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Tumefactive multiple sclerosis is a rare entity in children. Differential diagnosis includes other mass lesions such as neoplasm and abscess. A case of tumefactive multiple sclerosis in a child is presented. The open-ring pattern of enhancement on conventional MRI and magnetisation transfer imaging was important for the initial diagnosis and the evaluation of the course of the disease.
We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis.
In three women with multiple sclerosis, paroxysmal attacks of itching occurred. There were several similarities between these attacks and other types of paroxysmal phenomena previously described in multiple sclerosis. The attacks were brief, but usually lasted several minutes, they started and ended abruptly, and recurred several times a day. The were controlled effectively by carbamazepine. It is suggested that paroxysmal itching is caused by transversely spreading ephaptic activation of axons within a partially demyelinated lesion in pain-conducting fibre tracts in the central nervous system.
The Multiple Sclerosis Society Tissue Bank contains post-mortem central nervous system tissue from over 100 clinically and neuropathologically well-documented multiple sclerosis (MS) cases, and from normal control subjects. This bank is a resource centre which provides histologically screened snap-frozen material for immunological, neurochemical and nucleic acid studies in our own and other MS laboratories in Europe and the USA. In addition to immunopathological studies, Tissue Bank material has been used to investigate changes in CNS-specific proteins and lipids in MS plaques and responses of oligodendrocytes and astrocytes to the inflammatory demyelinating process. MS lesions detected in unfixed post-mortem brain and spinal cord by magnetic resonance imaging techniques prior to dissection have been characterized histologically and biochemically. A computer database on Tissue Bank post-mortem cases has been established to link clinical, pathological and scientific aspects of MS research.
Ninety-one subjects with multiple sclerosis were evaluated by carbon dioxide cystometry in the supine, sitting, and standing positions, and by water cystometry in the supine position. Detrusor responses in supine studies were characterized as normal, hyperreflexic, or areflexic. Carbon dioxide and water cystometry were without difference in determining types of detrusor responses. Positional changes (particularly standing) resulted in reassessing of normal supine bladder responses as hyperreflexic. Hyperreflexia was aggravated with sitting and standing. Positional changes did not demonstrate conversion of areflexia to hyperreflexia. The relatively small proportion of dyssynergic sphincter responses probably represents a population of patients with early stage multiple sclerosis. Carbon dioxide cystometry, with positional changes, is relatively safe, easily performed, and an accurate method of evaluating detrusor response in patients with multiple sclerosis who have a changing clinical course or unresponsiveness to treatment.
The dynamics of primary progressive multiple sclerosis differ from those of the more common secondary progressive form. The observation by MRI that the frequency of enhancement with gadolinium-DTPA, a marker for blood-brain barrier dysfunction, is significantly less in the primary progressive form, has led to the hypothesis that inflammation is less intense in this group. To test this, we have studied postmortem material from nine cases judged from a retrospective analysis of case notes to show clear clinical evidence of either primary progressive or secondary progressive disease. Five hundred and seventy-eight lesions were analysed. There was significantly more inflammation in secondary progressive multiple sclerosis (as judged by the frequency of perivascular cuffing and cellularity of the parenchyma) than in primary progressive disease. These observations have implications for therapeutic strategies in progressive multiple sclerosis.
Recent studies on the etiopathogenesis of multiple sclerosis (MS) all point out that there is a polygenetical predisposition for this illness. The so called "MS Trait" determines the reactivity of the immunological system upon ecological factors. The development of the glyphological science and the study of the characteristics of the digito-palmar dermatoglyphic complex (for which it was established that they are polygenetically determined characteristics) all enable a better insight into the genetic development during early embriogenesis. The aim of this study was to estimate certain differences in the dermatoglyphics of digito-palmar complexes between the group with multiple sclerosis and the comparable, phenotypically healthy groups of both sexes. This study is based on the analysis of 18 quantitative characteristics of the digito-palmar complex in 125 patients with multiple sclerosis (41 males and 84 females) in comparison to a group of 400 phenotypically healthy patients (200 males and 200 females). The conducted analysis pointed towards a statistically significant decrease of the number of digital and palmar ridges, as well as with lower values of atd angles in a group of MS patients of both sexes. The main discriminators were the characteristic palmar dermatoglyphics with the possibility that the discriminate analysis classifies over 80% of the examinees which exceeds the statistical significance. The results of this study suggest a possible discrimination of patients with MS and the phenotypically health population through the analysis of the dermatoglyphic status, and therefore the possibility that multiple sclerosis is genetically predisposed disease.
Multiple sclerosis is a common inflammatory disease of the CNS. A great number of immunologically active molecules have been identified in the CSF of these patients (CSF-MS), but the role of these substances in neuronal dysfunction, especially in the origin of transient symptoms, is unclear. Therefore, we investigated the effect of CSF from 13 multiple sclerosis patients on membrane currents of cultured cortical neurons from embryonic rat and compared it with the effect of CSF from 12 patients with non-inflammatory neurological diseases. We found an increase in Na+ current (INa) inactivation by a shift of the hoo curve to more hyperpolarizing potentials by 9.3 mV. This effect was reversible by washing and could be abolished by CSF-MS heat inactivation. The degree of the shift ranged from 4.3 mV to 17.6 mV and correlated with the IgG index, but not with the degree of pleocytosis, protein or albumin content. The maximal amplitude of INa was unchanged. We concluded that diffusible factors are released into the CSF which reduce neuronal excitability and thereby disturb the function of the neuronal network. These factors may well contribute to transient neurological symptoms seen in patients with "active' multiple sclerosis.
Clinical manifestations of multiple sclerosis cannot always be correlated with the type of lesion present. Plaques in certain regions may be clinically silent whereas, inversely, some neurological disorders appear not to be related to a demyelinization process. The pathophysiology of neurological symptoms and signs in multiple sclerosis may therefore be related to two other factors: 1) membrane phenomena observed in demyelinated fibers and leading to partial or complete conduction block, or 2) conduction blocks due to pathological phenomena that fail to provoke anatomical demyelinization. Demyelinization induces a sudden drop in impedance of the axon membrane which is responsible for the conduction block. Redistribution of sodium ionophores in the demyelinated axon enables transmission of certain messages but in a slower and unreliable manner. Sensitivity of demyelinated fibers to temperature and the extracellular ionic environment provides an explanation for the transient, recurrent stereotyped reactions provoked by fever, physical exercise or digestion. In the absence of demyelinization, a conduction block could be the result of either a minimal lesion at the paranodal myelin with denudation of the specialized parts between axon and glia,or of humoral blocking factors--of debatable specificity--or cellular factors that have been demonstrated recently. The existence of such mechanisms suggests the need for revision of the notion of acute episodes of multiple sclerosis. Finally, knowledge of the mechanisms involved in nerve conduction along demyelinated fibers suggests the possibility of therapy to restore conduction of these fibers by acting on extracellular ionic concentrations or directly on membrane ionic canals.
A case of multiple sclerosis initially presenting as a facial palsy is presented. A 35-yr-old U.S. Air Force aviator developed a purely right-sided facial palsy with no sensory abnormalities. She had no other neurologic findings except for a barely perceptible loss of coordination in her right upper extremity. Subsequent brain MRI revealed multiple white matter lesions. Further history and laboratory analysis confirmed multiple sclerosis. This case underscores the potential for multiple sclerosis to mimic other more benign conditions and the need for clinicians to carefully examine patients presenting with new neurologic abnormalities. The diagnosis and treatment of multiple sclerosis as well as military aviation policy regarding multiple sclerosis patients is discussed.
The trend to start disease-modifying therapy early in the course of multiple sclerosis makes it important to establish whether the benign form is a real entity. In previous studies, measures of magnetization transfer (MT) ratio (MTr) have been shown to provide good estimates of the amount of tissue damage occurring in multiple sclerosis brains. Thus, with the hypothesis that if benign multiple sclerosis patients were really benign, sensitive measures of subtle tissue damage would be less pronounced in these patients than in very early relapsing-remitting (RR) multiple sclerosis patients. We carried out conventional MRI and MT imaging in 50 patients with benign multiple sclerosis [defined as having Kurtzke Expanded Disability Status Score (EDSS) <3 and disease duration >15 years] and in 50 early RR patients selected to have similar disability (EDSS <3) and short disease duration (<3 years). Data were compared with those of 32 demographically-matched normal controls. We used a fully automated procedure to measure lesional-MTr, perilesional-MTr, normal-appearing white matter (NAWM) MTr and cortical-MTr. We found that, after correction for common effects of age, lesional-MTr and perilesional-MTr of benign patients were significantly (P < 0.0001) lower than WM of normal controls, but significantly (P < 0.0001) higher than corresponding tissues of RR patients. In NAWM and cortex, MTr values of benign patients were similar to those of normal controls (P > 0.5) and significantly higher than those of the RR patients (P < 0.0001 and P < 0.01, respectively). Similar differences in MTr measures between benign and RR patients were found when patient groups were selected to have no disability (EDSS < or = 2) and, for benign multiple sclerosis, very long disease duration (>20 years) or when both groups were matched for high lesion load (T2-weighted lesion volume >10 cm3). We conclude that lesional and non-lesional MTr values can be significantly less pronounced in benign multiple sclerosis than in a cohort of RR patients at their earliest disease stages, suggesting that brain tissue damage is milder in benign multiple sclerosis than in early RR disease. This can be due to an extraordinary beneficial response to demyelination of benign patients and may represent the evidence that benign multiple sclerosis truly exists and might be differentiated from other forms of this illness.
Multiple sclerosis is possibly one of the diseases that bets illustrates progress in Neurology over the last years. The present article reviews the most significant changes that have occurred in almost all the aspects of this disease. These changes have produced a profound modification in the understanding of multiple sclerosis and have encouraged the development of innovative therapies.
Therapy for multiple sclerosis (MS) is undergoing rapid changes. We discuss recent developments in the therapy of MS, failures as well as successes, and consider some newer approaches. Multiple sclerosis, a multifocal, initially remitting-relapsing, and in some cases primarily progressive, inflammatory central nervous system immune-mediated demyelinating disease, with some axonal involvement, is currently the most common disabling neurologic disease of young people in North America and Europe. Although much is known about the pathogenesis, there is no cure and the disease must be managed long-term. Recently, there have been a number of advances in the treatment of MS.
Disease-modifying treatments in multiple sclerosis emerged during the last few years, concerning mainly relapsing-remitting forms of the disease. They are essentially represented by beta-interferons. beta-interferons reduce relapse rate, achieving about 30 p. cent, and have an effect on brain lesions detected on MRI. They are indicated for use in ambulatory patients with relapsing-remitting multiple sclerosis characterized by at least 2 attacks of neurological dysfunction over the preceding 2 (or 3)-year period. Questions and controversies still remain concerning dose-response effect, early initiation and duration of treatment. Copolymer, which has a different mechanism of action, also decreases frequency of relapses, and the magnitude of the clinical effect is similar to beta-interferon. Copolymer is indicated for use in patients with relapsing-remitting multiple sclerosis, having either an intolerance or a contra-indication to beta-interferon.
Multiple sclerosis is a complex trait in which occurrence rates in offspring are 20-50-fold greater than in the general population. Parent-of-origin effects have been difficult to screen for, since most cases are sporadic. We have compared recurrence risks in half-siblings with respect to their parent in common. Of the 1567 index cases with half-siblings in multiple sclerosis clinics across Canada, we recorded 3436 half-siblings and 2706 full-siblings. Age-adjusted full-sibling risk was 3.11%. By contrast, half-sibling risk in the same families was significantly lower at 1.89% (chi2 test, p=0.006), but higher than expected if familial risk was simply polygenic. For maternal half-siblings, the risk was 2.35% (34 affected siblings of 1859), and 1.31% for paternal half-siblings (15 of 1577), (p=0.048). The difference in risk suggests a maternal parent-of-origin effect in multiple sclerosis susceptibility.
Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.
INTRODUCTION: The multiple sclerosis functional composite (MSFC) has been recommended by the National Multiple Sclerosis Society as a new clinical outcome measure. It is based on measurements in three clinical dimensions: leg function/ambulation (timed 25-foot walk), arm function (9 hole peg test) and cognitive function (paced auditory serial addition test). Scores on component measures are converted to standard scores (Z-scores), that reflect patient performance. This method has not yet been introduced into routine clinical practice. PATIENTS AND METHODS: Since March 2000 over the five years period the MSFC calculation was applied to 17 patients with relapsing-remitting multiple sclerosis (age mean: 37.4 +/- 10.8 years, duration of the disease: 5.5 +/- 4.9 years, EDSS: 2.7 +/- 1.4) seen at the neuroimmunological outpatient clinic to evaluate its usefulness and its correlation with the traditionally applied expanded disability status scale (EDSS). Thirteen patients received immunomodulatory treatment (interferon beta and glatiramer acetate), one patient received immunosuppressant therapy (azathioprine), and there was one patient, who developed secondary-progressive phase and we changed the interferon treatment to mitoxantrone. MSFC and EDSS were measured at 3., 6., 9, 12., 18 and 60 months of follow-up. RESULTS: The prospective study confirmed a strong correlation between EDSS and MSFC in multiple sclerosis. The MSFC was more sensitive to clinical changes than EDSS. Our results after 18 months of follow up are already published. After five years arm/hand function and leg function/ambulation were the most sensitive measures for disease progression. In contrast with the literature we did not experience correlation with cognitive changes. CONSEQUENCES: We demonstrated strong correlation between MSFC and EDSS after a longer period. MSFC is a simple method, suitable for follow-up of multiple sclerosis patients in everyday clinical practice.
Evidence on aetiology in multiple sclerosis suggests that the prevalence depends on the interaction of two factors, diet and exposure to visible sunlight. The dietary features which may be beneficial include supplementation with fish oils, avoidance of saturated fats, and the associated intake of antioxidants with unsaturated fatty acids. Inhibition, by antioxidants, of the enzyme lipoxygenase inhibits leukotriene synthesis, and the presence of fish oils leads to the production of leukotrienes with less inflammatory properties. This is of particular importance in the retina where leukotrienes might be the underlying cause of retrobulbar neuritis. The antioxidant properties of vitamin A may also lead to inhibition of leukotriene synthesis. Visible solar radiation could be of benefit therefore by releasing vitamin A from visual pigment rhodopsin. The interaction of these two factors may explain the epidemiological observations on the prevalence of multiple sclerosis.