Can sarcoidosis cause 6th (sixth) cranial nerve palsy?

Sarcoidosis Can Cause 6th Nerve Palsy

Yes, sarcoidosis can cause 6th nerve palsy as a manifestation of neurosarcoidosis, though it is a relatively uncommon presentation. 1, 2, 3

Neurosarcoidosis and Cranial Nerve Involvement

Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas that can affect virtually any organ system, including the nervous system. Neurosarcoidosis occurs in approximately 5-20% of sarcoidosis patients 1 and can involve:

• The cranial nerves (most common neurological manifestation)
• Brain parenchyma
• Leptomeninges
• Peripheral nerves

While the 7th cranial nerve (facial nerve) is the most frequently affected cranial nerve in neurosarcoidosis 4, the 6th cranial nerve can also be involved, leading to:

• Horizontal diplopia (double vision)
• Impaired abduction of the affected eye
• Compensatory head turn toward the affected side
• Incomitant horizontal misalignment 1

Diagnostic Considerations

When evaluating a patient with 6th nerve palsy, it's important to consider sarcoidosis in the differential diagnosis, especially when:

1. The palsy is persistent beyond 6 months (vasculopathic causes typically resolve within this timeframe) 1
2. There are other neurological or systemic manifestations of sarcoidosis
3. Imaging shows enhancing lesions in the cavernous sinus or along the course of the 6th nerve 3
4. The patient has known sarcoidosis in other organ systems

Diagnostic Approach for Suspected Neurosarcoidosis

1. Neuroimaging: MRI with gadolinium enhancement may show:

   • Enhancing lesions in the cavernous sinus
   • Leptomeningeal enhancement
   • Parenchymal lesions 3

2. Systemic evaluation:

   • Chest imaging (X-ray, CT) to look for hilar lymphadenopathy
   • Laboratory tests: ACE levels, calcium levels, vitamin D metabolism 1
   • Biopsy of accessible lesions (typically non-neural tissue) to demonstrate non-caseating granulomas

3. Exclusion of other causes:

   • Vasculopathic (diabetes, hypertension)
   • Neoplastic
   • Traumatic
   • Increased intracranial pressure
   • Demyelinating diseases 1

Treatment of Neurosarcoidosis with 6th Nerve Palsy

First-line Treatment

• High-dose glucocorticoids: Strongly recommended as initial therapy for all patients with clinically significant neurosarcoidosis, including cranial nerve palsies 1, 5
  • Typical regimen: Prednisone/prednisolone 20mg daily or higher, depending on severity

Second-line Treatment

• Methotrexate: Should be added if there is continued disease activity despite glucocorticoid treatment 1, 5
  • Dosing: 10-15 mg once weekly
  • Has been shown to significantly reduce neurosarcoidosis relapse rates (HR 0.47,95% CI 0.25–0.87; p=0.02) 5

Third-line Treatment

• Infliximab: Should be considered for patients who have continued disease despite glucocorticoids and methotrexate 1, 5

Alternative Agents

• Azathioprine: Can be considered if methotrexate is not tolerated 5
• Mycophenolate mofetil: Less effective than methotrexate (higher relapse rate) 5
• Cyclophosphamide: Reserved for refractory cases due to its side effect profile 5, 4

Monitoring and Follow-up

• Regular neurological examinations
• Follow-up MRI to assess treatment response
• Monitoring for medication side effects, particularly from long-term steroid use:
  • Diabetes
  • Hypertension
  • Osteoporosis
  • Cataracts and glaucoma 5

Prognosis

The prognosis for 6th nerve palsy in neurosarcoidosis varies:

• Some cases may resolve spontaneously 3
• Most respond well to appropriate immunosuppressive therapy
• Early treatment is essential to prevent irreversible neurological damage 5
• Prolonged therapy (>1 year) is often required 5

Clinical Pearls and Pitfalls

• Pearl: Consider neurosarcoidosis in cases of persistent or recurrent cranial nerve palsies, especially when multiple cranial nerves are involved or there are other systemic symptoms.
• Pitfall: Neurosarcoidosis can mimic other conditions like meningiomas on imaging, leading to misdiagnosis 3.
• Pearl: While 7th nerve palsy is the most common cranial nerve manifestation of neurosarcoidosis, any cranial nerve can be affected, including the 6th nerve.
• Pitfall: Isolated neurosarcoidosis without systemic manifestations can occur, making diagnosis challenging 6.