Biomedical subjects

H Otsubo

Publications and source records attributed to H Otsubo.

At least 19 recordsLinked to original sources

PubMed2007

Effects of the short chain sugar acid 2-buten-4-olide on the hypothalamo-pituitary-adrenal axis in normal and adjuvant-induced arthritic rats.

The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-adenohypophysial system were examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA) rats. In comparison with vehicle-treated rats, the plasma corticosterone and c-fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased significantly after i.p. administration of 2-B4O. Dual immunostaining revealed that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI) 120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly suppressed the expression of clinical symptoms and significantly increased plasma concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA levels in the anterior pituitary; however, they did not change arginine vasopressin mRNA levels in the parvocellular division of the PVN. These results suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary-adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the activation of the HPA axis by i.p. administration of 2-B4O may be associated with the inhibition of AA in rats.

4-Butyrolactone↗

PubMed2006

Magnetoencephalographic spike sources associated with auditory auras in paediatric localisation-related epilepsy.

OBJECTIVE: To characterise magnetoencephalographic spike sources in paediatric patients with auditory auras and recurrent localisation-related epilepsy. METHODS: Six patients (four boys and two girls (ages 7-14 years) were retrospectively studied. All patients had auditory auras as part of their initial seizure manifestation, including four patients who underwent previous brain surgery. Scalp video electroencephalography and magnetoencephalography (MEG) were carried out in six patients, intraoperative electrocorticography in three patients and extraoperative intracranial video electroencephalography in one patient. MEG auditory-evoked fields (AEFs) were studied in four patients. RESULTS: Three patients had elementary auditory auras, one had complex auditory aura and two had both complex and elementary auras. All six patients had clustered MEG spike sources with coexisting scattered spike sources. MEG clusters were localised in the superior temporal gyrus with surrounding scatters in four patients (two left and two right); two patients had scattered spikes in the superior temporal gyrus in addition to clustered MEG spike sources in the left inferior and middle frontal gyri or parieto-occipital region. AEFs were located within an MEG cluster in one patient and within 3 cm of a cluster in two patients. Surgical resection, including the regions of MEG clusters, was carried out in four patients. Three of four patients who had previous surgeries were seizure free at 2 years after excision of the MEG cluster region. CONCLUSIONS: MEG spike sources clustered in the superior temporal gyrus in six patients with auditory auras. These spike sources were in close proximity or seemed to engulf the magnetic AEF. Areas with MEG spike sources contained the residual or recurrent epileptogenic zone after incomplete cortical excision for lesional epilepsy.

Adolescent↗

PubMed2005

Persistent nucleated red blood cells in peripheral blood is a poor prognostic factor in patients undergoing stem cell transplantation.

We compared detection rates and counts of nucleated red blood cell (NRBC) in the peripheral blood of survivors and nonsurvivors (total 44 patients) of stem cell transplantation. The rate of NRBC detection increased to 79.5% after transplantation. After engraftment, the detection rate of NRBC decreased to 17.0% in survivors, but increased to 100% in nonsurvivors. The NRBC count increased after transplantation in both groups. This increase was transient in survivors, but increased after engraftment in nonsurvivors. The mean NRBC count after engraftment was 872 vs. 40.3 for nonsurvivors vs. survivors, respectively. At postengraftment, all patients who were negative for NRBC survived, but 10 of the 15 patients who were positive for NRBC died (66.7%). The survival rates of patients with a NRBC count >200 x 10(6)/l were significantly lower than those of patients whose counts were <100 x 10(6)/l. These data indicated that persistent NRBC in peripheral blood is a poor prognostic factor, and suggested that monitoring NRBC after SCT might provide useful clinical information.

Adolescent↗

PubMed2004

Dysembryoplastic neuroepithelial tumors in childhood: long-term outcome and prognostic features.

BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNTs) are associated with medically intractable epilepsy and a favorable prognosis after surgical resection. The authors describe the clinical, radiologic, and pathologic characteristics and outcomes in children after surgical resection of pathologically confirmed DNT to ascertain prognostic features for seizure recurrence following surgery. METHODS: Neurology, neurosurgery, and pathology databases from 1993 to 2002 at the Hospital for Sick Children were searched to retrospectively identify children with confirmed DNT and presentation with seizures. Risk factors for postoperative seizure recurrence were examined with respect to seizure outcome at 12 months and long-term follow-up. RESULTS: Of the 26 children identified (mean age at surgery 10.0 years) seizure outcome was good in 22 children (85%) at 12 months (Class 1). At longer follow-up (mean 4.3, range 1.0 to 11.0 years) only 16 (62%) remained seizure-free. Residual DNT was evident in 15 of the 24 children with available postoperative MRI. Three children demonstrated recurrence of tumor. At 12 months follow-up, older age (>10 years) and longer duration of epilepsy (>2 years) were associated with seizure recurrence. The presence of residual tumor was a risk factor for seizure recurrence at long-term follow-up (p = 0.02). CONCLUSIONS: Children with DNT and epilepsy may benefit from surgical management; however, seizure outcome is not always favorable. Although the majority of children remain seizure free after surgical excision of DNT, a considerable number have recurrent seizures. Short-term outcome is influenced by older age at surgery and longer duration of epilepsy. Residual tumor is a significant risk factor for poor seizure outcome. Recurrent tumor can occur.

Adolescent↗

PubMed2003

Immunosuppressive therapy with antithymocyte globulin and cyclosporine for prolonged marrow failure after hemophagocytic syndrome.

We describe a patient with typical hemophagocytic syndrome (HPS) in whom pancytopenia was refractory to steroid pulse therapy. He was successfully treated with immunosuppressive therapy using antithymocyte globulin (ATG) and cyclosporine (CyA), which is known to be effective for aplastic anemia (AA). Activation of histiocytes occurs in HPS as a response to several cytokines produced by activated T lymphocytes, while apoptosis of hematopoietic stem cells in AA is caused by T lymphocyte-derived cytokines. The response of this patient indicated that both diseases may have some similar immune-mediated conditions involving the activation of T lymphocytes and that intensive immunosuppressive therapy with ATG and CyA might be a useful strategy for steroid-resistant HPS.

Adult↗

PubMed2003

Secondary polycythemia as a paraneoplastic syndrome of testicular seminoma.

A 45-year-old man was referred to our hospital because of polycythemia. A physical examination revealed a large tumor in his scrotum enlarged to the size of 13 x 10 cm. A laboratory examination revealed severe erythrocytosis with a red blood cell count of 6,820 x 10(9)/L, a hemoglobin concentration of 21.2 g/dL, and a hematocrit of 59.8%. The total red cell volume was increased. A right radical orchidectomy was done with minimum bleeding, and he was diagnosed as having pure seminoma. After the operation, polycythemia improved spontaneously. Polycythemia is a rare complication of seminoma and only two cases have been reported previously. The precise mechanism of polycythemia in our patient could not be clearly evaluated, but clinical course did indicate a close relationship between two distinct disorders.

Hematologic Tests↗

PubMed2003

Malformations of cortical development with balloon cells: clinical and radiologic correlates.

BACKGROUND: Balloon cells are a key feature of tuberous sclerosis (TS) but are also seen in focal cortical dysplasia (FCD). The authors compare the clinical and MRI characteristics in children with medically refractory localization-related epilepsy who were found to have balloon cells on histology after cortical resections. METHODS: A retrospective review of clinical and MRI data in cases ascertained from a search of pathology records from 1990 until 2000 for those with a diagnosis of FCD or TS. Seventeen patients were identified with malformations of cortical development with balloon cells on histology. Seven had clinical diagnosis of TS and the remaining 10, FCD with balloon cells (FCDBC). RESULTS: Seventy percent of patients with FCDBC (mean follow-up 3.3 years) and 33% of patients with TS (mean follow-up 5.1 years) are seizure free after surgery. There was agreement between the diagnosis based on preoperative MR imaging and on histology in 60% of patients with FCDBC and 71% of patients with TS. Myelin depletion and calcification were noted more frequently in patients with TS. CONCLUSIONS: No significant differences were noted between patients with refractory epilepsy caused by TS or FCDBC. There was a trend toward better postoperative seizure control in the FCDBC group. These two conditions are difficult to distinguish on the basis of MR and histologic appearances. The authors conclude that FCDBC likely represents a phenotypic variation of TS, and as such, all patients with balloon cell dysplasias should be carefully screened for other features of TS to enable appropriate genetic counseling.

Cerebral Cortex↗

PubMed2003

Adhesion molecule expression by bone marrow CD34-positive cells in aplastic anemia before and after immunosuppressive therapy.

Appropriate adhesion between bone marrow stem cells and the marrow microenvironment is necessary for hematopoiesis, since signals that promote maturation or apoptosis are transmitted from stromal cells to stem cells. In aplastic anemia (AA), interferon-gamma produced by stromal cells has more influence on the pathogenesis of marrow failure than interferon-gamma produced by lymphocytes. We evaluated the expression of cell adhesion molecules, such as very late antigen-4 (CD49d), and -5 (CD49e) or c-kit receptor (CD117), by CD34-positive bone marrow cells in patients with AA who achieved hematological complete remission after immunosuppressive therapy. Before treatment, CD34-positive cells showed markedly higher expression of CD49d and CD49e than cells from healthy controls, indicating the strong adhesion of stem cells to the bone marrow stroma. Expression of CD49d and CD49e was significantly decreased, reaching normal levels, after hematological recovery. These findings suggest that changes in adhesion molecule expression by stem cells are important in the pathology of AA.

Adult↗

PubMed2003

Ictal magnetoencephalographic discharges from elementary visual hallucinations of status epilepticus.

PURPOSE: To report the rare opportunity to study ictal magnetoencephalography (MEG) in a 26 year old man with simple partial status epilepticus that presented as elementary visual hallucinations (EVHs) in the right upper visual field. METHODS: The patient described his EVHs as "snowing on TV," "flickering lights," and "rotating coloured balls" that continued for several days. MEG and simultaneous EEG were recorded twice: during an episode of EVHs (ictal recordings) and after EVHs were controlled by medications (interictal recordings). RESULTS: During EVHs, MEG showed continuous periodic epileptiform discharges over the left posterior superior temporal region, while simultaneous EEG showed rhythmic theta waves and sporadic spikes over the left temporal region. The MEG discharge consisted of a three phase spike complex. Equivalent current dipoles (ECDs), modelled from spike complexes, localised in the left superior temporal area. After drug treatment controlled the EVHs, interictal MEG and EEG showed rare spikes over the same left temporal region. The average ictal ECD moment (mean (SD)) (128.7 (32.8 nAm)) was significantly weaker than the average interictal ECD moment (233.0 (63.9) nAm) (p<0.05). CONCLUSIONS: The continuous, periodic, and clustered discharges seen on ictal MEG were the sources of EVH. The weaker ictal ECD sources were frequently not detected by scalp EEG, while the stronger interictal sources, presumably originating from an extensive interictal zone, were sufficiently large to be seen as EEG spikes.

Adult↗

PubMed2001

Neuromagnetic spectral distribution of implicit processing of words.

Neuromagnetic spectral distributions when silently viewing words and non-words were investigated using a 151-channel whole head MEG system. The data were analyzed with synthetic aperture magnetometry (SAM). The dominant changes of spectral power were identified in the parietal and occipital cortices in 15-30 Hz, 30-60 Hz and 60-125 Hz bands following both word and non-word stimulations. The changes in Broca's and Wernicke's areas were consistently observed in 60-125 Hz bands, mainly following word stimulation. The results indicated that the occipital and parietal cortices were most probably involved in visuospatial processing of words and non-words. The language areas, particularly Broca's and Wernickes's areas, might be involved in implicit word processing such as verbal searching and/or internal speech.

Adult↗

PubMed2001

Malignant rolandic-sylvian epilepsy in children: diagnosis, treatment, and outcomes.

OBJECTIVE: To describe the diagnosis, treatment, and outcomes in children with malignant rolandic-sylvian epilepsy (MRSE), defined as a form of epilepsy characterized by sensorimotor seizures, medical refractoriness, normal MRI, frontocentrotemporal EEG spikes, rolandic-sylvian spike sources on magnetoencephalography (MEG), and cognitive problems. METHODS: A retrospective chart analysis of seven patients who had shown these characteristics and undergone extensive diagnostic testing, including MEG and intracranial video-EEG was performed. RESULTS: Interictal scalp EEG spikes were seen over the frontocentrotemporal regions bilaterally (6) and unilaterally (1). MEG showed spike sources in the perisylvian region in two patients (both bilateral) and in the perirolandic fissure in five (two bilateral). Three patients required bilateral subdural strips to lateralize seizures before electrocorticography. Final electrocorticograms showed an ictal onset zone around the rolandic (four cases) and rolandic-sylvian regions (three cases). Six patients showed neuropsychological deficits. After cortical excision and multiple subpial transection, three were seizure free and four had seizures rarely (30 months' mean follow-up). No child had a permanent deficit in sensorimotor or cognitive functions, although two showed exacerbation of preexisting attentional deficits. Tissue analysis showed definite evidence of neuronal migration disorders (3) and gliosis (2). CONCLUSIONS: MEG was helpful for localizing both malignant rolandic-sylvian neuronal activities and functional cortex. Successive neuropsychological assessments are necessary to detect cognitive deterioration and indicate remedial programming. If, after careful observation over at least 5 years, surgery is considered to control refractory seizures, intracranial video-EEG is needed to localize the epileptogenic zone.

Adolescent↗

PubMed2001

Prognostic value of EEG in neonatal bacterial meningitis.

The contribution of electroencephalogram (EEG) findings early in the course of neonatal bacterial meningitis to the prediction of severe adverse outcome was assessed in a retrospective cohort study. Infants had known outcomes to 1 year of age and an EEG performed during the first week of illness. EEGs were subclassified as follows: overall EEG description, background activity, presence of positive rolandic sharp waves, presence of seizure activity, and presence of focal abnormal activity. EEG patterns predictive of severe adverse outcome were identified by univariate and multivariate analyses. Of 101 infants admitted with bacterial meningitis, 37 had an EEG performed. Of the 37 infants, 21 had adverse outcomes; nine infants died, and 12 infants had moderate or severe disability. EEG background activity and overall EEG description were identified as predictors of adverse outcome; multivariate analysis indicated that the latter was a stronger predictor (sensitivity 88%, specificity 90%). Infants with normal or mildly abnormal EEGs had good outcomes whereas those with moderate to markedly abnormal EEGs died or survived with adverse outcome. The accuracy of predictions increased when EEGs were repeated. In a high-risk population of infants with bacterial meningitis, moderate-to-markedly abnormal EEG reliably predicts adverse outcome.

Brain Damage, Chronic↗

PubMed2001

Extraoperative cortical stimulation of motor function in children.

The purpose of the study was to investigate factors altering the amperage threshold needed to provoke functional responses in children with epilepsy. Twenty patients (4-18 years of age) who underwent epilepsy surgery at our institution from 1996-2000 after insertion of subdural grid electrodes were reviewed retrospectively. Extraoperative electrical cortical stimulation was performed with 50-Hz biphasic pulses of 0.2 ms in duration using a "distance reference" technique. Amperage thresholds of primary motor responses and afterdischarges were evaluated. The patients were grouped according to underlying pathology: eight with neuronal migration disorders (group A) and 12 with other disorders (group B). The motor cortex was defined successfully in all children because the afterdischarges threshold was higher than the motor cortical threshold. Amperage thresholds ranged from 2-20 mA (mean = 7.7) for primary motor function. An inverse relationship was found between amperage threshold and age: the younger the patient, the higher the threshold (P = 0.0005). Patients in group A required a higher amperage (2-20 mA, mean = 8.6) for motor cortical mapping than those in group B (2-14 mA, mean = 6.4). Younger children with neuronal migration disorders require a higher amperage threshold to achieve adequate motor functional mapping with careful observation of afterdischarges.

Adolescent↗

PubMed2001

Radiologic-pathologic correlation in focal cortical dysplasia and hemimegalencephaly in 18 children.

To describe the radiologic-pathologic correlation in children who underwent epilepsy surgery for medically intractable epilepsy with pathologically confirmed focal cortical dysplasia and hemimegalencephaly, we conducted a retrospective review on the magnetic resonance imaging and pathology of 18 children (10 boys and 8 girls). The preoperative MRIs were reviewed by one neuroradiologist who did not know the radiologic diagnosis and the pathology reports. MRI revealed focal cortical dysplasia (10), hemimegalencephaly (3), hamartomas (2), polymicrogyria (1), pial hemosiderosis (1), and no abnormality (1). Pathologic examination revealed focal cortical dysplasia (9), forme fruste of tuberous sclerosis (5), hemimegalencephaly (3), and focal cortical dysplasia with mesial temporal sclerosis (1). MRI was accurate in making the preoperative diagnosis in 16 out of 18 patients. On MRI, 12 patients had abnormal gyral formation and 12 had abnormal cortical thickness. Eleven patients manifested loss of gray-white differentiation, and 11 patients had abnormal signal on T(2)-weighted image. Pathologically, 15 patients had neuronal heterotopia, 12 had misalignment or disorientation of neurons, 11 had large neurons, and 10 had abnormal cortical lamination. The presence of ectopic and large neurons and abnormal cortical lamination may be responsible for the MRI characteristics.

Biopsy↗

PubMed2001

MEG predicts epileptic zone in lesional extrahippocampal epilepsy: 12 pediatric surgery cases.

PURPOSE: To discover whether the spatial distribution of spike sources determined by magnetoencephalography (MEG) provides reliable information for planning surgery and predicting outcomes in pediatric patients with lesional extrahippocampal epilepsy. METHODS: We retrospectively studied 12 children with extrahippocampal epilepsy secondary to cortical dysplasia (CD), tumor, or porencephalic cyst. We compared interictal MEG spike source locations and somatosensory evoked fields derived from equivalent-current dipole modeling with intraoperative or extraoperative electrocorticography (ECoG). RESULTS: MEG spike sources were found in proximity to the lesion in all patients and extended from lesions in five patients with CD. Marginal spike sources were noted in three patients with tumors, one patient with a cyst, and one with CD, and extramarginal sources in three patients with tumors. Three patients with tumors underwent lesionectomy only; two had further cortical excisions. One patient with CD underwent lesionectomy only, three had lesionectomy and cortical excisions, and two had lesionectomy and multiple subpial transection. Asymmetric MEG spike sources correlated with ECoG findings in all patients. Residual epileptiform discharges on postexcisional ECoG corresponded to spike sources in three patients with tumors and one patient with a cyst. Eleven patients have been seizure free for 1-6 years (mean, 4 years). One patient had residual seizures after incomplete excision of right temporal CD. CONCLUSIONS: MEG delineated asymmetric epileptogenicity surrounding lesions and the eloquent cortex. Complete tumor resection produced favorable outcomes despite residual postexcisional ECoG spikes and extramarginal MEG spike sources. CD characterized by clusters of MEG spike sources within and extending from lesions seen on magnetic resonance imaging (MRI) should be removed to prevent seizures.

Adolescent↗

PubMed2001

Dipole localization for identification of neuronal generators in independent neighboring interictal EEG spike foci.

PURPOSE: We evaluated dipole localizations of independent neighboring interictal spike foci using scalp electroencephalogram (EEG) to identify neuronal generators of epileptic discharges. METHODS: Three pediatric patients with extratemporal lobe epilepsy who had two independent neighboring interictal spike foci on scalp EEG were studied. Prolonged video EEG was digitally recorded from 19 scalp electrodes, whose positions were registered using a three-dimensional digitizer. Interictal spikes were visually selected based on negative phase reversals on bipolar montages. We analyzed the dipole position and moment of each spike using a single moving dipole and three-shell spherical head model. The dipoles were overlaid onto magnetic resonance (MR) images and divided into two groups based on two spike foci. RESULTS: The dipoles of the two groups were oriented either tangentially or radially to the scalp in close proximity to each other. The dipoles oriented radially were located underneath the electrode with a negative peak; those oriented tangentially were between electrodes with a negative and positive peak. The positions of tangential dipoles were more concentrated than those of radial dipoles. The epileptogenic regions corresponded to the dipole localizations. Surgical excisions were performed based on the results of electrocorticography. After surgery, two patients were seizure free, and one had rare seizures (follow-up period, 13-31 months). CONCLUSIONS: We showed that dipoles in close proximity but with different orientations projected two negative maxima on scalp EEG in three patients with extratemporal localization-related epilepsy. Equivalent current dipole analysis of individual interictal spikes can provide useful information about the epileptogenic zone in these patients.

Adolescent↗

PubMed2001

Image-guided, frameless stereotactic sectioning of the corpus callosum in children with intractable epilepsy.

Corpus callosotomy is an effective neurosurgical procedure for children with intractable atonic or drop attack seizures. While this procedure has not changed significantly over the past three decades, some technical issues remain to be resolved. These include the intraoperative determination of the extent of the callosotomy, the need to stage the procedure, as well as side of approach of craniotomy. We report our 8-year experience with corpus callosotomy using a frameless stereotactic image-guided system (ISG Viewing Wand). Seventeen children with atonic seizures underwent sectioning of the corpus callosum. The mean patient age was 10.5 years. Six children underwent complete callosotomy while 11 underwent resection of the anterior two-thirds. MRI 3D reconstruction of the sagittal sinus and draining cerebral veins was undertaken in all cases. The side of the craniotomy was determined on the basis of favorability of the draining veins with respect to the extent of the callosotomy. The extent of the callosotomy was determined by intraoperative feedback using the ISG Viewing Wand((R)). Nine of 11 patients in the partial callosotomy group and 4 of 6 patients in the complete callosotomy group showed significant improvement in atonic seizures. We conclude that the use of frameless stereotaxy can function as an important adjunct in the planning and conduction of successful sectioning of the corpus callosum in children with intractable seizures.

Adolescent↗

PubMed2001

Magnetoencephalography and magnetic source imaging in children.

Magnetoencephalography is a technique that detects the magnetic fields associated with the intracellular current flow within neurons, unlike electroencephalography, which measures extracellular volume currents. Superconducting quantum interference devices are used to amplify these very small magnetic field signals. Magnetic source imaging is the combination of functional data derived from magnetoencephalographic recordings coregistered with structural magnetic resonance imaging (MRI). The utility of magnetic source imaging lies in the combination of the submillisecond temporal resolution of magnetoencephalography with the precise anatomic images provided by magnetic resonance imaging. As such, magnetic source imaging is a useful tool for noninvasive localization of the epileptogenic zone in children who are candidates for epilepsy surgery. Similarly, using magnetoencephalographic recordings with evoked and event-related potentials, magnetic source imaging holds great promise as a noninvasive method for precise localization of somatosensory, motor, language, visual, and auditory cortex. Finally, magnetic source imaging is proving a valuable research tool in the investigation of epilepsy, head trauma, brain plasticity, and disorders of language, memory, cognition, and executive function in children.

Cerebral Cortex↗