Elsevier

Clinical Radiology

Volume 71, Issue 1, January 2016, Pages 96-106
Clinical Radiology

Pictorial Review
Imaging of neurosarcoidosis: common, uncommon, and rare

https://doi.org/10.1016/j.crad.2015.09.007Get rights and content

Sarcoidosis is an idiopathic inflammatory disease that may affect any organ system and have protean manifestations. Neurosarcoidosis refers to involvement of the central nervous system and may occur in patients with known sarcoidosis, or be the initial manifestation of the disease. In the latter, it can be a source of considerable confusion, given the non-specific imaging appearance. The aim of this review is to describe the imaging spectrum of neurosarcoidosis, including follow-up imaging and superimposed infections, which may occur secondary to immunosuppression. An increased awareness of this great mimicker could potentially expedite diagnosis and reduce morbidity.

Introduction

Sarcoidosis is an idiopathic, non-infectious inflammatory disorder characterised by formation of non-caseating granulomas.1, 2, 3, 4 It may affect any organ system, although the involvement of the lungs, skin, and lymph nodes is most frequently observed.1, 3 The disease most commonly affects African-Americans and persons of Scandinavian descent, and is often seen in the third and fourth decades.2, 3, 5 The underlying aetiology has been variously attributed to infection, genetic predisposition, and environmental toxins, but continues to remain elusive.4, 5, 6 It is felt that the disease likely reflects an exaggerated response to a specific but unidentified antigen.4, 6

Neurosarcoidosis (NS) refers to the involvement of the central nervous system (CNS) and is seen on imaging in approximately 10% of patients with systemic sarcoidosis, even though pathological CNS involvement is observed in about 15–25% of patients on post-mortem studies.1, 2, 3 Clinical involvement is even less common, occurring in about 5% of patients.1, 3, 7 The disease can have protean neurological manifestations, although patients most frequently present with cranial nerve dysfunction or aseptic meningitis5, 6; however, based on the site of involvement, other presentations may include hypopituitarism or diencephalic syndromes (hypophyseal involvement), seizures, cognitive decline (parenchymal disease), or myelopathic symptoms (spinal involvement).1, 4, 6, 7, 8

Histopathologically, sarcoidosis is characterised by formation of non-caseating granulomas, primarily composed of epitheloid cells, helper T-cells and Langerhans' giant cells.4, 5, 9 Within the CNS, the disease has a propensity to involve the basal meninges.5, 7 The process often spreads to the nearby structures; commonly involving the pituitary–hypothalamic axis and optic chiasm.8 Preferential spread of inflammation along the perivascular Virchow–Robin spaces at the base of the brain leads to perivascular inflammation and parenchymal granulomas9, 10 (Fig 1).

Clinically, the diagnosis of NS relies on Zajicek criteria wherein the diagnosis is considered definite if there is biopsy confirmation from neural tissue, probable if there is evidence of neurological inflammation with systemic disease and possible when the presentation is typical and other potential causes have been excluded.5, 8, 9 Histopathological tissue confirmation forms the basis of diagnosis as there is paucity of reliable laboratory tests. The Kveim test has fallen out of favour due to risk of infection and is not approved by the US Food and Drug Administration.5 Values of serum/cerebrospinal fluid (CSF) angiotensin converting enzyme are variably abnormal and neither sensitive nor specific.3, 6 Similarly, the CSF is often abnormal but lacks specificity.3, 5, 8 Positive gallium-67 scintigraphy, showing both the lambda (uptake in bilateral hilar and right paratracheal nodes) and panda signs (symmetric uptake in bilateral lacrimal and parotid glands) is considered specific for sarcoidosis, but is not very sensitive, occurring in only about 60% of cases.11 In these cases, histopathological demonstration of systemic involvement in a patient with neural inflammation (as shown on contrast-enhanced craniospinal magnetic resonance imaging [MRI]) is a reasonable option if neural tissue biopsy is not feasible. 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) can be especially useful in such cases to search for possible biopsy site, and is more sensitive than gallium-67 to detect occult systemic involvement (Fig 2). These patients are also more likely to benefit from high-resolution computed tomography (CT) of the thorax, measurement of the CD4/CD8 ratio in bronchoalveolar fluid, or conjunctival biopsy (positive in up to 38% of NS patients, even in the absence of ocular disease) to detect extra CNS involvement and are being used more frequently.5

Often, the patients already carry the diagnosis of sarcoidosis by the time CNS involvement is discovered; however, neurological involvement may be the first or the only manifestation and can be a source of considerable confusion. The following sections discuss the protean imaging manifestations of NS. It should be noted, however, that as the imaging findings are often non-specific, the differential considerations in any given case tend to be broad, based on the predominant pattern of involvement (Table 1) and a detailed discussion about the various conditions that may mimic NS is beyond the scope of this text. A quick glance at the patient's demographics, history of presenting illness, past medical history, and clinical and biochemical findings could help narrow down the imaging-based diagnostic possibilities and is desirable, although not always available. Nevertheless, isolated NS remains a diagnosis of exclusion.

Section snippets

Brain

Within the CNS, the involvement of neuroparenchyma proper may manifest as multiple or solitary supra/infratentorial lesions, seen in about 35% and 10% of patients with NS, respectively.6, 7 The involvement is felt to be secondary to the spread of inflammation from the leptomeninges along the Virchow–Robin spaces.2, 7 Smaller parenchymal granulomas may be seen only after intravenous contrast medium administration6 (Fig 3). Larger masses are often iso-intense on T1-weighted images (T1WI) and show

Spine

Spinal involvement in NS was previously felt to be rare and affect less than 10% of patients.3 This perception is, however, changing with widespread use of MRI for spinal imaging. Currently, intramedullary involvement is reported in up to 25% of patients with NS and most commonly involves the cervical and upper thoracic spine.3, 5, 7, 8 Lesions often extend over multiple segments and show T1/T2 prolongation and patchy post-contrast enhancement, which is often peripheral.2, 4 There is often

Bones

Osseous involvement occurs in approximately 13% of patients with sarcoidosis and is felt to be underestimated, as most lesions are clinically asymptomatic.3, 7 It often involves the long tubular bones and appendicular skeleton.3 Involvement of the skull and vertebral column is uncommon, but usually involves the lower thoracic and upper lumbar spine.17 Lesions are most commonly lytic, but may appear as mixed or sclerotic on CT3, 7 (Fig 14). There may be an associated soft-tissue component. At

Follow-up imaging

Corticosteroids form the first-line therapy for patients with NS, with steroid-sparing immuno-suppressants reserved for resistant cases or as co-therapy to avoid side effects from long-term steroids.3, 5, 6 Optimal therapy can achieve clinical remission in about 70% along with variable improvement in imaging findings.5, 7 Interestingly, the two may not necessarily correlate. This is especially true for spinal lesions.3

Rarely, the lesions may paradoxically worsen post-therapy and the possibility

Conclusion

Sarcoidosis may involve the CNS and have protean clinical manifestations. Assessment of the CNS involvement is best done with contrast-enhanced MRI. Unfortunately, the imaging manifestations are broad and non-specific and sarcoidosis remains a diagnosis of exclusion. Imaging, however, may point towards the correct diagnosis, rule out various other disease entities, which mimic NS clinically, may help select the site for biopsy, and is useful to assess changes on follow-up imaging. Given the

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