The antihypertensive and diuretic effect of crude root extract and saponins from Solanum sisymbriifolium Lam., in L-NAME-induced hypertension in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum sisymbriifolium Lam., is used in Paraguayan folk medicine claiming antihypertensive and diuretic properties. AIM OF THE STUDY: This study aimed to determine the influence of chronic oral administration of the crude root extract and saponins obtained from S. sisymbriifolium Lam., on the blood pressure of male and female rats with hypertension induced by L-NAME, and its consequences on diuresis, the body weight, blood glucose, and level of serum parameters of liver and kidney functionality. MATERIALS AND METHODS: Wistar rats were randomly divided into seven male, and seven female groups (8 animals each), which received as 6-week pretreatment, 0.9% saline solution (two groups; 0.1mL/10 g of b.w.), L-arginine (100.0 mg/kg/day), enalapril (15.0 mg/kg/day), crude extract (CESs 100.0 mg/kg/day), and saponin purified fraction (1.0, and 10.0 mg/kg/day), and treated with L-NAME (20 mg/kg/day/i.p.) twice, 1, and 6 h after pre-treatment. The animals' body weight, glycemia, and blood pressure were recorded weekly, while serum, hepatic, renal, and histological parameters were analyzed at the end of 6-week of treatment. RESULTS: A protective effect of CESs (100.0 mg/kg/day), and saponins (1.0, and 10.0 mg/kg/day) against hypertension induced by L-NAME was verified in the systolic, diastolic, and mean blood pressure values, which were significantly lower than the positive L-NAME-hypertensive control group (male and female) at the end of the 6-week treatment. Also, pretreatment with enalapril (15.0 mg/kg/day) induced an efficient protective activity, which validates the method used. Likewise, the volume of urine, creatinine, uric acid, urea, and electrolyte excretion was enhanced at the end of 6-week of treatment in concordance with the reduction in serum level of the same parameters, compatible with the improvement of the diuretic activity. The glycemia, body weight, heart rate, and functional hepato-renal parameters were not modified after a 6-week of treatment, in comparison to the control group, indicating relatively acceptable harmless properties of CESs and saponins. Interestingly, the HDL level in females was increased in contrast to male rats by chronic saponins treatment when compared with the negative control group. CONCLUSIONS: It can be concluded that either the increment in blood pressure (systolic, diastolic, and median) or cardiorenal remodeling effects in male and female rats submitted to L-NAME-induced hypertensive condition, were prevented and well-preserved without a significant variation during a period of 6-week of pretreatment with CESs and saponins pretreatments. Likewise, an important diuretic effect was revealed after this period of treatment.

Immunological response of the Sub-Antarctic Notothenioid fish Eleginops maclovinus injected with two strains of Piscirickettsia salmonis.

Eleginops maclovinus is an endemic fish to Chile that lives in proximity to salmonid culture centers, feeding off of uneaten pellet and salmonid feces. Occurring in the natural environment, this interaction between native and farmed fish could result in the horizontal transmission of pathogens affecting the aquaculture industry. The aim of this study was to evaluate the innate and adaptive immune responses of E. maclovinus challenged with P. salmonis. Treatment injections (in duplicate) were as follows: control (100 µL of culture medium), wild type LF-89 strain (100 µL, 1 × 108 live bacteria), and antibiotic resistant strain Austral-005 (100 µL, 1 × 108 live bacteria). The fish were sampled at various time-points during the 35-day experimental period. The gene expression of TLRs (1, 5, and 8), NLRCs (3 and 5), C3, IL-1ß, MHCII, and IgMs were significantly modulated during the experimental period in both the spleen and gut (excepting TLR1 and TLR8 spleen expressions), with tissue-specific expression profiles and punctual differences between the injected strains. Anti-P. salmonis antibodies increased in E. maclovinus serum from day 14-28 for the LF-89 strain and from day 14-35 for the Austral-005 strain. These results suggest temporal activation of the innate and adaptive immune responses in E. maclovinus tissues when injected by distinct P. salmonis strains. The Austral-005 strain did not always cause the greatest increases/decreases in the number of transcripts, so the magnitude of the observed immune response (mRNA) may not be related to antibiotic resistance. This is the first immunological study to relate a pathogen widely studied in salmonids with a native fish.

Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.

ETHNO-PHARMACOLOGICAL RELEVANCE: Kyllinga brevifolia rhizomes (Cyperaceae) are used in Paraguayan traditional medicine as a refreshing beverage, and is claimed to own digestive, diuretic, sedative, tonic, antispasmodic and sudorific properties. We have previously reported that its hydro- ethanolic rhizome extract possess sedative, anxiolytic and anti-aggressive-like effects in mice. However, information on its potential for treatment of syndromes associated with mood disorders is scarce. AIM OF THE STUDY: The purpose of this study is to characterize the putative antidepressant-like effects of the hydro-ethanolic extract (CEKb) and the ethyl acetate fraction (KbF-ethyl-ac) obtained from the rhizome of K. brevifolia (Rottb) on male mice exposed to forced swimming test. Also, chemical characterization of the components of the active ethyl acetate fraction was described. MATERIALS AND METHODS: The antidepressant-like effects of CEKb and KbF-ethyl-ac were measured using the forced swimming test (FST) performance of male mice in single (acute), short-term and chronic modalities. Treatments in all modalities were made 1h before swimming test. The KbF-ethyl-ac was analyzed by LC-DAD-ESI-MS and LC-ESI-MS/MS in order to identify the active components. RESULTS: A single doses (1.0, 10.0 and 100.0mg/kg, p.o; p<0.05) of CEKb, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with oral short-term treatment (7 days) with doses of 10.0 and 100.0mg/kg/day (p<0.05) of CEKb. Moreover, in the treatments during 14 days with doses of 1.0 (p<0.05), 10.0 (p<0.05), and 100.0 (p<0.001) mg/kg, p.o, of CEKb, a statistically significant reduction of the immobility time were induced. Additionally, in a different set of experiments acute dose of 1.0 (p<0.05) and 10.0 (p<0.01) mg/kg, p.o, of KbF-ethyl-ac in male mice, a significant reduction of the immobility time were provoked. Likewise, short-term treatment (7 days) with 1.0, and 10.0mg/kg (p<0.05); and after 14 days of treatment with 0.01 (p<0.01) 0.1 (p<0.001), 1.0 (p<0.001), and 10.0 (p<0.05) mg/kg of KbF-ethyl-ac in male mice, a statistically significant reduction of the immobility time, were observed. Imipramine 32mg/kg/days, i.p, induced a statistically significant reduction of immobility time and was used as positive control to validate the method employed. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEKb or KbF-ethyl-ac (acute, short-term or chronic). Both, efficacy and potency were higher when repeated administration of CEKb was used, and surprisingly the efficacy of 1.0mg/kg of KbF-ethyl-ac (14 days) was similar to imipramine. The main constituents of the KbF-ethyl-ac were identified as catechins and their dimers by LC-DAD-ESI-MS and LC-ESI-MS/MS, according to their UV and MS spectra, as compared with the literature data. These results indicate an important antidepressant-like profile of action for the CEKb and KbF-ethyl-ac; and meanwhile, this effect may partially reside on catechins and their dimers isolated from the KbF-ethyl-ac. CONCLUSION: These findings indicate that K. brevifolia exerts antidepressant -like effects in mice and suggest its potential usefulness for the treatment of depression in humans and encourage us to pursue the isolation of the molecules associated to the effect observed in CEKb and KbF-ethyl-ac, and to determine the mechanism of antidepressant-like effect of Kyllinga brevifolia using adequate complementary test.

Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation.

OBJECTIVE: To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. METHODS: Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was tend; MR acquisitions performed at tend-2M, tend-4M and tend-6M (respectively 2, 4 and 6 months before tend) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∆B from tend-4M to tend-2M and ∆B from tend-6M to tend-4M. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. RESULTS: The fraction of hypoperfused tumor volume (F_hPg) was a relevant biomarker. A ratio R(F_hPg) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (≥0.61) was associated with more relapse at tend compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). CONCLUSION: Iterative analysis of F_hPg from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. KEY POINTS: • Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. • Biomarkers were assessed through their patterns of variation during the follow-up. • The fraction of hypoperfused tumour volume (F_hP g ) seemed to be a relevant biomarker. • An innovative ratio R(F_hP g ) could be an early surrogate marker of relapse. • A significant time gain could be achieved in the management of GBM patients.

Intramyocellular lipid variations in active older men: relationship with aerobic fitness.

AIMS: Intramyocellular lipid (IMCL) variations in older men are poorly explored. In young adults, IMCL can be influenced by both diet and exercise interventions; this flexibility is related to aerobic fitness. We evaluated in active older adults the influence of maximal aerobic capacity on short-term diet and exercise-induced variations in IMCL stores. METHODS: Intramyocellular lipids were measured by (1) H magnetic resonance spectroscopy ((1) H-MRS) after a 3-day fat depletion-replenishment diet (IMCL(FDR) ) and immediately after a 2-h exercise at 50% VO(2) max (IMCL(FDR) (_) (EX) ). To further explore diet influence, the protocol was repeated after a high-fat diet (HF), with both pre- and post-exercise measurements (IMCL(HF) and IMCL(HF) (_) (EX) ). RESULTS: In active older men (69.8 ± 5.2 years), IMCL(FDR) was lowered by exercise (IMCL(FDR) = 3.45 ± 1.52 vs. IMCL(FDR) (_) (EX) = 2.74 ± 1.15 mmol kg(-1) wet weight, P < 0.05), and exercise-induced variations were correlated to the initial store (P < 0.05, r = -0.72). IMCL(FDR) was linked with aerobic fitness (P < 0.05, r = 0.76), when adjusted by fat mass. IMCL(HF) was lower than IMCL(FDR) (P < 0.05), decreased after exercise (P < 0.05) and varied also as a function of initial store (P < 0.05, r = -0.89), but without link with aerobic fitness. Finally, diet-induced IMCL store variations were positively linked to aerobic fitness (P < 0.05, r = 0.89). CONCLUSION: Variations of the IMCL stores in physically active older adults appear related to aerobic fitness, with similarly fast adaptation to short-term interventions combining diet and exercise as young active adults.

Diffusion tensor-MRI evidence for extra-axonal neuronal degeneration in caudate and thalamic nuclei of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: MS is an inflammatory demyelinating disease affecting both WM and GM. While WM lesions are easily visualized by conventional MR imaging, the detection of GM alterations remains challenging. This diffusion tensor MR imaging study aimed to detect and characterize diffuse microscopic alterations in 2 deep GM structures, the caudate nucleus and the thalamus, in patients with RR and SP MS. The relationship between diffusivity markers, and atrophy of the caudate and the thalamus, as well as brain lesion load and clinical status of the patients was also explored. MATERIALS AND METHODS: Twenty-three RR and 18 SP patients, along with 27 healthy controls, underwent MR imaging examination including anatomic and DTI acquisitions. Volumes, mean FA, and MD of the caudate and the thalamus, as well as WM lesion volumes, were assessed. RESULTS: FA was significantly (P < .001) increased in the caudate and the thalamus of patients with MS compared with controls, and was higher in SP compared with RR patients. Increased FA was associated with volume decreases of caudate (r = -0.712; P < .001) and thalamus (r = -0.407; P < .01) in patients with MS. WM T2 lesion load was significantly associated with caudate (r = 0.611; P < .001) and thalamic (r = 0.354; P < .05) FA. Caudate FA, and, to a lesser extent, thalamic FA, were associated with functional deficits, as measured by EDSS and MSFC. CONCLUSIONS: Increased FA in the caudate and the thalamus may constitute a sensitive marker of MS pathologic processes, such as loss of dendrites and/or swelling of neuronal cell bodies.

Antihypertensive effect of nuatigenin-3-O-ß-chacotriose from Solanum sisymbriifolium Lam. (Solanaceae) (ñuatî pytâ) in experimentally hypertensive (ARH+DOCA) rats under chronic administration.

The aim of the study is to assess the hypotensive properties of the hydro-ethanolic crude root extract (CRE), the n-butanol fraction (F(BtOH)) and nuatigenin-3-O-ß-chacotriose, from Solanum sisymbriifolium Lam., in adrenal regeneration hypertension+deoxycorticosterone acetate (ARH+DOCA) rats, following a chronic administration. The roots of S. sisymbriifolium Lam. (Solanaceae) were extracted by reflux with ethanol-water 7:3 and the active extract was fractionated by bioassay-guided liquid-liquid separation. Nuatigenin-3-O-ß-chacotriose (B(3-1)) was identified as the main hypotensive compound from the crude drug by spectroscopic methods. Immature Wistar rats of both sexes were submitted to both surgery and deoxycorticosterone acetate treatment to obtain adrenal regeneration hypertensive rats (ARH+DOCA). Different groups of experimentally induced hypertensive rats were randomly allotted and received during 16 weeks a daily oral administration of 1% saline solution (0.1 mL/100g body weigh), 100.0 mg/kg of CRE, 10.0, 30.0 and 50.0 mg/kg of F(BtOH), and 1.0 mg/kg of B(3-1), respectively. In addition, two groups of ARH+DOCA rats were randomly assigned to receive either B(3-1) (1.0 mg/kg/day) or 1% of saline solution (0.1 mL/100g body weight/day) for 7 weeks and then a cross over procedure was performed in order to complete the 16th-week treatment. After 16 weeks of oral administration of crude root extract (CRE), butanolic fraction (F(BtOH)) and nuatigenin-3-O-ß-chacotriose (B(3-1)) a significant reduction of blood pressure value was induced in hypertensive animals (ARH+DOCA) in comparison to the control group receiving 1% saline solution, at the end of experiment. Administration of B(3-1) (1.0 mg/kg/day p.o.) to ARH+DOCA rats provoked a significant reduction of blood pressure, observed gradually from 5th week (p<0.05) to the end of the 16th week period of treatment (p<0.01). Moreover, in a cross over design it was observed that the reduction of blood pressure to normotensive condition is associated to B(3-1). The latest demonstrated that the blood pressure-lowering effect, in clearly hypertensive animals, is reversible and depend upon administration of nuatigenin-3-O-ß-chacotriose (B(3-1)). Our results demonstrated that daily oral administration of CRE, F(BtOH) and nuatigenin-3-O-ß-chacotriose from S. sisymbriifolium for a 16-week period exhibits an antihypertensive effect in experimentally hypertensive (ARH+DOCA) rats.

The antidepressant-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice.

The aim of the present work is to evaluate the putative antidepressant-like effects of a hydro-ethanolic extract (CEAp) and their fractions from the aerial parts of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) on the performance of male mice in the forced swimming test (FST). A single dose (100.0mg/kgp.o.) of CEAp, in male mice provoked a significant reduction of the immobility time (p<0.01). Such effect was also observed with short-term treatment (7 days) with single doses of 1.0 (p<0.01), 10.0 (p<0.05) and 100.0 (p<0.05)mg/kg/day of CEAp. Additionally, in a different set of experiments, repeated administration in a 24-h period (24, 18 and 1h before swimming test) with doses of 1.0 (p<0.05) and 10.0 (p<0.05)mg/kg p.o., of CEAp and 10.0mg/kgp.o., (p<0.05) of ethyl acetate fraction, provoked significant reduction of the immobility time of male mice in the FST. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEAp (acute, short-term or repeated). Both, efficacy and potency were higher when repeated administration of CEAp was used, and surprisingly the dose of 10mg/kg (24, 18 and 1h before swimming test) was more effective than imipramine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the CEAp in comparison to a single dose treatment. The ethyl acetate fraction submitted to TLC demonstrated that main and minor components are phenolics and terpenes, respectively. In addition, this fraction gives a negative Shinoda's test for flavonoids. These results indicate an antidepressant-like profile of action for the hydro-ethanolic extract and the component(s) of the ethyl acetate fraction obtained from A. polystachya, which deserve further investigation.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis--a two-year longitudinal MRI/MRSI study of corpus callosum.

BACKGROUND: Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. GOAL AND METHODS: To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. RESULTS: Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. CONCLUSION: These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice.

The aim of the present work is to demonstrate the putative sedative and anxiolytic-like effects of a hydro-ethanolic extract obtained from the aerial parts of Aloysia polystachya (Verbenaceae) in male mice using several behavioural assays. Groups of male mice orally treated with doses of 1.0, 10.0 and 100.0 mg/kg of the extract did not show any significant alteration of their locomotor activity, body temperature or motor coordination. The same treatment increased the duration of the sleeping time induced by 30.0 mg/kg i.p. of sodium pentobarbital. However, the sleeping time induced by ethyl ether was not modified by the oral administration of the extract, not confirming the putative sedative effect of the plant. The ethanolic extract also significantly increased the percentage of both entries (1.0 and 100.0 mg/kg) and the time spent (10.0 and 100.0 mg/kg) into the open arms of the elevated plus maze (EPM). Nevertheless, the binding of (3)H-flunitrazepam ((3)H-FNZ) to the benzodiazepine binding site (BDZ-bs), in washed crude synaptosomal membranes from rat cerebral cortex, was not affected by the semi-purified components from Aloysia polystachya. These results indicate an anxiolytic-like profile of action for the extract of Aloysia polystachya without sedative side effect, being this activity probably mediated by other mechanism than BDZ-bs modulation at the GABA(A) receptors.

A new steroidal saponin from Solanum sisymbriifolium roots.

Isonuatigenin-3-O-beta-solatriose (1) was isolated from the roots of Solanum sisymbriifolium. Its structure was determined by spectroscopic methods.

Functional MRI study of PASAT in normal subjects.

The paced auditory serial addition test (PASAT) is routinely used to evaluate the cognitive part of the multiple sclerosis functional composite (MSFC) score, the new reference index of patient disability. PASAT is sensitive to subtle cognitive impairment related to MS, although the cognitive components of this test still remain unclear. In order to better characterize brain systems involved during this complex task, functional magnetic resonance imaging (fMRI) experiments were conducted during PASAT in a population of ten normal subjects. The paradigm consisted of a series of 61 single-digit numbers delivered every 3 s. After each number, subjects were asked to overt vocalize the result of the addition of the two last numbers heard. A control task consisting of the repetition of the same series of single-digit numbers was used. Statistical group analysis was performed using the random effect procedure (SPM 99). Cortical activation was observed in the left prefrontal cortex, the supplementary motor area, the lateral premotor cortex, the cingulate gyrus, the left parietal lobe, the left superior temporal gyrus, the left temporal pole, and visual associative areas. fMRI activations underlying PASAT were consistent with an involvement of verbal working memory and the semantic memory retrieval network which could be related to arithmetic fact retrieval. This study on normal subjects could provide a base for the understanding of the potential abnormal cortical activation in MS patients performing this test for a cognitive evaluation.

Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis.

fMRI and structural equation modeling (SEM) were used to study effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis (MS), while performing paced auditory serial addition test (PASAT), a sensitive task to reveal subtle cognitive impairments related to working memory and information speed processing. The path model used for SEM included bilateral connections between left and right BA 46, left and right BA 40, left and right anterior cingulate cortex (ACC), left BA 44 and left BA 40, right BA 44 and right BA 40, and unidirectional ipsilateral connections from BA 46 to BA 44, from ACC to BA 46, and from ACC to BA 44. Experimental data from the two groups fit accurately the working memory model, in patients [chi20(2) = 13, P = 0.877] as well as in controls [chi20(2) = 13.54, P = 0.853]. The omnibus test indicated a significant difference of model fits in patients and in controls [chi40(2) = 160.07, P < 0.0001]. Connectivity strengths from right BA 46 to left BA 46, from left ACC to left BA 46 were lower in patients than in controls, and higher from right ACC to right BA 46, from left to right and from right to left ACC (stacked model). Effective connectivity inside the working memory network appears altered in patients at the earliest stage of MS. Modulation of effective connectivity is present in patients inside the executive subsystems of working memory, and could be related to adaptive cognitive control processes that may limit the clinical manifestation of MS.

MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis.

Atrophy of corpus callosum (CC) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of CC are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (CISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure CC volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/Cho) ratio, N-acetyl aspartate/total creatine (NAA/Cr) ratio and Cho/Cr ratio inside the CC of 46 CISSMS patients and 24 sex- and age-matched controls. No atrophy of CC was observed in the CISSMS group. CC of patients was characterized by decreased MTR and increased MD. No change in the NAA/Cr ratio was observed while the NAA/Cho ratio decreased and Cho/Cr ratio increased in the splenium and the central anterior part of CC. These abnormalities were present in patients with, but also without, macroscopic lesions inside the CC. Our results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin pathology, occur in the CC at the earliest stage of MS before any atrophy is detected.

[New MRI techniques in multiple sclerosis]. / Nouvelles techniques IRM et SEP: IRM de diffusion, spectroscopie et transfert d'aimantation.

Early imaging investigations in multiple sclerosis (MS) described focal signs. Technological progress now suggests this concept should be revisited as more diffuse anomalies of the central nervous system are described, sometimes involving regions that appear normal with conventional imaging techniques. This integrative concept results largely from the contribution of magnetic resonance imaging techniques recently broadened to in vivo investigations. Technical developments in MRI now provide new contrast images (magnetization transfer, diffusion, anisotropic diffusion, functional MRI using the BOLD method) as well as new variants of conventional sequences designed to demonstrate specific aspects of the MS lesions: FLAIR sequence (a T2-weighted sequence), black holes (a particular aspect on T1-weighted images), cord atrophy (quantification of the axial section of the cord on T1-weighted sequences). Together these new methods should improve diagnostic sensitivity (FLAIR) or provide prognosis information not provided by conventional sequences (T2 or T2 weighted images with or without gadolinium injection).

[Brain tumors: interest of magnetic resonance spectroscopy for the diagnosis and the prognosis]. / Néoformations intra-cérébrales: apport de la spectroscopie par résonance magnétique dans leur diagnostic et leur pronostic.

Magnetic resonance spectroscopy (MRS) is a tool for a non-invasive monitoring of brain tumor metabolism. In vivo proton MRS became possible with the development of whole-body high-field magnets. First, it allows to distinguish brain tumors from abscesses. Second, along with other imaging techniques, it permits the differentiation of primary brain tumors, mainly gliomas, from tumors of various origins such as meningiomas or metastasis. However, its ability to give a grading of gliomas stays controversial. Choline, a marker of cell membrane proliferation, could give information on the degree of malignancy but reports on its role are somewhat contradictory. Brain tumor biopsy and histology stay mandatory in the management of brain tumors. In vitro MRS spectra obtained from tumor extracts show that the signal at 3.2ppm, the so-called "cholin peak", corresponds to several compounds among them, glycerophosphocholine, phosphocholine, and choline. Their repartition differs with the grade of the tumor. In vivo proton MRS is the only metabolic technique of non-invasive monitoring of treated brain tumors. It can separate recurrence from radionecrosis. Improved methodology and availability of MR imagers will strengthen its importance in the future.

Perimetric visual field and functional MRI correlation: implications for image-guided surgery in occipital brain tumours.

OBJECTIVE: To compare the results of visual functional MRI with those of perimetric evaluation in patients with visual field defects and retrochiasmastic tumours and in normal subjects without visual field defect. The potential clinical usefulness of visual functional MRI data during resective surgery was evaluated in patients with occipital lobe tumours. METHODS: Eleven patients with various tumours and visual field defects and 12 normal subjects were studied by fMRI using bimonocular or monocular repetitive photic stimulation (8 Hz). The data obtained were analyzed with the statistical parametric maps software (p<10(-8)) and were compared with the results of Goldmann visual field perimetric evaluation. In patients with occipital brain tumours undergoing surgery, the functional data were registered in a frameless stereotactic device and the images fused into anatomical three standard planes and three dimensional reconstructions of the brain surface. RESULTS: Two studies of patients were discarded, one because of head motion and the other because of badly followed instructions. On the remaining patients the functional activations found in the visual cortex were consistent with the results of perimetric evaluation in all but one of the patients and all the normal subjects although the results of fMRI were highly dependent on the choices of the analysis thresholds. Visual functional MRI image guided data were used in five patients with occipital brain tumours. No added postoperative functional field defect was detected. CONCLUSIONS: There was a good correspondence between fMRI data and the results of perimetric evaluation although dependent on the analysis thresholds. Visual fMRI data registered into a frameless stereotactic device may be useful in surgical planning and tumour removal.

Virtual movements activate primary sensorimotor areas in amputees: report of three cases.

OBJECTIVE: In our multidisciplinary pain clinic, three patients with amputated limbs and with surgical indications for chronic motor cortex stimulation for phantom limb pain were selected for their ability to voluntarily move the missing limb. The sensation of being able to move a missing limb at will occurs quite frequently among traumatic amputees, but the ability to control it sufficiently to perform a functional magnetic resonance imaging (fMRI) examination is more rarely encountered. We used motor fMRI to study these virtual movements. METHODS: In two patients with upper-limb amputations, movements of the stump, the normal hand, and the missing arm were studied. In a third patient with both legs amputated, movements of the stumps and of the missing feet were studied. The fMRI data were analyzed with the Statistical Parametric Map 96 software and reformatted for integration into anatomic slices. RESULTS: Virtual movements of the missing limbs produced contralateral primary sensorimotor cortex and central sulcus activations in the patients with upper-limb amputation. Interhemispheric and bilateral activations were found in the patient with both legs amputated. These activation areas were different from the stump activation areas. Additionally, the significance thresholds chosen to generate the activation maps in virtual movements (although individual) were globally the same as those used to detect motor activation in the normal side of the patients. CONCLUSION: Cortical areas devoted to the missing limb seem to persist for several years after amputation. The precentral activations found in our patients are in agreement with the statement that the neural mechanisms involved in the mental representation of an action and in its execution are the same. Data from fMRI can be used to evaluate phantom limb virtual movements and to study cortical reorganization phenomena that can appear with time or as a result of some therapies. In these patients, fMRI data may be useful in assisting the neurosurgeon in the placement of chronic motor cortex electrodes.

Chronic motor cortex stimulation for phantom limb pain: a functional magnetic resonance imaging study: technical case report.

OBJECTIVE AND IMPORTANCE: Chronic motor cortex stimulation has provided satisfactory control of pain in patients with central or neuropathic trigeminal pain. We used this technique in a patient who experienced phantom limb pain. Functional magnetic resonance imaging (fMRI) was used to guide electrode placement and to assist in understanding the control mechanisms involved in phantom limb pain. CLINICAL PRESENTATION: A 45-year-old man whose right arm had been amputated 2 years previously experienced phantom limb pain and phantom limb phenomena, described as the apparent possibility of moving the amputated hand voluntarily. He was treated with chronic motor cortex stimulation. INTERVENTION: Data from fMRI were used pre- and postoperatively to detect shoulder and stump cortical activated areas and the "virtual" amputated hand cortical area. These sites of preoperative fMRI activation were integrated in an infrared-based frameless stereotactic device for surgical planning. Phantom limb virtual finger movement caused contralateral primary motor cortex activation. Satisfactory pain control was obtained; a 70% reduction in the phantom limb pain was achieved on a visual analog scale. Postoperatively and under chronic stimulation, inhibiting effects on the primary sensorimotor cortex as well as on the contralateral primary motor and sensitive cortices were detected by fMRI studies. CONCLUSION: Chronic motor cortex stimulation can be used to relieve phantom limb pain and phantom limb phenomena. Integrated by an infrared-based frameless stereotactic device, fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication. Pain control mechanisms and cortical reorganization phenomena can be studied by the use of fMRI.

Methodological and technical issues for integrating functional magnetic resonance imaging data in a neuronavigational system.

OBJECTIVE: The aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTS: Correspondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.