New video techniques for diagnosing stroke in patients with vertigo

David Jay, Clinical Scientist in Audiology Winston Churchill Memorial Trust Fellow 2017

New video techniques for diagnosing stroke in patients with vertigo

Acknowledgements .................................................................................................. 1

Abbreviations and Glossary .................................................................................... 1

About the fellow ....................................................................................................... 1

Background .............................................................................................................. 2

Dizziness in emergency settings –hidden strokes .................................................. 2

After the emergency – what about the ears? .......................................................... 4

Ocular motor assessment – the ears through the eyes .......................................... 4

The H.I.N.T.S protocol .............................................................................................. 6

The Head Impulse Test .......................................................................................... 7

Direction of spontaneous Nystagmus ..................................................................... 9

Skew deviation – a vertical misalignment ............................................................. 11

Combining the three tests - HINTS ....................................................................... 11

The acute dizzy service ......................................................................................... 12

Limitations of HINTS ............................................................................................. 13

The use of video-oculography .............................................................................. 15

Developing a “tele-dizzy” service .......................................................................... 16

AVERT .................................................................................................................. 17

The future ................................................................................................................ 17

Resistance to change ........................................................................................... 17

Lessons for the NHS ............................................................................................. 19

References .............................................................................................................. 21

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Acknowledgements

First and foremost, I would like to thank all the amazing staff on the Johns Hopkins Neuro-Visual and Vestibular

team; David Newman-Toker, Dan Gold, Amir Kheradmand, David Zee, Anthony J Brune III, Roksolyana

Tourkevich, Jorge Otero-Milan, Justin Bosley, Tamarkia Little and Rebecca Scholz. Also to the people in the ENT

department that made time for me including but not limited to John Carey, Michael Schubert and Eric Anson.

I would also like to thank my colleagues in Manchester, including Martin O’Driscoll, Rosie Butler, Julie Reading,

Andrew Causon and Debbie Cane. Many thanks to Simon Howe for his support over the years and encouraging

me in this area early on. Needless to say, I also owe a great debt of thanks to the staff at the Winston Churchill

Memorial trust, who supported me throughout the fellowship and made this journey possible.

Finally, my biggest thanks go to my amazing wife Sophie, who kept the home fires burning for a month, and did a

fantastic job of taking care of our incredible but demanding little girl while I was away.

Abbreviations and Glossary

AVS

AICA

CT

DWI

ENT

MRI

Acute vestibular syndrome

Anterior inferior cerebellar artery

Computed tomography

Diffusion weighted imaging

Ear, nose and throat

Magnetic resonance imaging

HINTS

HIT

PICA

vHIT

VOG

VOR

Head Impulse, Nystagmus, Test of Skew.

Head Impulse Test

Posterior inferior cerebellar artery

Video Head Impulse Test

Video-oculography

Vestibulo-ocular reflex

About the fellow

Having spent the 10 years following my undergraduate degree in Music, acoustics and recording working in the

music industry as an audio engineer and tour manager, my shift into audiology originally came because of my

long-standing interest in the science of sound. I completed a postgraduate diploma in audiology in 2014, and was

lucky enough to gain a place on the NHS Scientist Training Program at Manchester Royal Infirmary.

During these three years of training as a clinical scientist, I built on my knowledge of auditory physiology, and

added a keen interest in vestibular diagnostics and management, specifically around emerging video techniques

for vestibular assessment. As part of my MSc in Neurosensory sciences, I designed, carried out and wrote up a

research study on the video head impulse (vHIT) which gained me a distinction at Masters level. This is currently

being written up as a research paper.

Outside of work, I continue to play in two bands, enjoy hiking, cycling, reading and spending time with family and

friends.

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Background

Dizziness in emergency settings –hidden strokes

A dizzy patient in accident and emergency can be a real challenge to even very experienced emergency and on-

call doctors. The symptoms can often be non-specific and difficult for the patient to describe, and there may be no

obvious physical manifestations or remarkable findings on standard clinical investigations. Patients can present

with dizziness alongside other symptoms, or as the primary complaint. They can describe dizziness as a spinning

sensation (vertigo) accompanied by nausea, light-headedness or difficulty with walking. Symptoms can begin

gradually and become chronic, or start suddenly and slowly improve; occur as spontaneous episodes, or be

triggered by certain changes in head and body position. There are as many forms and causes of dizziness as

there are ways that patients describe it.

The possible causes of acute dizziness are many and the potential for misdiagnosis is substantial, carrying with it

significant risks. But how common is dizziness as a presentation in an emergency setting? Studies of how dizzy

patients are represented in emergency settings have primarily come out of the USA. Between one and four

percent of all visits to USA emergency departments have dizziness as the main complaint (1, 2). If we grossly

extrapolate these numbers to England alone (using 2015-2016 accident and emergency attendance figures of

20.5 million), this equates to approximately 205,000-820,000 visits every year, or 4,000-16,000 per week (3). The

largest proportion of dizzy presentations to USA emergency departments (approximately a third) are eventually

found to be due to benign conditions of the inner ear, the main sensory organ involved in balance (4–6). Of the

rest, 10-13% are idiopathic (a cause is never found) (4, 6), 17% are due to various medical causes (such as

systemic infection, drug ingestion/withdrawal or hypoglycemia), 13% are caused by changes in blood pressure

after brisk postural changes (postural hypotension), 4% have a cardiac cause and 4% are due to migraine (6). 10-

11% have a neurological cause (2,6), though only 3-5% are strokes, and these overwhelmingly occur in the back

part of the brain, the posterior fossa. This area of the brain contains the brainstem (where all of the sensory inputs

required for balance enter the central nervous system), and the cerebellum, our centre of coordination for

balance, posture, gait and eye movements (figure 1).

Of all the above causes of dizziness, posterior fossa

stroke is potentially the most dangerous; these strokes

being generally caused by a lack of blood flow to the

brain (ischaemia). Approximately 20% of all strokes

occur in this part of the brain (7), though they rarely

present with many of the giveaway ‘focal neurological’

signs of stroke such as one-sided muscle weakness

(hemiparesis), slurring of speech (dysarthria), confusion

or trouble with vision. Unfortunately, posterior fossa

strokes are often mimicked by (and not easily

distinguishable from) the most common cause of

dizziness; benign inner ear dysfunction (8). This can

often be due to a self-limiting inflammation of the

Figure 1. The posterior fossa

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balance nerve known as vestibular neuritis, which in many cases has a viral cause (9, 10). This report and my

Fellowship concentrates on the way that both of these differential diagnoses can present to emergency

physicians as ‘acute vestibular syndrome’ (AVS), and how techniques developed in the USA to differentiate

between the two might be applied to dizzy patients in UK emergency departments, in order to cut down

misdiagnosis, increase efficiency and save lives.

AVS is defined as a sudden onset of acute vertigo, nausea, vomiting and gait instability (11). Although this

combination of symptoms also describes a typical case of vestibular neuritis, this is the chief presentation for the

majority of posterior fossa strokes (12). Figure 2 illustrates the risks associated with minor strokes incorrectly

diagnosed as benign inner ear problems; a much larger stroke can often follow.

Figure 2. Minor strokes leading to major strokes. From Kim and Johnston, 2011 (13). Used with permission.

Accurately differentiating stroke from inner ear dizziness is vital not just because of the consequences of delaying

treatment for stroke patients, but also in terms of efficiently using healthcare resources. Patients suffering from

inflammatory inner ear events and other benign causes of dizziness can be treated quickly with anti-sickness

medication, educated on their condition, referred for balance rehabilitation and sent home that day; there is no

need to admit them or send them for neuroimaging. However, despite the fact that strokes only account for 3-5%

of acute dizziness, 20% of all dizzy patients in the USA are admitted (14) and 40% undergo CT or MRI scanning

(2). Estimates of the annual cost of such visits are in the billions of dollars. Furthermore, CT scanning is used in

approximately 80% of cases despite being generally inappropriate for ischaemic strokes in the posterior fossa

and carrying with it the risks of exposure to ionizing radiation. CT imaging is highly insensitive for strokes causing

dizziness (15–18), though even the most appropriate form of MRI scanning (diffusion-weighted imaging; DWI)

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misses approximately 20% in the first 48 hours (19, 20). Misdiagnosis of these types of strokes may be as high as

35% (21) and like all acute cerebrovascular events, without early recognition and treatment; there is the risk of

disability and death. A small sample of 15 misdiagnosed cerebellar stroke cases found that six people

subsequently died, five were left permanently disabled and only four made a full recovery (22). The stakes are

high.

After the emergency – what about the ears?

The study of balance anatomy and physiology is known as vestibular science, and the medical specialties

interested in patients suffering from dizziness and imbalance include Ear, Nose and Throat (ENT) doctors, Oto-

neurologists, vestibular audiologists and specialised physiotherapists. As a clinical scientist in audiology

specialising in vestibular diagnostics and rehabilitation, I rarely see acutely dizzy patients. Typically, patients in

our outpatient’s balance clinics may have been chronically dizzy for many months, if not years. A common finding

when taking a history in a vestibular assessment is that the patient did attend emergency or primary care with

acute dizziness months ago, and for various reasons that will become clear, may have had sub-optimal

assessment and treatment, and subsequently a long wait to see a specialist. For many acutely dizzy patients in a

hospital setting, once the more serious causes have been ruled out (whether accurately or not), patients can be

left without a clear diagnosis or plan for their recovery, and many are only referred to ourselves when they seek

help with their GP for ongoing chronic dizziness. Thankfully, a recent article in the British Medical Journal

highlights the overwhelming evidence for not starting long-term treatment with medications that suppress the

vestibular system’s ability to recover, but rather to expedite referral for tailored vestibular rehabilitation with an

audiologist or specialised physiotherapist (23).

Vestibular rehabilitation is an evidence-based exercise-based therapy that stimulates the vestibular system using

repetitive actions to improve gaze stability, postural control and gait-stability, and thereby optimize central

vestibular compensation (24). Earlier referrals into vestibular rehabilitation have been shown to improve long-term

outcomes (25, 26) and reduce the risk of the symptoms developing into the chronic, disabling and life-altering

conditions that we see so often, such as poorly compensated vestibulopathies and persistent postural perceptual

dizziness (PPPD). Furthermore easily treatable conditions such as benign paroxysmal positional vertigo (BPPV)

can go untreated for months or years when not properly diagnosed in the first instance, severely affecting quality

of life, ability to work and independence, especially in the elderly.

Ocular motor assessment – the ears through the eyes

In vestibular diagnostics one of our primary concerns is whether the patient’s symptoms are originating from their

peripheral vestibular system (the inner ears), or whether they may have a central source (the brain). In the acute

setting this can be very difficult, and most clinicians will defer to expensive neuroimaging to rule out a central

cause. As a vestibular audiologist in a tertiary healthcare centre, I have the rare luxury of time to take a detailed

history and perform a variety of assessments using sophisticated technology to help build up a picture of the

patient’s vestibular function. The organs and neural pathways that make up the peripheral and central vestibular

systems are small, deep in the skull and difficult to test directly. However, there are finely tuned connections and

reflexes between the ears and the eyes, and by looking for particular eye movements in certain conditions, we

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can infer function of the vestibular system. Therefore, many tests of vestibular function look at eye movements

(ocular motor assessment). So as I often tell my patients; though the assessments can feel like eye tests, we are

investigating the way the ears and brain control the eyes. There is a wealth of literature and research going back

decades on ocular motor assessment of the vestibular system (27, 28), though outside of the relevant

specialisms, these techniques are poorly understood.

Several years ago my interest in acutely dizzy patients began to grow as I read some of the published work of an

oto-neurologist (a neurologist interested in the ears) at Johns Hopkins Hospital in Baltimore, Maryland, USA. Dr.

David Newman-Toker and his team were using ocular motor assessment techniques at the patient’s bedside in

emergency settings and in a very particular way. This team had been specifically seeking to improve the accuracy

with which they could differentiate between benign inner ear conditions and posterior fossa strokes. They had

found that a combination of three of these examinations of eye movements, taking five to ten minutes to

complete, could differentiate between peripheral and central causes of dizziness with higher accuracy than MRI in

the first 48 hours (29), or than stroke risk stratification (30). They were referring to the protocol as HINTS in

reference to the three quick bedside tests that it brings together; assessment of the Head Impulse, Nystagmus

and the Test of Skew deviation. My curiosity was aroused, I knew that this was going to be an important next step

forward in the field. I emailed Dr. Newman-Toker out of the blue and with no prior contact, to ask if I could come

and see what his team were doing; how they were approaching their upcoming clinical trial, and how an acute

dizzy service might work. He responded positively, and extremely quickly. I would later realise how generous this

was for this extremely busy man; a professor at one of the top research hospitals in the world, leader of the

Armstrong Institute Center for Diagnostic Excellence, principal investigator on multiple research projects, training

manager for several junior staff and father of two.

Figure 3. The author (far left) with the JH Neuro-Visual & Vestibular team.

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With the blessing of my NHS department manager, I applied to the Winston Churchill Memorial trust for funding to

visit Johns Hopkins hospital for four weeks in summer 2017. I was lucky enough to be accepted for the travelling

Fellowship, and was able to spend a month with Dr. Newman-Toker’s team observing the use of the HINTS

protocol in an emergency setting, the development of their acute dizzy and remote consultation (tele-dizzy)

services, the development of a phase 2 trial clinical trial to establish HINTS as the gold standard diagnostic

technique for AVS, and the opportunity to observe some of the top names in the field in their outpatients clinics. A

lot of the seminal work in vestibular science has come out of Johns Hopkins over the years, and the Division of

Neuro-Visual & Vestibular Disorders team centres around faculty members Professor David Newman-Toker,

Professor David Zee (the author of the eye-movement Bible “The neurology of eye movements”), Dr. Amir

Kheradmand, Dr. Daniel Gold and several other talented doctors, clinicians, engineers and support staff (figure

3). Also working at Johns Hopkins in the complementary field of ENT were Dr. John Carey and Dr. Michael

Schubert, both hugely important figures in the field of vestibular treatment and research. I was lucky enough to be

able to spend time with all of them over the period I was in Baltimore, and learnt a great deal from each of them.

However, I will concentrate the majority of this report on my observations of the work on acute dizziness,

beginning with the HINTS protocol.

The H.I.N.T.S protocol

The HINTS protocol consists of three bedside ocular motor tests: Head Impulse, observation of Nystgamus and

Test of Skew. Combining all three tests with a bedside assessment of hearing has been shown to be 99%

sensitive and 97% specific for central causes of dizziness in AVS patients if either the head impulse is normal, the

nystagmus changes direction with gaze, or if the eyes are vertically misaligned (a skew deviation) (30). The

mnemonic used to indicate a central finding is INFARCT, as shown below. Each of these tests and the relevant

findings are described below.

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N ystagmus

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The Head Impulse Test

The first and most important of the three HINTS tests is the Head Impulse test (HIT), described first in 1988 (31).

This assesses the vestibulo-ocular reflex (VOR), the fastest reflex in the body and the means by which we

maintain a stable view of the world as our heads wobble around on top of our necks. Without this reflex, our vision

when walking would be like the shaky handheld video cameras of the “Blair witch project” rather than the steady

view we enjoy of whatever we choose to look at (our point of ‘fixation’). The VOR is constantly working, ensuring

head movements in all three planes of movement are accompanied by appropriate eye movements (figure 4).

Neural signals generated in the inner ear by nature’s spirit levels (the semi-circular canals) and gravity detectors

(the otolith organs) transmit information about the movements of the head to the brain, eyes and spinal cord.

Taking just the example of the horizontal angular VOR, if we want to maintain stable fixation on a point in space,

when the head turns to the right - the eyes must turn to the left by exactly the same amount and at the same

speed. If we want to test this reflex, and thereby test the ability of the semi-circular canals to detect head

movement, we can perform a HIT by turning the head quickly in one of the three planes of movement, and

examining the eyes to see if they make the appropriate compensatory movement in the opposite direction.

Figure 4. The horizontal vestibulo-ocular reflex (VOR) (Courtesy of OpenStax)

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In the most commonly used form of the HIT, which assesses the horizontal semi-circular canals responsible for

detecting horizontal head turns, the clinician is positioned directly in front of the patient, holding the head firmly

(figure 5). The patient is asked to relax their neck muscles and fixate on the bridge of the clinician’s nose. After

first slowing turning the head from side to side to assess cooperation and fixation, the clinician makes abrupt,

brief and unpredictable impulses to the left or right followed by a short pause (31, 32).

Healthy VOR function in the horizontal plane for high frequencies of rotation will mean that gaze is well

maintained; the patient keeps their eyes right on the clinician’s nose, a negative HIT result (figure 5 panel c).

Before rotation During rotation End of rotation

No

rmal su

bje

ct

a b c

Su

bje

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h r

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t ve

sti

bu

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d e f

Figure 5. The clinical Head Impulse Test (cHIT). The pictures show a right head impulse on a normal subject (a-c)

and on a subject with right-sided vestibular dysfunction (d-f)

However, if the VOR is not working at full capacity, the eyes do not move adequately in the opposite direction to

the movement, partly traveling with the head, and move away from the clinician’s nose (figure 5, panel e).

Immediately, a very fast eye movement (saccade) occurs to re-fixate on the clinician’s nose (figure 5, panel f). It

should be noted that this is not a conscious voluntary eye movement but is in itself reflexive. These ‘catch-up

saccades’ can be seen with the naked eye and are a clinical indicator of a peripheral vestibular weakness on the

side to which the head was turned.

To summarise the HIT; when we wish to know whether there is a problem with a patient’s VOR (emanating from

the ears or balance nerve as opposed to the brain), we turn the head quickly and look for a catch-up saccade. If

the VOR is intact, no saccade will be seen.

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An inflammatory process such as vestibular neuritis on the nerve leading from

the ear to the brainstem can often be the cause of acute VOR dysfunction.

Dizziness due to such a process tends to come in the form of severe vertigo,

beginning suddenly, and lasting continuously for hours to days, followed by a

recovery that can take weeks and sometimes months. Posterior fossa strokes

also produce very similar symptoms, and do not necessarily carry the focal

neurological signs we associate with the majority of strokes. However,

crucially, the VOR remains intact, because the majority of posterior fossa

strokes occur in the cerebellum, which is largely bypassed by the VOR. Therefore, in these patients, the HIT will

be normal. Early studies involving Dr. Newman-Toker showed that a negative HIT in patients with AVS is a highly

specific sign of dysfunction in the parts of the posterior fossa supplied by the posterior inferior cerebellar artery

(PICA) (33, 34). While the overwhelming majority of strokes presenting as dizziness tend to occur in this PICA

region (35), a small number occur in parts of the brainstem and inferior cerebellum, an area supplied by the

anterior inferior cerebellar artery (AICA). The VOR does pass through this territory, meaning that in these cases it

can be affected by the stroke and therefore the HIT can be positive– a finding that on the surface, suggests

vestibular neuritis. So a positive HIT does not always mean that the cause of a patient’s dizziness is definitely

peripheral; strokes occurring in AICA territory can also produce this result (34), and therefore the HIT alone is not

enough to differentiate between a peripheral and central cause of AVS.

Direction of spontaneous Nystagmus

Another clinical sign of vertigo is an involuntary repetitive eye movement called nystagmus; an alternating eye

movement consisting of a slow drift of both eyes in one direction, followed by a relatively quick flick back in the

opposite direction. This is often associated with vertigo; a hallucination of movement felt as a spinning sensation.

Figure 6. Right-beating nystagmus, from the point of view of the clinician

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Nystagmus can have many different causes, but in assessing AVS we are

looking for spontaneous nystagmus, a repetitive flick and drift of the patient’s

eyes that is persistent and continuous. We name the direction of the

nystagmus for the fast ‘phase’ (flick), and it is said to be ‘beating’ in this

direction (figure 6). Spontaneous nystagmus is most commonly caused by an

imbalance in the neural firing rate between the vestibular nerves on either side

of the head (a peripheral vestibular imbalance). We can use the analogy of an

aeroplane with a failing engine on one side (figure 7). The aeroplane

alternately tilts or drifts down towards the deficient wing, before correcting back towards the functional wing;

similarly the eyes drift towards the weaker ear, before flicking back to the healthy ear. The nystagmus ‘beats’ to

the healthy ear.

Figure 7. Aeroplane analogy for right-beating vestibular nystagmus.

It should be noted that in some cases, the vestibular nerve affected by an inflammatory inner ear event may

become hyperactive, in which case the opposite may be seen; the nystagmus will beat away from the healthy ear.

Either way, the important aspect of all peripheral vestibular nystagmus (i.e. originating from an inner ear event

rather than a brain event) is that the direction of this nystagmus will be the same no matter where the patient

looks, or in technical terms; the direction of the fast phase is unchanged by direction of gaze. Vestibular

nystagmus actually tends to increase in intensity when the patient looks in the direction of the fast-phase,

something described by Alexander’s law (11). In the majority of patients with a central cause for the dizziness; the

nystagmus will change direction depending on the direction of gaze, beating towards the right ear when the eyes

H

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look to the right, and to the left ear when the patient looks to the left (34). This gives HINTS another tool to

differentiate peripheral from central vertigo. However, unfortunately this rule does not hold true in every single

case (35), and so again we have a test that is not perfect on its own but adds weight to the HIT alone.

Skew deviation – a vertical misalignment

The final part of the HINTS examination involves examining the vertical

alignment of the eyes. A ‘skew deviation’ is a vertical asymmetry between the

eyes. This is rarely as obvious as in the picture below, though it can be

brought out by covering one eye and looking to see if the uncovered eye

moves vertically (36). Large skew deviations are almost always a result of

central dysfunction, though small skew deviations can been observed in

patients with peripheral vestibular dysfunction (37, 38), meaning this sign on

its own is not specific for a central cause, though again, adds weight to the

HIT and the assessment of spontaneous nystagmus.

Figure 8. Skew deviation

Combining the three tests - HINTS

When these three tests are combined as the HINTS exam, a specific finding

on any one of the three tests indicates a central cause. The mnemonic

INFARCT helps us remember what to look for: If the Impulse is Normal, or the

Fast-phase of the nystagmus is Alternating, or there is Refixation on Cover

Test; then the AVS is due to a central cause. In a 2009 study of high-risk AVS

patients, Dr. Newman-Toker and his team were able to show that in the hands

of experienced neuro-otologists, the finding of any one of these three signs is

100% sensitive and 96% specific for stroke as measured against gold

standard DWI MRI at 3 days (29). This means that in this small study, the HINTS examination did not miss any

strokes and only 4% of patients identified as having stroke did not actually have it. In contrast early MRI was only

72% sensitive (meaning it missed 28% of strokes that were later confirmed when they were large enough to be

H

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seen), though it was 100% specific (every stroke that MRI identified was indeed a stroke). These figures for early

vs. later MRI in posterior circulation strokes mirror those of other studies (19, 20). Further work by Dr. Newman-

Toker’s group confirmed the findings with respect to MRI (30), and showed that HINTS was more accurate than a

stroke risk stratification approach (40). These findings have since been confirmed by several other research

groups (41, 43). To tighten the net further, and make sure that HINTS does not miss even rarer inner ear strokes

that affect hearing, the group suggested modifiying the examination to “HINTS+”; meaning HINTS plus a hearing

test if the patient complains of any hearing loss (30). This is because strokes that occur due to a severe stenosis

of the basilar artery near the origin of the AICA behave just like peripheral vestibular illness; they affect hearing

and balance, and mimic vestibular neuritis in every way on the HINTS exam except for the addition of a sudden

one-sided hearing loss (12).

The acute dizziness service

I arrived at Johns Hopkins two weeks after the long-awaited start of the provision of an ‘acute dizzy on-call’

service to the emergency department, provided mainly by one of two clinical fellows with remote supervision by a

senior colleague. Dr. Newman-Toker‘s team has been successful in gaining funding to train two clinical fellows

each year. A fellow in the US is a medical doctor who has completed medical school and core training in their

chosen specialty (e.g. neurology). They are at the equivalent level of training as an ST5 doctor and undergo two

years of further sub-specialty training before applying for an attending position (what we in the UK would call a

consultant). The acute dizziness service meant that one of the two fellows would always be available on-call to

the emergency department on weekdays between 8AM and 5PM, and after much time and effort in the

organisation of this service, the following brief was given to the emergency department:

Please call us regarding:

o Any patient complaining of dizziness that does not have:

Clear focal neurological signs indicating a stroke

A clear medical cause (e.g. cardiac, pharmacological or other medical reason)

Emergency department physicians should page the dizzy service and the fellow will come down to the

emergency department as soon as possible for a consultation.

While I was there, the fellows were seeing on average one or two patients each day in the emergency

department, many of them quite unwell, and with a variety of dizziness and balance symptoms. I was able to see

firsthand the manner in which these specialists took a detailed history from the patient (not dissimilar to the

history-taking I perform on a regular basis), and the subsequent neurological and ocular motor exam. The ocular

motor exam of course included the HINTS protocol, and where applicable this was used diagnostically. One of the

main selling points to the emergency department was that the Neuro-Visual & Vestibular team would be trying to

drastically reduce the number of unnecessary CTs and MRIs, though would still order MRIs where indicated. This

had a clear financial incentive for the emergency department, as well as speeding up diagnosis time for their

patients and potentially freeing up valuable inpatient beds.

In discussions with Dr. Newman-Toker he revealed that so far the service had been very well received by the

emergency department, due to how prompt the consultations were (usually within the hour), the professional

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service, and the team’s ability to often discharge the patient within a few hours of consultation. Also, from the

point of view of the Neuro-Visual & Vestibular team, they have never had such an opportunity to study acutely

dizzy patients. Over the years they had been called to consult on occasional patients by neurology, emergency

medicine and other disciplines, though they have never had such a sustained, variable and interesting mix of

acutely dizzy patients.

Limitations of HINTS

One of the observations frequently discussed during my time there was the small proportion of these patients who

presented with continuous spontaneous nystagmus, and were therefore true AVS. Implicit within the published

work on HINTS, though admittedly not entirely clear to myself and some others that have read these papers, is

that all of the AVS patients in the studies had spontaneous nystagmus, and therefore HINTS in its current

incarnation is only applicable where spontaneous nystagmus is present, either with or without fixation.

Fixation can be removed using ‘Frenzel’ goggles (44), video goggles, or through techniques known as ‘occlusive

ophthalmoscopy’ (45), or the ‘penlight cover test’, developed by Dr. Newman-Toker for precisely this purpose

(46). Using the protocol to decide on imaging, admission and discharge status of each patient is only possible

when the patient has spontaneous nystagmus, and assessing the presence or absence of this is not a trivial

matter. Though I was only present in weeks 3 to 6 of the acute dizzy service, during this time the team estimated

that the proportion of patients that fitted this criteria was between 10 and 20 percent of all of the dizziness cases

they saw, similar to predictions that Dr Newman-Toker had previously made in building his case for the service.

This means that the elegant simplicity of HINTS was not always able to be deployed, and many of the patients

had much more complex assessments, many of them requiring neuroimaging to rule out central causes of

dizziness in the absence of any significant ocular motor findings.

Transforming the team’s work in to a toolkit for assessing dizzy patients that can be used by non-specialists might

begin with the question “is HINTS applicable?”, and making the judgement on the presence or absence of

spontaneous nystagmus requires a significant amount of experience. In general, the translational possibilities of

such bedside assessment techniques may be somewhat limited due to this factor. In conversation, Dr. Newman-

Toker reflected on a discussion he had with Dr. Ian Stiell, a widely respected US clinician, famous for developing

clinical decision rules. He had commented that such clinical decision rules work best with three to five elements,

such as the ABCD2 clinical prediction rule used to determine the risk for stroke in the days following a transient

ischemic attack (40). While HINTs does fit this description (for AVS patients), the reality for the wider acutely

dizzy population in emergency medicine is that you actually require multiple sets of three to five element rules.

Determining which diagnostic approach to take first involves assigning the patient to one of four groups based

almost entirely on the history (47):

Triggered episodic

Spontaneous episodic

Post-exposure acute

Spontaneous acute

The latter two of these categories are the only ones in which HINTS can be applied. This ‘TITRATE’ approach

(TIming, TRiggers, And Targeted Exams) shown in figure 9 reflects the complexity of the task, and was replicated

in even more extremely complicated flowcharts I glimpsed on whiteboards at the team’s offices. The HINTS

Page 14

paradigm alone was one small corner of these flowcharts, the rest an intricate web of neurological and otological

causes of dizziness, presenting and being assessed in many different ways. This impressed upon me the naiveté

of myself and possibly others who had read Dr. Newman-Toker’s work on HINTS and expected a panacea for the

assessment of acutely dizzy patients. The team’s focus is now on developing robust sets of clinical decision rules

and an algorithm to help reduce misdiagnosis, alongside quantifying the ocular motor assessment digitally for

remote consultation.

Figure 9. The TITRATE algorithm for differential diagnosis of acute dizziness and vertigo.

From Newman-Toker and Edlow, 2015 (47). Used with permission

Page 15

The use of video-oculography

Some studies have suggested that without the ability to call on a neuro-otologist, neuro-opthalmologist or other

vestibular specialist experienced in performing these tests, the accuracy may be reduced (48, 49). Understanding

the HINTS decision-making process is fairly simple, but accurate and confident identification of the give-away eye

movements can be difficult and requires experience. The literature suggests that many emergency doctors just do

not feel comfortable with detailed neurologic examination and diagnosis (50, 51) and would overwhelmingly

welcome a clinical decision rule to help identify central causes of dizziness (52). Luckily, help may be at hand, in

the form of rapidly developing technology for quantifying eye-movements using high-speed video cameras

mounted on lightweight goggles.

Part of what led me towards this fellowship was my interest in the technology of video-oculography (VOG) and

specifically, the development of the video Head Impulse Test (vHIT). As I was training in audiology, this technique

was coming to the fore as a digital version of the longstanding HIT assessment of the vestibulo-ocular reflex.

During 2016-2017 I designed and undertook a research study looking at vHIT, and wrote this up as a dissertation

for my Masters in Clinical Science. Modern VOG systems have the ability to record the eye, and produce graphs

of eye movement plotted against head movement data generated by motion detectors within the goggles. In the

case of the HIT, this quantifies the strength of the VOR, and allows the clinician to see certain eye movements

that the naked eye cannot, theoretically improving its sensitivity for picking up peripheral vestibular weakness

compared with the bedside HIT (Figure 10) (53).

Figure 10. Examples of normal VOR (left) and impaired VOR function (right). Notice in the right-hand figure that

the green eye traces do not perfectly match the blue head traces, meaning the eye drifts off the target and then

has to make catch-up saccades to move back onto the target (the red spikes in eye movement)

Contemporary versions of the goggles and their software also allow quantification of the other parts of HINTS; the

direction of nystagmus and the assessment of skew deviation. Dr. Newman-Toker’s team published a proof of

concept study in 2013, which suggested that using VOG in the context of HINTS for AVS patients was very

promising (54). These systems could potentially provide an opportunity to help improve the ocular motor

examination skills of emergency and acute on-call medics through systematic training programmes and expert

feedback. For clinicians who are still building the confidence to recognise the key eye-movements, the technology

gives them a chance to look again, to compare against norms and to receive second opinions from experts that

are not able to directly examine the patient. Taking the concept further into the realm of tele-medicine, patients

Page 16

with AVS where the diagnosis is unclear could undergo a strict protocol using VOG, performed by medics,

technicians, audiologists or nurse practitioners, and then the results could be sent anywhere in the world for an

expert neurological opinion (55, 56). Goggles could be used in ambulances, primary care settings and remote

locations where vestibular expertise is many miles away.

Developing a “tele-dizzy” service

During my time at Johns Hopkins, this tele-medicine service was in the early stages of development. For the

majority of consultations in the emergency department the fellow was accompanied by a non-medical technician

with a background in ocular testing, who was responsible for using VOG to perform a standardised battery of

tests. These included the three tests of the HINTS protocol as well as several others including the Dix-Hallpike

positioning test for BPPV, headshaking, saccades and gaze testing. This ocular motor data could then be sent

upstairs to the attending faculty member, who would review the test results and then discuss the case with the

clinical fellow, identifying where video results differed from clinical expertise. Whilst I was there the team was still

in the early stages of refining the technique of using video goggles, working on the intricacies of interpretation,

and standardising approaches to patient management based on these results.

Also on the horizon could be a technique for taking a complete dizzy history without the presence of a specialist.

Taking a vestibular history is a complex process, requiring a certain level of experience in order to tease out the

finer details of the patient’s symptoms. Indeed, the subject of Dr. Newman-Toker’s PhD thesis was ‘Why “what do

you mean by ‘dizzy’?” should not be the first question you ask’ (57). However, there is a potential for an adaptive

tablet-based history taking tool, initially asking very open questions and subsequently refining these down to

investigate fully the finer details of the symptoms; e.g. time course, frequency, severity, associated symptoms and

triggers. Experts in this field are rare and usually highly concentrated in specialist centres (this is true both in the

US and the UK). Therefore a computer-assisted history taking system (CAHTS) could be invaluable for

diagnosing dizziness, especially given the infamous lack of gold-standard tests and biomarkers for the main

causes of dizziness. Efforts to design such a tool in Europe for primary care doctors are already underway (58).

Development of this algorithm is in its early days, and the team fully understands the size of the task. Any

standard operating procedures for history taking and VOG examination will have to be extensively workshopped,

refined and exhaustively tested to be foolproof in a variety of situations. However, this work is extremely

promising. One or two non-medical clinicians in each emergency department could be trained to perform the

standardised operating procedure accurately and effectively, and then the data packets sent off to an expert who

could potentially have a recommendation back to the emergency physician within hours. One concern I do have is

that due to the nature of dizziness, and how common it can be to have no significant VOG findings, expert history

taking is the component that directly results in diagnosis in many, if not most cases. When used in combination, a

targeted examination based on history is the thing that makes HINTS so sensitive, and so my concern is that

rolling out a standard operating procedure for this has to be carefully monitored to avoid dangerous misdiagnosis.

This algorithm will have to be refined and refined, possibly taking many years to do so. Rigorous history taking is

necessary to avoid dangerous cases such as the following example:

Page 17

A patient attends with acute vertigo (which unbeknownst to the clinicians has a central origin). They

do not have a skew deviation or direction-changing nystagmus, and as their peripheral vestibular

system is currently unaffected, normally the HINTS would indicate a central origin because of a

normal vHIT. However, the vHIT is positive because of an old vestibular injury, thereby using

HINTS this would mean discharging the patient, when they are really having a cerebellar stroke. Only

a good history would bring to light the old vestibular episode.

There will be other such scenarios and much tweaking and troubleshooting as the algorthim is developed. But the

work is extremely promising, and in a country like the USA where major centres of excellence in the field are so

few and far between, this method could potentially mean one day that patients do not have to fly or drive for many

hours in order to obtain an expert opinion. Acutely dizzy patients could indeed be assessed and treated much

more accurately and effectively, regardless of their location.

AVERT

The team has been developing a federally funded, phase II clinical trial titled AVERT (Acute Video-oculography

for Vertigo in Emergency Rooms for Rapid Triage). AVERT is a randomised controlled trial comparing standard

procedures to care guided by VOG diagnosis, and will test the hypothesis that VOG-guided rapid triage does

accurately, safely and efficiently differentiate peripheral from central vestibular disorders in acutely dizzy patients

in an emergency setting. During the time I was at Johns Hopkins the AVERT trial was not quite ready to start

recruitment, but pilot studies were being carried out, and the protocol for the trial being developed. This was to be

carried out at three other hospitals in the Johns Hopkins community, and patients would be recruited from the

emergency department, providing they had spontaneous nystagmus, and that other neurological, medical and

cardiac causes of dizziness had been ruled out. Each patient recruited would then be randomised into either a

control group undergoing standard care, or a group that would have the care dictated by the HINTS protocol. Of

course, all patients were to have an MRI, including those who do not qualify for this due to HINTS, in order to

establish that HINTS gave the correct diagnosis. The below link describes the trial and includes interesting

inclusion and exclusion criteria for the study: https://clinicaltrials.gov/ct2/show/NCT02483429 AVERT began

formally recruiting in February 2018, is a phase 2 clinical trial across three specialist centers, and is expected to

take around two years, recruiting just over 200 participants. It is an explanatory trial that is focused on the

question “can this intervention work in ideal conditions”. The next step is a Phase III trial, which will likely have

thousands of participants and will attempt to establish the intervention across the broader population, asking the

question “does this intervention work under usual conditions”.

The future

Resistance to change

Dr. Newman-Toker is very aware that his mission to reduce stroke misdiagnosis and improve the quality and

accuracy of acute assessment and treatment of dizzy patients could potentially be a long, hard journey. Over the

years he has encountered much resistance to change, especially as his work goes against the increasing trend

Page 18

for more neuroimaging. Some healthcare professionals have reacted with alarm to the idea of discharging

potential stroke cases without brain scans, regardless of the fact that most emergency neuroimaging is performed

using CT, which is insensitive to posterior circulation stokes. Dr. Newman-Toker speculates that part of the

resistance he has encountered is related to the lack of understanding outside of his specialty of the following

problem: “Misdiagnosis of acute dizziness is a problem and leads to needless deaths, disabilities and

money spent on hospital admissions and neuroimaging”. He uses the analogy of the burning platform and

the bridge to safety; the medical community may not necessarily know that they need to improve treatment and

assessment for this patient group if they do not know how often misdiagnosis occurs and how dangerous this can

be. As well as the epidemiology studies he has published, Dr. Newman-Toker is raising awareness of this issue

by publicising cases where posterior circulation strokes have been missed and people have then had to live with

the consequences.

Regarding the resistance to his ideas from other healthcare individuals and institutions; he also reflects that the

very nature of ocular motor assessment is one that is somewhat foreign to acute and emergency medics. Rather

than the fast pace of emergency medicine, with its emphasis on biomedical testing and pharmaceutical or surgical

intervention, oto-neurology and vestibular audiology are quite different. Taking long histories and pondering the

finer details of eye movements are approaches that are understandably quite alien to an acute medical doctor.

Confidently taking responsibility for a discharge or a scanning request based solely on eye movements goes

against a lot of what they have been taught and possibly their personality type. One pilot study showed that

uptake of the HINTS protocol was far greater among neurologists, but potentially quite challenging for emergency

physicians (59).

Dr. Newman-Toker has had some experience with attempting to educate physicians to perform HINTS, and his

early strategies ran into some resistance, not least from extremely busy doctors who do not have the time to learn

a whole new diagnostic paradigm. He now feels that the scale of this task is just too large and the resistance may

be too great. It may be true that accurate and safe ocular motor diagnosis of acute dizziness requires too much

training and experience to be realistically employed by working acute and emergency medics (60). He gives the

example of a typical phone call after publishing the early HINTS papers:

Worried doctor: “I’ve just discharged a person with a positive head impulse, fixed-direction nystagmus and no

skew deviation - did I do the right thing?

David Newman-Toker: “Yes absolutely, as long as you saw what you say you saw”.

He admits that reading eye movements is something that took him many years of experience to be able to do,

during thousands of appointments with Professor Zee standing over his shoulder. I would have to agree with this,

it is a lifelong learning task. To expect young doctors to learn this quickly, and safely diagnose such patients may

be asking too much. This is where VOG is so vital; some of the diagnostic responsibility is deferred to a remote

expert. However, he does not rule out the approach of VOG-guided training; using video goggles has many

advantages including being able to check a trainee’s work, receive feedback on it and refine one’s practice.

Page 19

Dr. Newman-Toker reflected that in all change management there is a technical and adaptive component, and he

gives the example of the work of Peter Provonost who received a MacArthur genius grant for his five-item

checklist to reduce catheter infections (61). In this case the technical component was quite simple, but the social

manipulations, the leveraging of the nurses, and the incentivisation of clinicians to prioritise their patients despite

established workplace sociocultural norms was how he addressed the adaptive component. However, with the

problem of diagnostic error in acutely dizzy patients, unfortunately it is not that simple. As well as a large adaptive

component there is a hugely complex technical component, which compared with the example of the five-item

checklist is far more challenging. However, he is confident that the exponential nature of technological change

and associated development of diagnostic techniques means that progress may happen sooner than we think.

Eventually, he says, "a rising tide lifts all boats". During one conversation he pointed to the graph in figure 2 and

said to me “before I’m dead, I think we can squash that red shaded area down to nothing”.

Lessons for the NHS

It is clear from the published literature and the clinical experience of myself and other colleagues that there is

potentially a deep hole in the healthcare pathways of acutely dizzy patients, namely due to huge variations in the

safety, efficiency and accuracy of their diagnosis, and therefore the efficacy of their management. While there are

many differences between US, European and indeed British populations, and while no studies of epidemiology in

this area have been carried out outside of the US, it is likely that the same risk of misdiagnosis exists in this

country as it does in the US. Differences in healthcare systems and in vascular risk factors of the two populations

may mean that there are differences in the numbers, but if it is a problem there, it is likely a problem here.

Regardless of the stroke issues the question of timely management of the peripheral vestibular patient remains.

With proper diagnosis at the acute stage, these patients could be accessing vestibular rehabilitation much earlier,

thereby reducing the risk of developing chronic dizziness. Therefore, there are many lessons for the NHS to take

from the work at Johns Hopkins.

Alongside my own reading, my experiences in the US and my growing clinical experience, over the last year I

have also been talking to many doctors and other colleagues in vestibular audiology about this subject. In the UK,

expertise in ocular motor assessment is largely restricted to vestibular audiologists, a subset of ENT doctors, and

a small handful of neurologists. Generally, very few vestibular audiologists have ever seen an acutely dizzy

patient in the emergency department or on a ward. Surprisingly, this is also fairly rare in the ENT community. As

ENT is a surgical specialty, they rarely receive requests for consultations on dizzy patients as their on-call shifts

tend to be surgical on-calls. This job often falls to the medical on-call registrar, a doctor who can be as young as

25, and training in one of a number of unrelated specialties including gastroenterology, endocrinology, respiratory

medicine or geriatric medicine. Neurologists tend not to be called when there are no clear neurological signs and

stroke physicians may not be engaged in the cases of younger patients without vascular risk factors. There

appear to be no nationally agreed protocols or even professional discussions around approaches for triaging,

assessing and managing acutely dizzy patients. From informal conversation with registrars, the care varies case-

by-case, with the emphasis on ensuring that the patient is stable, ruling out a bleed on the brain using CT, and

monitoring in the hope of improvement. Attending an emergency department in the UK as an acutely dizzy patient

may be somewhat of a lottery; based on who is working that day, their experience and the experience of the

Page 20

consultants that have trained them. Again, in informal conversations with medics, very few doctors appear to be

comfortable with ocular motor assessment, and even a Dix-Hallpike test for BPPV may be something that

clinicians can only vaguely remember from medical school. Given the enormous pressures on the National Health

Service, and on individual registrars to complete their training whilst working grueling on-call shifts and

outpatients clinics, I feel that it is unreasonable to expect that these communities will be responsive to a drive to

educate them around acute dizziness. Rather, there may be an opportunity for experienced vestibular

audiologists to work alongside interested consultants in piloting interdisciplinary schemes to improve diagnostic

techniques for this patient population. The important role of such non-medical practitioners in this area and their

future importance for developing and improving evaluation techniques has already been recognized in the

literature (62).

I do not believe that a push in this direction is going to come from the medical community, rather it may take some

effort from the vestibular audiology community to build bridges in this direction. However, I must stress that final

responsibility for the care should always rest with a doctor, and that the audiologist’s role should be to bring their

experience of working with dizzy patients and their skills in history taking and diagnostics.

In order to move towards building such interdisciplinary partnerships, I believe the most important actions to take

at this point are:

1. Start conversations with medical colleagues around these issues, and develop an understanding of how

an interdisciplinary acute dizzy service could work in the UK.

2. Raise awareness in healthcare circles within the UK, producing condensed versions of this report for

publication in the magazines of related professional bodies.

3. Contribute to health education by teaching acute dizzy assessment techniques at training days and

teaching sessions for registrars in related fields, whilst emphasising the limitations of HINTS to accurately

triage the majority of dizzy patients in emergency settings. This should aim to give junior doctors some

tools for acute dizzy assessment, but teach them where the limits of their knowledge are and when to call

for further expertise.

4. Carry out epidemiology work in the UK through clinical audit to establish misdiagnosis rates of posterior

circulation strokes, and the cost to patients with peripheral vestibular dizziness in terms of delayed or

sub-optimal care, needless hospital admissions and unnecessary neuroimaging.

5. Work towards developing small pilot schemes in individual NHS trusts. Beginning simply by doing

vestibular assessment on the ward for stroke patients on a discharge list, where central causes of

dizziness have already been ruled out by MRI.

Overall, this Churchill fellowship has been hugely valuable to me, not just in informing me around the challenges

of assessing acutely dizzy patients, but also because of the opportunity I had to spend time with and learn from

the amazing clinicians and researchers at Johns Hopkins. I do feel that there is a distinct need for their work to be

expanded outside of the United States, and feel that in future the NHS could hugely benefit from such techniques

and approaches. I intend to continue to work and research in this area in order to make that a reality.

Page 21

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