Lupus and the Nervous System
Abstract & Commentary
By Joseph E. Safdieh, MD, Assistant Professor of Neurology, Weill Medical College, Cornell University; Dr. Safdieh reports no financial relationships relevant to this field of study.
Synopsis: Lupus can involve the nervous system in many ways and sometimes present with neuropsychiatric symptoms. Clinicians should consider the diagnosis of lupus in patients with unexplained neuropsychiatric symptoms.
Source: Joseph FG, et al. CNS lupus: a study of 41 patients. Neurology 2007;69:644-654.
Systemic lupus erythematosus is one of a large number of rheumatological conditions with neuropsychiatric manifestations. In fact, the American College of Rheumatology criteria for the diagnosis of lupus include neurological manifestations as one of 11 diagnostic features. The neuropsychiatric manifestations are protean; they include a large number of symptoms and signs, many of which are nonspecific in nature. These have traditionally included seizures, spinal cord dysfunction, psychosis, stroke, abnormal movements (chorea), and peripheral nervous system dysfunction. The authors of this study retrospectively identified patients with nervous system manifestations of lupus in an effort to better understand the natural history of this disease.
Joseph et al identified a total of 41 patients who satisfied the criteria for CNS lupus; 38 of these patients were female. The mean age for the first neuropsychiatric presentation was 41 years and the mean latency from diagnosis of lupus to presentation of neuropsychiatric symptoms was 5.75 years. The most commonly reported neuropsychiatric features included: headaches (54%), seizures (42%), visual disturbances (32%), fatigue (27%), hemiparesis (24%), memory impairment (24%), and confusion (24%). Arterial stroke was seen in 17% of patients. No cases of venous sinus thrombosis were identified in this series. Two of the patients with stroke had elevated antiphospholipid antibodies. Two patients developed myelopathy.
Of note, in 24% of these patients, neuropsychiatric manifestations were the initial presenting feature of lupus. The erythrocyte sedimentation rate (ESR) was elevated in the majority of these cases, but a normal ESR did not exclude CNS lupus. Neuropsychiatric manifestations in these patients were varied and included movement disorders, seizures, and meningeal involvement, among others. Symptoms included features not traditionally associated with lupus, including parkinsonism. The authors highlighted a case of a 74-year-old woman with levodopa-unresponsive parkinsonism who improved on hydroxychloroquine and prednisolone. This patient demonstrated other abnormalities on neurological examination, and also had an elevated ESR and positive ANA (anti-nuclear antibodies) with low complement levels.
The spinal fluid was abnormal in 39% of cases in which it was analyzed. Abnormalities included elevated protein, mild lymphocytic pleocytosis, and the presence of oligoclonal bands. The presence of abnormal CSF correlated with worse prognosis of CNS lupus. MRI imaging was abnormal in 64% of patients. These abnormalities included nonspecific white matter hyperintensities, infarcts, and in one case each, optic nerve enhancement and leptomeningeal enhancement. EEG was abnormal in 79% of patients, with the majority of patients demonstrating nonspecific slowing.
At the end of the study period, the majority of the patients demonstrated minor or moderate disability. Five patients were asymptomatic and five patients died. The majority of patients suffered repeat attacks and most patients received treatment with steroids, with or without other immunosuppressive agents.
This study demonstrates a number of important points. Primary neurological presentation of lupus is not rare, and the diagnosis should be considered in patients with unexplained neurological symptoms, especially those in the typical demographic group. Chorea, traditionally considered a common movement disorder in lupus, was less common than parkinsonism and myoclonus in this cohort of patients. Patients with primary neurological lupus can have a normal ESR. Abnormal CSF analysis correlates with a poorer prognosis. Seizures in lupus patients are common. In this cohort, the incidence is even higher than previously observed; however, this partly may be explained by case-ascertainment bias.
This is an important study for neurologists as well as internists and rheumatologists. Neurologists and psychiatrists should remember to keep lupus in the differential diagnosis of otherwise unexplained neuropsychiatric symptoms. Internists and rheumatologists caring for patients with lupus should carefully screen these patients for the development of neuropsychiatric manifestations, and adjust anti-inflammatory therapy accordingly as serious disability can result in some cases.