Vestibular neuronitis (“acute labyrinthitis”)

Vestibular neuronitis (“Acute labyrinthitis”)

I. What every physician needs to know.

Vestibular neuronitis (VN) is also known as neurolabyrinthitis or idiopathic acute vestibular dysfunction and is the second most common cause of peripheral vertigo after benign paroxysmal positional vertigo (BPPV).

Acute labyrinthitis is vestibular neuronitis that is associated with unilateral hearing loss due to involvement of the entire inner ear. The condition results from a selective inflammation of the vestibular nerve (eighth cranial nerve). The exact pathophysiology is unclear; although it is thought to be due to a virus; a history of a preceding viral illness is elicited in less than half of patients. Postmortem studies have shown atrophy of the vestibular nerve similar to findings in known viral disorders, and herpes simplex virus type 1 has been detected in the vestibular nerve on autopsy. Because of these findings, one hypothesis is that vestibular neuronitis is caused by reactivation of HSV-1 infection in the vestibular nerve.

Dizziness is a common symptom, accounting for 3-5% of clinical encounters across care settings. Classically, clinicians were taught that the patient’s description of dizziness, vertigo (sense of spinning or motion), pre-syncope, lightheadedness, and unsteadiness, provides diagnostically useful information. However, a study of more than 300 consecutive patients presenting to the ED with acute dizziness found that more than half were unable to reliably report which type of dizziness best describes their symptom and the type of dizziness was not a reliable predictor of the underlying cause.

The current paradigm groups the causes of acute dizziness into three vestibular syndromes based on the timing and triggers of the symptom. The use of the term vestibular refers to the symptom of dizziness and does not imply underlying cause.

Triggered, episodic vestibular syndrome (t- EVS) is characterized by repetitive episodes of dizziness triggered by an event. Patients are asymptomatic at rest. BPPV is the most common condition that causes t- EVS.
Spontaneous episodic vestibular syndrome (s- EVS)- recurrent episodes of dizziness lasting minutes to hours. Although there appear to be predisposing factors (e.g., environmental or lifestyle factors in vestibular migraine), there is no clear trigger.
Acute Vestibular Syndrome (AVS)- a monophasic, abrupt-onset dizziness that persists for days. It is distinguished from t- EVS in that the dizziness is continuous at rest and is exacerbated, but not triggered, by movement.

Vestibular neuronitis and posterior circulation stroke are the two important conditions in the differential diagnosis of AVS vestibular syndrome.

The key features of vestibular neuronitis include acute sustained severe dizziness associated with nausea and vomiting, and difficulty walking because of vertigo, although the actual ability to walk is intact. Although movement worsens dizziness, it is important to establish through careful interview that the dizziness remains at rest and is not triggered by head motion. There is a tendency for the patient to lean toward the affected side. Recovery after vestibular neuronitis is usually incomplete, although clinical improvement generally occurs after one or two days, with further gradual improvement over weeks to months from both partial restoration of peripheral labyrinthine function and central vestibular compensation for the imbalance in vestibular tone.

Potential treatments for vestibular neuritis include corticosteroids and symptomatic treatment acutely and vestibular rehabilitation after severe symptoms have subsided.

II. Diagnostic Confirmation: Are you sure your patient has vestibular neuronitis ?

The diagnosis of vestibular neuronitis is made based on history and clinical examination. There are no specific imaging or laboratory tests to confirm the diagnosis of vestibular neuronitis. Tests of audio-vestibular function have not been sufficiently studied and are not recommended for differentiating central from peripheral AVS. Viral studies are not recommended, as they cannot prove a causal relationship. Imaging may be necessary to rule out central causes of vertigo if there is concern for ischemia or hemorrhage, but imaging is not necessary to make the diagnosis of vestibular neuronitis and there are limitations to the use of brain imaging to exclude central causes of acute dizziness.

Central conditions that mimic vestibular neuritis include cerebrovascular and demyelinating conditions. As many as 25% of older patients presenting with AVS to the Emergency Department have cerebellar infarction as the underlying cause. Imaging to diagnose a central cause of AVS requires visualization of the posterior fossa, a region frequently obscured in CT scans by boney artifacts. MRI is frequently considered the gold standard, however, a study in which AVS patients with an initially negative study underwent repeat MRI for evolving symptoms reported a false negative in the earlier imaging in 12%. The estimated sensitivity of MRI imaging for posterior fossa lesions within 24 hours of symptom onset is estimated to be 80%; aggregate specificity from two studies is estimated at 97% and the negative likelihood ratio is 0.21. In AVS patients without deficits in the general neurologic examination, a battery of ocular tests has been found to be better than MRI with DWI in ruling out stroke during the first 48 hours of symptom onset (see below).

A. History Part I: Pattern Recognition:

As described earlier, Vestibular Neuritis presents classically as an Acute Vestibular Syndrome with the following features;

Acute onset vertigo that lasts days to weeks
Persistent dizziness that is exacerbated, but not triggered, by head motion
Nausea and vomiting associated with vertigo
Difficulty walking, although ability to walk is not impaired; veering toward one side
Spontaneous nystagmus consistent with a peripheral lesion (see below)
Unilateral hearing loss (in acute labrynthitis)
No other neurologic symptoms and an otherwise normal neurologic examination
No risk factors for CVA (e.g., tobacco use history, hypertension, diabetes, hyperlipidemia, atrial fibrillation, hypercoagulable state, recent cervical trauma, prior stroke or coronary artery disease)

A typical patient with this disease is a 45-year old man with no past medical history who has a sudden onset of acute dizziness. The dizziness starts abruptly, is severe for a few days, and gradually resolves over the course of a few weeks. He is able to sit with arms crossed unaided, walk to the bathroom, although he leans to the left, and he has nausea and vomiting associated with the dizziness. He has horizontal nystagmus but no other focal neurologic findings.

B. History Part 2: Prevalence:

Vestibular neuronitis is the second most common cause of peripheral vertigo (after BPPV), with an annual incidence of 3.5/100,000. It is rare for an individual to have more than one episode of VN; however, secondary BPPV may be more common following an episode of vestibular neuritis.

C. History Part 3: Competing diagnoses that can mimic vestibular neuronitis.

The duration of the symptom, timing (episodic or constant), triggering factors, and associated symptoms enable the clinician to classify acute dizziness into one of three diagnostic groups: Triggered, episodic vestibular syndrome (e.g., BPPV and orthostatic hypotension), Spontaneous episodic vestibular syndrome (e.g., vestibular migraine, Meniere’s disease, transient ischemic attack) and Acute Vestibular Syndrome (e.g., vestibular neuritis, stroke, multiple sclerosis).

Distinguishing peripheral from central nystagmus can differentiate between vestibular neuronitis and central causes of AVS. A patient with other neurologic symptoms suggests a central origin and additional work-up for central causes should be undertaken.

Patients describing brief (less than one minute), recurrent attacks of vertigo provoked by changes in head position and who are normal between episodes likely has BPPV. Occasionally, nausea may persist longer than one minute which may lead to overestimation of the duration of dizziness. Neck extension (reaching for objects on shelves), head motion relative to gravity (lying down, sitting up from supine, bending over), and turning in bed from side to side frequently trigger dizziness in BPPV. Exacerbation of dizziness with head motion is frequently reported by persons suffering from VN which may lead to a misdiagnosis of BPPV. In fact, dizziness from any cause is exacerbated by head movement. The Dix-Hallpike and Epley maneuvers can be used for diagnosis and treatment. Compared to BPPV, the symptom of VN is vertigo that lasts days to weeks, is not triggered by head movement, and does not normalize between episodes.

Meniere’s disease is a syndrome characterized by episodic spontaneous vertigo, unilateral fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The episodes of vertigo usually do not last longer than a few hours. Compared to those of Meniere’s disease, the symptoms of VN tend to last for days to weeks, to be non-episodic, and be associated with unilateral hearing loss only in acute labyrinthitis.

Transient ischemic attacks may be experienced as recurrent spontaneous attacks of dizziness over weeks to months. Cerebral vascular ischemia/infarction or hemorrhage usually has other associated neurologic symptoms. The neurologic signs and symptoms, however, may present subtly. Mild diplopia may result from a peripheral lesion, making it a less reliable discriminator. Although the presence of neurologic signs and symptoms strongly suggests a central cause, their absence is a poor predictor of a peripheral cause. When a patient has risk factors for a CVA, the threshold to image the patient is lower. Arterial dissection should be considered in patients who present with head and neck pain and history of trauma.

D. Physical Examination Findings.

The first distinction that should be made is that between peripheral and central vertigo. This distinction can often be made at the bedside. For AVS Vestibular Syndrome (acute, rapid onset, persistent dizziness which resolves over days to weeks), the most important conditions to differentiate are VN from posterior circulation stroke. Neurologic deficits, such as dysarthia, incoordination, numbness, or weakness, suggest a central origin of vertigo.The crucial first step is to perform a neurologic examination focusing on the cranial nerves, cerebellum (finger-to-nose, heel-to-shin) and gait. Patients with a peripheral lesion can usually stand and walk, although they lean toward the side of the lesion. If the patient is unable to walk unassisted, testing for truncal ataxia is performed by asking the patient to sit upright without using the arms. Severe truncal ataxia, defined as the inability to sit upright without the use of arms to stabilize, is predictive of a central lesion.

In a study of adults presenting with the chief complaint of dizziness, 3% were diagnosed with a stroke or TIA; 17% of these patients presented with isolated dizziness. In patients presenting with AVS who have a normal neurologic examination, the best predictor of a stroke is the aggregate of three oculomotor findings: a normal Horizontal Head Impulse Test; a horizontal nystagmus that changes direction with eccentric gaze; and skew deviation. This battery of tests goes by the mnemonic HINTS (Head Impulse, Nystagmus, Test of Skew).

Horizontal Head Impulse Test (h- HIT): h- HIT tests the vestibulo-ocular reflex on each side and is positive when a patient has VN. To perform this test, the patient fixes his or her gaze on the examiner’s nose. The examiner then grasps the patient’s head and applies a brief, small-amplitude (10 to 20 degrees) head turn, first to one side then the other. When there is a peripheral lesion, a corrective eye movement (saccade) back to the examiner’s nose is seen after the head is moved toward the affected side. As an internal control, for the normal side, the eyes will stay on the examiner’s nose after the head thrust toward the normal side. Of note, a normal h- HIT test predicts a central, more serious process.

Videos of normal head thrust and abnormal head thrust are available at: http://www1.imperial.ac.uk/departmentofmedicine/divisions/experimentalmedicine/neurosciences/clinneuroscience/movandbal/otology/mabdandv/.
It is important to define the pattern of nystagmus, its vector, direction, change with varying gaze positions. The nystagmus associated with VN is a unidirectional, principally horizontal pattern (although nystagmus will also have a slight torsional and vertical component). The nystagmus is named after the fast phase. During the first hours following symptom onset, the nystagmus is typically present on primary gaze (spontaneous). Subsequently, the nystagmus may only be detected during gaze testing. Nystagmus which changes direction on eccentric gaze (i.e., right beating nystagmus with right gaze and left beating nystagmus with left gaze, with or without nystagmus with forward gaze) is suggestive of a central etiology (e.g., posterior fossa stroke or structural lesion, Wernicke-Korsakoff syndrome, therapeutic phenytoin, alcohol intoxication). Spontaneous nystagmus of central origin is often purely horizontal, purely vertical, or torsional.

The presence of spontaneous nystagmus is first assessed by observing the eyes while at neutral gaze. The next step is to evaluate for gaze-evoked nystagmus by instructing the patient to follow one’s finger placed 10 inches from the face. The clinician looks for nystagmus at each direction of gaze and, if present, notes the direction of its fast phase.
Skew deviation is vertical ocular misalignment detected by alternate eye cover test and is a sign of posterior fossa pathology, with a specificity of 98%, but a low sensitivity (30%). While the patient focuses gaze on the examiner’s nose, the examiner alternately covers each eye. The examiner looks for vertical corrective movement on switching the cover from one eye to the other. On one side, one will detect an upward correction and on the other, a downward correction. The presence of vertical correction suggests a stroke.

The mnemonic INFARCT can be used to remember the oculomotor findings that predict a stroke (Impulse Normal,_ Fast-phase Alternating,_ Refixation on Cover Test).

In a prospective study of 101 patients with one or more stroke risk factors who presented with acute vertigo, nausea, vomiting, unsteady gait, with/ without nystagmus (AVS), 25 had vestibular neuritis and 76 had a central lesion. When compared with the presence of other neurological findings and early MRI- DWI, dangerous findings on HINTS testing was 100% sensitive and 96% specific for the presence of a central lesion, with a positive LR of 25 and negative LR of 0. The study authors concluded that in patients presenting with the AVS clinical picture without deficits in general neurologic examination or truncal ataxia, a benign HINTS examination ruled out stroke better than a negative MRI-DWI in the first 48 hours after onset of symptoms.

E. What diagnostic tests should be performed?

There are no specific imaging or laboratory tests to confirm the diagnosis of VN. Laboratory tests of audio-vestibular function (e.g., electronystagmography) can document unilateral vestibular loss but is rarely necessary to make the diagnosis.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Viral studies are not recommended, as they cannot prove a causal relation. There are no lab tests that can be ordered to establish the diagnosis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Imaging may be necessary to rule out central causes of vertigo if there is concern about ischemia or hemorrhage, but imaging is not necessary to make the diagnosis of vestibular neuronitis. Brain imaging should be performed if the patient has spontaneous nystagmus consistent with central origin, if there are neurologic findings on physical exam, if the patient is at high risk for CVA/TIA, or if a severe headache accompanies the vertigo. CT has low sensitivity for detecting acute infarction particularly in the posterior fossa (7- 42%). Although a head CT is an excellent test for ruling out cerebellar hemorrhage, this condition rarely presents as acute dizziness without other obvious worrisome clinical findings.

In the previously described study to diagnose stroke in at- risk patients who presented with AVS (HINTS study), neuroimaging by MRI-DWI performed within 48 hours of symptom onset was falsely negative in 12% of patients with a stroke.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

In a young patient whose physical exam findings are consistent with peripheral vertigo (see above) and who has no other neurologic findings, head imaging is usually unnecessary unless symptoms do not improve or worsen in one or two days.

III. Default Management.

Management of vestibular neuronitis is largely symptomatic, as the exact pathophysiology of the disease is unclear. The symptoms tend to resolve in a matter of days to weeks with central vestibular compensation for the imbalance in vestibular tone and partial restoration of peripheral labyrinthine function.

There is evidence, albeit from small, low methodologic quality studies, to support the use of corticosteroids in vestibular neuritis. A review of four randomized trials found that while oral corticosteroids was associated with complete vestibular recovery at one month as measured by caloric testing, it had no significant effect on caloric recovery at 12 months, on extent of caloric activity at 1 or 12 months, symptomatic recovery at 24 hours or Dizziness Handicap Inventory scores at any point of follow-up. A double-blind trial randomized patients within 3 days of the onset of vertigo to receive placebo, methylprednisolone, valacyclovir, and methylprednisolone plus valacyclovir. Treatment with methylprednisolone improved vestibular function compared to placebo at 12-month follow-up, but treatment with valacyclovir alone or combination of methylprednisolone plus valacyclovir was no more effective than treatment with methylprednisolone alone. The study did not assess duration and intensity of symptoms.

A. Immediate management.

When pharmacotherapy is necessary to treat symptoms, vestibular suppressants and antiemetics are frequently administered. The major classes of vestibular suppressant medications are antihistamines, benzodiazepines, and anticholinergics. The vestibular suppressants with anticholinergic and antihistamine properties also have antiemetic activity. In the acute phase, when a patient may have severe nausea and vomiting, intravenous (IV) agents are usually preferable to oral agents. Antivertigo medications, if necessary, should be administered only during the first few days as they are sedating and may delay central compensation of the vestibular deficit.

Few studies have compared the efficacy of one agent over another. A double-blind study that randomized patients presenting to the ED with peripheral vertigo to dimenhydrinate (an anticholinergic antiemetic) 50 mg IV or lorazepam 2 mg IV reported greater reduction in vertigo with dimenhydrinate compared to lorazepam. The ability to walk was judged to be better at one and two hours after treatment with dimenhydrinate; patients randomized to lorazepam experienced more drowsiness.

B. Physical examination tips to guide management.

Nystagmus, gait improvement, and improvement in nausea and vomiting should guide management. The patient should not be on standing medications for symptoms for more than two days, as these medications will slow central vestibular compensation.

C. Laboratory tests to monitor response to and adjustments in management.

None.

D. Long-term management.

Medications should not be used for long periods, as a prolonged suppression of vestibular activity can impair the central compensation response and delay recovery in the long term. Symptomatic relief can be provided for 24-48 hours, but the medications should be weaned after that period. Once the severe symptoms have waned, patients should be encouraged to resume activities as this facilitates central compensation for the asymmetric vestibular impulses.

There is evidence of moderate to high quality that vestibular rehabilitation improves functional measures and symptoms of VN compared to sham exercises, no rehabilitation, medications, or usual care. Components of vestibular rehabilitation include maneuvers to bring on the symptoms to “desensitize” the vestibular system, learning coordination between eye and hand movements, improving balance and gait, and education about the condition.

In a review of 39 randomized controlled trials of vestibular rehabilitation (n= 2441) for management of chronic unilateral peripheral vestibular dysfunction of various causes including vestibular neuritis, there was significant improvement in the primary outcome of changes in dizziness and functional measures, quality of life and physiologic measures. The studies showed positive gains that lasted for 3, 6, and 12 months without significant adverse effects.

E. Common pitfalls and side effects of management

Common pitfalls in the evaluation of acute dizziness include overreliance on the patient’s description of symptoms and on brain CT to exclude a central cause of acute vertigo. While the absence of other neurologic symptoms reduces the likelihood of a cerebrovascular diagnosis, it is a frequent misconception that isolated dizziness excludes a stroke etiology. Contrary to a common belief that the complaint of true vertigo is more predictive of a stroke etiology, a population based study reported that patients reporting vertigo did not have higher odds of being diagnosed with a stroke than those reporting “dizziness”. Another misconception is that dizziness worsened by head motion suggests a benign process; dizziness from any cause is exacerbated by head movement.

Many of the medications can be sedating. Continuing standing medications for more than two days will impair long-term recovery.

Commonly used agents for symptomatic treatment include dimenhydrinate 50 mg IV, promethazine 25 mg IV, meclizine 25 mg orally, scopolamine 0.2 mg IM or orally or the patch, compazine 10 mg IV, diazepam 5 mg IV, and lorazepam 1 mg IV. Responses tend to be dose-dependent, so if the initial dose is not effective, a higher dose should be administered.

Antiemetics that can be used include metoclopramide 5 to 10 mg IV, ondansetron 4 to 8 mg IV, and prochloperazine 5 to 10 mg.

Dosing of prednisone taper for vestibular neuronitis that may be prescribed:

Prednisone 60 mg days 1- 5

Prednisone 40 mg day 6

Prednisone 30 mg on day 7

Prednisone 20 mg on day 8

Prednisone 10 mg on day 9

Prednisone 5 mg on day 10

Gastric acid suppression for prophylaxis may be considered particularly for at-risk individuals.

IV. Management with co-morbidities

Doses of medications should be adjusted as necessary for patients with renal insufficiency and hepatic insufficiency. In elderly patients, doses of medications should be started at the lowest dose, as frail older adults are prone to experiencing side effects.

A. Renal insufficiency.

Adjust doses of medications as necessary for those medications that are renally cleared.