Medscape is available in 5 Language Editions – Choose your Edition here.


CNS Lupus Treatment & Management

  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Niranjan N Singh, MD, DM  more...
Updated: Jun 14, 2016

Approach Considerations

Patients with an acute neurologic presentation generally require an intensive care unit and neuroimaging facilities. Hemodialysis may be needed if acute renal failure occurs. Physician comfort and access to experienced multispecialty consultation are usually more of a problem than medical equipment limitation.

Treatment of systemic lupus erythematosus (SLE) should be provided in cooperation with a consulting rheumatologist. Therapeutic intensity correlates with the severity of an acute attack. Nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptomatic agents are used for less threatening symptoms. Corticosteroids are used in low-dose oral, high-dose oral, or high-dose intravenous (IV) regimens according to the severity of potential organ damage. Previous steroid therapy may provoke an adrenocortical deficiency state.

Clinical studies supporting this approach were generally performed in lupus nephritis because of its frequency, severity, and quantifiable improvement or deterioration, but the same treatment approaches are generally applied to other organ systems, including the central and peripheral nervous systems and muscular disease. This overall treatment approach should be familiar to neurologists who are accustomed to the evaluation and treatment of other autoimmune conditions such as multiple sclerosis, myasthenia gravis, or polymyositis.

With little evidence base to the therapeutic modalities, a logical approach to the treatment of cerebral lupus is to build a treatment strategy around the various possible pathogeneses: (1) ischemia due to thromboses secondary to the antiphospholipid syndrome, (2) small-vessel noninflammatory proliferative vasculopathy due to cell-mediated immune mechanisms, and (3) antibody-mediated damage to spinal cord and optic nerve—akin to Devic disease.[34]

Seropositive findings for neuromyelitis optica (NMO)–immunoglobulin G (IgG) antibody occurring with SS/SLE (Sjogren syndrome/SLE overlap) or non–organ-specific antibodies favors coexisting NMO (Devin syndrome) rather than a vasculitic process. Antibodies against the aquaporin 4 channel is an important evaluation for this common confusing situation.[35]

The standard treatment for the nonthrombotic syndromes associated with systemic lupus erythematosus (SLE) is immunosuppression, first with corticosteroids and with early recourse to cyclophosphamide. A Cochrane Database Systematic Review found no randomized controlled trials comparing these 2 treatments and concluded there was no evidence of a treatment advantage of cyclophosphamide.[36]


Medical Care


High-dose intravenous (IV) corticosteroid regimens consist of methylprednisolone 1-2 g daily for 3-6 doses, followed by oral prednisone 60 mg daily, then tapering according to clinical recovery. Less threatening flare-ups may be treated with as much as 100 mg or as little as 10 mg prednisone orally (PO) daily (qd) (or other agents in equivalent dosage), again tapering gradually according to clinical symptoms, with an increase of 10-20% during the taper if clinical disease flares again.

Tapering to an every-other-day steroid regimen reduces adverse effects substantially but probably will not be successful until the clinical disease is quite stable. In acute high dosage, steroids may provoke status epilepticus, psychosis, hypokalemia, hyperglycemia, or hypertension and clinical evidence of any intercurrent infection may be reduced.

With chronic use, steroids cause familiar adverse effects including weight gain, diabetes mellitus, cataracts, immunocompromise, and osteoporosis. Calcium supplementation (1 g daily for men or premenopausal women, 1.5 g daily for postmenopausal women) should be initiated early and continued even when steroids are tapered successfully to qod.

Thrush and herpetic outbreaks may be treated symptomatically or prophylactically.

Antimalarial agents

The discovery that Toll-like receptor signaling and interferon-alpha abundance are central elements of the systemic lupus erythematosus (SLE) disease process has led to a new appreciation for hydroxychloroquine as an essential baseline medication. Modulation of the immune system via B-cell depletion is entering clinical practice.

Antimalarials, especially hydroxychloroquine in dosage of 100-400 mg daily, are used as alternatives to steroids or as supplements to accelerate steroid taper. These agents have not been studied in central or peripheral nervous system disease. Antimalarials generally require months to become effective, and, therefore, they are not used in the acute treatment of organ-threatening disease.

Cytotoxic agents

Various steroid-sparing strategies have evolved for long-term use in systemic lupus erythematosus (SLE), including cyclophosphamide 0.5-2 mg/kg/d, azathioprine 1-2 mg/kg/d, and methotrexate 10-15 mg given once weekly with folate rescue, permitting gradual reduction or elimination of chronic steroid therapy. Higher dose ranges or dosing based on body surface area may be used for these medications based on the experience of individual clinicians.

All chronic cytotoxic regimens present substantial risks and should be followed only by physicians familiar with these agents. In acute, life-threatening illness, one option is to initiate cyclophosphamide PO or a single dose of 8-20 mg/kg IV, along with IV methylprednisolone.[37]

Jonsdottir et al reported that the majority of patients improved following rituximab plus cyclophosphamide.[38] The differential downregulation of anti-DNA of the immunoglobulin (Ig) G and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19+ cells at baseline predict a less impressive clinical and serologic response suggests that more flexible dosing could be advantageous.

Investigational pharmacologic approaches

Mycophenolate mofetil is an effective and safer alternative to cyclophosphamide for patients with lupus nephritis. Other therapeutic approaches under development include anticytokine therapies, costimulatory blockade, antigen-specific immune modulation, and hematopoietic stem cell transplantation.[39]

Epratuzumab, a monoclonal antibody against the B-cell surface antigen CD22, and atacicept, a chimeric molecule formed by a receptor for B-cell–activating factor and a proliferation-inducing ligand with immunoglobulin G (IgG), have both been promising in initial small trials; larger clinical trials are under way.[40] Clinical trial data have shown that B-cell targeting therapies are beginning to fulfill their promise as treatments for systemic lupus erythematosus (SLE), and there are good reasons to hope for further progress in the near future.


Management of Devic Syndrome

The treatment of Devic syndrome (neuromyelitis optica) in isolated myelopathy or optic neuropathy associated with the antiphospholipid syndrome (APLS) or lupus needs further study. In view of their lack of pathologic similarity to classical multiple sclerosis, treatments such as interferon-beta cannot be justified. Also, there is no hard evidence to support the use of anticoagulation, in the absence of evidence for progressive ischemia of isolated anatomic sites. Therefore, therapy is generally aimed at circulating pathogenic antibodies, with steroids and cyclophosphamide. Plasma exchange has proven effective in nonlupus Devic disease. Because of the analogy with nonlupus Devic disease, plasma exchange is also an attractive alternative in systemic lupus erythematosus (SLE)–Devic disease.[41]


Myopathy/Polyneuropathy Management

Generally, mild myopathy or polyneuropathy may be treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptomatic medications (e.g., anticonvulsants, tricyclics [TCAs], other medications used for neurogenic or musculoskeletal pain). Symptoms may be caused by medications (e.g., steroids, antimalarials) or other etiologies in addition to systemic lupus erythematosus (SLE). If alternative explanations are unlikely and symptoms are more bothersome, low- to medium-dose prednisone may be tried, possibly with a longer-term transfer to antimalarial therapy.


Polyradiculopathy Management

If a patient with systemic lupus erythematosus (SLE) presents with acute polyradiculopathy resembling Guillain-Barré syndrome or chronic relapsing polyradiculopathy resembling chronic inflammatory demyelinating polyneuropathy, treatment with intravenous immunoglobulin (IVIg) in conventional doses should be considered. When IVIg is unavailable or poorly tolerated, plasma exchange should be considered as an alternative. Unfortunately, few therapeutic studies exist on these rare presentations of SLE.


Management of Seizures

Seizures are common sequelae of systemic lupus erythematosus (SLE) and may result from acute or chronic disease. Acute electrolyte disturbance, response to high-dose steroids, or other acute disturbance may only require temporary anticonvulsant treatment, whereas more chronic epileptogenic foci may require lifetime prophylaxis.

Anticonvulsants may be used in a conventional fashion, emphasizing medications most effective for focal onset or secondarily generalized seizures. Phenytoin and other agents associated with drug-induced lupus are unlikely to actually increase disease activity in SLE, but with chronic use may cause diagnostic confusion for physicians.


Management of APLS

Treatment of the antiphospholipid syndrome (APLS) remains controversial, with therapy based predominantly on anecdotal experience. Although many authorities recommend full anticoagulation with warfarin (Coumadin) (despite there being no randomized clinical trial to prove this), other authorities support antiplatelet therapy initially, with stronger measures reserved for repeated stroke, progressive myelopathy, or other clear-cut, clinical treatment failure.

It is clear that aiming for an international normalized ratio (INR) of 2.0–3.0 is as good at reducing the risk of further events as more intensive anticoagulation.[42] This could be done possibly in conjunction with immunosuppressant therapy to suppress production of the antibody.



If neurologic signs or symptoms present in a patient with SLE that is well established, the need for additional consultations beyond the treating internist or rheumatologist is determined by the presence and severity of concomitant organ disease.

Cerebral lupus, like the neurologic vasculitides, is best managed jointly by neurologists, clinical immunologists, renal physicians, rheumatologists, and the primary physicians.



Generally, new-onset systemic lupus erythematosus (SLE) diagnosed based on neurologic symptoms should be managed in conjunction with a rheumatologist or internist.

If neurologic signs or symptoms present in a patient with SLE that is well established, the need for additional consultations beyond the treating internist or rheumatologist is determined by the presence and severity of concomitant organ disease.

Cerebral lupus, like the neurologic vasculitides, is best managed jointly by neurologists, clinical immunologists, renal physicians, rheumatologists, and the primary physicians.


Long-Term Monitoring

The overall outcome of central nervous system (CNS) lupus, quality of life, and prognosis can be enhanced with close follow-up and coordination between the individual's neurologist, rheumatologist, and primary care physician. Neurologists and rheumatologists usually do not act as primary care physicians and leave healthcare maintenance to practitioners who need to be reminded to screen for various comorbidities associated with inflammation and complications of medication. Rheumatologists need to take the responsibility to ensure that their patients with lupus have optimal primary care access, which includes a working relationship with them.[43]

Contributor Information and Disclosures

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Florian P Thomas, MD, PhD, Drmed, MA, MS Director, National MS Society Multiple Sclerosis Center; Professor and Director, Clinical Research Unit, Department of Neurology, Adjunct Professor of Physical Therapy, Associate Professor, Institute for Molecular Virology, St Louis University School of Medicine; Editor-in-Chief, Journal of Spinal Cord Medicine

Florian P Thomas, MD, PhD, Drmed, MA, MS is a member of the following medical societies: Academy of Spinal Cord Injury Professionals, American Academy of Neurology, American Neurological Association, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Niranjan N Singh, MD, DM Associate Professor of Neurology, University of Missouri-Columbia School of Medicine

Niranjan N Singh, MD, DM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

Additional Contributors

Thomas A Kent, MD Professor and Director of Stroke Research and Education, Department of Neurology, Baylor College of Medicine; Chief of Neurology, Michael E DeBakey Veterans Affairs Medical Center

Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, Royal Society of Medicine, Stroke Council of the American Heart Association, American Neurological Association, New York Academy of Sciences, Sigma Xi

Disclosure: Nothing to disclose.

  1. Honczarenko K, Budzianowska A, Ostanek L. Neurological syndromes in systemic lupus erythematosus and their association with antiphospholipid syndrome. Neurol Neurochir Pol. 2008 Nov-Dec. 42(6):513-7. [Medline].

  2. Hawro T, Bogucki A, Sysa-Jedrzejowska A, Bogaczewicz J, Wozniacka A. [Neurological disorders in systemic lupus erythematosus patients]. Pol Merkur Lekarski. 2009 Jan. 26(151):43-8. [Medline].

  3. Greenberg BM. The neurologic manifestations of systemic lupus erythematosus. Neurologist. 2009 May. 15(3):115-21. [Medline].

  4. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999 Apr. 42(4):599-608. [Medline].

  5. Hanly JG, Urowitz MB, Su L, Bae SC, Gordon C, Wallace DJ, et al. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 2010 Mar. 69(3):529-35. [Medline]. [Full Text].

  6. Steup-Beekman GM, Zirkzee EJ, Cohen D, Gahrmann BM, Emmer BJ, Steens SC. Neuropsychiatric manifestations in patients with systemic lupus erythematosus: epidemiology and radiology pointing to an immune-mediated cause. Ann Rheum Dis. 2013 Apr. 72 Suppl 2:ii76-9. [Medline].

  7. Borowoy AM, Pope JE, Silverman E, Fortin PR, Pineau C, Smith CD. Neuropsychiatric lupus: the prevalence and autoantibody associations depend on the definition: results from the 1000 faces of lupus cohort. Semin Arthritis Rheum. 2012 Oct. 42(2):179-85. [Medline].

  8. Unterman A, Nolte JE, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum. 2011 Aug. 41(1):1-11. [Medline].

  9. Mina R, Brunner HI. Pediatric lupus--are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus?. Rheum Dis Clin North Am. 2010 Feb. 36(1):53-80, vii-viii. [Medline]. [Full Text].

  10. Kamphuis S, Silverman ED. Prevalence and burden of pediatric-onset systemic lupus erythematosus. Nat Rev Rheumatol. 2010 Sep. 6(9):538-46. [Medline].

  11. Kampylafka EI, Alexopoulos H, Kosmidis ML, Panagiotakos DB, Vlachoyiannopoulos PG, Dalakas MC. Incidence and prevalence of major central nervous system involvement in systemic lupus erythematosus: a 3-year prospective study of 370 patients. PLoS One. 2013. 8(2):e55843. [Medline].

  12. Taddio A, Rossetto E, Rosé CD, Brescia AM, Bracaglia C, Cortis E, et al. Prognostic impact of atypical presentation in pediatric systemic lupus erythematosus: results from a multicenter study. J Pediatr. 2010 Jun. 156(6):972-7. [Medline].

  13. Ishimori ML, Pressman BD, Wallace DJ, Weisman MH. Posterior reversible encephalopathy syndrome: another manifestation of CNS SLE?. Lupus. 2007. 16(6):436-43. [Medline].

  14. Mikdashi J, Krumholz A, Handwerger B. Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus erythematosus. Neurology. 2005 Jun 28. 64(12):2102-7. [Medline].

  15. Joseph FG, Lammie GA, Scolding NJ. CNS lupus: a study of 41 patients. Neurology. 2007 Aug 14. 69(7):644-54. [Medline].

  16. Keane JR. Eye movement abnormalities in systemic lupus erythematosus. Arch Neurol. 1995 Dec. 52(12):1145-9. [Medline].

  17. Hernando Rubio I, Belzunegui Otano J, Máiz Alonso O, Alvarez Rodríguez B. Transverse myelitis and bilateral optic neuritis in a patient with systemic lupus erythematosus. Reumatol Clin. 2012 Sep-Oct. 8(5):298-9. [Medline].

  18. Zou X, Zhuang Y, Dong FT, Zhang F, Chen YX. Sequential bilateral central retinal artery occlusion as the primary manifestation of systemic lupus erythematosus. Chin Med J (Engl). 2012 Apr. 125(8):1517-9. [Medline].

  19. Lee JH, Sung IY, Park JH, Roh JL. Recurrent laryngeal neuropathy in a systemic lupus erythematosus (SLE) patient. Am J Phys Med Rehabil. 2008 Jan. 87(1):68-70. [Medline].

  20. Iannuccelli C, Spinelli FR, Guzzo MP, Priori R, Conti F, Ceccarelli F, et al. Fatigue and widespread pain in systemic lupus erythematosus and Sjögren's syndrome: symptoms of the inflammatory disease or associated fibromyalgia?. Clin Exp Rheumatol. 2012 Nov-Dec. 30(6 Suppl 74):117-21. [Medline].

  21. Sanna G, Bertolaccini ML, Cuadrado MJ, Laing H, Khamashta MA, Mathieu A, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003 May. 30(5):985-92. [Medline].

  22. Azarpazhooh MR, Mokhber N, Orouji E, Chambers BR, Hatef MR, Rezaieyazdi Z, et al. Microembolic signals in patients with systemic lupus erythematosus. Can J Neurol Sci. 2010 May. 37(3):371-5. [Medline].

  23. Ellis SG, Verity MA. Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955--1977. Semin Arthritis Rheum. 1979 Feb. 8(3):212-21. [Medline].

  24. Yuan H, Ni JD, Pan HF, Li LH, Feng JB, Ye DQ. Lack of association of FcgammaRIIIb polymorphisms with systemic lupus erythematosus: a meta-analysis. Rheumatol Int. 2010 Mar 19. [Medline].

  25. AlSaleh J, Jassim V, ElSayed M, et al. Clinical and immunological manifestations in 151 SLE patients living in Dubai. Lupus. 2008. 17(1):62-6. [Medline].

  26. El-Chennawi FA, Mosaad YM, Habib HM, El-Degheidi T. Comparative study of antinuclear antibody detection by indirect immunofluorescence and enzyme immunoassay in lupus patients. Immunol Invest. 2009. 38(8):839-50. [Medline].

  27. Merkel PA, Chang Y, Pierangeli SS, et al. The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases. Am J Med. 1996 Dec. 101(6):576-83. [Medline].

  28. Choojitarom K, Verasertniyom O, Totemchokchyakarn K, et al. Lupus nephritis and Raynaud's phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies. Clin Rheumatol. 2008 Mar. 27(3):345-51. [Medline].

  29. Offenbacher H, Fazekas F, Schmidt R, Freidl W, Flooh E, Payer F. Assessment of MRI criteria for a diagnosis of MS. Neurology. 1993 May. 43(5):905-9. [Medline].

  30. Zanardi VA, Magna LA, Costallat LT. Cerebral atrophy related to corticotherapy in systemic lupus erythematosus (SLE). Clin Rheumatol. 2001. 20(4):245-50. [Medline].

  31. Castellino G, Padovan M, Bortoluzzi A, et al. Single photon emission computed tomography and magnetic resonance imaging evaluation in SLE patients with and without neuropsychiatric involvement. Rheumatology (Oxford). 2008 Mar. 47(3):319-23. [Medline].

  32. Valdés-Ferrer SI, Vega F, Cantú-Brito C, et al. Cerebral changes in SLE with or without antiphospholipid syndrome. a case-control MRI study. J Neuroimaging. 2008 Jan. 18(1):62-5. [Medline].

  33. Glanz BI, Laoprasert P, Schur PH, et al. Lateralized EEG findings in patients with neuropsychiatric manifestations of systemic lupus erythematosus. Clin Electroencephalogr. 2001 Jan. 32(1):14-9. [Medline].

  34. Coles A. Looks like multiple sclerosis, but the ANA is positive: does my patient have lupus?. Pract Neurol. 2004. 4(4):212-221.

  35. Pittock SJ, Lennon VA, de Seze J, Vermersch P, Homburger HA, Wingerchuk DM. Neuromyelitis optica and non organ-specific autoimmunity. Arch Neurol. 2008 Jan. 65(1):78-83. [Medline].

  36. Trevisani VF, Castro AA, Neves Neto JF, Atallah AN. Cyclophosphamide versus methylprednisolone for the treatment of neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database Syst Rev. 2000. CD002265. [Medline].

  37. Fernandes Moça Trevisani V, Castro AA, Ferreira Neves Neto J, Atallah AN. Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database Syst Rev. 2013 Feb 28. 2:CD002265. [Medline].

  38. Jónsdóttir T, Gunnarsson I, Risselada A, et al. Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Ann Rheum Dis. 2008 Mar. 67(3):330-4. [Medline].

  39. Ermann J, Bermas BL. The biology behind the new therapies for SLE. Int J Clin Pract. 2007 Dec. 61(12):2113-9. [Medline].

  40. Looney RJ. B cell-targeted therapies for systemic lupus erythematosus: an update on clinical trial data. Drugs. 2010 Mar 26. 70(5):529-40. [Medline].

  41. Weinshenker BG, O'Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999 Dec. 46(6):878-86. [Medline].

  42. Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med. 2003 Sep 18. 349(12):1133-8. [Medline].

  43. Wallace DJ. Improving the prognosis of SLE without prescribing lupus drugs and the primary care paradox. Lupus. 2008. 17(2):91-2. [Medline].

This axial, T2-weighted brain magnetic resonance image (MRI) demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with longstanding systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. The distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to the distribution.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.