A scoping review of seizure onset pattern in SEEG and a proposal for morphological classification.

BACKGROUND: Seizure onset pattern (SOP) represents an alteration of electroencephalography (EEG) morphology at the beginning of seizure activity in epilepsy. With stereotactic electroencephalography (SEEG), a method for intracranial EEG evaluation, many morphological SOP classifications have been reported without established consensus. These inconsistent classifications with ambiguous terminology present difficulties to communication among epileptologists. METHODS: We reviewed SOP in SEEG by searching the PubMed database. Reported morphological classifications and the ambiguous terminology used were collected. After thoroughly reviewing all reports, we reconsidered the definitions of these terms and explored a more consistent and simpler morphological SOP classification. RESULTS: Of the 536 studies initially found, 14 studies were finally included after screening and excluding irrelevant studies. We reconsidered the definitions of EEG onset, period for determining type of SOP, core electrode and other terms in SEEG. We proposed a more consistent and simpler morphological SOP classification comprising five major types with two special subtypes. CONCLUSIONS: A scoping review of SOP in SEEG was performed. Our classification may be suitable for describing SOP morphology.

Cortical and white matter substrates supporting visuospatial working memory.

OBJECTIVE: In tasks involving new visuospatial information, we rely on working memory, supported by a distributed brain network. We investigated the dynamic interplay between brain regions, including cortical and white matter structures, to understand how neural interactions change with different memory loads and trials, and their subsequent impact on working memory performance. METHODS: Patients undertook a task of immediate spatial recall during intracranial EEG monitoring. We charted the dynamics of cortical high-gamma activity and associated functional connectivity modulations in white matter tracts. RESULTS: Elevated memory loads were linked to enhanced functional connectivity via occipital longitudinal tracts, yet decreased through arcuate, uncinate, and superior-longitudinal fasciculi. As task familiarity grew, there was increased high-gamma activity in the posterior inferior-frontal gyrus (pIFG) and diminished functional connectivity across a network encompassing frontal, parietal, and temporal lobes. Early pIFG high-gamma activity was predictive of successful recall. Including this metric in a logistic regression model yielded an accuracy of 0.76. CONCLUSIONS: Optimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways. SIGNIFICANCE: This study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts.

[Surgical Treatment of Mesial Temporal Lobe Epilepsy Focusing on Anatomical Understanding].

Surgical treatment is an effective option for medically intractable epilepsy. Amygdalohippocampectomy for mesial temporal lobe epilepsy is a surgically remediable epileptic syndrome. It is a well-established surgery and various approaches to the mesial temporal lobe have been reported. To reduce the complication rate, surgeons should have sufficient knowledge of anatomy in the mesial temporal region. Here, we summarize the surgical treatments for mesial temporal lobe epilepsy, focusing on anatomical understanding. We described in detail the surgical anatomy of amygdalohippocampectomy and various approaches to the mesial temporal region. In addition, we describe hippocampal transection aimed at preserving memory function, which is an alternative surgery in patients without hippocampal sclerosis. An anatomical understanding of the mesial temporal region helps surgeons not only in the field of epilepsy surgery, but also in other fields of neurosurgery, such as brain tumor and vascular surgery.

Visualization of Resected Area in Endonasal Endoscopic Approach versus Transcranial Approach for Skull Base Meningiomas by Voxel-Based-Lesion Mapping.

BACKGROUND: We aimed to evaluate the resected area of endonasal endoscopic approach (EEA) and transcranial approach (TCA) for skull base meningiomas (SBMs) using voxel-based-lesion mapping and visualized the appropriate tumor location in each approach. METHODS: We retrospectively examined 182 patients with SBMs who underwent tumor resection in our hospital between 2014 and 2019. Pre- and post-operative SBMs were manually delineated on MRI to create the voxels-of-interest (VOIpre and VOIpost) and were registered onto the normalized brain (normalized VOIpre and normalized VOIpost). The resected map was created by subtracting normalized VOIpost from the normalized VOIpre divided by the number of cases. The resected maps of TCA and EEA were compared by subtracting them. RESULTS: Twenty patients underwent EEA and 135 patients underwent TCA. The tumor resected map demonstrated that the resected area of EEA frequently accumulated on the central skull base, while that of TCA accumulated near the central skull base. The border of both approaches matched the circle that connects neural foramens at the skull base. CONCLUSIONS: The resected area of SBMs by EEA and TCA was well visualized by voxel-based-lesion mapping. The circle connecting the neural foramens was the border of EEA and TCA.

Maximum 11C-methionine PET uptake as a prognostic imaging biomarker for newly diagnosed and untreated astrocytic glioma.

This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II-IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10-0.41, p < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23-22.8, p = 0.025; glioblastoma: HR 11.52, 95% CI 2.27-58.47, p = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09-0.62, p = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08-0.71, p = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81-109.2, p = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II-IV astrocytic glioma.

Disconnection surgery to cure or palliate medically intractable epileptic spasms: a retrospective study.

OBJECTIVE: Surgery is a treatment option for medically intractable epileptic spasms (ESs). However, outcomes of ES after surgery are not well understood, especially when surgeries aimed at seizure palliation are included. The purpose of the present study was to 1) investigate the proportion of favorable postoperative ES outcomes, 2) explore the preoperative factors related to favorable postoperative ES outcomes, and 3) examine the timing of ES recurrence after disconnection surgeries, including both curative and palliative indications. METHODS: This retrospective study included patients who underwent disconnection surgery for medically intractable ES at the authors' institution between May 2015 and April 2021. Patients with suggested focal-onset ES based on preoperative evaluations initially underwent lobar disconnection. Patients with suggested generalized or unknown-onset ES underwent corpus callosotomy (CC). If evaluations after initial CC showed focalized or lateralized change, they were considered secondarily revealed focal-onset ES, and lobar disconnection was performed. ES outcomes were evaluated using the International League Against Epilepsy classification. ES outcomes were divided into classes 1-4 as favorable outcomes and classes 5 and 6 as unfavorable outcomes. The relationship between the favorable postoperative ES outcomes and the following preoperative factors was analyzed: sex, age at onset (< or > 1 year), duration between seizure onset and initial surgery (< or > 2 years), type of seizure at onset (ES or others), presence of other types of seizures, substrate, hypsarrhythmia, and MRI abnormalities. The period between the last surgery and ES recurrence was also analyzed. RESULTS: A total of 41 patients were included, of whom 75.6% achieved favorable ES outcomes. A longer seizure duration between seizure onset and initial surgery, presence of hypsarrhythmia, and positive MRI findings led to poorer postoperative ES outcomes (p = 0.0028, p = 0.0041, and p = 0.0241, respectively). A total of 60.9% of patients had ES recurrence during the follow-up period, and their ES recurred within 13 months after the last surgery. CONCLUSIONS: Disconnection surgery is an effective treatment option for medically intractable ES, even when the preoperative evaluation suggests a generalized or unknown onset.

Discrepancy between SAA and CRP levels linked to the difference of SAA/CRP ratio in the patients with early rheumatoid arthritis.

OBJECTIVES: Indeed, serum amyloid A (SAA) and C-reactive protein (CRP) reportedly seem to have moderate correlation, but discrepancies between CRP and SAA levels have often been reported in patients with early rheumatoid arthritis (ERA). This study aimed to determine the reasons for this discrepancy. METHODS: ERA patients (n = 206) were enrolled and treated with anti-RA drugs. Clinical features and disease activities were estimated. CRP and SAA levels were monitored, and the SAA/CRP ratio was compared. Correlations between CRP and SAA levels in individuals and between individuals and disease activity scores were examined. RESULTS: In a follow-up study, the SAA/CRP ratio remained almost constant over time in the same patients. However, SAA/CRP ratios differed widely between patients (0.233-106.3). In patients with high SAA/CRP ratios (>6.52), many (26.2%) had abnormal SAA values only. In patients with low SAA/CRP ratios (<6.52), not a few (6.8%) exhibited abnormal CRP values only. CONCLUSIONS: The SAA/CRP ratio remained virtually constant in the same patients but differed dramatically between patients, which clarifies the discrepancy between CRP and SAA levels. CRP is the better marker in low-ratio patients but not in high-ratio patients; the SAA/CRP ratio is critical for its interpretation.

Ratio of serum amyloid A to C-reactive protein is constant in the same patients but differs greatly between patients with inflammatory diseases.

C-reactive protein (CRP) is commonly monitored to track the activity of inflammation and has become the gold standard in the management of all inflammatory diseases. Indeed, serum amyloid A (SAA) have seemed to correlate moderately with CRP, but the discrepancy of CRP and SAA levels has often been reported, especially in rheumatoid arthritis. Then, we examined CRP reflects a real magnitude of inflammation in patients with rheumatic and infectious inflammatory diseases. A total of 414 patients with infectious and non-infectious inflammatory diseases were enrolled. At initial visit, each patient underwent a clinical assessment and had also laboratory tests such as SAA and CRP. In each patient, we carried out a longitudinal analysis of CRP and SAA levels. We determined the inter-individual correlation between SAA and CRP and also clarified intra-individual changes of SAA/CRP ratio. SAA and CRP levels changed approximately linearly over time within individuals irrespective of rheumatic and infectious inflammatory diseases. However, SAA/CRP ratios differed dramatically between patients (from 0.117 to 50.8, median 5.71). In patients with high SAA/CRP ratio (>8.44), SAA is a better predictor of inflammation than CRP. In contrast, CRP is a better predictor in patients with low ratio (<3.52). Our results suggest that the SAA/CRP ratio differed greatly between individuals but was constant in intra-individuals. Low CRP levels could be accompanied by SAA levels predicting any degree of inflammation, implying that CRP is not reflecting a real magnitude of inflammation. To evaluate the real magnitude of inflammation, to access the SAA/CRP ratio in advance is essential.

Phase-amplitude coupling of interictal fast activities modulated by slow waves on scalp EEG and its correlation with seizure outcomes of disconnection surgery in children with intractable nonlesional epileptic spasms.

OBJECTIVE: Epileptic spasms (ESs) are classified as focal, generalized, or unknown onset ESs. The classification of ESs and surgery in patients without lesions apparent on MRI is challenging. Total corpus callosotomy (TCC) is a surgical option for diagnosis of the lateralization and possible treatment for ESs. This study investigated phase-amplitude coupling (PAC) of fast activity modulated by slow waves on scalp electroencephalography (EEG) to evaluate the strength of the modulation index (MI) before and after disconnection surgery in children with intractable nonlesional ESs. The authors hypothesize that a decreased MI due to surgery correlates with good seizure outcomes. METHODS: The authors studied 10 children with ESs without lesions on MRI who underwent disconnection surgeries. Scalp EEG was obtained before and after surgery. The authors collected 20 epochs of 3 minutes each during non-rapid eye movement sleep. The MI of the gamma (30-70 Hz) amplitude and delta (0.5-4 Hz) phase was obtained in each electrode. MIs for each electrode were averaged in 4 brain areas (left/right, anterior/posterior quadrants) and evaluated to determine the correlation with seizure outcomes. RESULTS: The median age at first surgery was 2.3 years (range 10 months-9.1 years). Two patients with focal onset ESs underwent anterior quadrant disconnection (AQD). TCC alone was performed in 5 patients with generalized or unknown onset ESs. Two patients achieved seizure freedom. Three patients had residual generalized onset ESs. Disconnection surgeries in addition to TCC consisted of TCC + posterior quadrant disconnection (PQD) (1 patient); TCC + AQD + PQD (1 patient); and TCC + AQD + hemispherotomy (1 patient). Seven patients became seizure free with a mean follow-up period of 28 months (range 5-54 months). After TCC, MIs in 4 quadrants were significantly lower in the 2 seizure-free patients than in the 6 patients with residual ESs (p < 0.001). After all 15 disconnection surgeries in 10 patients, MIs in the 13 target quadrants for each disconnection surgery that resulted in freedom from seizures were significantly lower than in the 26 target quadrants in patients with residual ESs (p < 0.001). CONCLUSIONS: In children with nonlesional ESs, PAC for scalp EEG before and after disconnection surgery may be a surrogate marker for control of ESs. The MI may indicate epileptogenic neuronal modulation of the interhemispheric corpus callosum and intrahemispheric subcortical network for ESs. TCC may be a therapeutic option to disconnect the interhemispheric modulation of epileptic networks.

Diagnostic Performance of [11C]Methionine Positron Emission Tomography in Newly Diagnosed and Untreated Glioma Based on the Revised World Health Organization 2016 Classification.

BACKGROUND: The relationship between uptake of amino acid tracer with positron emission tomography (PET) and glioma subtypes/gene status is still unclear. OBJECTIVE: To assess the relationship between uptake of [11C]methionine using PET and pathology, IDH (isocitrate dehydrogenase) mutation, 1p/19q codeletion, and TERT (telomerase reverse transcriptase) promoter status in gliomas. METHODS: The participants were 68 patients with newly diagnosed and untreated glioma who underwent surgical excision and preoperative [11C]methionine PET examination at Osaka City University Hospital between July 2011 and March 2018. Clinical and imaging studies were reviewed retrospectively based on the medical records at our institution. RESULTS: The mean lesion/contralateral normal brain tissue (L/N) ratio of diffuse astrocytomas was significantly lower than that of anaplastic astrocytomas (P = 0.00155), glioblastoma (P < 0.001), and oligodendrogliomas (P = 0.0157). The mean L/N ratio of IDH mutant gliomas was significantly lower than that of IDH wild-type gliomas (median 1.75 vs. 2.61; P = 0.00162). A mean L/N ratio of 2.05 provided the best sensitivity and specificity for distinguishing between IDH mutant and IDH wild-type gliomas (69.2% and 76.2%, respectively). The mean L/N ratio of TERT promoter mutant gliomas was significantly higher than that of TERT promoter wild-type gliomas (P = 0.0147). Multiple regression analysis showed that pathologic diagnosis was the only influential factor on L/N ratio. CONCLUSIONS: Distinguishing glioma subtypes based on the revised 2016 World Health Organization classification of the central nervous system tumors on the basis of [11C]methionine PET alone seems to be difficult. However, [11C]methionine PET might be useful for predicting the IDH mutation status in newly diagnosed and untreated gliomas noninvasively before tumor resection.

Comparison of the keyhole trans-middle temporal gyrus approach and transsylvian approach for selective amygdalohippocampectomy: A single-center experience.

Several approach routes exist for selective amygdalohippocampectomy (SAH); however, previous reports regarding a comparison of these routes are limited. Here, we compared trans-middle temporal gyrus (T2) SAH and transsylvian (TS) SAH in terms of seizure outcome, visual-field defect, memory function, and operation time in our institution. This retrospective study examined the data of 16 patients with medically intractable mesial temporal lobe epilepsy. Six patients underwent trans-T2 SAH and 10 patients underwent TS SAH between July 2014 and February 2019 in Osaka City University Hospital. In trans-T2 SAH, we performed a keyhole temporal craniotomy and a small corticotomy on T2. In TS SAH, we performed a 1.5 cm corticotomy along the inferior periinsular sulcus after opening the sylvian fissure. Amygdalohippocampectomy after reaching the inferior horn of the lateral ventricle was performed in the same manner in both procedures. The seizure outcome, visual-field defect, memory function, and operation time were retrospectively compared between the procedures. Seizure-free outcomes were achieved for six patients in the trans-T2 SAH and eight patients in the TS SAH group. There were no significant differences in the seizure outcome, visual-field defect, and memory function. The operation time was significantly shorter for trans-T2 SAH than TS SAH. The postoperative scar was less conspicuous for trans-T2 SAH. Trans-T2 SAH and TS SAH were comparable in terms of the seizure outcome, visual-field defect, and memory function. The operation time and length of the skin incision were shorter for trans-T2 SAH, suggesting that it may be preferable for general epilepsy surgeons.

Burr hole drainage without irrigation for chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions, with different strategies for treatment. Most recent trials favor the use of drainage to reduce the recurrence rate. However, few reports have discussed the efficacy of burr hole drainage without irrigation for treating CSDH. This study aimed to examine the efficacy of burr hole drainage without irrigation in a series of 385 symptomatic CSDH lesions. METHODS: This retrospective study included a series of 385 symptomatic CSDH lesions in 309 patients, who underwent burr hole drainage without irrigation, between September 2009 and August 2017 at the Department of Neurosurgery, Yao Tokushukai General Hospital, Japan. The risk of recurrence was evaluated based on the patients' age, sex, preoperative magnetic resonance imaging (MRI) findings, preoperative anticoagulants, hematoma drainage rate, and bilaterality. RESULTS: Of the 385 lesions, 41 cases (16 with inadequate follow-up periods and 25 with contraindications for MRI) were excluded from the analysis. The overall recurrence rate in the index study was 4.9% (17/344 lesions). The effects of the preoperative hematoma volume and nonhyperintensity on T1-weighted imaging on the recurrence rate were significant. CONCLUSION: Our findings indicated that burr hole drainage without irrigation is a good surgical modality in patients with CSDH, and preoperative MRI findings can evaluate the risk of recurrence.

Anatomic Understanding of Subtotal Hemispherotomy Using Cadaveric Brain, 3-Dimensional Simulation Models, and Intraoperative Photographs.

BACKGROUND: When the epileptogenic foci skip the motor area, the epilepsy can be cured by surgery while preserving the motor function. This surgery has been reported as subtotal hemispherectomy. The disconnective variant of this surgery, subtotal hemispherotomy, is described. OBJECTIVE: To demonstrate each step clearly, a cadaveric brain, 3-dimensional reconstruction and simulation model, and intraoperative photographs were used. METHODS: A formalin-fixed cadaveric brain was dissected to show each step of this surgery. For the 3-dimensional model, several brain structures were reconstructed from preoperative images, and the surgery was simulated. Intraoperative photographs and postoperative magnetic resonance images were taken from the representative cases. RESULTS: Temporo-parieto-occipital disconnection is performed to disconnect these lobes and the insula, limbic system, and splenium of the corpus callosum. The postcentral sulcus is the anterior border of the disconnection. Next, prefrontal disconnection is performed to disconnect the frontal lobe and the insula, frontal lobe and basal ganglia, and the anterior part of the corpus callosum. The precentral sulcus is the posterior border of the disconnection. Finally, corpus callosotomy of the central part is performed. After these steps, subtotal hemispherotomy, with preservation of the pre- and postcentral gyrus, is achieved. The 3-dimensional model clearly shows the anatomic relationships between deep brain structures. In the representative cases, postoperative motor deterioration was transient or none, and seizure-free status was achieved after surgery. CONCLUSION: Subtotal hemispherotomy is generally difficult because of the complicated anatomy and narrow and deep surgical corridors. Combined use of these methods facilitates a clearer understanding of this surgery.

Adult-Onset Mixed Germ Cell Tumor Composed Mainly of Yolk Sac Tumor Around the Pineal Gland: A Case Report and Review of the Literature.

BACKGROUND: Mixed germ cell tumors (MGCTs) usually occur in children. In the present report, we discuss an extremely rare case of adult-onset MGCT composed mainly of yolk sac tumor (YST) around the pineal gland. CASE DESCRIPTION: A 54-year-old Japanese man presented with disturbance of consciousness, Parinaud's syndrome, and gait disturbance. Magnetic resonance imaging revealed a pineal mass lesion, and subtotal resection of the tumor was achieved. The histologic diagnosis was MGCT, consisting mainly of YST. Although he underwent 5 courses of chemotherapy and craniospinal irradiation after surgery, tumor dissemination could not be controlled, and he died 10 months postoperatively. CONCLUSION: The present case highlights the need for clinicians to include YST in the differential diagnosis of acute progressive lesions around the pineal region, even in adult patients.

Efficacy and safety of extending intravenous tocilizumab intervals from 4 to 6 weeks in rheumatoid arthritis patients with good response to 4-week intervals.

A period of 4 weeks (w) has been recommended for rheumatoid arthritis (RA) patients as the interval between intravenous (IV) tocilizumab (TCZ, 8 mg/kg). In a previous paper, we showed the possibility that the interval between successive IV TCZ can be extended from 4 to 6 weeks in more than 60% of patients with low diseases activity (LDA) at 4-week intervals. Herein, we aimed to investigate the efficacy and safety of extending the interval from 4 to 6 weeks. A retrospective observational study was conducted by enrolling patients in whom the intervals of TCZ infusions could be extended from 4 to 6 weeks with an LDA for more than 2 years. We compared the efficacy and side effects of TCZ infusions at intervals of 4 and 6 weeks in a cohort of patients. We also examined serum lipid, platelet, IL-6, and trough TCZ levels. A total of 125 patients with an LDA at 4 weeks intervals were enrolled in this study, of which 78 patients maintained LDA at 6-week intervals of TCZ infusion. After extending the infusion intervals, the efficacy of the treatment was maintained, and the side effects decreased significantly. In addition, the levels of total cholesterol and triglyceride were returned to normal, and the serum trough levels of TCZ became undetectable at 6-week intervals. We proved that intervals between TCZ infusions can be extended from 4 to 6 weeks in more than 60% of RA patients along with a decrease in the side effects, thus suggesting the need to change the infusion intervals in suitable patients.

Anatomic Understanding of Posterior Quadrant Disconnection from Cadaveric Brain, 3D Reconstruction and Simulation Model, and Intraoperative Photographs.

BACKGROUND: Posterior quadrant disconnection is a surgery for refractory unilateral temporoparieto-occipital epilepsy to limit propagation of epileptic discharges. As incomplete disconnection can lead to residual seizures, detailed procedures are presented using a cadaveric brain, three-dimensional (3D) reconstruction and simulation models, and intraoperative photographs. METHODS: A formalin-fixed adult cadaveric brain was dissected to show each step in posterior quadrant disconnection. Using 3D preoperative planning software, we reconstructed 3D models of operative views from computed tomography and magnetic resonance imaging. Intraoperative photographs were taken from the case of a 7-year-old girl with temporoparieto-occipital epilepsy. RESULTS: Frontotemporoparietal craniotomy was performed. The Sylvian fissure was widely dissected, and the insular cortex was exposed. The temporal stem was disconnected along the inferior peri-insular sulcus. The disconnection was extended from the limen insulae to the atrium of the lateral ventricle. The fibers between the head of the hippocampus and the amygdala were disconnected. The parietal lobe was disconnected along the postcentral sulcus, and the disconnection was connected to the atrium of the lateral ventricle. At the medial surface of the parietal lobe, the disconnection was continued to the corpus callosum. The splenium of the corpus callosum was disconnected via the medial wall of the lateral ventricle. The fornix was divided in the atrium of the lateral ventricle. After these steps, disconnection of the unilateral tempoparieto-occipital lobe was achieved while preserving the arteries and veins. CONCLUSIONS: Inclusion of views from cadaveric brain, 3D reconstruction and simulation models, and intraoperative photographs facilitates a clearer anatomic understanding of posterior quadrant disconnection.

Successful extension of tocilizumab infusion intervals from 4 weeks to 6 or 5 weeks in 90% of RA patients with good response to 4-week intervals.

OBJECTIVES: A period of 4 weeks (w) has been recommended as the interval between tocilizumab (TCZ) infusions for rheumatoid arthritis (RA). However, treating the patients with TCZ (8 mg/kg), we experienced that longer intervals were also effective. We conducted the study to investigate whether the intervals of TCZ infusions could extend from 4w to 5 or 6w. METHODS: This was a retrospective observational study. RA patients who had shown good response to TCZ infusions at 4w intervals were enrolled, and the intervals of TCZ infusions were extended to 5w. Next, the intervals of TCZ infusion were extended to 6w for the patients who had maintained good response with 5w intervals. The patients who had maintained good response for more than two years were estimated as responders. RESULTS: One hundred patients were enrolled in the present study, and 62 patients maintained good response with 6w-interval infusions, and 28 patients with 5w-interval infusions, indicating that 90% of patients who had shown good response with 4w intervals could extend the intervals from 4w to 5 or 6w. CONCLUSIONS: The present study provides evidence that most of RA patients who showed good response to TCZ infusions at 4w could extend the intervals to 6w or 5w. This finding should be of great interest for both financial and labour reasons.

Evaluation of lasting high levels of CRP among the patients with metabolic syndrome.

"Low-grade" systemic inflammation is common findings in patients with metabolic syndrome (MetS). When we assessed 256 MetS patients, we found eight patients who presented high levels of C-reactive protein (CRP) which are between 40 and 15 mg/L for more than 3 years. They have not satisfied any criteria of inflammatory diseases such as rheumatoid arthritis and the area of visceral fat estimated by computed tomography was more than 200 cm(2). All the other MetS patients of visceral fat over 200 cm(2) presented low levels of CRP which are less than 10 mg/L. Insulin resistance and ultrasound study of carotid plaques showed no differences between high and low levels of CRP patients. There are a series of MetS patients who show high levels of CRP without clinical symptoms of inflammatory diseases. High levels of CRP merely cannot be explained by visceral fat area, insulin resistance, or carotid plaques.