Ophelia Syndrome: Acute Stupor as a Primary Manifestation of Hodgkin Lymphoma Diagnosed by Fluorodeoxyglucose Positron Emission Tomography.

Ophelia syndrome is a rare form of paraneoplastic limbic encephalitis associated with Hodgkin lymphoma, mediated by autoantibodies targeting the metabotropic glutamate receptor type 5 (mGluR5). It is characterized by a spectrum of neurological and psychiatric manifestations. Impaired consciousness progressing to stupor as the presenting feature is uncommon and, combined with a non-diagnostic structural MRI, can substantially delay diagnosis and treatment. We report a 59-year-old male with recently diagnosed classical Hodgkin lymphoma who developed acute unexplained stupor after recovery from a hospital-acquired pneumonia, prior to any onco-specific treatment. A comprehensive workup, including brain MRI with 3-Tesla epilepsy protocol, cerebrospinal fluid analysis, viral multiplex PCR, flow cytometry, and extensive metabolic and autoimmune panels, was either normal or non-diagnostic. Only low-titer antinuclear antibodies (ANA, 1:80, speckled pattern) were detected. An empirical trial of levetiracetam for suspected non-convulsive status epilepticus produced no response. Given persistent stupor and exhaustive exclusion of alternative etiologies, a fluorodeoxyglucose brain positron emission tomography was performed. It revealed marked bilateral hippocampal hypermetabolism, diffuse cortical hypometabolism with relative metabolic preservation of the primary motor and visual cortices (the "tiara sign"), and hypermetabolism of the basal ganglia, a functional pattern highly consistent with paraneoplastic limbic encephalitis. Integrating these findings with subsequent histopathological confirmation of mixed-cellularity classical Hodgkin lymphoma yielded a Paraneoplastic Neurologic Syndrome (PNS)-Care Score of 7, classifying the case as definite paraneoplastic neurological syndrome. Rescue immunosuppression with methylprednisolone pulses (1 gram per day for three days) led to dramatic neurological recovery within 72 hours, and chemotherapy produced complete resolution of the neurological syndrome. This case highlights that a normal structural MRI does not exclude paraneoplastic limbic encephalitis. When unexplained stupor or coma occurs in an oncological patient with a non-diagnostic conventional workup, molecular functional imaging should be incorporated early into the diagnostic algorithm, as its functional metabolic signature enables timely classification under PNS-Care Score criteria and initiation of immunosuppressive therapy capable of reversing potentially life-threatening neurological deficits.