What is the differential diagnosis for an adult patient presenting with new-onset horizontal nystagmus?

Differential Diagnosis for Horizontal Nystagmus

Primary Peripheral Vestibular Causes

Horizontal nystagmus in adults most commonly results from benign paroxysmal positional vertigo (BPPV) affecting the lateral semicircular canal, which produces direction-changing horizontal nystagmus that is either geotropic (beating toward the ground) or apogeotropic (beating away from the ground). 1, 2

Lateral Canal BPPV (Most Common)

• Geotropic variant (more common): Horizontal nystagmus beats toward the undermost ear on both sides during supine roll testing, with the most intense nystagmus indicating the affected ear 1, 2
• Apogeotropic variant: Horizontal nystagmus beats toward the uppermost ear on both sides, with the side opposite the strongest nystagmus being the affected ear 1, 2
• Onset typically occurs within 0.7-0.8 seconds of positioning, with paroxysmal nystagmus lasting 11.7-47.9 seconds in canalolithiasis 3
• Can develop after repositioning maneuvers for posterior canal BPPV due to "canal switch" phenomenon 1, 2

Cupulolithiasis

• Produces persistent apogeotropic horizontal nystagmus that does not fatigue 3, 4
• Nystagmus persists as long as the position is held, with slower decay (65-81% of peak velocity remains at 40 seconds) 3
• May occur when debris becomes attached to the cupula of the horizontal semicircular canal 4

Acute Unilateral Vestibulopathy

• Vestibular neuritis/labyrinthitis: Produces unidirectional horizontal nystagmus beating away from the affected side 5
• Ménière's disease: Can present with persistent apogeotropic horizontal nystagmus 6, 3
• Sudden sensorineural hearing loss with vertigo: May demonstrate periodic alternating nystagmus that progresses to unidirectional nystagmus within 48 hours 6

Peripheral Periodic Alternating Nystagmus

• Direction-changing spontaneous horizontal nystagmus with quiescent intervals observed in Ménière's disease, acute labyrinthitis, and vestibular schwannoma 6
• Suppressed by visual fixation with normal oculomotor tests 6
• Transient, typically progressing to unidirectional nystagmus within 48 hours 6

Central Nervous System Causes

Any horizontal nystagmus that persists without decay, lacks visual suppression, or is associated with other neurological signs warrants urgent neuroimaging to exclude serious structural pathology. 2, 7

Cerebellar Lesions

• Lower cerebellar lesions: Can produce unidirectional horizontal nystagmus directed toward the lesion side or direction-changing apogeotropic positional nystagmus enhanced when lying on the non-affected side 5
• Dorsal vermis lesions: May cause central paroxysmal positioning vertigo with persistent horizontal nystagmus 8
• Associated with truncal ataxia, dysmetria, and dysdiadochokinesia 2

Brainstem Pathology

• Cervicomedullary junction lesions: Can produce horizontal nystagmus, though downbeat nystagmus is more characteristic 2, 7
• Dorsolateral fourth ventricle lesions: Associated with central positional nystagmus 8
• Typically accompanied by motor palsy, sensory deficits, dysarthria, or ocular motor palsies 5

Other Central Causes

• Vestibular migraine: Produces persistent geotropic or apogeotropic horizontal nystagmus with slower decay (61% of peak velocity at 40 seconds) 3
• Intracranial tumors: Including vestibular schwannoma can cause horizontal nystagmus 2, 6
• Vertebrobasilar insufficiency: Should be considered in the differential 7

Critical Distinguishing Features

Peripheral vs. Central Differentiation

Visual suppression is the single most reliable distinguishing feature: peripheral horizontal nystagmus suppresses with visual fixation, while central nystagmus does not. 6

Peripheral Characteristics:

• Latency of 0.7-0.8 seconds before nystagmus onset 1, 3
• Paroxysmal with clear decay (typically <60 seconds for canalolithiasis) 3
• Suppressed by visual fixation 6
• Normal saccadic and smooth pursuit eye movements 6
• Canal paresis on bithermal caloric testing 6

Central Characteristics:

• Persistent nystagmus without decay or fatigability 8, 3
• Baseline nystagmus present in primary position 2
• Not suppressed by visual fixation 6
• Associated cerebellar signs (ataxia, dysmetria) or cranial nerve palsies 2, 5
• Abnormal oculomotor testing 6

Diagnostic Algorithm

Step 1: Perform Positioning Maneuvers

• Dix-Hallpike maneuver: Primarily for posterior canal BPPV but essential to exclude conversion to horizontal canal involvement 2
• Supine roll test: The definitive test for lateral canal BPPV, performed by rotating the head 90 degrees to each side while supine 1, 2
• Check for baseline nystagmus in primary position before positioning 2

Step 2: Characterize Nystagmus Features

• Direction: Geotropic vs. apogeotropic 1, 2
• Temporal profile: Paroxysmal (<60 seconds) vs. persistent 3
• Visual suppression: Test with and without fixation 6
• Intensity decay: Rapid decay suggests peripheral canalolithiasis; minimal decay suggests cupulolithiasis or central pathology 3

Step 3: Assess for Red Flags Requiring Neuroimaging

• Persistent nystagmus without decay 8, 3
• Lack of visual suppression 6
• Abnormal oculomotor tests (saccades, smooth pursuit, optokinetic nystagmus) 6
• Associated neurological signs (ataxia, cranial nerve palsies, motor/sensory deficits) 2, 5
• Downbeat component on Dix-Hallpike 2, 7

Step 4: Obtain Appropriate Imaging

• MRI of the brain is the preferred imaging modality when central pathology is suspected 2, 7
• CT scans are inadequate for visualizing posterior fossa structures 7
• Neuroimaging is mandatory for acquired nystagmus with central features to exclude brainstem/cerebellar structural lesions 7

Step 5: Consider Vestibular Function Testing

• Vestibulo-ocular reflex assessment 2, 7
• Vestibular evoked myogenic potentials (VEMPs) 2, 7
• Bithermal caloric testing to identify canal paresis 6

Common Pitfalls

The most dangerous error is misdiagnosing central positional nystagmus as BPPV when proper diagnostic maneuvers are not performed or central features are overlooked. 2

• Assuming all direction-changing horizontal nystagmus is benign: Central lesions can produce direction-changing positional nystagmus that mimics BPPV 8, 5
• Failing to test visual suppression: This is the most reliable differentiating feature between peripheral and central causes 6
• Not performing both Dix-Hallpike and supine roll testing: Missing lateral canal involvement is common when only Dix-Hallpike is performed 2
• Overlooking subtle cerebellar signs: Truncal ataxia may only become apparent in standing position 5
• Relying solely on temporal features: While helpful, latency and duration can overlap between peripheral and central causes in individual cases 8
• Accepting "persistent BPPV" without further workup: True BPPV should resolve or significantly improve within weeks to months; persistent symptoms warrant neuroimaging 8, 4