How do you approach a patient with isolated opsoclonus (involuntary, chaotic eye movements)?

Approach to a Patient with Isolated Opsoclonus

The initial evaluation of a patient with isolated opsoclonus must include urgent neuroimaging (MRI brain with contrast) and comprehensive paraneoplastic/autoimmune antibody testing to identify potentially life-threatening underlying causes. 1

Clinical Presentation and Definition

Opsoclonus is characterized by:

• Involuntary, chaotic, conjugate saccadic eye movements in all directions
• Movements that persist during sleep and cannot be suppressed voluntarily
• Often accompanied by myoclonus, ataxia, and encephalopathy in full syndrome (OMS)

Diagnostic Evaluation Algorithm

Step 1: Confirm True Opsoclonus

• Distinguish from other eye movement disorders (nystagmus, ocular flutter)
• Document persistence during fixation attempts
• Video recording may be helpful for documentation and consultation

Step 2: Urgent Neuroimaging

• MRI brain with contrast with special attention to:
  • Brainstem
  • Posterior fossa structures
  • High-resolution T2-weighted images of cranial nerves 1
• Include dedicated orbital imaging if any orbital signs/symptoms present

Step 3: Laboratory Evaluation

• Complete blood count with differential
• Comprehensive metabolic panel
• Inflammatory markers (ESR, CRP)
• Cerebrospinal fluid analysis:
  • Cell count, protein, glucose
  • Oligoclonal bands
  • Cytology
  • Viral PCR panel

Step 4: Comprehensive Antibody Testing

• Paraneoplastic antibody panel including:
  • Anti-neuronal nuclear antibodies (ANNA)
  • Anti-Ri (ANNA-2)
  • Anti-Yo
  • Anti-Hu
  • Anti-Ma2
• Surface antibody testing:
  • NMDA receptor
  • VGCC
  • GlyR antibodies 1

Step 5: Malignancy Screening

• Age-appropriate cancer screening
• CT chest/abdomen/pelvis
• Consider whole-body PET-CT if high suspicion for malignancy
• Special attention to:
  • Breast and lung cancer in older women
  • Small cell lung cancer in smokers 1
  • Neuroblastoma in pediatric patients

Etiologic Classification

1. Paraneoplastic:

   • Breast cancer and small cell lung cancer in adults 1
   • Neuroblastoma in children

2. Post-infectious/Parainfectious:

   • Following viral infections
   • Consider recent infections or vaccinations

3. Autoimmune non-paraneoplastic:

   • Idiopathic autoimmune opsoclonus

4. Toxic-metabolic:

   • Medication-induced
   • Drug intoxication

Treatment Approach

For Paraneoplastic Opsoclonus:

• Treatment of underlying malignancy is primary
• Immunotherapy:
  • Corticosteroids (prednisolone 1-2 mg/kg/day) 2
  • Intravenous immunoglobulin (IVIG) 3
  • Rituximab for refractory cases 4

For Non-paraneoplastic Opsoclonus:

• First-line:
  • Corticosteroids (prednisolone 1-2 mg/kg/day)
  • IVIG (2 g/kg divided over 2-5 days)
• Second-line:
  • Rituximab (375 mg/m²/week for 4 weeks) 4
  • Plasmapheresis

Monitoring and Follow-up

• Regular neurological examinations to assess response to treatment
• Repeat imaging and antibody testing if symptoms persist or recur
• Long-term monitoring for:
  • Cognitive impairment
  • Development of new neurological symptoms
  • Late-appearing malignancies

Prognosis

• Adult-onset idiopathic OMS: Generally monophasic with good response to immunotherapy 1
• Paraneoplastic OMS: Prognosis tied to underlying malignancy
• Relapses may occur during immunotherapy taper, requiring retreatment 4

Pitfalls to Avoid

• Do not mistake opsoclonus for seizure activity - EEG is typically normal in opsoclonus, and antiepileptic medications will not resolve symptoms 2
• Do not delay immunotherapy while awaiting complete diagnostic workup if clinical suspicion is high
• Do not stop at negative initial malignancy screening - some tumors may appear later, requiring periodic reassessment
• Do not overlook cognitive and behavioral symptoms that may accompany or follow opsoclonus, particularly in children 5