Objective: The primary goals of this pilot study is to (1) describe the safety profile of administration of mangafodipir in patients with epilepsy and (2) determine if peri-ictal administration will allow focal entry of mangafodipir through the blood-brain-barrier and manganese enhanced magnetic resonance imaging (MEMRI) visualization of seizure foci. Secondary objectives are further exploration of MEMRI properties in patients with epilepsy. Study population: 16 patients with drug-resistant epilepsy. Design: Screening of enrolled participants will include a medical history, physical exam, blood and urine laboratory testing. Patients will be imaged interictally with a gadolinium enhanced MRI session. The administration of mangafodipir will be done as an inpatient during long-term video EEG recording, to ensure administration in the periictal period. Patients will receive a baseline MRI scan, IV mangafodipir injection and will then be serially scanned with non-contrast MRI scans. Outcome measures: The primary outcomes are (1) description of the safety profile of mangafodipir administration in patients with epilepsy, and (2) evaluation of the difference between T1-weighted signal intensity in the brain measured after mangafodipir administration in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the homologous contralateral region.
- INCLUSION CRITERIA: - Age 18-60 - Able to give written informed consent directly. - Drug resistant epilepsy participants will be defined as having clinically documented seizures with consistent EEG evidence as defined by the 1981 International Classification of Epileptic Seizures, refractory to standard anti-seizure treatment for at least one year prior to enrolling in this study and with an average of at least one seizure per month. This criterion will be established by preliminary screening in NINDS Clinical Epilepsy Service under protocol 18-N-0066. Seizure focus localization will be determined by standard clinical, neurophysiologic, and imaging studies. Prior or concurrent enrollment in 18-N-0066 is required. EXCLUSION CRITERIA: General exclusions: - Patients with epilepsy who are not surgical candidates - Positive test for HIV. - History of post-ictal psychosis or post-ictal aggression - Significant structural brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on the baseline MRI scan. - Pregnancy or breast-feeding. - Planning to get pregnant in the next 2 months - Claustrophobia to a degree that the subject would feel uncomfortable in the MRI machine. - Cannot lie on their back for at least two hours. - Risk for MRI scan, (e.g., any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects or body piercings that cannot be removed, or history of being a welder or metal worker due to small metal fragments in the eye) - History of clinically significant liver or kidney disease, that could potentially increase the risk of CNS damage due to manganese exposure - A history of drug or alcohol abuse/dependence (subjects scoring 8 or higher on the AUDIT scale) - Screening lab abnormalities, demonstrating values more than 2 times the upper limit of normal for AST, ALT, bilirubin, alkaline phosphatase, BUN, creatinine - Previous presumed occupational exposure to manganese (i.e., having worked in a mine, foundry, smelter, dry cell battery manufacturing facility, or agriculture) - Allergy to manganese - On-going treatment with calcium-channel blocker - Iron-deficiency anemia - Personal history of Parkinson's Disease or Parkinsonism or presence of this disease in a 1st degree relative - Unwilling to allow sharing and/or use in future studies of coded data that are collected for this study Gadolinium enhanced MRI component specific exclusions (not applicable for patients opting out of this portion of the study): - Estimated GFR < 60, tested within 1 week of scan - Allergy to gadolinium