Role of 18F-FDG-PET imaging in the diagnosis of autoimmune encephalitis

Abstract

Establishing the clinical diagnosis of autoimmune encephalitis can be challenging as patients present with various unspecific symptoms.1Graus F Titulaer MJ Balu R et al.A clinical approach to diagnosis of autoimmune encephalitis.Lancet Neurol. 2016; 15: 391-404Summary Full Text Full Text PDF PubMed Scopus (1935) Google Scholar In a Position Paper1Graus F Titulaer MJ Balu R et al.A clinical approach to diagnosis of autoimmune encephalitis.Lancet Neurol. 2016; 15: 391-404Summary Full Text Full Text PDF PubMed Scopus (1935) Google Scholar in The Lancet Neurology, Francesc Graus and colleagues proposed an initial diagnostic work-up relying on conventional neurological evaluation and standard diagnostic tests such as MRI, CSF sampling, and EEG. This approach would enable clinicians to make a timely diagnosis of “possible autoimmune encephalitis”, allowing initiation of immunotherapy. In a second step, the authors proposed comprehensive antibody testing to help to establish a diagnosis of “probable autoimmune encephalitis” or “definite autoimmune encephalitis”, potentially enabling refinement of treatment.1Graus F Titulaer MJ Balu R et al.A clinical approach to diagnosis of autoimmune encephalitis.Lancet Neurol. 2016; 15: 391-404Summary Full Text Full Text PDF PubMed Scopus (1935) Google Scholar With regards to brain imaging, the proposed diagnostic framework solely relies on MRI. However, as acknowledged by Graus and colleagues,1Graus F Titulaer MJ Balu R et al.A clinical approach to diagnosis of autoimmune encephalitis.Lancet Neurol. 2016; 15: 391-404Summary Full Text Full Text PDF PubMed Scopus (1935) Google Scholar limbic encephalitis is known to occur in a relevant fraction of patients with normal or non-specific MRI findings.2Baumgartner A Rauer S Mader I Meyer PT Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types.J Neurol. 2013; 260: 2744-2753Crossref PubMed Scopus (141) Google Scholar In limbic encephalitis, 18fluorodeoxyglucose (18F-FDG) PET imaging has been reported to typically reveal medial temporal lobe hypermetabolism even in MRI-negative or inconclusive cases, suggesting that it could be more sensitive than MRI (figure).2Baumgartner A Rauer S Mader I Meyer PT Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types.J Neurol. 2013; 260: 2744-2753Crossref PubMed Scopus (141) Google Scholar In the Position Paper1Graus F Titulaer MJ Balu R et al.A clinical approach to diagnosis of autoimmune encephalitis.Lancet Neurol. 2016; 15: 391-404Summary Full Text Full Text PDF PubMed Scopus (1935) Google Scholar by Graus and colleauges, this important evidence is mentioned only as a footnote in panel 2. Although we commend the Position Paper,1Graus F Titulaer MJ Balu R et al.A clinical approach to diagnosis of autoimmune encephalitis.Lancet Neurol. 2016; 15: 391-404Summary Full Text Full Text PDF PubMed Scopus (1935) Google Scholar we suggest a stronger consideration of 18F-FDG-PET imaging in supporting the diagnosis of autoimmune encephalitis. This proposal is also supported by results of one of the largest multimodal neuroimaging case series2Baumgartner A Rauer S Mader I Meyer PT Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types.J Neurol. 2013; 260: 2744-2753Crossref PubMed Scopus (141) Google Scholar in limbic encephalitis, which demonstrated that 18F-FDG-PET imaging might even have a diagnostic role in patients with autoantibody-negative limbic encephalitis. Furthermore, the differences in PET-based glucose metabolism patterns in such patients support the existence of limbic encephalitis subtypes associated with antibodies that are yet to be identified.2Baumgartner A Rauer S Mader I Meyer PT Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types.J Neurol. 2013; 260: 2744-2753Crossref PubMed Scopus (141) Google Scholar Apart from the stated potential of 18F-FDG-PET imaging for improved early diagnosis of limbic encephalitis, we propose the following scenarios in which diagnoses of autoimmune encephalitis could be supported in the future by this molecular imaging approach. First, in limbic encephalitis and in other autoimmune encephalitis subtypes 18F-FDG-PET imaging also shows, in a relevant number of patients, extra-limbic metabolic abnormalities (mainly in the brainstem, cerebellum, or cerebral cortex). These PET findings were associated with clinical symptoms and active disease status more strongly than the MRI findings.3Ances BM Vitaliani R Taylor RA et al.Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates.Brain. 2005; 128: 1764-1777Crossref PubMed Scopus (372) Google Scholar Thus, 18F-FDG-PET imaging has the potential to improve estimation of disease severity in patients with autoimmune encephalitis, with implications for follow-up evaluation and therapy monitoring.4Trevino-Peinado C Arbizu J Irimia P Riverol M Martínez-Vila E Monitoring the effect of immunotherapy in autoimmune limbic encephalitis using 18F-FDG PET.Clin Nucl Med. 2015; 40: e441-e443Crossref Scopus (11) Google Scholar Second, in the future, 18F-FDG-PET imaging might have a role in the diagnosis of anti-NMDA receptor encephalitis, an entity for which MRI has poor sensitivity.5Dalmau J Lancaster E Martinez-Hernandez E Rosenfeld MR Balice-Gordon R Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.Lancet Neurol. 2011; 10: 63-74Summary Full Text Full Text PDF PubMed Scopus (1758) Google Scholar Several 18F-FDG-PET imaging studies in these patients have shown metabolic abnormalities in different brain areas, including the frontal, temporal, and occipital lobes, and the basal ganglia, cerebellum, and brainstem.2Baumgartner A Rauer S Mader I Meyer PT Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types.J Neurol. 2013; 260: 2744-2753Crossref PubMed Scopus (141) Google Scholar, 6Leypoldt F Buchert R Kleiter I et al.Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease.J Neurol Neurosurg Psychiatry. 2012; 83: 681-686Crossref PubMed Scopus (137) Google Scholar Again, the PET findings were more clearly associated with the clinical picture (ie, basal ganglia involvement and presence of movement disorders), disease severity, and recovery after therapy than the MRI findings.6Leypoldt F Buchert R Kleiter I et al.Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease.J Neurol Neurosurg Psychiatry. 2012; 83: 681-686Crossref PubMed Scopus (137) Google Scholar Finally, on a practical note, 18F-FDG-PET imaging is an attractive future addition to the proposed work-up for two reasons. First, whole-body 18F-FDG-PET imaging is often done in patients with paraneoplastic syndromes to screen for malignancy. Such whole-body imaging can easily be extended to cover the brain without increases in radiation burden. Second, in the past few years, with the introduction of combined PET and MRI systems, many groups have already started to replace MRI with PET–MRI in the diagnostic algorithm for other brain disorders.7Teipel S Drzezga A Grothe MJ et al.Multimodal imaging in Alzheimer's disease: validity and usefulness for early detection.Lancet Neurol. 2015; 14: 1037-1053Summary Full Text Full Text PDF Scopus (185) Google Scholar We encourage feasibility studies for the use of this method in autoimmune encephalitis. We agree that, as a next step, the proposed diagnostic framework for autoimmune encephalitis needs to be tested in clinical practice.8Antoine JC Autoimmune encephalitis: paving the way for early diagnosis.Lancet Neurol. 2016; 15: 349-350Summary Full Text Full Text PDF Scopus (11) Google Scholar Further testing can also provide an opportunity to assess the contribution of 18F-FDG-PET imaging in the scenarios discussed here. In parallel, the imaging community needs to refine standard procedures for acquisition and reading of PET imaging data in autoimmune encephalitis, and to confirm the results in large prospective studies. We declare no competing interests. Role of 18F-FDG-PET imaging in the diagnosis of autoimmune encephalitis – Authors' replyWe thank Silvia Morbelli and colleagues for their comments on the role of brain 18fluorodeoxyglucose (18F-FDG) PET imaging in the management of autoimmune encephalitis. We agree about the potential use of 18F-FDG-PET in the diagnosis and evaluation of the response to immunotherapy in autoimmune encephalitis.1 However, two reasons led us to downplay the role of 18F-FDG-PET imaging in our Position Paper.2 First, this technique remains unavailable in many hospitals and rarely can be obtained on an emergency basis. Full-Text PDF