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Reevaluating the relevance of 18F-FDG PET findings for diagnosis of neurosarcoidosis: a case series



The diagnosis of neurosarcoidosis (NS) remains challenging due to the difficulty to obtain central nervous system (CNS) biopsies. Various diagnostic parameters are considered for the definition of possible, probable and definite NS. Magnetic resonance imaging (MRI) is the imaging gold standard and considered in diagnostic criteria. Fluorodeoxyglucose positron emission (18F-FDG PET) is sometimes performed additionally to identify possible systemic biopsy targets. However, at present, its findings are not incorporated into the diagnostic criteria for neurosarcoidosis (NS).


We conducted a single center retrospective search for the period 2020–2022, for patients with neurological symptoms in a diagnostic context of suspected NS who underwent MRI and additional 18F-FDG PET scans to identify potential hypermetabolism in the CNS and biopsy targets.


We identified three cases of NS, where Gadolinium-enhanced MRI scans did not show abnormalities while 18F-FDG PET revealed hypermetabolic lesions in areas of the CNS. Additional MRI scans were still inconclusive for structural changes. We diagnosed a “probable” NS in all cases with histopathological confirmation of systemic sarcoidosis which led to an intensified therapy regime.


18F-FDG PET is an early indicator for metabolic changes. It appears to be a useful add-on to improve accuracy of diagnostic criteria in suspected NS without MRI findings.


Sarcoidosis is an inflammatory disease typically characterized by formation of epithelioid cell granuloma in various organs, with around 25–35% neurological involvement (neurosarcoidosis, NS) [1]. In contrast to lung or lymph node affection, NS has a higher rate of relapse probability and more severe consequences for long-term disability. Therefore, stronger treatment regimens are commonly necessary for controlling neurosarcoidosis [2]. Granulomatous inflammation sites may reside in any central or peripheral nervous structures (CNS, PNS) leading to very heterogeneous clinical manifestations and thus often pose a diagnostic challenge. Diagnostic tools typically include the analyses of blood and cerebrospinal fluid (CSF), magnet resonance imaging (MRI) of the CNS and further electrophysiological tests (neurography, myography). Fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an established sensitive method to detect increased cell metabolism. In a review of previous literature, we identified three case reports describing discordances between contrast enhanced MRI and 18F-FDG PET, suggesting additional value of 18F-FDG PET to diagnose NS [3,4,5]. However, to date 18F-FDG PET findings are currently not taken into account when making a diagnosis for possible, probable or definite NS [6].

This report describes three cases where findings by 18F-FDG PET were relevant for the diagnosis of NS, underlining the question if 18F-FDG PET findings should be considered as a criterion for NS.

Case presentation

From 2020–2022 we observed three cases of probable NS, where Gadolinium-enhanced MRI scans did not show any abnormalities while 18F-FDG PET revealed hypermetabolic lesions in areas of the CNS. Two patients had a new onset of neurologic symptoms of unknown etiology without other systemic symptoms. The remaining patient was a referral with known systemic sarcoidosis but till then undiagnosed NS. Clinical manifestations were heterogeneous ranging from visual disturbance to sensory spinal cord syndrome or spastic/ataxic gait disorder (Table 1). All these patients presented with a pleocytosis in the CSF. Since MRI was negative or inconclusive 18F-FDG PET was performed to (1) identify MRI-negative CNS inflammation and/or (2) screen for the extent of systemic inflammatory sites in order to evaluate best medical treatment options (Table 1).

Table 1 Diagnostic results of three patients

In the CNS, we identified areas of increased tracer uptake in the cervical and thoracic spinal cord in two patients. The other case presented with increased uptake within the precuneus area bilaterally (Fig. 1). Pulmonary and lymph node manifestations of sarcoidosis were already diagnosed during chest X-ray and computed tomography (CT) scan in two cases (patient 2 and 3). Patient 1 was first diagnosed by 18F-FDG PET scan with pulmonary lymph node manifestation. All of them had histopathological confirmation of suspected sarcoidosis in a lymph node biopsy. Neural tissue was not obtained due to sensitive regions. In knowledge of 18F-FDG PET abnormalities, an additional MRI scan was performed in every patient with non-standard VIBE sequences for spinal cord imaging, but remained inconspicuous. A follow up 18F-FDG PET scan was not performed. We diagnosed all three patients with a “probable” NS taking the positive 18F-FDG PET scans as an imaging substitute for MRI results. Patients 1 and 2 were started on immunosuppressive treatment with a steroid pulse resulting in a remission of symptoms in Patient 2 and visual improvement with residual deficits in Patient 1. Both received oral prednisolone in a tapering dose (1 mg/kg bodyweight) with additional azathioprine or methotrexate as a long-term treatment. The treatment regime for patient 3 was changed from methotrexate to mycophenolate-mofetil with additional oral prednisolone tapering dose (1 mg/kg bodyweight). In our outpatient clinic follow up (2–2.5 years depending on the patient case), all three patients remained stable without new disease relapses. Patient 1 is currently treatment-free after two years of treatment and remains stable. sIL2R as a suggestive disease activity marker was normal in a routine control.

Fig. 1
figure 1

18F-FDG PET and MRI scans of three patients. A.1B.1 18F-FDG PET (A1 sagittal PET Data; B1 transaxial fused PET/CT-Data) showing intense hypermetabolism in the lower thoracical spinal cord (blue arrow). C.1 Transaxial MRI-scan (T1_TSE_FS) showing no abnormal Gadolinium enhancement in the lumbar spinal cord (blue arrow). A.2B.2 18F-FDG PET (A2 sagittal PET Data; B2 transaxial fused PET/CT-Data) showing hypermetabolism in the cervical spinal cord (blue arrow). C.2 Transaxial MRI-scan (T1_TSE_FS) showing no abnormal Gadolinium enhancement in the cervical spinal cord (blue arrow). A.3B.3 18F-FDG PET (A3 sagittal PET Data; B3 transaxial fused PET/CT-Data) showing bilateral hypermetabolism the precuneus region (blue arrow). C.3 Transaxial MRI-scan (T1_MPRAGE) showing no abnormal Gadolinium enhancement in precuneus region (blue arrow)


We present clinical and imaging data of three patients with “probable” NS. In all patients, we observed discordances between the imaging standard (Gadolinium-enhanced MRI) and metabolic imaging using 18F-FDG PET in the CNS. In the end, all presented cases had histopathological lymph node confirmation of sarcoidosis.

The review of literature underlined the relevance of 18F-FDG PET findings in the diagnostic pathway with three similar cases reported from 2012 on. Recently, the clinical utility of 18F-FDG PET was investigated in 110 patients with suspected NS who underwent 18F-FDG PET in a retrospective single-center approach [7]. In total, 27 of 110 patients were diagnosed with possible, probable or definite NS. Remarkably, upon those 19 of 27 (70%) patients with NS had 18F-FDG PET avidities suspicious of NS. Also, among those 27 patients, certain 18F-FDG PET and MRI discordances were observed. Authors conclude, that 18F-FDG PET should be included to the diagnostic evaluation to facilitate a “probable” NS diagnosis if other imaging modalities remain inconclusive. With our clinical experience, we observe a certain group of patients at higher risk for prolonged diagnosis of NS, namely those with (1) exclusive neurological symptoms suggestive of chronic inflammatory disease but inconclusive MRI scans and those with (2) known sarcoidosis, unclear neurological symptoms and inconclusive MRI scans. 18F-FDG PET provides a useful supportive diagnostic tool in cases where MRI and CT scans remain inconclusive concerning CNS inflammation. 18F-FDG PET is a highly sensitive imaging test for changes of glucose metabolism and may detect inflammatory changes better than standard MRI imaging. Concerning MRI imaging modalities, non-standard contrast enhanced axial VIBE sequences for spinal cord imaging might be a more sensitive way to detect subtle inflammatory leptomeningeal enhancement and should be considered when NS is suspected. However, 18F-FDG PET avidities especially in the CNS need to be carefully interpreted because they are not specific to differentiate NS from other e.g. inflammatory conditions. We believe that systemic tracer uptake (e.g. pulmonary) paired with CNS avidity is helpful as a criterion suggestive of NS. The result of isolated positive 18F-FDG PET findings in the CNS pose a diagnostic challenge because the difficulty of obtaining tissue for histopathological analysis remains. Therefore, 18F-FDG PET results need to be interpreted in the overall diagnostic context when a chronic-inflammatory condition is suggestive after the canonical diagnostic workflow. However, with limited data available further (prospective) studies are needed to elucidate the possible gain in the accuracy of the diagnosis of NS by 18F-FDG PET; thus, a systematic and prospective setting should be emphasized.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.



Central nervous system


Fluorodeoxyglucose positron emission tomography


Magnet resonance imaging


Neurofilament light chain




Soluble interleukin 2 receptor


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Data obtained during routine diagnostics.

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Authors and Affiliations



JC/GM/CF/GB/VS: case description, acquisition of data, analysis, and interpretation. JC/CF/VS: manuscript preparation and revision. All authors read and approved the final manuscript.

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Correspondence to Jessy Chen.

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Chen, J., Metzger, G., Furth, C. et al. Reevaluating the relevance of 18F-FDG PET findings for diagnosis of neurosarcoidosis: a case series. Neurol. Res. Pract. 6, 12 (2024).

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