Beyond the Anterior–Posterior Gradient: An Atypical FDG-PET Pattern in Anti–NMDA Receptor Encephalitis

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A previously healthy woman in her early thirties presented with a subacute onset of neuropsychiatric symptoms, including behavioural changes like agitation, irritability and sleep disturbance over 7–10 days, followed by progressive confusion and apathy. Subsequently, she developed new-onset generalized tonic–clonic seizures, which evolved into refractory status epilepticus and required intensive care management.

There was no definite history of preceding febrile illness or systemic infection, and no prior autoimmune disease. Moreover, there was no known malignancy, and a systematic malignancy workup, including pelvic imaging for ovarian teratoma, was also negative. On examination, the patient had an altered sensorium with prominent neuropsychiatric features. Routine metabolic and infectious investigations were unremarkable. Cerebrospinal fluid analysis showed normal cellularity and biochemistry. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain was unremarkable, with no signal abnormalities or contrast enhancement.

A diagnosis of Anti-n-methyl-d-aspartate (Anti-NMDA) Receptor Encephalitis was established based on compatible clinical features and positive serum anti-NMDA receptor antibodies.

Fluorodeoxyglucose-positron emission tomography (FDGPET) was performed 8 days after symptom onset and 36 hours after the last seizure, in the interictal/post-ictal state, with no electroclinical seizures in the preceding period. The patient was not sedated during FDG uptake; she was on Antiseizure medications (namely Levetiracetam, Valproate and Perampanel). FDG-PET demonstrated diffuse bilateral cortical hypometabolism involving the frontal, temporal, parietal, and occipital cortices. In contrast, there was relative hypermetabolism of the cerebellar hemispheres and vermis [Fig 1]. This contrasts with the previously described anteroposterior gradient, characterised by frontal hypermetabolism and posterior hypometabolism, and therefore represents an atypical metabolic configuration distinct from the classically described anterior–posterior gradient pattern. The basal ganglia showed normal metabolism with symmetrical uptake.

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Fig 1: (A) Scenium database-based stereotactic surface projection (SSP) analysis demonstrating relative hypermetabolism involving the bilateral cerebellar hemispheres and vermis, with diffuse cortical hypometabolism most pronounced in the occipital and parietal cortices; (B) Axial FDG-PET brain images showing diffuse cortical hypometabolism involving bilateral frontal, temporal, parietal and occipital cortices, with relative hypermetabolism of the cerebellar hemispheres and vermis. SD: Standard deviation; SUV: Standardised uptake value; AAL: Automated anatomical labelling; FDG-PET: Fluorodeoxyglucose-positron emission tomography; L: Left; R: Right

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FDG-PET abnormalities in Anti–NMDA Receptor Encephalitis are dynamic and stage-dependent. Early disease may show focal cortical hypermetabolism, whereas advanced or prolonged disease may demonstrate widespread cortical hypometabolism due to synaptic dysfunction because of antibody-mediated NMDA receptor internalisation.^[1] The observed hyper-metabolism in cerebellum probably reflects disinhibition of cerebello–thalamo–cortical circuits, suggesting network-level/connectome dysfunction rather than isolated cortical pathology.^[2] Importantly, FDG-PET interpretation must consider confounding factors, including timing of imaging, seizure-related metabolic changes (ictal vs post-ictal state), and effects of sedation, all of which can significantly influence cerebral glucose metabolism.

The present case highlights a rare and atypical FDG-PET metabolic configuration characterised by diffuse cortical hypometabolism with prominent cerebellar/vermian hypermetabolism and occipital predominance.^[3] Recognition of such atypical configurations or imaging patterns is clinically relevant, particularly when MRI is normal, as FDG-PET may provide early diagnostic clues and insights into disease stage and functional connectome involvement.^[4]