Albumin Index May Predict Severity, Disability in Neurosarcoidosis

ST. LOUIS — Assessing blood-brain barrier permeability by using the ratio of cerebrospinal fluid (CSF) and serum albumin, known as the albumin index, could have important clinical utility as a biomarker predicting disease severity and disability in neurosarcoidosis, new research suggests.

Neurosarcoidosis is a long-term inflammatory disorder that affects the nervous system.

"To the best of our knowledge, we could be among the first to have specifically evaluated the albumin index as a marker in a significant cohort of neurosarcoidosis patients and to explore its possible association with global neurological dysfunction, especially in the long term," lead author Ruth A. Salazar-Camelo, MD, Department of Neurology in the Division of Neuroimmunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.

Because it is readily available in most cases, the albumin index "could be factored into the CSF profile analysis alongside the white blood cell count and protein levels; and it might serve as an additional argument when evaluating whether a patient could have a more severe, widespread inflammation — and as such, might need a more aggressive treatment approach," Salazar-Camelo added.

The findings were presented here at ANA 2019: 144th Annual Meeting of the American Neurological Association.

Lack of Biomarkers

Neurosarcoidosis occurs in an estimated 5% to 15% of cases of sarcoidosis, with symptoms ranging from vision impairments and seizures to disease of the spinal cord. Its severity ranges from self-limited episodes, such as Bell's palsy, to a chronic, debilitating illness, such as chronic meningitis or encephalomyelitis.

The course of disease, as well as the needed treatment approach, can be tough to predict — and biomarkers to help determine disease severity and outcomes are lacking.

To evaluate the predictive role of the CSF/serum albumin ratio as a surrogate measurement for blood-brain barrier permeability, the investigators performed a retrospective review of 120 patients with definite or probable neurosarcoidosis. They longitudinally followed the patients for at least 18 months.

All were evaluated for their ratio of CSF and serum albumin using age-dependent normal values. Among the 49 patients included in the final analysis, 16 had an albumin index indicating normal blood-brain barrier permeability and 33 had an index indicative of increased blood-brain barrier permeability.

Those with an elevated albumin index at baseline showed significantly higher levels of disability at the latest follow-up of more than 30 months compared with patients with a normal index, as assessed by median modified Rankin scale (mRankin, 3.0 v 2.0; P = .03).

In addition, an increasing albumin index value was positively correlated with a greater disability score at latest clinical follow-up (Spearman's rho, 0.385; P = .005). Higher levels of CSF protein at baseline were also associated with higher disability at latest follow-up (rho, 0.323; P = .02).

Importantly, none of the patients with normal albumin index had a worsening of their disability by mRankin score during the follow-up.

The albumin index may reflect processes in blood-brain barrier dysfunction that are related with worsening disease, Salazar-Camelo said.

"We suspect that blood-brain barrier dysfunction in neurosarcoidosis is not only a consequence of inflammation in the central nervous system but it might play a role in the chronicity, localization, and extension of the granulomatous inflammation," she added.

Even though the albumin index is potentially already available in lab results, it is not a parameter that is usually looked at during CSF analysis.

"This is not a test that would need to be ordered as extra in most cases, as it is easily calculated from values needed for the IgG index," Salazar-Camelo noted. The IgG index is a CSF parameter commonly ordered when neuroinflammatory conditions are in the differential.

Significant Role in Other Neurologic Conditions

Recent research has shown potential significance of an increased albumin index in other neuroimmunological conditions. One study published in 2018 suggested that the index represents a biomarker for severity prediction in neuromyelitis optica spectrum disorders. Another study, published in 2015, suggested a role for the index in multiple sclerosis (MS) in predicting greater disability.

In the latter study, however, the findings in relation to MS were not as consistent in the clinical setting as seen in the research, Tomas Uher, MD, PhD, a co-author on that study, told Medscape Medical News.

"Associations were relatively strong at a group level, but not satisfactory for individual use," said Uher, of the Department of Neurology and Center of Clinical Neuroscience, Charles University and General University Hospital, Prague, Czech Republic.

"Indeed, the vast majority of MS patients have/had [albumin index] in normal ranges," he said. "It was surprising that even normal values . . . correlated well with magnetic resonance imaging [MRI] markers. There was only weak or absent association with clinical outcomes, because the sample of patients was young, with low disability, and followed over a short period of time."

Uher pointed out several limitations of the albumin index, including the potential to be influenced by degenerative spine diseases and that it is highly affected by CSF flow. If there are spinal lesions in the lower thoracic spine, the albumin index tends to also be higher, he added.

"It is also important, which portion of CSF is analyzed," Uher said. First portions of CSF in milliliters may have a higher protein concentration compared with last portions, he explained.

In disorders in which a higher rate of blood-brain barrier disruption is present, the albumin index "might have even greater usefulness," he said.

Notably, Uher and his colleagues found no association between albumin index and MRI measures in MS patients who were already taking other treatments.

"Maybe treatment has potential to improve [blood-brain barrier] integrity leading to loss of association with other measures," he speculated. "It would be interesting to see if this is also present in another diagnoses."

The study was funded in part by the Bart McLean Fund for Neuroimmunology Research. The investigators and Uher have disclosed no relevant financial relationships.

ANA 2019: 144th Annual Meeting of the American Neurological Association: Abstract M295. Presented October 14, 2019.

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