Simultaneous 18F- FDG PET/MRI in Autoimmune Limbic Encephalitis.

Limbic encephalitis is an autoimmune disorder characterized by inflammation of the brain with rapidly progressing dementia which requires definitive neurological evaluation. We describe both clinical as well as imaging findings in a case of limbic encephalitis using positron emission tomography/magnetic resonance imaging.

Introduction

Autoimmune limbic encephalitis is an autoimmune-mediated inflammation typically affecting the medial temporal lobes and other limbic structures (cingulate gyrus, orbital cortex, and hypothalamus).[1] Patients affected usually show rapidly progressive short-term memory deficits, psychiatric symptoms, and seizures. Final diagnosis requires either neuropathological or neuroradiological interventions for the involvement of the limbic system besides the typical clinical syndrome. We here present a clinical case of limbic encephalitis with findings of simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI).

Case Report

A 47-year-old female presented with recurrent generalized myoclonic jerks worsening over a period of the past 6 months accompanied by progressive memory loss and worsening behavioral disturbances. Routine blood investigations including hemogram, serum electrolytes, routine biochemistry, viral markers, thyroid profile, and a complete cerebrospinal fluid (CSF) analysis were normal. Two previous MRI brain examinations were also reported normal. Electroencephalography (EEG) record demonstrated normal background activity with no epileptiform discharge. A clinical suspicion of neurodegenerative disorder versus paraneoplastic encephalitis versus Creutzfeldt-Jakob disease was raised, and the patient was referred for simultaneous PET/MRI. The patient also tested negative for paraneoplastic, voltage-gated potassium channel, and NMDA (N-methyl-D-aspartate) antibodies.

She underwent simultaneous integrated fluorine-18 fluorodeoxyglucose (18F-FDG) PET/MRI 60 min after injection 8 mCi of 18F-FDG. MR component of the simultaneous PET/MR demonstrated mild fluid-attenuated inversion recovery (FLAIR) and T2 hyperintensity in the brain involving the bilateral medial temporal lobes including the hippocampus, bilateral basal ganglia and cingulate gyrus with minimal gyral thickening/swelling and no evidence of diffusion restriction, hemorrhage, or contrast enhancement. The corresponding simultaneously acquired PET and PET/MRI fusion images demonstrated marked FDG hypermetabolism in bilateral basal ganglia involving the caudate nuclei and putamen and asymmetrical FDG hypermetabolism in bilateral medial temporal lobes (right > left) [Figure 1]. The whole-body simultaneous PET/MRI (Positron Emission Tomography/Magnetic Resonance Imaging) did not show any abnormal FDG uptake elsewhere in the body. On the basis of the clinical and PET/MR findings, a diagnosis of nonneoplastic limbic encephalitis was rendered.

Figure 1

A 47-year-old female presented with recurrent generalized myoclonic jerks was referred for simultaneous positron emission tomography/magnetic resonance imaging. Fluid-attenuated inversion recovery axial (a and e), postcontrast T1-weighted (b and f), positron emission tomography axial (c and g), and fused PET/MRI images (d and h) images show hyperintensity in bilateral basal ganglia (arrowheads in a). There was no evidence of diffusion restriction. Positron emission tomography (PET) and fused PET/MRI images demonstrate marked hypermetabolism in bilateral basal ganglia (arrowheads in d) involving the caudate nuclei and asymmetrical hypermetabolism in bilateral medial temporal lobes (arrowheads in h) (right > left)

Discussion

Autoimmune limbic encephalitis is divided into two groups – paraneoplastic and nonneoplastic based on whether the antibodies are due to the presence of an underlying tumor, common tumors being squamous cell carcinoma lung, testicular germ cell tumor, and thymic, breast, renal, colonic, esophageal, ureteric bud, and ovarian carcinomas.[1] The nonneoplastic group of patients usually responds favorably to immunotherapy.[2]

The diagnosis of autoimmune encephalitis requires to meet the following five criteria: (1) Subacute onset, (2) Bilateral brain abnormalities on T2 FLAIR MRI, highly restricted to medial temporal lobes, (3) CSF pleocytosis and detectable antibodies in CSF, (4) Abnormal EEG with epileptic or slow-wave activity on temporal lobe, and (5) Reasonable exclusion of other causes of encephalitis.[3]

Definitive diagnosis is characterized by the presence of specific antibody in serum or CSF and response to immunotherapy.[4] On MRI, T2-weighted FLAIR images show hyperintensities with swelling usually restricted to the mesial-temporal cortex. Asymmetric bilateral involvement being most common (60%). Basal ganglia are also frequently involved with less common involvement of the lateral temporal lobe and insula. Contrast enhancement is rare with no diffusion restriction and hemorrhage.

Various studies have demonstrated hypermetabolism on PET even in MRI-negative or inconclusive cases.[5] FDG PET in autoimmune encephalitis usually shows hypermetabolism in the mesial temporal and orbitofrontal cortex, occipital hypometabolism, and symmetrical hypermetabolism in the corpus striatum and amygdala and may even resemble neurodegenerative disease in older patients.[67]

Although PET may help in identifying an underlying disease to some extent, the diagnosis of autoimmune limbic encephalitis is still challenging due to the varied presentation and nonspecific initial laboratory as well as imaging findings. Simultaneous PET/MRI combines high-resolution structural and functional information from multiparametric MRI along with metabolic information from PET to localize the abnormality, to rule out other primary abnormalities in the brain, and to identify any other malignancy in the body to rule out paraneoplastic limbic encephalitis. Although, both FDG PET and MRI have been used for the diagnostic intervention in autoimmune limbic encephalitis, simultaneous PET/MRI holds the dual advantage of providing PET and MRI in single temporal as well as spatial domain. Hence, the role of this imaging modality is instrumental and holds promise in diagnosis of aggregation-induced emission.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.