Biomedical subjects

S P Miller

Publications and source records attributed to S P Miller.

At least 19 recordsLinked to original sources

PubMed2006

Does perinatal asphyxia impair cognitive function without cerebral palsy?

Some studies on neurodevelopmental outcomes after neonatal encephalopathy have suggested that cognitive deficits do not occur in the absence of cerebral palsy. It is increasingly apparent that childhood survivors of overt neonatal encephalopathy may have cognitive impairments, even in the absence of functional motor deficits. The risk of cognitive deficits is related to the severity of neonatal encephalopathy and the pattern of brain injury on neuroimaging, particularly the watershed pattern of injury. A better understanding of the risk factors for cognitive abnormalities after neonatal encephalopathy will ultimately lead to interventions to prevent these deficits. Identifying the full spectrum of neurodevelopmental outcomes after neonatal encephalopathy will also allow care givers to identify children requiring early intervention to maximise their potential for independent function throughout development.

Animals↗

PubMed2006

Association of a single nucleotide polymorphism in the calpastatin gene with carcass and meat quality traits of beef cattle.

Calpastatin (CAST) is a naturally occurring protein that inhibits the normal tenderization of meat as it ages postmortem. A SNP was identified in the CAST gene (a G to C substitution) and genotyped on crossbred commercially fed heifers (n = 163), steers (n = 226), and bulls (n = 61) from beef feedlots, and steers (n = 178) from a University of Guelph feeding trial. The association of the CAST SNP with carcass and meat quality traits was studied. Carcass traits included fat, lean, and bone yield; grade fat; LM area; and HCW. Meat quality traits included marbling grade; i.m. fat content of LM; tenderness evaluation of LM (Warner-Bratzler shear force) at 2, 7, 14, and 21 d of postmortem aging; and tenderness evaluation of semitendinosus muscle at 7 d of postmortem aging. The mixed model used in the analyses included fixed effects of CAST genotype, sex, slaughter group, and breed composition (linear covariate); sire was a random effect. For the analysis of shear force, i.m. fat content of LM was also included in the model as a linear covariate. Shear force measures were analyzed within days of postmortem aging and by repeated measures analysis. The CAST SNP allele C was more frequent (63%) in the crossbred population than allele G. The CAST SNP was associated with shear force across days of postmortem aging (P = 0.005); genotype CC yielded beef that was more tender than GG (-0.32 kg +/- 0.13), and CG had intermediate tenderness. The corresponding average allele substitution effect (G to C substitution) was also highly significant (-0.15 +/- 0.05 kg, P = 0.002). A lower percentage of unacceptably tough steaks (shear force > 5.7 kg) at 2 and 7 d postmortem was associated with an increasing number of C alleles (P < or = 0.05). At 7 d postmortem, the percentage of unacceptably tough steaks decreased by 24 and 35%, respectively, for animals carrying 1 and 2 copies of the C allele relative to animals with no C alleles. However, genotype CC had a greater fat yield (+1.44 +/- 0.56%; P = 0.037) than genotype GG, with a corresponding allele substitution effect of 0.67 +/- 0.27% (P = 0.015). Therefore, the CAST SNP allele C was associated with increased LM tenderness across days of postmortem aging and, importantly for the beef industry, had a significant reduction in the percentage of steaks rated unacceptably tough by consumers based on an assumed threshold level.

Animals↗

PubMed2006

Genetic correlations between live yearling bull and steer carcass traits adjusted to different slaughter end points. 1. Carcass lean percentage.

We studied genetic relationships between age-constant live yearling beef bull growth and ultrasound traits and steer carcass traits with dissected steer carcass lean percentage adjusted to slaughter age-, HCW-, fat depth-, and marbling score-constant end points. Three measures of steer carcass lean percentage were used. Blue Tag lean percentage (BTLean) was predicted from HCW, fat depth, and LM area measurements. Ruler lean percentage (RulerLean) was predicted from carcass fat depth and LM depth and width measurements. Dissected lean percentage (DissLean) was based on dissection of the 10-11-12th rib section. Both BTLean (h2 = 0.30 to 0.44) and DissLean (h2 = 0.34 to 0.39) were more heritable than RulerLean (h2 = 0.05 to 0.14) at all end points. Genetic correlations among DissLean and RulerLean (rg = 0.61 to 0.70), DissLean and BTLean (rg = 0.56 to 0.72), and BTLean and RulerLean (rg = 0.59 to 0.90) indicated that these traits were not genetically identical. Adjusting Diss-Lean to different end points changed the magnitude, but generally not the direction, of genetic correlations with indicator traits. Ultrasound scan-age-constant live yearling bull lean percentage estimates were heritable (h2 = 0.26 to 0.42) and genetically correlated with each other (rg = 0.68 to 0.99) but had greater correlations with DissLean at slaughter age (rg = 0.24 to 0.48) and HCW (rg = 0.16 to 0.40) end points than at fat depth (rg = -0.08 to 0.13) and marbling score (rg = 0.02 to 0.11) end points. Scan-age-constant yearling bull ultrasound fat depth also had stronger correlations with DissLean at slaughter age (rg = -0.34) and HCW (rg = -0.25) than at fat depth (rg = -0.02) and marbling score (rg = -0.03) end points. Yearling bull scan-age-constant ultrasound LM area was positively correlated with DissLean at all endpoints (rg = 0.11 to 0.23). Genetic correlations between yearling bull LM method 1 width (rg = 0.38 to 0.56) and method 2 depth (rg = -0.17 to -0.38) measurements with DissLean suggested that LM shape may be a valuable addition to genetic improvement programs for carcass lean percentage at slaughter age, HCW, and fat depth constant end points. At all end points, steer carcass fat depth (rg = -0.60 to -0.64) and LM area (rg = 0.48 to 0.59) had stronger associations with DissLean than did corresponding live yearling bull measurements. Improved methods that combine live ultrasound and carcass traits would be beneficial for evaluating carcass lean percentage at fat depth or marbling score end points.

Adipose Tissue↗

PubMed2006

Genetic correlations between live yearling bull and steer carcass traits adjusted to different slaughter end points. 2. Carcass fat partitioning.

Partial carcass dissection data from 1,031 finished crossbred beef steers were used to calculate heritabilities and genetic correlations among subcutaneous, intermuscular, and body cavity fat percentage and marbling score adjusted to slaughter age-, HCW-, fat depth-, and marbling score-constant endpoints. Genetic correlations were also calculated among these fat partitions with live growth and ultrasound traits evaluated in yearling beef bulls (n = 2,172) and steer carcass measurements. Heritabilities of the different fat partitions ranged from 0.22 (marbling score-constant body cavity fat) to 0.46 (HCW-constant marbling score). Genetic correlations between subcutaneous fat and intermuscular fat (rg = 0.16 to 0.32) and between intermuscular fat and body cavity fat (rg = 0.38 to 0.50) were more highly associated than subcutaneous fat and body cavity fat (rg = -0.08 to 0.05), indicating that fat depots are not under identical genetic control. Adjusting fat depots to different end points affected the magnitude but usually not the sign of the genetic correlations. Bull postweaning gain was associated with intermuscular (-0.24 to -0.35), body cavity (-0.24 to -0.29), and marbling fat (-0.24 to -0.39) in steers. Bull hip height was associated with body cavity (-0.20 to -0.29) and marbling fat (-0.20 to -0.47) in steers. Bull ultrasound fat depth was associated with subcutaneous (0.11 to 0.29), intermuscular (0.05 to 0.36), body cavity (0.27 to 0.49), and marbling fat (0.27 to 0.73) in steers. Bull ultrasound intramuscular fat percentage was associated with subcutaneous (-0.22 to -0.44) and intermuscular fat (-0.06 to 0.31) in steers. Bull ultrasound LM area was associated with body cavity (-0.25 to -0.31) and marbling fat (-0.25 to -0.30) in steers. Ultrasound LM width measurements were negatively correlated with subcutaneous fat (rg = -0.09 to -0.18), intermuscular fat (rg = -0.53 to -0.61), body cavity fat (rg = -0.63 to -0.69), and marbling score (rg = -0.75 to -0.87) at slaughter age-, HCW-, and fat depth-constant endpoints; correlations were generally lower at a marbling score-constant end point (rg = 0.07 to -0.49). Ultrasound indicator traits measured in seedstock may be useful in altering fat partitioning in commercial beef carcasses.

Adipose Tissue↗

PubMed2006

MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy.

BACKGROUND: Although the imaging, spectroscopic, and diffusion characteristics of brains of infants with neonatal encephalopathy have been described, the time course during which these changes evolve is not clear. The results of sequential MR imaging studies--including anatomic MR imaging, proton MR spectroscopy, and diffusion tensor imaging (DTI)--of 10 patients enrolled prospectively in a study of neonatal encephalopathy are reported to help to clarify the time course of changes in different brain regions during the first 2 weeks of life. METHODS: Ten neonates were prospectively enrolled in a study of the evolution of MR findings in neonatal encephalopathy and were studied 2 (8 patients) or 3 (2 patients) times within the first 2 weeks of life. The MR examination included spin-echo T1 and T2-weighted images, DTI, and long echo time (288 milliseconds) proton MR spectroscopy. Diffusion parameters (diffusivity [D(av)], fractional anisotropy [FA], and individual eigenvalues) were calculated for 10 1-cm2 regions of interest in each hemisphere that were placed based on anatomic landmarks. D(av) and FA were then measured manually in the same areas on a workstation. Metabolite ratios (NAA/Ch, Cr/Ch, Cr/NAA, Lac/Ch, and Lac/NAA) were calculated in 7 regions of interest. Imaging appearance, diffusion parameters, and metabolite ratios were then evaluated longitudinally (comparing with other studies on the same patient at different times) and cross-sectionally (comparing all studies performed on the same postnatal day). RESULTS: In most of the patients a characteristic evolution of DTI and MR spectroscopy parameters was seen during the first 2 weeks after birth. Although the anatomic images were normal or nearly normal on the first 2 days after birth in most patients, abnormalities were detected on DTI (both visually and by quantitative interrogation of D(av) maps) and proton MR spectroscopy (abnormal metabolite ratios). These parameters tended to worsen until about day 5 and then normalize, though in several patients abnormal metabolite ratios persisted. Of interest, as areas of abnormal diffusivity pseudonormalized within one region of the brain they would develop in other areas. Therefore, the pattern of injury looked very different when imaging was performed at different times during this evolution. CONCLUSION: Patterns of injury detected by standard anatomic imaging sequences, DTI sequences, and proton MR spectroscopy varied considerably during the first 2 weeks after injury. The appearance of new areas of reduced diffusion simultaneous with the pseudonormalization of areas that had reduced diffusion at earlier times can result in an entirely different pattern of injury on diffusivity maps acquired at different time points. Awareness of these evolving patterns is essential if studies are performed and interpreted during this critical period of time.

Brain Diseases↗

PubMed2005

Additive, dominance, and epistatic loss effects on preweaning weight gain of crossbred beef cattle from different Bos taurus breeds.

(Co)variance components, direct and maternal breed additive, dominance, and epistatic loss effects on preweaning weight gain of beef cattle were estimated. Data were from 478,466 animals in Ontario, Canada, from 1986 to 1999, including records of both purebred and crossbred animals from Angus, Blonde d'Aquitaine, Charolais, Gelbvieh, Hereford, Limousin, Maine-Anjou, Salers, Shorthorn, and Simmental breeds. The genetic model included fixed direct and maternal breed additive, dominance, and epistatic loss effects, fixed environmental effects of age of the calf, contemporary group, and age of the dam x sex of the calf, random additive direct and maternal genetic effects, and random maternal permanent environment effects. Estimates of direct and maternal additive genetic, maternal permanent environmental and residual variances, expressed as proportions of the phenotypic variance, were 0.32, 0.20, 0.12, and 0.52, respectively. Correlation between direct and maternal additive genetic effects was -0.63. Breed ranking was similar to previous studies, but estimates showed large SE. The favorable effects of direct and maternal dominance (P < 0.05) on preweaning gain were equivalent to 1.3 and 2.3% of the phenotypic mean of purebred calves, respectively. The same features for direct and maternal epistatic loss effects were -2.2% (P < 0.05) and -0.1% (P > 0.05). The large SE of breed effects were likely due to multicollinearity among predictor variables and deficiencies in the dataset to separate direct and maternal effects and may result in a less reliable ranking of the animals for across breed comparisons. Further research to identify the causes of the instability of estimates of breed additive, dominance, and epistatic loss genetic effects, and application of alternative statistical methods is recommended.

Animals↗

PubMed2005

Estimation of genetic effects in the presence of multicollinearity in multibreed beef cattle evaluation.

Breed additive, dominance, and epistatic loss effects are of concern in the genetic evaluation of a multibreed population. Multiple regression equations used for fitting these effects may show a high degree of multicollinearity among predictor variables. Typically, when strong linear relationships exist, the regression coefficients have large SE and are sensitive to changes in the data file and to the addition or deletion of variables in the model. Generalized ridge regression methods were applied to obtain stable estimates of direct and maternal breed additive, dominance, and epistatic loss effects in the presence of multicollinearity among predictor variables. Preweaning weight gains of beef calves in Ontario, Canada, from 1986 to 1999 were analyzed. The genetic model included fixed direct and maternal breed additive, dominance, and epistatic loss effects, fixed environmental effects of age of the calf, contemporary group, and age of the dam x sex of the calf, random additive direct and maternal genetic effects, and random maternal permanent environment effect. The degree and the nature of the multicollinearity were identified and ridge regression methods were used as an alternative to ordinary least squares (LS). Ridge parameters were obtained using two different objective methods: 1) generalized ridge estimator of Hoerl and Kennard (R1); and 2) bootstrap in combination with cross-validation (R2). Both ridge regression methods outperformed the LS estimator with respect to mean squared error of predictions (MSEP) and variance inflation factors (VIF) computed over 100 bootstrap samples. The MSEP of R1 and R2 were similar, and they were 3% less than the MSEP of LS. The average VIF of LS, R1, and R2 were equal to 26.81, 6.10, and 4.18, respectively. Ridge regression methods were particularly effective in decreasing the multicollinearity involving predictor variables of breed additive effects. Because of a high degree of confounding between estimates of maternal dominance and direct epistatic loss effects, it was not possible to compare the relative importance of these effects with a high level of confidence. The inclusion of epistatic loss effects in the additive-dominance model did not cause noticeable reranking of sires, dams, and calves based on across-breed EBV. More precise estimates of breed effects as a result of this study may result in more stable across-breed estimated breeding values over the years.

Animals↗

PubMed2005

Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle.

Studies with different populations are required to properly characterize the robustness of associations of polymorphisms in candidate genes with economically important traits across beef cattle populations before this sort of genetic information can be used efficiently in breeding and management decisions. The objective of this study was to evaluate the association of previously reported SNP in the bovine leptin gene with carcass and meat quality traits from a large sample of crossbred beef cattle. Five SNP (UASMS1, UASMS2, UASMS3, E2JW, and E2FB) were genotyped on 1,111 crossbred bulls, heifers, and steers. The measured traits included fat, lean, and bone yield (%) by partial rib dissection, grade fat, LM area, HCW, quality grade, LM i.m. fat, and tenderness evaluation of LM and semitendinosus muscle. Only four SNP were analyzed (UASMS1, UASMS2, E2JW, and E2FB), because UASMS1 and UASMS3 were completely linked. A uni-variate mixed-inheritance animal model was used to evaluate the association of either genotypes or haplo-types with the traits. The two leptin exon 2 SNP were associated with fat and lean yield and grade fat (E2JW, P < 0.01; E2FB, P < 0.05), and they interacted in their effect on LM tenderness (P < 0.01). The leptin promoter SNP were either not associated with any of the traits (UASMS2) or with fat yield only (UASMS1). Three haplotypes (TCAC, CCAT, TTAC) were at high frequency in the population (88%) and had similar effects on all the traits. Compared with the common haplotypes, one haplotype (CCTT) showed a significantly different effect on fat and lean yield and grade fat (P < 0.01), and one haplotype (TTTT) had a different effect on LM tenderness (P < 0.03). Therefore, important associations between SNP within the leptin gene with lean yield, fatness (fat yield and subcutaneous fat), and tenderness were detected. Results confirm some of the previously reported associations, but diverge with respect to others, showing that further efforts are required to validate some prospective associations.

Adipose Tissue↗

PubMed2004

Perinatal stroke in term infants with neonatal encephalopathy.

In a prospective cohort of 124 encephalopathic term infants, six infants had an acute focal stroke. All six encephalopathic patients with strokes presented with seizures. Neurodevelopmental outcome at 30 months was abnormal in all six patients and significantly worse when compared with the entire cohort overall. These findings suggest that in newborns with encephalopathy, acute focal strokes are an uncommon but serious occurrence with substantial risk for abnormal neurodevelopmental outcome.

Adult↗

PubMed2002

Multiple risk factors in neonatal sinovenous thrombosis.

The etiology of neonatal sinovenous thrombosis is poorly understood. The authors report the risk factors and radiologic features of neonatal sinovenous thrombosis seen over an 11-year period. Of 30 patients, 29% received extracorporeal membrane oxygenation treatment, and 23% had congenital heart disease. Genetic thrombophilias were present in four of the seven infants tested. Eighteen neonates had multiple maternal, neonatal, perinatal, or prothrombotic complications. Sinovenous thrombosis was often accompanied by infarction (50%) or intraventricular hemorrhage (33%).

Chorioamnionitis↗

PubMed2002

Seizure-associated brain injury in term newborns with perinatal asphyxia.

BACKGROUND: There is controversy over whether seizures, the most common manifestation of neonatal brain injury, may themselves damage the developing brain. OBJECTIVE: To determine if neonatal seizures are independently associated with brain injury in newborns with perinatal asphyxia. METHODS: Ninety term neonates were studied with MRI and single-voxel (1)H-MRS on median day of life 6 (range 1 to 13 days). The severity of MR abnormality in the (1)H-MRS regions of interest was scored using a validated scale. Seizure severity was scored based on seizure frequency and duration, EEG findings, and anticonvulsant administration. Multivariable linear regression tested the independent association of seizure severity with impaired cerebral metabolism measured by lactate/choline and compromised neuronal integrity measured by N-acetylaspartate/choline in both regions. RESULTS: Clinical seizures occurred in 33 of 90 infants (37%). Seizure severity was associated with increased lactate/choline in both the intervascular boundary zone (p < 0.001) and the basal nuclei (p = 0.011) when controlling for potential confounders of MRI abnormalities and amount of resuscitation at birth. Each increase in seizure score was independently associated with a 21% increase in lactate/choline in the intervascular boundary zone (95% CI, 5.1-38.2%) and a 15% increase in the basal nuclei (95% CI, 0.1-31.7%). Seizure severity was independently associated with diminished N-acetylaspartate/choline in the intervascular boundary zone (p = 0.034). CONCLUSION: The severity of seizures in human newborns with perinatal asphyxia is independently associated with brain injury and is not limited to structural damage detectable by MRI.

Asphyxia Neonatorum↗

PubMed2002

Two-step and random regression analyses of weight gain of station-tested beef bulls.

Our objectives were to compare a two-step model and a joint procedure via random regression model for evaluating weight gain of beef bulls, weighed every 28 d on 140-d test, and to estimate genetic, environmental, and phenotypic parameters. Two-step analysis consisted of fitting fixed linear regressions to weights of each bull to determine weight gain on test. In the second step, gain on test was analyzed by a mixed model that included fixed effects of breed, test group, and starting age and random effects of weaning herd-year group and animal (additive genetic). The random regression model included the same effects as the two-step mixed-model analysis with an additional random animal permanent environment effect. Fourth-order Legendre polynomials of days on test were fitted for all fixed and random effects in the random regression model, except for breed. Breed effects and residual variances varied for each measurement period. Variance components and EBV for gain were obtained from the covariance function and estimates of random regression coefficients for weight, respectively. Random regression heritability estimates for gain on test increased over time, being maximum at end of test (0.38) and equal to two-step estimate. Permanent environment variance ratio estimates also increased over time and were greater than heritability estimates. Estimate of weaning herd-year variance ratio was approximately constant over time, being equal to 0.07 at end of test and similar to two-step estimate. Genetic correlations between gain through different periods on test given by random regression model were high (from 0.81, between 28 and 140-d gain on test, to 0.99, between 112 and 140-d gain on test). Genetic correlations between gain on discrete 28-d intervals were moderate to high (e.g., 0.49 and 0.99 between the last 28 d on test and the first and fourth 28 d, respectively). Rank correlations between EBV for 140-d gain by the two procedures were 0.98, 0.84, and 0.73 for all bulls and the 5% and 1% of bulls with highest random regression EBV, respectively. Results indicated that the two procedures rank top bulls quite differently for 140-d gain on test. Random regression model accounted for changes over time of genetic and environmental effects on the test weight gain curve of the bulls. Use of 112-d instead of a 140-d test provided similar ranking of bulls on the basis of EBV for gain on test.

Animals↗

PubMed2001

Expression of the yeast glycogen phosphorylase gene is regulated by stress-response elements and by the HOG MAP kinase pathway.

Yeast glycogen metabolism responds to environmental stressors such as nutrient limitation and heat shock. This response is mediated, in part, by the regulation of the glycogen metabolic genes. Environmental stressors induce a number of glycogen metabolic genes, including GPH1, which encodes glycogen phosphorylase. Primer extension analysis detected two start sites for GPH1, one of which predominated. Sequences upstream of these sites included a possible TATA element. Mutation of this sequence reduced GPH1 expression by a factor of 10 but did not affect start site selection. This mutation also did not affect the relative induction of GPH1 upon entry into stationary phase. Three candidates for stress response elements (STREs) were found upstream of the TATA sequence. Mutation of the STREs showed that they were required for regulation of GPH1 expression in early stationary phase, and in response to osmotic shock and heat shock. These elements appeared to act synergistically, since the intact promoter exhibited 30-fold more expression in stationary phase than the sum of that observed for each element acting independently. HOG1, which encodes a MAP kinase, has been implicated in control mediated by STREs. For GPH1, induction by osmotic shock depended on a functional HOG1 allele. In contrast, induction upon entry into stationary phase was only partially dependent on HOG1. Furthermore, the heat shock response, which can also be mediated by STREs, was independent of HOG1. These observations suggest that the GPH1 STREs respond to more than one pathway, only one of which requires HOG1.

Base Sequence↗

PubMed2001

Diagnostic profile of neonatal hypotonia: an 11-year study.

The profile of disorders presenting with neonatal hypotonia to the neonatal intensive care unit has not been studied previously. An 11-year retrospective cohort study of neonates, who were identified through computer database records and were admitted to the Neonatal Intensive Care Unit from January 1989 to December 1999 at the Montreal Children's Hospital (Montreal, Québec), is presented. The final diagnoses, tests obtained, and outcome were determined from a structured review of the subject's hospital record. The database search generated 95 records, of which 50 neonates met the inclusion criteria. The hypotonia was classified as central in 33 patients (66%) and peripheral in 17 (34%). Hypoxic-ischemic encephalopathy (n = 13), Prader-Willi syndrome (n = 6), myotonic dystrophy (n = 6), other muscle disorders (n = 6), chromosomal disorders (n = 4), and peripheral nerve disorders (n = 3) were the most common diagnoses. The genetic tests of highest yield were fluorescent in situ hybridization for Prader-Willi syndrome, DNA methylation studies for Prader-Willi syndrome, trinucleotide repeat testing for myotonic dystrophy, and karyotype analysis. A diagnostic approach is proposed based on the results.

Chromosome Aberrations↗

PubMed2001

Teaching mathematics to students with mild-to-moderate mental retardation: a review of the literature.

A systematic search of the literature from 1989 through 1998 was conducted to identify and analyze mathematics interventions for students with mild-to-moderate mental retardation. We found that the focus of instruction has shifted from basic skills instruction to computation and problem-solving instruction. Techniques such as constant-time delay, peer tutoring, time trials, and direct instruction proved beneficial in improving mathematics skills. Further, students with mental retardation learned to employ cognitive strategies successfully when these techniques were included. Although this information is promising, we recommend that further studies be conducted in secondary schools and in inclusive settings.

Adolescent↗

PubMed2000

Septo-optic dysplasia plus: a spectrum of malformations of cortical development.

The authors describe three children with septo-optic dysplasia (SOD)-plus: SOD and an associated malformation of cortical development. All three children had developmental delay, and two of the children had significant associated motor deficits. The associated cortical malformations with SOD include a spectrum of disorders of neuronal organization, not limited, as previously described, to schizencephaly. SOD-plus should be suspected in children with SOD and developmental delay.

Abnormalities, Multiple↗

PubMed2000

Medial temporal lobe neuronal damage in temporal and extratemporal lesional epilepsy.

OBJECTIVE: To assess the extent of medial temporal lobe (TL) abnormalities of the neuronal marker N-acetylaspartate (NAA) in TL and extra-TL lesional partial epilepsy, and to determine whether decreases in NAA are related to lesion location, to lesion pathology, or to the seizures themselves. METHODS: The authors studied 19 patients with intractable partial epilepsy and an isolated structural cerebral lesion (10 TL, 9 extra-TL; 10 cortical dysplasia [CD], 9 non-CD lesions). Proton MRS imaging was used to determine the average relative resonance intensity of NAA for the TL regions of the left and right hemispheres. Values less than two SDs below the mean of normal control subjects were considered abnormal. RESULTS: Fourteen patients (74%) had abnormally low NAA relative to creatine (NAA/Cr) in at least one TL. Three-way analysis of variance (ANOVA; lesion pathology, lesion location, side of NAA/Cr decrease) showed that ipsilateral NAA/Cr was lower than contralateral (p = 0. 04). Three-way ANOVA (lesion location, generalized tonic-clonic seizures, side of NAA/Cr decrease) showed that generalized tonic-clonic seizures were associated with lower TL NAA/Cr (p = 0. 02). Lesion location and pathology showed no main effect on the NAA-to-Cr ratio in either analysis (p > 0.05). Linear regression analyses between seizure duration and NAA/Cr decrease was not significant. CONCLUSION: The authors demonstrated abnormally low TL NAA/Cr in the majority of patients with structural cerebral lesions. This abnormality did not differ with lesion location or pathology. They propose that the altered function of neuronal networks by an isolated structural cerebral lesion results in remote "functional dual pathology."

Action Potentials↗

PubMed2000

Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin.

Acute disseminated encephalomyelitis (ADEM) is a presumed immune-mediated, demyelinating disease of the CNS for which the standard treatment is high-dose steroids. We describe two patients with ADEM in whom treatment with IV methylprednisolone coincided with deterioration in their clinical status. They were subsequently treated with IV immunoglobulin and exhibited dramatic clinical improvement, with return to their previous level of functioning.

Acute Disease↗