SUMMARYPurpose: Fluorodeoxyglucose positron emission computed tomography (FDG-PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PETpositive, MRI-negative patients and compared them with those of patients with MTS. Methods: We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI)). We compared this group to the group of patients who underwent ATL and who had MTS on MRI. Patients with discordant ictal electroencephalography (EEG) were excluded. Surgical outcomes were compared using percentages of Engel class I outcomes at 2 and 5 years as well as KaplanMeier survival statistic, with time to seizure recurrence as survival time. A subgroup of PET+/MRI) patients who underwent surgical implantation prior to resection was compared to PET+/MRI) patients who went directly to resection without implantation. Key Findings: There were 46 PET+/MRI) patients (of whom 36 had 2-year surgical outcome available) and 147 MTS patients. There was no difference between the two groups with regard to history of febrile convulsions, generalized tonic-clonic seizures, interictal spikes, depression, or family history. Mean age at first seizure was higher in PET+/MRI) patients (19 ± 13 vs.14 ± 13 years, Mann-Whitney test, p = 0.008) and disease duration was shorter (14 ± 10 vs. 22 ± 13 years, student's t-test, p = 0.0006). Class I surgical outcomes did not differ significantly between the PET+/MRI) patients and the MTS group (2 and 5 year outcomes were 76% and 75% for the PET+/MRI) group, and 71% and 78% for the MTS group); neither did outcomes of the PET+/MRI) patients who were implanted prior to resection versus those who went directly to surgery (implanted patients had 71% and 67% class I outcomes at 2 and 5 years, whereas. nonimplanted patients had 77% and 78% class I outcomes, p = 0.66 and 0.28). Kaplan-Meier survival statistics for both comparisons were nonsignificant at 5 years. Dentate gyrus and hilar cell counts obtained from pathology for a sample of patients also did not differ between groups. Significance: PET-positive, MRI-negative TLE patients in our study had excellent surgical outcomes after ATL, very similar to those in patients with MTS, regardless of whether or not they undergo intracranial monitoring. These patients should be considered prime candidates for ATL, and intracranial monitoring is probably unnecessary in the absence of discordant data.

The most-used treatments for epilepsy worldwide are older-generation drugs such as phenytoin, carbamazepine, phenobarbital, and valproic acid, which have prominent enzymatic effects. Our sense of comfort with these treatments is starting to fade, however, as more and more potential long-term consequences of these drugs come to light. Epidemiologic studies demonstrate that ischemic disease of the heart and brain is more common among patients with epilepsy. Enzyme-inducing drugs are associated with elevations in a host of surrogate markers of vascular risk, suggesting that they could be responsible for increased rates of cardiovascular and cerebrovascular disease. The enzymeinhibiting drug valproate may have adverse consequences of its own pertaining to glucose and lipid metabolism. These effects stand in addition to those well established in the literature regarding bone metabolism, hormonal abnormalities, and drug-drug interactions. Because patients with epilepsy require medication for years, and often for life, it is difficult to justify the long-term use of these agents when there are capable alternatives. Many of the adverse effects of the older drugs appear to be rapidly reversible, prompting consideration of whether patients who are currently treated with these agents should be switched to alternative therapies, even in the absence of obvious side effects. Newer medications without effects on hepatic enzymes likely do not have these chronic metabolic consequences, and we recommend their use over older-generation drugs whenever possible.

Autoimmune status epilepticus is a rare condition but one that has been increasingly recognized by neurologists and clinicians in the intensive care unit. As more cases are described in the literature and more antibody tests become commercially available, diagnosis is now feasible; however, early diagnosis remains a challenge. For practical purposes, status epilepticus may be considered as possibly autoimmune if it is refractory to anticonvulsant treatment and there is no other known cause; this may then lead to empiric immunomodulatory therapy. Major factors that raise the index of suspicion are recent cognitive or behavioral alterations, a history of malignancy or tumor, or presence of other neurological features. There is a lack of high level evidence in the literature for treatment of status epilepticus, and almost none for autoimmune encephalitis. Patients with autoimmune status epilepticus may be treated with immunomodulatory therapy, including steroids, intravenous immunoglobulin (IVIG), plasmapheresis (PLEX), and other immunosuppressive agents while maximizing their anticonvulsant therapy. For some patients, resective surgery may be necessary, such as hemispherectomy for Rasmussen's encephalopathy. In the case of status epilepticus due to paraneoplastic autoantibodies, urgent and aggressive testing and treatment of a primary malignancy is needed. Importantly, any suspicion of autoimmune mediated status epilepticus should prompt the transfer of the patient to a specialized center with experience in refractory status epilepticus whenever possible.

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