Neurologic Manifestation of Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus is a rare autoimmune disease, affecting 15–124 per 100.000 individuals worldwide. The disease is most common in women of child-bearing age and its prevalence decreases with increasing age. Elderly-onset lupus, which is generally defined as lupus first occurring in patients aged 50–65 years, accounts for 10–20% of patients with the disease and is 5-fold more common in women than in men. Changes in cellular immunity and menopause may contribute to the development of lupus in older individuals (1).

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with diverse clinical manifestations in all organ systems of the body, and a variable course and prognosis. It is characterized by the production of antibodies to components of the cell nucleus. Involvement of the nervous system is one of the most profound manifestations of the disease, which encompasses a wide variety of neurologic (N) and psychiatric (P) manifestations. Since the first report of stupor and coma in SLE in 1875, a variety of neuropsychiatric syndromes have been reported in SLE patients, with approximately two-thirds of subjects with SLE presenting neuropsychiatric (NP) manifestations. To date, NP lupus is the most poorly understood subset of the disease. The pathogenic mechanisms involved are obscure, although proposed mechanisms include vascular occlusion due to vasculopathy, vasculitis, leukoaggregation or thrombosis, and antibody-mediated neuronal cell injury or dysfunction. Moreover, therapies are empirical, and the course and prognosis for individual patients who present with an NP event is unclear (2).

Neurologic and psychiatric manifestations of SLE have been most commonly termed as central nervous system (CNS) lupus, although several other terms have also been applied, such as CNS vasculitis, lupus cerebritis, neurolupus and neuropsychiatric lupus. The term CNS lupus is inappropriate because the peripheral nervous system (PNS) may also be involved (although CNS manifestations predominate), ‘neuro’ does not include psychiatric manifestations, and ‘vasculitis’ and ‘cerebritis’ imply inflammatory processes which are not always present. The preferred term is neuropsychiatric SLE (NPSLE), since this encompasses the range of possible manifestations. Neuropsychiatric SLE includes the neurologic syndromes of the central, peripheral and autonomic nervous systems, and the psychiatric syndromes observed in patients with SLE in which other causes have been excluded (2).

There are a wide variety of neurologic (N) and psychiatric (P) manifestations of systemic lupus erythematosus (SLE) which extend beyond those identified in the current American College of Rheumatology (ACR) classification criteria for SLE (2,3).

In 1999, the ACR research committee produced a standard nomenclature and set of case definitions for NP-SLE. Using a consensus approach and drawing on a pool of experts from a variety of subspecialties including rheumatology, neurology, immunology, psychiatry and neuropsychology, NP syndromes (Table 1) were defined and diagnostic criteria developed (2,3).

The 19 NP syndromes can be divided into three clinical categories: (i) diffuse psychiatric/neuropsychological syndromes (anxiety disorder, acute confusional state, cognitive disorder, mood disorder and psychosis); (ii) neurologic syndromes of the CNS (cerebrovascular disease, demyelinating syndrome, headache, aseptic meningitis, chorea, seizures and myelopathy); and (iii) neurologic syndromes of the PNS (acute inflammatory demyelinating polyradiculoneuropathy, mononeuropathy, autonomic disorder, plexopathy and polyneuropathy) according to the anatomic location of pathology and clinical manifestation (2).

The most common four of the 19 NP syndromes in each of the five SLE cohorts are summarized in table 3. Most of the other NP syndromes were infrequent, with a prevalence of less than 1% in the majority of cases (3).

It may help to differentiate between severe and mild manifestations and between thrombotic and non-thrombotic CNS disease, although to make a clear-cut differentiation may be challenging. In this context, a better approach in the management is represented by (i) the recognition of the APS (a common thrombotic disease) and its treatment with anticoagulants, (ii) a more conservative use of steroids, especially in patients with mild manifestations and (iii) the use of pulse cyclophosphamide in diffuse/non-thrombotic CNS lupus. Current therapeutic approach for CNS disease in SLE is summarised in Table 1 (4).

Refferences :

1. Adis Data Information BV. Early detection and individualized treatment of elderly-onset systemic lupus erythematosus optimizes symptom control. Drugs Ther Perspect 2008; Vol. 24, No. 6.
2. Sang-Cheol BAE. The ACR classification of neuropsychiatric systemic lupus erythematosus: how this helps in diagnosis and treatment. APLAR Journal of Rheumatology 2003; 6: 188–191.
3. Hanly JG. ACR classification criteria for systemic lupus erythematosus: limitations and revisions to neuropsychiatric variables. Lupus 2004; 13: 861–864. 
4. Sanna G, Bertolaccini ML, Khamashta MA. Neuropsychiatric Involvement in Systemic Lupus Erythematosus: Current Therapeutic Approach. Current Pharmaceutical Design 2008; 14: 1261-1269.