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Look Before You Leap: Test for Mimics of Small Vessel Primary Angiitis of the CNS Before Jumping to Brain Biopsy

By Daniel J. Bonthius, MD, PhD | Winter 2023

Mimics of pediatric small vessel primary angiitis of the central nervous system. CM Stredny, MM Blessing, V Yi, et al. Annals of Neurology 2023;93:109-119.

What the researchers did:

Primary angiitis of the central nervous system in children is a rare, but serious, disease. Its signs and symptoms, which often occur in previously healthy children, include altered mental status, headaches, seizures, and focal neurologic deficits. The disease is an inflammatory vasculitis that is restricted to the central nervous system. If the inflamed brain vessels are medium or large in size, then primary angiitis of the central nervous system is diagnosable by angiography. However, in many cases, only small vessels are involved. In these cases, referred to as “small vessel primary angiitis of the central nervous system,” the angiography will be negative, and the diagnosis requires brain biopsy. Because brain biopsy is an invasive procedure with some associated potential morbidity, it would be highly desirable to avoid brain biopsy whenever possible. Emerging evidence suggests that other inflammatory conditions of the nervous system may mimic primary angiitis of the nervous system. Furthermore, some of these conditions may be diagnosable without a brain biopsy. To investigate this possibility, Dr. Coral Stredny and her colleagues at Boston Children’s Hospital conducted a retrospective study in which they reviewed all cases of suspected small vessel primary angiitis of the CNS in children over recent years who underwent brain biopsy at their institution and determined their ultimate diagnosis.

What the researchers found:

The investigators identified 21 children over a 19-year period who underwent brain biopsy for suspected small vessel angiitis of the CNS. Of these 21 patients, 14 of them (two thirds) were ultimately diagnosed with a disease other than primary angiitis of the CNS. The most common of these unexpected diseases was anti-myelin oligodendrocyte glycoprotein antibody associated disease (anti-MOG disease), which was diagnosed in nine patients. Other diagnoses included central nervous system-restricted hemophagocytic lymphohistiocytosis (in 3 patients), anti-GABAA receptor encephalitis (in 1 patient) and Aicardi-Goutieres syndrome (in 1 patient). Importantly, these alternative diagnoses can now all be diagnosed without the need for a brain biopsy. Specifically, anti-MOG disease and anti-GABAA receptor encephalitis can be diagnosed through antibody testing on CSF, while central nervous system-restricted hemophagocytic lymphohistiocytosis and Aicardi-Goutieres syndrome can be diagnosed by whole exome sequencing.

What the research means:

Pediatric small vessel primary angiitis of the central nervous system is a neuroinflammatory disease that can be mimicked, clinically and radiographically, by multiple other disorders. Ultimately, the diagnosis of this disease requires a brain biopsy. However, many of the diseases in the differential diagnosis can be diagnosed with non-invasive testing. One of the most common mimickers of pediatric small vessel primary angiitis of the central nervous system is anti-MOG disease, which can be diagnosed by lumbar puncture. The results of this study underline the importance of considering and recognizing mimics of the disease that should prompt additional non-invasive testing prior to embarking upon brain biopsy. Promptly testing for these mimics can avoid an invasive brain biopsy and can accelerate appropriate treatment.