Role of neurological examination and risk factors

The ‘ABCD2’ is a stroke risk assessment tool based on five parameters (age, blood pressure, clinical features, duration and presence of diabetes) that was initially developed to stratify patients with anterior cerebral ischaemia.^{Reference Navi, Kamel, Shah, Grossman, Wong and Poisson6} Newman-Toker et al.^{Reference Newman-Toker, Kerber, Hsieh, Pula, Omron and Saber Tehrani7} examined 190 adults with acute vestibular syndrome, and found that relying on the ‘ABCD2’ score would have missed nearly 40 per cent of the stroke cases and over-diagnosed stroke in nearly 40 per cent of peripheral vestibular cases. As a result, relying on vascular risk factors is cited as a frequent error when triaging patients with vertigo and dizziness, contributing to misdiagnosis-related harms in young patients in particular.^{Reference Kerber and Newman-Toker8}

Regardless of vascular risk factors, around 30–60 per cent of patients with posterior circulation strokes will exhibit at least one deficit on neurological examination.^{Reference Edlow and Newman-Toker9,Reference Edlow, Newman-Toker and Savitz10} In their meta-analysis, Shah et al.^{Reference Shah, Oliveira, Farah, Seisa, Balla and Christensen11} found that most neurological examination findings have low sensitivity and high specificity for a central cause, implying that the absence of typical neurological symptoms or signs should not be relied upon to exclude stroke in acute dizziness. Ten per cent of patients with a cerebellar infarct, usually in the medial branch of the posterior inferior cerebellar artery, will have isolated vertigo, without other localising findings on motor, sensory, reflex, cranial nerve or limb co-ordination examinations.^{Reference Lee, Sohn, Cho, Lee, Ahn and Park12}

There is increasing evidence to support that truncal ataxia is an important part of the neurological examination.^{Reference Edlow and Newman-Toker9,Reference Lee, Sohn, Cho, Lee, Ahn and Park12,Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe13} Carmona et al.^{Reference Carmona, Martínez, Zalazar, Moro, Batuecas-Caletrio and Luis14} examined 114 patients with acute vestibular syndrome and found that patients who fell while standing upright likely had a central lesion as the cause of their acute vestibular syndrome, with a high degree of certainty (sensitivity of 67 per cent and specificity of 100 per cent). Although ataxia was less sensitive than the specific oculomotor examination, the authors argued that truncal ataxia is an easy sign that can be recognised even by physicians without specialised training. In another case series, Lee et al.^{Reference Lee, Sohn, Cho, Lee, Ahn and Park12} also found that 71 per cent of patients with cerebellar infarction and isolated vertigo will present with the inability to walk without support.

Another helpful vestibulospinal sign is the Babinski asynergy sign, which is the inability to sit up from a supine position without using the arms.^{Reference Philippon and Poirier15} Carmona et al.^{Reference Carmona, Martínez, Zalazar, Moro, Batuecas-Caletrio and Luis14} found that this sign had excellent sensitivity (93 per cent) and specificity (100 per cent), in the same study described previously. This seems particularly useful because it can also be administered to severely nauseous patients who are too symptomatic to walk, but the results may need replicating.

Role of imaging

Computed tomography scans are excellent at detecting intracerebral haemorrhage, but this rarely manifests as dizziness without other concerning physical signs.^{Reference Kerber, Burke, Brown, Meurer, Smith and Lisabeth16} The sensitivity of brain CT for posterior circulation acute ischaemic stroke ranges from 7 per cent to 42 per cent,^{Reference Chalela, Kidwell, Nentwich, Luby, Butman and Demchuk17–Reference Ozono, Kitahara, Fukushima, Michiba, Imai and Tomiyama20} such that CT scans are typically not clinically useful and can be misleadingly reassuring.^{Reference Grewal, Austin, Kapral, Lu and Atzema21–Reference Wasay, Dubey and Bakshi24}

Magnetic resonance imaging, on the other hand, is the ‘gold standard’ for diagnosing acute ischaemic stroke. However, even an MRI with diffusion-weighted imaging sequences can miss up to 20 per cent of posterior fossa strokes in the first 48 hours,^{Reference Tao, Liu, Fisher, Wang, Li and Furie25,Reference Shah, Oliveira, Farah, Seisa, Kara Balla and Christensen26} which is specifically true in patients with dizziness.^{Reference Kattah, Talkad, Wang, Hsieh and Newman-Toker27–Reference Park, Kim, Lee, Jung and Chae29} Patients may therefore require a further delayed diffusion-weighted imaging MRI or final clinical diagnosis as the gold standard.

Oculomotor examination

Specific oculomotor examinations have been found to distinguish ‘central’ and ‘peripheral’ disorders in the acute vestibular syndrome (acute-onset, prolonged dizziness or vertigo).

The Head Impulse Test is used to assess the vestibulo-ocular reflex. An abnormal vestibulo-ocular reflex is usually a sign of a peripheral vestibular disorder, while a normal vestibulo-ocular reflex with the head impulse is a strong sign of a central problem.

Spontaneous nystagmus is usually present in the acute vestibular syndrome. ‘Peripheral’ nystagmus is unidirectional and horizontal-torsional. It worsens when looking in the direction of the fast phase (according to Alexander's Law) and suppresses with fixation. However, these features can also be seen with vestibular nuclei, cerebellar or brainstem lesions.^{Reference Newman-Toker, Kerber, Hsieh, Pula, Omron and Saber Tehrani7,Reference Kattah, Talkad, Wang, Hsieh and Newman-Toker27,Reference Newman-Toker, Kattah, Alvernia and Wang30} On the other hand, spontaneous vertical or direction-changing nystagmus should be presumed to have a central aetiology.^{Reference Lee, Sohn, Cho, Lee, Ahn and Park12}

The test of skew is used to look for skew deviation. Although skew deviation is not a sensitive marker of central pathology, it is specific for detecting brainstem lesions in patients with acute vestibular syndrome (15 per cent vs 98 per cent respectively).^{Reference Korda, Zamaro, Wagner, Morrison, Caversaccio and Sauter31,Reference Fracica, Hale and Gold32}

These tests make up the component parts of the Head Impulse-Nystagmus-Test of Skew (‘HINTS’) examination, as discussed below. However, there are other classes of eye movements to consider, such as saccadic dysmetria, impaired smooth pursuit, impaired vestibulo-ocular reflex suppression, ocular lateropulsion, ocular tilt reaction, subjective visual vertical test, eye range of movement, central patterns of head-shaking and central positional nystagmus. These can all complement the Head Impulse-Nystagmus-Test of Skew examination and allow for specific topographical diagnosis of central posterior fossa lesions in acute vertigo (see Fracica et al.^{Reference Fracica, Hale and Gold32} for a full review).

Head Impulse-Nystagmus-Test of Skew plus hearing examination

In 2009, Kattah et al.^{Reference Kattah, Talkad, Wang, Hsieh and Newman-Toker27} published their seminal paper on the Head Impulse-Nystagmus-Test of Skew examination. Combining these tests addressed their individual shortcomings, as a ‘central’ finding on any of the tests leads to the assumption of central aetiology until proven otherwise. This is why it is a three-step test and not a one-step test. Another helpful acronym ‘INFARCT’ can be used to remember the dangerous signs: Impulse Normal, Fast-phase Alternating, and Refixation on Cover Test. In their analysis of consecutive patients with acute vestibular syndrome who had at least one stroke risk factor, a benign Head Impulse-Nystagmus-Test of Skew examination finding ‘ruled out’ stroke better than negative results on MRI with diffusion-weighted imaging in the first 24–48 hours after symptom onset, with excellent specificity (96 per cent).

Along with the Head Impulse-Nystagmus-Test of Skew examination, the evaluation of auditory function with finger rub was subsequently added in 2013, making up the Head Impulse-Nystagmus-Test of Skew plus hearing (‘HINTS+’) examination.^{Reference Newman-Toker, Kerber, Hsieh, Pula, Omron and Saber Tehrani7} This is because hearing loss, when present as part of the acute vestibular syndrome, can indicate labyrinthine ischaemia, which is usually caused by anterior inferior cerebellar artery territory strokes,^{Reference Lee, Sohn, Jung, Cho, Lim and Yi33} especially if otoscopy findings are normal.

Since its creation, the Head Impulse-Nystagmus-Test of Skew has been replicated, and has been reported as more sensitive than diffusion-weighted imaging MRI in several reports.^{Reference Kattah34} Although the Head Impulse-Nystagmus-Test of Skew is therefore useful in acute vestibular syndrome cases when the patient is still exhibiting nystagmus in the emergency department, it does not address other relevant clinical presentations. Importantly, the original paper and subsequent reports also rely on subspecialist examiners rather than general emergency physicians. In their systematic review, Ohle et al.^{Reference Ohle, Montpellier, Marchadier, Wharton, McIsaac and Anderson35} concluded that the HINTS examination may not be sufficiently accurate to rule out a stroke in those presenting with acute vestibular syndrome when used in isolation by emergency physicians.

Timing, triggers and targeted bedside eye examinations algorithm

Classifying patients based on dizziness ‘type’, such as vertigo versus ‘light-headedness’, is not only non-specific, but patients frequently change their description over time.^{Reference Newman-Toker, Cannon, Stofferahn, Rothman, Hsieh and Zee1} Instead, Newman-Toker and Edlow^{Reference Newman-Toker and Edlow36} propose grouping patients based on the timing and triggers of dizziness. The timing, triggers and targeted bedside eye examinations (‘TiTrATE’) algorithm begins by helpfully triaging other general medical causes that are often apparent from the clinical context, co-symptoms and vital signs. The ‘timing’ is used to identify two acute syndromes (acute vestibular syndrome vs episodic), further subdivided into whether the symptoms are spontaneous or triggered, which is then used to select the appropriate targeted examination. For example, if a patient presents with an acute vestibular syndrome, which is spontaneous, the Head Impulse-Nystagmus-Test of Skew examination is performed. The result of the targeted examination then dictates the appropriate laboratory or imaging test required.

The advantage of the timing, triggers and targeted bedside eye examinations algorithm is that it helps to select the right patient for the right examination. It includes the Head Impulse-Nystagmus-Test of Skew examination for acute vestibular syndrome; however, it is much more extensive, as it is the only algorithm to consider presentations such as the acute vestibular syndrome following a traumatic or toxic exposure, or spontaneous episodic vestibular conditions such as Ménière's disease or migraine. It has been specifically designed to address the many common pitfalls observed in clinical practice.^{Reference Kerber and Newman-Toker8,Reference Edlow37} However, it has not yet been fully validated amongst emergency physicians.

Associated symptoms, timing and triggers, examination signs and testing algorithm

The associated symptoms, timing and triggers, examination signs and testing (‘ATTEST’) algorithm is the revised and renamed timing, triggers and targeted bedside eye examinations paradigm, adopting the timing and triggers diagnostic approach in a simpler flow diagram.^{Reference Edlow, Gurley and Newman-Toker38} It was created using the same evidence-based guidelines as the timing, triggers and targeted bedside eye examinations, although no clinical studies have been conducted.

Spontaneous nystagmus, direction, head impulse testing and standing protocol

Vanni et al.^{Reference Vanni, Pecci, Casati, Moroni, Risso and Ottaviani39} published their four-step algorithm called ‘STANDING’ (SponTAneous Nystagmus, Direction, head Impulse test, standiNG) in 2014, and found excellent levels of sensitivity (100 per cent) and specificity (94 per cent). In their full validation study in 2017, they found similarly high levels of accuracy (88 per cent), sensitivity (95 per cent) and specificity (87 per cent).^{Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe13}

Similar to, but not as extensive as, the timing, triggers and targeted bedside eye examinations, the spontaneous nystagmus, direction, head impulse testing and standing protocol also includes guidelines on how to evaluate acutely dizzy patients who do not show spontaneous nystagmus, as it includes gait and positional testing. It does go further than the timing, triggers and targeted bedside eye examinations in terms of positional testing, however, as it suggests performing the Pagnini–McClure manoeuvre to assess for the horizontal canal variant before performing the Dix–Hallpike manoeuvre, which is used to identify the more commonly affected posterior canal. In their validation study, Vanni et al.^{Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe13} found a 20 per cent rate of the horizontal canal BPPV variant, a higher figure than seen in non-acute settings.

The spontaneous nystagmus, direction, head impulse testing and standing protocol also differs from the Head Impulse-Nystagmus-Test of Skew examination in its approach to the acute vestibular syndrome, as it does not include the test of skew. The reason for this is not clear, but it seems it was not thought to be necessary given that a normal Head Impulse Test finding was the best bedside predictor of stroke in the study by Kattah et al.^{Reference Kattah, Talkad, Wang, Hsieh and Newman-Toker27} Vanni et al.^{Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe13} also found that a negative Head Impulse Test finding, as well as altered equilibrium, were the most sensitive findings for central vertigo. The spontaneous nystagmus, direction, head impulse testing and standing protocol also omits hearing. Nevertheless, these omissions did not appear to result in unacceptable levels of sensitivity compared with final clinical diagnosis, although it should be noted that the emergency physicians performing the protocol had received extensive training. The use of emergency physicians in the validation is a particular strength of the spontaneous nystagmus, direction, head impulse testing and standing protocol, but it is not clear how the protocol will perform when implemented by less experienced examiners given that it places a relatively higher weighting on the Head Impulse Test, which probably requires the greatest level of skill and interpretation.

Table 1 provides a summary of the pros and cons of the diagnostic algorithms discussed above.

Table 1. Pros and cons of diagnostic algorithms for differential diagnosis of vertigo in the emergency department

HINTS+ = Head Impulse-Nystagmus-Test of Skew plus hearing examination; AVS = acute vestibular syndrome; TiTrATE = timing, triggers and targeted bedside eye examinations; ATTEST = associated symptoms, timing and triggers, examination signs and testing algorithm; BPPV = benign paroxysmal positional vertigo; STANDING = spontaneous nystagmus, direction, head impulse testing and standing protocol; HIT = Head Impulse Test

What does a ‘good protocol’ look like?

Comparing the Head Impulse-Nystagmus-Test of Skew examination to the timing, triggers and targeted bedside eye examinations, or the associated symptoms, timing and triggers, examination signs and testing algorithm, and the spontaneous nystagmus, direction, head impulse testing and standing algorithm, may be misleading because the Head Impulse-Nystagmus-Test of Skew examination is only concerned with acute vestibular syndrome, whereas the others include aetiologies such as BPPV. As a result, the Head Impulse-Nystagmus-Test of Skew examination should not be used in isolation for the differential diagnosis of vertigo in the emergency department.

Other protocols and pathways that have not yet been mentioned include minor modifications but adhere to similar principles, such as the one advocated by Johns and Rosenberg.^{Reference Johns and Rosenberg40} This algorithm, like the spontaneous nystagmus, direction, head impulse testing and standing algorithm, looks for the ability to stand or walk unaided in order to clearly identify strokes, and includes positional testing for BPPV, but incorporates the full Head Impulse-Nystagmus-Test of Skew examination in the case of the acute vestibular syndrome.

What these protocols do share is the principle that the most effective way to exclude a life-threatening disorder such as posterior cerebrovascular disease is to confirm the presence of a peripheral vestibular disorder. The spontaneous nystagmus, direction, head impulse testing and standing protocol, for example, had an excellent negative predictive value (99 per cent) but a poor positive predictive value (48 per cent), according to validation study by Vanni et al.^{Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe13} Therefore, clinical pathways should consider the tools required to recognise the most common peripheral vestibular disease resulting in acute vertigo.

Other vestibular disorders, such as vestibular migraine and Ménière's disease, may also present to the emergency department, and can be difficult to diagnose at first, even in the hands of subspecialists. As a result, emergency department physicians may need to use the bedside examination to rule out ‘clear cases’, rather than making a definitive diagnosis, to ensure patient safety. Although this would reduce specificity, it is preferable to low sensitivity.

Who should see these patients?

The success of any protocol depends on who carries it out. A common criticism of vertigo protocols is the lack of validation in non-specialist point of care emergency physicians.^{Reference Ohle, Montpellier, Marchadier, Wharton, McIsaac and Anderson35,Reference Nakatsuka and Molloy41} These tests are not uniquely difficult to perform, although they do require some level of subjective interpretation.

Some localised protocols utilise allied health professionals instead. For example, one study from Australia found that utilising a specialist vestibular physiotherapist led to greater diagnostic specificity.^{Reference Stewart, Rosbergen, Tsang, Hoffman, Kwan and Grimley42} However, there was no reference standard used to measure diagnostic accuracy, and the pathway led to higher rates of hospital admission and longer length of stay.

In the end, the ideal person to see the patient is the one who is available and the most qualified to do so, but it is unclear what training is necessary to achieve competency. Emergency physicians carried out the spontaneous nystagmus, direction, head impulse testing and standing protocol, following 5 hours of didactic and practical sessions, including 15 proctored examinations.^{Reference Vanni, Pecci, Casati, Moroni, Risso and Ottaviani39} This was then extended to 6-hour workshops, comprising 4-hour lectures and 2-hour demonstrations on normal volunteers, followed by 10 proctored examinations on emergency department patients and 1-month use in daily practice under the supervision of a neuro-otologist.^{Reference Vanni, Pecci, Edlow, Nazerian, Santimone and Pepe13}

In another study, Kotwal et al.^{Reference Kotwal, Fanai, Fu, Wang, Bery and Omron43} found that 9 hours of deliberate practice using a case library of virtual patients significantly increased the diagnostic skills of medicine interns evaluating real-world dizziness. There is a need for putting more resources into developing condensed educational experiences, such as virtual simulation training, to enhance diagnostic education.

Role of technology

Advances in technology have provided vestibular clinicians with a number of new methods for determining vestibular function. Video-oculography allows for quantitative recording of eye movements. In addition, the introduction of the video Head Impulse Test permits objective evaluation of the vestibulo-ocular reflex in the planes of all six semi-circular canals, a so-called ‘eye ECG’.^{Reference Newman-Toker, Curthoys and Halmagyi44}

‘AVERT’ is an ongoing randomised, controlled diagnostic strategy trial (unique identifier: NCT02483429), which is focused on comparing such a novel video-oculography guided diagnostic strategy to standard care. The goal is for a fully automated ‘eye ECG’ conducted by local providers, with backup telediagnosis made by subspecialists. However, it is worth noting that technologies such as video Head Impulse Test systems come with their own challenges and pitfalls, requiring training and careful administration. The ‘AVERT’ study utilises the services of a specialist audiological scientist, and the review is conducted by an expert otoneurologist, not accessible in most emergency departments. Again, the ability and, more importantly, the willingness of emergency physicians to use these technologies would have to be evaluated.

In future, smartphones may be used to record and evaluate oculomotor examination findings. This would have several advantages, as these are readily available, quick to complete and should be easier to administer. Early proof of concept results are very promising.^{Reference Otero-Millan, Parker, Badihian, Hassoon, Tehrani and Farrell45,Reference Parker, Farrell, Otero-Millan, Kheradmand, McClenney and Newman-Toker46} ‘Deep learning’ models would allow nystagmus identification and interpretation,^{Reference Wagle, Morkos, Liu, Reith, Greenstein and Gong47} but have some way to go before being commercially available.