Albert E. Telfeian

Layer‐Specific Pathways for the Horizontal Propagation of Epileptiform Discharges in Neocortex

Summary: Purpose: Epileptiform discharges that resemble interictal spikes can be generated by slices of neocortex treated with antagonists of γ‐aminobutyric acid A (GABAA) receptors. These discharges can propagate horizontally for long distances. We tested the hypothesis that propagation occurs through preferred horizontal pathways that lie in a particular cortical layer.

Complications of Invasive Monitoring Used in Intractable Pediatric Epilepsy

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.

Epileptiform Propagation Patterns Mediated by NMDA and Non-NMDA Receptors in Rat Neocortex

Summary: Purpose: The neocortex can generate various forms of epileptiform activity, including one that depends on N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptors (NMDARs), and another dependent on non‐NMDA‐type (AMPA) glutamate receptors (AMPARs). Previous work in vitro suggests that both forms of activity are initiated by neurons of layer 5, but the spatial patterns of horizontal propagation have been studied only for the AMPAR form. We have tested the hypothesis that both types of epileptiform activity spread via common pathways in one cortical layer, suggesting that lamina‐specific intervention might selectively interrupt both.

Widely integrative properties of layer 5 pyramidal cells support a role for processing of extralaminar synaptic inputs in rat neocortex

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.

Recovery of Language after Left Hemispherectomy in a Sixteen-Year-Old Girl with Late-Onset Seizures

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.

Differential Expression of GABA and Glutamate-receptor Subunits and Enzymes Involved in GABA Metabolism between Electrophysiologically Identified Hippocampal CA1 Pyramidal Cells and Interneurons

Summary:  Purpose: 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, γ‐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.

Clinical success of transforaminal endoscopic discectomy with foraminotomy: A retrospective evaluation

OBJECTIVE Transforaminal endoscopic surgery has evolved from an intradiscal procedure to a true foraminal epidural procedure where both a targeted discectomy and foraminal decompression can be performed. The success of transforaminal decompression for radiculopathy using preoperative selective nerve root block as part of a treatment algorithm for single level and multilevel lumbar disc herniations is described here. METHODS After Institutional Review Board Approval, charts from 195 patients with complaints of lower back and radicular pain who received one or more endoscopic discectomy procedures were reviewed. Visual Analog Scale was applied to each patient preoperatively and 6 months after the procedure. RESULTS Patients with multi-level pathologies receiving one procedure have an average relief of 69.7% attributed to correct diagnosis of the inflicting level as opposed to 83.9% improvement in patients with a single level herniation. CONCLUSION Patients with single level lumbar herniations receiving one endoscopic discectomy have excellent outcomes, but with a good response to a selective nerve root block as a preoperative adjunct, patients with multilevel disc herniations also have significant benefit from single level endoscopic discectomy.

Heterogeneous GABAA receptor subunit expression in pediatric epilepsy patients

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.

Local pathways of seizure propagation in neocortex

Publisher Summary Partial seizures of the neocortex can be initiated by the relatively small and localized collections of neurons. Anticonvulsant drugs are very successful for treating most cases of partial epilepsy, but they produce unwanted side effects in the large majority of the brain that is not epileptic. For some patients, drugs simply fail to control seizures adequately. In selected cases, surgery can be a dramatically effective and selective therapy for partial seizures. Unfortunately, the inherent uncertainties of mapping both pathology and function in the cortex often lead to a removal of important, nonepileptic tissue. A better understanding of the cellular basis of epilepsy might lead to more targeted therapeutic strategies. One tactic for preventing the onset of partial seizures is to disconnect, in a literal sense, the offending neurons and so, prevent their paroxysmal collusion. Multiple subpial transection is currently being used, on a limited and usually adjunct basis, to treat some forms of partial seizure disorders. Understanding the optimal requirements for preventing and containing focal seizures by disconnection will require a detailed knowledge of the structure and function of local neocortical circuits. This chapter summarizes selected research on the neurons, axons, synaptic connections, and epileptiform activity of the neocortex to illuminate the substrates that mediate seizure propagation.

Patient radiation exposure during transforaminal lumbar endoscopic spine surgery: a prospective study

OBJECTIVE The aim of this study was to describe patient radiation exposure during single-level transforaminal endoscopic lumbar discectomy procedures at levels L2-5 and L5-S1. METHODS Radiation exposure was monitored in 151 consecutive patients undergoing single-level transforaminal endoscopic lumbar discectomy procedures. Two groups were studied: patients undergoing procedures at the L4-5 level or above and those undergoing an L5-S1 procedure. RESULTS For the discectomy procedures at L4-5 and above, the average duration of fluoroscopy was 38.4 seconds and the mean calculated patient radiation exposure dose was 1.5 mSv. For the L5-S1 procedures, average fluoroscopy time was 54.6 seconds and the mean calculated radiation exposure dose was 2.1 mSv. The average patient radiation exposure dose among these cases represents a 3.5-fold decrease compared with the senior surgeons first 100 cases. CONCLUSIONS Transforaminal lumbar endoscopic discectomy can be used as a minimally invasive technique for the treatment of lumbar radiculopathy in the setting of a herniated lumbar disc without the significant concern of exposing the patient to harmful doses of radiation. One caveat is that both the surgeon and the patient are likely to be exposed to higher doses of radiation during a surgeons early experience in minimally invasive endoscopic spine surgery.