A risk of developing multiple sclerosis following an outbreak of optic neuritis during a mean follow-up of 4.5 years

OBJECTIVE: The current study was designed to determine the risk of developing clinically definite multiple sclerosis (CDMS) after an isolated idiopathic optic neuritis (ON). PATIENTS AND METHODS: We retrospectively studied 28 patients (range from 18-45 years) who presented a unilateral acute ON between 1 st April and 31 st December. We excluded optic neuropathy of other causes, a previous diagnosis of MS or systemic diseases associated with ON. Patients underwent brain MRI, visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs). The mean interval between ON onset and MRI was 3.1 months. 24 patients were treated with corticosteroids in different ways: oral prednisone (14) and intravenous methylprednisolone (10). Mean duration of the follow-up was 4.5 years in 26 patients. RESULTS: Brain MRI detected white matter areas with increased signal in 10 of 25 patients (40%). Eight (30%) had bilateral anormalities on VEP, while SEPs and BAEPs revealed anormalities in one patient (5.5%). Two out 26 patients (7.7%) developed CDMS; one was treated with oral prednisone and the other with intravenous corticosteroids. No patients with normal MRI developed MS compared to 20% of patients with lesions on initial brain MRI. The only patient with abnormal SEPs and BAEPs did not develop MS. CONCLUSIONS: We found in our population low rate of developing CDMS with higher risk for those ON with abnormalities on initial brain MRI.     

Soluble ICAM-1, demyelination, and inflammation in multiple sclerosis and acute optic neuritis

We measured sICAM-1 in paired samples of serum and cerebrospinal fluid (CSF) from patients with an attack of multiple sclerosis (MS) (n = 50) and patients with acute monosymptomatic optic neuritis (ON) as a possible first attack of MS were also included (n = 25). Based on calculations of extended indices we found evidence of intrathecal synthesis of sICAM-1 both in patients with clinically definite MS and in patients with idiopathic ON compared to neurological control subjects. The amount of intrathecally synthesized sICAM-1 correlated significantly to the CSF leukocyte count and to the concentration of myelin basic protein in the CSF. The serum concentrations of sICAM-1 were not increased in patients with demyelinating disease compared to the neurological control subjects.     

Risk factors for multiple sclerosis: a case-control study in Israel

This case-control study was aimed at identifying environmental risk factors for multiple-sclerosis (MS). Ninety-three Israeli-born MS patients identified in country-wide studies and 94 age- and sex-matched controls were interviewed. The questionnaire covered a large span of factors at ages 0, 10 and onset of the disease, with particular emphasis on socioeconomic status (SES) and sanitary conditions (SAN). A significantly larger percentage of patients reported frequent respiratory educational levels than controls. The SES and SAN at age 10 were also systematically higher among patients, but significance was reached only when the frequencies of conditions indicating extremely low values of SES or SAN were compared. It is possible that the protective effect of low SES or SAN on risk of MS can be detected only when living conditions are well below average, as is frequent in developing countries.     

Risk factors for reduced pulmonary function after malignant lymphoma in childhood

The aim was to study pulmonary function after Hodgkin disease or non-Hodgkin Lymphoma in childhood and to evaluate if younger age at diagnosis and therapy is a risk factor for reduced pulmonary function. We studied a population-based sample of survivors of Hodgkin disease (n = 22) or non-Hodgkin lymphoma (n = 19) in childhood. Pulmonary function test results were compared with reference values for our laboratory, generated by adjusting published reference values fit 348 healthy never-smokers from a local population study. Data were analyses as standardised residuals, which are [observed minus predicted value] divided by the residual standard deviation of the reference equations. At a median of 11 years after diagnosis (range 2 to 24), the participants had significantly reduced lung volumes and transfer factor, unrelated to the few pulmonary symptoms. On average, the total lung capacity was reduced to -0.9 standardised residual and the transfer factor was reduced to -1.3 standardised residual. Young age at therapy seemed to be a risk factor for reduced lung function, especially when treatment included thoracic irradiation. No significant toxic synergism was observed between smoking and previous cancer therapy. Therapy without thoracic irradiation but with doxorubicin and cyclophosphamide was almost as toxic to lung function as therapy with thoracic irradiation but without doxorubicin and cyclophosphamide. In conclusion, lung volumes and transfer factor were reduced several years after childhood Hodgkin disease of non-Hodgkin lymphoma, with young age at therapy as a risk factor, especially when combined with thoracic irradiation.     

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.     

Risk factors for multiple intracranial aneurysms

OBJECTIVE: Risk factors that predispose to the formation of multiple intracranial aneurysms, which are present in up to 34% of patients with intracranial aneurysms, are not well defined. In this study, we examined the association between known risk factors for cerebrovascular disease and presence of multiple intracranial aneurysms. METHODS: We reviewed the medical records and results of conventional angiography in all patients with a diagnosis of intracranial aneurysms admitted to the Johns Hopkins University hospital between January 1990 and June 1997. We determined the independent association between various cerebrovascular risk factors and the presence of multiple aneurysms using logistic regression analysis. RESULTS: Of 419 patients admitted with intracranial aneurysms (298 ruptured and 121 unruptured), 127 (30%) had multiple intracranial aneurysms. In univariate analysis, female gender (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.1-3.3) and cigarette smoking at any time (OR = 1.8; 95% CI, 1.1-3.0) were significantly associated with presence of multiple aneurysms. In the multivariate analysis, cigarette smoking at any time (OR = 1.7; 95% CI, 1.1-2.8) and female gender (OR = 2.1; 95% CI 1.2-3.5) remained significantly associated with multiple aneurysms. Hypertension, diabetes mellitus, and alcohol and illicit drug use were not significantly associated with presence of multiple aneurysms. CONCLUSION: Cigarette smoking and female gender seem to increase the risk for multiple aneurysms in patients predisposed to intracranial aneurysm formation. Further studies are required to investigate the mechanism underlying the association between cigarette smoking and intracranial aneurysm formation.     

Residual symptoms and signs after untreated acute optic neuritis. A one-year follow-up

PURPOSE: To study the symptoms and signs one year after optic neuritis. METHODS: Seventy population-based untreated patients, (44F, 26M; median age 35 years, range 14-48 years) were eligible for study, but the 11 bilateral cases were excluded. Among 59 patients participating in a one-year follow-up of the visual function, 58 answered a questionnaire. RESULTS: At follow-up 59% of the patients complained of visual impairment, though 49% of these patients had a Snellen visual acuity of 6/9 or better. The affected eyes showed decreased visual acuity in 34%, decreased contrast sensitivity in 63%, an abnormal score in 40% with the Lanthony D-15 desaturated panel, and in 13% with the Ishihara test, prolonged latencies of VEP in 58%, and decreased amplitudes of VEP in 41%. CONCLUSIONS: All tests except for VEP correlated significantly to the degree of perceived visual impairment. Subjective visual complaints and more sensitive tests than visual acuity should be used to evaluate the visual function following optic neuritis.     

Personality factors and change with multiple sclerosis.

Assessed body-image variables, depression, and locus of control (Rotter's Internal–External Locus of Control Scale) in relation to age, duration of disease, and degree of disability in a cross-sectional study of 60 22–72 yr old multiple sclerosis (MS) outpatients. Results indicate that internal locus of control was negatively related to depression but was uncorrelated with disease duration or disability. Body-image anxieties were highest in the early stages of the disease when impairment was least severe but were unrelated to depression. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bioelectromagnetic applications for multiple sclerosis

There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.     

Interferon beta for multiple sclerosis

OBJECTIVE: To introduce readers to the use of a new agent, interferon beta-1b (IFN beta ser), in the treatment of relapsing-remitting multiple sclerosis (RRMS). Therapeutic and economic issues surrounding IFN beta ser are discussed, as are its pharmacology, clinical efficacy, adverse effects, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including clinical trials and reviews. STUDY SELECTIONS: All available trials were reviewed. DATA EXTRACTION: Since trials evaluating subcutaneously administered interferon beta are sparse, clinical trials evaluating intrathecal IFN beta ser were included, as was toxicology information from the oncology population. DATA SYNTHESIS: IFN beta ser has recently been approved by the Food and Drug Administration for the treatment of RRMS. Its exact mechanism of action is unknown, but it may downregulate interferon gamma (IFN gamma) production and the IFN gamma-stimulated major histocompatibility complex antigen expression, and/or augment T-suppressor cell function. Primary adverse effects include flu-like symptoms, fever, chills, myalgia, sweating, and injection-site reactions. Clinical efficacy has been investigated in 372 ambulatory patients with RRMS. IFN beta ser treatment resulted in a reduction in the annual exacerbation rate and a greater proportion of exacerbation-free patients. Burden of central nervous system disease was also significantly reduced in treated patients. However, no reductions were detected on the Scripps Neurologic Rating Scale or with confirmed endpoint scores on the Kurtzke Expanded Disability Status Scale. Although many questions remain concerning IFN beta ser's long-term efficacy, its benefits in patients with other types of multiple sclerosis (MS), and its effect on progression of disease and ultimate disability, IFN beta ser is the first treatment modality that has substantially altered the natural course of MS in a controlled clinical trial. CONCLUSIONS: IFN beta ser is not a cure for MS, but it is well tolerated and patients with RRMS have shown significant improvements in exacerbation rates and burden of central nervous system disease. IFN beta ser should be considered a definite improvement in RRMS treatment, although many therapeutic issues remain unanswered. Additional clinical trials are needed.     

Nitric oxide synthase in developing retinas and after optic tract section

Protein kinase C (PKC) is a key enzyme in the intracellular signaling network. Upon activation by 12-O-tetradecanoylphorbol 13-acetate, the alpha-isoform of PKC translocates to the detergent-soluble and the detergent-insoluble fractions. Besides cofactors, the activity and stability of this protein is critically regulated by multisite phosphorylations. At least three distinct sites, Thr497, Thr638 and Ser657, are involved. We have previously shown that the replacement of Ser657 by alanine leads to a premature down-regulation in the detergent soluble compartment of LLC-PK1 cells [Gysin, S. & Imber, R. (1996) Eur. J. Biochem. 240, 747-750]. More detailed analysis revealed that, in contrast to the wild-type molecule, the down-regulation of the mutant protein is in vivo preceded by a rapid dephosphorylation after phorbol-ester-induced translocation to both the detergent-soluble and insoluble compartments. The [Ala657]PKC-alpha mutant protein molecule showed in vitro a strongly increased sensitivity towards protein phosphatase 2A whereas its overall proteolytic sensitivity remained unchanged when compared to wild type. The in vitro studies led to the suggestion that further dephosphorylation of the mutant protein is a prerequisite in order to become proteolytically down-regulated. Therefore phosphorylation of Ser657 controls the duration of activation of this PKC isozyme upon agonist-induced translocation by preventing premature proteolytic down-regulation via protecting the protein from dephosphorylation.     

Nutritional factors and multiple sclerosis in Gorski Kotar, Croatia

An analysis was made of the possible influence of nutritional factors on the etiology of multiple sclerosis in Gorski Kotar (Croatia), a high-risk zone for this disease. A total of 46 MS patients and 92 controls, native-born residents of the area studied, participated in a case-control study. The questionnaire comprised 51 questions concerning dietary habits. An odds ratio (OR) estimate was obtained for all the factors which were more frequently found in the patients than in the controls. Large differences were found in the daily consumption of different quantities of full fat unskimmed milk (OR 21.7; chi 2 42.34; LL 7.12), potatoes with lard and fresh or smoked meat (OR 20.7; chi 2 15.52; LL 2.72), and new potatoes (OR 20.7; chi 2 15.52; LL 2.72). The consumption of unpasteurized milk, animal fat, smoked meat and potatoes are nutritional risk factors which could have an influence on the severity of primary demyelinization in a high-risk area for multiple sclerosis.     

Bilateral optic neuropathy with IgGkappa multiple myeloma improved after myeloablative chemotherapy

A 49-year-old woman with immunoglobulin GK multiple myeloma developed progressive visual loss with bilateral upper and lower central arcuate scotomas. Funduscopic and electrophysiologic studies indicated bilateral optic neuropathy. The immunoglobulin G fraction of the patient's serum reacted with retinal ganglionic cells in bovine retina. The visual abnormalities remitted after myeloablative chemotherapy and disappearance of the paraprotein.     

Risk factors for stress in children after parental stroke.

Objectives: To assess risk factors for stress in children 3 years after parental stroke. Participants: Questionnaires were filled in by 44 children aged 7–18 years, parents who suffered a stroke and healthy spouses from 29 families recruited in 9 participating rehabilitation centers across the Netherlands. Method: We measured patient functioning (cognitive disorders, communicative disorders and ADL dependency), parental depression and perceived quality of marital relationship at 4 assessments, from the start of rehabilitation until 3 years post-stroke. Children assessed their stress level 3 years after parental stroke. Results: Girls experienced more stress than boys. Spouses' depressive symptoms during the first year after stroke were positively correlated with stress in children. Patients' depressive symptoms 2 months post-rehabilitation (2 months after discharge from the rehabilitation center), 1 year and 3 years post-stroke were also positively correlated with stress in children. The perceived quality of marital relationship decreased over time and at 2 months postrehabilitation, it was related to stress in children. Stress was not related to patient gender and functioning. Conclusions: Early prediction of long-term stress in children after parental stroke may be most accurate on the basis of children's female gender and depressive symptoms of the patient. (PsycINFO Database Record (c) 2010 APA, all rights reserved)