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Biomedical subjects

P D Adelson

Publications and source records attributed to P D Adelson.

At least 37 records · Page 2Linked to original sources

A randomized, controlled study of a programmable shunt valve versus a conventional valve for patients with hydrocephalus. Hakim-Medos Investigator Group.

OBJECTIVE: A multicenter prospective randomized controlled study was performed to assess the safety and efficacy of a Codman Hakim programmable shunt valve (Codman/Johnson & Johnson, Raynham, MA) versus a conventional valve system of the surgeon's choice for the treatment of patients with hydrocephalus. METHODS: Enrollment was stratified on the basis of whether the patient was undergoing initial shunt insertion or revision of an existing valve system at study entry. Study end points were: 1) valve explantation, and 2) shunt failure (surgical intervention for any component of the shunt). A total of 377 patients were enrolled onto the study, with 235 undergoing first shunt insertion (119 experimental, 116 control) and 142 undergoing revisions (75 experimental, 67 control). RESULTS: During a follow-up interval of 104 weeks after the first implantation on-study, explantation of the valve was required in 62 (32%) of 194 experimental valves, compared with 71 (39%) of 183 control valves. Two-year survival rates of the original shunt without revision of any component were 52% (62 of 119) and 50% (58 of 116) in experimental and control patients, respectively, who underwent initial shunt insertion, and 43% (32 of 75) and 43% (29 of 67) in experimental and control patients, respectively, who underwent replacement of an existing valve. No statistically significant difference was observed between experimental and control patients in the survival of either the valve or the overall shunt system. Control of hydrocephalus as assessed symptomatically and by imaging was comparable in the two treatment groups. Although problems related to inability to achieve the desired pressure setting were reported in 22 experimental valves, in all but four instances no additional programming was attempted because the patients were functioning well clinically. The most common reasons cited for valve explantation and shunt revision were infection (9.8% frequency in the overall cohort) and proximal shunt malfunction, which occurred with comparable frequency in the experimental and control groups. CONCLUSION: Safety and efficacy of the Codman Hakim programmable shunt valve is comparable to conventional valves in the overall population of patients with hydrocephalus. However, the current study was not designed to assess the efficacy of programmable versus conventional valves in the management of individual hydrocephalus problems, and it had insufficient statistical power to support such comparisons. This study provides a rationale for examining whether the theoretical advantages of a programmable valve for managing challenging hydrocephalus problems can translate into meaningful improvements in shunt and valve survival.

Adolescent↗

Noninvasive continuous monitoring of cerebral oxygenation periictally using near-infrared spectroscopy: a preliminary report.

PURPOSE: To report on the use of near-infrared spectroscopy (NIRS) to examine the changes in cerebral oxygenation in the periictal period in patients with seizures. METHODS: Cerebral hemoglobin oxygen availability was monitored continuously and noninvasively with NIRS in three patients (one in the pediatric intensive care unit (ICU) and two in epilepsy-monitoring units) in conjunction with continuous EEG monitoring. Ictal events were recorded and compared with the pre-, intra-, and postictal periods for cerebral oxygen availability, as defined by oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and the redox state of cytochrome oxidase (cytox). RESULTS: Several important preliminary observations were made by using this technology. First, a preictal increase in cerebral oxygenation began between 1 and 2 h and >10 h before the ictal event. Second, despite adequate perfusion, based on an observed increased HbO2, reduction in cytox indicates a perfusion-metabolism mismatch during seizure activity. Third, continued seizure activity and even isolated ictal events were associated with decreased cerebral oxygen availability. Fourth, differences in cerebral oxygen availability were noted between different types of seizures (e.g., electrographic seizures were accompanied by rapid reductions in HbO2 and cerebral blood volume without reduction of cytox, whereas electroclinical seizures were characterized by marked increases in HbO2 with or without reduction of cytox). CONCLUSIONS: In this preliminary report on the use of NIRS for patients with seizures, we believe that NIRS allows continuous and noninvasive monitoring of changes in cerebral oxygenation periictally, thereby permitting investigations into the pathophysiology of seizures and the exploration of the potential of cerebral oximetry as a tool for seizure localization.

Brain↗

Large chronic cephalohematoma without calcification.

Cephalohematomas following birth normally resorb within the 1st month of life. In cases of prolonged resorption, over greater than 1 month, cephalohematomas typically begin to calcify. We report the case of a 3-month-old child with a persistent, large cephalohematoma that did not calcify. After observation alone failed to demonstrate a decrease in the size of the hematoma, 30 cm3 of old blood was aspirated, and the patient's head was wrapped. Unlike calcified cephalohematomas, this noncalcified lesion did not require open surgical intervention. A treatment protocol for cephalohematomas is presented.

Birth Injuries↗

Cervical spine evaluation in obtunded or comatose pediatric trauma patients: A pilot study.

A uniformly accepted protocol for evaluation and clearance of the cervical spine of pediatric trauma patients with altered mental status does not currently exist. We sought to detect cervical spine injuries in this group with minimal risk. Patients were evaluated with standard three-view cervical spine radiographs and CT when necessary. Those patients without radiographic abnormality and altered mental status underwent flexion-extension of the cervical spine using fluoroscopy with somatosensory evoked potential (SSEP) monitoring. Those with abnormal movement by fluoroscopy or changes in SSEP underwent MRI. Fifteen patients were evaluated with this protocol. Two patients had movement on flexion-extension of the cervical spine and 5 had SSEP changes. Three patients had an MRI with only 1 showing injury. Five patients had residual hemiparesis. Evaluation of the cervical spine in obtunded or comatose pediatric trauma patients can be done safely with flexion-extension under fluoroscopy and SSEP monitoring. Further prospective studies are required to determine the efficacy of SSEP monitoring for cervical spine clearance in this select population.

Adolescent↗

Coexistence of a ganglioglioma and Rasmussen's encephalitis.

A small number of recent reports have documented coexisting cerebral pathologic entities in patients with Rasmussen's encephalitis. We report the case of a 4-year-old boy who presented with refractory seizures and was found to have both a ganglioglioma and Rasmussen's encephalitis of the same hemisphere. The patient ultimately underwent a functional hemispherectomy with excellent seizure control. We also review the clinical and pathologic hallmarks of both gangliogliomas and Rasmussen's encephalitis. We hope that the addition of this patient to the small but growing literature on dual pathology in Rasmussen's encephalitis may help shed some light on the etiology of this mysterious disease.

Brain↗

Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy.

OBJECTIVE: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients. METHODS: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters). RESULTS: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon's horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. CONCLUSIONS: Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.

ATP-Binding Cassette Transporters↗

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Adult↗

Blood brain barrier permeability and acute inflammation in two models of traumatic brain injury in the immature rat: a preliminary report.

We sought to investigate the course and magnitude of blood brain barrier (BBB) permeability following focal and diffuse traumatic brain injury (TBI) in immature rats and examine the time course of markers of acute inflammation (neutrophil accumulation and E-selectin [E-sel] expression) following these two types of injury. We measured BBB permeability using i.v. injection Evans Blue (EB) and the extent of inflammation using immunohistochemical techniques identifying neutrophils (monoclonal antibody RP-3) and the endothelial adhesion molecule, E-selectin. Male Sprague-Dawley immature (17 day-old) rats (30-45 g, n = 80) were subjected to a controlled cortical impact (CCI: 2 mm, 4 m/s), a closed head diffuse injury (DI: 150 g/2m) or a corresponding sham procedure (with or without craniotomy). EB was injected i.v. at 30 min before sacrifice, which occurred at 1 h, 4 h, or 24 h after injury. BBB permeability was observed in both the CCI and DI rats at 1 h after injury which largely resolved by 24 h. In the CCI, EB extravasation was seen within and around the contusion. In DI, diffuse BBB permeability was seen. DI was not associated with acute inflammation since there was neither neutrophil accumulation nor E-selectin expression. The CCI rats though had 5.1 +/- 2.2 neutrophils/hpf and 3.0 +/- 0.4 endothelial cells/hpf expressing E-selectin (mean +/- SEM) (both p < 0.05 vs sham and DI). These data suggest that BBB breakdown occurs in the immature rat after both focal and diffuse TBI. This early BBB permeability was not associated with acute inflammation in DI but was in CCI. These data also suggest that contusion is a key factor in the development of a traditional acute inflammatory response after TBI in the immature rat.

Animals↗

The use of near infrared spectroscopy (NIRS) in children after traumatic brain injury: a preliminary report.

Children commonly develop diffuse cerebral swelling after traumatic brain injury (TBI) which is believed due to a secondary response to the injury. Near infrared spectroscopy (NIRS), a continuous, direct, and noninvasive monitor of cerebral oxygenation and cerebral blood volume (CBV), could be helpful in understanding these secondary responses. The aims of our study were to determine whether NIRS used in children with severe TBI will provide insight into the pathophysiology of injury. Ten children (1 mo to 15 years old) with severe TBI (admission GCS < or = 7) were continuously monitored by NIRS by placing optodes over the frontalparietal region. Relative values of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and total hemoglobin (THb) were obtained and compared to intracranial pressure (ICP), mean arterial pressure (MAP), electroencephalography (EEG), and arterial PCO2 (PaCO2). Episodes of intracranial hypertension (ICP > 20 Torr [T]), changes in ICP > 10 T, changes in PaCO2 > or = 8 T, and changes in MAP > 20 T frequently resulted in changes in HbO2, Hb, and THb. Hyperventilation with decreased PaCO2 always resulted in cerebral oxygen desaturation irregardless of ICP. Often, high ICP correlated with increased THb and HbO2 indicating increased CBV and cerebrovascular dilatation. In two children, posttraumatic seizures were preceded by an unexplained rapid cerebral hyperoxygenation several hours prior to the onset of the clinical seizures. NIRS reliably detects changes in cerebral hemodynamics in children and may be used to further understand the etiology of the diffuse cerebral swelling seen in children after severe TBI.

Adolescent↗

Intraoperative hypothermia and ventricular shunt infections.

Several recent studies have demonstrated a relationship between intraoperative hypothermia and postoperative infection. A study was therefore conducted to evaluate the relationship between intraoperative hypothermia and ventricular shunt infections. Sixty-eight children who underwent ventricular shunt placement, including revisions, over a six year period subsequently developed a shunt infection (overall shunt infection rate of 5%). Mean age was 8 years (range, neonate to 20 years). The last 74 children who underwent ventricular shunt placement without subsequent infection served as a comparison group. The anesthetic records of all cases were reviewed to determine the lowest core temperature recorded during the surgical procedure. The lowest core temperature varied from 33.9 degrees C to 37.7 degrees C (mean 36.0 degrees C). Hypothermia was defined as a temperature less than 35.1 degrees C. No relationship was found between hypothermia and the subsequent occurrence of a shunt infection (P = 0.45). When those children less than 2 years old were excluded from analysis, there was a trend towards statistical significance (P = 0.07). In summary, this study failed to show any significant relationship between the occurrence of intraoperative hypothermia and subsequent ventriculoperitoneal shunt infection in a group of pediatric patients.

Adolescent↗

Soluble adhesion molecules in CSF are increased in children with severe head injury.

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.

Adolescent↗

Increased hippocampal AMPA and NMDA receptor subunit immunoreactivity in temporal lobe epilepsy patients.

This study determined if hippocampal AMPA and NMDA subunit immunoreactivity (IR) in temporal lobe epilepsy patients was increased compared with nonseizure autopsies. Hippocampi from hippocampal sclerosis patients (HS; n = 26) and nonsclerosis cases (non-HS: n = 12) were compared with autopsies (n = 6) and studied for GluR1, GluR2/3, NMDAR1, and NMDAR2 IR gray values (GV) along with fascia dentata and Ammon's horn neuron densities. Compared with autopsies, non-HS cases with similar neuron densities and HS patients with decreased neuron densities showed: (a) Increased GluR1 GVs in the fascia dentata molecular layer: (b) increased NMDAR1 GVs in the CA3-1 stratum radiatum and greater IR within pyramids; and (c) increased GluR2/3 and NMDAR2 GVs throughout all hippocampal subfields. Furthermore, HS patients showed that relative to the outer molecular layer: (a) GluR1 GV differences were decreased in the CA4/hilar region and CA1 stratum radiatum compared with autopsies; and (b) NMDAR2 GV differences were increased in the inner molecular layer compared with non-HS cases. In temporal lobe seizure patients, these results indicate that AMPA and NMDA receptor subunit IR was increased in HS and non-HS hippocampi compared with nonseizure autopsies. In humans, these findings support the hypothesis that glutamate receptor subunits are increased in association with chronic temporal lobe seizures, which may enhance excitatory neurotransmission and seizure susceptibility.

Adult↗

Head injury in children.

Trauma in the United States is the leading cause of death and disability in the pediatric population. Differences of age and development affect recovery and outcome following head injury. Mechanisms and pathophysiology of head injury are varied in both the pediatric and adult populations. Assessments of injury are varied and some measurements are more sensitive than others as well as more specific with regard to certain types of injury. Treatment and management should be tailored to each case in order to effect a positive outcome with respect to brain functioning. Aggressive intervention for prevention of primary and secondary injury must be continued and understanding of the impact of these injuries should provide for a brighter future for these patients.

Adolescent↗

Comparison of the interleukin-6 and interleukin-10 response in children after severe traumatic brain injury or septic shock.

Inflammation may play an important role in the evolution of damage after traumatic brain injury (TBI). IL-6 and IL-10 are markers of inflammation that are pro- and anti-inflammatory in nature, respectively. They have been used as an index of the degree of inflammation in diseases including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the cerebrospinal fluid (CSF) of children after TBI. We measured ventricular CSF concentrations of these metabolites (ELISA) each of the first 3 days after TBI in 15 children. CSF IL-6 was increased on day 1 (p < 0.05 vs days 2 or 3). CSF IL-10 was similarly increased on day 1 (p < 0.05). CSF IL-6 after TBI is similar to serum IL-6 levels previously reported in children with septic shock. In contrast, the CSF IL-10 response was markedly attenuated following TBI compared to sepsis. These data suggest a unique balance between pro- and anti-inflammatory cytokines in brain after TBI.

Brain Injuries↗

Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children.

Cytokines may play an important role in the pathophysiology of traumatic brain injury (TBI) in children. Interleukin-6 (IL-6) is a proinflammatory cyotkine that plays a role in regenerative processes within the central nervous system (CNS), whereas interleukin-10 (IL-10) is an antiinflammatory cytokine. Both have been measured in serum and cerebrospinal fluid (CSF) as an index of the degree of inflammation in diseases, including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the CSF of children after severe TBI. Fifteen children who sustained severe TBI (Glascow Coma Score [GCS] < or = 7) were studied. Standard neurointensive care was provided. Ventricular CSF collected the first 3 days after TBI was analyzed for IL-6 and IL-10 concentrations by ELISA. Controls were 20 children who were evaluated for meningitis with diagnostic lumbar puncture subsequently found to have no CSF pleocytosis and negative cultures. IL-6 was increased in children after TBI versus controls on all days studied (day 1, 3158.2 +/- 621.8 pg/ml; day 2, 1111.6 +/- 337.0 pg/ml; day 3, 826.7 +/- 193.5 pg/ml vs. 20.6 +/- 5.8 pg/ml, p < 0.0001, Mann-Whitney Rank Sum). IL-10 was increased in children after TBI vs controls on all days studied (day 1, 47.2 +/- 12.9 pg/ml; day 2, 21.0 +/- 6.7 pg/ml; day 3, 15.5 +/- 5.9 pg/ml vs. 8.9 +/- 7.5 pg/ml, p < 0.01). Increased IL-10 concentrations were independently associated with age < 4 years and mortality (p = 0.004 and 0.04, respectively, multivariate linear model). This study demonstrates that IL-6 is increased after TBI in children to levels similar to those reported in adults and is the first to show that IL-10 is increased in CSF of humans after TBI. These data suggest that there may be an age-dependent production of IL-10 after TBI in children.

Adolescent↗

Motor and cognitive functional deficits following diffuse traumatic brain injury in the immature rat.

To determine the motor and cognitive deficits following a diffuse severe traumatic brain injury (TBI) in immature Sprague Dawley rats (17 days), four groups of animals were injured at different severity levels using a new closed head weight drop model: (sham, severe injury [SI: 100 g/2 m], SH [SI + hypoxemia (30 min of an FiO2 of 8% posttrauma)], and ultra severe injury [US: 150 g/2 m]). Latency on beam balance, grip test performance, and maintenance of body position on an inclined board were measured daily after injury to assess vestibulomotor function. Cognitive function was assessed on days 11-22 using the Morris water maze (MWM). Balance beam latency and inclined plane body position were reduced in both SI and SH rats (n = 20) (p < 0.05 vs. sham) (maximally at 24 h), and lasted 3-4 day postinjury; however, SH did not differ from SI. In the US group (n = 10), motor deficits were profound at 24 h (p < 0.05 vs. all other groups) and persisted for 10 days. The groups did not differ on grip test. In cognitive performance, there were no differences between sham, SI, and SH. US, however, produced significant cognitive dysfunction (vs. sham, SI, and SH), specifically, greater latencies to find the hidden platform through 22 days. Swim speeds were not significantly different between any of the injury groups and shams. These data indicate that (1) beam balance, inclined plane and MWM techniques are useful for assessing motor and cognitive function after TBI in immature rats; (2) SI produces motor but not cognitive deficits, which was not augmented by transient hypoxia; and (3) US created a marked but reversible motor deficit up to 10 days, and a sustained cognitive dysfunction for up to 22 days after TBI.

Animals↗

Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients.

This study was designed to determine whether hippocampal neuronal AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) mRNA levels were differentially increased in temporal lobe epilepsy patients compared with those measured in control tissue from non-seizure autopsies. Hippocampi from hippocampal sclerosis patients (n = 28) and temporal mass lesion cases (n = 12) were compared with those from the autopsies (n = 4), and studied for AMPA GluR1-3 and NMDAR1-2 mRNAs using semi-quantitative in situ hybridization, along with fascia dentata and Ammon's horn neuron densities. Compared with the autopsies, and without correction for neuron counts, the mass lesion cases with neuron densities similar to autopsies showed: (i) significantly increased NMDAR2 hybridization densities for fascia dentata granule cells; (ii) increased AMPA GluR3 mRNA densities for Ammon's horn pyramids; and (iii) similar or numerically increased mRNAs for all other subunits and hippocampal subfields. Compared with the autopsies, hippocampal sclerosis cases with decreased neuron densities showed: (i) significantly decreased AMPA GluR1-2 and NMDAR1-2 hybridization densities for Ammon's horn pyramids and (ii) similar or numerically decreased mRNAs for all other subunits and subfields. However, correcting for changes in neuron densities showed that hippocampal sclerosis patients had increased AMPA and NMDA mRNA levels per neuron compared with autopsies, and in the CA2 resistant sector GluR2 mRNA levels were numerically greater than autopsies and mass lesion cases. Furthermore, relative to autopsies both sclerosis and mass lesion hippocampi showed that, in the stratum granulosum, the greatest mRNA increases were in AMPA GluR1 and NMDAR2 compared with the other mRNAs. In chronic temporal lobe seizure patients these results indicate that mass lesion and sclerosis cases show differential increases in hippocampal AMPA and NMDA mRNA levels per neuron compared with autopsies, especially for AMPA GluR1 and NMDAR2 in fascia dentata granule cells. These findings support the hypothesis that temporal lobe seizures are associated with increased ionotropic glutamate receptor mRNA levels and alterations in receptor subunit composition that probably contribute to neuronal hyperexcitability, synchronization and seizure generation.

Adult↗