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Biomedical subjects

A Canady

Publications and source records attributed to A Canady.

At least 19 recordsLinked to original sources

Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex.

OBJECTIVE: Using interictal alpha-[11C]methyl-l-tryptophan ([11C]AMT) PET scan, the authors have undertaken a quantitative analysis of all tubers visible on MRI or 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET, to determine the relationship between [11C]AMT uptake and epileptic activity on EEG. BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder, often associated with cortical tubers and intractable epilepsy. The authors have shown previously that [11C]AMT PET scans show high tracer uptake in some epileptogenic tubers and low uptake in the remaining tubers. METHODS: Eighteen children, age 7 months to 16 years, were studied. Patients underwent video-EEG monitoring, PET scans of [11C]AMT and [18F]FDG, and T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. [11C]AMT uptake values were measured in 258 cortical tubers delineated with coregistered MRI or [18F]FDG scans. Uptake ratios were calculated between the [11C]AMT uptake in tubers and those for normal cortex (tuber/normal cortex). Using the region of epileptiform activity, the authors performed receiver operator characteristics (ROC) analysis and determined the optimal uptake ratio for detecting presumed epileptogenic tubers. RESULTS: Tuber uptake ratios ranged from 0.6 to 2.0. Tuber uptake ratios in the epileptic lobes were higher than those in the nonepileptic lobes (p < 0.0001). All 15 patients with focal seizure activity showed one or more lesions with uptake ratio above 0.98 in the epileptic lobe. ROC analysis showed that a tuber uptake ratio of 0.98 resulted in a specificity of 0.91. CONCLUSIONS: Cortical tubers with [11C]AMT uptake greater than or equal to normal cortex are significantly related to epileptiform activity in that lobe. Together, interictal [11C]AMT PET and FLAIR MRI improve the detection of potentially epileptogenic tubers in patients with TSC being evaluated for epilepsy surgery.

Adolescent↗

Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.

OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.

Adolescent↗

The effects of multiple shunt revisions on neuropsychological functioning and memory.

The focus of this study was to determine the effect of multiple shunt revisions on cognition and memory. The present study attempted to document a discrepancy in the functioning of children with hydrocephalus having numerous shunt revisions compared to those with only an initial shunt surgery. Researchers have found an increasing number of children with hydrocephalus requiring shunt revisions. In the current literature there are many conflicting views regarding the effects of hydrocephalus on cognition and memory. Many researchers report that properly treated hydrocephalus will not have a negative impact on cognitive functioning. Furthermore, researchers found that factors such as the total number of shunt revisions do not negatively impact global intellectual ability. Forty-six subjects between the ages of six and 16 years participated in the study. The subjects were recruited from the Department of Neurosurgery at an urban pediatric hospital. Specific inclusion and exclusion criteria were met. Independent variables for the study included shunt revisions, seizures, and Attention Deficit Hyperactivity Disorder (ADHD). Subject groupings were based on whether the subjects required multiple shunt revisions or single shunt placement and the presence or absence of seizures and ADHD. Dependent variables included the subject's performance on measures of cognition and memory. Measures of functioning included the Wechsler Intelligence Scale for Children--Third Edition and the Wide Range Assessment of Learning and Memory-Screener. The results of this study did not support the presence of cognitive or memory impairments as a result of multiple shunt revisions. Anecdotal findings noted that seizures were the only independent variable to significantly account for the observed variance in scores of cognition, specifically Full Scale IQ, Verbal Comprehension, and Perceptual Organization.

Adolescent↗

Altered in vitro and in vivo flumazenil binding in human epileptogenic neocortex.

In vitro and in vivo parameters of flumazenil (FMZ) binding were measured in spiking and nonspiking neocortex identified by intraoperative electrocorticography in epileptic patients who underwent cortical resection for seizure control. In vitro measures of receptor affinity (K(D)), number (Bmax) and laminar distribution for [3H]-FMZ binding in the epileptic focus (n = 38) were compared to nonspiking cortex from a subgroup of the patients (n = 12) and to tissue obtained from trauma patients (n = 5). The in vitro binding parameters were compared to in vivo [11C]-FMZ binding measured with positron emission tomography (PET) (n = 19). The Bmax was higher in the 38 spiking tissues as compared to the 12 nonspiking tissues (P = .012). Paired comparison of spiking versus nonspiking binding in the 12 patients from whom nonspiking tissue was available showed increases in both K(D) (P = .037) and Bmax (P = .0047) in spiking cortex. A positive correlation was found between K(D) and Bmax values for 38 patients (r = 0.55, P < .0001), the magnitude of the K(D) increase being twice that of the Bmax increase. In addition, there was a significant correlation between the asymmetry indices of the in vivo FMZ binding on PET and in vitro K(D) of spiking cortex (n = 19, r = 0.52, P = .02). The laminar distribution of [3H]-FMZ showed increased FMZ binding in cortical layers V-VI in spiking cortex compared to nonspiking and control cortex. The increased receptor number in spiking cortical layers V-VI may be a compensatory mechanism to decreased GABAergic input. The increased Bmax in spiking cortex was accompanied by a larger decrease in the affinity of FMZ for the receptor suggesting that decreased FMZ binding in the epileptic focus measured with PET is due to a decrease in the affinity of the tracer for the receptor.

Adolescent↗

Objective method for localization of cortical asymmetries using positron emission tomography to aid surgical resection of epileptic foci.

We designed a semiautomated method for the objective detection of abnormal regions of tracer accumulation in the brain. The purpose of the present study was to examine the diagnostic performance of this method by applying it to patients with clinically intractable epilepsy of unilateral origin; they underwent [F-18] deoxyglucose positron emission tomography (PET) prior to surgical resection of epileptic foci. A semiautomated method for assessment of asymmetries in the brain cortex was developed that compares activity concentrations in homotopic cortical areas. When these differences exceeded a predefined threshold, the areas with lower activity were marked and 3-dimensional surface rendered images were created to guide placement of intracranial electrodes (ECoG) followed by surgical resection. The normal amount of asymmetry between small (0.5-0.7 cm2) homotopic cortical regions was determined as 5.9 +/- 4.0% (mean +/- SD). The false-positive fraction was determined for cutoff thresholds of 1 SD (10%), 1.5 SD (12%), and 2 SD (15%) outside the mean and was found to be 89, 44, and 0%, respectively. The obtained sensitivity-specificity pairs for correct localization of epileptogenic lobes based on the ECoG results were best for the 15% threshold (80/94%, accuracy 0.90). This objective PET method allows the accurate determination of cortical asymmetries, and it proved to be highly efficient in guiding epilepsy surgery.

Adolescent↗

Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography.

Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.

Brain↗

Permanent I-125 brain stem implants in children.

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Brachytherapy↗

Chemical meningitis from bile reflux in a lumbar-gallbladder shunt.

OBJECTIVE AND IMPORTANCE: The gallbladder is used to divert cerebrospinal fluid (CSF) in patients with hydrocephalus when all other sites have been exhausted. This is seen in hydrocephalic patients who have reached teenage years but have undergone multiple shunt revisions, abdominal operations and repeated neck vein cannulations during childhood. One complication of the lumbar-gallbladder shunt is discussed as well as its pathophysiologic theory and management. CLINICAL PRESENTATION: A case of a patient with a lumbar-gallbladder shunt who developed chemical meningitis from reflux of bile into the CSF space is presented. The patient presented with generalized seizures. INTERVENTION: Included: ventilatory support, externalization of the shunt, correction of the metabolic abnormalities and administration of anticonvulsants and steroids. CONCLUSION: This case illustrates an unusual occurrence of reflux of bile into the CNS through a lumbar-gallbladder shunt in a patient with long-term complex communicating hydrocephalus. It also demonstrates its mode of presentation and successful management. To our knowledge, this is the first case report of its kind.

Adult↗

Component bone marker displacements revealed by image-corrected cephalometric analysis. A lateral cephalometric study of the cranium in normal and craniosynostosis--an implant study.

Displacement of bony component anatomy has not been comprehensively described in human cranial development. In this study, tantalum implants were used to define cranial bone position on serial cephalometric surveys. Image correction (ICCA method) was used to eliminate artifactual shift of component markers before serial analysis was used to define implant movement. In addition, applicable normative standards were used to assess all case presentations. Three normal subjects comprised a normal mixed longitudinal sample aged 2 to 84 months. Two plagiocephaly subjects were studied, one from 6 to 77 months and the other from 16 to 44 months of age. Three syndromic craniosynostosis subjects demonstrated both abnormal and normalized growth following craniotomy, from 14 to 45, from 0.5 to 5.5, and from 2 to 75 months of age. A pattern of backward rotation of cranial component anatomy was observed in three normal subjects and two plagiocephaly subjects. The posterior fossa (PF) showed the greatest growth activity, with displacement adjustments throughout the study, and the anterior cranial fossa (ACF) least growth activity, with imperceptible frontal bone movement after age 3 years. After traditional bifrontal craniotomy, an abnormal displacement growth pattern was observed from age 14 to 45 months in the patient with syndromic craniosynostosis (Pfeiffer syndrome). Extensive fronto-parietal "bossing" and grossly deficient movement in the PF were observed. However, after a bifrontal craniotomy that also crossed lambdoid sutures, a normalized pattern of displacement growth was observed in two Apert syndrome patients. These two patients with extensive syndromic craniosynostosis had cranial component pattern adjustments as in the normal and plagiocephalic subjects.

Cephalometry↗

Transcranial sonography through the burr hole for detection of ventriculomegaly. A preliminary report.

Detection of ventriculomegaly in a child with a ventricular shunt is important in the diagnosis of shunt malfunction. The feasibility of visualizing the ventricles through a 2-cm burr hole, with the use of a small-footprint 7-MHz transducer, was evaluated in five infants. Each burr hole remained patent during the study (2-6 months), and in all infants correlation between views through the anterior fontanelle and the burr hole were in agreement. When ventriculomegaly can be detected by this technique, the need for CT evaluation may be obviated. Further study is necessary to evaluate extended burr holes in older children compared to their CT examinations.

Arachnoid Cysts↗

Instability of the cervical spine after decompression in patients who have Arnold-Chiari malformation.

Stability of the cervical spine was studied in two groups of children who had myelomeningocele. Group I consisted of twenty children who had an Arnold-Chiari Type-II malformation in whom a suboccipital craniectomy (partial occipital craniectomy through the suboccipital route) and cervical laminectomy was done to decompress the brain stem. The average duration of follow-up in this group (excluding one patient) was 4.7 years (range, 2.3 to 10.4 years) after the operation. Group II consisted of twenty children who had myelomeningocele but had not had an operation for decompression. Lateral radiographs of the cervical spine in flexion and extension showed no instability between the occiput and atlas or between the atlas and axis in either group. In contrast, translation between the second and third cervical vertebrae averaged four millimeters in Group I and one millimeter in Group II (p less than 0.01), and angulation between the third and fourth cervical vertebrae averaged 17 degrees in Group I and 6 degrees in Group II (p less than 0.01). Nineteen of the twenty patients in whom a suboccipital craniectomy and cervical laminectomy (Group I) had been done had instability of the cervical spine.

Arnold-Chiari Malformation↗

Outcome after posthemorrhagic ventriculomegaly in comparison with mild hemorrhage without ventriculomegaly.

The neurodevelopmental sequelae in 33 low birth weight neonates with moderate or severe hemorrhage and ventriculomegaly (VM group) and in 39 neonates with mild hemorrhage only (non-VM group) were evaluated prospectively. Both groups were comparable in birth weight, gestational age, and socioeconomic status. Ventriculoperitoneal shunts were inserted in 23 of the 33 VM group infants at a mean age of 26 days. Eighty-two shunt revisions were performed, for obstruction (71 revisions) or infection (11 revisions), in 18 of the 23 children. At a mean age of 50 months, 19 of 33 children in the VM group had sequelae; 14 children had moderate or severe neurologic deficits, and 5 children had mild sequelae. In the non-VM group, only 3 of 39 children had deficits, all of which were mild (p less than 0.05). In the VM group, 19 of 33 children had mental developmental delay in comparison with 8 of 39 in the non-VM group (p less than 0.05), and 17 of 33 children in the VM group had motor developmental delay in comparison with 5 of 39 in the non-VM group (p less than 0.01). Within the VM group, the number of children with neurodevelopmental sequelae did not differ significantly among the 23 children with shunts, in comparison with the 10 who did not require shunting. Among the children with shunts, a higher incidence of sequelae occurred when lack of ventricular decompression was noted immediately after shunt insertion (p less than 0.005) and when shunt infections occurred (p less than 0.01). The most important predictor of mental and motor outcome in the group with shunts was lack of ventricular decompression immediately after shunt insertion. We speculate that, in some infants, loss of brain tissue, cerebral atrophy, or both may occur before insertion of the ventriculoperitoneal shunt, even when the shunt is inserted early.

Cerebral Hemorrhage↗

Role of aggressive intracranial pressure control in management of pediatric craniocerebral gunshot wounds with unfavorable features.

During a 6-year period, 14 consecutive children with penetrating craniocerebral gunshot wounds (GSW) were studied. Eleven patients were comatose on admission. Five had an admission Glasgow Coma Scale (GCS) score of 4 or less and developed clinical signs of brain death within 12 hours despite maximum therapeutic efforts. The remaining six patients, all of whom had three or more of the previously described unfavorable prognostic features, were aggressively managed with prophylaxis and treatment of intracranial hypertension. Intracranial pressure (ICP) was controlled with mechanical hyperventilation, mannitol osmotherapy, pentobarbital, and surgical decompression. Substantial intracranial hypertension occurred for up to 10 days after admission. There were four survivors. Neurobehavioral and intellectual functions were evaluated over a period of 1 to 2 years. Although serious cognitive deficits were noted, all survivors had sufficient functional recovery to warrant aggressive cardiopulmonary resuscitation and measures to control ICP in the management of comatose victims of craniocerebral GSW.

Brain Injuries↗

Paraparesis in a child with a herniated thoracic disc.

Herniated thoracic disc after minor trauma, causing paraparesis in an 11-year-old boy, proved difficult to diagnose. Myelogram and computer tomography of the thoracic spine appeared normal, but magnetic resonance imaging demonstrated a small herniation at T4-T5. Disc material adherent to the dura was found at laminectomy. The child made progressive recovery preoperatively and postoperatively and was able to ambulate in parallel bars with a left knee-ankle-foot orthorsis at the time of discharge from the hospital.

Child↗

Dural closure.

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Dura Mater↗

Feasibility of invasive monitoring of intracranial pressure in term neonates.

Seven term neonates with encephalopathy resulting from asphyxia and/or intracranial hemorrhage underwent invasive monitoring of intracranial pressure through the epidural or intracerebral space. The average age (in hours) at insertion of the monitor was 27 h in the 3 neonates with asphyxia and 70 h in the 4 neonates with hemorrhage. Intracranial hypertension was noted in 6 neonates. The management of the hypertension included hyperventilation followed by mannitol for pressures that were sustained above 20 mmHg and pentobarbital for pressures above 30 mmHg. The duration of the hypertension varied in 5 neonates from 4 to 72 h, while in the remaining neonates, the pressure remained elevated until death at 70 h. All 4 survivors with intracranial hemorrhage have minimal neuromotor deficits on follow up and 2 survivors with asphyxia have cognitive deficits and are microcephalic. From this small series, it appears that in the management of term neonates with intracranial hemorrhage, monitoring of intracranial pressure should be considered.

Asphyxia↗