Difficulty Walking in Darkness and on Foam/Uneven Surfaces

The Three-Sensor Balance System

1. Proprioception - joint position sense and vibration sense (large-fiber afferents, dorsal columns)
2. Vision - compensates when proprioception is impaired
3. Vestibular system - detects head acceleration and spatial orientation

• Darkness removes visual compensation → gait becomes severely unstable
• Foam/uneven surfaces "confuse" or overwhelm remaining proprioceptive signals → similar destabilization

Sensory Ataxia vs. Other Gait Patterns

• Patient looks down at their feet while walking (visual substitution)
• Does poorly in the dark - the classic complaint
• Positive Romberg sign (falls when eyes closed)
• Destabilized on foam/uneven surfaces (foam pad test removes plantar proprioception)

Localizing the Lesion: Where Is the Proprioceptive Pathway Disrupted?

1. Peripheral Neuropathy (Large-Fiber Type)

• Loss of joint position sense + vibration sense in legs
• Absent or reduced ankle reflexes (areflexia)
• Pseudoathetosis (writhing finger movements with eyes closed, arms outstretched)
• Causes: Diabetes mellitus, vitamin B12 deficiency, Sjögren syndrome, cisplatin toxicity, hereditary sensory neuropathies, paraneoplastic sensory neuronopathy, HIV neuropathy

2. Dorsal Column (Spinal Cord) Disease

• Loss of proprioception + vibration sense bilaterally below the lesion
• Pain and temperature sensation preserved (spinothalamic tract spared)
• Positive Romberg sign
• Classic cause: Subacute combined degeneration (Vitamin B12/cobalamin deficiency)
  • Demyelination of posterior AND lateral columns
  • Associated with pernicious anemia, other autoimmune conditions
• Other causes: HIV vacuolar myelopathy, HTLV-1 myelopathy, copper deficiency myelopathy, tabes dorsalis (neurosyphilis - the "classic" example), cervical spondylotic myelopathy

3. Sensory Neuronopathy / Ganglionopathy

• Selective destruction of dorsal root ganglion cells
• Often severe, can be asymmetric
• Marked sensory ataxia + pseudoathetosis
• Causes: Paraneoplastic (anti-Hu antibodies, small cell lung cancer), Sjögren syndrome, cisplatin

4. Bilateral Vestibular Loss (Different mechanism, similar presentation)

• Also worsens in dark and on soft surfaces
• But here, the vestibulo-ocular reflex is impaired, causing oscillopsia (visual bouncing with head movement)
• Romberg positive; tandem gait impaired
• Causes: Bilateral vestibular neuritis, ototoxic drugs (gentamicin), Meniere disease (bilateral)

Key Examination Findings to Look For

Causes to Investigate (Red Flag History)

Clinical Pearl

"The stance in such patients is destabilized by eye closure; they often look down at their feet when walking and do poorly in the dark."

• Harrison's Principles of Internal Medicine 22E, p. 222

Summary

• B12, folate, glucose, HbA1c
• Syphilis serology (VDRL/RPR, TPHA)
• Nerve conduction studies / EMG (to confirm large-fiber neuropathy)
• MRI spine (to identify dorsal column signal change)
• Paraneoplastic panel if subacute and unexplained
• Audiometry + vestibular testing if oscillopsia is present

Cisplatin Vestibulotoxicity in Bladder Cancer Patients

Why Cisplatin Causes Bilateral Vestibular Loss

1. Oxidative stress - generates reactive oxygen species that destroy hair cells
2. Apoptosis - direct triggering of hair cell programmed cell death
3. Inflammatory cytokines - secondary inflammatory cascade amplifies damage

• Dose-dependent - higher cumulative cisplatin doses = greater vestibular destruction
• Bilateral - systemic drug reaches both inner ears simultaneously
• Largely irreversible - unlike cochlear hair cells (which also do not regenerate), vestibular hair cell loss is permanent in most cases

Cochlear vs. Vestibular Toxicity: An Important Distinction

• Vestibular testing is not routinely performed during chemotherapy monitoring
• Symptoms are often attributed to "chemo side effects" or deconditioning
• Unlike unilateral vestibular loss (which causes dramatic vertigo), bilateral loss causes NO vertigo - only gait instability and oscillopsia

The Classic Clinical Picture of Cisplatin Bilateral Vestibulopathy

"Prolonged exposure to these agents produces a bilateral vestibulopathy without vertigo. Instead, there tends to be a disequilibrium associated with oscillopsia. The symptoms are especially troublesome when the patient moves. Often the disequilibrium is not discovered until a bedbound patient tries to walk."

Risk Factors for Greater Cisplatin Ototoxicity

Confirming the Diagnosis

1. Video Head Impulse Test (vHIT) - detects reduced vestibulo-ocular reflex gain bilaterally; the most practical bedside/clinic test
2. Caloric testing (bithermal) - will show bilaterally absent or severely reduced caloric responses
3. Rotary chair testing - gold standard for bilateral vestibular loss; shows reduced VOR gain across frequencies
4. VEMP (cervical and ocular) - assesses utricular and saccular function specifically
5. Audiogram - to document co-existing cisplatin cochleotoxicity (high-frequency SNHL)
6. Dynamic visual acuity test - loss of >2 lines on Snellen with head shaking confirms bilateral VOR deficit

Management

• Vestibular rehabilitation therapy (VRT) - the most effective intervention; trains visual and somatosensory substitution for lost vestibular input
• Fall prevention - night lights, grab rails, avoidance of uneven/foam surfaces without support
• Avoid further ototoxins - aminoglycosides, loop diuretics (furosemide) potentiate damage
• Driving assessment - oscillopsia can impair driving, especially at night
• Future chemotherapy - note in records; carboplatin substitution may be considered if re-treatment needed (lower vestibulotoxic potential, though not zero)

Summary

Corrective Saccades on Head Impulse Test: What This Means

What Just Happened Physiologically

Two Types of Corrective Saccades

Interpreting the Finding in This Patient's Context

• Cisplatin chemotherapy for bladder cancer
• Gait instability in darkness and on foam surfaces
• Bilateral corrective saccades on HIT (if seen on both sides)

• Confirms bilateral VOR deficit
• Consistent with cisplatin toxicity (systemic drug, damages both labyrinths)
• The VOR gain is reduced on both sides

• Could represent asymmetric cisplatin damage
• Or an alternative/additional cause (e.g. prior vestibular neuritis on one side)

The HINTS Framework: Why This Finding Is PERIPHERAL, Not Central

"Peripheral vestibular lesions can cause a lag in the patient's eyes returning to fixation on the examiner... In patients with vertigo, presence of either normal head impulse test, direction-changing nystagmus in eccentric gaze, or skew deviation is highly sensitive and specific for central lesions."

• Neuroanatomy through Clinical Cases, 3rd Ed.

Completing the Assessment

• Quantifies VOR gain for all 6 semicircular canals (3 per side: lateral, anterior, posterior)
• Normal VOR gain = ~0.9-1.0
• BVH typically shows gain < 0.6 bilaterally in lateral canals
• Also captures covert saccades missed at bedside
• Will confirm and quantify severity of cisplatin-induced damage

• Tests the low-frequency end of lateral canal VOR (0.003 Hz)
• In BVH: bilaterally absent or severely reduced caloric responses (< 5°/sec total)
• Complements vHIT (which tests high-frequency VOR)

• cVEMP: tests the saccule and inferior vestibular nerve
• oVEMP: tests the utricle and superior vestibular nerve
• Cisplatin research shows utricular damage is particularly prominent (Fleihan et al., 2024 - PMID 39421409)
• Absent or reduced amplitudes bilaterally expected

• Document any co-existing cisplatin cochleotoxicity
• High-frequency SNHL (4-8 kHz loss first) is the cochlear counterpart

Summary of the Clinical Picture So Far

Patient: Bladder CA → Cisplatin chemotherapy
Symptoms: Gait instability in darkness, foam/uneven surfaces; NO vertigo
Examination: Positive HIT (corrective saccades bilaterally)
Diagnosis: Cisplatin-induced Bilateral Vestibular Hypofunction (BVH)
Mechanism: Dose-dependent vestibular hair cell destruction (utricle predominant)
                  via oxidative stress + apoptosis
Next steps: vHIT (quantify gain), caloric testing, VEMPs, audiogram
Management: Vestibular rehabilitation therapy (VRT)