What is the diagnosis and treatment for optic neuritis with negative infectious disease tests and a family history of psychosis and pulmonary fibrosis?

Diagnosis and Treatment of Optic Neuritis with Negative Infectious Disease Tests and Family History of Psychosis

The most likely diagnosis is optic neuritis requiring immediate treatment with high-dose intravenous methylprednisolone (1000 mg daily for 3 days), followed by an oral prednisone taper to prevent vision loss and improve outcomes.

Diagnostic Approach

Clinical Evaluation

• Optic neuritis presents with the classic triad of:
  • Visual loss (can be unilateral or bilateral)
  • Periocular pain (especially with eye movement)
  • Dyschromatopsia (color vision impairment) 1
• Fundoscopic examination may reveal papilledema/papillitis/optic disc swelling in acute cases 2
• Assess for neurological symptoms that might suggest demyelinating disease

Imaging Studies

• MRI of orbits and brain with and without contrast is the primary imaging study for initial assessment of suspected optic neuritis 3
  • Evaluates for abnormal enhancement and signal changes within the optic nerve
  • Assesses for intracranial demyelinating lesions that predict development of multiple sclerosis
  • T1-weighted post-contrast images with fat suppression identify abnormal enhancement in 95% of cases 2
  • Coronal images with fat suppression and T2 sequences with submillimetric resolution are recommended 2

Laboratory Testing

• Serum testing for:
  • Aquaporin-4 immunoglobulin G antibody (AQP4-IgG) to rule out neuromyelitis optica spectrum disorders (NMOSD) 3
  • Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) to rule out MOG-associated disorder 3
  • Complete blood count to check for eosinophilia (can rarely cause recurrent optic neuritis) 4
• CSF analysis to check for:
  • Oligoclonal bands (common in MS-related optic neuritis)
  • Pleocytosis (neutrophilic pleocytosis or WCC > 50/μl suggests MOG-IgG associated disorder) 3

Differential Diagnosis

The negative infectious disease tests (including Lyme disease) and family history of psychosis require careful consideration of several potential diagnoses:

1. Multiple Sclerosis (MS)-associated optic neuritis

   • Most common cause of demyelinating optic neuritis 1
   • Brain MRI may show periventricular white matter lesions

2. Neuromyelitis Optica Spectrum Disorders (NMOSD)

   • Associated with AQP4-IgG antibodies
   • More severe visual outcomes than MS-related optic neuritis 3
   • Requires different treatment approach than MS 3

3. MOG-IgG Associated Disorder

   • Can present with isolated or recurrent optic neuritis 3
   • Often bilateral and associated with disc edema 3

4. Idiopathic Optic Neuritis

   • Diagnosis of exclusion when other causes are ruled out 5
   • Accounts for approximately one-third of optic neuritis cases 5

5. Autoimmune-Related Optic Neuritis

   • Family history of autoimmune conditions (like psychosis potentially associated with autoimmune encephalitis) may be relevant

Treatment Algorithm

Acute Treatment

1. First-line therapy: Intravenous methylprednisolone

   • Dose: 1000 mg daily for 3 days 2, 6
   • Followed by oral prednisone taper 2
   • Initiate as early as possible, ideally within the first few hours of symptom onset 2
   • IMPORTANT: Oral prednisone alone (without prior IV methylprednisolone) at 1 mg/kg/day should be avoided as it may increase risk of recurrent optic neuritis 2

2. For steroid-refractory cases:

   • Consider plasmapheresis (plasma exchange) early in severe attacks 2
   • Clinical improvement seen in approximately 79.2% of patients with this approach 2

Long-term Management

• Based on the underlying etiology:
  • If MS is diagnosed: Consider disease-modifying therapies like interferon β-1a,b which have been shown to reduce risk of MS progression 1
  • If NMOSD is diagnosed: Consider rituximab as first-line therapy, particularly for patients with severe disease 2
  • If MOG-IgG positive: Consider immunosuppressive therapy with rituximab, azathioprine, or mycophenolate mofetil 2

Monitoring and Follow-up

• Monitor visual acuity, color vision, contrast sensitivity, and visual fields
• These parameters may remain impaired even after good recovery of visual acuity 1
• Regular MRI follow-up may be needed to monitor for development of MS or other demyelinating disorders
• Screen for hepatitis B infection before initiating immunosuppressive treatment 6

Important Precautions

• Live or attenuated vaccines are contraindicated during immunosuppressive corticosteroid therapy 6
• High-dose IV methylprednisolone can rarely cause toxic hepatitis; discontinue if this occurs 6
• Avoid corticosteroids in patients with active ocular herpes simplex, systemic fungal infections, or cerebral malaria 2, 6
• Monitor for steroid-related complications including hyperglycemia, hypertension, and mood changes 6

Clinical Pearls

• The family history of psychosis should not delay treatment of optic neuritis but may warrant additional neuropsychiatric evaluation
• The pulmonary fibrosis in family history is likely unrelated to optic neuritis but should be noted
• Visual outcomes are generally better with prompt treatment, highlighting the importance of early diagnosis and intervention 7
• Relapses are common (50-60%) during corticosteroid dose reduction, highlighting the need for careful tapering and potential maintenance therapy 2