Multiple Sclerosis and Antiphospholipid Syndrome Are Not Always Easy to Differentiate

abstracts & commentary

Sources: Cuadrado MJ, et al. Can neurologic manifestations of Hughes (antiphospholipid) syndrome be distinguished from multiple sclerosis? Analysis of 27 patients and review of the literature. Medicine 2000;79:57-68; Kovacs B, et al. Transverse myelopathy in systemic lupus erythematosus: An analysis of 14 cases and review of the literature. Ann Rheum Dis 2000;59:120-124.

Cuadrado and colleagues retrospectively reviewed 27 consecutive patients at a London hospital with an initial diagnosis of clinically probable or definite multiple sclerosis (MS), who were referred over a two-year period to a lupus unit to exclude underlying collagen-vascular disease. All 27 patients were women, with a mean age of 38 years (range 18-45), and a mean duration of MS diagnosis of 57 months (range 7-72). Anticardiolipin antibodies of IgG and IgM were detected in 74% and 78% of patients, respectively. Lupus anticoagulant was positive in seven of 21 patients tested.

Of the 27 patients, 16 were thought to have a primary antiphospholipid syndrome (APS) whose initial clinical involvement was largely cerebral or cerebellar. The remaining 11 patients had secondary APS associated with systemic lupus erythematosus (SLE), and were more likely to present with myelopathy and optic neuropathy. During follow-up, 19 of 27 (70%) patients developed some other SLE- or APS-related features, including photosensitivity, hair loss, arthralgias, livedo reticularis, venous thrombosis, or miscarriages.

Blinded review of brain MRIs were not thought to be significantly different from a control group of MS patients, with 14 patients demonstrating the majority of lesions in the white matter, but nine patients showed damage in both the white and grey matter, and four patients with a normal MRI. Analysis of cerebrospinal fluid (CSF) was performed in only six patients; oligoclonal bands (OCBs) were found in four patients, all of whom had APS secondary to SLE. Treatment included warfarin, aspirin, and prednisone, with secondary APS patients typically doing worse.

Kovacs and colleagues described 14 patients presenting with transverse myelopathy (TM) from a population of 600 SLE patients at two Philadelphia hospitals. In seven of 14 patients (50%), TM was an initial symptom of SLE. Optic neuritis also occurred in four of 14 patients. In their series, 55% of patients tested positive for anticardiolipin antibodies or lupus anticoagulant. CSF typically showed a pleiocytosis and elevated protein, but OCBs were not described. Patients were treated with intravenous (IV) methylprednisolone and cyclophosphamide or plasmapheresis, with complete to partial recovery in only five patients (36%).


These two papers address a significant concern for the neurologist constructing a differential diagnosis in patients presenting with possible MS. The presence and significance of anticardiolipin antibodies in demyelinating disease has been studied in previous reports, most recently by Karussis and associates (Karussis D, et al. Ann Neurol 1998;44:629) and D’Ohlaberriague and associates (D’Ohlaberriague L, et al. Neurology 1998; 51:1376). For example, Karussis et al found low to significant titers of IgG and IgM antibodies in up to 20 of 100 of MS patients with classic brain MRIs and clinical presentations, more commonly with myelopathy, optic neuropathy, and headache. CSF OCBs were detected in only three of 20 patients.

The distinction between MS and APL syndromes is more than an academic issue, since clinical management will differ between the two disorders. The MS patient would typically be treated with interferon-beta or glatiramer acetate, whereas the APL syndrome might require therapy with antiplatelet or anticoagulant agents (or even plasmapheresis in the case of fulminant catastrophic APL syndrome). Patients should have a careful evaluation for any clinical signs or symptoms of systemic collagen-vascular disease. It is well described in the literature that many MS patients can have a slightly elevated ESR, ANA, ACE, or ACLA (see Neurol Alert). Indeed, a few of the patients described by Cuadrado et al may fall into this category. Low titers of anticardiolipin antibodies, particularly IgM, are common and are not thought to have much pathogenic significance, while high titers of IgG may be relevant. A careful medical history (e.g., for thrombosis or fetal loss), other subtle findings of systemic disease, consistently abnormal serologies, atypical lesion localization on MRI, and negative CSF OCBs may help guide an accurate diagnosis and optimal management. —bra

Which of the following is false?

a. Anticardiolipin antibodies occur in demyelinating conditions of the CNS.

b. Fetal loss and thrombosis are associated with the antiphospholipid syndrome.

c. Anticardiolipin antibodies do not occur in transverse myelopathy or optic neuropathy.

d. Systemic manifestations collagen-vascular disease do not always precede neurologic symptoms.

e. Brain MRI scans in the antiphospholipid syndrome may be similar in appearance to MS.