CNS Lupus

No Results

No Results

processing….

Neurologic manifestations are among the features of systemic lupus erythematosus (SLE), a multisystem autoimmune connective tissue disorder with various clinical presentations. SLE affects many organ systems, including the central and peripheral nervous systems and muscles. ^[1]

Central nervous system (CNS) lupus is a serious but potentially treatable illness, which still presents very difficult diagnostic challenges (see the following image). This condition is in the differential diagnosis for many neurologic conditions. Thus, neurologists and other clinicians need to be aware of the various presentations and neurologic complications of SLE; patients with SLE often have neurologic symptoms, and SLE is sometimes diagnosed after patients present for treatment of a neurologic event. ^{[2, 3]}

See also Pediatric Systemic Lupus Erythematosus, Neonatal and Pediatric Lupus Erythematosus, Systemic Lupus Erythematosus and Pregnancy, Discoid Lupus Erythematosus, Bullous Systemic Lupus Erythematosus (BSLE), Acute Cutaneous Lupus Erythematosus (ACLE), Subacute Cutaneous Lupus Erythematosus (SCLE), and Physical Medicine and Rehabilitation for Systemic Lupus Erythematosus.

The pathophysiology of SLE has not been defined fully, although many genes that affect immune function, particularly the human leukocyte antigen (HLA), may augment susceptibility to clinical disease. Most monozygotic (identical) twins are discordant for clinical SLE, strongly suggesting that additional factors, probably environmental, trigger the widespread development of autoimmunity in susceptible individuals.

Certain medications (e.g., phenytoin, hydralazine, procainamide, and isoniazid) may produce drug-induced lupus, but this disorder differs from classic SLE in its autoantibody profile (e.g., antihistone antibody positive) and in sparing the kidneys and CNS. Once triggered, SLE’s autoimmune reaction affects many sites through multiple mechanisms such as deposition of immune complexes, effects of cytokines and other chemical neuromodulators, direct attack by autoantibodies or activated leukocytes, and others.

Non-neurologic sites of damage include the renal glomeruli, joints, pleural or pericardial serosa, integument, cardiac or vascular endothelium, cardiac valves, and the oral and conjunctival mucosa. Multiple sites may be involved within the nervous system.

Among the neurologic manifestations of systemic lupus erythematosus (SLE), the most common are the organic encephalopathies. These diffuse syndromes correlate poorly with the extent of vasculitis or frank thromboembolism. Functional studies such as positron emission tomography (PET) scanning, functional magnetic resonance imaging (MRI), or single photon emission computerized tomography (SPECT) scanning demonstrate patchy areas of dysfunction in brain areas not demonstrable on conventional MRI, findings that suggest an uncoupling of metabolic processes independent of obstruction to cerebral blood flow. The mechanism of these apparent metabolic alterations is unknown. (See CT Scanning and MRI.)

In areas of apparent vasculitis, histology demonstrates degenerative changes in small vessel walls, often with minimal or no inflammatory infiltrates. Chronic effects of immune complex deposition offer one potential mechanism for SLE vasculopathy; cytokine-mediated effects on vascular endothelium or local brain parenchyma are another. Inflammatory and noninflammatory SLE vasculopathies may be clinically indistinguishable. The terms cerebritis and vasculitis are well embedded in the literature and will be used in this article, keeping in mind the evolving understanding of the underlying processes.

In addition to small vessel vasculopathy, inflammatory changes may occur in large- to medium-sized vessels, giving a more classic vasculitis, sometimes with clinical stroke syndromes resulting from local thrombosis or artery-to-artery emboli. Other potential stroke etiologies include local thrombosis from antiphospholipid antibodies, which may involve small or medium-sized arteries or veins, including the venous sinuses.

Emboli can occur as a result of Libman-Sacks endocarditis (LSE), a sterile endocardial inflammation that produces vegetations on the heart valves, seen in greater frequency in the presence of antiphospholipid antibodies. LSE may also cause a diffuse microembolization pattern that is clinically hard to distinguish from vasculitis or cerebritis. In focal clinical syndromes, overt or covert cardiac emboli are more frequently responsible than focal vasculitic or thrombotic processes. (See Biopsies and Histologic Features.)

Antiphospholipid antibodies comprise one category of the multiple autoantibodies that may be associated with SLE. In addition to their association with LSE and local arterial or venous thrombosis, these antibodies also may be associated with a hemorrhagic diathesis, myelopathy, and non-neurologic manifestations such as spontaneous abortion.

Dural sinus thrombosis is a rare complication of SLE-associated hypercoagulability and is often seen in association with antiphospholipid antibodies. Radiologically, flow defects in one or more venous sinuses may be imaged with MRI, MR venous angiography, conventional angiography, or radionuclide brain scanning. Associated edema or hemorrhagic infarcts may be obvious on MRI or CT scans.

The most common type of drug-induced myopathy is steroid-induced myopathy. It usually presents with progressing painless muscle weakness, fatigability, and muscle atrophy, and is an adverse effect of glucocorticoid use (though fluorinated glucocorticoid has a higher chance of causing this).

Muscle biopsy often reveals slight variation in fiber size with type 2b atrophy, with little or no fiber necrosis and no inflammatory cells. Biopsy also often reveals slight myofibrillar loss with accumulations of glycogen, lipids, and aggregates of mitochondria. (See Biopsies and Histologic Features.)

Amphiphilic drug myopathies are often caused by drugs with hydrophobic moiety and hydrophilic region containing amine group. They produce multisystem disorders including neuropathy, myopathy, and cardiomyopathy. Chloroquine and hydroxychloroquine cause vacuolar myopathy, often given in a 500 mg daily dose of chloroquine for 1 year or longer. At extracellular pH, this drug is poorly ionized and penetrates membranes. With acid pH in lysosome, cationic region interacts with polar materials.

Muscle biopsy reveals vacuoles with lipid and membranous material, with strong acid phosphatase staining in muscle fibers and normal periodic acid-Schiff (PAS) staining for glycogen. (See Biopsies and Histologic Features.)

According to a set of definitions of 19 neuropsychiatric systemic lupus erythematosus (NPSLE) syndromes and their diagnostic criteria from the American College of Rheumatology (ACR), less than 40-50% of events are due to underlying CNS lupus activity (primary NPSLE). The rest are indirectly associated to the disease and can be the consequence of metabolic disturbances, infections, or drug effects (secondary NPSLE). ^{[4, 5, 6]}

Data from large cohorts suggest prevalence rates of approximately 30–40% for NPSLE. ^{[7, 8]} Further studies show NPSLE is at least as common in children as it is in adults. ^{[9, 10]}

A three-year prospective study of 370 SLE patients with no previous history of CNS involvement determined that clinically severe CNS involvement is rare in SLE patients, accounting for 7.8/100 person years. ^[11]

Central nervous system (CNS)-specific statistics are not available, however, neuropsychiatric events in systemic lupus erythematosus (SLE) have a more favorable outcome than events secondary to non-SLE causes. Events attributed to SLE generally occur during the early course of the illness, do have a negative impact on the quality of life of the patient, and do vary in severity and frequency. ^[5]

Neurologic complications worsen prognosis, especially in the presence of refractory seizures, encephalopathy, or paralysis from stroke or myelopathy.

Taddio et al concluded that presence of atypical manifestations of pediatric SLE at presentation and early kidney disease correlated with poor outcome. Similarly, during follow-up, kidney and CNS diseases were associated with worse outcome. ^[12]

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].

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].

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

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

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].

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].

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].

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].

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].

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

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].

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].

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

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].

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

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

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].

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].

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].

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].

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].

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].

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].

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].

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].

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].

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].

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].

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].

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

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].

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].

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].

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

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].

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].

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].

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].

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

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].

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].

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].

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

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.

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, MA, MS Chair, Neuroscience Institute and Department of Neurology, Director, Multiple Sclerosis Center and Hereditary Neuropathy Centers, Hackensack University Medical Center; Founding Chair and Professor, Department of Neurology, Hackensack Meridian School of Medicine at Seton Hall University; Professor Emeritus, Department of Neurology, St Louis University School of Medicine; Editor-in-Chief, Journal of Spinal Cord Medicine

Florian P Thomas, MD, PhD, 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.

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM Adjunct Associate Professor of Neurology, University of Missouri-Columbia School of Medicine; Medical Director of St Mary’s Stroke Program, SSM Neurosciences Institute, SSM Health

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM 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.

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.

CNS Lupus

Research & References of CNS Lupus|A&C Accounting And Tax Services
Source

Share on Facebook

Tweet

Follow us