BERLIN – The prevalence of major central nervous system manifestations in patients with systemic lupus erythematosus is considerably lower than commonly reported, according to a 3-year study presented at the annual European Congress of Rheumatology.
The prevalence of major CNS involvement was found to be "very low" at 4.3% (7.8 cases/100 person-years), "whilst in most studies when the prevalence of all CNS events is recorded, this figure can be between 15-40%," said Dr. Eleni Kampylafka of the pathophysiology department at the National University of Athens.
Dr. Eleni Kampylafka
Previous studies of CNS involvement probably yielded high estimates because they did not tease out minor from major CNS events, clouding the true picture. "There are lots of nonspecific manifestations such as headache and mild depression, and we wanted to know the true prevalence of major events, which have an impact on the patient’s status and outcome," she said.
In the study, Dr. Kampylafka and her colleagues also investigated associations between CNS involvement, disease activity, and neuromyelitis optica (NMO)-IgG antibodies, which can be predictors of disease and are highly specific for both neuromyelitis optica and myelitis in lupus, though not lupus itself.
According to Dr. Kampylafka, minor CNS manifestations included headache, mild cognitive dysfunction, depression, and anxiety. Major CNS involvements were seizures, demyelinating syndrome, acute confusional state, psychosis, aseptic meningitis, chorea, myelopathy, and cerebral vascular events (mainly stroke).
From an initial cohort of 1,093 patients with systemic lupus erythematosus (SLE), the investigators focused on 458 patients who underwent regular follow-up for the 3 years. Only patients without a prior history of SLE-related CNS involvement were included, leaving 370 in the analysis.
Of these patients, 16 (4.3%) were found to have major CNS involvement. All CNS manifestations were recorded and codified according to American College of Rheumatology criteria, but minor CNS events were excluded. Furthermore, patients’ disease activity was evaluated using the ECLAM (European Consensus Lupus Activity Measurement) score and the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) SELENA Modification. Accumulated damage associated with the disease was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/ACR) Damage Index.
Patients were routinely assessed for 3 years using clinical, laboratory, neurological, serological, and immunological tests. "Whenever a new CNS event occurred, an expert neurologist conducted neurological tests with magnetic resonance imaging, electroencephalograms, and cerebrospinal fluid studies, if necessary," reported Dr. Kampylafka.
Out of a total of 23 CNS events, the most common were epileptic seizures (35%), strokes (26%), and myelopathy (22%).
"We also found that nearly half of our patients presented their CNS event at diagnosis," she noted. "This shows that CNS involvement is an early event in lupus, which is something expected."
There was a stark contrast in disease activity measures between patients with CNS involvement and those without it. Lupus patients with CNS involvement had a mean ECLAM score of 4.8, versus 1.4 in patients who lacked CNS involvement (P less than .001). The mean SLEDAI score was 18 in lupus patients with CNS involvement, in contrast to 3 in patients without CNS involvement (P less than .001).
"An important finding here is the presence of NMO-IgG antibodies, which have been shown to exist in patients with lupus and myelopathy specifically, which is a subgroup of manifestations in the disease," said Dr. Kampylafka.
Epileptic seizures correlated with a high ECLAM/SLEDAI score; myelopathy correlated with low ECLAM/SLEDAI scores and NMO-IgG antibody levels; and strokes correlated with antiphospholipid syndrome.
Dr. Kampylafka concluded that overall, the study results demonstrate that CNS involvement correlates with high disease activity at the time of its appearance. But she added a note of caution: Patients presenting with a neurological complication should always receive a complete assessment, because the event might not be related to the patient’s lupus.
Dr. Kampylafka reported having no conflicts of interest.