How is neuro‑Sjögren’s disease (neurological involvement such as peripheral neuropathy, cranial neuropathy, or central nervous system lesions) treated in Canada?

Treatment of Neuro-Sjögren's Disease in Canada

Neurological involvement in Sjögren's syndrome requires systemic immunosuppression with glucocorticoids combined with immunosuppressive agents, with treatment intensity determined by the severity and type of neurological manifestation.

Initial Assessment and Risk Stratification

• Determine whether neurological involvement is peripheral (neuropathy, ganglionopathy) or central (CNS lesions, myelitis, cranial neuropathy), as treatment approaches differ significantly 1, 2
• Use ESSDAI scoring to quantify disease activity; neurological manifestations with severe motor deficit, ataxia, or cryoglobulinemic multineuritis are classified as life-threatening and require aggressive therapy 1, 3
• Obtain nerve conduction studies and electromyography for peripheral neuropathies to distinguish sensory neuronopathy from axonal neuropathy, as prognosis and treatment response vary 4, 5
• Perform contrast-enhanced MRI for suspected CNS involvement or cranial neuropathy to exclude alternative diagnoses and assess extent of disease 1

Treatment Algorithm by Neurological Manifestation Type

Peripheral Neuropathy (Including Sensory Neuropathy and Mononeuritis Multiplex)

For severe peripheral neuropathy with motor deficit or mononeuritis multiplex:

• Initiate combination therapy with glucocorticoids (prednisone 1 mg/kg/day, maximum 60 mg/day) plus an immunosuppressive agent 1
• Add cyclophosphamide (2 mg/kg/day orally or 0.5 g IV every 15 days) for severe cases with marked motor deficit 1, 3
• Mycophenolate mofetil or azathioprine are appropriate alternatives for less severe but progressive neuropathy 3, 5
• Response rates of 60-75% have been reported with glucocorticoid and immunosuppressive combination therapy 1

For sensory neuronopathy (ganglionopathy):

• This is the most characteristic neurological complication of Sjögren's and presents with ataxia, areflexia, and asymmetric sensory loss 2, 5
• Corticosteroids combined with mycophenolate mofetil showed positive results in a 13-patient series with median 3-year follow-up 5
• Intravenous immunoglobulin (IVIG) has shown disappointing results for sensory neuronopathy despite earlier anecdotal reports 2, 5
• Prognosis is generally poor with chronic, insidious progression despite treatment; average disability remains moderate (mRS 2-2.4) 5

CNS Involvement (Myelitis, Encephalitis, Cerebral Vasculitis)

For severe CNS manifestations:

• Timely induction therapy with high-dose intravenous methylprednisolone followed by intravenous cyclophosphamide should be instituted as soon as possible 1
• Pulse methylprednisolone (typically 1000 mg IV daily for 3-5 days) combined with cyclophosphamide is the recommended regimen 1
• Neurological response typically occurs within days to 3 weeks if treatment is initiated promptly 1
• Delays >2 weeks in initiating therapy are associated with worse neurological outcomes 1

For transverse myelitis or myelopathy:

• Combination of intravenous methylprednisolone and intravenous cyclophosphamide is effective if used within the first few hours 1
• Relapses occur in 50-60% during corticosteroid dose reduction, necessitating maintenance immunosuppressive therapy 1
• Plasma exchange may be considered in severe refractory cases 1

Cranial Neuropathy (Including Optic Neuritis)

For optic neuritis:

• Pulse intravenous methylprednisolone in combination with intravenous cyclophosphamide is recommended 1
• Visual outcomes are often poor; only 30% maintain visual acuity >20/25 despite treatment 1
• Relapses are common and merit chronic immunosuppressive maintenance therapy 1
• Perform complete ophthalmological evaluation including funduscopy, fluoroangiography, MRI, and visual evoked potentials 1

For other cranial neuropathies (trigeminal, facial, vestibulocochlear):

• Glucocorticoids alone or with immunosuppressive therapy based on severity 2, 6
• Exclude brainstem stroke and meningitis before attributing to Sjögren's 1

Maintenance Therapy and Long-Term Management

• After achieving remission, continue maintenance immunosuppression with azathioprine, mycophenolate mofetil, or methotrexate to prevent relapses 1, 3
• Taper glucocorticoids to the lowest effective dose, recognizing that some patients require prolonged low-dose therapy 3
• No fixed duration for maintenance therapy is established; follow strategies used for other systemic autoimmune diseases with a two-stage sequential regimen (induction then maintenance) 1
• Monitor for treatment response using ESSDAI scores; therapeutic success is defined as ≥3 point reduction 3, 7

Refractory Disease

For severe, refractory neurological manifestations:

• Rituximab (1 g IV every 15 days × 2 doses) is advised for refractory systemic disease 3
• Plasma exchange may be considered for severe refractory myelitis or severe peripheral neuropathy 1
• IVIG has been used in small fiber neuropathy and sensory ataxic neuropathy with variable benefit, but results are disappointing for sensory neuronopathy 2, 5

Critical Pitfalls to Avoid

• Never delay treatment: Delays >2 weeks in initiating therapy for CNS involvement or severe peripheral neuropathy are associated with irreversible neurological deficits 1
• Do not use immunosuppressive monotherapy: Glucocorticoids should always be combined with immunosuppressive agents for severe neurological manifestations; >95% of reported cases used combination therapy 3, 7
• Do not attribute all neurological symptoms to Sjögren's: Exclude infection (especially meningitis), stroke, and other structural lesions before initiating immunosuppression 1, 6
• Recognize that neurological symptoms often precede sicca symptoms: In 11 of 13 patients with sensory neuronopathy, neurological manifestations preceded or coincided with Sjögren's diagnosis 5, 6
• Understand that treatment response is unpredictable: Sensory neuronopathy tends to be chronic and debilitating despite aggressive treatment, with heterogeneous progression 5, 6