PubMed Health⌕ Search

Biomedical subjects

I Savic

Publications and source records attributed to I Savic.

At least 19 recordsLinked to original sources
PubMed2002

Relationship between clinical data and urodynamic findings in patients with lumbar intervertebral disk protrusion.

The relationship between voiding disturbances and urodynamic diagnosis in patients with lumbar intervertebral disk protrusion is controversial. The objective of this study was to determine the association between clinical data and urodynamic diagnosis, in order to reveal whether bladder dysfunction can be assessed on the basis of urological symptoms and signs. We prospectively studied 122 patients with lumbar intervertebral disk protrusion. Detrusor areflexia was found in 32 of these patients, while in the remaining 90 detrusor activity was normal. All patients with detrusor areflexia reported difficulty voiding by abdominal straining. The patients with normal urodynamic findings were either free of voiding disturbances (77 patients) or complained of frequent voiding (13 patients). In conclusion, there are cases of lumbar intervertebral disk protrusion in which the presence of bladder dysfunction can be predicted on the basis of clinical urodynamic testing, i.e. clinical neurological alterations, decreased bladder sensation, voiding by straining, increased bladder capacity, residual volume, and intermittent or continuous low flow curve on free uroflowmetry.

Adult↗
PubMed2001

Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans.

The anatomical pathways for processing of odorous stimuli include the olfactory nerve projection to the olfactory bulb, the trigeminal nerve projection to somatosensory and insular cortex, and the projection from the accessory olfactory bulb to the hypothalamus. In the majority of tetrapods, the sex-specific effects of pheromones on reproductive behavior is mediated via the hypothalamic projection. However, the existence of this projection in humans has been regarded as improbable because humans lack a discernable accessory olfactory bulb. Here, we show that women smelling an androgen-like compound activate the hypothalamus, with the center of gravity in the preoptic and ventromedial nuclei. Men, in contrast, activate the hypothalamus (center of gravity in paraventricular and dorsomedial nuclei) when smelling an estrogen-like substance. This sex-dissociated hypothalamic activation suggests a potential physiological substrate for a sex-differentiated behavioral response in humans.

Adult↗
PubMed2001

Brain activation during odor perception in males and females.

Several studies indicate that women outperform men in olfactory identification tasks. The psychophysical data are more divergent when it comes to gender differences at levels of odor processing which are cognitively less demanding. We therefore compared cerebral activation with H2(15)O PET in 12 females and 11 males during birhinal passive smelling of odors and odorless air. The odorous compounds (odorants) were pure olfactory, or mixed olfactory and weakly trigeminal. Using odorless air as the baseline condition, activations were found bilaterally in the amygdala, piriform and insular cortices in both sexes, irrespective of the odor. No gender difference was detected in the pattern of cerebral activation (random effect analysis SPM99, corrected p < 0.05) or in the subjective perception of odors. Males and females seem to use similar cerebral circuits during the passive perception of odors. The reported female superiority in assessing olfactory information including odor identification is probably an effect of a difference at a cognitive, rather than perceptive level of olfactory processing.

Adult↗
PubMed2001

Processing of odorous signals in humans.

from the first contact of an odor molecule with a receptor in the olfactory epithelium, to the coding and processing of this information in the central nervous system, the arousal of feelings and the storage of memories. The present chapter gives a short overview over the major components of these processes in humans.

Animals↗
PubMed2000

PET shows that odors are processed both ipsilaterally and contralaterally to the stimulated nostril.

The olfactory nerve is the only cranial nerve with established ipsilateral primary cerebral anatomical projections. Whether these projections correspond to the functional pathways for monorhinal processing of odor perception is, however, unknown. We therefore studied cerebral blood flow (rCBF) with [15O]butanol-PET in 18 healthy females during monorhinal smelling of single odors (OS) and odorless air (AS). Compared with AS, OS activated right amygdala and piriform cortex (confluent cluster), right orbitofrontal cortex, left insula, right thalamus, and anterior cingulate. A post hoc analysis showed that the first three regions were activated independently of the stimulated side, but that right orbitofrontal rCBF was higher during the right nostril stimulations. Left insula was activated mainly by the right nostril stimuli, and right thalamus by the left nostril stimuli. Odors seem to be processed both ipsi and contralaterally, with a right hemisphere preponderance irrespective of the stimulated nostril.

Adult↗
PubMed2000

Olfactory functions are mediated by parallel and hierarchical processing.

How the human brain processes the perception, discrimination, and recognition of odors has not been systematically explored. Cerebral activations were therefore studied with PET during five different olfactory tasks: monorhinal smelling of odorless air (AS), single odors (OS), discrimination of odor intensity (OD-i), discrimination of odor quality (OD-q), and odor recognition memory (OM). OS activated amygdala-piriform, orbitofrontal, insular, and cingulate cortices and right thalamus. OD-i and OD-q both engaged left insula and right cerebellum. OD-q also involved other areas, including right caudate and subiculum. OM did not activate the insula, but instead, the piriform cortex. With the exception of caudate and subiculum, it shared the remaining activations with the OD-q, and engaged, in addition, the temporal and parietal cortices. These findings indicate that olfactory functions are organized in a parallel and hierarchical manner.

Adult↗
PubMed2000

In vivo measurements of glutamine + glutamate (Glx) and N-acetyl aspartate (NAA) levels in human partial epilepsy.

OBJECTIVE: To investigate whether cerebral levels of N-acetyl aspartate (NAA), and glutamine + glutamate (Glx), are interictally altered in the epileptogenic regions of patients with partial seizures. MATERIAL AND METHODS: NAA, Glx, creatine (Cr), choline (Cho) and myo-inositol (mI) was measured in 28 patients with partial epilepsy and 10 healthy controls using localized 1H magnetic resonance spectroscopy. According to the multimethodological consensus, the epileptogenic region was mesial temporal in 18 and neocortical in 10 patients. RESULTS: The Glx/NAA and Glx/Cr ratios in epileptogenic regions were higher, and the NAA/Cr ratios lower than in the homologous regions (P=0.013, P=0.002 and P<0.0001). Applying the 95% confidence interval of controls, 17 of the 20 mesial temporal epileptogenic regions were correctly identified by an increased Glx/NAA and 15 of 20 by a decreased NAA/Cr ratio. Among patients with neocortical epilepsy the Glx/NAA ratio was increased in 8 of the 10 epileptogenic regions, whereas the NAA/Cr ratio was decreased in three. CONCLUSION: Both Glx and NAA are useful to identify the epileptogenic zone. The Glx/NAA ratios may be particularly useful to indentify neocortical epileptogenic regions.

Adolescent↗
PubMed2000

Right-nostril dominance in discrimination of unfamiliar, but not familiar, odours.

In a recent PET study on processing of unfamiliar odours we observed that odour discrimination performance was superior during right compared with left nostril presentations, and that mainly the right cerebral hemisphere was activated. In the present study we investigated whether the asymmetric performance is present also during the processing of familiar odours. Seventy-one right-handed healthy subjects (age 21-49 years, 40 females) with normal nasal anatomy and olfactory thresholds participated. Forty pairs of odours (20 familiar and 20 unfamiliar) were presented in the same/different paradigm, alternating nostrils and balancing the order. The number of errors during the discrimination task was compared with respect to nostril and odour familiarity. The overall odour discrimination performance was superior on the right side. However, this difference was valid only for unfamiliar odours, whereas the performance for familiar odours was symmetrical. Familiar odours were easier to discriminate than unfamiliar ones. The present data are congruent with the idea of a semantic influence on odour processing. Odours seem to be processed with a right sided preponderance when not clearly familiar, and symmetrically when language becomes involved. Future studies on odour processing should therefore take into account odour familiarity and side of presentation.

Adult↗
PubMed2000

MR spectroscopy shows reduced frontal lobe concentrations of N-acetyl aspartate in patients with juvenile myoclonic epilepsy.

PURPOSE: Neuropsychological studies suggest frontal lobe dysfunctions in patients with juvenile myoclonic epilepsy (JME). In this study we investigated whether an underlying mechanism could be a regional neuronal damage not visible with structural magnetic resonance (MR), but detectable with magnetic resonance spectroscopy (MRS). METHODS: The study included 15 patients with JME and 10 matched healthy controls. Quantitative single voxel MRS was conducted at 1.5 Tesla by using a STEAM sequence (TR/TE/TM = 6,000/30/13.7 ms). The voxels were placed over the right cerebellum, right thalamus, and the prefrontal and occipital cortex. The quantitation included fitting of transmitter gain, and correction for partial volume of cerebrovascular fluid. LC-Model was used for estimation of the absolute concentrations of total N-acetyl aspartate (NAA), cholines, total creatine, and myoinositol. RESULTS: Patients with JME had significantly reduced prefrontal concentrations of NAA in relation to controls (9.1 +/- 1.0 vs. 10.2 +/- 0.8 mM; p = 0.031 after Bonferroni correction). The other regions showed normal NAA values, as did the other metabolites. CONCLUSIONS: The observed reduction in NAA levels suggests a prefrontal neuronal lesion in patients with JME.

Adult↗
PubMed1998

Brain distortions in patients with primarily generalized tonic-clonic seizures.

PURPOSE: A precondition for the diagnosis of primarily generalized epilepsy with tonic-clonic seizures (GTCS) is absence of brain pathology. This definition, based on normal findings on computed tomography (CT) and magnetic resonance imaging (MRI) is challenged however, by observation of microscopic migrational disturbances in patients with GTCS. In the present study, we examined whether hitherto undiscovered gross manifestations of the reported migrational disturbances may be detected by analysis of CT and MRI scans with a computerized anatomic brain atlas. METHODS: The atlas program permitted group comparisons of size, intrinsic proportion, and shape of the brain. Healthy men (n = 20), patients with partial seizures (n = 8), secondarily generalized partial seizures (n = 8), and patients with GTCS (n = 10) were studied. The contours of the brain of the computerized atlas were first transformed and adjusted to the contours, central structures, and ventricles of each subject's MRI scans. During this process, the specific parameters for the shape, size, and proportion of the brain were determined, resulting in a set of values for each subject. These values were then applied for comparisons between the four investigated groups. RESULTS: In relation to the controls, patients with GTCS had brains significantly flattened in the craniocaudal direction (p = 0.002), with a disproportionally small caudal part. The anterior portion of their brain was also, relatively elongated as compared with the posterior portion (p = 0.04). Similar systematic abnormalities were not observed in patients with partial epilepsy. CONCLUSIONS: The observed deformations are compatible with previously reported findings of Purkinje cell degeneration and frontal lobe microdysgenesis in GTCS. The study suggests a new approach to identify effects of morphologic abnormalities in the brain when results of conventional structural neuroimaging are normal.

Adult↗
PubMed1998

Regional increases in [11C]flumazenil binding after epilepsy surgery.

INTRODUCTION: Animal experiments suggest that epileptic seizures alter the expression of mRNA for neuro-receptors. PET measurements with [11C]flumazenil show that patients with partial seizures have a reduced density of benzodiazepine (BZ) receptors in the epileptogenic regions (ER) and some of the target areas for seizure activity, the so called projection areas. Recent data suggest that the degree of BZ receptor reduction in ER is correlated to seizure frequency. We therefore hypothesized that seizure activity can alter the BZ receptor binding, and that some of these changes could normalize when the seizures disappeared. METHODS: In 4 patients whose seizures were generated by mesial temporal lobe structures, BZ receptor density was measured with [11C]flumazenil PET before, and 1 year after the epilepsy surgery and cessation of seizures. By use of a computerized anatomical brain atlas the same regions were analyzed in both PET scans, and the results related to data from 7 healthy controls. RESULTS: Presurgical PET scans showed reductions in BZ receptor density in the epileptogenic region and some of its primary projection areas. Other cortical regions had normal values. Postsurgically, the calculated BZ receptor density normalized (29+/-17% increase) in several of the affected projection areas, whereas the values in other cortical regions remained unaltered. CONCLUSION: Regional reductions in BZ receptor density may be dynamic and related to seizures. The present preliminary observations encourage further studies on seizure-related changes in regional receptor binding in humans.

Adult↗
PubMed1998

Sex differences in patients with mesial temporal lobe epilepsy.

Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.

Adult↗
PubMed1998

Bladder function in patients with lumbar intervertebral disk protrusion.

PURPOSE: We prospectively studied the effect of lumbar intervertebral disk protrusion on bladder function. Cystometry findings were particularly examined according to spinal level of disk protrusion and urological symptoms. MATERIALS AND METHODS: We evaluated 77 men and 37 women 25 to 63 years old with lumbar intervertebral disk protrusion. Urodynamic investigation included uroflowmetry and simultaneous recording of intravesical, abdominal and detrusor pressure during bladder filling and voiding. RESULTS: Detrusor areflexia was noted in 31 of the 114 patients (27.2%), while detrusor activity was normal in the remaining 83. According to the spinal level of disk protrusion, detrusor areflexia was evident in 3 of the 8 cases of L3, 10 of the 54 L4 and 18 of the 52 L5 disk protrusion. All 31 patients with detrusor areflexia reported difficult voiding with straining. CONCLUSIONS: Detrusor areflexia develops in approximately a quarter of the patients with lumbar intervertebral disk protrusion. We did not find that the spinal level of lumbar disk protrusion had an effect on detrusor activity. All patients with detrusor areflexia had voiding disorders that manifested as voiding with straining.

Adult↗
PubMed1997

Pattern of interictal hypometabolism in PET scans with fludeoxyglucose F 18 reflects prior seizure types in patients with mesial temporal lobe seizures.

BACKGROUND: Interictal hypometabolism is routinely used as an indicator of the epileptogenic zone in patients with complex partial seizures (CPSs). However, the regional pattern of hypometabolism varies without obvious reasons, even among patients with identical epileptogenic zones and causes. OBJECTIVE: To investigate whether this pattern may be related to the electroencephalographic and clinical features of the seizure that precedes the positron emission tomographic (PET) scan with fludeoxyglucose F 18. PATIENTS AND METHODS: Fifty-three patients with CPSs were first classified into 4 groups, depending on the features of the seizure that preceded the PET scan (determined from findings from electroencephalography and videotelemetry). In 14 patients, this seizure was focal limbic (characterized by aurae or staring spells); in 18, the CPS was widespread limbic (including automatisms). Ten patients had a CPS with posturing, and 11 had a secondarily generalized CPS. Regions with a hemisphere-normalized concentration of fludeoxyglucose F 18 below the 95% confidence interval of values from 8 control subjects were defined as hypometabolic. The location of these regions was then compared among the 4 groups, and the degree of hypometabolism was related to the time from the seizure to the PET scan with fludeoxyglucose F 18. RESULTS: The hypometabolic area was limited to the epileptogenic zone if the preceding seizure was focal limbic, whereas in patients with widespread limbic seizures, it included one or several additional areas of the limbic cortex (P = .03). Patients with posturing differed from both previous groups by having hypometabolism in the extralimbic frontal lobe (P < .001), and subjects with secondarily generalized seizures differed from all others because of cerebellar (P < .001) and parietal lobe (P < .05) reductions. The time between the seizure and the performance of the PET scan did not correlate with the degree or extent of hypometabolism. CONCLUSIONS: Mechanisms involved in the generation of a seizure that precedes a PET scan with fludeoxyglucose F 18 seem to influence the "interictal" hypometabolic pattern. Therefore, caution should be used when interpreting scans that are preceded by a nonhabitual seizure.

Adolescent↗
PubMed1997

Olfactory bedside test. A simple approach to identify temporo-orbitofrontal dysfunction.

BACKGROUND: Olfactory memory and discrimination are processed by the anteromesial temporal cortex and the orbitofrontal cortex. Both functions may therefore be impaired in limbic epilepsy. METHODS: Twenty-seven patients with mesial temporal lobe seizures (MTLS), 10 patients with neocortical seizures (NS), and 10 matched healthy control subjects underwent evaluation for olfactory quality discrimination (OD) and delayed recognition memory (OM). All patients were referred for presurgical evaluation. The olfactory tests were performed in a same-different paradigm with 10 seconds (OD) and 60 minutes (OM) between presentations of the odors, using the standardized University of Pennsylvania Smell Identification Test. The presentations were monorhinal in the OD and birhinal in the OM tests. The results were related to regional glucose metabolism measured with fludeoxyglucose F 18 positron emission tomography. RESULTS: Patients with MTLS had an impaired OD ipsilateral to the epileptogenic region (P < .001) and a higher total number of errors (including both tests) (P = .002). They also had lower OM scores, but not significantly lower than those of patients with NS (P = .05). The combined OM and OD tests correctly identified patients with MTLS with a sensitivity of 85% and a specificity of 90%, offering a correct lateralization in 74% of patients. Patients with MTLS whose OD was more impaired than OM differed from those with more impaired OM by having a significant hypometabolism not only over the neocortex of the epileptogenic temporal lobe (P = .02) but also in the ipsilateral anterior (P = .008) and orbitofrontal cortex (P = .007) (2-way analysis of variance). CONCLUSIONS: Tests of olfactory function are useful in distinguishing between NS and MTLS. The impairments of OM and OD can be dissociated in pathological states and therefore mediated by different structures.

Adult↗
PubMed1996

Localized cerebellar reductions in benzodiazepine receptor density in human partial epilepsy.

BACKGROUND: Previous studies suggest that the morphological substrate for cerebellar dysfunction is destruction of Purkinje cells, but disagree on whether this is caused by seizure- or drug-related toxicity. The benzodiazepine (BZ) receptor antagonist flumazenil tagged with carbon 11 is a sensitive marker of Purkinje cells. OBJECTIVE: To investigate whether cerebellar dysfunction in partial epilepsy is related to seizures through cerebrocerebellar connections. DESIGN: Positron emission tomography with [11C] flumazenil was conducted in 5 patients with frontal lobe seizures, 12 patients with mesial temporal lobe seizures, and 7 healthy men. Eight patients also had [18F]-fluorodeoxyglucose positron emission tomography. Cerebellar regions of interest were delineated using magnetic resonance imaging and a computerized anatomical brain atlas, and the epileptogenic regions were determined with a multimethod assessment. RESULTS: Patients with frontal lobe seizures had a significantly reduced BZ receptor density in the anterior cerebellum contralateral to the seizure onset region (P < or = .001), 2-way repeated-measure analysis of variance). Patients with mesial temporal lobe seizures had reductions in the ipsilateral (posterior and anterior) cerebellum (P < or = .001 for both). No significant asymmetries were found in regional glucose metabolism. CONCLUSIONS: The observed distribution of BZ receptor reductions is congruent with animal experiments showing tht frontal lobe projections to the cerebellum are crossed, whereas projections from mesial temporal loe are predominantly ipsilateral. The results thus indicate a functional relation with seizures and may reflect excitotoxic lesions or specific changes in the gamma-aminobutyric BZ system.

Adult↗