PubMed Health⌕ Search

Biomedical subjects

J T Rutka

Publications and source records attributed to J T Rutka.

At least 19 recordsLinked to original sources
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

Ocular manifestations of crush head injury in children.

AIMS: To review the ocular manifestations of crush head injuries in children. METHODS: Retrospective clinical and pathological reviews. Group 1: A total of 16 children admitted with crush head injuries from television tip over. Group 2: Nine autopsy findings in crush head injury. RESULTS: Group 1: A total of 11 children had fundus examination: three by neurosurgeons, eight by ophthalmologists. Scattered posterior pole preretinal and blot haemorrhages extending to mid equator region observed in one child. No evidence of traumatic retinoschisis or retinal folds in any patient. Group 2: All with multiple skull fractures and six with subdural haemorrhage. Posterior pole retinal haemorrhages in four children, extending to the ora serrata in one after motor vehicle accident. No child had retinal folds. Subinternal limiting membrane haemorrhages in three children. Optic nerve sheath haemorrhage in three children. CONCLUSIONS: Intraretinal and preretinal haemorrhages, predominantly in the posterior pole, can occur in crush injury to the paediatric head. Haemorrhage under the internal limiting membrane or extending to the ora serrata were only seen in situations where crush injury was part of a fatal trauma scenario related to motor vehicles. Retinal folds and the typical macular retinoschisis associated with abusive head injury were not observed.

Accidents, Home↗
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

Effect of PSC 833, a potent inhibitor of P-glycoprotein, on the growth of astrocytoma cells in vitro.

Malignant astrocytomas have been found to express P-glycoprotein (Pgp, mdr1 gene product). It was hypothesized that in addition to conferring multidrug resistance, Pgp is intimately associated with the development of astrocytomas. Accordingly, we studied the effect of PSC 833 (PSC, Novartis), a potent inhibitor of Pgp, on the growth of Pgp-expressing astrocytoma cells. The results showed that in all the cell lines tested, PSC (10-60 microM) inhibited the growth as well as induced cell death. Cells exposed to PSC exhibited DNA ladder characteristic of apoptosis. PSC-induced cell death could be reversed by Z-VAD-fmk, a general caspase inhibitor, indicating that PSC-induced cell death was characteristic of caspase-mediated apoptosis. These results suggest a novel therapeutic strategy in the treatment of malignant astrocytomas by inhibitors of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
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

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

The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth.

The unique INK4A/ARF locus at chromosome 9p21 encodes two distinct proteins that intimately link the pRB and p53 tumour suppressor pathways. p16INK4A has been identified as an inhibitor of the cell cycle, capable of inducing arrest in G1 phase. p14/p19ARF on the other hand can induce both G1 and G2 arrest due to its stabilizing effects on the p53 transcription factor. In addition to their roles in growth arrest, both proteins are involved in cellular senescence and apoptosis. The frequent mutation or deletion of INK4A/ARF in human tumours as well as the occurence of tumours in the murine knockout models have identified both p16 and ARF as bona fide tumour suppressors.

Animals↗
PubMed2001

Cip/Kip cell-cycle inhibitors: a neuro-oncological perspective.

The cell cycle is a precisely controlled cellular program that ensures normal cellular proliferation and development. The cyclin-dependant kinases (CDK) are molecules central to the continued progression through the cell-cycle checkpoints and as such are regulated by various mechanisms including cyclin levels, phosphorylation/dephosphorylation and cyclin-dependant kinase inhibitors (CKI). The CKIs are grouped into two families based on their structure and function, four lnk4 CKIs and three Cip/Kip CKIs. Abnormalities in these proteins can give rise to developmental defects and cancer. In this review, we will discuss the biochemistry and cell biology of the each of the Cip/Kip CKIs, their role in development as evidenced by targeted mutations in mice, and their role as possible tumor suppressor genes.

Animals↗
PubMed2001

Hyaluronate receptors mediating glioma cell migration and proliferation.

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

Antibodies, Monoclonal↗
PubMed2001

Molecular genetics of pineal region neoplasms.

A large variety of mass lesions have been reported in the region of the pineal gland. Pineal parenchymal tumors and germ cell tumors (GCTs) are especially characteristic of this region. Despite their rarity, a number of excellent studies on the cytogenetics and molecular genetics of pineal parenchymal tumors and pineal region GCTs have been published. These studies draw attention to a number of distinct genomic regions recurrently involved in the various subtypes of malignancies of the pineal gland. Outcomes for tumors in this location vary widely between patients and among differing histologies. Development of novel therapies for patients with poor prognoses will depend on the acquisition of a more detailed understanding of the molecular basis associated with the etiopathogenesis of these neoplasms. We review the literature on cytogenetics, familial syndromes, animal models and molecular genetics of pineal region neoplasms.

Animals↗
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

MIB-1 staining index of pediatric meningiomas.

OBJECTIVE: For adult meningiomas, the staining index (SI) for the anti-Ki-67 monoclonal antibody MIB-1 is well correlated with histological atypia and tumor recurrence. MIB-1 SIs for meningiomas in the pediatric population have not been previously reported. Meningiomas tend to be more histologically aggressive and to recur more frequently in children, compared with adults. The objectives of this study were to determine whether MIB-1 SIs are correlated with pathological atypia and recurrence among pediatric meningiomas and to compare the MIB-1 SIs of pediatric meningiomas with those of adult meningiomas. METHODS: MIB-1 SIs were assessed on paraffin-embedded sections of 14 pediatric meningiomas (patient age, 2-17 yr), 5 of which contained atypical or malignant features. For comparison with benign pediatric meningiomas, MIB-1 SIs were also assessed on paraffin-embedded sections of 14 adult meningiomas (patient age, 38-90 yr), none of which displayed atypical or malignant features or recurred within a 5-month median follow-up period. RESULTS: MIB-1 SIs of pediatric meningiomas ranged from 1.2 to 31.6% (median, 9.1%). Significant differences were observed between the MIB-1 SIs for tumors with atypical or malignant features (median, 12.3%; range, 7.0-31.6%) and those for tumors without atypia (median, 7.0%; range, 1.2-12.6%; P = 0.045). There were six recurrences after gross total resection, during a 36.5-month median follow-up period. All five of the tumors with pathological atypia recurred; one tumor without atypia recurred. Significant differences were observed between MIB-1 SIs for nonrecurrent tumors (median, 6.6%; range, 1.2-12.2%) and those for recurrent tumors (median, 12.5%; range, 7.0-31.6%; P = 0.012). The median MIB-1 SI for adult control specimens was 8.8% (range, 1.2-19.3%), which did not differ significantly from that for pediatric meningiomas without atypia (P = 0.68). CONCLUSION: For this cohort of pediatric meningiomas, pathological atypia and the tendency to recur were correlated with elevated MIB-1 SIs. The median MIB-1 SI for pediatric meningiomas without histological atypia did not differ significantly from that for adult meningiomas without atypia, suggesting that the more aggressive clinical features of meningiomas in children may be attributable to factors other than the rate of cellular proliferation.

Adolescent↗
PubMed2001

Spontaneous intraparenchymal hemorrhage in full-term neonates.

OBJECTIVE: Spontaneous intraparenchymal hemorrhage is extremely rare in full-term newborns. Reports to date have been limited to descriptions of individual cases, small groups within larger studies of intracranial hemorrhage, and one series of four patients. Structural lesions are rarely identified, and the majority of patients described have been managed without surgical intervention. METHODS: Analysis of a computerized database of pediatric neurosurgical patients from January 1960 to February 2000 identified full-term newborns younger than 3 months of age with nontraumatic intraparenchymal hemorrhages. Prenatal histories, labor and delivery histories, clinical presentations, imaging studies, management, and outcomes were reviewed. RESULTS: Eleven full-term newborns with spontaneous intraparenchymal hemorrhages were identified. The majority had normal prenatal courses. Most presented within the first 2 days of life (6 of 11 patients), and the most common presenting sign was seizure (7 of 11 patients). No cause was identified in 6 of 11 patients; the remainder were attributed to coagulopathy (n = 3), ruptured intracranial aneurysm (n = 1), or hemorrhagic infarction (n = 1). Eight patients underwent surgical hematoma evacuation on the basis of radiographic evidence of significant mass effect, evidence of signs of elevated intracranial pressure, or both. Three patients did not receive surgical intervention. There were no subsequent hemorrhages or deaths during a mean follow-up period of 4.5 years (range, 1-16 yr). Four patients had normal neurological outcomes, four had motor deficits (one of whom additionally demonstrated cognitive delay), and three had delayed speech. CONCLUSION: No cause is identified in most newborns with spontaneous intraparenchymal hemorrhage. Radiographic evidence of mass effect or signs of elevated intracranial pressure may necessitate surgical hematoma evacuation. Outcome varies widely and may be normal, even in patients with sizeable intraparenchymal hemorrhages.

Aneurysm, Ruptured↗
PubMed2001

Medulloblastoma in a child with Rubenstein-Taybi Syndrome: case report and review of the literature.

Although medulloblastoma is usually sporadic, there are a number of uncommon predisposing germline mutation syndromes, including: Gorlin's Syndrome, Turcot's Syndrome and Li-Fraumeni Syndrome. Patients with Rubenstein-Taybi Syndrome secondary to mutation/deletion of the CBP gene on chromosome 16 are predisposed to a variety of developmental anomalies as well as cancer. We report a child with Rubenstein-Taybi syndrome who developed a cerebellar medulloblastoma and review the literature on Rubenstein-Taybi Syndrome and pediatric medulloblastoma. As the product of the CBP gene functions in a variety of signaling pathways, we discuss the molecular implications of findings a medulloblastoma in a child with Rubenstein-Taybi Syndrome.

Abnormalities, Multiple↗
PubMed2001

Total resection of an intracerebral hemangioendothelioma in an infant. Case report and review of the literature.

Hemangioendotheliomas (HEs) are vasoformative tumors rarely seen in the CNS. Histopathological features determining aggressive phenotypes have not been well defined. Potential cytogenetic alterations in these tumors have not been previously reported. We present a 4-month-old male infant with a temporal lobe HE. Fluorescence in situ hybridization and spectral karyotype analysis revealed translocation of chromosome 11q23. This case constitutes the first report of a gross total resection of an intracerebral HE in the pediatric age group, and of potential cytogenetic alterations involved in its pathogenesis. Based on our report and review of the literature, we note a discrepancy between histopathological criteria of aggressive tumor biology and clinical behavior. Further study of chromosomal abnormalities may be helpful in defining factors associated with a higher risk of malignant behavior. We conclude that gross total resection is currently the best available treatment option for these tumors, regardless of histology.

Biomarkers, Tumor↗