The Search for Prognostic Markers in Patients with Primary Angiitis of the Central Nervous System

By Rula Hajj-Ali, MD

As Associate Director of the Center for Vasculitis Care and Research at Cleveland Clinic, I see many patients with both common and rare vasculitides. The patients I diagnose with primary angiitis of the central nervous system (PACNS) often present with severe functional and cognitive symptoms, and we are only beginning to understand the long-term outcomes of this disease. My colleagues and I recently published the longest reported follow-up of patients with PACNS in Clinical and Experimental Rheumatology. We found that long-term disability is mild, perhaps thanks to improvements in diagnosis and treatment, but that opportunities remain to improve patient quality of life and identify prognostic markers.

Our cohort

We identified patients diagnosed with central nervous system vasculitis by either cerebral angiogram results typical of vasculitis plus inflammatory cerebrospinal fluid (CSF) or findings of vasculitis on pathologic examination of brain tissue. Of 78 patients meeting the inclusion criteria, 27 responded to the four mailed questionnaires: the Barthel Index (to assess disability), European Quality of Life Questionnaire (EuroQol; EQ-5D), the Brief Patient Health Questionnaire (BPHQ-9) (to assess depression) and a treatment history survey. Researchers also administered Modified Rankin Scale (MRS), a disability assessment. Median follow-up was 60 months (0-204), compared with 35 and 13 months reported in previous cohorts.

Our decision to only include patients whose diagnosis was established by brain biopsy (74.1%) or by the presence of both abnormal cerebral angiography and cerebrospinal fluid findings (25.9%) distinguishes our study. Cohorts in prior studies were diagnosed based on pathologic findings in only about one-third of cases. Our study is also the first to address patient-centered outcomes.

Long-term quality of life outcomes

Most patients (n = 19; 70.4%) had mild disability, while around a fifth (n = 5; 18.5%) experienced severe disability. Mobility issues were not present in 51.9% (n = 14) of patients, and 66.7% (n = 18) had no problems with self-care. Fifteen (55.6%) respondents reported no issues with usual activities, and a similar number (n = 14; 51.9%) reported no pain. Almost one-third (n = 8; 29.6%) reported no anxiety, and about 70% had minimal or no depression.

Our search for prognostic markers uncovered two potential targets. We noticed that patients with stroke demonstrated significantly higher rates of depression/anxiety (P = 0.04), which is expected given that about one-third of stroke patients will experience post-stroke depression. One-third to one-half of patients with PACNS present with stroke, so it seems reasonable that the reported 30% incidence of clinical depression in this population is underrecognized.

Though we found no other statistically significant correlations between outcomes and treatment history, diagnostic method or clinical findings, the presence of grey matter enhancement in radiological findings correlated with worsened anxiety/depression (R = 0.4, P = 0.04), mobility (R = 0.4, P = 0.04), PHQ-9 scores (R = 0.5, P = 0.03) and visual analogue scale (R = -0.6, P = 0.009). Given the paucity of currently available prognostic predictors, these data offer direction for further research.

Significant mortality and the need for prognostic markers

Not long ago, PACNS was only diagnosed postmortem. The progress toward establishing standard diagnostic criteria and effective treatment protocols since Cupps et al. first described sustained clinical remission in 1983 has helped patients achieve a generally favorable disease course. Our efforts in this study to characterize long-term quality of life factors allow us to understand areas of opportunity for improved diagnosis and treatment. Mortality remains high in patients with PACNS (11% of the 78 patients who met our inclusion criteria), and studies of larger cohorts to identify prognostic markers are needed.

Dr. Hajj-Ali is Associate Director of the Center for Vasculitis Care and Research.