MRI visualization of multiple sclerosis lesions

Magnetic resonance imaging represents voxels (volume elements) of the body placed in a magnet, by their magnetization determined under various acquisition conditions weighting the contrast of the image by the density of free water protons and their relaxation times T1 and T2. Thus, the sensitivity in depicting lesions is high but pathological specificity is poor. Efforts are made to increase the diagnosis powerfulness of M.R.I. in multiple sclerosis: a careful correlation with the clinical presentation and the use of better M.R.I. criteria increase the specificity of the conventional T2 sequences. New sequences such as fast spin echo (F.S.E.), turbo spin echo (T.S.E.) or derived from inversion recovery (F.L.A.I.R.: fluid attenuated inversion recovery) improve the detection of lesions. Under specific conditions M.R.I. can be used to monitor the evolution of M.S. Acute phase monitoring focuses on changes in disease activity, new, recurring, enlarging, gadolinium (Gd) enhancing lesions, and chronic phase monitoring appreciate the burden of the disease. However M.R.I. is always considered as a secondary outcome in the phase III trials because insufficient correlations with the clinical disability. In the neurological daily practice conventional M.R.I. is of poor interest in the follow up of individual M.S. patients considering the weakness of prognosis value and the problems in the measurement of the lesions load which is emphasized in the methodology of the clinical trials. Nevertheless, there is a continuing search for techniques which correlate better with clinical measures of the disease such as the quantification of "black holes" on T1 w images or the cerebral and spinal atrophy. New techniques allow to weight the signal by the movement (diffusion imaging), by the complexity of the molecular architecture (magnetization transfer imaging), by the chemical shift (chemical shift imaging) or by the local status of oxygenation (functional M.R.I.). The basic aspects of the pathological lesions in M.S., edema, membrane disruption, demyelination, gliosis, cellular infiltration and axonal loss can be studied more precisely by these new M.R. techniques which should better describe the actual clinical impact of the destructive process. In the last year the importance of axonal loss has simultaneously been confirmed by M. R. spectroscopy and pathological findings. However, magnetization transfer imaging, M.R. diffusion imaging and functional M.R.I. are intensively under investigation for a better analysis of these different factors conditioning the reversibility of the patient disability.     

Physiologic MRI of a tumefactive multiple sclerosis lesion

Structural and physiologic MRI were performed after subacute onset of left hemiparesis in a patient with MS. MRI showed a large ring-enhancing lesion with surrounding edema and mass effect; differential diagnosis included a neoplasm or a large MS plaque. Physiologic MRI showed reduced blood flow and magnetization transfer, as well as increased diffusion, in the large lesion. Because these findings suggested a tumefactive MS plaque rather than a neoplasm, the patient received steroid treatment for acute MS exacerbation. Three months later the patient improved clinically and on MRI.     

MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

Objective: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls. Method: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients. Results: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p p p p     

Failure of intravenous immunoglobulin to arrest progression of multiple sclerosis: a clinical and MRI based study

Due to the modest benefit, inconvenience and high cost of currently available therapies for MS, it is appropriate to seek alternative treatments. Based on anecdotal evidence suggestive of benefit for i.v.IG in MS, we conducted an open-label, unblinded protocol of i.v.IG in nine MS patients. The patients were given induction doses of i.v.IG followed by monthly boosters for 1 year and had clinical, MRI and CSF analyses performed. Patients included were both progressive and relapsing. There was no clinical benefit nor apparent MRI benefit utilizing this protocol. During treatment the majority of patients continued to progress or have attacks and MRI demonstrated continued accumulation of T2-weighted lesions. CSF was unaffected by treatment.     

A pyramidal approach for automatic segmentation of multiple sclerosis lesions in brain MRI

The oxygen radical absorbance capacity (ORAC) was measured both in whole (ORAC-T) and deproteinized (ORAC-AS) plasma samples of human, pig, cow, rabbit, dog, cat, sheep, horse, dolphin, turkey, guinea-hen and chicken. In the 12 species, ORAC-T data, expressed as micromoles of peroxyl radicals trapped by 11 of sample, were found scattered between 8,600 and 23,000 micromol/l. The species with the highest ORAC-T values were cat among mammals and chicken among avies. ORAC-AS values ranged between 600 and 2000 micromol/l, with the highest values found in dolphin and sheep among mammals, while chicken was first among avies. In the 12 species, the relative contribution of ORAC-AS in relation to ORAC-T ranged from 5% to 20%. Protein SH-groups and uric acid were measured in plasma of all species, but no significant correlation was found between thiols and ORAC-T values or between uric acid and ORAC-AS values. Our results show that: (1) the ORAC method is reproducible and sensitive enough to be used in the comparison of the peroxyl-radical absorbance capacity of protein and non-protein plasma components in different animal species; (2) both in mammals and in avies, there is a deep intra-class heterogeneity of ORAC-T and ORAC-AS values; (3) by considering most species, plasma proteins and lipoproteins account for about 85-90% of the overall peroxyl-radical trapping capacity. In the dolphin only, the protein contribution decreases to 80%; (4) uric acid accounts for about one-half of the ORAC-AS value in human, guinea-hen and for about one-third in chicken, while it provides a very limited contribution in other species. We conclude that species with the highest ORAC-T, like cat and chicken, or with the highest ORAC-AS, like dolphin, are interesting models to study the reasons of such a marked antioxidant defense in the plasma.     

Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis

OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.     

Determinants of Gd-enhanced MRI response to IFN-beta-1a treatment in relapsing-remitting multiple sclerosis

BACKGROUND: With the prevalence of antibiotic use, the diagnosis and management of Clostridium difficile disease requires assessment. METHODS: In a retrospective review, patients with a positive culture, toxin, or both during 1 year were identified. Recent literature was reviewed. Results of culture and toxin, prior antibiotic use, antibiotic treatment history and cost were analyzed. RESULTS: Of 592 patients tested, 101 were positive; 96 of 101 were available for review. Of those positive tested for both, 45% were positive for toxin and culture. Sixty-two of 96 were treated with antibiotics; metronidazole was used in 90%. Ten of 62 antibiotic treatments were changed (mean 3 days). Ten days of metronidazole is 1/200th the cost of vancomycin. CONCLUSIONS: In 55% of the positive cases in which culture and toxin were obtained, one test was negative. As metronidazole's efficacy and cost compares favorably with vancomycin, metronidazole is the drug of choice. Any changes made to antibiotic regimens occurred prior to the 6 days recommended in the literature.     

Erectile impotence in multiple sclerosis: a neurophysiological study

Pudendal evoked potentials, motor evoked potentials of the bulbocavernosus muscle to magnetic stimulation and bulbocavernosus reflex were recorded in 34 patients with multiple sclerosis (MS). Responses were delayed in 26, 20 and 3 cases respectively. No relationship was found between neurophysiological abnormalities and the presence or severity of erectile dysfunction, showing that these tests have little diagnostic usefulness in MS patients with impotence. Nocturnal penile tumescence was assessed in 14 cases: the test result was normal in 10 patients, including 3 severely paraplegic subjects.     

Autonomic involvement in multiple sclerosis: a pupillometric study

A simple method to cultivate pollen tubes in a gelatin medium is presented. After the growth of the pollen tubes in the culture medium, they are fixed, dehydrated, and embedded in resin for ultramicrotomy. The method is easy and does not require the purchase of special materials beyond those needed for the usual techniques for studying biological specimens under transmission electron microscopy.     

Pregnancy and multiple sclerosis. A prospective study

OBJECTIVE: To conduct a prospective assessment of pregnancy on women with multiple sclerosis (MS), focusing on pregnancy outcome and relapses during gestation and up to 6 months after delivery. DESIGN: Expected numbers of relapses were based on data for (1) "self-controls": the mothers ("cases") themselves prior to becoming pregnant and (2) "matched controls": female patients with MS "matched" to the mothers for year of birth, age of MS onset, MS type, MS course, and initial MS symptom(s). SETTING: Cases and controls were identified from an ambulatory care MS clinic that serves the province of British Columbia, Canada. PATIENTS OR OTHER PARTICIPANTS: Women with a diagnosis of MS who attended the MS clinic during 1982 through 1986 and subsequently became pregnant during 1982 through 1989 inclusive were included in this study as cases. Matched controls were women with MS who attended the MS clinic during the same period but did not become pregnant. RESULTS: No significant increase in relapse rate was found for cases during the first two trimesters of gestation. The number of relapses was significantly less than expected during the third trimester compared with matched controls (chi 2 = 6.80, df = 1, P < .02), but not compared with self-controls (chi 2 = 3.39, df = 1, P > .05). The observed number of relapses for the 6 months after delivery did not differ significantly from expected (self-controls: chi 2 = 2.84, df = 2, P > .05; matched controls: chi 2 = 1.76, df = 2, P > .05). CONCLUSION: These data suggest that neither pregnancy nor the 6-month period after delivery is a risk factor for relapse in MS. They are consistent with previous observations that, in the long term, pregnancy does not influence subsequent MS disability.     

MRI and brainstem auditory evoked potential evidence of eighth cranial nerve involvement in multiple sclerosis

An MS patient experienced sudden hearing loss. Brainstem auditory evoked potentials, previously normal, showed substantial abnormalities that suggested the impairment of the distal part of the acoustic nerve. MRI detected a small hyperintense lesion along the acoustic nerve; the lesion decreased in size and then disappeared after steroid treatment. This demonstrates that a demyelinating lesion in the distal tract of the eighth cranial nerve may cause an acute hearing loss in MS.     

Familial multiple sclerosis: a study of six families

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disorder of the CNS, of autoimmune pathology and unknown aetiology. Several theories regarding its aetiology have been suggested, although none seems to be completely convincing. Genetically predisposed persons are affected, therefore groups of MS are seen in certain families. OBJECTIVES: To describe the family links, type of illness and evolution of 12 patients from six families with two or more members diagnosed as having MS, and to evaluate any differences from the other cases recorded in our data base. PATIENTS AND METHODS: We studied 12 patients diagnosed on the criteria of Poser, and with at least one first or second degree relation with MS. We compared clinical data, form of presentation and course with 127 patients recorded in the data base. RESULTS: We describe six families: two homozygotic twins, two families in which transmission was from father to child and three families with first degree cousins affected. We found no clinical variation in the presentation, number of attacks or evolution, as compared with the other patients. Nor was there homogeneity between the familial forms of MS. CONCLUSIONS: Familial forms make up approximately 10% of the series. We do not have any data available for early diagnosis nor for prognostic significance of familial MS.     

Neuroimaging in multiple sclerosis

Neuroimaging in multiple sclerosis is now dominated by MR imaging. This article will focus primarily on conventional MR imaging studies in multiple sclerosis, but will also discuss briefly some of the more recent advances related to MR imaging. Fast spin-echo imaging, fluid attenuated inversion recovery MR studies, three-dimensional volumetric studies, magnetization transfer, and magnetic resonance spectroscopy as it applies to multiple sclerosis are examined.     

Prognosis in multiple sclerosis

Prognosis of the natural course of multiple sclerosis is most often measured on Kurtzke's "expanded disability status scale" (EDSS), a non-linear scale over 20 steps, heavily weighted on mobility. Optic neuritis and sensory disturbances as initial symptoms, lower age at onset of the disease, female sex and a longer interval between relapses are indicators of a more favorable prognosis. As a rule, disability as measured on this scale 5 years after onset corresponds to 3/4 of the disability status after 15 years. The number of relapses diminishes naturally over the course of the disease. Presence and extent of lesions on the initial MRI of the brain in clinically isolated syndromes are valuable predictors of dissemination of the disease process over the following 5-10 years. New therapies (e.g. interferon beta 1b and 1a, copolymer 1) reduce relapse frequency by 1/3 and diminish the extent of pathological lesions in brain MRI, but fail to show (as yet) significant influence on disability.     

Injuries in the etiopathogenesis of multiple sclerosis

An injury might derange the protective function of the blood-brain barrier, and thus it represents one of the possible pathogenetic factors in the demyelination of the neural axis. However, the effect of injury on the occurrence or deterioration of multiple sclerosis is still controversial. According to most authors, the importance of injury in individual cases of multiple sclerosis is undeniable, as well as the fact that injuries are factors of progression and deterioration of the disease, but never its cause. Consequently, injuries can cause only temporary disability, and not permanent. Nevertheless, the incidence of multiple sclerosis increases proportionally to the severity of injury. The length of the period from the occurrence of injury to possible demyelination is still not established. Studies and clinical reports point to the fact that in the evaluation of injury as a precipitating factor for the vulnerability of the blood-brain barrier, the severity of the injury is of greater importance than its site.     

The influence of clinical relapses and steroid therapy on the development of Gd-enhancing lesions: a longitudinal MRI study in relapsing-remitting multiple sclerosis patients

A two-round Delphi study was performed in Pediatric Nursing at a large midwestern teaching hospital. The purpose of the study was to identify research priorities for the Pediatric Research committee for future projects. The initial survey was sent to all pediatric nursing staff. Sixty-two staff (19%) responded to the first round. Forty-five separate research topics/themes of interest were identified. The second round survey was sent to the 62 staff who responded to Round 1. Forty-eight staff (76%) responded. Participants were given a list of the 45 topics identified in Round 1, and asked to identify their top five priorities. Results were analyzed by unit and by Division. The identified priorities for the Division are described here.