Focal encephalitis as an etiology of temporal lobe epilepsy.
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Biomedical subjects
Publications and source records attributed to N M Barbaro.
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Frontal opercular gliosis in the dominant hemisphere caused medically refractory partial epilepsy in two patients. Both patients were aphasic during their seizures, but otherwise had normal speech. Magnetic resonance images showed well-demarcated lesions resembling tumors in each patient; on heavily T2-weighted images, the lesions were hyperintense compared with normal brain. Cortical mapping with subdural grids localized speech to the area of the lesions; therefore, the resections were performed under local anesthesia and speech was tested throughout the procedure. Postoperatively, both patients were seizure-free and had no new neurological deficits. Well-demarcated lesions, even in the dominant operculum, can be safely removed in patients with medically refractory partial epilepsy.
We prospectively analyzed MR studies of 32 patients with intractable complex partial seizures, who later underwent resection of EEG-proven seizure foci. Twenty-seven patients were imaged at 1.5, 4 at 0.35, and 1 at 0.5 Tesla. Correlation was obtained on all patients with EEG and surgical pathology. Of 19 patients with mesial temporal sclerosis (MTS), 13 exhibited an MR abnormality at the site of pathology as determined by EEG and surgery. Abnormalities included increased (8) or decreased (1) signal intensity, distortion of gray-white interface (1) and temporal lobe atrophy (3). Six patients had no abnormalities at the site of the diseased focus. MR was more sensitive in patients with other structural lesions which included tumor, encephalitis, polymicrogyria, cryptic vascular malformation, and tuberous sclerosis. Prior studies indicate some usefulness of MR in intractable seizure patients, but many report relative insensitivity of MR in defining an abnormality (as low as 11%). Our results demonstrate the usefulness of high-resolution thin-section multiplanar MR using cardiac gating or flow compensation techniques in this patient population.
The calcium-binding proteins calbindin-D28K (CaBP) and parvalbumin (PV) were localized in the "normal" and "epileptic" human hippocampus to address the possible relationship between the expression of these constitutive cytosolic calcium-binding proteins and the resistance or selective vulnerability of different hippocampal neuron populations in temporal lobe epilepsy. Compared to rodents and a baboon (Papio papio), the pattern of CaBP-like immunoreactivity (LI) in the "normal" human hippocampus is unique. CaBP-LI is present in the dentate granule cells, neurons of the "resistant zone" (area CA2), and presumed interneurons of all regions. Unlike rodent and baboon CA1 pyramidal cells, human CA1 pyramidal cells appear to be devoid of CaBP-LI. Thus, the relatively resistant dentate granule cells and CA2 pyramidal cells are the only human hippocampal principal cells that contain CaBP-LI normally. As in lower mammals, PV-LI is present exclusively in interneurons of all human hippocampal subregions. CaBP- and PV-LI were localized in hippocampi surgically removed in the treatment of intractable temporal lobe epilepsy to determine whether surviving hippocampal cells were those that express these calcium-binding proteins. Hippocampi removed from patients with tumors or arteriovenous malformations that were associated with complex partial seizures arising from this region appeared relatively normal histologically. CaBP- and PV-LI in this patient group appeared similar to that seen in autopsy controls. Conversely, "cryptogenic" epileptics, who exhibit hippocampal sclerosis as the only lesion associated with the epilepsy, exhibited a preferential survival of hippocampal cells that were CaBP- or PV-immunoreactive. In the dentate hilus, which normally contains few CaBP-LI neurons, most of the few surviving hilar neurons were CaBP-immunoreactive. Their number and darkness of staining suggests that CaBP synthesis may be increased in cells that survive. Despite an obvious decrease of PV-LI specifically in the damaged parts of the sclerotic hippocampi, PV-immunoreactive interneurons were often among the few surviving cells. Nevertheless, large expanses of the surviving granule cell layer appeared to have lost the PV-immunoreactive axosomatic fiber plexus. These results reveal a unique and striking correlation between the human hippocampal cells that normally express these calcium-binding proteins and those that survive in the sclerotic epileptic hippocampus.
Suppression of the tail-flick reflex by microstimulation of the rostral medial medulla in rats lightly anesthetized with barbiturates was studied with regard to spatial and temporal variations in electrical threshold. Trains of constant-current pulses with linearly descending amplitudes (called 'ramps') were passed through the extracellular brain microelectrode during noxious heating of the tail. The pulse amplitude at the time of the reflex, after allowance for conduction and reaction latencies, was taken as the threshold reading. This new method revealed a range of vertical electrode positions corresponding roughly to the nucleus raphe magnus, where the thresholds tended to be lowest (a mean of 4.1 microA for 0.4-ms pulses delivered at 50 Hz). In confirmation of the technique's validity neither the duration of the ramp nor its starting amplitude, within their useful range, significantly affected the measured threshold. Pronounced temporal fluctuation was seen in thresholds measured every 2 min. Spatial variability within the low-threshold region and differences between preparations were statistically much smaller sources of variation. The temporal fluctuation appeared to have a stationary mean for at least 20 min under constant conditions of anesthesia. In some experiments, action potentials from single neurons were recorded through the stimulating electrode, and classified into those inhibited during the tail-flick (off-cells), those excited (on-cells), and those unaffected (neutral cells). The thresholds where off-cells exhibited their maximum action potential were on average significantly lower than corresponding thresholds for on-cells. Short-range (less than 0.2 mm) spatial variations in the threshold appeared however to be uncorrelated with the distance to an individual recorded off-cell or on-cell.(ABSTRACT TRUNCATED AT 250 WORDS)
A 'time-on' theory to explain the cerebral distinction between conscious and unconscious mental functions proposes that a substantial minimum duration ('time-on') of appropriate neuronal activations up to about 0.5 s is required to elicit conscious sensory experience, but that durations distinctly below that minimum can mediate sensory detection without awareness. A direct experimental test of this proposal is reported here. Stimuli (72 pulses/s) above and below such minimum train durations (0-750 ms) were delivered to the ventrobasal thalamus via electrodes chronically implanted for the therapeutic control of intractable pain. Detection was measured by the subject's forced choice as to stimulus delivery in one of two intervals, regardless of any presence or absence of sensory awareness. Subjects also indicated their awareness level of any stimulus-induced sensation in each and every trial. The results show (1) that detection (correct greater than 50%) occurred even with stimulus durations too brief to elicit awareness, and (2) that to move from mere detection to even an uncertain and often questionable sensory awareness required a significantly larger additional duration of pulses. Thus simply increasing duration ('time-on') of the same repetitive inputs to cerebral cortex can convert an unconscious cognitive mental function (detection without awareness) to a conscious one (detection with awareness).
Improved control of postoperative pain is now known to reduce the incidence of morbidity. Although spinally administered narcotics have found a clear role in chest and abdominal surgery, their role in lumbar spinal surgery is debated. We conducted a prospective, double-blind, randomized, placebo-controlled trial of intrathecally administered morphine sulfate after lumbar spinal surgery in 56 patients. Patients received 0, 0.125, 0.25, or 0.5 mg of intrathecally administered morphine during extradural lumbar spinal operations, and the effects on postoperative analog pain scores, narcotic consumption, complications, and length of hospitalization were assessed. As compared with systemic narcotic administration, intrathecally administered morphine provided superior analgesia in a dose-dependent fashion without an increase in narcotic side effects. Consumption of parenteral narcotics on the first postoperative day and over the total hospitalization period decreased in correlation with increasing doses of intrathecally administered morphine. Mean length of hospitalization was significantly decreased, as compared with the control group, in patients receiving 0.25 or 0.5 mg of intrathecally administered morphine. When proper precautions are observed, intrathecally administered morphine can improve the postoperative care of patients undergoing lumbar spinal surgery.
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Among 55 patients undergoing temporal lobectomy for refractory epilepsy, patients with seizures in the week following surgery had a poor long-term, seizure-free outcome compared with patients without seizures. Outcome for patients with single seizures or seizures restricted to the first postoperative day seemed favorable compared with patients with multiple or later seizures. Seizure type and similarity to preoperative events did not predict outcome.
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Enhanced responsiveness to noxious stimulation is a reliable sign of opioid withdrawal and is therefore a measure of physical dependence. In lightly anesthetized rats, naloxone, given i.v. 15 min following i.v. morphine, caused a significant shortening of tail flick latency (hyperalgesia). At each dose of naloxone (0.1, 1.0 or 2.0 mg/kg), the magnitude of the observed hyperalgesia was a function of the preceding dose of morphine (0.5, 1.0 or 2.0 mg/kg). Thus morphine rapidly induces two dose-related opposing processes: one results in antinociception and the other in the potential for hyperalgesia.
Hyperresponsiveness to noxious stimulation (hyperalgesia) is observed with naloxone-precipitated morphine withdrawal in several experimental models, and may be due to changes in central nervous system neurons. Previous studies have demonstrated that certain neurons in the rostral ventromedial medulla (on-cells) discharge just prior to nocifensive withdrawal reflexes and are inhibited by morphine. Because the tail flick latency (TFL) is shorter when on-cells are active, it has been proposed that on-cells facilitate nocifensive reflexes. The present study examined the hypothesis that the hyperalgesia observed following naloxone-precipitated withdrawal from morphine is caused by increased on-cell discharge. Rats were maintained in a lightly anesthetized state with chloral hydrate. Administration of saline (1.25 cc, i.v.) or morphine sulfate (1.25 mg/kg, i.v.) was followed by naloxone (1.0 mg/kg, i.v.). On- and off-cell activity was continuously recorded and was correlated with TFL and paw withdrawal threshold (PWT). As previously reported, morphine increased off-cell activity, blocked on-cell activity, and suppressed the tail flick and paw withdrawal reflexes. When naloxone was given after morphine, TFL and PWT were reduced to values significantly below baseline (hyperalgesia). Both spontaneous and reflex-related on-cell activity increased to levels greater than the premorphine baseline. Spontaneous off-cell activity decreased abruptly to near zero when morphine was followed by naloxone. Linear regression analysis during the hyperresponsive state revealed a significant correlation between increased on-cell activity and reduced TFL, but not between decreased off-cell activity and TFL. These findings are consistent with the hypothesis that on-cells facilitate spinal nocifensive reflexes, and that the naloxone-precipitated hyperalgesia is at least in part accounted for by increased on-cell activity. A neural model of opiate dependence, tolerance, and withdrawal is proposed.
Recent work in this laboratory has identified two classes of putative nociceptive modulating neurons in the rostral ventromedial medulla (RVM) of the rat: "off-cells," which pause beginning just prior to the tail flick response (TF) evoked by noxious heat, and "on-cells," which accelerate shortly before the occurrence of the TF. In the unstimulated, lightly anesthetized rat, the spontaneous firing pattern of individual on- and off-cells consists of alternating periods of silence and activity lasting from several seconds to a few minutes. In the present study, simultaneous recordings were made from pairs of TF-related neurons, and the relationships among the firing patterns of cells within a class and between cells of different classes were determined. All cells of a given class showed fluctuations in spontaneous discharge that were in phase. On the other hand, there was a striking reciprocity of firing between the two cell classes, such that a decrease in activity of cells of one class was accompanied by an increase in activity of cells of the other class. These observations point to the existence of integrating mechanisms that coordinate the activity of all members of each class of TF-related neurons. Thus, the pattern of activity of any single on- or off-cell provides a useful index of the excitability of all cells of that class. Moreover, because of the highly reciprocal nature of the firing of the two classes, it is possible to infer the current state of both cell populations from the pattern of activity of any single TF-related neuron.
In the unstimulated, lightly anesthetized rat, both on- and off-cells exhibit alternating periods of silence and activity lasting from several seconds to a few minutes. In the preceding paper, we showed that the active periods of all cells of the same class are always in phase, whereas the firing of cells of different classes is invariably out of phase. Thus, the pattern of firing of any single on- or off-cell provides a useful indication of the excitability of all on- and off-cells in the rostral ventromedial medulla (RVM). In this study, we measured the latency of the tail flick response (TF) at set intervals while recording from TF-related neurons in RVM, and were able to demonstrate a significant relationship between the spontaneous firing of both on- and off-cells and the latency of the TF response. If noxious heat is applied at a time when an off-cell is spontaneously active (or an on-cell is silent), the TF latency is longer than if the TF trial falls during a period in which the off-cell is silent (or the on-cell is active). This correlation between on- and off-cell firing and changes in TF latency is consistent with a nociceptive modulatory role for either or both cell classes. These findings support the hypothesis that off-cells inhibit and on-cells facilitate spinal nociceptive transmission and reflexes.
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Pain relief was evaluated in 40 patients with various types of deafferentation pain that were treated with dorsal root entry zone (DREZ) lesions produced with microsurgical lasers. Good long-term pain relief was evident in some paraplegics and in all patients with brachial plexus avulsion. Several other small subgroups of patients benefited from laser DREZ lesions as well. Pain associated with arachnoiditis and peripheral nerve injury or neuropathy did not respond to laser DREZ lesioning. Based upon the smaller lesion dimensions produced with the lasers, it is proposed that interruption of impulses in the tract of Lissauer may be a mechanism of pain control in patients that responded to laser DREZ lesions.
Five patients had intradural arachnoid cysts of the thoracic spinal canal associated with syringomyelia or posttraumatic intramedullary spinal cord cysts. Three cases were diagnosed 6 to 18 years after spinal surgery and two 14 to 17 years after spinal cord trauma. In each case, delayed progression of symptoms led to the identification of the lesions. The diagnosis was assisted by the use of myelography and delayed computerized tomography scanning in two cases and by magnetic resonance imaging in all five. In each case, the arachnoid cyst appeared to compress the spinal cord or nerve roots; in three cases, the syrinx cavities appeared to exert a significant mass effect. In the two trauma-related cases, the intramedullary cysts were small and may have represented areas of cystic myelomalacia. In four cases, intraoperative real-time ultrasonography helped to localize the arachnoid and intramedullary cavities. All five patients were treated by fenestration of the arachnoid cyst; additional peritoneal shunting of the cyst was performed in one case and of the intramedullary cavity in three. In one patient, the two lesions appeared to have a balancing effect; after drainage of the arachnoid cyst, the syrinx cavity expanded and had to be treated separately. The neurological deficits were reduced in four patients and stabilized in one. Intradural arachnoid cysts and intramedullary cysts may occur together as a late complication of spinal surgery or spinal cord trauma, and either or both lesions may cause delayed neurological deterioration.