ro-16-0154 and Seizures

Epilepsy is one of the most prevalent neurologic disorders and affects approximately 1% of the population. Most complex seizures arise from the temporal lobes and the condition of 20-30% of these patients is refractory to medication. Many can be rendered seizure free with surgery. Epilepsy surgery requires accurate identification of the site and extent of the epileptogenic area responsible for seizures. EEG is accepted as a gold standard, however only 50% of the patients are safely diagnosed. The need for invasive monitoring with possible hemorrhage or infection has been greatly reduced by the introduction of new technologies such as PET, SPECT and MRI in the clinical practice. MRI demonstrate morphologic changes in approximately 80% of patients with epilepsy. However, structural lesions may not always correlate with clinical, EEG and pathologic localization of epileptogenic foci. Seizures are associated with pronounced changes in regional cerebral blood flow. The real power of SPECT lies in the opportunity of ictal examinations, with a sensitivity ranging from 90 to 97%. Interictal PET studies using 18F-FDG measure regional glucose metabolism, have been investigated for their value as non-invasive focus-localizing techniques. These studies have sensitivity ranging from 80 to 85%. The benzodiazepine binding site that are associated with and modulate the activity of GABA receptors have been imaged by SPECT (using 123I-iomazenil) and PET (using 11C-Flumazenil). Combined measurements of benzodiazepine binding sites and perfusion/metabolism provide a more accurate visualization of epileptogenic site than perfusion or metabolism measurements alone. Functional imaging modalities (PET and SPECT) are highly important in the presurgical evaluation of patients with medically refractory complex partial seizures.

Topics: Animals; Brain; Cerebrovascular Circulation; Epilepsy; Flumazenil; Fluorodeoxyglucose F18; GABA Modulators; Humans; Iodine Radioisotopes; Radiopharmaceuticals; Receptors, Cholinergic; Receptors, GABA; Receptors, GABA-A; Receptors, Histamine H1; Receptors, Opioid; Seizures; Sensitivity and Specificity; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10-20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of. A 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies.. An anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.

Topics: Adolescent; Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Female; Flumazenil; Humans; Iodine Radioisotopes; Neoplasm Recurrence, Local; Receptors, N-Methyl-D-Aspartate; Seizures; Tomography, Emission-Computed, Single-Photon; Young Adult

Brain single photon emission computed tomography (SPECT) for epilepsy is divided into two types (using three radionuclide tracers)-perfusion SPECT (123I-IMP or 99 mTc-ECD), identifying epileptogenic foci by detecting abnormality in regional cerebral blood flow, and 123I-iomazenil SPECT, identifying epileptogenic foci based on distribution of central benzodiazepine receptors. This study aimed to statistically evaluate and compare the SPECT effectiveness for the three tracers. Statistical parametric mapping (SPM) analysis was performed on 30 mesial temporal lobe epilepsy (mTLE) patients. The radionuclide and patient data were categorized as follows: abnormality in the medial temporal lobe on the operated hemisphere (AAA), in the entire temporal lobe on the operated hemisphere (AA), in the dominantly affected temporal lobe on the operated hemisphere (A), in bilateral temporal lobes (B), with no abnormalities in bilateral temporal lobes (C), and with abnormality in the temporal lobe on the nonoperated hemisphere (D). For analyses of (AAA), (AA), and (A), examining the hemisphere containing epileptogenic foci, IMP-SPECT was significantly superior to ECD-SPECT (P<0.05). For (AAA), indicating localization, IMZ-SPECT was significantly superior to the other two (P<0.05). IMP-SPECT was superior for lateralizing and IMZ-SPECT was useful for localizing epileptogenic foci in mTLE patients though the applicability of the results in extratemporal lobe epilepsy is unknown.

Topics: Adolescent; Adult; Brain Mapping; Drug Resistance; Epilepsy, Temporal Lobe; Female; Flumazenil; Functional Laterality; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neurosurgical Procedures; Radiopharmaceuticals; Retrospective Studies; Seizures; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Young Adult

Accurate evaluation of status epilepticus or clusters of seizures in patients with epilepsy is a critical issue in epilepsy care units. Although the need for continuous electroencephalographic monitoring has been recognized, it has been difficult to evaluate the frequency of ictal changes in electroencephalography (EEG) data in real time. Amplitude-integrated EEG (aEEG) has been reported to be useful for neuromonitoring, particularly in newborn infants. However, few reports of the utility of aEEG in older children with epilepsy have been published. We employed aEEG in combination with conventional EEG in an 11-year old boy presenting with clusters of seizures and were able to accurately evaluate the frequency of seizures in real time. The combination of aEEG and conventional EEG may be a useful tool in both neonatal intensive care units and epilepsy care units.

Topics: Child; Cluster Analysis; Electroencephalography; Epilepsy, Frontal Lobe; Flumazenil; Humans; Iodine Isotopes; Magnetic Resonance Imaging; Male; Seizures; Tomography, Emission-Computed, Single-Photon

To investigate changes in free benzodiazepine receptor density in response to repeated, long-term administration of diazepam in epilepsy, we assessed 125I-iomazenil (125I-IMZ) binding in a mouse model.. El mice were divided into two groups of 12 mice each which received either no diazepam (E1(D[-]) group) or 2 mg/kg of diazepam per week (El(D[+]) group). Nine ddY mice were used as a control. Once each week from the age of 5 to 19 weeks, the El mice received stimulation to produce epileptic seizures 20 minutes after receiving intraperitoneal injections. At 20 weeks of age, a total dose of 0.37 MBq of 125I-IMZ was injected in all mice and their brains were rapidly removed 3 hours later. The incidence of epileptic seizures at the age of 19 weeks and the autoradiograms of the brain were compared.. The incidence of epileptic seizures in response to weekly stimulation was significantly lower in the E1(D[+]) group than in the E1(D[-]) group (p < 0.001). The percent injected doses of 125I-IMZ per gram of tissue in the cortex, hippocampus and amygdala were significantly lower in the E1(D[+]) group than in the E1(D[-]) group (p < 0.05).. The results suggest that diazepam binds competitively to 125I-IMZ as an agonist to free benzodiazepine receptor sites in the cortex, hippocampus and amygdala and shows anticonvulsant effect in E1 mice.

Topics: Animals; Anticonvulsants; Autoradiography; Brain; Diazepam; Disease Models, Animal; Epilepsy; Flumazenil; Iodine Radioisotopes; Mice; Protein Binding; Receptors, GABA-A; Seizures; Time Factors

Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE).. Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB.. A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively).. Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.

Topics: Adolescent; Adult; Binding Sites; Disease Progression; Epilepsy, Temporal Lobe; Female; Flumazenil; Functional Laterality; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Radionuclide Imaging; Receptors, GABA-A; Seizures; Time Factors