Differential Diagnoses: Central Vertigo with Abnormal VNG Findings

• Spinning vertigo triggered by lying on either side and sitting from supine (positional, but not BPPV - negative Dix-Hallpike and supine roll test)
• Abnormal smooth pursuit - indicates cerebellar/brainstem dysfunction
• Abnormal VOR (vestibulo-ocular reflex impairment) on VNG
• Head-shake nystagmus - presence indicates a central lesion when combined with the above
• Gait imbalance - suggests cerebellar involvement
• 3-week duration, severe vomiting

Priority Differentials (Most Likely First)

1. Posterior Fossa / Cerebellar Infarction (Ischemic Stroke)

• Territory: PICA (posterior inferior cerebellar artery) or AICA (anterior inferior cerebellar artery) territory
• Features here that fit: vomiting, gait imbalance, abnormal VOR, head-shake nystagmus, positional vertigo unresponsive to Epley
• HINTS criteria strongly favor central cause: abnormal smooth pursuit + abnormal VOR (negative HIT equivalent) + gait instability
• The HINTS exam (Head Impulse / Nystagmus / Test of Skew) has greater sensitivity than early MRI for posterior circulation stroke
• Age 43 in a female: consider risk factors (hypertension, migraine, OCP use, vasculitis)

2. Vertebral Artery Dissection (VAD)

• Accounts for ~2% of all ischemic strokes but a disproportionately large fraction of strokes in patients under 45
• Symptoms: dizziness (most frequent - occurs in 58%), neck pain, headache, nausea/vomiting
• Often initially mistaken for migraine or musculoskeletal disorder
• Leads to posterior circulation stroke/TIA
• Diagnosis: CT-Angiography or MR-Angiography of cervical vessels

3. Vertebrobasilar Insufficiency (VBI) / TIA

• Episodic vertigo lasting minutes, often with associated neurologic symptoms (diplopia, dysarthria, ataxia, weakness)
• In this patient with 3-week history and positional component: posterior circulation TIA must be considered
• Note: isolated vertigo alone is usually not attributed to VBI/TIA unless combined with other posterior circulation symptoms

4. Multiple Sclerosis (MS)

• Vertigo is the presenting symptom in 7-10% of MS patients, appearing in the course of disease in one-third
• Can cause severe vertigo with nausea and vomiting
• Signs: horizontal, rotary, or vertical nystagmus; Internuclear Ophthalmoplegia (INO) is highly suggestive
• Demyelinating plaques in brainstem/cerebellum cause abnormal smooth pursuit and VOR disturbance
• VNG findings in this patient (abnormal smooth pursuit, VOR, head-shake nystagmus) are consistent with a brainstem MS plaque
• Look for: other historical attacks with varying neurologic signs, history of optic neuritis, sensory disturbances

5. Central Positional Vertigo (Cerebellar/Brainstem Lesion)

• Positional vertigo from lesions of the dorsolateral fourth ventricle or dorsal vermis can mimic BPPV-like presentation
• Distinguished from BPPV by: short latency (no delay), atypical nystagmus direction, non-fatigable, unresponsive to Epley
• Etiology: isolated cerebellar infarction (nodulus), demyelination, or tumor
• Nystagmus pattern is heterogeneous and can spontaneously resolve

6. Wallenberg Syndrome (Lateral Medullary Infarction)

• PICA or vertebral artery occlusion
• Classic constellation: vertigo, nausea, vomiting + ipsilateral facial pain/temperature loss, contralateral body pain/temperature loss, Horner syndrome, dysphagia, hoarseness, ipsilateral limb ataxia
• Head-shake nystagmus can be present due to vestibular nucleus involvement
• Abnormal VOR from ipsilateral vestibular nuclei involvement

7. Vestibular Migraine (Migrainous Vertigo)

• Vertigo attacks can occur without headache or during headache-free intervals
• Features: imbalance, head motion intolerance, photophobia, phonophobia
• Most patients have a family/personal history of migraine
• No residual neurologic/otologic signs between attacks
• Can produce central-pattern VNG findings during active phase
• In a 43-year-old female, migraine is epidemiologically common
• However, the persistent 3-week course with severe vomiting and gait imbalance would be atypical unless in prolonged migraine aura

8. Posterior Fossa Tumor

• Space-occupying lesions (ependymoma, metastasis, meningioma, cerebellar astrocytoma) can cause progressive vertigo, vomiting, and gait ataxia
• Signs of raised ICP (morning headache, papilledema) may accompany
• Typically subacute to chronic onset; 3-week history warrants exclusion
• Abnormal smooth pursuit and VOR point toward cerebellar/brainstem mass

9. AICA Infarction

• Classic triad: sudden unilateral hearing loss + vertigo + facial numbness
• Can cause abnormal VOR, gait ataxia, and head-shake nystagmus
• Distinguishable from peripheral cause by ipsilateral Horner, facial palsy, limb ataxia

Summary Table

Recommended Workup

1. MRI brain with DWI + FLAIR + gadolinium - superior to CT for posterior fossa; DWI detects infarct within 1 hour. Note: early MRI may be falsely negative for posterior circulation stroke - clinical HINTS assessment is more sensitive at <24-48 hours
2. MR-Angiography of cervical vessels - vertebral artery dissection, vertebrobasilar stenosis
3. Visual evoked potentials + CSF oligoclonal bands - if MS suspected
4. Full ophthalmologic exam - papilledema (tumor), INO (MS), skew deviation (central)
5. Vascular risk factor assessment - lipid profile, HbA1c, BP, ECG, echo
6. OCP history - increases stroke/VAD risk

The most urgent differential to exclude is posterior circulation stroke/vertebral artery dissection, as early management (antiplatelet/anticoagulation, reperfusion) is time-sensitive. The negative DHT/supine roll effectively rules out BPPV, and the VNG pattern with abnormal smooth pursuit + VOR + head-shake nystagmus makes a central etiology highly likely per HINTS criteria.

Detailed VNG Analysis and Revised Differential Diagnosis

Systematically Interpreting Each Finding

1. Hypometric Saccades

• Brainstem (paramedian pontine reticular formation / omnipause neurons)
• Demyelinating brainstem lesion (MS) - classic cause of slow + hypometric saccades together (Scott-Brown's Otorhinolaryngology describes this pattern explicitly with a demyelinating brainstem lesion example)
• Lateral medullary (Wallenberg): hypometric saccades away from the side of the lesion due to ipsipulsion - here, hypometria rightward = right-directed saccades undershoot, suggesting left lateral medullary or left cerebellar peduncle involvement
• Cortex, basal ganglia, neurodegenerative causes - but these are less likely here given the age and acute/subacute onset
• Note: saccadic hypermetria is more classically cerebellar; hypometria points more to brainstem

2. Rightward and Downward Smooth Pursuit Abnormality

• Ipsilateral pursuit is impaired by lesions of the ipsilateral flocculus, middle cerebellar peduncle, or pontine nuclei
• A left cerebellar or left pontine lesion would cause rightward (contralateral) pursuit failure in some paradigms, OR a right pontine/cerebellar lesion causing ipsilateral rightward failure
• Here, combined with the left caloric hyporeflexia (see below), the rightward pursuit deficit likely reflects a left-sided cerebellar/brainstem lesion causing failure to pursue targets moving away from the lesion side (contralateral direction = rightward)
• In lateral medullary syndrome (Wallenberg): smooth pursuit tracking targets moving away from the lesion is impaired; pursuit toward the lesion side is relatively spared - this fits exactly: left Wallenberg = rightward pursuit abnormal

• Downward smooth pursuit is subserved by dorsal pons, MLF (medial longitudinal fasciculus), dorsal paramedian pontine region, and cerebellum (uvula/vermis pyramid)
• Vertical pursuit impairment (especially downward) without full downgaze palsy raises concern for:
  • Early PSP (progressive supranuclear palsy) - vertical saccades slow first, then downward pursuit
  • Brainstem MS plaque affecting MLF/dorsal pontine pathways
  • Pontomesencephalic or midbrain lesion
  • Cervicomedullary junction lesion
• In a 43-year-old female, MS and brainstem infarct are higher on the list than PSP (which usually presents >60 years)

3. No Spontaneous Nystagmus, Normal Gaze With and Without Fixation

• The lesion is not acutely destabilizing the tonic vestibular balance (as a large acute peripheral lesion or acute posterior fossa hemorrhage would)
• Subacute or chronic process - either a slowly evolving lesion or a demyelinating lesion (which can produce bizarre eye movement abnormalities without classic spontaneous nystagmus)
• Rules out: acute uncompensated unilateral vestibular hypofunction (which always produces spontaneous beating nystagmus away from lesion)
• Supports: MS, vertebrobasilar insufficiency causing chronic ischemia, cerebellopontine angle tumor, or a well-compensated process

4. Right-Beating Nystagmus on High-Frequency Head Shake

• Right-beating HSN = left-sided vestibular asymmetry (the fast phase beats away from the weak/hypo-functioning side)
• This is consistent with the left caloric hyporeflexia (both point to left vestibular underactivity)
• However, HSN in the context of abnormal smooth pursuit and hypometric saccades also indicates this asymmetry has a central component - a purely peripheral HSN would not be accompanied by such central ocular motor findings
• High-frequency HSN specifically tests the higher frequency range of the VOR (above caloric testing) and can indicate central velocity storage dysfunction when combined with other central signs

5. Left Caloric Hyporeflexia with 24.20% Asymmetry

• Peripheral: damage to left vestibular nerve (superior division), left labyrinth, or left horizontal canal
• Central: lesion of left vestibular nucleus or its afferents in the brainstem
• The absence of spontaneous nystagmus despite 24% canal paresis argues against an acute peripheral lesion (which would produce strong spontaneous nystagmus) and favors either:
  • A chronic/compensated peripheral process (old vestibular neuritis)
  • A central lesion reducing left vestibular nucleus responsiveness

6. Left Unterberger (Fukuda Stepping Test) Deviation

• Left deviation confirms left vestibular hypofunction (consistent with left caloric hyporeflexia)
• This is a semi-static vestibulospinal test - it confirms the left-sided vestibular asymmetry is influencing postural/locomotor pathways

Synthesizing the Pattern: Anatomical Localization

Revised and Refined Differential Diagnoses

Rank 1: Multiple Sclerosis (MS) - Brainstem/Cerebellar Plaque

• MS produces demyelinating plaques preferentially at the floor of the fourth ventricle, lateral brainstem, and cerebellar peduncles
• Can cause the exact triad: hypometric saccades (demyelinating brainstem lesion) + ipsilateral smooth pursuit deficit + central VOR abnormality
• The downward pursuit abnormality fits an MLF plaque (MLF demyelination also causes INO)
• Left canal paresis with absent spontaneous nystagmus fits a chronic or subacute demyelinating process where central compensation has occurred
• No spontaneous nystagmus is characteristic - MS plaques can cause bizarre combinations of central findings without the full pattern of a complete acute vestibular deafferentation
• 3-week duration matches a demyelinating attack
• Female, age 43 - right in the peak MS demographic

Rank 2: PICA Territory Infarction / Lateral Medullary (Wallenberg) Syndrome - Left Side

• Rightward smooth pursuit deficit (tracking away from left lesion impaired) ✓
• Hypometric saccades directed rightward (away from left lesion - ipsipulsion) ✓
• Left caloric hyporeflexia (involvement of left vestibular nucleus) ✓
• Head-shake nystagmus (vestibular nucleus asymmetry) ✓
• Positional vertigo without classic BPPV pattern ✓

Rank 3: Vertebral Artery Dissection (Left)

• Left VAD can cause a left Wallenberg-equivalent by left PICA infarction
• Age 43 female is typical (mean age 46, female predominance)
• May be painless (neck pain absent in majority)
• MRA cervical vessels is diagnostic

Rank 4: Cerebellopontine Angle (CPA) Tumor - Left Side

• Compressing the left vestibular nerve (→ left caloric hyporeflexia, left Unterberger deviation, right HSN)
• Simultaneously compressing the left cerebellar peduncle/flocculus (→ rightward pursuit deficit, hypometric saccades)
• Compressing the lateral pons (→ downward pursuit deficit, VOR abnormality)

• Acoustic neuroma (vestibular schwannoma) - most common CPA tumor; causes progressive unilateral sensorineural hearing loss + vestibular hypofunction; the central signs here suggest either a large tumor or additional brainstem compression
• Meningioma - CPA meningiomas can compress both nerve and brainstem
• Epidermoid cyst - can fill the CPA and cause mixed pattern

Rank 5: Vestibular Migraine with Central Features

• Can cause transient VOR abnormalities and pursuit deficits
• However, the combination of persistent hypometric saccades + directional pursuit deficit + caloric asymmetry is too persistent and structured to be typical migraine
• Remains a diagnosis of exclusion, especially if MRI is normal

Rank 6: Vertebrobasilar TIA / Ischemia (Recurrent)

• Episodic posterior circulation ischemia producing stuttering deficits
• The 24% caloric asymmetry indicates a fixed (not transient) deficit, so a single TIA is unlikely to explain everything - would require recurrent events or evolving infarction

Summary of the Clinical Picture

The VNG profile is characteristic of a left-sided lesion involving both the peripheral vestibular apparatus (left labyrinth/nerve - caloric hyporeflexia, Unterberger deviation, right-beating HSN) and central pathways (brainstem/cerebellar - hypometric saccades, rightward + downward smooth pursuit deficit). The absence of spontaneous nystagmus despite a 24% caloric asymmetry is the key clue pointing away from an acute peripheral process and toward either a demyelinating lesion (MS) or a chronic/subacute posterior fossa pathology (CPA tumor, late-stage PICA infarct, chronic VAD).

Recommended Next Steps

1. MRI brain with gadolinium (T2/FLAIR/DWI, thin cuts through posterior fossa, CPA) - mandatory
2. MRA cervical vessels (vertebral artery dissection)
3. Pure tone audiogram (asymmetric SNHL would strongly raise vestibular schwannoma)
4. Visual evoked potentials (VEP) - prior optic neuritis silent plaques would confirm MS
5. CSF - oligoclonal bands, IgG index if MS suspected after MRI
6. Formal neuro-ophthalmology exam - INO on clinical examination (adduction lag), skew deviation
7. Vascular risk factors - lipid panel, HbA1c, BP, ECG, echo