IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.

The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

Honig's model of working memory and brain activation: an fMRI study.

The present study investigated changes in neuronal activation with fMRI related to Honig's model of working memory, which is much less studied compared with other working memory models. In contrast to other studies which have applied recognition procedures, the primary aim with the present study was to examine brain activation when subjects had to continuously recall and forget items held in working memory. The results showed that the mid-ventrolateral frontal cortex was particularly activated in the left hemisphere, whereas the mid-dorsolateral frontal cortex was particularly activated in the right hemisphere during execution of the working memory task. The findings are discussed in relation to process- and domain-specific accounts of working memory.

[Early CT changes in acute cerebral infarction]. / Tidlige CT-forandringer ved akutt hjerneinfarkt.

BACKGROUND: The aim of this study was to evaluate neurological clinical findings and cerebral computed tomography (CT) findings in patients with acute stroke within six hours after stroke onset. MATERIAL AND METHODS: 42 patients with presumed stroke in the middle cerebral artery territory were clinically assessed with the Scandinavian Stroke Scale Score. CT scans were assessed in a standardized manner by one neuroradiologist. RESULTS: The clinical deficit did not forecast the CT findings. Patients with several early CT signs of ischaemia, and especially those with hypodensity in less than one third of the middle cerebral artery area had lower clinical scores than patients with fewer signs. Hypodensity in the insular region was the overall most frequent finding. INTERPRETATION: Clinical findings do not give definite information about the ischaemic damage in the acute phase of cerebral infarction. CT scans may give valuable information primarily when there are positive findings.

Common pathways in mental imagery and pain perception: an fMRI study of a subject with an amputated arm.

The present paper reviews data from two previous studies in our laboratory, as well as some additional new data, on the neuronal representation of movement and pain imagery in a subject with an amputated right arm. The subject imagined painful and non-painful finger movements in the amputated stump while being in a MRI scanner, acquiring EPI-images for fMRI analysis. In Study I (Ersland et al., 1996) the Subject alternated tapping with his intact left hand fingers and imagining "tapping" with the fingers of his amputated right arm. The results showed increased neuronal activation in the right motor cortex (precentral gyrus) when tapping with the fingers of the left hand, and a corresponding activation in the left motor cortex when imagining tapping with the fingers of the amputated right arm. Finger tappings of the intact left hand fingers also resulted in a larger activated precentral area than imagery "finger tapping" of the amputated right arm fingers. In Study II (Rosen et al., 2001 in press) the same subject imagining painful and pleasurable finger movements, and still positions of the fingers of the amputated arm. The results showed larger activations over the motor cortex for movement imagining versus imagining the hand being in a still position, and larger activations over the sensory cortex when imagining painful experiences. It can therefore be concluded that not only does imagery activate the same motor areas as real finger movements, but also that adding instructions of pain together with imaging moving the fingers intensified the activation compared with adding instructions about non-painful experiences. From these studies, it is clear that areas activated during actual motor execution to a large extent also are activated during mental imagery of the same motor commands. In this respect the present studies add to studies of visual imagery that have shown a similar correspondence in activation between actual object perception and imagery of the same object.

[Early CT signs in acute cerebral ischemia]. / Tidlige CT-tegn ved akutt cerebral iskemi.

BACKGROUND: Patients who suffer from acute stroke should be examined with computed tomography (CT) of the brain immediately after admission. If evaluated systematically, this examination may give more information than just "bleeding excluded". MATERIAL AND METHODS: CT scans of the brain in four patients with acute ischaemic stroke admitted to our department illustrate the typical early CT signs in acute cerebral ischaemia. RESULTS: This article describes the systematic evaluation of a CT in acute stroke, when the following questions need to be answered: Is there a hyperdense middle cerebral artery sign (HMCAS), or hypodensity in other major intracranial arteries? Is there a hypodensity in the basal ganglia? Is there hypodensity (loss of cortical-subcortical discrimination) or oedema (decreasing volume of the Sylvian fissure) in the insular region? Is there hypodensity (loss of cortical-subcortical discrimination) or oedema (effacement of sulci or compression of ventricles) in other parts of the distribution of the middle cerebral artery or other arteries? INTERPRETATION: An early CT in acute stroke patients may yield valuable information if evaluated properly. The presence or absence of early CT sign have implications for diagnosis, prognosis, choice of supplementary examinations, and choice of treatment.

Different brain areas activated during imagery of painful and non-painful 'finger movements' in a subject with an amputated arm.

The purpose of the present study was to investigate differences in brain activation with functional magnetic resonance imaging (fMRI) during imagery of painful and non-painful 'finger movements' and 'hand positioning' in a subject with an amputated arm. The subject was a right-handed man in his mid-thirties who lost his right arm just above the elbow in a car-train accident. MRI was performed with a 1.5 T Siemens Vision Plus scanner. The basic design involved four conditions: imagining 'painful finger movements', 'non-painful finger movements', 'painful hand positioning', 'non-painful hand positioning'. Imagery of finger movements uniquely activated the contralateral primary motor cortex which contains the classic 'hand area'. The lateral part of the anterior cerebellar lobe was also activated during imagery of finger movements. Imagery of pain uniquely activated the somatosensory area, and areas in the left insula and bilaterally in the ventral posterior lateral nucleus of the thalamus. It is suggested that the insula and thalamus may involve neuronal pathways that are critical for mental processing of pain-related experiences, which may relate to a better understanding of the neurobiology of phantom limb pain.

Functional magnetic resonance imaging (fMRI) study of sex differences in a mental rotation task.

The main purpose of the present study was to: 1) to investigate differences between males and females in brain activation when performing a mental rotation task, 2) investigate hemisphere differences in brain activation during mental rotation. Brain activation was measured with functional magnetic resonance imaging (fMRI). Image acquisition was performed with a 1.5 Tesla Siemens Vision MR scanner equipped with 25 m T/m gradients. Scanning of anatomy was done with a T1-weighted 3D FLASH pulse sequence. Serial imaging with 70 BOLD sensitive echo planar (EPI) whole brain measurements was done during stimulus presentations, divided into 7 blocks of 10 EPI multi-slice volume measurements each. Eleven subjects were presented with black-and-white drawings of 3-D shapes taken from the set of 3-D perspective drawings developed by Shepard and Metzler [1], alternated with 2-D white bars as control stimuli. In the experimental condition, the subjects were shown 36 pairs of 3-D drawings, presented in three blocks of 12 pairs of drawings. The drawings were always presented pairwise. On half of the trials, the two 3-D shapes were congruent but portrayed with different orientation, in the other half the two shapes were incongruent. MR data were analyzed with the SPM-96 analysis software. After subtraction of activity related to the 2-D control stimuli, clusters of significant activation were found in the superior parietal lobule (BA 7), more intensely over the right hemisphere, and bilaterally in the inferior frontal gyrus (BA 44/45). Males showed predominantly parietal activation, while the females showed inferior frontal activation. It is suggested that males and females may differ in the processing strategy used when approaching a 3-D mental rotation task, males using a 'gestalt' strategy and females using a 'serial' reasoning strategy.

Left frontal activation during a semantic categorization task: an fMRI-study.

In the present study we measured brain activation, with functional magnetic resonance imaging (fMRI) during the execution of a covert semantic categorization task. This involves activation of working memory and internal concept generation. Previous brain imaging studies of covert verbal fluency have shown widespread activation in the frontal and temporal lobes, and anterior cingulate. However, most of these studies have employed simple stimulus tasks with repetition of words e.g., beginning with a certain letter of the alphabet. Moreover, the subject is typically cued (either visually or auditory) every 2-5 second. In the present study we used a "single-cue" instruction at the beginning of each activation period where the subject was instructed to internally generate category specific names related to: "States in the USA," "UK Soccer clubs," and "Male names" during 54s periods. The three activation periods were compared to three baseline periods in which the subject was instructed to imagine mentally "lying on a beach and looking at the sky." Functional MRI was performed with a 1.5T Siemens Vision scanner. Initial TIW 3D FLASH scanning of anatomy was done, and thereafter, serial imaging with 60 BOLD sensitive echo planar whole brain measurements were done during the active and passive tasks. Main activation areas were found in the left middle frontal gyrus, partially overlapping with Brodmann area 9. This is in agreement with previous studies of increased activation in the left frontal lobe, and may indicate a left frontal neural network for accessing the mental lexicon.

Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of interferon-alpha2a (IFN-alpha2a) in relapsing-remitting MS (RRMS). BACKGROUND: Several immune-modulating therapy regimens of IFN-alpha have shown varying results in MS. A recent pilot study suggested benefits from IFN-alpha2a. METHODS: Ninety-seven patients were randomized to receive subcutaneous injections of placebo (33 patients) or 4.5 million international units (mIU) (32 patients) or 9.0 mIU (32 patients) of IFN-alpha2a three times weekly for 6 months, with a further 6 months of follow-up. Monthly gadodiamide-enhanced MRI was the primary method of evaluating efficacy. RESULTS: IFN-alpha2a treatment resulted in fewer new MRI lesions during the treatment period (p < 0.003). The probability of no new lesions during treatment was >2.5 times higher with 9.0 mIU IFN-alpha2a than with placebo (p < 0.005). The median number of lesions at the end of treatment was lower with IFN-alpha2a treatment than with placebo (p = 0.0004), but the difference disappeared during follow-up. The total number of lesions (mean) increased by 4.78 with placebo, 0.86 with 4.5 mIU IFN-alpha2a, and 0.28 with 9.0 mIU IFN-alpha2a during treatment (p = 0.030). No treatment effect on exacerbation rate, progression of disability, or quality of life was detected. Nine patients discontinued treatment, five because of adverse events. CONCLUSIONS: IFN-alpha2a treatment significantly reduced disease activity as measured by MRI, but the efficacy disappeared within 6 months after discontinuation of treatment. A long-term study of more patients using disability as a primary outcome measure is needed to evaluate the clinical impact.

Central auditory processing, MRI morphometry and brain laterality: applications to dyslexia.

We review data from our laboratory related to a view of dyslexia as a biological disorder, or deficit, caused by both structural and functional brain abnormalities. The review is focused on central auditory processing in dyslexia, and the possibility that impairments in the auditory or acoustic features of the phonological code may be at the heart of the impairments seen in dyslexia. Three methodological approaches by which to investigate central auditory processing deficits are outlined: dichotic listening (DL) to consonant-vowel syllables; magnetic resonance imaging (MRI), and the use of event-related potentials (ERPs). Consonant-vowel syllable DL is a technique for probing the functional status of phonological processing areas in the superior temporal gyrus, particularly in the left hemisphere. MRI is a corresponding structural, or morphological, measure of anatomical abnormalities in the same brain region, particularly covering the planum temporale area. The ERP technique, and particularly the mismatch negativity (MMN) component, reveals cortical dysfunctions in sensory processing and memory related to basic acoustic events. For all three approaches, the dyslexic children were seen to differ from their control counterparts, including absence of modulation of the right ear advantage (REA), in DL through shifting of attention, smaller left-sided planum temporale asymmetry, and prolonged latency in the MMN ERP complex, particularly in the time-deviant stimulus condition.

Neuroblastoma and venous sinus thrombosis in an adult patient.

A 35-year-old woman developed symptoms consistent with intracranial venous sinus occlusions that were demonstrated by MR angiography. After a few weeks of anticoagulant therapy, she became paraplegic due to haemorrhages in the caudal spinal canal. A decompressive laminectomy did not improve her neurological deficits. Up to this point, we assumed her condition to be caused solely by the intracranial venous thrombosis and complications of the treatment. A tumour diagnosis had so far not been considered. A few months later she became tetraplegic. MRI revealed fresh bleeding in the upper spinal cord and a dissemination of tumour along the entire craniospinal axis. Biopsy specimens obtained from the spinal canal contained tumour cells with the characteristics of neuroblastoma.

Phantom limb imaginary fingertapping causes primary motor cortex activation: an fMRI study.

A conventional 1.0 T MR-scanner was used to detect signal intensity changes in blood oxygenation level dependent-sensitive acquisitions of motor cortex during real (left hand) and imaginary (right hand) fingertapping in a man who had his right arm amputated. The subject was instructed alternately to move the intact left hand fingers and to imagine tapping his 'fingers' on the amputated right hand. Activated areas were detected using a cross-correlation technique with superimposition of highly correlated voxels on to a corresponding high resolution, anatomical 3D image. Activation was observed in the right motor cortex during fingertapping with the intact left hand, and a corresponding activation in the left motor cortex for imaginary movements of the amputated right hand fingers.

Treatment of relapsing-remittent multiple sclerosis with recombinant human interferon-alfa-2a: design of a randomised, placebo-controlled, double blind trial in Norway.

A multicentre, randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of 4.5 and 9.0 MIU recombinant human interferon alfa-2a (Roferon-A) given thrice weekly in patients with relapsing-remittent multiple sclerosis is described. The patients are treated for 6 months followed by a 6 months drug-free period. The primary objective is to determine new disease activity analysed by monthly MRI with gadodiamide (GdDTPA-BMA, Omniscan). The study is conducted at eight centers in Norway and is completed in January 1996.

Functional magnetic resonance imaging of primary visual processing using a 1.0 Tesla scanner.

Recent advances in functional magnetic resonance imaging (fMRI) at > or = 1.5 T magnetic field strength and with high speed single-shot echo planar imaging techniques have made it possible to monitor local changes in cerebral blood volume, cerebral blood flow, and blood oxygenation level in response to sensory stimulation, simple motor activity, and possibly also to more complex cognitive processing. However, fMRI has also been accomplished on conventional MR scanners of medium field strength (approximately 1.0 T) using special pulse sequences and appropriate methods for image analysis. We present results from six subjects on photic stimulation using a standard 1.0 T MR scanner together with special software for off-line image analysis. Continuous serial T2-weighted imaging were performed for 6 minutes in the plane of the calcarine fissure. There were 3 repetitions of 1 minute resting state of darkness (OFF) and 1 minute activated state (ON) with 8 Hz flicker stimulation. To directly map these functional images to the underlying anatomy we also acquired a high resolution T1-weighted image from the same axial slice. The results demonstrated that stimulus-related signals can be obtained from primary visual cortex with a conventional 1.0 T MR scanner. Further methodological improvements are discussed and related to present and future possibilities for the use of fMRI within psychophysiology.

In vivo comparison of 3D ultrasonography and magnetic resonance imaging in volume estimation of human kidneys.

The objective of this study was to evaluate the accuracy of a three-dimensional ultrasound system (3D-US) compared with Magnetic Resonance Imaging (MRI) in volume estimation of human kidneys in vivo. Twenty healthy volunteers were scanned fasting in supine position with MRI and with a 3D-US. An ultrasound sector scanner with a mechanical transducer coupled to a tilting motor provided images of multiple sections of kidneys. A 3.25-MHz transducer was tilted through 88 degrees yielding 81 frames, and volume estimation was performed on a Unix workstation after manual contour indication. Data acquisition with MRI was performed by using a 1-T magnet. Eighteen included kidneys [mean +/- standard deviation (SD)] measured 155.7 +/- 26.4 mL (range 110.0-205.0 mL) by 3D ultrasound and 171.8 +/- 24.6 mL (range 127.5-211.0 mL) by MRI, yielding a good correlation (r = 0.82, p < 0.001) between the two methods. The mean difference was -16.1 +/- 15.6 mL (SD) and the limits of agreement were -49.0 mL. We conclude that this 3D-US is accurate in volume estimation of human kidneys in vivo.

Tumour volume reduction following gamma knife radiosurgery: the relationship between X-ray and histological findings.

The case histories of two young ladies with Cushing's disease are described. Both patients were treated first with Gamma Knife radiosurgery and subsequently by microsurgery. The radiosurgery caused a marked reduction in tumour volume but only a partial relief of the endocrinopathy. Comparison of the histological findings with the radiological findings following radiosurgery indicates that confluent necrosis is not a prerequisite for a reduction in tumour volume. It seems more likely that the reduction in tumour volume is related to changes in cellular dynamics.

Radiosurgical treatment of gliomas of the diencephalon.

The results of Leksell Gamma Knife treatment of diencephalic gliomas are presented. Eight tumours in seven patients form the basis of this report. 7 patients, 4 males and 3 females. The age range was 7.5 to 33 years with a mean of 18 years. Mean follow-up was 21 +/- 12 months. In 4 patients the tumour had been reduced in volume by an open internal decompression procedure. The location of the tumour will determine the risks of treatment. With anterior lesions there is risk of endocrinological and visual pathway damage. With a pineal region lesion there is a risk of diplopia. In this series no tumour has increased in volume. Four have decreased and one has disappeared. Two patients suffered temporary diplopia. No visual disturbance has been observed to date. No hypothalamic disturbance has been observed yet. These tumours are dangerous not so much because of their biological nature as because of their location. However, the biological nature of the tumours, with the close concordance between the radiological and actual extent make them appropriate targets for radiosurgery as a primary treatment. The present study gives preliminary support to this line of treatment.

Gas in a cervical vertebral body. A case report with CT confirmation.

A case of intravertebral gas in the body of C6 is described. Three intervertebral discs also contained gas. The aetiology is assumed to be degenerative lesions.

Comparison of peritoneal macrophages from germfree and conventional mice.

Morphology, lysosomal enzyme activities, and phagocytosis via immunological receptors were tested in peritoneal macrophages from germfree and conventional mice. Nonstimulated macrophages from germfree mice showed less spreading and were more easily detached when seeded on glass than conventional macrophages. The activities of the lysosomal acid phosphatase and cathepsin D were similar in the two cell groups, whereas beta-glucuronidase showed higher activity in macrophages from germfree mice. F(c) receptor-mediated phagocytosis of opsonized sheep erythrocytes was equally effective in germfree and conventional macrophages, and both cell types attached but did not internalize erythrocytes via the C(3)b receptor. Intraperitoneal injections of mineral oil caused a significantly higher influx of macrophages in conventional mice than in germfree mice, whereas the influx of polymorphonuclear cells was enhanced in both animals. Stimulation in vivo with oil or Escherichia coli endotoxin increased cell size, spreading ability, membrane ruffling, and lysosomal enzyme activities in macrophages from both conventional and germfree mice. The Fc-mediated phagocytosis was not influenced by stimulation, whereas the capacity to internalize via C(3)b receptor was triggered in macrophages from conventional mice, but not in corresponding cells from germfree mice. Similar results were obtained after stimulation with endotoxin in vitro. Culture in fetal calf serum for 72 h caused intracellular rises in all three enzyme activities tested in macrophages from conventional mice, whereas only the activity of acid phosphatase was increased in macrophages from germfree mice. Stimulation with zymosan in vitro caused selective release of lysosomal enzyme activity in macrophages from both animal groups. We conclude that peritoneal macrophages from germfree mice share several properties with cells from conventional mice, however, unstimulated beta-glucuronidase activity was increased, whereas spreading on glass, chemotactic response, in vitro induction of lysosomal enzymes, and the capacity to internalize via the C(3)b receptor after stimulation were reduced or absent.