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    Home » Neuropathy in Systemic Lupus Erythematosus
    ABSTRACT & COMMENTARY

    Neuropathy in Systemic Lupus Erythematosus

    June 1, 2019
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    Keywords

    Neuropathy

    lupus

    By Michael Rubin, MD

    Professor of Clinical Neurology, Weill Cornell Medical College

    Dr. Rubin reports he is a consultant for Merck Sharp & Dohme Corp.

    SYNOPSIS: Systemic lupus erythematosus may be associated with a variety of neuropsychiatric syndromes, including peripheral neuropathy, mostly sensorimotor types. However, all parts of the peripheral and central nervous system may be affected, and careful and repeated neurological evaluation is important.

    SOURCE: Bortoluzzi A, Piga M, Silvagni E, et al. Peripheral nervous system involvement in systemic lupus erythematosus: A retrospective study on prevalence, associated factors and outcome. Lupus 2019;28:465-474.

    Neurologic or psychiatric symptoms occur in 12-95% of patients with systemic lupus erythematosus (SLE). The wide range reflects differences in study design, varied definitional criteria of neurologic and psychiatric disease, and divergent exclusion and inclusion criteria. Common clinical syndromes include cognitive dysfunction, stroke syndromes, seizures, headache, and neuropathy. What is the prevalence of peripheral neuropathic involvement in SLE and what forms does it take?

    Medical records of SLE patients, seen between 2000 and 2014, at two tertiary care referral centers in Cona and Cagliari, Italy, were reviewed retrospectively. Inclusion criteria required a diagnosis of SLE based on the 1997 American College of Rheumatology revised classification, and evidence of peripheral nerve involvement was based on recorded clinical and laboratory documentation. Follow-up for at least one year was necessary for inclusion, and sex-matched and disease duration-matched SLE patients, without neuropsychiatric abnormalities, served as controls. Pure compression neuropathies, such as carpal tunnel syndrome, were not included. A statistical analysis comprised the chi-square or Fisher’s exact test, as appropriate, and a two-tailed Student’s t-test or nonparametric Mann-Whitney U test for continuous variables, with P < 0.05 considered significant.

    Among 1,224 patients, 85 patients (6.9%) experienced 97 peripheral nervous system (PNS) events. Of these, 61 patients (4.9%) were deemed to have experienced their PNS event as attributable to SLE. Most (67%) PNS events occurred at least three months following SLE diagnosis. However, in two cases it preceded diagnosis, and in 26 patients (31%) it appeared at disease onset. Combined peripheral and central nervous system (CNS) involvement was seen in 47% (n = 40), concomitant in 32.5%, CNS subsequent in 2%, and preceding the PNS event in 65%.

    Peripheral polyneuropathy was the most common PNS event (43.3%), sensorimotor in 25% of events, sensory in 13%, and small fiber in 4.1%, with autonomic neuropathy and plexopathy accounting for 1% each. Cranial neuropathy accounted for 30.9% of events, peripheral mononeuropathy for 12.4%, and multiple mononeuropathy for 8.2%. Myasthenia gravis was seen in 3.1%, and no instances of acute or chronic inflammatory demyelinating polyradiculoneuropathy were noted.

    Compared to controls, SLE patients with PNS involvement were significantly older at the time of diagnosis and were more likely to have higher scores on SLE Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index. Sjögren’s syndrome was more common in the PNS group, as was livedo reticularis, hypertension, diabetes, and smoking, whereas malar rash and photosensitivity were more common in controls. Careful neurologic evaluation is necessary in SLE, particularly in older patients who are more likely to have neurologic involvement and more aggressive disease.

    COMMENTARY

    Neuropsychiatric lupus, formerly termed lupus cerebritis, occurs in up to 50% of SLE patients, and encompasses a wide range of symptoms and syndromes, including headache, cognitive impairment, acute confusional states, psychosis, memory loss, stroke, and seizures. Some may be related to coagulopathy, but the affective and cognitive manifestations remain poorly understood. Anti-phospholipid antibodies activate platelets and endothelial cells and, with consequent shedding of prothrombotic microparticles, may be the underlying mechanism of thrombosis in the venous and arterial circulation and pregnancy loss. However, neurobehavioral deficits also have been described following their intraventricular injection in mice models. Intrathecal injection of anti-N-methyl-d-aspartate (anti-NMDA) receptor antibodies into mice produce affective and cognitive symptoms, whereas anti-ribosomal P protein antibodies bind limbic structures, thereby affecting memory and mood, and promote inflammation and blood-brain barrier impairment due to production of tumor necrosis factor. Improved understanding of the pathophysiology of neuropsychiatric lupus will be required to best treat its multifaceted manifestations.1

    REFERENCE

    1. Schwartz N, Stock AD, Putterman C. Neuropsychiatric lupus: New mechanistic insights and future treatment directions. Nat Rev Rheumatol 2019;15:137-152.

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    Neurology Alert

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    Neurology Alert (Vol. 38, No. 10) - June 2019
    June 1, 2019

    Table Of Contents

    Eculizumab Shows Benefit in a Treatment Trial of NOSD

    Neuropathy in Systemic Lupus Erythematosus

    Late Sunsets, Sleep Deprivation, and Adverse Outcomes

    Treatment of Progressive Multifocal Leukoencephalopathy With Pembrolizumab

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    Financial Disclosure: Neurology Alert’s Editor in Chief Matthew Fink, MD; Peer Reviewer M. Flint Beal, MD; Editorial Group Manager Leslie Coplin; Editor Jonathan Springston; and Accreditations Manager Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.

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