Perampanel during pregnancy: Description of four cases.

Perampanel (PER) is approved in Italy as an adjunctive treatment for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCs), and it could be an alternative to valproate in young women diagnosed with idiopathic generalized epilepsy. Nevertheless, clinical data about the outcome of pregnancies in women exposed to PER are lacking. Here, we report retrospectively collected data from four women suffering from FOS who were exposed to PER during pregnancy. Three pregnancies were carried out with PER as add-on therapy during the entire gestation (8 mg/day in two patients and 6 mg/day in one), without seizure frequency variations. The fourth patient started PER 2 mg/day as monotherapy during the 13th week of pregnancy due to seizure relapse and continued it until delivery with complete seizure control. All pregnancies showed good outcomes, and their newborns did not possess major congenital malformations. Apgar scores and auxological parameters at birth were normal. Fetal pathology in follow-up during pregnancies was absent in all cases. In our patients PER was well tolerated and appeared safe for the fetuses and did not result in major malformations or adverse events at birth. Nevertheless, this is a report involving a small number of patients and it does not suggest the general use of PER is safe during pregnancy.

Eyelid myoclonia with absences, intellectual disability and attention deficit hyperactivity disorder: a clinical phenotype of the RORB gene mutation.

Eyelid myoclonia with absences is recently included in the category of childhood epileptic syndromes. It is clinically characterized by brief seizures of eyelid myoclonia, sometimes followed by absences, and it is associated to EEG generalized discharges of polyspikes or polyspike-waves, which are triggered by eyes closure in a well-lit room. This epileptic syndrome probably has a genetic origin, as well as other genetic generalized epilepsies, in particular photosensitive epilepsies. We describe the case of a patient affected by eyelid myoclonia with absences, intellectual disability, and attention deficit hyperactivity disorder (ADHD), with a de novo mutation of the RORB gene (retinoid-related orphan receptor ß); this gene is involved in vivo in different neuronal processes among which are migration and differentiation. We suggest that its mutation in our patient can be considered the cause of the aberrant functioning of the cerebral cortex, which is clinically expressed by epilepsy and neurodevelopment disorders.

Positron emission tomography of pituitary macroadenomas: hormone production and effects of therapies.

Positron emission tomography with [18F]fluorodeoxyglucose (FDG) was carried out in 24 patients with pituitary macroadenomas (32 studies) to assess the glucose utilization of these tumors in vivo. The adenoma metabolic index, which is the ratio of FDG uptake of tumor to a whole brain slice, was calculated. Comparisons were made between tumor uptake of FDG and hormone secretion and response to therapies. In each positron emission tomography study, the macroadenoma could be easily identified visually as an area of increased FDG uptake near the region of the sella. FDG uptakes were highest for nonfunctional adenomas, and the prolactin, growth hormone, and thyroid-stimulating hormone-producing groups displayed similar levels of glucose metabolism. The adenoma metabolic index for all tumors averaged 1.3, ranging from 0.3 for a thyroid-stimulating hormone adenoma to 3.5 for a nonfunctional tumor. Tumors did not exhibit metabolic rates that could characterize the type of hormone produced. Recurrent macroadenomas displayed metabolism similar to tumors not operated on, whereas irradiated adenomas showed lower glucose uptake than nonirradiated tumors. Drug therapy with bromocriptine or the long-acting somatostatin analogue octreotide also decreased the glucose utilization of the tumor. There was no correlation between the amount of hormone produced and the adenoma metabolic index when a group of tumors was analyzed. Patients scanned more than once, however, demonstrated changes in hormone levels that changed or did not change in parallel with tumor metabolism. Thus, positron emission tomography offers the potential capability for predicting and defining the growth of pituitary adenomas. This may be of particular value when plasma hormone assays and conventional imaging techniques prove inadequate for monitoring patient response to therapy.

Role of iron and ferritin in MR imaging of the brain: a study in primates at different field strengths.

The authors measured in vivo signal intensity on magnetic resonance (MR) images and postmortem iron concentrations in the brains of three young and two old rhesus monkeys. T2-weighted MR imaging was done at 0.5, 1.5, 2.0, and 4.7 T. Relative assessment of iron concentration was made from the optical density of brain sections stained with the Perls' method intensified with diaminobenzidine. MR imaging and optical density measurements were made in the centrum semiovale (white matter) and in four gray matter areas: the insular cortex, caudate nucleus, putamen, and globus pallidus, the latter three of which accumulate significant iron deposits with age. High optical density and decreased signal intensity were found in these areas, and the inverse correlation between gray matter/white matter signal ratio and optical density was in good agreement with the theory of T2 shortening caused by diffusion of water through magnetic inhomogeneities. However, the dependence of T2 shortening on field strength was not quadratic, as expected for paramagnetic iron, but instead showed a marked leveling off at higher field strengths. This magnetic "saturation" is explainable by antiferromagnetism and superparamagnetism of the ferritin core and has been observed in ferritin solutions at low temperatures. Similar observations at body temperature are needed before the iron-ferritin explanation for T2 shortening can be considered proved.

Positron emission tomography in the detection of malignant degeneration of low-grade gliomas.

The management of low-grade gliomas represents a challenge to the physician as a significant proportion may undergo malignant degeneration to a high-grade tumor. We present the positron emission tomography (PET) scans, using [18F] fluorodeoxyglucose (FDG), of 12 patients who have histological and/or clinical evidence of malignant degeneration of a low-grade glioma. Each scan displays a focal area of hypermetabolism similar to that of malignant gliomas which arise de novo. Three patients also underwent PET scanning prior to malignant degeneration. When the initial scan is compared with the postmalignant degeneration study, a difference in tumoral glucose uptake can be recognized. A region previously shown to be hypometabolic develops focal hypermetabolism as malignant changes evolve. This study displays the utility of FDG-PET in the evaluation of malignant degeneration of low-grade gliomas. The knowledge that a neoplasm has altered its biological behavior may influence subsequent therapeutic options. If these findings can be confirmed in larger series and by other investigators, it is possible that FDG-PET may be adopted as one of the diagnostic tools for guiding the management of low-grade gliomas.

MR imaging of thoracic disk herniations.

Magnetic resonance (MR) is of value in imaging intervertebral disk disease. We present the MR findings in two patients with thoracic disk herniations who required surgical intervention. The advantages of MR over CT myelography are ease of obtaining sagittal sections, rapid assessment of the entire thoracic spine, and a high rate of patient acceptance related to the noninvasive nature of MR and lack of morbidity and complications. For these reasons, we currently rely, almost exclusively, on MR for evaluating thoracic disk disease.