High‐frequency oscillations: The state of clinical research

Modern electroencephalographic (EEG) technology contributed to the appreciation that the EEG signal outside the classical Berger frequency band contains important information. In epilepsy, research of the past decade focused particularly on interictal high‐frequency oscillations (HFOs) > 80 Hz. The first large application of HFOs was in the context of epilepsy surgery. This is now followed by other applications such as assessment of epilepsy severity and monitoring of antiepileptic therapy. This article reviews the evidence on the clinical use of HFOs in epilepsy with an emphasis on the latest developments. It highlights the growing literature on the association between HFOs and postsurgical seizure outcome. A recent meta‐analysis confirmed a higher resection ratio for HFOs in seizure‐free versus non–seizure‐free patients. Residual HFOs in the postoperative electrocorticogram were shown to predict epilepsy surgery outcome better than preoperative HFO rates. The review further discusses the different attempts to separate physiological from epileptic HFOs, as this might increase the specificity of HFOs. As an example, analysis of sleep microstructure demonstrated a different coupling between HFOs inside and outside the epileptogenic zone. Moreover, there is increasing evidence that HFOs are useful to measure disease activity and assess treatment response using noninvasive EEG and magnetoencephalography. This approach is particularly promising in children, because they show high scalp HFO rates. HFO rates in West syndrome decrease after adrenocorticotropic hormone treatment. Presence of HFOs at the time of rolandic spikes correlates with seizure frequency. The time‐consuming visual assessment of HFOs, which prevented their clinical application in the past, is now overcome by validated computer‐assisted algorithms. HFO research has considerably advanced over the past decade, and use of noninvasive methods will make HFOs accessible to large numbers of patients. Prospective multicenter trials are awaited to gather information over long recording periods in large patient samples.     

Serum levels of macrophage colony-stimulating factor and aortic calcification in hemodialysis patients.

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 +/- 0.2 ng/ml) as compared with controls (1.5 +/- 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 +/- 0.2 ng/ml vs. polysulfone 3.8 +/- 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca x P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.     

Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy

Introduction  To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes. Case report  A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m²) on days 1, 8 and 15 in combination with docetaxel (60 mg/m²) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs. Conclusion  The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities.     

Elevation of a tumor associated antigen CA 19-9 levels in patients with rheumatic diseases

We investigated the incidence and characteristics of an elevated tumor associated antigen CA 19-9 in patients with rheumatic diseases. Serum concentration of CA 19-9 was increased in 13 of 39 patients (33.3%) with definite or classical rheumatoid arthritis (RA), in 6 of 19 patients (31.6%) with systemic lupus erythematosus (SLE), in 3 of 9 patients (33.3%) with progressive systemic sclerosis (PSS) and in 9 of the other 35 patients (25.7%). Malignant neoplasm was not detected in any of the patients with rheumatic diseases. Pretreatment of mouse serum with patients' sera did not reduce the measured CA 19-9 values obtained by the conventional assay. The CA 19-9 antigen found in sera from patients with RA was present in a non-IgG fraction, and had the same molecular weight as that in one patient with pancreatic cancer, as determined by gel filtration. These results demonstrated that serum CA 19-9 levels were increased in some patients with rheumatic diseases.     

Surgical management of cervicomedullary compression in achondroplasia

Achondroplasia is often associated with cervicomedullary dysfunction. MRI sagittal imaging was performed to determine whether surgical intervention was necessary to relieve cervicomedullary compression. Cervicomedullary compression was classified into severe and mild types based on the ratios of the brain stem diameter at the foramen magnum, the site of the most severe stenosis to the diameter at the pontomedullary junction and C3 level, where it is normal. This classification was found to be closely correlated with the severity of clinical symptoms and important in determining whether surgical intervention is necessary. Moreover, since the incidence of sudden death is high in patients aged 4 years or younger with achondroplasia, surgical intervention should be considered in all such patients if cervicomedullary compression is present.     

Partial seizures triggering infantile spasms in the presence of a basal ganglia glioma.

Infantile spasms associated with brain tumors have been reported. A focal cortical lesion can induce infantile spasms by triggering the brainstem and basal ganglia in this vulnerable age group. We report the case of a female infant with a low-grade glioma in the right basal ganglia, spreading to the cortical area. She presented at the age of five months with left hemiparesis and partial seizures. She developed infantile spasms at the age of 12 months. This is the first video clip report of partial seizures triggering symmetrical spasms in series, secondary to a basal ganglia glioma extending to the cortex. [Published with video sequences].