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A Consensus Panel Establishes Criteria for Diagnosing Neurosarcoidosis

Fitzgerald, Susan

doi: 10.1097/01.NT.0000553609.16741.9d
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ARTICLE IN BRIEF:

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Figure

A consensus group comprising 10 neurologists and four pulmonologists have developed a set of criteria to help physicians sort out suspected cases of neurosarcoidosis, a chronic condition with heterogenous symptoms that is challenging to diagnosis. The group established three categories of diagnosis of neurosarcoidosis: possible, probable, and definite.

Neurosarcoidosis, a chronic condition of unknown etiology that most commonly involves the lungs, lymph nodes, eyes, and skin but can also involve the central and peripheral nervous systems, can be a difficult condition to diagnose.

Clinical symptoms are very heterogeneous and can resemble any number of neurologic conditions. Diagnosing the condition invariably entails ruling out other possible diagnoses using a number of tests, including a physical and neurologic exam, MRI, or other imaging and cerebrospinal fluid testing to look for evidence of infection or malignancy.

Now, in a paper in the December issue of JAMA Neurology, 10 neurologists and four pulmonologists comprising the Neurosarcoidosis Consensus Group have developed a set of criteria to help physicians sort out suspected cases. The group established three categories of diagnosis of neurosarcoidosis: possible, probable, and definite.

Establishing clearly delineated diagnostic criteria will help ensure that the biomarkers and therapies are tested in the right group of people, the authors of the consensus paper wrote, adding: “Development of criteria for diagnosis is essential for the design of clinical trials for neurosarcoidosis.”

“Our goal is to promote optimal patient care,” said Barney Stern, MD, FAAN, professor of neurology at Johns Hopkins University, who was a member of the consensus committee and a lead author of the paper. “Part of the challenge is that you want to treat rapidly, but you have to balance the speed and intensity of treatment with the goal of having a definitive diagnosis.”

The consensus group noted that the presence of granulomas is critical in establishing a diagnosis of sarcoidosis, but things aren't always clear-cut, because granulomas can also be present in other disorders such as infectious and inflammatory diseases, various immunodeficiency states, and malignant neoplasms.

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How the Group Worked

The consensus group reviewed the medical literature from January 1, 2007 to October 1, 2017, and used the best available evidence and clinical experience to develop a set of diagnostic criteria. The paper did not focus on treatment.

Figure. MRI

Figure. MRI

The proposed criteria was then submitted to the executive committee of the World Association of Sarcoidosis and Other Granulomatous Disorders, which reviewed and endorsed them, Dr. Stern said. (See “Proposed Diagnostic Criteria for Neurosarcoidosis.”)

“The goal is to increase diagnostic certainty,” said Dr. Stern, who noted that the new criteria should be helpful for both doctors in the community setting and clinicians at referral centers.

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Why It's a Difficult Diagnosis

“A major challenge regarding NS [neurosarcoidosis] is the difficulty of obtaining neural tissue for histologic and microbiologic analyses,” according to the paper. “If a patient has clinical evidence of nervous system inflammation consistent with NS and pathologic proof of sarcoidosis in another organ system, nervous system involvement representative of the same pathologic process is typically assumed. This assumption may or may not be true, as two or more diseases may coexist.”

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Figure

“Furthermore, for the subset (approximately 10 percent to 19 percent) of patients with presumptive NS and no evidence of systemic extra neural inflammation, the diagnosis can be confirmed only with nervous system biopsy,” which may not be easy depending on the accessibility of the affected site, the consensus group wrote.

If immunosuppressant therapy is started for presumptive neurosarcoidosis, it may make the diagnosis of systemic disease difficult, the paper said, though corticosteroids may be essential for keeping the patient from deteriorating.

Because of these and other challenges, the study authors proposed “a pragmatic approach to the diagnosis of NS that emphasizes the degree of diagnostic certainty.” They said that “defining degree of diagnostic certainty can serve as an important reminder to reconsider the diagnosis at regular intervals, particularly in the absence of an anticipated therapeutic response.”

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Expert Commentary

Tarakad S. Ramachandran, MD, professor of neurology at SUNY Upstate Medical University, agreed that neurosarcoidosis “is a great masquerader, and it mimics many other medical conditions.” He added, “It is one of the most difficult diagnoses to make, so these guidelines will give good guidance to physicians.”

Dr. Ramachandran said he sees about four cases of neurosarcoidosis a year. The last case involved a patient who presented with double vision and headache.

Dr. Ramachandran described the multiple steps he would typically take to arrive at a diagnosis. He shared these notes based on a single case: The patient had cranial nerve palsies with impaired extraocular movements associated with double vision and squint. Spinal tap revealed aseptic meningitis. Serum and CSF ACE titres were elevated. She had pulmonary sarcoidosis as well. Dr. Ramachandran said the diagnosis was made by a history, physical, past history and work-up including a biopsy showing a noncaseating lesion of sarcoid, classic hilar adenopathy, elevated ACE titre, and brain MRI with meningeal enhancement.

Mohammad Abdoli, MD, a clinical fellow in multiple sclerosis (MS) and a resident in neurology at University of Ottawa, published a paper in 2015 in Multiple Sclerosis and Related Disorders in which he and a colleague described the challenges of diagnosing neurosarcoidosis, in part because of its many modes of presentations. Symptoms may resemble MS, for instance, or lymphoma, or infectious diseases such as Lyme disease. Dr. Abdoli recently had a case that presented with symptoms characteristics of a brain tumor, but a biopsy found the patient had neurosarcoidosis.

Without a confirmatory biopsy showing evidence of sarcoidosis in the nervous system, patients are often left with a diagnosis of “possible neurosarcoidosis,” Dr. Abdoli said. His published paper also contained suggested diagnostic criteria, which were fairly similar to the new ones outlined in JAMA Neurology.

Dr. Abdoli said getting a correct diagnosis is important so that treatment can be optimized as quickly as possible. Neurosarcoidosis that involves the central nervous system, can, without proper treatment, result in disability or even death in about 5 to 10 percent of patients, he said.

Although there may be few new ideas in this new paper, its criteria should be useful for clinicians as a guideline to make the diagnosis with more confidence and treat patients with the proper medication, Dr. Abdoli continued. Having a consensus criteria may also be useful in terms of finding uniform groups of patient with NS for research studies.

The challenge would be relying on a pathological confirmation for definite diagnosis, Dr. Abdoli said, although he added that it might not be feasible for many patient suspicious for neurosarcoidosis. “Future research can be considered in the future update of criteria,” he said, “and hopefully other laboratory or imaging findings can be used as a substitute for earlier and easier diagnosis of NS.”

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Disclosures

Dr. Stern has received royalty payments from UptoDate, Inc., for an article on neuroscarcoidosis and received payments for serving as an expert witness in legal procedings related to narcosarcoidosis. As an associate editor of Neurology Today, he has received support from the AAN.

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Proposed Diagnostic Criteria for Neurosarcoidosis

POSSIBLE:

  1. The clinical presentation and diagnostic evaluation suggest neurosarcoidosis, as defined by the clinical manifestations and MRI, CSF, and/or/EMG/NCS findings typical of granulomatous inflammation of the nervous system and after rigorous exclusion of other causes.
  2. There is no pathological conformation of granulomatous disease.

PROBABLE:

  1. The clinical presentation and diagnostic evaluation suggest neurosarcoidosis, as defined by the clinical manifestations and MRI, CSF, and/or EMG/NCS findings typical of granulomatous inflammation of the nervous system after rigorous exclusion of other causes.
  2. There is pathologic conformation of systemic granulomatous disease consistent with sarcoidosis.

DEFINITE:

  1. The clinical presentation and diagnostic evaluation suggest neurosarcoidosis, as defined by the clinical manifestations and MRI, CSF, and/or EMG/NCS findings typical of granulomatous inflammation of the nervous system after rigorous exclusion of other causes.
  2. The nervous system pathology is consistent with neurosarcoidosis. Type a: Extraneural sarcoidosis is evident. Type b: No extramural sarcoidosis is evident (isolated CNS sarcoidosis).
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Link Up for More Information

•. Stern BJ, Royal W III, Gelfand JM, et al. Definition and consensus diagnostic criteria for neurosarcoidosis: From the Neurosarcoidosis Consortium Consensus Group https://jamanetwork.com/journals/jamaneurology/fullarticle/2696970. JAMA Neurol 2018:75(12):1546–1553.
    © 2019 American Academy of Neurology