the non-expert. More accurate diagnosis of vertigo in the ED would help in deciding which patients need admission, treatment or investigation [1]. With randomized trial evidence suggesting benefit of corticosteroids in VN [7] it is now important to differentiate VN reliably from other peripheral disorders, as well as from central disorders. We aimed to assess the benefit of being able to observe spontaneous nystagmus in the diagnosis of patients presenting to the ED with vertigo. We compared ED physician notes of physical signs
http://dx.doi.org/10.1016/j.jocn.2014.09.011 0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
2
D. Pavlin-Premrl et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
and/or diagnosis with those of neurologists with an interest in vestibular disorders. 2. Methods Consecutive patients with acute vertigo were recruited from our ED and examined by the authors following referral by the ED physician. Epworth Hospital Richmond is a 520 bed private hospital with a busy neuroscience unit and its own ED in the centre of a city of 4 million people. Potential participants were enrolled on the day of admission and within 48 hours of symptom onset, and were identified by ED physicians, neurologists and by the study team regularly reviewing the ED electronic census during weekdays. Patients who could be treated and discharged from the ED without hospital admission were also included. Written informed consent was obtained from all participants and the study was approved by the Human Research Ethics Committees of Epworth HealthCare and Monash University. Patients with chronic vertigo were excluded, as were patients unable to give first person consent. Patients with any of the following conditions were excluded: previous cerebellar or brainstem stroke; acoustic neuroma or other posterior fossa lesion; previous VN with incomplete recovery; previous diagnosis of vestibular migraine; and bilateral or unilateral vestibular failure from prescription drugs, autoimmune diseases or other causes. Participants underwent a structured history and examination by the investigators, following the assessment by the ED physician. ED diagnosis was not governed by this study protocol, but according to routine practice. In the investigators’ examination, spontaneous nystagmus was diagnosed on direct inspection. If not present, ophthalmoscopy, with and without visual fixation, was undertaken to look for more subtle spontaneous nystagmus [8]. Nystagmus was confirmed to be non-direction changing. Next, the horizontal head impulse test (hHIT) was performed,
and finally the Dix–Hallpike test was performed in those in whom there was no spontaneous nystagmus or hHIT abnormality. Close attention was paid to fixation suppression of spontaneous nystagmus. This was performed macroscopically with a large white piece of linen, or ophthalmoscopically by occluding the other eye. Patients were tested for head-shaking nystagmus, abnormal smooth pursuit, skew deviation and other eye movement abnormalities, pupillary abnormalities and facial sensory loss [3]. A general neurological examination was performed including assessment of gait, when feasible. The ED physician diagnosis and examination findings were recorded. The clinical presentation, examination findings and previous history were used to determine whether the patient had migraine. Patients were reexamined at least once daily during their admission. Patients were diagnosed according to the following criteria. VN = spontaneous non-direction changing nystagmus in torsionalhorizontal pattern or positive hHIT or both; negative examination for signs of central lesion location. Benign paroxysmal positional vertigo (BPPV) = positive Dix–Hallpike test, characterized by torsional-upbeat nystagmus with latency and fatigability. Migraine = history of migraine, associated headache and absence of physical signs. Stroke = physical signs consistent with a central lesion and/ or positive MRI. Where patients did not fit any of the above criteria, they were assigned to the uncertain diagnosis category. Brain MRI was sought for research purposes if not considered clinically indicated by the managing neurologist. MRI was performed using a 3 Tesla scanner (Siemens, Verio, Erlangen, Germany) including a diffusion weighted sequence with a B value of 0 and 1000. Apparent diffusion coefficient maps were reviewed. Non-contrast CT scans were performed on a multislice CT scanner with multiplanar reconstruction. The sensitivity, specificity, likelihood ratios and post-test probabilities of spontaneous nystagmus for a diagnosis of VN were calculated, along with the same measures for the hHIT.
Table 1 Vestibular diagnosis and examination findings Patient
Neurologist diagnosis
ED diagnosis
Neurologist spontaneous nystagmus
ED spontaneous nystagmus
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Uncertain BPPV Stroke VN VN VN VN Migraine BPPV VN Uncertain Migraine VN VN BPPV Migraine VN Uncertain VN VN BPPV BPPV VN VN VN VN VN BPPV
BPPV VN BPPV VN VN ?BPPV ?VN ?BPPV BPPV BPPV No diagnosis BPPV Migraine BPPV BPPV No diagnosis ?VN BPPV BPPV BPPV Peripheral vestibular No diagnosis BPPV No diagnosis No diagnosis Peripheral vestibular disease or stroke BPPV Referred ?VN BPPV
No No Yes Yes Yes Yes Yes No No Yes No No Yes Yes No No Yes Uncertain Yes Yes No No Yes Yes Yes Yes Yes No
NR NR NR NR NR No NR No NR Yes NR NR Yes No No Yes Yes No Yes No No No No No No No Yes No
Dix-Hallpike test (neurologist)
Horizontal head impulse test (neurologist)
+ ND ND ND
+ +
ND + ND ND
+ +
+
+ + ND ND ND ND ND +
+ + + + +
BPPV = benign paroxysmal positional vertigo, ED = emergency department, ND = not done, NR = not recorded, VN = vestibular neuritis, + = present/positive, negative.
= absent/
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
D. Pavlin-Premrl et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
3. Results We recruited 28 patients, 17 women (61%) and 11 men. The mean age was 62.7 years (range 38–91). Twelve patients (43%) were examined within 24 hours of onset and the remainder within 48 hours. VN was the final diagnosis in 15 (54%), six (21%) had BPPV and three (11%) had migraine (Table 1). There was one stroke and in three patients the diagnosis was uncertain. No patient was on medication that could cause nystagmus. Sixteen of the 28 patients had spontaneous nystagmus. All patients with VN had spontaneous nystagmus. An 82-year-old woman, extremely nauseated and unable to walk, had spontaneous nystagmus detectable only on ophthalmoscopy, not suppressible with fixation. She had a negative hHIT and no other signs. She was deemed likely to have a stroke. Brain MRI confirmed a right cerebellar nodular infarct. Some patients declined MRI. Fourteen of the 28 had MRI of the brain, and eight others had brain CT scans. All other brain MRI were normal. Spontaneous nystagmus had a sensitivity for VN of 100% (95% confidence interval [CI]: 79.6% to 100%), specificity of 92.3% (95% CI: 66.7% to 98.6%), positive likelihood ratio of 9 (95% CI: 2 to 41.1), negative likelihood ratio of 0.04 (95% CI: 0.002 to 0.54), positive predictive value of 93.8% (95% CI: 71.7% to 98.9%) and negative predictive value of 100% (95% CI: 75.8% to 100%). Four out of the 16 patients (25%) with spontaneous nystagmus required an ophthalmoscope to detect this. Fixation suppression of spontaneous nystagmus was found in eight of the 11 patients (73%) where fixation-suppression was tested. In three the nystagmus was subtle and the effect of fixation suppression was difficult to determine. The hHIT had a sensitivity of 80% for VN (95% CI: 54.8% to 93.0%), specificity of 100% (95% CI: 77.2% to 100%), positive likelihood ratio of 21.9 (95% CI: 1.42 to 336.8), negative likelihood ratio of 0.23 (95% CI: 0.1 to 0.58), positive predictive value of 100% (95% CI: 75.7% to 100%) and negative predictive value of 81.3% (95% CI: 57.0% to 93.4%). For VN diagnosis, spontaneous nystagmus was 20% (95% CI: 4.2% to +45.2%) more sensitive than the hHIT. The hHIT was 7.7% (95% CI: 6% to +33.3%) more specific than spontaneous nystagmus. Out of the 12 patients for whom data on detection of spontaneous nystagmus was available, ED physicians correctly identified five patients (36%). Ten of these 12 patients had spontaneous nystagmus detectable macroscopically. In those where a specific diagnosis from the ED was recorded, the ED diagnosis accorded with the neurologist’s diagnosis in six of 23 (26.1%). Had the rate of detection of spontaneous nystagmus, correctly interpreted, been 100%, the correct diagnosis might have been made in 16 of 23 (70%) patients. This would have included improvement in the rate of VN diagnosis, and a reduction in the false positive rate of BPPV diagnosis in true VN. 4. Discussion We found that spontaneous nystagmus, sometimes detectable only by ophthalmoscopy, is always present in VN, and could potentially be used to differentiate VN from the other causes of vertigo. We found that the majority of vertigo cases presenting to our ED had VN, and that the rate of successful observation and interpretation of spontaneous nystagmus in the ED is low. A number of patients classified by us as having VN early after the onset of symptoms had complete resolution of all signs inside 24 hours. This is a very quick recovery for VN, and it raises the possibility of an alternative pathology, such as vestibular migraine. One of the limitations of this study is the diagnostic criteria for VN: spontaneous nystagmus, the physical sign we studied, is one of
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the criteria for the diagnosis, along with a positive head impulse test and the absence of focal signs referable to the cerebellum or brain stem. The lack of acute MRI in some patients might be considered a deficiency, but a detailed clinical examination can be more sensitive than MRI for small brainstem infarcts [3]. In our one patient with stroke the diagnosis was made clinically before the MRI. The HINTS paper [3] reported on those signs most useful for indicating a central rather than peripheral cause of the acute vestibular syndrome. These were direction changing nystagmus, a normal head impulse test, and skew deviation of the eyes detected by cover/uncover testing. Because we saw only the one stroke our study could not replicate those findings. Training of ED personnel regarding subtle fixation suppressible spontaneous nystagmus might lead to more accurate diagnosis of vestibular disorders in the ED. Technological aids to amplify nystagmus, such as the direct ophthalmoscope, PanOptic ophthalmoscope (Welch Allyn, Skaneateles Falls, NY, USA) [9], Fresnel lenses or automated devices such as portable vestibular testing goggles [10] might aid diagnosis, but these are either expensive, not made available or are ubiquitous but not well used in the ED [11]. More accurate diagnosis will allow earlier decisions on patients for discharge, with BPPV for instance, or admission with VN or stroke. There is evidence that ED physicians are skilled in differentiating serious from less serious causes of vertigo [12], but more accurate diagnosis of peripheral disorders will allow earlier treatment with steroids for VN, if indicated, and may help limit the number of investigations such as CT scans and MRI. Spontaneous nystagmus which does not change direction and is fixation-suppressible is a useful but often missed physical sign in the examination of patients with acute vertigo, and was present in all patients with VN. It should be easier to detect than subtle abnormalities of the bedside hHIT which we found to be less sensitive, but more specific. Careful inspection for spontaneous nystagmus would increase the accuracy of ED diagnosis of patients with acute vertigo. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgements Funded by a grant from the Epworth Research Institute. Presented at the Combined Asian and Oceanian Congress of Neurology and Australian and New Zealand Association of Neurologists Annual Scientific Meeting, Melbourne, Australia, June 2012; and in part at the Annual Scientific Meeting of the Neuro-Otology Society of Australia, Newcastle, October 2011. References [1] Newman-Toker DE, Hsieh YH, Camargo Jr CA, et al. Spectrum of dizziness visits to US emergency departments: cross-sectional analysis from a nationally representative sample. Mayo Clin Proc 2008;83:765–75. [2] Cnyrim CD, Newman-Toker D, Karch C, et al. Bedside differentiation of vestibular neuritis from central ‘‘vestibular pseudoneuritis’’. J Neurol Neurosurg Psychiatr 2008;79:458–60. [3] Kattah JC, Talkad AV, Wang DZ, et al. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke 2009;40:3504–10. [4] Chen L, Lee W, Chambers BR, et al. Diagnostic accuracy of acute vestibular syndrome at the bedside in a stroke unit. J Neurol 2011;258:855–61. [5] Hotson JR, Baloh RW. Acute vestibular syndrome. N Engl J Med 1998;339:680–5. [6] Newman-Toker DE, Kattah JC, Alvernia JE, et al. Normal head impulse test differentiates acute cerebellar strokes from vestibular neuritis. Neurology 2008;70:2378–85. [7] Fishman JM, Burgess C, Waddell A. Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane Database Syst Rev 2011;5:CD008607.
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
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[8] Zee DS. Ophthalmoscopy in examination of patients with vestibular disorders. Ann Neurol 1978;3:373–4. [9] Petrushkin H, Barsam A, Mavrakakis M, et al. Optic disc assessment in the emergency department: a comparative study between the PanOptic and direct ophthalmoscopes. Emerg Med J 2012;29:1007–8. [10] Manzari L, Burgess AM, MacDougall HG, et al. Objective verification of full recovery of dynamic vestibular function after superior vestibular neuritis. Laryngoscope 2011;121:2496–500.
[11] Bruce BB, Lamirel C, Wright DW, et al. Nonmydriatic ocular fundus photography in the emergency department. N Engl J Med 2011;364:387–9. [12] Hansen CK, Fisher J, Joyce N, et al. Emergency department consultations for patients with neurological emergencies. Eur J Neurol 2011;18:1317–22.
Please cite this article in press as: Pavlin-Premrl D et al. Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.09.011
