Peri-orbital electrodes as a supplemental recording for detection of ictal discharges in medial temporal lobe epilepsy

Objective: The feasibility of peri-orbital electrodes, which are not invasive and do not induce pain, as a supplemental electrode for detection of ictal discharges in medial temporal lobe epilepsy (MTLE) was examined. Methods: Patients with MTLE, who underwent video-EEG monitoring with simultaneous peri-orbital and sphenoidal electrodes and obtained good outcome following standard anterior temporal lobectomy, were subjects in this study. Initial ictal discharge amplitudes were compared between sphenoidal (Sp1/ 2), standard anterior temporal in 10-20 system (F7/ 8), peri-orbital (superior orbital lateral: SOL, inferior orbital medial: IOM), frontopolar (Fp1/ 2), frontal (F3/4) and ear (A1/ 2) electrodes. Results: A total of 34 consecutive seizures from 20 patients were analyzed, with a maximum amplitude observed at Sp1/2 (57.57±5.59), followed by F7/8 (54.89±5.59), SOL (50.97±5.59), IOM (46.95±5.59), A1/2 (45.07±5.69), Fp1/2 (44.78±5.62), and F3/4 (37.75±5.66) (mean±standard error, μV). There was no statistical difference between Sp1/2, F7/8, SOL, and IOM values. When the sphenoidal electrode was omitted, 13 seizures (13/34, 38.2%) resulted in the highest amplitude at peri-orbital electrodes and 10 seizures (10/ 34, 29.4%) at F7/8. Conclusions: Peri-orbital electrodes could detect ictal discharges in MTLE as well as sphenoidal and standard anterior temporal electrodes in 10-20 system and are useful for supplemental recording for detecting ictal epileptiform discharges in MTLE.

Analysis of cerebrospinal fl uid cytokines and growth factors in multiple sclerosis patients with and without chronic headaches

Background: We previously reported that, in Japanese patients with multiple sclerosis (MS), the frequency of chronic headaches was signifi cantly higher after administration of interferon beta (IFNβ). However, the mechanisms underlying IFNβ-related chronic headaches were unknown. Objective: To clarify the mechanisms underlying IFNβ-induced chronic headaches in MS patients by analyzing cytokine levels in cerebrospinal fl uid (CSF). Methods: We measured the levels of 27 CSF cytokines and growth factors using a fl uorescent bead-based immunoassay, during a headache-free period, in 34 MS patients enrolled in our previous survey on chronic headaches. Results: There were no signifi cant differences in CSF cytokine levels between the 21 MS patients with chronic headaches and the 13 without chronic headaches. Among the 14 patients receiving IFNβ therapy, the 5 patients with chronic headaches showed signifi cantly lower levels of interleukin (IL) 15, IL17 and chemokine (C-C motif) ligand 2 (CCL2) (also known as monocyte chemoattractant protein 1; MCP1) compared with the 9 patients without chronic headaches (P < 0.05). Conclusions: The present survey revealed that in MS, chronic headache sufferers on IFNβ therapy had decreased levels of IL15, IL17 and CCL2 in CSF. This suggests that chronic headaches may tend to develop in good responders to IFNβ.

Opticospinal multiple sclerosis in Japanese

Antibodies to aquaporin-4 (AQP4) are found in a number of Japanese opticospinal multiple sclerosis (OSMS) patients. Whether anti-AQP4 antibody-positive and -negative OSMS patients are afflicted with an identical disease remains unknown. To clarify immunological differences between the two groups of patients, we studied serum antibody titres against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified any relationships with immunological parameters. The anti-AQP4 antibody positivity rate was higher in patients with OSMS (36.2%), idiopathic recurrent myelitis (23.5%), and recurrent optic neuritis (26.9%) than in conventional MS patients (8.0%), and those with other diseases (0%). Anti-AQP4 antibody titre was significantly higher in patients with SS-A/B antibodies than in those without. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4+ IFN-γ+ IL-4- T cell percentages and intracellular IFN-γ/IL-4 ratios than anti-AQP4 antibodypositive patients, anti-AQP4 antibody-negative conventional MS patients, and healthy controls. As well, CD4+ IFN-γ+ IL-4- T cell percentages were negatively correlated with anti-AQP4 antibody titres. In CSF, OSMS patients had significantly higher levels of IFN-γ and granulocyte colony-stimulating factor levels than patients with non-inflammatory neurological diseases and other causes of myelitis. A significant increase of IL-17 compared with non-inflammatory neurological diseases patients was only found in OSMS patients, irrespective of the presence or absence of anti-AQP4 antibody. These findings suggest that high titres of anti-AQP4 antibodies are produced as a result of heightened humoral autoimmunity, and that they are likely to contribute to extensive lesion development through disturbed resolution of vasogenic oedema. Moreover, since intrathecal up-regulation of IL-17 and IFN-γ is characteristic of OSMS, Th17/Th1 cells may be critical for the initiation of inflammation and the disruption of blood-brain barrier (BBB); rendering anti-AQP4 antibody get across the BBB.

Multiple sclerosis in Japan: Nationwide surveys over 30 years

There are two different phenotypes of multiple sclerosis (MS) in Asians: opticospinal (OSMS) and conventional (CMS). In Japan, four nationwide surveys of MS have been performed. The first three were in 1972, 1982 and 1989, and we conducted the fourth in 2004. Based on clinically estimated sites of lesions, 1,493 patients with clinically definite MS were classified as having CMS (57.7%), optic-brainstem-spinal MS (5.8%), brainstem-spinal MS (4.6%), OSMS (16.5%), spinal MS (10.6%) or unclassified MS (4.9%). The latest survey revealed the following: a four-fold increase in the estimated number of clinically definite MS patients in 2003 (9,900; crude MS prevalence, 7.7/100,000) compared with 1972; a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; a successive proportional decrease in optic-spinal involvement in clinically definite MS patients; a significant north-south gradient for the CMS/OSMS ratio; after subdivision of the mainland (30-45° North) into northern and southern parts at 37°N, northern-born northern-residents showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern-residents; among northern patients, the absolute numbers of CMS patients and those with Barkhof brain lesions rapidly increased with advancing birth year. Based on MRI findings, MS patients were further subdivided into those with OSMS with or without longitudinally extensive spinal cord lesions extending over three or more vertebral segments (LESCLs) and those with CMS with or without LESCLs. Although disease duration did not differ significantly among the four groups, EDSS scores were significantly higher in patients with LESCLs than in those without, irrespective of OSMS or CMS phenotype. Similar trends were found for the frequencies of bilateral visual loss, transverse myelitis, and marked CSF pleocytosis and neutrophilia. Increased IgG index, frequencies of brain lesions fulfilling the Barkhof criteria and secondary progression were more commonly found in CMS patients than in OSMS patients, while negative brain MRIs were more commonly encountered in OSMS patients than CMS patients, irrespective of the presence of LESCLs. These findings suggest that MS phenotypes are drastically changed by environmental factors, such as latitude and “Westernization”, and that demographic features not only vary based on CMS or OSMS phenotype, but also with the presence or absence of LESCLs.