Did I hear dizziness?

Dizzying foto from Flickr, Creative Commons

We recently suffered through an M&M meeting about a patient that presented with vertigo and hearing loss. While clinically a typical vestibular neuritis, the importance of sudden hearing loss was grossly understated, with arguments like “this is all the more a peripheral disease” and “belongs to EENT then, anyway”. I certainly grew up with a standard operating procedure that allowed to turf “vertigo + hearing loss” without further workup, unless there were signs or symptoms of CNS involvement.

In this blog entry, I try to work through the numbers, invoking some recent publications.

Unilateral sudden hearing loss (USHL)

(bilateral hearing loss is a different animal altogether)

  • more than 30 dB hearing reduction in < 3d (in at least three frequencies)
  • quite frequent ~ 27/100.000
  • usually middle aged
  • about a third have vertigo, depending on how strictly you define it


As in so many other cranial nerve dysfunctions we don’t really know the etiology of your average run-of-the-mill USHL. It usually seems to be benign, because otherwise people would be dying all over the place, so depending on your prejudices you can suspect anything from viral to vascular.

It is really quite surprising that these etiologically occult cases have been ascribed by some to vascular causes (without any proof except for risk factors) as if this were benign in any way, similar to cases of mononeuropathic cranial nerve dysfunctions such as trochlear, abducens or facial palsy where the “microvascular” theory is built on the epidemiologic association with risk factors such as hypertension and diabetes. If those entities were “microvascular”, we ought to treat them it with tPA, GP-IIb/IIIa inhibitors (analogously to microvascular stroke #lacune), or at least include them into a risk factor reduction program and ASS them.

The viral theory (which seems to be accepted for the case of bell’s palsy) is also difficult to establish – at least antivirals don’t seem to work.

There are plenty of cool differential diagnoses, such as Cogan’s or Syphilis (see this article for a table), but of course you cannot exclude all the zebras in the average case.

Differential diagnosis

So what is in the differential that is acutely endangering the patient and, in particular, what changes if vertigo is added to the symptoms?

  • Vertebrobasilar stroke – see below.
  • Acoustic neuroma: this needs to be recognized, but not acutely.
  • Migraine – not dangerous, but eminently treatable.
  • Blood problems – sickle cell, leukemia, … – it seems that an ESR and a CBC are enough.
  • Real infections: syphilis mainly, maybe HIV?

Then there are things that usually only EENT specialists care for, such as Meniere’s and perilymphatic fistulas, cholesteatomas and many more. All these seem to me to be not that urgent and therefore safe to send away, if symptoms have been covered.

The literature, being written by neurootologists (a quite intellectual bunch), stresses the differentiation between central and peripheral causes, with multiple sclerosis, migraine and stroke among the most frequent central causes. As an ED physician I would rather stress stroke as the main cause to be identified acutely, deferring the decision when to MRI vertigo patients to the clinic.

Acute vestibular syndrome plus hearing loss

About 3-15% of vertigo patients turn out to have a vascular problem, either a stroke or a TIA due to serious stenosis. Now in the past, neurologic myth had it that hearing symptoms (SHL or tinnitus) reduce this risk, so that it is safe to turf the patient to EENT. It turns out that the opposite is true – nearly double the amount: 5,5%1, at least in this recent population based survey, which should all but overestimate the risk.

I will try to give an explanation for this fact in a second.

First let us consider the practical implications. We have learned to filter acute vertigo patients (it is superbly unclear what acute means but for the sake of simplicity I assume this means < 3 weeks), using a good history and physical/neuro exam, including (but not limited to) the head thrust maneuver (aka head impulse test). Some would want to simplify this to HINTS or INFARCT, which amounts to reducing the rest of the neuro exam to nystagmus (direction changing?) and cover test (vertical disconjugation?), which in my humble opinion is too brief in the hands of a Neurologist. But even if you limit yourself to HINTS you miss at most 1 percent of strokes and thus improve on MRI (which misses up to 20-30% of strokes in the acute phase).

Why is that? The only way that a stroke mimics vestibular neuritis with a positive Halmagyi sign (Halmagyi-positive pseudoneuritis), is that it hits the nerve root entry zone around the fourth ventricle. And this region is highly collateralized as it can derive it’s blood supply from small perforators, AICA, PICA and even dural and petrosal arteries.

On the other hand, a true vestibular neuritis that causes permanent vertigo usually will cause the horizontal vestibuloocular reflex (hVOR) to suffer, except for the rare case of inferior vestibular neuritis (as opposed to your standard superior neuritis which affects nerve fibres to the horizontal canal) – this occurs in only 9 of 703 cases of vestibular neuritis overall according to this retrospective case series. So most of the patients should have impaired hVOR, yet not all of them are discovered during the clinical head impulse test, because covert saccades (fixation-correcting saccades during the thrust rather than afterwards) are impossible to see without videooculography and sometimes the hVOR impairment is not serious enough to cause correcting saccades at all. We don’t really know the percentage of covert saccades in real patients, but in dizziness clinics it can be up to 30%. Personally, I see way more covert correcting saccades with the slow motion app of my iphone, which has not been properly studied but definitely improves the clinical HIT as it makes it objective. One problem with all the investigations into sensitivities of neurootological testing vs. HIT is the lack of a gold standard – there is no other biomarker for vestibular neuritis than VOR (plus other sophisiticated vestibular lab tests) and this is defined by gain reduction (i.e. eye movement divided by ear movement) to 0,7 or less in the vestibular lab in order to preserve test quality indicators, so we might miss some cases with only slight VOR reduction.

Pseudolabyrinthitis: Acute vestibular syndrome with hearing loss due to ischemia

This corresponds to a stroke in the territory of the labyrinth artery, which usually (98%) derives from the AICA or the basilar artery (in the remaining cases it branches off the PICA, but this is exceedingly rare – see this 2015 case report) and does not have collaterals, so that it serves as a Letzte Wiese of the vertebrobasilar system. For instance, a high grade basilar artery stenosis (or equivalently a vertebral artery stenosis in the frequent case of hypoplastic contralateral supply) might cause temporary hearing loss and vertigo with nystagmus. Although the whole labyrinth is expected to suffer, the resulting nystagmus at least in part will be horizontal as in a status post labyrinthectomy.

Now we don’t know the percentage of AVS+HL patients that have a real vascular cause but the above mentioned case series suggests taking it even more seriously – this has lead to the so-called HINTS+ scheme, adding hearing loss to your AVS workup as harbinger for possible vascular (if not necessarily central) cause, without reducing specificity of your workup.

The odds

  • Between 5-25% of AVS pt. have a vascular cause
  • About 15-20% of vascular cause AVS are AICA in origin
  • 68% of AICA strokes have auditory symptoms
  • 50% of AICA strokes have a “falsely peripheral” HIT

Transient audiovestibular symptoms

What about the patients that had a serious vertigo spell but recover before you see them in the ER? Some have dubbed this entity ATVS – acute transient vestibular syndrome. It hasn’t been studied much yet, but from what has been said above we should conclude that it merits a proper TIA workup (even if vertigo itself does not count as a TIA symptom in most guidelines), including (at least clinical) vestibular testing – see below – and an MRI, possibly with MR-perfusion if you read this recent Stroke 2017 paper.

My vertigo workup

  1. Do a proper history, asking explicitly about auditory symptoms and craniocervical pain. Take your time for that.
  2. Do a proper neuro exam.
  3. Do a proper neurootological base exam
    1. Frenzel screen for spontaneous, gaze-evoked and head shake nystagmus
    2. Extraocular eye movement tests including vergence, saccades, smooth pursuit
    3. VOR cancellation test
    4. tragus pressure test
    5. Romberg’s and Unterberger’s
  4. Do some simple vestibular testing using devices everyone should have in their ER
    1. HIT (using iphone’s slow motion camera)
    2. hearing test (using an iphone app such as MiMi)
    3. bucket test or subjective vertical iphone app
    4. dynamic visual acuity (have them read something while turning their head)
    5. Dix-Hallpike, head roll test, head hanging test

Recommended reading



On Spencer’s curve

2000px-znak_a-1-svg1In our recent ultrasound refresher course, I tried to give a talk on the vagaries of stenosis graduation (mainly) for extracranial stenoses. The gist of the talk is outlined in the following notes.

The Bernoulli principle

While Bernoulli’s equation is rather intricate, the underlying principle of conservation of flow along a stenosed tube is simple. Consider a tube with a short stenosis with laminar flow of a Newton fluid. Then the bigger area A1 multiplied with the flow  velocity v1 (take psv for simplicity, although this is not really correct) should be the same as the smaller area A2 multiplied with v2. Thus the increase of flow is proportional of A1 / A2, so that the reduction to a third of the area leads to an increase by the factor 3 of the flow velocity, a reduction to a tenth leads to ten times the flow velocity in the stenosis.img_7579

Adding friction

Since we usually don’t observe velocities higher than 5 m/sec, there must be a limiting principle and this is the resistance offered by the stenosis, which reduces flow in the whole vessel. This resistance can be approximated by the law of Hagen-Poiseuille and is proportional to the length of the stenosis, the inverse of r^4 and the inverse of viscosity. Again, this only holds for laminar flow and the case of blood offers some more complications, but the core message is: the longer the stenosis the higher the flow reduction. Also the flow reduction grows much more with decreasing vessel diameter than the flow velocity increase by Bernoulli’s principle can compensate. Very tight and long stenoses show a flow velocity reduction despite there high grade. If you  find a psv of only 2,4m/sec this might therefore mean either a mere medium grade stenosis or a very tight stenosis (near occlusion).img_7578

Spencer’s curve

Taking these two principles into account, Spencer and Reid (in their brilliant 1979 stroke article) deduced the famous curve now known as Spencer’s curve (see Alexandrov’s papers for a more detailled exposition).

Since at the time duplex sonography was technically not feasible, the Spencer curve is based on the theoretical assumption of a 2 mm stenosis and thus does not correct for the length of the stenosis (as well as the other factors mentioned below). This explains why the cw-doppler-data in their paper does not really fit the theoretical model. Still it is the best approximation we have to a theoretical foundation of stenosis quantification.

Measuring diameters

Diameter instead of area

Most of the studies have been done with angiographic imaging of stenoses or ultrasound measurements of the stenosis diameter rather than the area. Of course, the area could easily be calculated from the diameter (r^2 pi) if it were a circle, but then it isn’t. In ultrasound we could measure the area itself (if no shadowing artifacts are present), yet no one does really. Therefore you should remember that most of calculations of the stenosis area from the diameter are systematically invalid.

Where, when and how to measure diameters

For some absurd reason, Europeans kept to the local stenosis degree (i.e., diameter of perfused lumen divided by the original vessel diameter), at least in their ECST trial, while the NASCET trial used the more reasonable distal stenosis degree (i.e., minimal lumen diameter divided by non-stenosed distal ICA diameter). Since the ICA bulb varies in its bulbiness and distends with age and blood pressure (and with stenosis degree), the local stenosis degree is usually a shot in the dark. The distal (NASCET) degree suffers from pseudoocclusion, i.e., collapse of the distal vessel in very high grade stenosis. All attempts to calculate the NASCET stenosis degree from ECST and vice versa are irrational.

Being faithful to both traditions, I measure all the lumina (minimal lumen, original vessel lumen, distal lumen). The only really interesting number is the residual diameter (combined with the length of the minimal lumen), because this determines the hemodynamic compromise.

Other important factors


Neither is blood a Newton fluid, nor is all the viscosity (rarely measured today) explained by the hematocrit alone. Yet the hematocrit is an important number to factor into your interpretation of ultrasound data. You should note it.


Every vessel wall abnormality leads to small perturbations of flow and thus turbulence. Turbulence reduces anterograde flow and thus reduces the distal pressure after a stenosis. While very hard to quantify it is essential to mention turbulent flow when you see it. Remember that to distinguish retrograde (i.e. turbulent) flow from flow increase with aliasing you need to look at the color bar on the side of your duplex image, noting that flow increase jumps over the upper limit of the color spectrum while retrograd flow (usually) passes the black zero flow region.


decreases over the lifetime, even more if severe hypertension or calcification of vessel walls is present. This, again, is very hard to quantify, but often easy to recognize qualitatively in your duplex image, when you recognize the pulsation of the vessel wall. Reduced elasticity has to lead to increased flow velocities.


Since blood flow is not continuous but pulsatile and this in varying shapes, we should really be using mean flows in our stenosis calculations. This has historically not been done. As a consequence, valve abnormalities (aortic stenosis, insufficiency) have to be factored in, when we try to calculate the stenosis degree from peak systolic velocities.

Blood pressure and atrial fibrillation

The (pulsating) blood pressure is the driving force of cerebral blood flow, trying to overcome venous and intracerebral pressure as well as the distal blood pressure offered by collaterals (see below). At least, you should note the blood pressure and relativize your stenosis graduation in cases of extreme values. When the patient has atrial fibrillation, you probably should use an “average” heartbeat rather than the extreme values. But bear in mind that absolute arrhythmia is a risk factor for arterioarterial embolization in itself.

The geometry of the stenosis

usually is far from being that of a tube. Rather, the blood flow curves around plaques, rotating and hitting small plaques on the distal wall. Again, the effects are impossible to quantify, but at least the geometry should be noted. The shape of the stenosis area should be remarked upon, if it isn’t circular.

The role of collaterals

The pressure difference along a stenosis is not only determined by the resistance of the stenosis itself, but also by the collateral blood flow which leads to an increase of distal pressure (mostly but not only in diastole). This leads to a reduction of the blood flow velocity in the case of good collateralization, thus also reduced flow velocities.

The danger of a stenosis

In the neurovascular clinic, I try to estimate four risks of a stenosis: the hemodynamic risk (what happens if the stenosis were to increase?), the embolic risk (how high is the risk of an embolic event from the stenosis?), risk factors and other risks.

Hemodynamic risk

The hemodynamic risk is determined by

  • the current hemodynamic compromise (jet flow velocity, CCA flow vs. ICA flow, pulsatilities, MCA flow, CO2 reserve)
  • the dynamics of the stenosis (how long has this been going on? was there time to develop collaterals?)
  • the completeness of the circle of Willis (variations such as A1 hypoplasia, Pcomm hypoplasia)
  • secondary stenoses in the collateral circulation.

The problem is that we cannot foresee whether the stenosis will be slowly progressive or suddenly close up (as in plaque rupture). At least in asymptomatic stenoses I require CT- or MR-angiography to determine the completeness of the circle of Willis.

Embolic risk

The embolic risk is determined by

  • Plaque morphology and
  • Plaque type
  • Whether the atherosclerotic process is active or burnt out.
    As in coronaries, it is not reasonable to revascularise every severe asymptomatic stenosis. But in a patient where the overall atherosclerotic process is currently active (after an NSTEMI, say), we can expect the plaques to rupture.
  • Previous embolic events can be noted on MRI.
  • Emboli detection
  • Is the anti-platelet medication working? Multiplate or similar tests.

Risk factors

  • Did the patient stop smoking? How long ago?
  • Can we use high dose statins in this patient? Statins are highly effective against plaque deterioration, but also have serious side effects (less exercise tolerance, diabetes, muscle problems), especially in the high doses we like to use for severe stenosis.
  • Is the patient’s blood pressure controllable? Note that severe stenosis lead to very labile blood pressures as one of the most important sensors of the system is damped.
  • Exercise? Although this has not been studied properly in carotid artery stenosis, I surmise that health by fitness should improve the prognosis of carotid artery stenosis.

Other risks

  • Central or mixed sleep apnea syndrome – very prevalent among ICA stenosis patients, leading to a bag of systemic problems, not the least being poor blood pressure control.
  • Bad blood pressure control (see above)
  • Development of secondary stenoses in the collateral vessels (contralateral, ECA, …)
  • Development of a collateral rete with its danger of bleeding


I don’t see any better physical theories coming. Also, we can never expect better data than NASCET and this is a bad foundation. Therefore you have to tackle all the complexities outlined above and refrain from simplifying an ICA stenosis to a mere number (always the worst approach).




ICU fever

Differential for (new, resistant) fever in the acute care ward aka ICU.

  • Wrong site:
    • The obvious five: lung, lines, abdomen, skin, urine
    • The hidden five: endocarditis, meningitis, translocation, sinusitis, abscess
    • The weird fevers: drug, central
  • Wrong bug – viruses, fungi
  • Wrong antibiotic – wrong spectrum, MDR pathogens

DNI/DNR and what it means

As you probably know, doctors love DNI/DNRs and everything that clearly prescribes what to do. So the first thing we try to establish with an elderly seriously sick patient is whether intensive care or resuscitation is really an option.

Yet a DNI/DNR label might signify many things to the team:

  1. In an emergency, don’t tube, don’t CPR
  2. Avoid advanced and invasive treatments, such as operations for intracerebral hematoma
  3. If in doubt, don’t try to cure the patient, prefer comfort measures in a palliative setting.
  4. The prognosis is judged to be bad, either mortality-wise or with respect to quality of life.

Although meaning 1 is usually what is intended and agreed upon, meanings 2 and 4 are often used as reasons, and meaning 2 is sometimes implied, even if – as in our house – the difference is made explicit even by SOPs.

Concerning prognosis, we know that

  • Neurological emergencies are very hard to prognosticate in the first 24, even 72 hours
  • Even epidemiological data is scarce – the best evidence exists for mortality of intracerebral hemorrhage (e.g. ICH score) and proximal occluded cerebral arteries; quality of life is a different beast altogether.
  • Stating a prognosis early leads to self-fulfilling prophecies

Our discussion of the subject does not lead to clear procedural standards, but it sensitizes…




Even in the most advanced discussions of modern times’ patient management, I have not once met a colleague who understood p-values. Not that I do.

In last Friday’s session we did the classical experiment (described e.g. in this article) of offering various choices of an explanation of how to interpret p-values to the audience, with actually none of them correct. Which is funny. Then we discussed the core definition. Which is simple. And worked through the examples on the Wikipedia entry (by the way: Wikipedia provides excellent articles on statistics!), such as computing p for simple random variables (such as the number of heads in n tosses of a coin). Which is hard.

Just for completeness: the p-value is the probability of obtaining the data’s test statistics or more extreme values, assuming the null hypothesis to be true.

Unfortunately we did not get far enough to discuss the Bayesian alternatives to p values and their decision theoretic applications.

Here are my take home messages:

  • p-values are a statistical property of the data.
  • You require a statistical model and have to assume the null hypothesis to be true to be able to compute them.
  • They say nothing about the truth of the null hypothesis or (even less so!) any alternative hypothesis.
  • They may increase with effect size yet small effect sizes may have the tiniest ps and vice versa.
  • They cannot be compared among studies.


Central venous access

Have you ever experienced the following: you instruct a peer in how to do a particular procedure while he is doing it, but then realize that you cannot really presuppose knowledge about the theoretical facts, such as indications, anatomy and so on?

We use the case of central venous catheter access to review the most important indications, anatomy, differential access site indications and so forth, then go through the basic steps and try to list details that you could never explain if doing a live instruction.

References: any modern ICU book. I use Irwin & Rippe’s, which is rather conservative. For some cool facts, I can recommend the book Evidence-based critical care.

Blink reflex

Starting with a patient with probable Fisher syndrome, we discuss the various ways to electrically image the brainstem. Here is what we came up with (there are other tests for research purposes, but this is what we routinely can or should be able to do):

  • Blink reflex
  • AEP
  • Calorics or rotating chair, or better: quantitative Halmagyi
  • VEMPs (we don’t do these, but they are easy to perform)
  • of course: long tracts (SEP, MEP)

We plough throught the neuroanatomy of the blink reflex, it’s technical aspects and various lesions with their typical and atypical blink reflex pathologies.

The blink reflex used to be an issue in the seventies and eighties, then with MRI we rediscovered it’s localizing potential (as opposed to – say – the masseter reflex). But it is really only useful if the MRI is negative, i.e., in those MRI-negative strokes and inflammatory lesions as well as cranial neuropathies. In the case of the latter I have to admit that a proper examination is often more effective than a good blink reflex.

As for references I turn to my beloved book on neurophysiology, which is now available in a new edition.