Clinicians should watch for neurological involvement in patients with primary Sjogren's syndrome (pSS), especially in those with high disease activity or previous neurological involvement, researchers suggested.
In findings from the prospective French ASSESS (Assessment of Systemic Signs and Evolution in Sjogren's Syndrome) cohort), published in RMD Open, 18.9% of 392 patients had previous or current neurological manifestations at baseline.
The peripheral nervous system was involved in 16.1% of patients and the central nervous system in 3.6% -- results consistent with studies observing neurological symptoms in about 20% of pSS patients, reported Alain Saraux, MD, of the University of Western Brittany in Brest, France, and colleagues. While central nervous system manifestations are less common, they can cause severe morbidity.
"This is good news for patients," Saraux commented to MedPage Today. "The prevalence of central neurological manifestations is shown to be low, and new neurological manifestations are rare for patients with low disease activity and no prior neurological involvement." He added that higher-risk pSS patients at his institution will receive careful evaluation.
In the chart-review analysis, the mean age of participants (94% female) -- recruited during 2006-2009 at 15 French tertiary autoimmune disease centers -- was 58±12 years, mean age at diagnosis was 51±12, and mean follow-up was 33.9 months. The average EULAR Sjogren's syndrome disease activity index (ESSDAI) was 5.3±5.6. Evaluated by case report form, in terms of prevalence, 9.2% of symptoms were of pure sensory neuropathy, 5.3% of sensorimotor neuropathy, 1.3% of cerebral vasculitis, and 1.0% for myelitis.
Symptoms were associated with greater ESSADI-scored pSS activity: 9.4±6.8 versus 4.3±4.8 (P<0.001). The affected group also had more patients taking immunosuppressant or immunomodulatory drugs: 32.4% versus 13.8% (P=0003). By drug type the P values were: glucocorticoids (P<0.001), immunosuppressive or immunomodulatory drugs (P<0.001), and rituximab (P=0.004).
New neurological symptoms occurred at more than three times the rate in patients with previous symptoms: relative risk 3.918 (95% CI 1.91- 8.05, P<0.001).
The authors noted that follow-up in a Spanish study of systemic involvement in 921 pSS patients found peripheral and central nervous system manifestations in 10.4% and 2.7% of patients, respectively.
"The apparent discrepancy between these findings and ours may be ascribable to the use in the Spanish study of the ESSDAI to define neurological involvement, as opposed to a specific list of neurological manifestations in the [case report form] used in our study," Saraux and co-authors wrote. "Past or subtle neurological manifestations may therefore have been underestimated in the earlier study."
Saraux said he would like to see these results confirmed by magnetic resonance imaging studies comparing pSS patients and healthy people.
Commenting on the paper for MedPage Today, Daniel El-Bogdadi, MD, of Arthritis & Rheumatism Associates in Rockville, Md., said, "The large number of patients is a strong point for the study. However, the study is of course difficult to extrapolate to other populations regarding prevalence as all the study centers were in France. And I would have preferred to see a prospective evaluation rather than a chart review."
El-Bogdadi further noted that although symptomatic patients have greater disease activity, "this is limited by the fact that neurological manifestations contribute to the composite ESSDAI score, and elimination of the neurological manifestation results in no significant difference in ESSDAI scores between those with and without neurological manifestations. So it is not clear if neurologic manifestation is the result of higher disease activity."
In addition, the 14-symptom case report-based analysis may have underestimated the presence of subtle neurological manifestations and may have been inaccurate in diagnosis, El-Bogdadi said. The study had a higher prevalence of Sjogren's-related neurologic symptoms than studies using ESSDAI criteria but a lower prevalence than studies that used broader definitions of neurological manifestations such as psychiatric abnormalities and neurogenic bladder and fibromyalgia/fatigue.
He said that in terms of autoantibodies, 60% of patients were anti-SSA-positive and 30% were SSB-positive. "That is in line with previous studies noting that more than 50% of patients with neurological manifestations of Sjogren's may not have autoantibodies," he said. "This is significant in that the diagnosis of Sjogren's may not be clear initially."
He also observed that since SS is a long-term chronic disease, "we may not have a true accurate number for the actual prevalence of neurological manifestations over many years of the disease. The study assumes that neurologic manifestations may occur early in disease process."
El-Bogdadi pointed out that the causal link between SS and neurological manifestations remains unclear: "Occasionally in my clinic there are patients who present with both multiple sclerosis and the diagnosis of Sjogren syndrome, and delineating which is the primary process can be difficult. I think that close coordination with neurologists is important in this instance, and the determination of the actual primary process should not be solely the rheumatologist's opinion as in this study."
A positive finding of the study is that those developing neurologic manifestations usually have a history of neurologic symptoms or diagnosis before being diagnosed with SS, he added. But the treatment of the SS neurologic manifestations remains largely empirical and based on experience in treating neurologic involvement in systemic lupus erythematosus. "A more favorable therapeutic response maybe be seen in only a certain subtype of neurological involvement, and the same therapies cannot be applied to all the patients with peripheral neurologic manifestations or central nervous system manifestations."
El-Bogdadi called for proper categorization of which symptoms among patients respond favorably to treatment. "The specification of 7 peripheral and 7 central nervous system manifestations may be helpful to be able to better organize clinical trials," he said.
Addressing the study's limitations, he also pointed to the French-only study sites and the definition of manifestations via case report from criteria in the absence of a clear definition of pSS-related neurological manifestations, which may have missed a small proportion of manifestations. As for central nervous system or cranial nerve involvement, the number of affected patients was too small to draw firm conclusions, he said.
The study was supported by the French Ministry of Health.
The authors reported no financial disclosures.
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