This narrative review synthesizes current approaches to diagnosing and managing central nervous system (CNS) complications in adults with common autoimmune rheumatic diseases. The authors conducted a literature review focusing on CNS manifestations within rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome, and vasculitis, emphasizing the challenges posed by overlapping syndromes and the risk of permanent CNS damage.

Large-Vessel Cerebrovascular Disease (LVCVD)

• This condition refers to a disruption of blood flow through large and medium arteries, either due to thrombosis or vasculitis.
• Symptoms include sudden neurological deficits that correspond to the area affected by ischemia.
• Rheumatic conditions that can lead to LVCVD include systemic lupus erythematosus (SLE), polyarteritis nodosa (PAN), Takayasu arteritis (TAK), and giant cell arteritis (GCA).
• Diagnosis involves MRI, possibly along with ANA and aPL testing for SLE, CTA and MRA for TAK and GCA, temporal artery ultrasound or biopsy for GCA, and abdominal imaging for PAN.
• Treatment typically follows standard stroke management guidelines, but immunosuppression may be necessary if the stroke is believed to be immune-mediated.
• High-dose glucocorticoids are recommended for TAK and GCA.
• For SLE and PAN, treatment includes methylprednisolone pulses combined with cyclophosphamide (CYC) for remission induction.
• Maintenance therapy for SLE involves hydroxychloroquine, oral glucocorticoids, and mycophenolate mofetil (MMF) or azathioprine (AZA), while PAN maintenance includes oral glucocorticoids, methotrexate (MTX), or AZA.

Small-Vessel Cerebrovascular Disease (SVCVD)

• SVCVD results from the obstruction of small arteries or capillaries, usually due to thrombi or inflammation.
• Symptoms may include seizures, movement disorders, acute psychosis, or confusion.
• SVCVD is associated with SLE, granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
• Diagnosis typically involves imaging, EEG, and CSF analysis to exclude other causes.
• Treatment for SLE involves methylprednisolone pulses with CYC or rituximab (RTX) for remission induction.
• Maintenance therapy includes hydroxychloroquine, oral glucocorticoids, and MMF or AZA.
• For ANCA-associated vasculitis (AAV), treatment is similar, with the addition of avacopan for GPA and MPA, and mepolizumab for EGPA.

Optic Neuropathy

• Optic neuropathy can result from ischemic optic nerve neuropathy, optic nerve inflammation and demyelination, or pachymeningitis.
• Symptoms may include sudden, painless vision loss, eye pain, and dyschromatopsia.
• This condition is associated with GCA, SLE, Sjogren disease (SD), and EGPA.
• Diagnosis is often clinical, with MRI as a possible tool.
• Treatment typically involves pulsed intravenous methylprednisolone followed by oral prednisone.
• Glucocorticoid-sparing agents, such as tocilizumab (for GCA), methotrexate, CYC, RTX, AZA, MMF, or mepolizumab (for EGPA), may be added.

Inflammatory Myelopathy

• Inflammatory myelopathy is believed to result from a combination of neuronal damage and vasculopathy.
• Symptoms may include paraparesis, quadriparesis, sphincter dysfunction, and sensory deficits.
• It is associated with SD, SLE, Behcet's disease (BD), and AAV.
• Diagnosis generally requires spinal imaging and CSF analysis.
• Treatment typically involves pulsed methylprednisolone and CYC, with RTX, IVIg, and plasmapheresis as rescue therapies.
• For BD, AZA is preferred over CYC, and anti-TNF antibodies may also be considered.
• Maintenance therapy may involve hydroxychloroquine (for SLE), MMF or AZA, aspirin or warfarin (for antiphospholipid syndrome), RTX (for AAV), and AZA (for BD).

Meningeal Disease

• Meningeal disease includes aseptic meningitis (AM) and hypertrophic pachymeningitis (HP).
• AM is characterized by headache, fever, and meningeal irritation, while HP involves progressive thickening of the dura mater.
• AM is associated with rheumatoid arthritis (RA), SLE, SD, BD, AAV, and sarcoidosis, while HP is associated with AAV, IgG4-related disease (IgG4-RD), sarcoidosis, and RA.
• Diagnosis of AM typically involves CSF analysis, while HP is diagnosed using MRI.
• Treatment for AM and HP generally involves pulsed methylprednisolone or high-dose prednisone.
• Glucocorticoid-sparing agents may include hydroxychloroquine, CYC, RTX, MTX, and AZA, depending on the underlying condition.

Demyelinating Disease and Encephalitis

• Demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica (NMO), involve the loss of the myelin sheath around nerves.
• Conditions like SD, SLE, and BD can present with symptoms that resemble demyelinating diseases.
• Treatment for demyelinating disease and encephalitis varies based on the underlying condition but may include corticosteroids, immunosuppressants (CYC, AZA, MMF, RTX), IVIg, and plasmapheresis.

The authors emphasize the importance of individualized, syndrome-specific treatment plans to address the complex needs of patients with rheumatic diseases involving the CNS. They advocate for the use of immunosuppressive therapies tailored to each condition and stress the need for advanced diagnostic tools, such as functional MRI and MR spectroscopy, to enhance diagnostic accuracy. The review concludes by underscoring the essential role of thorough clinical reasoning and examination in diagnosing and managing these multifaceted CNS manifestations in rheumatic disease patients.