Transcriptional features of low-grade neuroepithelial tumors with the BRAF V600E mutation associated with epileptogenicity.

Low-grade neuroepithelial tumors are major causes of drug-resistant focal epilepsy. Clinically, these tumors are defined as low-grade epilepsy-associated neuroepithelial tumors (LEATs). The BRAF V600E mutation is frequently observed in LEAT and linked to poor seizure outcomes. However, its molecular role in epileptogenicity remains elusive. To understand the molecular mechanism underlying the epileptogenicity in LEAT with the BRAF V600E genetic mutation (BRAF V600E-LEAT), we conducted RNA sequencing (RNA-seq) analysis using surgical specimens of BRAF V600E-LEAT obtained and stored at a single institute. We obtained 21 BRAF V600E-LEAT specimens and 4 control specimens, including 24 from Japanese patients and 1 from a patient of Central Asian origin, along with comprehensive clinical data. We submitted the transcriptome dataset of 21 BRAF V600E-LEAT plus 4 controls, as well as detailed clinical information, to a public database. Preliminary bioinformatics analysis using this dataset identified 2134 differentially expressed genes between BRAF V600E-LEAT and control. Additionally, gene set enrichment analysis provided novel insights into the association between estrogen response-related pathways and the epileptogenicity of BRAF V600E-LEAT patients. Our datasets and findings will contribute toward the understanding of the pathology of epilepsy caused by LEAT and the identification of new therapeutic targets.

[Deep Brain Stimulation for Tourette's Syndrome and Challenging for Neuropsychiatric Disease].

The efficacy of deep brain stimulation(DBS)for Tourette's syndrome is being well established. Herein, we performed DBS in 38 patients and confirmed that its efficacy was comparable with that reported internationally. Although many patients experience severe symptoms, the indications for surgery remain controversial. One reason for this is that Tourette syndrome has the potential for spontaneous remission, while DBS treatment results in the need for long-term management, which can be difficult for some patients. Furthermore, while several targets for DBS have been reported, no treatment guidelines have yet been established. The efficacy of DBS for neuropsychiatric disorders, such as obsessive-compulsive disorder, depression, and dementia, is gradually being reported. However, this use has many limitations in terms of expectations similar to those seen with Tourette's syndrome, leading to problems with expanding indications for these disorders. Indications for these disorders should be addressed in conjunction with ethical issues. It is expected that more data on this topic will be collected in the future.

Focal ictal direct current shifts by a time constant of 2 seconds were clinically useful for resective epilepsy surgery.

OBJECTIVE: Ictal direct current shifts (icDCs) and ictal high-frequency oscillations (icHFOs) have been reported as surrogate markers for better surgical outcomes in epilepsy surgery. icDCs have been classified into two types: rapid and slow development. icDCs have been investigated with a time constant of 10 s (TC10s); however, many institutes use electroencephalography with a time constant of 2 s (TC2s). This study aimed to evaluate whether icDCs can be observed adequately with TC2s; moreover, it examined the relationship between the resected core area of icDCs or icHFOs and surgical outcomes, occurrence rate of each type of icDCs, and relationship between each type of icDCs and pathology. METHODS: Twenty-five patients with intractable focal epilepsy were analyzed retrospectively. icDCs and icHFOs were defined according to common metrics. The amplitude of icDCs was defined at >200 µV and even <200 µV. The two electrodes producing the most prominent icDCs and icHFOs were defined as core electrodes. The correlation between the resected core electrode area and degree of seizure control after surgery was analyzed. icDCs were classified into two types based on a peak latency value cutoff of 8.9 s, and the occurrence rates of both patterns were investigated. RESULTS: icDCs (142/147 seizures [96.6%]) and icHFOs (135/147 seizures [91.8%]) occurred in all patients (100%). Compared with the amplitude of icDCs with TC10s reported in previous studies, the amplitude of icDCs with TC2s was attenuated in the current study. A significant positive correlation was observed between the resected core electrode area and degree of seizure control in both icDCs and icHFOs. A rapid development pattern was observed in 202 of 264 electrodes (76.5%). SIGNIFICANCE: Similar to icDCs with TC10s, those with TC2s were observed adequately. Furthermore, favorable outcomes are expected using TC2s, which is currently available worldwide.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Periodic cycles of seizure clustering and suppression in children with epilepsy strongly suggest focal cortical dysplasia.

AIM: We investigated characteristic seizure patterns in epilepsy caused by focal cortical dysplasia (FCD), which differ from epilepsy by other aetiologies in surgical cases with lesions on magnetic resonance imaging (MRI), then examined if these features were applicable to patients with epilepsy without any lesions on MRI. METHOD: We retrospectively studied clinicopathological features in 291 (143 females) children with epilepsy who had undergone resective surgery after comprehensive evaluation, including 277 cases with lesions on MRI (136 females, age at resection 0-17 years [mean 6 years 10 months, SD 5 years 7 months]) and 14 cases without any lesions on MRI (seven females, age 0-16 years [mean 7 years 8 months, SD 4 years 8 months]). RESULTS: Among 277 patients with lesions on MRI, 87 cases exhibited recurrent periodic cycles of seizure clustering (≥5 seizures/day for ≥1 week) and suppression (no seizures for ≥1 week); of these, 80 cases (92%) were pathologically diagnosed with FCD. Other pathologies included glial scar, hippocampal sclerosis, hemimegalencephaly, and cortical tuber in three, two, one, and one case respectively. All 14 patients without any lesions on MRI had significant recurrent periodic seizure cycles and FCD histopathologically. INTERPRETATION: Periodic seizure cycles characterized by clustering and suppression in patients with epilepsy strongly suggest the presence of FCD regardless of MRI findings, and comprehensive evaluations for epilepsy surgery should be proceeded.

[Hemispherectomy and Hemispherotomy in the Treatment of Drug-Resistant Epilepsy].

Hemispherectomy/hemispherotomy is an important surgical procedure for patients with drug-resistant epilepsy who have a unilateral large epileptogenic lesion associated with neurological deficits, such as hemiparesis. Hemispherotomy consists of corpus callosotomy and dissection of projection fibers into the internal capsule. Hemispherotomy has two major approaches: periinsular lateral hemispherotomy(PIH)and vertical parasagittal hemispherotomy(VH). The white matter is incised along the periinsular sulcus to disrupt the internal capsule before corpus callosotomy is performed within the lateral ventricle in PIH. Corpus callosotomy is performed first with an interhemispheric approach, the lateral ventricle is entered, and the internal capsule is disconnected just lateral to the thalamus in the VH. Both approaches have similar efficacy for seizure control; however, a recent study suggested the possible superiority of VH. The chance of complete seizure freedom for one or two postoperative years has been reported to be 70% or greater. The risk of postoperative hydrocephalus is as high as 20%, particularly in young children. In this article, we present and discuss the surgical anatomy of hemispherotomy techniques.

Optogenetic stimulus-triggered acquisition of seizure resistance.

Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such "kindling" process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed using in vivo microdialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.

Association between lack of functional connectivity of the frontal brain region and poor response inhibition in children with frontal lobe epilepsy.

PURPOSE: We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE). METHODS: We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep. We estimated functional connectivity using the phase lag index (PLI) that captures the synchronization of EEG. We also performed continuous performance tests (CPTs) on the children and obtained questionnaire responses on attention deficit hyperactivity disorder and oppositional defiant disorder (ODD). RESULTS: The average gamma PLI was lower in the FLE group than in the TDC group, especially between long-distance frontoparietal pairs, between interhemispheric frontal pairs, and between interhemispheric parietotemporal pairs. Gamma PLIs with long-distance frontoparietal and interhemispheric frontal pairs were positively associated with inattention, ODD scores, omission error, and reaction time in the FLE group but not in the TDC group. Conversely, they were negatively associated with age, hyperactivity score, and commission error. CONCLUSIONS: A lack of functional connectivity of the frontal brain regions in children with FLE was associated with poor response inhibition.

Adaptive behavior and its related factors in children with focal epilepsy.

OBJECTIVE: We aimed to clarify the strengths and weaknesses in adaptive behavior in children with focal epilepsy and show children-associated factors related to adaptive behavior. MATERIALS AND METHODS: Sixty-three children with focal epilepsy aged 5-18 years with intellectual quotient (IQ) ranging from 67 to 135 were enrolled in this study. Adaptive behavior was evaluated using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II). The children performed continuous performance test and tests of reading, writing, and IQ; parents answered questionnaires regarding attention-deficit hyperactivity disorder and autism spectrum disorder (ASD). Participants were categorized into four groups based on IQ and adaptive behavior scores for statistical comparisons. RESULTS AND DISCUSSION: Children with low adaptive behavior were more likely to show a reduction in daily living skills, and those with both low adaptive behavior and IQ were more likely to show a reduction in daily living skills and communication. Lower adaptive behavior was related to more severe autistic symptoms, lower academic achievement in children with IQ > 85, and lower executive function in children with IQ ≤ 85. There was a qualitative difference of cognitive dysfunction in adaptive behavior between both groups. CONCLUSIONS: There were differences in VABS-II domain and subdomain characteristics between children with focal epilepsy and those with ASD; however, it was more difficult for children with more severe ASD and coexisting focal epilepsy to show age-equivalent adaptive behavior.

Transient water-electrolyte disturbance after hemispherotomy in young infants with epileptic encephalopathy.

PURPOSE: This study aimed to elucidate the clinical features of water-electrolyte disturbance (WED) as a sequela of hemispherotomy. METHODS: We performed a retrospective chart review to identify the clinical features of diabetes insipidus (DI) as a complication in < 12-month-old patients who underwent hemispherectomy or hemispherotomy for severe epilepsy between 2007 and 2018. Central DI was diagnosed if a patient developed polyuria (urine output > 5 mL/kg/h), abnormally high serum osmolality (> 300 mOsm/kg), high serum sodium level (> 150 mEq/L), either abnormally low urine specific gravity (< 1.005) or low urine osmolality (< 300 mOsm/kg) or both, and effective control of polyuria with arginine vasopressin (AVP). The clinical course of post-hemispherotomy WED, complications other than WED, and seizure outcomes were analyzed. RESULTS: The review identified that 3 of 23 infants developed WED. All patients developed polyuria within 2 days after surgery, with high serum osmolality and hypotonic urine; AVP was effective in treating these symptoms. The clinical course was compatible with central DI. Two patients subsequently developed hyponatremia in a biphasic or triphasic manner. All patients had multiple seizures that were probably related to WED. Two patients developed asymptomatic cerebral sinovenous thrombosis, possibly because of the surgical procedure and dehydration; anticoagulant treatment was provided. All patients were treated for WED for up to 2 months and had no residual pituitary dysfunction. CONCLUSION: Systemic complications other than intracranial ones can occur in patients who have undergone hemispherotomy. Perioperative systemic management of young infants undergoing this procedure should include careful water and electrolyte balance monitoring.

Multiplex ligation-dependent probe amplification analysis is useful for detecting a copy number gain of the FGFR1 tyrosine kinase domain in dysembryoplastic neuroepithelial tumors.

PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are slow-growing glioneuronal tumors, and their genetic backgrounds are getting unveiled. Recently, fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain (TKD) has been demonstrated by whole-genome sequencing. METHODS AND RESULTS: Here, we analyzed 22 DNTs using multiplex ligation-dependent probe amplification (MLPA) with formalin-fixed paraffin-embedded specimens and found a copy number gain in TKD of FGFR1 (13 cases, 59%), which suggested the presence of FGFR1-ITD. Another 5 DNTs harbored FGFR1 hot spot mutations including a double mutant case, and FGFR1 alterations were detected in 18 DNTs (82%). The BRAF V600E mutation, another important mutation in DNTs, was not observed. CONCLUSIONS: With recent findings of less frequent or absent FGFR1-ITD in pilocytic astrocytomas or rosette-forming glioneuronal tumors, the analysis of FGFR1 aberrations, especially FGFR1-ITD, was suggested to be helpful to discriminate DNTs from their histological mimics.

Altered Expression of Astrocyte-Related Receptors and Channels Correlates With Epileptogenesis in Hippocampal Sclerosis.

BACKGROUND: Hippocampal sclerosis (HS) is one of the major causes of intractable epilepsy. Astrogliosis in epileptic brain is a peculiar condition showing epileptogenesis and is thought to be different from the other pathological conditions. The aim of this study is to investigate the altered expression of astrocytic receptors, which contribute to neurotransmission in the synapse, and channels in HS lesions. METHODS: We performed immunohistochemical and immunoblotting analyses of the P2RY1, P2RY2, P2RY4, Kir4.1, Kv4.2, mGluR1, and mGluR5 receptors and channels with the brain samples of 20 HS patients and 4 controls and evaluated the ratio of immunopositive cells and those expression levels. RESULTS: The ratio of each immunopositive cell per glial fibrillary acidic protein-positive astrocytes and the expression levels of all 7 astrocytic receptors and channels in HS lesions were significantly increased. We previously described unique astrogliosis in epileptic lesions similar to what was observed in this study. CONCLUSION: This phenomenon is considered to trigger activation of the related signaling pathways and then contribute to epileptogenesis. Thus, astrocytes in epileptic lesion may show self-hyperexcitability and contribute to epileptogenesis through the endogenous astrocytic receptors and channels. These findings may suggest novel astrocytic receptor-related targets for the pharmacological treatment of epilepsy.

Biological variation of procalcitonin levels in hemodialysis patients.

BACKGROUND: There is no obvious evidence regarding biological variation of procalcitonin (PCT) levels in hemodialysis (HD) patients without infections. The aim of this study was to determine the within- and between-person biological variation of PCT levels in HD patients without infections. METHODS: A multicenter, prospective, cohort study enrolled 123 HD patients without any signs of infectious disease. Baseline PCT levels were determined pre- and post-HD, and then repeated pre-HD PCT measurements were performed at 2, 4, 8, 12, 16, 20, and 24 weeks after baseline blood-sampling, regardless of the presence or absence of infectious disease. Analytical variation (CVa), the within-person biological variation (CVi), between-person biological variation (CVb), individual index (II), and the reference change value (RCV) were calculated. RESULTS: The mean age was 62.4 years, 76.4% were male, and 32.5% had diabetes. The mean duration of HD was 87 months. The median value for baseline pre-HD PCT was 0.23 ng/mL, which is much higher than the reference level for healthy individuals. PCT levels decreased of 46.6% after a single HD session. CVi was 24.9%, CVb was 54.2%, II was 0.46, and RCV was calculated as 96.4% with 99% probability. CONCLUSIONS: The PCT level was significantly higher in stable HD patients without manifest bacterial infection. CVb was more variable than CVi in HD patients, which indicates that relative change is more important than absolute PCT levels for diagnosing bacterial infection, and doubling or more of the baseline PCT level may imply the presence of a bacterial infection in HD patients.

Resistance to Erythropoiesis-Stimulating Agents in Pre-Dialysis and Post-Dialysis Mortality in Japanese Incident Hemodialysis Patients.

BACKGROUND/AIMS: There is lack of definitive evidence about the association between erythropoiesis-stimulating agent (ESA) responsiveness in the pre-dialysis phase and mortality. Therefore, we conducted a hospital-based, retrospective, cohort study to assess the predictive value of ESA response for prognosis in incident hemodialysis patients. METHODS: A total of 108 patients without preexisting cardiovascular disease who had been started on maintenance hemodialysis were studied. ESA responsiveness just before starting dialysis was estimated using an erythropoietin resistance index (ERI). The endpoint was defined as all-cause death. RESULTS: During a mean follow-up period of 3.1 ± 1.6 years, 18 (17%) patients died. Overall, the multivariate Cox regression analysis revealed that the log-transformed ERI remained an independent predictor of all-cause death after adjustment using a propensity score (hazard ratio 2.25, 95% CI 1.25-4.06). CONCLUSIONS: Among incident hemodialysis patients, hyporesponsiveness to ESA may be associated with mortality.

Association of Circulatory Iron Deficiency With an Enlarged Heart in Patients With End-Stage Kidney Disease.

OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD. DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease.

Poor survival of dialysis patients with unhealed wounds because of critical limb ischemia: Limb salvage and survival requires wound healing.

Maintenance of blood flow in the wound area is required to heal wounds of critical limb ischemia (CLI) in dialysis patients. However, many dialysis patients have both a stenotic lesion in below-knee blood vessels and a cardiovascular event as complications, and thus, it may be difficult to ensure sufficient blood flow. Therefore, many deaths occur because of problems with wound healing. The aim of this study is to identify the optimal treatment, including revascularisation and amputation, from the perspective of wound healing by analysing the survival of hemodialysis patients with CLI who had healed or unhealed wounds in a lower extremity. The subjects were 52 patients who received maintenance dialysis at our clinic, including 27 with healed CLI wounds and 25 with unhealed CLI wounds. The Kaplan-Meier method was used to compare survival between the two groups. Multivariate analysis was conducted to examine the effect of an unhealed wound on mortality. The mean follow-up period was 1.7 ± 1.1 years. In the unhealed wound group, the 1-, 2-, and 3-year survival rates were 48%, 20%, and 12%, respectively. The overall survival rate was significantly lower in the unhealed wound group compared with the healed wound group (12% vs 63%, P = .0002 by log-rank test). In multivariate analysis, unhealed CLI wounds had a significant independent association with mortality (hazard ratio 3.32; 95% confidence interval [CI]: 1.41-8.77, P = .0054). In this study, the 3-year survival rate suggested a significantly poorer prognosis of hemodialysis patients with unhealed CLI wounds compared with those with healed wounds. An unhealed wound is an independent risk factor for mortality in hemodialysis patients with CLI.

Thallium-201 washout rate of stress myocardial perfusion imaging as a predictor of mortality in diabetic kidney disease patients initiating hemodialysis: an observational, follow-up study.

BACKGROUND: Thallium-201 washout rate of stress myocardial perfusion imaging (MPI) has been reported to correlate with coronary flow reserve which is a parameter of myocardial microcirculation. However, the evidence for its use in diabetic kidney disease (DKD) has been lacking, and the association between thallium-201 washout rate and adverse outcomes including death is unknown. Therefore, the present study was conducted to evaluate the predictive ability of thallium-201 washout rate for mortality in DKD patients initiating hemodialysis. METHODS: A total of 96 patients with type 2 diabetes who had been started on maintenance hemodialysis undergoing stress MPI with thallium-201 within 1 year, 72 men and 24 women, with a median age of 67 years, were studied. The endpoint was defined as all-cause death. The Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: During the mean follow-up period of 3.4 ± 2.1 years, 18 (18.8%) deaths occurred. Cumulative survival rates during the follow-up period, with thallium-201 washout rate levels in the lowest tertile (3.1-36.2%), the middle tertile (36.5-46.3%), and the highest tertile (46.4-66.2%), were 51.0, 86.5, and 85.3%, respectively. Overall, the multivariate Cox regression analysis revealed that thallium-201 washout rate remained an independent predictor of death after adjusting by confounding variables (HR 0.91, 95% CI 0.85-0.97). CONCLUSIONS: Among DKD patients initiating hemodialysis, thallium-201 washout rate seems to be useful for predicting death.

Differences in sleep architecture between left and right temporal lobe epilepsy.

To investigate whether seizure lateralization affects sleep macrostructure in patients with left and right temporal lobe epilepsy (TLE), as rapid eye movement (REM) sleep is shorter in patients with right hemispheric cerebral infarction than with left. We retrospectively analyzed data from 16 patients with TLE (6 men and 10 women aged 34.9 ± 11.4 years) who underwent polysomnography as well as long-term video electroencephalography. Ten patients were diagnosed with left TLE and six patients with right TLE. Sleep stages and respiratory events were scored based on the American Academy of Sleep Medicine criteria. Sleep and respiratory parameters were compared between the patient groups. Percentage of REM stage sleep was significantly (p < 0.05) lower in patients with left TLE (median 8.8 %, interquartile range 5.5-13.8 %) than in patients with right TLE (median 17.0 %, interquartile range 14.1-18.3 %). The other parameters showed no significant differences. Shorter REM sleep in patients with left TLE sharply contrasts with the previous report of shorter REM sleep in patients with right cerebral infarction. Laterality of the irritative epileptic focus versus destructive lesion may have different effects on the sleep macrostructures.

Point of care assessment of cardiac troponin T level in CKD patients with chest symptom.

We challenged to identify the cutoff value of cTnT in chronic kidney disease (CKD) patients by point of care assessment way. A single center, prospective cross-sectional study was planned and performed. 201 consecutive patients who were visited emergency room for chest symptoms were enrolled in this study. All patients were performed routine practice for differential diagnosis of chest symptom by cardiologist. Simultaneously, semiquantitative measurement of cTnT was performed using same blood sampling on the blind condition to cardiologists for this study. Study patients were divided into four groups according to the estimated glomerular filtration rate (eGFR), CKD1-2, CKD3, CKD4-5, and CKD5D. Usefulness of semiquantitative measurement for diagnosing ACEs was investigated in each group. 77 (38%) of total patient was diagnosed as acute coronary events (ACEs). About 50% of patients were showing cTnT level less than 0.03 ng/mL. The cTnT level over 0.1 ng/mL was found in 30% of total subjects. Mean quantitative value of cTnT was 0.29 ± 0.57 ng/mL in total subjects. Estimated cutoff value in CKD3 patients was 0.088 ng/mL with a sensitivity of 59.3% and specificity of 80.0%. Interestingly, the cutoff values of CKD1-2, CKD4-5, and CKD5D were 0.047, 0.18, and 0.27 respectively, which are half, two times, and three times of CKD3 cutoff value 0.088. The specificities of four cutoff values in each CKD group were showing over 80%, which is higher than sensitivity, respectively. In CKD patients, semiquantitative, point of care assessment of cTnT could be a useful tool for screening for ACEs.

The FRAX ® as a predictor of mortality in Japanese incident hemodialysis patients: an observational, follow-up study.

The World Health Organization Fracture Risk Assessment Tool (FRAX(®)) was recently developed to estimate the 10-year absolute risk of osteoporotic fracture among the general population. However, the evidence for its use in chronic kidney disease patients has been lacking, and the association between the FRAX(®) and mortality is unknown. Therefore, a hospital-based, prospective, cohort study was conducted to evaluate the predictive ability of the FRAX(®) for mortality in hemodialysis patients. A total of 252 patients who had been started on maintenance hemodialysis, 171 men and 81 women, with a mean age of 67 ± 14 years, was studied. The endpoint was defined as all-cause death. The Cox proportional hazards model was used to calculate hazard ratios and 95 % confidence intervals. During the mean follow-up period of 3.4 ± 2.7 years, 61 deaths occurred. The median (interquartile range) of the FRAX(®) for major osteoporotic fracture was 6.9 (4.6-12.0) % in men and 19.0 (7.6-33.0) % in women. Cumulative survival rates at 5 years after starting dialysis, with the FRAX(®) levels above and below the median, were 51.9 and 87.9 %, respectively, in men and 67.4 and 83.7 %, respectively, in women. Overall, in men, the multivariate Cox regression analyses revealed that the log-transformed FRAX(®) remained an independent predictor of death after adjusting by confounding variables. However, in women, the significant association between the FRAX(®) value and the outcome was eliminated if age was put into these models. Among Japanese hemodialysis patients, the FRAX(®) seems to be useful for predicting death, especially in men.