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PubMed1994

[Organic personality syndrome in multiple sclerosis and effect of stress on recurrent attacks].

This study focuses on a sample of 35 patients who had recently suffered an attack of multiple sclerosis. They were first subjected to the so-called life stress method in order to look for a connection between life stresses and the attacks of multiple sclerosis. The sample was compared with a paired control population composed of patients recruited from admission departments and medical emergency departments. The AMDP psychopathological evaluation method was applied to the sample, to establish a characteristic mental profile of these patients. Three types of results are highlighted. First, the comparison of the event scores shows a significant difference between the population of patients suffering from an outbreak of multiple sclerosis and the control population. A connection between "life stresses" and the triggering of the outbreaks of multiple sclerosis is therefore mentioned and discussed. Second, the application of the system of the Association de méthodologie et de documentation psychiatrique brings out a mental profile common to patients suffering from multiple sclerosis, consisting of a very specific association of mood disorders: dysphoria, euphoria and mania on the one hand, and depression, anxiety and dramatization on the other, with relative anosognosia. The correlation between dysphoria, the syndrome's principal characteristic, and the event score adds another argument in favour of the connection between life stresses and the evolution of the disease. The main components of this mental profile are primarily correlated with the existence of a neuropsychology suggestive of a medial basal frontal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Multiple ring-enhancing lesions in a child with relapsing multiple sclerosis.

The presence of ring-enhancing lesions in brain magnetic resonance images (MRIs) often raises the concern of an infectious etiology, although this radiographic finding is also seen in patients with multiple sclerosis. Multiple ring-enhancing lesions have been reported in adult patients diagnosed with multiple sclerosis but have not yet been reported in childhood multiple sclerosis. We report here a 14-year-old girl with recurrent neurologic symptoms. Her initial brain MRI showed multiple ring-enhancing lesions involving numerous white-matter fiber tracts. An extensive investigation for infectious etiologies was unrevealing. Studies of cerebrospinal fluid showed an elevated myelin basic protein and the presence of an oligoclonal band not seen in the serum. The results of electrophysiologic studies suggested a demyelinating process. The patient responded rapidly to high-dose corticosteroid treatment. However, she suffered a clinical relapse 3 months later, presenting with dysesthesia and weakness of the right arm. Repeat MRI showed multiple new active lesions. This case report illustrates that multiple ring-enhancing lesions in the brain MRI can be seen in children with multiple sclerosis and that multiple sclerosis should be considered as part of the differential diagnosis when encountering a pediatric patient with similar radiographic findings.

Adolescent↗
PubMed2004

Autism and tuberous sclerosis.

The co-occurrence of autism spectrum disorder and tuberous sclerosis complex has been recognized for decades. The prevalence of tuberous sclerosis complex in the autism spectrum disorder population is 1 to 4%, whereas features of autism spectrum disorder are present in 25 to 50% of individuals with tuberous sclerosis complex. The underlying reason for this association might be a nonspecific disruption of brain function owing to tuberous sclerosis complex, including tuber location, seizures and their effect on brain development, cognitive impairment, a disturbance in brain development in regions associated with autism spectrum disorder, or, less likely, a linkage between a TSC gene and an autism susceptibility gene. Awareness of the relationship between autism spectrum disorder and tuberous sclerosis complex is important during the evaluation of individuals with either disorder. Better delineation of the association and its causative factors is needed for the development of possible interventions.

Autistic Disorder↗
PubMed1998

Tuberous sclerosis complex and neonatal seizures.

Tuberous sclerosis complex is a multisystemic neurocutaneous disorder, manifesting variably during infancy and childhood that remains poorly described in neonates. When described in this population, tuberous sclerosis complex is most commonly associated with cardiac rhabdomyomas and brain tumors, but is rarely mentioned as an etiology for neonatal seizures. We report two children with tuberous sclerosis presenting for neonatal seizures. Neuroimaging findings of neonatal tuberous sclerosis complex are discussed. Given the absence of many of the traditional stigmata of tuberous sclerosis complex in the neonate, seizures should be considered an important presenting feature of this disorder in this particular age group.

Brain↗
PubMed1995

Clinical and subclinical neurological involvement in children of conjugal multiple sclerosis patients.

We report the occurrence of clinically definite multiple sclerosis in an offspring of a couple with conjugal multiple sclerosis. Extensive investigation of all members of this family, which includes two additional asymptomatic children, eliminated the possibility of alternative neurological diagnoses. All family members were studied with magnetic resonance imaging (MRI), evoked potentials, and human leukocyte antigen (HLA) typing. An asymptomatic child had subtle white matter abnormalities on MRI, suggesting subclinical neurological involvement. This study documents the third case of multiple sclerosis in the child of conjugal multiple sclerosis patients and provides the first report of MRI lesions in an asymptomatic offspring of the same parents. Neurodiagnostic and immunogenetic investigations of such rare family clusters may contribute to the elucidation of the pathogenesis of multiple sclerosis.

Adolescent↗
PubMed1998

Cerebrospinal fluid and serum nitric oxide metabolites in patients with multiple sclerosis.

Nitric oxide is hypothesised to play a role in the immunopathogenesis of multiple sclerosis. Raised cerebrospinal fluid and serum levels of the nitric oxide metabolites nitrate and nitrite have been described in patients with multiple sclerosis. Cerebrospinal fluid and serum nitrate and nitrite were measured in patients with multiple sclerosis, inflammatory and non-inflammatory neurological diseases, and correlated with the albumin quotient, an index of blood-brain-barrier dysfunction. Patients undergoing diagnostic lumbar and vene puncture were prospectively recruited, clinical data were obtained from the hospital records, and the CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. Nitrate and nitrite, were raised in the CSF and serum of patients with multiple sclerosis and other inflammatory neurological diseases compared to patients with non-inflammatory neurological disorders (median nitrate and nitrite: cerebrospinal fluid = 10.3 microM vs 15.4 microM vs 6.6 microM, P < 0.001, and serum = 49.0 microM vs 46.4 microM vs 38.8 microM, P = 0.02, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient (n = 59, r = 0.42, P < 0.001). This study provides further evidence for a role of nitric oxide in the immunopathogenesis of multiple sclerosis and supports a role for nitric oxide as a possible mediator of inflammatory blood-brain-barrier dysfunction.

Adult↗
PubMed2006

Neuropsychiatric manifestations of multiple sclerosis.

Multiple sclerosis is one of the most frequently observed neurological causes of progressive disability in early to middle adulthood. The disease is variable in its presentation and course, affects roughly 100 to 300 per 100,000 persons within the US alone and is slightly more common among females than males. Multiple sclerosis places substantial burdens on patients, families and caregivers. Its presentation includes disturbances in cognitive abilities and psychiatric functioning, as well as motor difficulties. This article reviews the current literature on the neuropsychiatric manifestations of multiple sclerosis. Cognitive domains discussed include general cognitive functioning, learning and memory ability, attention, processing speed, executive functioning, visual perceptual ability and language functioning. Attention is also given to alterations in neuropsychiatric functioning associated with disease progression and across various disease subtypes. In addition, reports are also reviewed regarding various psychiatric disturbances, affective changes, quality of life issues and fatigue and pain in individuals with multiple sclerosis. Finally, factors pertaining to pediatric populations in multiple sclerosis are addressed.

Attention↗
PubMed2004

Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy.

BACKGROUND: What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. METHODS: Thirty one patients (9 male and 22 female) with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0-5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. RESULTS: A statistically significant correlation was found (r = -0.38 p < 0.05) between disability (measured by Expanded Disability Scale Score) and N-Acetyl Aspartate (NAA/Cr ratio) levels in normal appearing white matter in these patients. No correlation was found between the NAA/Cr ratio and disability measured by any of the other disability assessment scales. CONCLUSIONS: There is correlation between disability (measured by Expanded Disability Scale Score) and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor.

Adolescent↗
PubMed2005

Early B-cell Factor gene association with multiple sclerosis in the Spanish population.

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them.

Chromosome Mapping↗
PubMed2006

Validation of the severity index by cardiac catheterization and Doppler echocardiography in patients with aortic sclerosis and stenosis.

The severity index is a new echocardiographic measure that is thought to be an accurate indicator of aortic leaflet pathology in patients with AS. However, it has not been validated against cardiac catheterization or Doppler echocardiographic measures of AS severity nor has it been applied to patients with aortic sclerosis. The purposes of this study were to compare the severity index to invasive hemodynamics and Doppler echocardiography across the spectrum of calcific aortic valve disease, including aortic sclerosis and AS. 48 patients with aortic sclerosis and AS undergoing echocardiography and cardiac catheterization comprised the study population. The aortic valve leaflets were assessed for mobility (scale 1 to 6) and calcification (scale 1 to 4) and the severity index was calculated as the sum of the mobility and calcification scores according to the methods of Bahler et al. The severity index increased with increasing severity of aortic valve disease; the severity indices for patients with aortic sclerosis, mild to moderate AS and severe AS were 3.38 +/- 1.06, 6.45 +/- 2.16 and 8.38 +/- 1.41, respectively. The aortic jet velocity by echocardiography and the square root of the maximum aortic valve gradient by cardiac catheterization correlated well with the severity index (r = 0.84, p < 0.0001; r = 0.84, p < 0.0001, respectively). These results confirm that the severity index correlates with hemodynamic severity of aortic valve disease and may prove to be a useful measure in patients with aortic sclerosis and AS.

Aortic Valve Insufficiency↗
PubMed2002

Validity of the TEMPA for the measurement of upper limb function in multiple sclerosis.

OBJECTIVE: To investigate concurrent and construct validity of the TEMPA (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Agées) in patients with upper limb dysfunction due to multiple sclerosis. SUBJECTS: Forty-three patients with upper limb dysfunction due to multiple sclerosis. DESIGN: Patients performed upper limb tests and were assessed on measures of functional independence. SETTING: National Multiple Sclerosis Centre, Melsbroek, Belgium. MAIN OUTCOME MEASURES: TEMPA, Jebsen Handfunction Test, Nine Hole Peg Test, Functional Independence Measure (FIM) and activities of daily living (ADL) self-questionnaire. RESULTS: The correlation between TEMPA and Jebsen Handfunction and the Nine Hole Peg test respectively is good (0.56-0.87) and high (0.79-0.9). The correlation between TEMPA and the FIM and ADL self-questionnaire was moderate (0.44-0.61) although mostly higher than the correlation between the Jebsen Handfunction and the Nine Hole Peg test respectively and the measures of functionality (0.22-0.55/0.1-0.47). CONCLUSIONS: This study provides data supporting the concurrent validity of the TEMPA with the Jebsen Handfunction and the Nine Hole Peg Test in patients with multiple sclerosis. The results suggest construct validity of the TEMPA for the measurement of functionality during activities of daily life in patients with upper limb dysfunction due to multiple sclerosis.

Activities of Daily Living↗
PubMed2006

Health problems and health-related quality of life in people with multiple sclerosis.

OBJECTIVE: To explore the interrelationship between a number of common multiple sclerosis-related problems and health-related quality of life independent of the effect of physical disease impact. DESIGN: A cross-sectional postal survey. SETTING: The study was conducted in seven treatment centres within England. SUBJECTS: Nine hundred and twenty-nine people with multiple sclerosis. MEASURES: The severity of the multiple sclerosis problems (fatigue, pain, urinary incontinence, bowel, depression, pressure ulcers, sexual and employment problems) was assessed using 5-point self-report ordinal scales. Disease impact was measured using the Multiple Sclerosis Impact Scale-29. Health-related quality of life was measured using the 36-Item Short Form Health Survey, version 2 (SF-36). The relationship between the problems, disease impact and health-related quality of life was determined using multivariate analysis of covariance. RESULTS: Seventy four per cent of the sample experienced four or more of the selected problems. The extent and severity of problems increased with the level of disease impact (P< 0.001). Fatigue, pain, employment, depression and relationship problems were all found to have negative effect on the SF-36 scales independent to the effect of disease impact. SF-36 scores were most compromised in patients experiencing multiple problems. The data suggest an interdependent relationship between depression, fatigue and pain. CONCLUSION: The data suggest that many multiple sclerosis complications negatively affect health-related quality of life, independent of the effect of overall disease impact.

Adolescent↗
PubMed2006

Activities of daily living and social activities in people with multiple sclerosis in Stockholm County.

OBJECTIVE: To describe independence in personal and instrumental activities of daily living (ADL), and frequency of social/lifestyle activities in a population-based sample of people with multiple sclerosis in Stockholm. DESIGN: Population-based survey. SETTING: Data collection in home environment. SUBJECTS: One hundred and sixty-six people with multiple sclerosis. INTERVENTIONS: Data were collected using measurements and structured interviews. MAIN MEASURES: Independence in ADL was assessed by the Barthel Index; independence in personal and instrumental ADL by the Katz Extended ADL Index; and frequency of social/lifestyle activities by the Frenchay Activities Index. RESULTS: The mean age was 51 +/- 12 years in the included 166 people with multiple sclerosis, of whom 71% (n = 118) were women. Fifty-two per cent (n = 85) were independent in personal ADL, 30% (n = 50) in instrumental ADL, and 35% (n = 57) had normal frequency of social/lifestyle activities. Most frequently affected ADL items were cleaning indoors and outdoors transportation (62%, n = 102) and the social/lifestyle items of household maintenance (59%, n = 97), walking outside (59%, n = 97), heavy housework (61%, n = 100), and gardening (68%, n = 112). CONCLUSIONS: ADL and social/lifestyle activities were affected in two-thirds of people with multiple sclerosis in Stockholm. The most affected items were items that could be classified as mobility-related and physically demanding, underlining the importance of developing and using evidence-based exercise treatments and rehabilitation to increase independence in people with multiple sclerosis in Stockholm.

Activities of Daily Living↗
PubMed1975

Quantitative estimation of cerebrospinal fluid globulins in multiple sclerosis. A comparison of electrophoretic and immunologic methods.

CSF samples were obtained from 44 multiple sclerosis patients during exacerbation and from 50 age and sex-matched non-multiple sclerosis controls. In an attempt ot select the most suitable test for diagnosis of multiple sclerosis, each sample was analyzed by three methods: (1) electrophoresis, (2) electroimmunodiffusion, and (3) radial immunodiffusion (RID). Electrophoresis, electroimmunodiffusion, and radial immunodiffusion yielded positive results in 50, 55, and 59 percent of the multiple sclerosis patients respectively. Electrophoresis, electroimmunodiffusion, and radial immunodiffusion yielded 10, 12, and 8 percent false positives (beyond mean +/- 1 S.D.) respectively. Thus the three tests did not differ much with regard to yield of true or false positive results. When factors such as simplicity, time and equipment involved, and the interval between the test and results are taken into account, radial immunodiffusion appears to be most suitable for an avverage CSF diagnostic laboratory. For a laboratory with special interest in multiple sclerosis, agarose gel-electrophoresis of concentrated CSF appears to be the test of choice.

Adult↗
PubMed1976

Genetic association of multiple sclerosis and HL-A determinants.

Segregation of HL-A haplotypes was analyzed in 10 families in which there were at least two cases of multiple sclerosis. In nine families, multiple sclerosis was associated with only one parental HL-A haplotype. Specific HL-A determinants associated with multiple sclerosis differed among the families, suggesting that another histocompatibility-linked factor, possibly a gene determining susceptibility (or lack of resistance) played an etiologic role. Lod score analysis based on nine families suggested a close association between such a gene (labeled MSS) and the HL-A gene complex. However, when all 10 available families were analyzed, the association approached but did not reach statistical significance. Thus, the HL-A haplotype segregation did not prove that a histocompatibility-linked gene is related to the cause of multiple sclerosis, but study of additional multiplex families is certainly warranted. Other factors, possibly genetic (although not HL-A-linked), environmental, or the two together, may be required for multiple sclerosis to become clinically apparent.

Epitopes↗
PubMed1977

Myelin encephalitogenic protein fragments in cerebrospinal fluid of persons with multiple sclerosis.

With a double-antibody radioimmunoassay performed on unconcentrated cerebrospinal fluid, eight of 14 patients in an acute phase of multiple sclerosis had levels of 3.4 to 15.4 ng per milliliter of the P1 fragment (residues 43-88) of myelin encephalitogenic protein. Encephalitogenic protein-P1 was found only in the acute phase and was present in six of seven persons in the first week of an exacerbation and absent in 29 multiple sclerosis patients who were stable or had a gradually progressive course. Six of 117 controls had detectable cerebrospinal fluid encephalitogenic protein-P1. Only in two of these, one with a recent cerebral infarction and one with diabetic nephropathy who was in coma, were the levels in the range encountered in patients in the acute phase of multiple sclerosis. Although not entirely specific for multiple sclerosis, the presence of material in the cerebrospinal fluid of multiple sclerosis patients cross-reacting with encephalitogenic protein-P1 appears to be a characteristic of acute exacerbations.

Adolescent↗
PubMed1977

Multiple sclerosis in Asia.

Cases of multiple sclerosis were collected by Asian neurologists from recognized medical centers, using standardized formats similar to those used for the Japan nationwide multiple sclerosis survey. As a result, information on a total of 61 cases was collected from six neurologic centers in five Asian countries excluding Japan. Multiple sclerosis appears to be a rare disease throughout Asia. Certain clinical characteristics that had been previously noted in Japanese and other individual Asian series were again observed in the present Asian series. When compared with Western multiple sclerosis, the Asian multiple sclerosis cases showed a relatively higher frequency of optic nerve involvement, frequently bilateral and severe, at the onset, as well as during the course of illness, and no rare occurrence of Devic's syndrome.

Asia↗
PubMed1987

Cystatin C, alias post-gamma-globulin: a marker for multiple sclerosis?

Cystatin C, alias post-gamma-globulin or gamma-trace protein, has been shown to be a potent inhibitor of cysteine proteinases; this protein is normally present in different biological fluids, but particularly so in cerebrospinal fluid. The concentration of cystatin C was determined by radial immunodiffusion in cerebrospinal fluid from patients affected with multiple sclerosis, patients affected with various neurological diseases and in controls; it was also determined in brain tissue from 2 patients affected with multiple sclerosis and 3 control brains. Cystatin C cerebrospinal fluid levels were undetectable or depressed in many multiple sclerosis cases and the median value differed significantly from the control one. Its low concentration in multiple sclerosis suggests that the regulation of cysteine proteinases is impaired in this disease; hence enhanced activity of cysteine proteinases could initiate, or increase the breakdown of myelin. Although it is perhaps a little premature to consider cystatin C as a marker for multiple sclerosis, this protein is nevertheless associated to demyelination; consequently its biochemical assay in cerebrospinal fluid is recommended as a complementary diagnostic tool.

Adolescent↗