Alteration of the cortical motor map in a patient with intractable focal seizures.

Patients with epilepsia partialis continua may develop progressive neurological deficits of unclear origin. It is possible that repetitive epileptic spikes induce plastic changes in the cortex analogous to the changes observed following direct microstimulation. A child is reported with focal cortical dysplasia, intractable focal seizures, worsening hemiparesis, and alteration of the cortical motor map over time. At age 7, he underwent cortical motor mapping before partial resection of a seizure focus within the right postcentral gyrus. No deficits were present after surgery, and seizure frequency declined by more than 90%. Seizures subsequently worsened and a progressive left hemiparesis developed. Cortical remapping at age 12 showed motor centres for left arm, face, and eye movements in an unusual configuration. The location of the motor representation of the face differed from the location obtained at age 7. This case provides direct electrophysiological evidence of reorganisation of the cortical motor map in the human brain.

Intracranial lipoma of the sylvian fissure. Case report and review of the literature.

The authors present a rare case of lipoma of the sylvian fissure found in a 34-year-old man who presented with seizures. The patient underwent craniotomy and an attempted resection of the lesion, which was initially believed to be a dermoid tumor. The imaging characteristics of dermoids and lipomas are extremely similar. Given the difference in the natural history and resectability of these lesions, lipomas should be included in the differential diagnosis of lesions with imaging characteristics similar to dermoids. Currently, tumor location, density of the lesion or computerized tomography scans, and signal homogeneity of the lesion on magnetic resonance images can help one to distinguish these radiographically similar, but pathologically different, entities. As this case confirms, resection of a sylvian fissure lipoma is extremely difficult and potentially dangerous; in addition it is unlikely to improve symptoms. A short review of 10 cases reported in the literature and therapeutic options for these lesions are also discussed.

Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture.

Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of rodent and human malignant glioma cell lines, we demonstrated that millimolar concentrations of acetylsalicylate, acetaminophen, and ibuprofen all significantly reduce cell numbers after several days of culture. However, their mechanisms of action may vary, as demonstrated by (1) differences in the morphological changes produced by these compounds; (2) varied responses to these drugs with respect to toxicity kinetics; and (3) respective rates of cell proliferation, DNA synthesis, and mitotic index. We studied the effects of acetaminophen on relative cell number further. Evidence is presented that acetaminophen induced cell death by an apoptotic mechanism after a brief burst of mitosis in which cell numbers increased transiently, followed by a reduction in cell number and an increase in DNA fragmentation, as evidenced by terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis. Using cultures of adult human brain and embryonic rat brain, we demonstrated that glioma cells were several-fold more sensitive to acetaminophen than normal brain cells in culture. Finally, subtoxic doses of acetaminophen increased the sensitivity of the human glioma cells in culture to ionizing radiation. Taken together, these results suggest that acetaminophen may prove to be a useful therapeutic agent in the treatment of human brain tumors.

False localizing signs in upper cervical spinal cord compression.

Proprioceptive loss, paresthesias, and atrophy of the hands can occur with disorders afflicting the upper cervical spinal cord. The diagnosis might be erroneous, because compression in this region might produce signs and symptoms that seem to originate in the lower cervical cord. This article reviews the clinical presentation and radiographic data of a consecutive series of 11 patients who presented between 1992 and 1994 with an extradural lesion above the C4 level. Each patient had a characteristic syndrome of finger and hand dysesthesia, hand atrophy, and occipital or cervical pain. These complaints usually preceded the development of spasticity and gait disturbance. Initial diagnoses included brachial plexopathy, shoulder dysfunction, viral syndrome, and cervical spondylosis at a lower segment. Cervical spondylosis or a herniated disc was the most common pathogenesis. The most commonly involved level was C3-C4. Nine patients underwent a surgical procedure; eight showed significant postoperative improvement (mean time of follow-up examination, 9.7 mo; follow-up range, 1-24 mo). One patient was lost to follow-up. Although the pathophysiology of these findings is unknown, theories include anterior spinal artery ischemia, venous obstruction, and differential decussation of the forelimb and hindlimb fibers of the corticospinal tract. Recognition of this syndrome might prevent inappropriate operative intervention in patients with coexisting pathological conditions of the lower cervical spinal cord.

Basic fibroblast growth factor-like activity and receptors are expressed in a human glioma cell line.

Basic fibroblast growth factor (bFGF), a potent mitogen and angiogenic peptide, has been examined as an autocrine regulator of glioma cell growth. The addition of purified bovine pituitary bFGF to an established human glioma cell line, SNB-19, doubled the density of these cells in chemically defined medium. Half-maximal stimulation occurred at 8.2 ng/ml (480 pM). Also, human recombinant bFGF (hr-bFGF) significantly enhanced the growth of SNB-19 cells in soft agar. SNB-19 cells expressed both high and low affinity binding sites for hr-bFGF. These cells expressed approximately 13,000 high affinity sites/cell (Kd = 16.6 +/- 1.7 pM) and 9.5 x 10(6) low affinity sites/cell (Kd = 61.2 +/- 4.1 nM). The results of cross-linking experiments with iodinated hr-bFGF demonstrated the presence of two bands with molecular masses of 145 and 130 kDa. High affinity receptors were also demonstrated in SNB-19 tumors grown in nude mice. SNB-19 cell extracts contained mitogenic activity that eluted from heparin-agarose with high salt (1.2-2 M NaCl) and exhibited many properties normally associated with authentic bFGF. This material cross-reacted with a monoclonal antibody to hr-bFGF, comigrated with hr-bFGF by Western blot analysis, competed with 125I-hr-bFGF in a radioreceptor assay, and stimulated SNB-19 cell growth. These results indicate that a human glioma cell line both expresses and utilizes a bFGF-like growth factor. Such a factor may be an important autocrine regulator of glioma cell growth and may also facilitate its neoplastic progression.

Changes in respiratory control induced by amino acid infusions.

We compared the metabolic and respiratory responses to a 4-h infusion of an amino acid solution consisting primarily of branched-chain amino acids (BCAA) to those after a standard amino acid solution in healthy subjects. Both the BCAA solution and the standard amino acid solution increased minute ventilation (mean increase 22%, p less than .001, and 18%, p less than .01, respectively), mean inspiratory flow (19%, p less than .01, and 19%, p less than .05) and oxygen consumption (9%, p less than .02, and 5%, NS). PaCO2 decreased (mean decrease 6%, p less than .01); there was a major increase in the ventilatory response to CO2 inhalation during administration of the BCAA solution but not the standard amino acid solution. Increased plasma norepinephrine concentration (mean increase 75%, p less than .001) during the infusion of the standard amino acid solution but not the BCAA solution suggested increased sympathetic activity. The results demonstrate augmented respiratory effects of amino acid infusions by BCAA enrichment, and a dissociation between the respiratory stimulation, metabolic rate, and sympathetic activity.

Effect of parasympathetic blockade on ventilatory and cardiac depression induced by opioids.

We have previously shown that delta-opioid agonists decrease ventilation and heart rate. Because of these results and the known interactions between opioid and acetylcholine metabolism, we hypothesized that opioids induce cardiorespiratory changes via the parasympathetic nervous system. To test this hypothesis, we administered atropine sulfate (systemically) at maximal effect of D-Ala-D-Leu-enkephalin (DADLE; a preferential delta-opioid agonist), injected intracisternally, and examined its effect on cardiorespiratory function. All experiments were performed on chronically instrumented and conscious adult dogs. Mean instantaneous minute ventilation or VT/TTOT decreased and PaCO2 increased after DADLE; atropine had little effect on these changes. Naloxone, even in small doses, reversed opioid effects on VT/TTOT and PaCO2. Atropine, however, reversed the DADLE-induced depression in cardiac rate. In doses that reversed this cardiac depression, atropine had no effect on cardiorespiratory function at rest, i.e., with no prior administration of DADLE. We conclude that DADLE decreases heart rate by increasing parasympathetic activity to the heart and induces hypoventilation by a different mechanism. We speculate that the opioid-induced ventilatory depression is due to either direct opioid action on central respiratory regulation or parasympathetic non-muscarinic or non-cholinergic mediating mechanisms.

The influence of preoperative total parenteral nutrition upon morbidity and mortality.

This study was done to examine the criteria for determining the adequacy of preoperative total parenteral nutrition (TPN). We hypothesized that an important criterion for adequate preoperative nutrition should be a contraction of the expanded extracellular fluid compartment known to occur in malnourished patients undergoing surgical treatment. Clinical evidence of this included a rise in the serum albumin level and weight loss. Fifty-nine patients requiring preoperative nutritional support for at least five days were admitted to the study. The patients were divided into three groups (group 1, group 2a and group 2b) based upon the response of the patients to TPN. Group 1 consisted of 23 patients who demonstrated a rise in serum albumin value, loss in body weight and diuresis after seven days of TPN. Group 2 was made up of 36 patients who failed to demonstrate a rise in the albumin level in response to nutritional support for one week. Of these patients, 20 underwent operation at the end of a week of nutritional support (group 2a) while 16 patients received four to six weeks of nutritional support preoperatively (group 2b). The complication rate in the three groups was 4.3 per cent for those in group 1; 45 per cent for those in group 2a and 12.5 per cent for those in group 2b (p less than 0.05), group 2a versus group 2b). The results of this study demonstrate a high mortality and morbidity in patients who fail to increase the serum albumin level after one week of TPN. The data suggest that a prolonged period of parenteral nutrition results in a substantial decrease in perioperative complications in this group of patients.

Effect of immediate postoperative nutritional support on length of hospitalization.

This study is a retrospective review of the effect of nutritional support on duration of hospitalization in patients undergoing radical cystectomy. Thirty-five patients were randomly assigned to receive either 5% dextrose (D5W) solution plus electrolytes or total parenteral nutrition (TPN) following operation. The assigned nutritional regimen was continued for 1 week after operation until oral intake resumed. If the patients receiving D5W remained incapable of oral intake after 1 week, TPN was instituted. The group receiving immediate postoperative TPN had a median duration of hospitalization of 17 days, while the median duration for the group receiving 5% dextrose solution was 24 days. All other patient characteristics, such as age, sex, stage/grade of tumor, and extent of preoperative radiotherapy, were similar in the two groups. These results demonstrate that immediate postoperative institution of nutritional support reduced hospitalization time following radical cystectomy. This indicates that the routine use of 5% dextrose as postoperative nutrition should be reevaluated.

Response to total parenteral nutrition in the extremely malnourished patient.

Changes in serum albumin levels and body weight are often used as indicators of the efficiency of a nutritional support regimen. Patients with moderate nutritional depletion demonstrate two distinct patterns of response during refeeding. The first is characterized by a decrease in the previously expanded extracellular fluid space with a rise in serum albumin and a loss of weight and the second by continued fluid retention with weight gain and no rise in serum albumin concentration. The second pattern has been observed in patients with ongoing stress such as infection. This study examines severely malnourished patients with no apparent inflammatory complications and demonstrates that this group responds to nutritional support in a pattern similar to that seen in the stressed patient. Eight patients with profound malnutrition were studied during the 1st week of nutritional support. Nitrogen balance was measured and the findings confirmed that all patients were anabolic. Sodium balances were used as an indicator of changes in the extracellular fluid compartment. Body weight and serum albumin were assessed daily. Body weight increased from 59 +/- 4 to 62 +/- 4% of normal (p less than 0.01) while serum albumin changed insignificantly (3.00 +/- 0.27 to 2.85 +/- 0.23 g/100 ml, NS) during the initial week of an adequate nutritional support regimen (nitrogen balance was +21.0 +/- 4.3 g, p less than 0.05). These changes were associated with a positive sodium balance (+215 +/- 20 mEq, p less than 0.05). These data confirm that some extremely malnourished patients do not experience a diuresis during the initial phase of nutritional support but rather may retain water and increase body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of protein intake on ventilatory drive.

Previous studies have demonstrated that if isotonic amino acid infusions were administered at a rate that approximated normal daily protein requirements, a leftward shift of the minute ventilation X PaCO2 relationship occurred. This study examined the effect of the administration of parenteral nutrition, at a fixed caloric intake and two levels of nitrogen (N) intake, on the ventilatory response to CO2 in nutritionally depleted patients. The intent was to determine whether increasing protein intake from normal to twice normal requirements would result in a further enhancement of the ventilatory response to CO2. Eight patients with nutritional depletion (greater than 10% weight loss) were studied. The resting energy expenditure (REE) was measured during administration of 5% dextrose, using principles of indirect calorimetry. Each patient received parenteral nutrition for a 2-week period. Two diets were examined for a 1-week period each: 1) a high N intake-15 mg nitrogen per kcal REE (approximately 21 g/day), or b) a low N intake--7.5 mg nitrogen per kcal REE (approximately 11 g/day). The initial diet was assigned randomly. Total energy intake was set at 1.35 X REE as measured during administration of 5% dextrose solution. Nonprotein calories were administered as 50% glucose and 50% fat. Breathing patterns at rest and during inhalations of 2 and 4% CO2 were analyzed using a canopy-computer-spirometer system. With an increased nitrogen intake there was a significant reduction in resting arterial PaCO2 from 39.9 to 37.6 mmHg (P less than 0.05) with no significant change in pH.(ABSTRACT TRUNCATED AT 250 WORDS)

The response to TPN. A form of nutritional assessment.

Malnutrition in surgical patients is associated with an increased incidence of postoperative mortality and morbidity. Preoperative nutritional support has been shown to be efficacious in reducing the incidence of these complications, although the postoperative complication rate in these patients continues to be greater than in their wellnourished counterparts. This study attempts to determine whether the postoperative course can be either influenced by or predicted from the preoperative response to nutritional support. Thirty-two patients with nutritional depletion who received an average of 1 week of total parenteral nutrition prior to a major abdominal operation were studied. These patients were followed for postoperative complications. Of the 16 patients who exhibited the characteristic response to early nutritional support, diuresis of the expanded extracellular fluid compartment with a resultant loss of weight (127.9 +/- 5.7 to 124.6 +/- 5.8 (SEM) lbs, p less than .001) and rise in serum albumin (3.21 +/- 0.14 to 3.46 +/- 0.15 gms%, p less than 0.001), only one developed a complication in the postoperative period. The other 16 patients did not exhibit this response. They retained additional fluid, gained weight (119.3 +/- 8.1 to 121.3 +/- 8.2 lbs, p less than .025), and showed a decrease in serum albumin levels (3.14 +/- 0.14 to 3.00 +/- 0.14%), p less than 0.01). Eight of these patients developed a total of 15 postoperative complications (p less than 0.01). This study demonstrates that the response to preoperative TPN is an important factor in assessing operative risk and morbidity. The need to individualize preoperative nutritional support and the timing of surgical intervention is clearly demonstrated.

The effect of parenteral nutritional repletion on muscle water and electrolytes. Implications for body composition.

Nutritional depletion and repletion are associated with changes in the size of the extracellular and intracellular fluid compartments. Although the effect of nutrition on whole body composition is well established, the distribution of changes among the various body tissues is not. This study correlates changes in skeletal muscle composition with whole body electrolyte and nitrogen balance in an attempt to establish the contribution made by skeletal muscle to the changes in whole body fluid and electrolyte composition. Total parenteral nutrition was administered to ten patients for 16 to 25 days. Oxygen consumption, CO2 production, and balances of N, Na, and K were measured daily. Muscle biopsies were taken prior to administration of TPN, in the middle, and at the end of the nutritional regimen. Prior to administration of parenteral nutrition, muscle concentrations of water, sodium, and chloride were significantly higher than normal. With institution of the nutritional support regimen, all three concentrations decreased. The calculated loss in muscle water could account, at most, for only one-sixth of the loss in total body water. Muscle Na loss could account for approximately one-half of the whole body change. Potassium concentrations in the depleted patients were not significantly decreased from normal values and showed a negligible increase with TPN. Since the ratio of K to dry fat-free solids in muscle was constant, most of the whole body changes could be accounted for by assuming that nearly all N is deposited in muscle. Nutritional support results in restoration of cell mass with a contraction of the extracellular fluid (ECF) compartment. The changes in the ECF must occur in tissues other than muscle, while the restoration of cell mass occurs primarily in muscle.

The saphenous system for long-term parenteral nutrition.

Three case reports describing the use of inferior vena caval catheterizations for total parenteral nutrition (TPN) are presented. Five anterior femoral vein cutdowns were advanced through the saphenous bulb, femoral, and iliac veins into the inferior vena cava. Four catheters were used for the purpose of TPN administration, the 5th for blood product administration and intraoperative monitoring. Five catheters were left in place without thrombotic or septic complications for a total of 10 months. The technique of elastomer catheter insertion in the tributary of the greater saphenous vein under local anesthesia is described.

Nutrients and ventilation.

Nutritional support of the patient with respiratory failure may play a key role in recovery. Nutritional intake not only indirectly influences lung function by altering body composition and most defense mechanisms but interacts directly with respiratory function in a variety of ways. This review will focus on 2 such interactions; the effect of glucose on CO2 production and the effect of protein on ventilatory drive. Glucose administration results in increases in CO2 production via 2 mechanisms; 1) a thermogenic effect and 2) an increase in the respiratory quotient (RQ). In the hypermetabolic, acutely ill patient, both the thermogenic effect and the rise in the RQ contribute to the rise in CO2 production. In the malnourished patient, a rise in the RQ is the primary mechanism for the increase. In either case, the increased need for CO2 elimination results in an increase in ventilatory demand which may precipitate respiratory distress in a patient with previously compromised pulmonary function. Infusions of amino acids, either alone or as a part of a complete nutritional support regimen, results in an enhanced ventilatory response to CO2. This seems to be a result of the thermogenic effect of protein and an increase in the ratio of the plasma concentration of the large amino acids to tryptophan. We postulate that brain uptake of tryptophan which is a precursor to serotonin (a known respiratory inhibitor) is reduced by the presence of increased amounts of the large neutral amino acids that compete with tryptophan for transport across the blood brain barrier, thereby resulting in respiratory stimulation.