the detection of novel autoantibodies has provided etiological insight into epileptic disorders of previously unknown causes . forerunners in this area of investigation include voltage - gated potassium channel ( vgkc ) antibodies , antibodies against the n - methyl - d - aspartate receptor ( nmdar ) , and antibodies against glutamic acid decarboxylase ( gad ) . other noteworthy antibodies include those against ampa receptors and the gabab receptor as well as against onconeural antigens . often , the diagnosis of an autoantibody - related epileptic disorder is made during the evaluation of an acute limbic encephalitis ( le ) , at times within the setting of drug - resistant status epilepticus . however , autoantibody testing has also returned positive results during the recovery phase of an apparent monophasic illness with acute seizures or in patients with less severe chronic epilepsy . at times , the positive antibodies are not clearly directly causative for seizures but may be nonspecifically raised and serve as immune markers , implicating that there is a significant inflammatory component . for example , a significant subset of patients diagnosed with anti - nmdar encephalitis is found to have ovarian teratomas , which are therapeutically removed . but in many cases , these antibodies are nonparaneoplastic , and immunotherapy may be the only major intervention along with antiepileptic medications . we describe a clinical case in which the use of antibody testing and pet / mri imaging aided in the identification of voltage - gated potassium channel antibody - related limbic encephalitis ( vgkc - le ) . magnetic resonance imaging findings alone did not definitively demonstrate structural abnormalities , even when repeated over time , despite clinical observations that his memory and cognition were progressively worsening . in addition to antibody testing , brain pet was obtained to evaluate for regions of hypometabolic abnormalities that might support our clinical suspicions of a limbic encephalitis . we were fortunate to have access to pet / mri technology at our institution , which was used in this case . in vivo - dedicated brain pet / mri is a novel multimodal technology that allows for the noninvasive simultaneous acquisition of high - resolution structural data and functional imaging within the same scanning period . conceptually similar to standard pet / ct , pet / mri offers better structural imaging of most body tissues than pet / ct , especially soft tissue , and uses a much lower dose of radiation . the ability to immediately analyze superimposed , coregistered images makes it possible to detect anatomical features and pathology that might have gone underappreciated with separately acquired single modality tests . areas of differential metabolism or ligand specificity on pet can be examined more carefully for structural identification and analysis using mri , and the limitations that currently exist for the resolution of pet images can be minimized by the much better spatial resolution afforded by immediate , precise coregistration of the mri . we present the pet / mri images to showcase this novel technology and to present findings in a patient suffering from vgkc - le . a single patient underwent an inpatient evaluation which included a comprehensive paraneoplastic panel and brain pet / mri imaging using a siemens biograph mmr system . a 64-year - old , right - handed man presented in referral for an 11-month history of seizures . witnessed episodes during wakefulness included behavioral arrest , staring , and confusion lasting minutes , which had progressively increased in frequency to multiple per day . he also had nocturnal episodes of arousal , moaning , repetitive hand movements , and confusion lasting seconds . titrated to 2000  mg twice daily , he continued to have worsening memory , behavioral changes , difficulty paying bills , and trouble navigating his own home . extensive evaluation 6  months from onset , including head ct , cbc , cmp , ua , vitamin b12 testing , thyroid testing , coagulation profile , creatine kinase , and csf hsv-1 pcr , was unremarkable . a lumbar puncture showed elevated protein at 72  mg / dl , and eeg revealed left frontotemporal epileptiform abnormalities . an initial brain mri with contrast and another repeated four months later showed possibly increased t2-weighted signal in the bilateral medial temporal lobes and insular cortex . however , the appearance of these areas did not significantly change over time despite his progressively worsening symptoms ( fig .  1 ) . during reevaluation on presentation to our institution , a repeat lumbar puncture again showed elevated protein at 72  mg / dl without other abnormalities . brain pet / mri revealed bitemporal and bilateral insular hypometabolism ( fig .  2 ) . otherwise , extensive infectious , autoimmune , neoplastic , paraneoplastic , prion disease workup , ct of the chest , abdomen , and pelvis , and body mri were unrevealing . treatment included the addition of lamotrigine as a second antiepileptic agent and oral steroids ( prednisone 1000  mg each weekend for 8  weeks , then every other weekend for 8 doses ) . this patient presented with a clinical picture of medically refractory temporal lobe epilepsy complicated by memory and cognitive problems . the majority of testing was unrevealing , and even brain mri repeated over time did not show any definitive structural abnormalities to support an active region - specific pathological process . as the patient 's behavior and thinking progressively worsened , the possibility of an ongoing limbic encephalitis was evaluated by comprehensive paraneoplastic antibody panel and advanced brain imaging . brain pet / mri technology , available at our institution , afforded us the opportunity to repeat the brain mri once more while also simultaneously assessing for functional abnormalities using pet . the pet / mri findings proved to be key supportive evidence of bilateral temporal and insular abnormalities where serial mri had fallen short . although bilateral hypometabolism in these regions is not specific for limbic encephalitis and could be seen in patients with other forms of temporal lobe epilepsy , the pet / mri results were concordant with the clinical suspicion . these results along with positive vgkc antibodies clarified the diagnosis and improved confidence in moving forward with both additional antiepileptic treatment and immunotherapy , which ultimately kept the patient seizure - free and significantly improved his cognition . voltage - gated potassium channel antibody - related limbic encephalitis typically includes encephalopathy , seizures , and mesial temporal lobe structural abnormalities [ 710 ] . classically , regional abnormalities in the mesial temporal lobes in vgkc - le are not seen in other vgkc antibody - related neurological disorders , namely morvan 's or isaac 's syndromes . imaging abnormalities typical of vgkc - le have also been reported in patients manifesting personality changes and memory deficits without evidence of seizures . furthermore , patients with vgkc - le have been reported to have a normal brain mri but bitemporal hypometabolism on brain pet , similar to findings in our patient . however , correlations of pet and mri in vgkc - le have previously been described . in seven patients with subacute limbic encephalitis , one with vgkc antibodies , the authors reported that the neuroimaging findings of pet and mri did not overlap in half the patients but , when combined , revealed temporal pathology in all of them . one patient with vgkc - le had serial brain mri and pet studies for two years , revealing a successive switch in prominence from right to left mesial temporal lobe changes . of special relevance to the case presented , the pet findings were prominent earlier than the mri findings during the development of left mesial temporal pathology , despite over a year of seizures prior to that time . in this case report , the use of brain pet / mri and antibody testing aided in the diagnosis of vgkc - le . antibody testing should be considered in cases of acute epilepsies of unknown cause , especially if they are drug - resistant or severely debilitating . brain pet and mri are complementary technologies for assessing regional abnormalities , and brain pet may reveal focal findings in patients with vgkc - le missed by brain mri alone . simultaneous brain pet / mri multimodal technology has synergistic potential for identifying focal abnormalities that separately - acquired single modality testing might miss .
preclinical and clinical studies have demonstrated the significance of inflammation and autoantibodies in epilepsy , and the use of immunotherapies in certain situations has become an established practice . 
 temporal lobe epilepsy can follow paraneoplastic or nonparaneoplastic limbic encephalitis associated with antibodies directed against brain antigens . here , we focus on a patient with worsening confusion and temporal lobe seizures despite treatment with antiepileptic medications 
 . serial brain mris did not conclusively reveal structural abnormalities , so the patient underwent brain pet / mri to simultaneously evaluate brain structure and function , revealing bitemporal abnormalities . 
 the patient was diagnosed with voltage - gated potassium channel antibody - related limbic encephalitis based on clinical presentation , imaging findings , and antibody testing . 
 treatment included the addition of a second antiepileptic agent and oral steroids . 
 his seizures and cognitive deficits improved and stabilized .