Stroke and disequilibrium

By Marcello Cherchi, MD PhD

For patients

For individuals with abrupt-onset disequilibrium, inner ear causes are significantly more common than stroke-related causes. However, in an acute setting (such as an emergency department) it can be difficult to tell these apart. An emergency room doctor may use physical examination, brain imaging, or other tests to distinguish these.

For clinicians

Overview

The acute vestibular syndrome (AVS) is abrupt-onset disequilibrium often associated with nausea and vomiting. In the acute setting (typically an emergency room) the main differential diagnosis is between more common “peripheral” causes (usually vestibular neuritis) and less common “central” causes (usually posterior circulation stroke). Posterior circulation stroke is estimated to account for 2.1% – 3.6% of AVS cases evaluated in emergency departments in the United States. An ocular motor approach to this scenario involves “HINTS,” which is an acronym for head impulse test, nystagmus, and test of skew deviation; in the hands of a skilled examiner, specific combinations of these findings have been shown to distinguish between vestibular neuritis and posterior circulation stroke more accurately than MRI (which is often falsely negative in the first 48 hours).

Introduction

Stroke can affect any part of the central nervous system, and thus its presentation is quite variegated. Vascular territories usually supply neuroanatomical areas that subserve different functions, so it is common for stroke to present with multiple symptoms and physical examination findings. Thus, although some patients with stroke may complain of disequilibrium, it is usually accompanied by other symptoms (weakness, somatosensory disturbances, language deficits, visual deficits, etc.).

However, in some cases the lesion resulting from a stroke can be sufficiently focal that it presents with predominantly or exclusively one symptom. In a minority of cases, disequilibrium can be the presenting symptom of stroke. While such presentation is not especially common, it is important to recognize since its management and prognosis are quite different than, for example, most otologic causes of disequilibrium.

Epidemiology

The phrase “acute vestibular syndrome” (AVS) refers to disequilibrium presenting apoplectically (Hotson and Baloh 1998).

Abrupt-onset symptoms often prompt emergency department visits. Kerber and colleagues surveyed nearly 26 million emergency department visits in the United States for the 10 year period from 1995 – 2004, and of the 285,622 sampled visits, 7,160 were for “dizziness” or “vertigo,” which amounts to about 2.5% of all emergency department encounters (Kerber et al. 2008). Other estimates identify a slightly broader range of emergency department encounters for these symptoms, from 2.1% – 3.6% (Edlow et al. 2023).

In the acute setting (typically an emergency department), the main clinical concern when assessing a patient with acute vestibular syndrome (AVS) is distinguishing stroke from otologic causes. Tarnutzer and colleagues “estimate that there are about 70,000 to 100,000 strokes per year in the United States with dizziness as a prominent or presenting symptom” (Tarnutzer et al. 2011). Given that the pathway for management of stroke is very different from most otologic causes of AVS, and given that missing a diagnosis of stroke can adversely impact outcomes, emergency department physicians have a low threshold for suspecting stroke, and this concern drives the use of imaging in the United States, which accounts for a substantial proportion of the $10 billion annually spent in the acute workup of these patients (Edlow et al. 2023), even though the usual imaging modality in the emergency department — CT scanning — has relatively little diagnostic value (Kerber et al. 2010). Many papers have been published regarding missed stroke diagnoses in the evaluation of AVS patients (Arch et al. 2016). Newman-Toker and colleagues estimate that of all AVS patients evaluated in the United States each year, 15,000 – 165,000 may have strokes that are missed (Newman-Toker et al. 2014).

For a patient presenting with AVS, estimates of the likelihood of stroke vary by an order of magnitude. Kerber and colleagues studied 1666 patients presenting to the emergency department or admitted to the hospital with “dizziness” and concluded that 53 (3.2%) were ultimately diagnosed with stroke or transient ischemic attack (Kerber et al. 2006). Newman-Toker and colleagues report that about 4% of AVS patients evaluated in the emergency department are ultimately diagnosed with stroke (Newman-Toker et al. 2013b). Doijiri and colleagues evaluated 221 consecutive AVS patients and concluded that 11% with “isolated vertigo or dizziness attack” were ultimately diagnosed with stroke (Doijiri et al. 2016). Tarnutzer and colleagues “estimate the true proportion of acute vestibular syndrome due to stroke to be about 25% ± 15%” (Tarnutzer et al. 2011).

Pathophysiological mechanism of disease

In the United States about 18% of all strokes involve the posterior circulation; however, for AVS patients in whom stroke is ultimately identified as the cause, about 83% are in the posterior circulation (Tarnutzer et al. 2011), and the usual etiologies are cerebellar stroke (Armato et al. 2014; Morita et al. 2011; Perloff et al. 2017), often in the territory of the posterior inferior cerebellar artery (Doijiri et al. 2016). Relatively few cases involve labyrinthine infarction (Eliezer et al. 2019; Liqun et al. 2018), which can mimic labyrinthitis (Nam et al. 2021); such cases involve the labyrinthine artery, which usually branches off the anterior inferior cerebellar artery. Occasional cases are reported in which infarction is so focal as to involve exclusively the vestibular nucleus (Kim and Lee 2010; Kim et al. 2014).

Clinical presentation

By definition, patients with acute vestibular syndrome present with apoplectic onset of disequilibrium, often associated with nausea and vomiting.

Physical examination: components of HINTS

Literature is accumulating that when evaluating an AVS patient, the combination of several physical examination findings — and specifically ocular motor findings — has greater sensitivity and specificity for stroke than MRI within the first 48 hours (Newman-Toker et al. 2013a; Newman-Toker et al. 2013b). The ocular motor findings in question comprise what has come to be known by the acronym “HINTS,” which stands for head impulse test, nystagmus, and test of skew deviation. This combination of ocular motor tests will tend to reveal different findings for “peripheral vertigo” (which essentially refers to vestibular neuritis) and “central vertigo” (which essentially refers to posterior fossa stroke).

Physical examination: head impulse

The horizontal head impulse test relies on integrity/failure of the horizontal rotational vestibulo-ocular reflex (VOR) during rapid head movements. The head impulse test has been shown to distinguish posterior fossa stroke from vestibular neuritis (Newman-Toker et al. 2008).

In peripheral vestibular weakness (such as vestibular neuritis) the horizontal vestibulo-ocular reflex is inadequate, so when the patient’s head is moved passively and rapidly, this will “drag” the eyes off target (this is the “low gain” of the VOR), and the patient will execute a corrective saccade to keep the eyes on the intended target — this constitutes a “positive” head impulse test.

In contrast, cerebellar lesions usually do not affect the vestibulo-ocular reflex, which is why head impulse testing tends to be “negative” (normal) in cerebellar stroke. However, exceptions to this general rule have been reported (Witsch et al. 2018), and it has been estimated that about 9% of patients with posterior circulation stroke have a positive (abnormal) head impulse test (Newman-Toker et al. 2008).

Physical examination: nystagmus

In a unilateral peripheral vestibular lesion (such as vestibular neuritis), the “nystagmus” component of the physical examination refers to a repetitive eye movement that:

• Is spontaneous.
• The rapid component is unidirectional (usually just horizontal, but there may be an ipsitorsional component).
• May increase (in amplitude and frequency) when the patient looks in the direction of the fast phase, and decrease when the patient looks in the direction of the slow phase. This pattern is said to “obey Alexander’s law.”

In contrast, in a posterior fossa lesion (typically a stroke in the territory of PICA), the “nystagmus” component of the physical examination refers to a repetitive eye movement that:

• Is gaze-evoked (i.e., absent on primary position of gaze, but present on eccentric gaze) (Strupp et al. 2014).
• Is direction changing. Typically the direction of the fast phase of the nystagmus will be identical to the direction of gaze.
• The rapid component is therefore multi-directional.
• These characteristics are believed to be attributable to a failure of the “gaze holding mechanism” (Baier and Dieterich 2011) which usually helps maintain eccentric gaze.

Physical examination: test of skew deviation

In the context of a HINTS examination, “skew deviation” refers to vertical strabismus. This finding generally reflects brainstem dysfunction, and can occur in posterior fossa stroke. Skew deviation rarely occurs in vestibular neuritis (Eggers and Kattah 2020; Park et al. 2019; Vibert et al. 1996).

Summary of HINTS

The components of HINTS, and the findings for vestibular neuritis and posterior fossa stroke, respectively, are summarized in the Table below.

	“Peripheral” — i.e., a unilateral peripheral deficit (usually vestibular neuritis)	“Central” — i.e., posterior fossa pathology (usually an infarct in the territory of the posterior inferior cerebellar artery)
Head impulse test	“Positive,” i.e., a rapid horizontal head movement elicits a refixation saccade.	“Negative,” i.e., the eyes stay on target after a rapid head movement.
Nystagmus	Nystagmus is spontaneous, unidirectional, and obeys Alexander’s law.	Nystagmus is gaze-evoked, direction-changing and multi-directional.
Test of skew	“Negative” — vertical skew deviation is absent.	“Positive” — vertical skew deviation is present.

Newman-Toker and colleagues (Newman-Toker et al. 2013a) report that when the three ocular motor examination findings are combined, they exhibit a 96.5% sensitivity and an 84.4% specificity for posterior fossa stroke.

Although HINTS has demonstrated success in discriminating posterior fossa stroke from peripheral vestibular disease in AVS patients, an important caveat is that this is in the hands of an expert user, or “appropriately trained clinician” (Tarnutzer et al. 2023).

HINTS: bedside HIT versus video HIT

The bedside horizontal head impulse test (bHIT) requires some skill in execution and interpretation. It turns out that highly reliable interpretation of the horizontal head impulse test can be achieved through computer algorithms applied to videonystagmography — in other words, the video head impulse test (vHIT).

Despite the greater utility of vHIT in general, there is debate regarding whether bHIT and vHIT operate differently in the context of HINTS. Some investigators have observed vHIT to be superior to bHIT in this regard (Choi et al. 2018b), while others conclude that bHIT and vHIT are equivalent for HINTS (Guler et al. 2017).

Testing: vestibular

Modest literature has examined the combination of vHIT and vestibular evoked myogenic potentials for distinguishing vestibular neuritis from posterior fossa stroke (Calic et al. 2020), or those tests plus caloric testing (Nham et al. 2023).  While such studies are interesting, it is probably not realistic to expect that vestibular evoked myogenic potentials or caloric testing could be performed in the acute setting (such as an emergency department), so this is more of academic interest rather than for practical application.

Imaging

Although MRI is a sensitive imaging modality for stroke, small strokes in the posterior fossa may not be detectable by MRI in the first 48 hours (Choi et al. 2018a; Choi and Kim 2018; Edlow et al. 2017; Frey et al. 2002; Morita et al. 2011; Saber Tehrani et al. 2014).

Differential diagnosis

AVS has a broad differential diagnosis, but the main concern in the acute setting (typically an emergency department) is to distinguish “peripheral” causes (usually vestibular neuritis) from “central” causes (usually posterior circulation stroke).

Treatment and prognosis

For the differential diagnosis above, the distinction between vestibular neuritis and a posterior circulation stroke is important because of the implications for treatment and prognosis.

• Vestibular neuritis: Immediate treatment is supportive, longer-term treatment is vestibular rehabilitation, and prognosis is generally quite good, with recurrence being uncommon.
• Posterior fossa stroke: Immediate treatment may involve tPA; long-term management depends on mechanism of stroke (e.g., anticoagulation for atrial fibrillation versus treatment of vascular risk factors for atherosclerotic disease); prognosis is variable.

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