Can Sjogrens syndrome affect the brain?

Can Sjögren's Syndrome Affect the Brain?

Yes, Sjögren's syndrome can attack the brain and central nervous system, occurring in approximately 10-17% of patients with primary Sjögren's syndrome, though peripheral nervous system involvement is far more common. 1, 2

Neurological Manifestations Overview

The neurological involvement in Sjögren's syndrome follows a clear hierarchy of frequency:

Peripheral Nervous System (Most Common)

• Pure sensory polyneuropathies are the most frequent neurological manifestation, including sensory ataxic neuropathy and small fiber sensory painful neuropathy 3
• Peripheral neuropathy affects approximately 57% of patients with neurological involvement in primary Sjögren's syndrome 4
• Small fiber neuropathy can present without clinically obvious features like muscle weakness or decreased deep tendon reflexes, making it easily overlooked 5
• Trigeminal neuralgia and other cranial neuropathies occur in about 15-20% of neurological cases 1, 4, 5

Central Nervous System Involvement (Less Common but Significant)

• CNS involvement occurs in 10-17% of primary Sjögren's syndrome patients, with neurological manifestations being the initial presenting symptom in approximately 31% of these cases 1, 2, 4
• The most common CNS manifestations include:
  • Hemiparesis (35.7%) and paraparesis (28.6%) 2
  • Dysphonia (31%) and blurred vision (21.4%) 2
  • Dysfunctional proprioception (23.8%) 2
  • Psychiatric or cognitive dysfunction 6

Brain Imaging Findings

• MRI abnormalities are detected in 75% of patients with active CNS disease, showing focal lesions predominantly in subcortical and periventricular white matter 6
• Common imaging findings include:
  • Cerebral infarction (57.1%) - the most frequent finding 2
  • Demyelination (31%) 2
  • Myelitis (23.8%) 2
  • Angiostenosis (21.4%) 2
• MRI is more sensitive than CT or cerebral angiography for detecting these lesions 6

High-Risk Indicators for CNS Involvement

Three key risk factors predict CNS involvement in Sjögren's syndrome:

1. Pulmonary involvement 2
2. Positive anti-SSA/Ro antibody 2
3. Reduced complement C3 levels 2

Additional concerning features include:

• Kidney involvement and hematologic abnormalities 2
• Immune thrombocytopenia 2
• High-titer ANA (≥1:1000) 2
• Reduced complement C4 levels 2

Diagnostic Evaluation for Suspected CNS Involvement

Cerebrospinal Fluid Analysis

• CSF findings are often non-specific and inconsistent - inflammatory changes are rarely found and don't show a characteristic pattern 4
• When abnormal, findings may include:
  • Mild pleocytosis (8-107 cells/µL) in 9-25% of cases depending on manifestation type 4
  • Elevated intrathecal IgG and total protein in approximately 50% of CNS cases 2
  • Oligoclonal bands indicating intrathecal IgG synthesis in 20-26% of cases 4

Critical pitfall: The absence of inflammatory CSF changes does NOT exclude Sjögren's-related neurological disease 4

Neuroimaging

• Brain MRI is essential for all patients with suspected CNS involvement 2, 6
• MRI detects focal cerebral lesions even in patients with only psychiatric or cognitive dysfunction 6

Pathophysiological Mechanisms

The mechanisms of neural injury in Sjögren's syndrome are multifactorial:

• Dorsal root ganglionitis and peripheral nerve vasculitis have been documented on histological examination 3
• Humoral autoimmune mechanisms play a fundamental role 3
• Specific autoantibodies (including anti-aquaporin 4 in some cases of optic neuritis) may directly induce nervous system injury 5

Treatment Approach

For CNS involvement, high-dose glucocorticoids combined with immunosuppressive therapy is the standard approach:

• Approximately 60% of patients with CNS involvement respond to treatment with high-dose glucocorticoids and immunosuppressive agents 2
• 37% remain unresponsive to treatment 2
• Mortality occurs in approximately 2.6% of CNS cases 2

For specific manifestations:

• Corticosteroids are particularly effective for mononeuritis multiplex 3
• Intravenous immunoglobulin shows benefit for small fiber or sensory ataxic neuropathy 3

Essential Clinical Considerations

Maintain High Index of Suspicion

• Neurological manifestations, particularly peripheral neuropathy, are often the presenting feature of Sjögren's syndrome 3
• Suspect Sjögren's in female patients with:
  • Non-length-dependent painful or ataxic sensory neuropathies 3
  • Trigeminal sensory involvement 3
  • Autonomic involvement 3
  • Unexplained chronic cough with dry eyes (led to diagnosis in 36% of previously undiagnosed patients) 1

Co-Management Requirements

• All patients with Sjögren's syndrome and neurological involvement require co-management with rheumatology due to systemic complications and the 5% risk of lymphoma development 1, 7
• Regular monitoring for disease progression and lymphoproliferative disorders is essential 1, 7