Do atmospheric pressure changes influence seizure occurrence in the epilepsy monitoring unit?

In a prior study of epilepsy and atmospheric pressure, we were able to show a small association between changes in atmospheric pressure and increased seizure frequency in consecutive patients with epilepsy undergoing video telemetry. In this study, we used a larger data set of similar patients undergoing telemetry at another Seattle institution, and examined the possible impact of atmospheric pressure (AP) changes on seizure onset in subtypes of seizures (focal, generalized, and nonepileptic). Comparisons were made between AP score at time of seizure onset and AP score at selected time ranges prior to the event (hour of seizure and 3, 6, and 24 hours prior) and a random sample of AP scores collected over similar time frames using nonparametric testing with correction for multiple comparisons. We could find no evidence to suggest atmospheric pressure changes made seizure occurrence more likely in any of the seizure groups across any of the time periods.

Primate model of cerebral hematoma.

Using specific anesthetic agents, permanent segmental occlusion of the proximal middle cerebral artery (MCA) causes ischemic infarction limited to the putamen and other deep hemispheral structures in primates. Using this model, 25 rhesus monkeys were subjected to acute arterial hypertension before, during and up to 5 days after onset of MCA occlusion in order to reevaluate the possible role of the ischemic process in pathogenesis of cerebral hemorrhage. Norepinephrine infusion induced prompt rapid rise in mean arterial pressure (MAP) and intracranial pressure (ICP) limited to the duration of infusion. This procedure produced acute ischemic lesions which were totally bland but topographically more extensive than untreated controls; in chronic lesions, however, deep nuclear masses showed hemorrhagic infarction. Animals given 5% CO2 air had slowly progressive elevation in ICP and MAP. Acute specimens showed intact, widely-dilan hypercarbia was induced 5 days after MCA occlusion, animals developed intracerebral hematoma involving putamen, external capsule and claustrum, occasionally dissecting through to ipsilateral ventricle. In acute cerebral ischemia, elevated MAP produced only quantiative changes in lesion size. In the vasoproliferative stages of mature infarction, MAP elevation induced by a cerebral vasoconstrictor caused hemorrhagic infarctions while cerebral vasodilation caused intracerebral hematomas.

The colchicine experimental epileptic focus: an intracellular study.

A new experimental epileptic focus is described in which colchicine is topically applied to neocortex. Stable epileptiform discharges developed, with bursts of action potentials, coincident with the surface epileptiform events. There were depolarizing and hyperpolarizing neuronal potentials and glial depolarizations concomitantly with the surface epileptic spikes.

Posttraumatic syringomyelia. Case report.

The ninth case of posttraumatic syringomyelia with postmortem confirmation is presented. Onset of symptoms occurred 19 years after the original trauma. The review of the literature with a discussion of postulated mechanisms of syrinx distention follows. The present case differs from previously reported postmortem cases in that there was communication through the medullary parenchyma with the fourth ventricle.

Spinal Cord Stimulation for the Relief of Pain: Proceedings of a Symposium during the 4th International Congress of the International Neuromodulation Society, September 16-20, 1998, Lucerne, Switzerland.

Spinal cord stimulation has become an accepted technique used in the management of chronic neuropathic pain syndromes. However, a number of problematic questions remain unanswered. This introduction states some of these problems and concentrates on the problem of whether low back pain can be relieved by stimulation. This paper introduces subsequent contributions to this symposium, which offer some interesting new techniques, and attempts to answer some of the problems presented.

Spinal cord stimulation for complex regional pain syndrome: a prospective study of 19 patients at two centers.

Objectives. Prospective studies using specific outcome measures for the treatment of complex regional pain syndromes (CRPS) using spinal cord stimulation are lacking in the literature. The current prospective study followed 19 patients with the objective of analyzing such patients using specific outcome measures including the McGill Pain Rating Index, the Sickness Impact Profile, Oswestry Disability, Beck Depression Inventory, and Visual Analog Scale Scores. Materials and Methods. Nineteen patients are reported as a subgroup enrolled at two centers participating in a multicenter study of efficacy/outcomes of spinal cord stimulation. These patients were specifically identified as having CRPS and followed as a separate group. Specific preimplant and postimplant tests to measure outcome were administered. Results. Statistically significant improvement in the Sickness Impact Profile physical and psychosocial subscales is documented. The McGill Pain Rating Index words chosen and sensory subscale also improved significantly as did Visual Analog Scale scores. The Beck Depression Inventory trended toward significant improvement. Conclusions. Patients with CRPS benefit significantly from the use of spinal cord stimulation, based on average follow-up of 7.9 months.

Initiation and propagation of regenerative Ca(2+)-dependent potentials in dendrites of layer 5 pyramidal neurons.

The initiation and propagation of dendritic Ca(2+)-dependent regenerative potentials (CDRPs) were investigated by imaging the Ca(2+)-sensitive dye Fluo-4 during whole cell recording from the soma of layer 5 pyramidal neurons visualized in a slice preparation of rat neocortex by the use of infrared-differential interference contrast microscopy. CDRPs were evoked by focal iontophoresis of glutamate at visually identified sites 178-648 microm from the soma on the apical dendrite and at sites on the basal dendrites. Increases in [Ca(2+)](i) were maximal near the site of iontophoresis and were graded with iontophoretic current that was subthreshold for evoking CDRPs. CDRP initiation was associated with a [Ca(2+)](i) rise that differed from a just-subthreshold response in both magnitude and spatial extent but whose amplitude declined both proximal and distal to the iontophoretic site. These [Ca(2+)](i) rises, whether associated with subthreshold or regenerative voltage responses, were minimally affected by blockade of N-methyl-D-aspartate receptors but were abolished by Cd(2+), suggesting that Ca(2+) influx through voltage-gated channels caused the rise of [Ca(2+)](i). On the assumption that the rise of [Ca(2+)](i) during a CDRP marks the spatial extent of regenerative Ca(2+) influx, we conclude that CDRPs can be evoked at any point on the main apical or basal trunk where membrane potential reaches CDRP threshold rather than at discrete "hot spots," the CDRP is initiated at a spatially restricted site, and it propagates decrementally both distal and proximal to its initiation site. These results raise the possibility that synaptic integration may occur first in the dendrites to evoke a CDRP. Because these responses propagate decrementally to the soma, they are able to sum with input from other regions of the cell so that the cell as a whole remains integrative.

Dendritic calcium spikes in layer 5 pyramidal neurons amplify and limit transmission of ligand-gated dendritic current to soma.

Long-lasting, dendritic, Ca(2+)-dependent action potentials (plateaus) were investigated in layer 5 pyramidal neurons from rat neocortical slices visualized by infrared-differential interference contrast microscopy to understand the role of dendritic Ca(2+) spikes in the integration of synaptic input. Focal glutamate iontophoresis on visualized dendrites caused soma firing rate to increase linearly with iontophoretic current until dendritic Ca(2+) responses caused a jump in firing rate. Increases in iontophoretic current caused no further increase in somatic firing rate. This limitation of firing rate resulted from the inability of increased glutamate to change evoked plateau amplitude. Similar nonlinear patterns of soma firing were evoked by focal iontophoresis on the distal apical, oblique, and basal dendrites, whereas iontophoresis on the soma and proximal apical dendrite only evoked a linear increase in firing rate as a function of iontophoretic current without plateaus. Plateau amplitude recorded in the soma decreased as the site of iontophoresis was moved farther from the soma, consistent with decremental propagation of the plateau to the soma. Currents arriving at the soma summed if plateaus were evoked on separate dendrites or if subthreshold responses were evoked from sites on the same dendrite. If plateaus were evoked at two sites on the same dendrite, only the proximal plateau was seen at the soma. Just-subthreshold depolarizations at two sites on the same dendrite could sum to evoke a plateau at the proximal site. We conclude that the plateaus prevent current from ligand-gated channels distal to the plateau-generating region from reaching the soma and directly influencing firing rate. The implications of plateau properties for synaptic integration are discussed.

Laboratory note. EEG changes after acute cerebral embolism.

Embolism of the right middle cerebral artery regularly failed to induce clinical or electrical seizure activity during acute ischemia in primates. This negative correlation casts some doubt on the popular interpretation of seizures at the outset of clinical stroke as evidence of cerebral embolism.

Altered ligand specificity by protonation in the ligand binding domain of cyclic nucleotide-gated channels.

Cyclic nucleotide-gated (CNG) ion channels are the critical mediators between the second messengers of sensory transduction and the cell's membrane potential. The photoreceptor CNG channels are activated by the direct binding of cGMP but can also be activated to a much lesser extent by cAMP. In rod CNG channels expressed in Xenopus oocytes, we demonstrate two types of potentiation by protons. One type potentiated cGMP-bound and cAMP-bound channels to the same extent, while another potentiated only cAMP-bound channels. Both types of potentiation could be described by a mechanism in which protons bound primarily to the channel open configuration. The potentiation specific to cAMP-bound channels could be accounted for by protonation of aspartic acid 604 (D604). It is the unfavorable electrostatic interaction between the carboxylate of D604 and the purine ring of cAMP that accounts for the normally poor activation of the channels by cAMP. Protonation at this site removed the unfavorable interaction and allowed cAMP to act as nearly a full agonist. Protonation of a second amino acid, H468, contributed to the nucleotide-nonspecific potentiation and is likely to be an element of the channel gating assembly. Protons potentiate native rod channels less than channels formed from subunit 1. In heteromultimeric channels formed by coexpressing subunit 1 with subunit 2, we found a similar attenuation of potentiation. The absence of protonatable amino acids in subunit 2 at positions corresponding to H468 and D604 can explain the reduced effects of pH on native channels.

Epidural spinal cord stimulation with a multiple electrode paddle lead is effective in treating intractable low back pain.

The objective of this paper is to examine the outcomes of patients with intractable low-back pain treated with epidural spinal cord stimulation (SCS) utilizing paddle electrodes and a radio frequency (RF) stimulator. A multicenter prospective study was performed to collect data from patients suffering from chronic low-back pain. The study was designed to collect data from 60 patients at four centers and examine their outcomes at, or up to two years post implantation. Patients' participation included written responses to a series of preoperative questionnaires that were designed to collect previous surgical history information, leg and low back pain characteristics, and routine demographic information. Outcome measurements included the visual analog scale (VAS), the Oswestry Disability Questionnaire, the Sickness Impact Profile (SIP), and a patient satisfaction rating scale. Data were collected at each site during patient visits or by mail, at approximately six months, 12 months, and 24 months. A total of 44 patients have been implanted with a SCS system at the time of this writing. Follow-up data were available for 41 patients. Preoperatively, all patients reported more than 50% of their pain in the low back. All patients had pain in both their backs and legs. All patients showed a reported mean decrease in their 10-point VAS scores compared to baseline. The majority of patients reported fair to excellent pain relief in both the low back and legs. At six months 91.6% of the patients reported fair to excellent relief in the legs and 82.7% of the patients reported fair to excellent relief in the low back. At one year 88.2% of the patients reported fair to excellent relief in the legs and 68.8% of the patients reported fair to excellent relief in the low back. Significant improvement in function and quality of life was found at both the six-month and one-year follow-ups using the Oswestry and SIP, respectively. The majority of patients reported that the procedure was worthwhile (92% at six months, 88% at one year). No patient indicated that the procedure was not worthwhile. We conclude that SCS proved beneficial at one year for the treatment of patients with chronic low back and leg pain.

Treatment of chronic pain in failed back surgery patients with spinal cord stimulation: a review of current literature and proposal for future investigation.

Objective. The authors attempted to design and conduct a randomized, prospective study to investigate the efficacy of spinal cord stimulation (SCS) for patients with chronic back and leg pain following at least one previous surgery. While the scientific advantages of the randomized, prospective trial are considerable, the authors encountered numerous practical and ethical difficulties with conducting these trials. These are reviewed and an alternative investigative technique proposed. Materials and Methods. The literature on interventional and minimally invasive treatments for this population group is reviewed, and the strengths and weaknesses of different methodologies for conducting clinical research in an interventional setting are examined. Results. The difficulties inherent in a randomized, prospective study for an intervention vs. a nonintervention group are addressed, and an alternative methodology is proposed-that of a randomized interventional design. In this design, patients are assigned to a given treatment group, with each treatment exclusively available at different centers. Conclusions. By utilizing a randomized interventional study design, problems of comparability of procedures, provider reluctance to participate in randomized clinical trials, provider bias, detection bias, and transfer bias are eliminated. It is suggested that future investigations, particularly those which are interventionally or device-based, conform to this particular model.

An instrument for stable single cell recording from pulsating human cerebral cortex.

An instrument has been developed for positioning microelectrodes near neurons in the exposed pulsating cerebral cortex of man or animals. The electrode moves with the cortex and maintains a fixed relationship with the desired neuron. Stable extracellular single cell recordings have been obtained for 17.5 min from an exposed human brain that pulsated 1.5 mm at the surface.