Faculty Bibliography

AIM/OBJECTIVE:Mortality from malignant middle cerebral artery infarction (MMCAI) approaches 80% in adult series. Although decompressive craniectomy decreases mortality and leads to an acceptable outcome in selected adult patients, there are few data on MMCAI in children with stroke. This study evaluated the frequency of MMCAI and the use of decompressive craniectomy in children. METHOD/METHODS:We retrospectively reviewed cases of MMCAI from five pediatric tertiary care centers. RESULTS:Ten children (two females, eight males; median age 9y 10mo, range 22mo-14y) had MMCAI, with a median Glasgow Coma Scale score of 6 (range 3-9). MMCAI represented fewer than 2% of cases of pediatric arterial ischemic stroke. Three patients who did not undergo decompression, all of whom had monitoring of intracranial pressure, developed intractable intracranial hypertension, and fulfilled criteria for brain death. In contrast, seven patients underwent decompressive craniectomy and survived, with rapid improvement in their level of consciousness postoperatively. All seven survivors now walk independently with mild to moderate residual hemiparesis and speak fluently, even though four had left-sided infarcts. INTERPRETATION/CONCLUSIONS:Decompressive craniectomy can lead to a moderately good outcome for children with MMCAI and should be considered, even with symptomatic stroke and deep coma. Monitoring of intracranial pressure may delay life-saving treatment.

Postlaminectomy spinal deformity is a frequent problem after resection of a pediatric spinal cord tumor. However, the use of spinal fusion done at the time of resection in preventing the development of deformity is unknown. The purpose of our study was to assess the effectiveness of single-stage laminectomy, spinal cord decompression, and fusion for the prevention of postlaminectomy spinal deformity in children with intramedullary spinal cord tumors. Clinical charts and radiographs of 33 children with spinal cord tumors were reviewed for treatment description, preoperative spinal alignment, postoperative spinal alignment, and subsequent medical and surgical treatment. Spinal deformity was graded by predefined criteria. Significant spinal deformity developed in 10 of 17 children with laminectomy only, 3 of 4 children with laminoplasty, and 3 of 12 children with spinal fusion (2/6 with instrumentation, 1/6 with in situ fusion). Excluding patients that progressed to paraplegia, 9 of 16 patients treated with resection without fusion compared with 1 of 10 patients treated with resection and fusion developed a spinal deformity (P = 0.04). Among skeletally mature children that did not progress to paraplegia, 9 of 15 treated with resection without fusion compared with 1 of 7 patients treated with resection and fusion developed a deformity (P = 0.05). Removal of greater than 4 laminae (P = 0.03) was found to be associated with the development of postresection spinal deformity.

The gamma-amino-butyric acid type A receptors (GABAAR) are a heteropentameric receptor complex, composed of 16 possible subunits in various combinations, forming a ligand-gated ion channel. Subunit composition is the primary determinant of GABAAR physiology and pharmacology. Here we have measured mRNA levels for 16 GABAAR subunits in isolated dentate granule neurons (DGN) from eight pediatric patients undergoing resective surgery for intractable epilepsy. We found tightly correlated expression of a subset of GABAAR subunit mRNAs within a single DGN (alpha1, gamma1, and gamma2; alpha4, alpha5, and beta2; alpha4 and beta3). Analysis of inter-patient variability (ANOVA) of eleven highly expressed GABAAR subunit mRNAs found seven of the subunits varied between patients, as did whole cell GABAAR currents. Due to inter-patient differences, there is heterogeneity in DGN GABAAR subunit mRNA and physiology within pediatric epilepsy patients. Patient-specific GABAAR expression might contribute to variability in anti-epileptic drug efficacy, side-effect profiles, and seizure susceptibility.

STUDY DESIGN/METHODS:A unique case of the congenital formation of an intraspinal osseous vertebral ring causing spinal cord compression is reported. OBJECTIVES/OBJECTIVE:To our knowledge, such an osseous ring has not yet been described. The authors detail the clinical presentation, imaging, and treatment of the intraspinal osseous ring. SUMMARY OF BACKGROUND DATA/BACKGROUND:There are two traditional categories of congenital vertebral anomalies, that of failure of formation and of segmentation. The authors propose that this ring may not fit into either of these categories and may represent a new category of failure of migration. METHODS AND RESULTS/RESULTS:Surgical decompression using a costotransversectomy approach was performed. Adequate decompression the spinal cord was achieved. Anterior and posterior fusions with instrumentation were used to stabilize the spinal cord. CONCLUSIONS:An intraspinal osseous vertebral ring is a unique anomaly that, to our knowledge, has not been reported to date. The authors discuss the pathology, imaging, and treatment of this unique condition.

This 17-year-old male patient with tuberous sclerosis developed increased headaches and lethargy. Magnetic resonance imaging of the brain revealed increased ventricle size and increased size of a subependymal giant cell astrocytoma at the foramen of Monro, as well as spinal cord metastases of giant cell tumors. Decompressive surgery of the foramen of Monro lesion resulted in temporary resolution of the hydrocephalus. Increased Ki-67 labeling of tumor as well as rare spinal enhancement both possibly indicated malignant features for this entity.

Invasive monitoring for intractable epilepsy is useful when the epileptogenic focus is in question even after an extensive noninvasive presurgical evaluation, or when the epileptogenic focus is located in or near eloquent cortex. From June 1989 to June 2001 at the Children's Hospital of Philadelphia, 64 children with intractable epilepsy underwent 67 invasive monitoring procedures as part of their presurgical evaluation. The average age at implantation was 10 years. In all but two cases, subdural strips and grids were used. Depth electrodes, when used, were placed stereotactically or under direct vision. The average duration of the monitoring period was 5.87 days. Every patient had intradural cultures sent during removal of the electrodes, and lumbar punctures were performed in 15 patients. Twenty-one patients had at least one episode of a CSF leak. Of the 67 patients, 10 had positive intradural cultures, only 1 of whom had a positive lumbar puncture and none of whom developed clinically significant meningitis. No clinically relevant hemorrhages occurred as a result of the invasive monitoring. One patient did have a transient visual field loss after placement of an occipital grid. While CSF leaks are common after invasive monitoring despite precautions, clinically significant CSF infections are uncommon and appear to be unrelated to the duration of monitoring, the occurrence of a CSF leak or the length of time the patient is on perioperative antibiotics. We conclude that invasive monitoring for intractable epilepsy is generally safe.

PURPOSE/OBJECTIVE:The balance between synaptic excitation and inhibition within the hippocampus is critical for maintaining normal hippocampal function. Even mild reduction in inhibition or enhancement of excitation can produce seizures. Synaptic excitation is produced by pyramidal cells and granule cells, whereas inhibition is produced by a smaller number of interneurons. To understand how two subpopulations of these excitatory and inhibitory neurons are regulated at the molecular level, we analyzed specific mRNA expression profiles for receptors that are significantly involved in synaptic transmission and in the synthesis and storage of the principal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Our hypothesis was that differences in gene expression between inhibitory and excitatory neurons in the rat hippocampus might point to specific new targets for seizure pharmacotherapy. METHODS:We combined the techniques of (a) whole-cell patch clamping in rat hippocampal slices, (b) biocytin staining for cell identification, (c) single-cell mRNA amplification, and (d) small-scale cDNA microarray analysis to allow us to obtain expression profiles for candidate genes from identified CA1 pyramidal neurons and interneurons. Electrophysiologic and morphologic data and expression profiles were obtained from 12 stratum pyramidale and seven stratum radiatum cells. RESULTS:Presumed inhibitory neurons expressed significantly more GAD65, GAD67, vGAT, GABA(A)-receptor alpha3, and N-methyl-d-aspartate (NMDA)-receptor IIB mRNA, and presumed excitatory neurons expressed more GABA(A)-receptor alpha1, and NMDA-receptor I mRNA. CONCLUSIONS:Differential expression of candidate neurotransmitter-receptor subunits distinguished CA1 pyramidal neurons from interneurons. These differences may indicate potential new targets for altering the balance of inhibition and excitation in the treatment of epilepsy.

We have compared the length, strength, conduction velocity and divergence of horizontal connections onto layers 2/3 and 5 neurons in slices of rat primary somatosensory neocortex. Slices were cut along laminar borders to eliminate most vertical connections, and excitatory postsynaptic potentials (EPSPs) were recorded from pyramidal cells in adjacent uncut tissue. When electric stimuli were delivered within the same layer as the recorded cell, EPSPs could be evoked up to 2000 microm away for both layers 2/3 and 5 pyramids. Estimates of horizontal axonal conduction velocities ( approximately 0.4 m/s) and the thresholds for activation also did not differ between layers. However, layers 2/3 cells rarely responded to stimuli delivered to isolated deeper layers, while layer 5 neurons were often excited by horizontal inputs from isolated layers 2/3 and 4.

OBJECT/OBJECTIVE:The diagnosis, treatment, and postoperative care of morbidly obese patients undergoing spinal surgery require modifications for body habitus. With a growing percentage of the United States population becoming morbidly obese, the surgeon may need elective or emergency treatment plans that address the special needs of these patients. The authors retrospectively reviewed the diagnosis, treatment, and postoperative care of the severely obese patient undergoing spinal surgery. METHODS:To assess the associated results and complications of management that required modification for body habitus, 12 patients were included in the study (nine females); the mean age was 50 years and mean weight was 320 lb. Cases of cervical (two cases), thoracic (four cases), and lumbar surgeries (six cases) were included. The follow-up period ranged from 6 months to 2 years. Patients presented with myelopathy (five cases), radicular pain and weakness (four cases), radiculopathy (two cases), and cauda equina syndrome (one patient). Chronic progressive neurological deterioration secondary to spinal cord compression was demonstrated in nine patients and acute pain and/or weakness secondary to nerve root compression was observed in three patients. CONCLUSIONS:The authors found that although morbidly obese patients may present late in the course of their symptoms and require modifications in the use of standard neuroimaging, operative facilities, and treatment plans, open mindedness and persistence can yield satisfactory results in most cases.

Hemispherectomy is a very effective surgical treatment for intractable seizures that occur in the setting of Rasmussen's syndrome. The decision of when to perform a dominant hemispherectomy depends greatly on how late the surgeon believes some shift in language to the nondominant hemisphere can occur. We report a right-handed patient with Rasmussen's syndrome who underwent a left hemispherectomy at the age of 16 and has had excellent control of her seizures and remarkable language recovery. Our results indicate that dominant hemispherectomy in adolescence in the setting of late-onset seizures and Rasmussen's syndrome in the profoundly aphasic patient does not commit the patient to the prognosis of a fixed language deficit.