Biomedical subjects

W M Mueller

Publications and source records attributed to W M Mueller.

At least 19 recordsLinked to original sources

PubMed2006

Presurgical and intraoperative mapping of the motor system in congenital truncation of the precentral gyrus.

A 43-year-old man presented with a grade II astrocytoma in the left postcentral gyrus and superior parietal lobule. Preoperative functional MR imaging and diffusion tensor imaging mapped distal upper-extremity primary motor cortex and white matter, respectively, adjacent to the tumor, within a congenitally truncated precentral gyrus. Because of the congenital anomaly, this region of primary motor cortex was inaccessible to direct visualization or intraoperative electrocortical stimulation. The integration of preoperative and intraoperative mapping data facilitated resection of the tumor while avoiding a postoperative motor deficit.

Adult↗

PubMed2003

Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery.

BACKGROUND: Left anterior temporal lobectomy (L-ATL) may be complicated by confrontation naming deficits. OBJECTIVE: To determine whether preoperative fMRI predicts such deficits in patients with epilepsy undergoing L-ATL. METHODS: Twenty-four patients with L-ATL underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language dominance, and pre- and postoperative neuropsychological testing. fMRI laterality indexes (LIs), reflecting the interhemispheric difference between activated volumes in left and right homologous regions of interest, were calculated for each patient. Relationships between the fMRI LI, Wada language dominance, and naming outcome were examined. RESULTS: Both the fMRI LI (p < 0.001) and the Wada test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity and 73% specificity in predicting significant naming decline. Both fMRI and the Wada test were more predictive than age at seizure onset or preoperative naming performance. CONCLUSIONS: Preoperative fMRI predicted naming decline in patients undergoing left anterior temporal lobectomy surgery.

Adult↗

PubMed2001

Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores.

PURPOSE: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L-ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L-ATL. METHODS: We compared 6-month postoperative verbal memory change scores and seizure outcome in L-ATL patients with either an expected (n=12) or reversed WMA (n=9) pattern on Wada memory testing. RESULTS: L-ATL patients showing a reversed WMA score had a poorer verbal memory outcome and poorer seizure control after surgery compared with patients showing a WMA score in the expected direction. CONCLUSIONS: L-ATL patients with a reversed WMA score have a greater risk for memory morbidity and poorer seizure outcome than do patients with a WMA score in the expected direction. The WMA score was the best predictor of memory outcome after L-ATL. When the WMA score is not considered, both individual Wada hemisphere scores (contralateral and ipsilateral) provided significant and independent contribution to predicting postoperative verbal memory functioning. These findings are discussed in the context of the functional reserve and hippocampal adequacy models of memory change after temporal lobectomy.

Adult↗

PubMed2001

Magnetic resonance analysis of postsurgical temporal lobectomy.

BACKGROUND AND PURPOSE: The effect of temporal lobe transection area, volume of postoperative gliosis, and surgical technique on patients' seizure-free outcome is unknown. The authors studied the effects of these variables on patients' seizure-free outcome. METHODS: A retrospective review of magnetic resonance imaging examinations acquired 3 to 18 months after temporal lobe resection was carried out for 18 patients with intractable temporal lobe seizures and known postsurgical outcomes for more than 2 years. The total volume of radiologically probable gliosis evident on axial proton-density-weighted images was calculated for each patient using software on an independent console. The total area of temporal lobe surface transected by the scalpel was calculated as well, using sagittal T1-weighted images. The total volume of gliosis, the total area of transected temporal lobe, and the specific type of surgery (sparing vs no sparing of the superior temporal gyrus) were then correlated with the postsurgical outcome of the patients. An examiner with no prior knowledge of the patients' postsurgical outcomes carried out the above calculations and measurements. The patients' postoperative outcome was defined using Engel classifications, and patients were divided into 2 groups: group A with Engel class 1 (n = 9) and group B with Engel classes 2-4 (n = 9). RESULTS: The mean volumes of postoperative gliosis were not significantly different between group A (3592.3 mm3) and group B (4270 mm3). The mean area of transected temporal lobe was also similar between group A (1865.2 mm2) and group B (1930 mm2). With regard to surgical technique, there were 5 patients who had the superior temporal gyrus resected and 13 who did not. Eighty percent of patients with the superior temporal gyrus resected were Engel class 1 or 2, whereas only 20% were of Engel class 3 or 4. CONCLUSIONS: The authors found no clear association between postoperative outcome and residual temporal lobe gliosis, the surgical technique, or the total area of temporal lobe transected by the scalpel.

Adult↗

PubMed2001

Prognostic value of the consistency of lateralizing ictal features and ictal EEG in patients undergoing temporal lobectomy for refractory complex partial seizures.

PURPOSE: Ictal and postictal clinical manifestations have lateralizing value in the presurgical evaluation of intractable seizures. The consistency and frequency of these signs during seizures and the associated implications for postoperative seizure outcome are unknown. METHODS: The videotaped complex partial seizures of 49 patients with known postoperative outcomes greater than 2 years after temporal lobectomy were blindly reviewed for: (1) unilateral hand posturing (UHP), (2) unilateral hand automatism (UHA), (3) forced and nonforced head turning (HT), and (4) postictal dysphasia (PID). The presence and laterality of each assessable sign were recorded. Data were analyzed as follows: (1) the prevalence of each sign in patients with Engel class 1 and Engel class 2-4, and (2) the postsurgical outcome when the sign was present in more than or less than 50% of the seizures for each patient. We reviewed patients' presurgical work-up, specifically ictal EEG and MRI. RESULTS: The prevalence of UHP, UHA, HT, and PID was similar for Engel class 1 and Engel class 2-4 patients. Engel class 1 outcome when UHP, UHA, HT, and PID were present for greater than 50% of seizures was no different compared to when these signs were present for less than 50% of seizures. Patients who had concordant ictal EEG and MRI abnormalities had the best postsurgical outcome. CONCLUSIONS: The consistency and frequency of ictal manifestations in the presurgical evaluation of complex partial seizures does not predict seizure outcome. The presence of any specific lateralizing sign need not be present in every complex partial seizure for the sign to hold predictive value. Concordant ictal EEG and MRI abnormalities are still the best predictors of outcome.

Electroencephalography↗

PubMed2000

Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes.

OBJECTIVE: We have reported that glucose utilization regulates leptin expression and secretion from isolated rat adipocytes. In this study, we employed two antidiabetic agents that act to increase glucose uptake by peripheral tissues, metformin and vanadium, as pharmacological tools to examine the effects of altering glucose utilization on leptin secretion in primary cultures of rat adipocytes. RESEARCH METHODS AND PROCEDURES: Isolated adipocytes (100 microL of packed cells per well) were anchored in a defined matrix of basement membrane components (Matrigel) with media containing 5.5 mM glucose and incubated for 96 hours with metformin or vanadium. Leptin secretion, glucose utilization, and lactate production were assessed. RESULTS: Metformin (0.5 and 1.0 mM) increased glucose uptake in the presence of 0.16 nM insulin by 37 +/- 10% (p < 0.005) and 62 +/- 8% (p < 0.0001) over insulin alone, respectively. Metformin from 0.5 to 5.0 mM increased lactate production by 105 +/- 43% (p < 0.025) to 202 +/- 52% (p < 0.0025) and at 1.0 and 5.0 mM increased the proportional rate of glucose conversion to lactate by 78 +/- 18% (p < 0.005) and 166 +/- 41% (p < 0.0025), respectively. At concentrations less than 0.5 mM, metformin did not affect leptin secretion, but at 0.5 mM, the only concentration that significantly increased glucose utilization without increasing glucose conversion to lactate, leptin secretion was modestly stimulated (by 20 +/- 9%; p < 0.05). Concentrations from 1.0 to 25 mM inhibited leptin secretion by 25 +/- 8% (p < 0.005) to 89 +/- 4% (p < 0.0001). Across metformin doses, leptin secretion was inversely related to the percentage of glucose taken up and released as lactate (r = -0.74; p < 0.0001). Vanadium (5 to 20 microM) increased glucose uptake from 20 +/- 7% (p < 0.01) to 34 +/- 13% (p < 0.02) and increased lactate production at 5 microM by 17 +/- 8% (p < 0.025) and 10 microM by 61 +/- 20% (p < 0.02) but did not alter the conversion of glucose to lactate. Vanadium (5 to 50 microM) inhibited leptin secretion by 33 +/- 6% (p < 0.0025) to 61 +/- 8% (p < 0.0001). DISCUSSION: Both metformin and vanadium increase glucose uptake and inhibit leptin secretion from cultured adipocytes. The inhibition of leptin secretion by metformin is related to an increase in the metabolism of glucose to lactate. The inhibition by vanadium most likely involves direct effects on cellular phosphatases. We hypothesize that the effect of glucose utilization to stimulate leptin production involves the metabolism of glucose to a fate other than anaerobic lactate production, possibly oxidation or lipogenesis.

Adipocytes↗

PubMed2000

Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.

BACKGROUND: Low-fat diets can increase plasma triacylglycerol and reduce HDL cholesterol. Changes in energy intake and body weight can influence the lipoprotein response. OBJECTIVE: We sought to prospectively examine the effects of euenergetic and ad libitum dietary fat restriction on plasma lipoproteins in healthy postmenopausal women. DESIGN: Participants first received a controlled euenergetic diet in which dietary fat was reduced stepwise from 35% to 25% to 15% over 4 mo. Thereafter, participants followed an ad libitum 15%-fat diet for 8 mo; 54 women completed the intervention. RESULTS: During the controlled euenergetic diet, plasma triacylglycerol increased from 1.70 +/- 0.10 to 2.30 +/- 0.16 mmol/L, total cholesterol decreased from 5.87 +/- 0.13 to 5.53 +/- 0. 13 mmol/L, LDL cholesterol decreased from 3.41 +/- 0.10 to 2.87 +/- 0.10 mmol/L, HDL cholesterol decreased from 1.76 +/- 0.08 to 1.50 +/- 0.08 mmol/L, and apolipoprotein (apo) A-I decreased from 5.11 +/- 0.14 to 4.78 +/- 0.14 mmol/L (P < 0.0001 for all changes). Hormone replacement therapy did not affect the relative change in HDL cholesterol. Plasma glucose, insulin, hemoglobin A(1C,) free fatty acid, and apo B concentrations did not change significantly. During the ad libitum 15%-fat diet, participants lost 4.6 +/- 0.4 kg. Plasma triacylglycerol and LDL cholesterol returned to baseline values (1.77 +/- 0.12 and 3.31 +/- 0.08 mmol/L, respectively), whereas HDL cholesterol and apo A-I remained low (1.40 +/- 0.08 and 4.82 +/- 0.18 mmol/L, respectively). HDL cholesterol and apo A-I concentrations stabilized in subjects who were not receiving hormone replacement therapy but continued to decline in women who were receiving hormone therapy. CONCLUSIONS: The ad libitum 15%-fat diet resulted in significant weight loss. The euenergetic but not the ad libitum diet caused hypertriacylglycerolemia. HDL cholesterol decreased during both low-fat diets.

Aged↗

PubMed1999

Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05.

OBJECTIVE: To perform an open-label, long-term efficacy and safety/tolerability study of vagus nerve stimulation (VNS) of 454 patients with refractory epilepsy. METHODS: Subjects were enrolled from five clinical trials of VNS between 1988 and 1995 after undergoing an implantation of a pulse generator in the chest and a left cervical vagus nerve-stimulating lead coil. Patients were assessed at 6-month intervals until device approval. Seizure frequencies, medication treatment, and adverse events (AEs) were recorded and entered into a database. RESULTS: A total of 454 patients were implanted, and 440 patients yielded assessable data. A > or =50% seizure reduction postimplantation occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years. Median seizure reductions compared with baseline were 35% at 1 year, 44.3% at 2 years, and 44.1% at 3 years. Most common AEs postimplantation at 1 year were hoarseness (28%) and paraesthesias (12%), at 2 years were hoarseness (19.8%) and headache (4.5%), and at 3 years was shortness of breath (3.2%). Continuation rates were 96.7% at 1 year, 84.7% at 2 years, and 72.1% at 3 years. CONCLUSION: Long-term, open-label vagus nerve stimulation (VNS) provided seizure reduction similar to or greater than acute studies, for median reductions and for those reaching a > or =50% seizure reduction. VNS remained safe and well tolerated, with nearly three-quarters of the patients choosing to continue therapy.

Adult↗

PubMed1999

Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.

Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.

Acoustic Stimulation↗

PubMed1998

Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.

Circulating leptin secreted from adipocytes is correlated with fat mass and plasma insulin concentrations in humans and rodents. Plasma leptin, insulin, and glucose decrease during fasting and increase after refeeding; however, the underlying mechanisms regulating the changes of leptin secretion are not known. To investigate the role of insulin-stimulated glucose metabolism in the regulation of leptin secretion, we examined the effects of insulin and inhibitors of glucose transport and metabolism on leptin secretion from rat adipocytes in primary culture. Insulin (0.16-16 nM) increased leptin secretion over 96 h; however, the increase in leptin was more closely related to the amount of glucose taken up by the adipocytes (r = 0.64; P < 0.0001) than to the insulin concentration per se (r = 0.20; P < 0.28), suggesting a role for glucose transport and/or metabolism in regulating leptin secretion. 2-Deoxy-D-glucose (2-DG), a competitive inhibitor of glucose transport and phosphorylation, caused a concentration-dependent (2-50 mg/dl) inhibition of leptin release in the presence of 1.6 nM insulin. The inhibitory effect of 2-DG was reversed by high concentrations of glucose. Two other inhibitors of glucose transport, phloretin (0.05-0.25 mM) and cytochalasin-B (0.5-50 microM), also inhibited leptin secretion. Inhibition of leptin secretion by these agents was proportional to the inhibition of glucose uptake (r = 0.60 to 0.86; all P < 0.01). Two inhibitors of glycolysis, iodoacetate (0.005-1.0 mM) and sodium fluoride (0.1-5 mM), produced concentration-dependent inhibition of leptin secretion in the presence of 1.6 nM insulin. In addition, both 2-DG and sodium fluoride markedly decreased the leptin (ob) messenger RNA content of cultured adipocytes, but did not affect 18S ribosomal RNA content. We conclude that glucose transport and metabolism are important factors in the regulation of leptin expression and secretion and that the effect of insulin to increase adipocyte glucose utilization is likely to contribute to insulin-stimulated leptin secretion. Thus, in vivo, decreased adipose glucose metabolism may be one mechanism by which fasting decreases circulating leptin, whereas increased adipose glucose metabolism would increase leptin after refeeding.

Adipocytes↗

PubMed1998

Side of seizure focus predicts left medial temporal lobe activation during verbal encoding.

OBJECTIVE: Functional MRI (FMRI) was used to investigate the effect of medial temporal lobe (MTL) pathology on activation of language encoding areas in patients with temporal lobe epilepsy (TLE). METHODS: Whole-brain FMRI was obtained. Twenty-eight patients with either left TLE (LTLE) or right TLE (RTLE) performed a semantic decision task alternating with an auditory perceptual task. RESULTS: Activation of language areas in the frontal and parietal lobes was similar in both groups, with no group differences in the total number of active voxels. However, the RTLE group showed much stronger activation of the left MTL, including the hippocampus, parahippocampal gyrus, and collateral sulcus, than did the LTLE group. CONCLUSIONS: Activation of the left MTL during semantic encoding discriminates patients with RTLE and LTLE. This FMRI technique may potentially be of use in determining memory lateralization and for predicting the side of seizure focus in TLE.

Adult↗

PubMed1998

Radioimmunoassay of rat leptin: sexual dimorphism reversed from humans.

Adipose tissue secretes leptin, which interacts with receptors in the hypothalamus. In rodent models of obesity, leptin increases metabolism and decreases food intake, which helps to maintain normal body composition. Accurate and precise methods to quantitate circulating leptin concentrations are needed for physiological studies. We developed an RIA to measure leptin in rat plasma, serum, or adipocyte culture fluids. The working range of the assay, defined by the detection limit and the highest calibrator, was 0.5-50 micrograms/L. Recovery of 1.6-11.6 micrograms/L leptin added to serum was 92-103%. The rat leptin RIA correlated well with a previously developed mouse RIA when rat plasma was assayed with both methods (r = 0.94), but the mouse leptin assay underestimated rat leptin in plasma. Within- and between-run CVs were 2.4% to 5.7%. Plasma leptin concentrations correlated directly with percentage of body fat, and correlation improved when the results were separated by gender (r = 0.796, P < 0.001 for males; r = 0.710, P < 0.001 for females). Leptin concentrations were generally higher in male rats than in females; plasma leptin increased 0.60 microgram/L for each percentage of increase in body fat for males but only 0.22 microgram/L for females. We conclude that rat serum/plasma leptin concentrations are accurately and precisely measured with this new RIA.

Adipocytes↗

PubMed1997

Functional magnetic resonance imaging of the somatosensory cortex.

Functional magnetic resonance (fMR) imaging, like positron emission tomography (PET), shows regions of activation in the brain resulting from the neuronal activity associated with cognitive, sensory, or motor function. An advantage of fMR imaging is that the functional and the reference anatomic images are acquired simultaneously. Additionally, fMR imaging is generally more available than PET or magnetoencephalography. This article reviews the applications of fMR imaging for studying the sensorimotor cortex prior to craniotomy.

Brain Diseases↗

PubMed1997

Functional MR activation correlated with intraoperative cortical mapping.

PURPOSE: To evaluate the spatial specificity of functional MR imaging by comparing it with intraoperative electrocortical mapping. METHODS: Functional MR imaging was performed in 28 patients before awake craniotomy and intraoperative electrocortical mapping. Activation was mapped for finger movement, lip movement, tongue movement, word generation, and counting paradigms. During surgery, finger movement, lip movement, tongue movement, counting, and/or speaking were mapped. The functional images and the photographic recordings of the brain functions mapped during surgery were converted to bit maps and coregistered by a computer program. The distance between the intraoperatively mapped function site and the MR activation site for a comparable function was measured. RESULTS: Forty-six functions were recorded on MR images and intraoperative maps. In 100% of correlations, the intraoperative site and the MR activation site were within 20 mm; in 87% of correlations they were within 10 mm. For each paradigm, 67% or more of the intraoperative stimulation maps correlated within 10 mm of the MR activation site. CONCLUSIONS: For the tasks used in this study, the activation site on functional MR images correlated well with the site at which intraoperative stimulation identified function.

Afferent Pathways↗

PubMed1996

Functional magnetic resonance imaging mapping of the motor cortex in patients with cerebral tumors.

OBJECTIVE: The purpose of this study was to determine the usefulness of functional magnetic resonance imaging (FMRI) to map cerebral functions in patients with frontal or parietal tumors. METHODS: Charts and images of patients with cerebral tumors or vascular malformations who underwent FMRI with an echoplanar technique were reviewed. The FMRI maps of motor (11 patients), tactile sensory (12 patients), and language tasks (4 patients) were obtained. The location of the FMRI activation and the positive responses to intraoperative cortical stimulation were compared. The reliability of the paradigms for mapping the rolandic cortex was evaluated. RESULTS: Rolandic cortex was activated by tactile tasks in all 12 patients and by motor tasks in 10 of 11 patients. Language tasks elicited activation in each of the four patients. Activation was obtained within edematous brain and adjacent to tumors. FMRI in three cases with intraoperative electrocortical mapping results showed activation for a language, tactile, or motor task within the same gyrus in which stimulation elicited a related motor, sensory, or language function. In patients with > 2 cm between the margin of the tumor, as revealed by magnetic resonance imaging, and the activation, no decline in motor function occurred from surgical resection. CONCLUSIONS: FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors.

Adolescent↗

PubMed1996

Determination of language dominance using functional MRI: a comparison with the Wada test.

We performed functional MRI (FMRI) in 22 consecutive epilepsy patients undergoing intracarotid amobarbital (Wada) testing and compared language lateralization measures obtained with the two procedures. FMRI used a single-word semantic decision task previously shown to activate lateralized language areas in normal adults. Correlation between the two tests was highly significant (r = 0.96; 95% CIs 0.90 to 0.98; p < 0.0001). These results validate the FMRI technique and suggest that "active" areas observed with this semantic processing task correspond to those underlying hemispheric dominance for language. This strong correlation observed supports the view that language lateralization is a continuous rather than a dichotomous variable. In addition to lateralization information, FMRI consistently demonstrated focal regions of activity in lateral frontal and temporo-parieto-occipital cortex. These functional maps may be helpful in defining the boundaries of surgical excisions.

Adolescent↗

PubMed1995

Functional magnetic resonance imaging mapping of the sensorimotor cortex with tactile stimulation.

The purpose of this study is to compare tactile stimulation of the palm with voluntary movement of the fingers as paradigms for mapping the sensorimotor cortex in functional magnetic resonance imaging. In 22 subjects, 24 sets of functional magnetic resonance images were obtained with echoplanar acquisitions and cross-correlation image processing techniques. Two tasks were employed: a motor task in which subjects moved the thumb and index finger of one hand and a sensory task in which the palm was scratched by another person. The activation from the two tasks coincided entirely in 20 sets and partially in 3 sets. In one case, no activation was seen with the motor task. The study suggests that tactile stimulation of the palm is useful and reliable for mapping the sensorimotor cortex.

Adult↗

PubMed1995

A comparison of functional MR activation patterns during silent and audible language tasks.

PURPOSE: To compare word generation tasks performed silently and aloud as paradigms for functional MR. METHODS: Images were obtained at 1.5 T, with echoplanar acquisition in nine subjects performing word generation aloud or silently. Functional images created from the echoplanar images by means of cross-correlation techniques were superimposed on anatomic reference images. The location of activation from the two tasks was tabulated; the number of activated pixels in each region from the two tasks was compared. RESULTS: Both silent and aloud word generation produced activation in the inferior frontal lobes, sensorimotor cortex regions, supplementary motor areas, and anterior cingulate gyri, predominantly in the dominant hemisphere. Significantly more activated pixels and fewer artifacts were detected with silent word generation than with word generation aloud. CONCLUSION: Word generation silently or aloud produce activation in the brain. Greater activation can be detected in the left frontal lobe with silent word generation, although the subject's performance of the task cannot be monitored independently during silent word generation.

Adult↗