Computer tomography of the neurocranium

The experience with computer tomography of the neurocranium in 300 patients submitted for computer tomography of the brain is reported. The more appropriate projections which may be obtained with the second generation of scanners in combination with an elaborated reconstruction technique seem to constitute a replacement of conventional skull films.     

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.     

MRI in the study of multiple sclerosis

Magnetic resonance imaging (MRI) has provided considerable insight into the pathological process and disease activity and progression in multiple sclerosis. MRI has become an important tool for the diagnosis of multiple sclerosis, and increasingly for monitoring treatment trial. The growing use of MRI calls for careful consideration in applications so that the technology is not misused. Here we propose a summary of the literature on MRI in application in clinical neurology.     

Childhood multiple sclerosis

Multiple sclerosis begins before the age of 17 years in 0.4 to 0.5% of the cases, but the diagnosis is exceptionally made before the age of 10 years. Female predominance is more marked in early onset multiple sclerosis. The general features of the disease (clinical expression, progression, prognostic) and the findings of complementary explorations are comparable with those found when the disease begins in adulthood although acute onset and signs of brain stem involvement have been reported. The diagnosis must be made with prudence, especially when progression is slow from the beginning. An analysis of the influence of infective environmental factors and puberty has not provided new insight. Corticosteroids can be used in case of flare-ups. Management requires a multidisciplinary approach to maintain appropriate educational activities.     

Genetics of multiple sclerosis

The cause of MS is unknown. There is considerable circumstantial evidence that MS is a complex trait, probably autoimmune in nature, and is determined by both genetic and environmental factors. At present, it must be acknowledged, however, that our understanding of the pathogenesis of MS is minimal. Very little is known about the genes determining disease susceptibility and perhaps even less is understood about environmental factors that influence penetrance or the geographic distribution. This lack of knowledge results neither from lack of effort nor from a shortage of fertile imaginations. Almost every imaginable hypothesis has, in the past, found some support. The intractability of the problem could well result from its complexity, because answers to testable hypotheses are commonly negative or ambiguous. Today, the opportunity exists for researchers to provide such answers because of recent major developments. The first development is the recognition that MS research requires a relatively large pool of well-ascertained, carefully diagnosed, and longitudinally well-characterized MS patients. The last two developments are the identification and successful application of statistical and molecular genetic techniques carrying sufficient power to allow the exploration of complex traits such as MS.     

Mitoxantrone immunotherapy in multiple sclerosis

We compared the effects of postural changes on intraocular pressure, systemic blood pressure, and pupil size with and without induced mydriasis in 15 chronic chagasic patients and 20 healthy age-matched controls. The chagasic patients showed a marked fall in intraocular pressure on rising. However, systemic systolic blood pressure changes and pupil size in patients did not differ from those measured in controls. Our findings may be explained by an alteration in the autonomic ocular system that regulates homeostasis of ocular pressure and the probable existence of a baroreceptor arc-reflex that restores the equilibrium of sudden changes in the intraocular pressure.     

Genetic factors in multiple sclerosis

OBJECTIVE: To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease. DATA SOURCES: MEDLINE, bibliography review of published data, and unpublished studies. STUDY SELECTION: Published studies using novel molecular approaches to analyze the role of the major histocompatibility complex (MHC) and TCR gene complexes, as well as other candidate genes, in susceptibility to MS. We analyze epigenetic events involving TCR genes in individuals with MS and describe recent clinical trials in which immunotherapy has been attempted. DATA SYNTHESIS: Consistent with a polygenic model for disease predisposition, MHC and TCR gene associations with MS are relatively weak. Despite intensive research, no other putative "MS genes" have been firmly established. The analysis of TCR rearrangements in the brain lesion has helped to identify a major target of the immune response in MS. CONCLUSION: Understanding the genetic basis for autoimmune demyelination will offer new possibilities for the treatment of this illness.     

Paroxysmal itching in 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.     

Current developments in the area of multiple sclerosis

The expression pattern of transforming growth factor-beta 1 (TGF-beta 1) during the stages of complete carcinogenesis in the hamster cheek pouch model was studied. The right cheek pouches of 18 male hamsters were treated with 0.5%, 7,12-dimethylbenz[a]anthracene (DMBA) for 16 wk. TGF-beta 1 was detected immunohistochemically in the resulting samples with two different polyclonal monospecific antibodies that recognize intracellular and extracellular forms of TGF-beta 1. In the normal cheek pouch, extracellular protein stained the corium strongly, but the reaction was not evenly distributed. As treatment progressed, the reaction increased in both area and intensity; the peak was reached at 8 wk. Intracellular TGF-beta 1 expression followed a similar pattern, with a peak at 4 wk of treatment. The results of northern blot analysis were concordant with the immunohistochemical results. Overexpression of TGF-beta 1 was also observed in the malignant tumors, but only the extracellular form of the protein was present; intracellular TGF-beta 1 was not detected in these tumors. The expression of TGF-beta 1 in this carcinogenesis model seems to have two formal stages, the first being an overexpression step as a reaction to the uncontrolled growth and the second being one in which tumors have no internal expression of TGF-beta 1 but in which external protein accumulates in the surrounding stroma. A possible explanation of this paradox may be that TGF-beta 1 has functions other than its growth-repressing activity.     

Changes in the concept of multiple sclerosis]

The author summarizes the newest knowledge in the past 10 years that has changed our way of thinking as well as the treatment strategy of the still incurable Multiple Sclerosis. The sophisticated immunological methods have brought new insight into the inflammatory process of the central nervous system. The MR examinations and the newly developed techniques allow examining the dynamism of the disease and the underlying histological alterations. The testing of new drugs--which proved to be efficient--made it possible to follow more precisely not only the classification of the pathological process but the clinical history as well. The new drugs give the patients some hope and the doctors new tools. It enables of slow down the disease progression, so it can reduce the tissue damage caused by the inflammation and can improve the quality of life of the patient until new, more effective therapies are developed.     

Copolymer-1 in the treatment of multiple sclerosis

Recent research in the treatment of multiple sclerosis (MS) has yielded new therapies. Specifically, copolymer-1, a mixture of synthetic polypeptides composed of four amino acids has been effective in reducing relapse rates and disability in patients with relapsing-remitting MS. In a two-year multicenter, randomized, double-blind, placebo-controlled trial of 251 patients, copolymer-1 was shown to reduce relapses by an average of 29% when compared with placebo. Sustained disability was also slightly reduced in the copolymer-1-treated group. The results of the clinical trial indicate that copolymer-1 positively alters the course of relapsing-remitting MS. With the present availability of copolymer-1, nurses are challenged to maintain current knowledge of nursing implications, interventions, patient education and goals for treatment.     

Axonal transection in the lesions of multiple sclerosis

We explored the relationship between mutans streptococcal infection and the development of salivary IgA antibody during initial colonization. Repetitive swabbing (n = 292) of the teeth of 33 children revealed that 45% became infected with mutans streptococci between 13 and 36 months of age. In contrast, mutans streptococci could not be detected in 18 children whose last sample was taken at 39-81 months of age (median age = 62 months). During the period of mutans streptococcal infectivity, immunoglobulin A (IgA) antibody to several mutans streptococcal antigens appeared in most children, whether or not infection had been demonstrated. Robust responses to mutans streptococcal components occurred during or shortly after, but not before the period of mutans streptococcal infectivity. No consistent differences were observed among the summarized patterns of response of infected and uninfected groups of children, although the IgA Western blot patterns of individual subjects were often quite distinct. For example, sets of siblings, who would be presumed to be challenged with similar maternal mutans streptococcal clonotypes, were shown to develop qualitatively different salivary IgA responses to mutans streptococcal components. These results support a discrete period for mutans streptococcal infection and may suggest that the level of maternal infection is a factor in the success of infection of the child during this period. The data also suggest that exposure to mutans streptococci is a sufficient condition for robust mucosal IgA responses to mutans streptococcal antigens during the period of infectivity and that these responses may be different, even among siblings.