Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SCLEROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,369 records · Page 76Linked to original sources
PubMed2002

A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis.

Genetic factors influence susceptibility to multiple sclerosis but the responsible genes remain largely undefined, association with MHC class II alleles being the only established genetic feature of the disease. The Nordic countries have a high prevalence of multiple sclerosis, and to further explore the genetic background of the disease, we have carried out a genome-wide screen for linkage in 136 sibling-pairs with multiple sclerosis from Denmark, Finland, Norway and Sweden by typing 399 microsatellite markers. Seventeen regions where the lod score exceeds the nominal 5% significance threshold (0.7) were identified-1q11-24, 2q24-32, 3p26.3, 3q21.1, 4q12, 6p25.3, 6p21-22, 6q21, 9q34.3, 10p15, 10p12-13, 11p15.5, 12q21.3, 16p13.3, 17q25.3, 22q12-13 and Xp22.3. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.

Denmark↗
PubMed2006

Renal vascular sclerosis is associated with inherited thrombophilias.

Vascular sclerosis is often seen in renal biopsies. It is usually associated with diabetes mellitus, hypertension, smoking, etc. However, whether inherited thrombophilic states such as factor V gene mutation, prothrombin gene mutation, and methylenetetrahydrofolate reductase (MTHFR) gene mutation are associated with the vascular sclerosis is not known. Renal biopsies that showed vascular disease were grouped into five groups: (1) diabetic patients, (2) hypertensive patients, (3) diabetic and hypertensive patients, (4) smokers, and (5) vascular sclerosis of unknown etiology (idiopathic renal disease). Renal biopsies with no vascular sclerosis were used as controls. Frozen tissue was analyzed for factor V Leiden mutation, prothrombin G20210A mutation, and MTHFR C677T. Factor V Leiden mutation and prothrombin G20210A mutation was not seen in patients with diabetes, hypertension, or smoking, whereas MTHFR C677T polymorphism in these groups was not significant, compared to the controls. In the idiopathic renal disease group, three of the 17 patients (17.6%) had prothrombin G20210A mutation, two of the 17 patients (11.8%) had the factor V Leiden mutation, and five of the 17 (29.4%) were homozygous for the MTHFR C677T polymorphism. When the data were evaluated as a whole, 10 mutations were found in 17 patients (P<0.0005 compared to controls) or eight of the 17 patients (47%) were observed to have at least one of the three forms of inherited thrombophilia (P<0.001 compared to controls). These findings indicate that renal vascular lesions, in the absence of diabetes, hypertension, or smoking appears to be associated with inherited thrombophilias.

Adult↗
PubMed1999

Multiple sclerosis with extensive lesions left hemiplegia, mental dysfunction and retrobulbar neuritis.

Multiple sclerosis (MS) is usually diagnosed on the basis of the typical clinical course, with remission and exacerbation in multiple parts of the central nervous system (CNS). Recently, magnetic resonance imaging (MRI) has made a large contribution to the diagnosis of patients with MS. But it is difficult to make a definite diagnosis due to clinical variability of the disease and variable MRI findings. We report the case of a 26-year-old woman who developed progressive left hemiplegia, mental dysfunction, and had extensive bilateral cerebral white matter lesions diagnosed by brain MRI. Complete recovery from the left hemiplegia followed the use of corticosteroid, and her brain MRI findings also improved after medication. Early in the clinical course it was difficult to differentiate between multiple sclerosis and granulomatous angiitis of the CNS. After recovery from the first episode of left hemiplegia and mental dysfunction, she developed acute visual disturbance five months after her first admission. Readmission followed and her retrobulbar neuritis was successfully treated by methylpredonisolone pulse therapy. In summary, she experienced two episodes of neurological deficit, had left hemiplegia and mental dysfunction associated with multiple lesions in bilateral cerebral white matter in brain MRI, and the left retrobulbar neuritis with delay of P100 by visual evoked potential study. Due to these two episodes we concluded that she had multiple sclerosis. Though the initial diagnosis was difficult, prompt treatment and close follow-up was important, since multiple sclerosis and granulomatous angiitis of the CNS can both recur.

Adult↗
PubMed2001

Renal angiomyolipoma associated with micronodular pneumocyte hyperplasia of the lung with tuberous sclerosis.

Tuberous sclerosis complex is an autosomal-dominant disorder characterized by the triad of mental retardation, epilepsy and adenoma sebaceum. Micronodular pneumocyte hyperplasia is a rare but distinctive pulmonary epithelial lesion, usually associated with tuberous sclerosis. To the authors' knowledge, the relationship between renal angiomyolipoma and micronodular pneumocyte hyperplasia in cases of tuberous sclerosis has not received attention in the urological literature. The case of a woman with renal angiomyolipomas associated with micronodular pneumocyte hyperplasia of the lung with tuberous sclerosis is reported here.

Adult↗
PubMed2000

Symptomatic intraocular inflammation in multiple sclerosis.

PURPOSE: The aim of this study was to determine the type and outcome of uveitis in patients with multiple sclerosis. METHODS: A retrospective study of 16 patients attending the uveitis clinic who had a clinically definite diagnosis of multiple sclerosis and symptomatic intraocular inflammation. The type of uveitis and complications present as well as the outcome of therapeutic intervention, either medical or surgical, was determined. RESULTS: Chronic, bilateral anterior uveitis was present in six patients. Secondary cataracts requiring surgery occurred in 10 eyes, and trabeculectomy was done on five eyes for secondary glaucoma. Symptomatic vitritis (visual blurring and/or visually significant floaters) occurred in eight patients and was bilateral in four. Occlusive peripheral retinal vasculitis with subsequent areas of ischaemia and neovascularization requiring panretinal laser photocoagulation developed in eight eyes, five of which also required vitrectomy. Other posterior segment complications included macular oedema (four) and epiretinal membrane involving the macula (two). Five patients required systemic steroids for control of posterior uveitis. The median visual improvement following cataract surgery or vitrectomy was 3 Snellen lines to a median visual acuity of 6/18. CONCLUSIONS: A wide range of clinical patterns of uveitis, which may be both symptomatic and sight-threatening, occur in patients with multiple sclerosis. In addition, the complications of uveitis may cause significant visual morbidity, much of which is amenable to appropriate surgical intervention. It is important that these potentially remediable conditions are recognized and treated to ensure that patients with multiple sclerosis retain optimum visual function.

Adult↗
PubMed2002

Delayed sclerosis, neuroprotection, and limbic epileptogenesis after status epilepticus in the rat.

PURPOSE: Hippocampal sclerosis and massive neurodegeneration in other parts of the limbic system are considered hallmarks of temporal lobe epilepsy. Using the rat model of kainate-induced status epilepticus, we sought to determine if limbic sclerosis after an excitotoxic insult follows a delayed type of neurodegeneration and is thus accessible to neuroprotective intervention after the insult. Effective pharmacologic neuroprotection after status epilepticus also addresses the old question of whether degenerative morphologic changes after an epilepsy-inducing event like status epilepticus are the primary cause of epileptogenesis (i.e., the development of recurrent spontaneous seizures) during the following weeks. METHODS: Female Wistar rats after 90 min of generalized status epilepticus were used. Molecular biologic and histologic techniques were used to demonstrate markers of delayed cell death (apoptosis) 48 h after the status. The neuroprotective effects of i.c.v. injections of caspase inhibitors and systemic injections of the anticonvulsant drugs (AEDs) dizocilpine and retigabine after the status epilepticus were studied. The effect of neuroprotective intervention on the development of recurrent spontaneous seizures was investigated by behavioral observation of the rats. RESULTS: After generalized status epilepticus in Wistar rats, massive sclerosis of the hippocampus and the piriform cortex occurred. TUNEL labeling and electron microscopy revealed that apoptosis is involved in the degenerative processes. Immunohistochemical analysis of the time course of the expression of the proapoptotic protein Bax suggested a maximal induction of apoptosis 24-48 h after the status. Application of caspase inhibitors before or after the status did not reduce lesions, although Bax labeling was reduced. Injection of dizocilpine and to a lower extent also of retigabine after the status prevented limbic neurodegeneration and expression of markers of apoptosis. However, the neuroprotection by dizocilpine did not prevent the development of recurrent spontaneous seizures. CONCLUSIONS: Prolonged seizure activity can induce delayed sclerosis in the hippocampus and other parts of the limbic system. This delayed cell loss can be prevented by neuroprotective drugs after a status epilepticus. However, the damage in limbic brain regions is not the main reason for limbic epileptogenesis and the occurrence of recurrent spontaneous seizures.

Animals↗
PubMed2005

Acute-onset, steroid-sensitive, encapsulating peritoneal sclerosis in a renal transplant recipient.

Encapsulating peritoneal sclerosis is a severe complication of peritoneal dialysis. Immunosuppressive drugs have been claimed to be helpful in the treatment of this disease, although the pathophysiological background is poorly understood. In this report, we present a patient with encapsulating peritoneal sclerosis after successful renal transplantation. Maintenance immunosuppressive therapy consisted of mycophenolate mofetil, tacrolimus, and low-dose corticosteroids. The patient was treated successfully with high doses of corticosteroids. A subsequent relapse of the encapsulating peritoneal sclerosis, probably resulting from fast tapering of the corticosteroid dose, responded well to an increase in corticosteroid dose. Our case strongly supports a therapeutic role for high-dose steroids in the treatment of encapsulating peritoneal sclerosis during its initial inflammatory stage.

Acute Disease↗
PubMed1990

Tuberous sclerosis in pregnancy.

Tuberous sclerosis is an autosomal dominant disorder of hamartoma formation in which manifestations may occur in skin, brain, and viscera. In the past, it was believed that the typical presentation included seizures, mental retardation, and facial angiofibromas ("adenoma sebaceum"). This disorder is now recognized to show wide variability of expression. There are only four cases of tuberous sclerosis in pregnancy in the literature. Two of these had favorable maternal and fetal outcomes and the remaining two presented with serious maternal and fetal complications. These included acute intra-abdominal bleeding due to a ruptured renal tumor, which led to renal failure requiring hemodialysis, and severe preeclampsia with pathologically enlarged kidneys noted at the time of cesarean section. This study presents two more cases of tuberous sclerosis in pregnancy. The first case had renal involvement with bleeding into a renal cyst, renal failure, preeclampsia, and severe intrauterine growth retardation. The second case was complicated by preterm premature rupture of the membranes and preterm labor. Renal involvement appears to be the single most important prognostic factor in pregnancies with tuberous sclerosis. Renal evaluation should be performed in any patient who presents for preconceptional counseling.

Adult↗
PubMed1997

[Optic nerve neuritis after 50 years of age: symptom of a previously undiagnosed multiple sclerosis].

BACKGROUND: The onset of multiple sclerosis after the age of 50 years is rare. We report four patients with optic neuritis and oligoclonal bands or increased IgG production in the cerebrospinal fluid. Three of them subsequently developed clinically definite multiple sclerosis. PATIENTS: Four apparently healthy women, 62, 56, 50 and 50 years of age, presented with progressive visual loss, three patients in one eye and one patient in both eyes. The diagnostic work-up revealed no findings indicating an ischemic process, an infectious, systemic inflammatory, or neoplastic disease. Examination of the cerebrospinal fluid revealed oligoclonal bands and/or increased production of IgG. Visual acuity recovered during the following weeks to 8 months. Three of the 4 patients subsequently developed additional neurologic signs compatible with multiple sclerosis. CONCLUSION: Optic neuritis can be the presenting sign of multiple sclerosis even after the age of 50.

Diagnosis, Differential↗
PubMed1985

A case of childhood multiple sclerosis with peripheral neuropathy.

A twelve-year-old girl with multiple sclerosis and peripheral neuropathy is reported. When nine years old, she was diagnosed as having Devic disease (optic atrophy and transverse myelitis). During the three years after onset of her illness, she suffered from three relapses and remissions of her multiple sclerosis. On the third occasion, neurological examination revealed signs of cerebellar dysfunction including ataxic gait, nystagmus and dysmetria, and absence of all tendon reflexes with muscle weakness especially on the left side. Markedly slowed conduction velocity in her ulnar nerve especially on the left and elevated CSF protein were noted. Biopsied sural nerve showed decreased density of myelinated fibers and a selective loss of large diameter fibers. Electron microscopy disclosed onion-bulb formation, myelin debris within Schwann cell cytoplasm and demyelinated axons. These findings showed demyelination and remyelination of the peripheral nervous system in this patient with multiple sclerosis. We discuss the relation of multiple sclerosis and peripheral neuropathy.

Biopsy↗
PubMed1991

Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity.

BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. METHODS AND RESULTS: We evaluated 23 families with familial amyotrophic lateral sclerosis for linkage of the gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score--5.03--was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P less than 0.0001) of genetic-locus heterogeneity in the families. CONCLUSIONS: The localization of a gene causing familial amyotrophic lateral sclerosis provides a means of isolating this gene and studying its function. Insight gained from understanding the function of this gene may be applicable to the design of rational therapy for both the familial and sporadic forms of the disease.

Adolescent↗
PubMed2000

Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group.

BACKGROUND: Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value. METHODS: We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis. RESULTS: During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months. CONCLUSIONS: Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.

Adult↗
PubMed2002

Birth outcomes and need for hospitalization after delivery among women with multiple sclerosis.

OBJECTIVE: The purpose of this study was to determine whether women with multiple sclerosis who deliver singleton infants are more likely to have pregnancy or delivery complications or to have infants with low birth weight, preterm gestation, or malformations than women without multiple sclerosis and to compare their need for rehospitalization during the 2 years after delivery. STUDY DESIGN: This was a population-based cohort study that used Washington State linked birth certificate-hospital discharge records for singleton births from 1987 through 1996. Pregnancy course, birth outcomes, and need for rehospitalization within 2 years after delivery were compared for 198 women with multiple sclerosis and a comparison group of 1584 women. RESULTS: With the exception of maternal anemia, women with multiple sclerosis were no more likely to have pregnancy or delivery complications, nor were their infants more likely to be low birth weight or preterm or to have malformations. Affected women were, however, twice as likely to be rehospitalized during the 3 months after delivery. CONCLUSION: The increased risk of rehospitalization emphasizes a need for strong support systems and close monitoring during the 3 months after delivery.

Adult↗
PubMed1979

Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis.

Lymphocytes from normal adult donors exposed in vitro to inactivated measles virus were found to exert significant suppression (33.9%) of the concanavalin A responses of cryopreserved, autochthonous responder cells. In marked contrast, lymphocytes from multiple sclerosis patients exhibited significantly reduced suppression (1.5%), and in 80% of cases failed to suppress at all. The degree of suppression increased slightly with age of the patient but did not vary with the clinical stage of disease. There was no apparent genetic restriction of suppressor activity. Although specificity of this phenomenon for measles virus has not been established, no differences in the responses of lymphocytes from normal or multiple sclerosis patient donors were found with subacute sclerosing panencephalitis, Sendai, canine distemper, mumps, or influenza viruses. Supernates of measles-treated lymphocytes from normal donors possessed both suppressive and antiviral activities. Both activities were resistant to pH 2 treatment and were neutralized by an anti-human leukocyte interferon antiserum, strongly suggesting that interferon (probably type I) was the mediator of suppression. Consistent with their inability to suppress concanavalin A responses, lymphocytes from multiple sclerosis patients failed to produce significant amounts of interferon in response to measles challenge in vitro. These results extend previous observations that multiple sclerosis patients are unable to respond appropriately to measles virus antigen in vitro.

Adult↗
PubMed1991

Preferential T-cell receptor beta-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis.

Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of beta-chain variable region (V beta) 5.2 and, to a lesser extent, V beta 6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of V beta 5.2 for BP recognition did not reflect altered expression of this V beta in the peripheral repertoire. Interestingly, shared V beta 5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express V beta 5.2 and V beta 6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.

Base Sequence↗
PubMed1995

Early onset of multiple sclerosis with autopsy confirmation.

A female had her first generalized epileptic seizure at age 11 yrs. Apart from intermittent seizures she remained well until 15 yrs of age when she developed double vision, unsteadiness and bilateral plantar responses which resolved spontaneously. Brain MRI scan at this stage revealed changes typical of multiple sclerosis. She died at 17 yrs of age from asthma and epilepsy. Autopsy confirmed the presence of multiple sclerosis and showed the disease to be very active. We consider it likely that multiple sclerosis was present at the age of 11 yrs when she had her first epileptic seizure. This case of multiple sclerosis is presented because of the rarity of the early age of onset, unusual presentation with epilepsy, marked activity of disease and early death. Also it is uncommon to have autopsy confirmation of such disease.

Adolescent↗
PubMed2006

Quantitative magnetic resonance imaging of brainstem volumes, plaques, and surface area in the occipital regions of patients with multiple sclerosis.

PURPOSE: To determine brainstem volumes, number of plaques, and surface areas in the occipital lobes of patients with relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and to investigate whether there is any correlation between brainstem volume and the number/surface areas of plaque in the occipital lobes. MATERIAL AND METHODS: Magnetic resonance imaging was obtained on 14 relapsing-remitting (RR) and 13 secondary progressive (SP) MS patients and 26 female control subjects. The Cavalieri method was used by modern design stereology to measure brainstem volume. The point-counting grid was used to evaluate sclerotic plaque surface areas in the occipital lobe. The number of plaques in the imaging section was calculated. RESULTS: Brainstem volumes for RR and SP with multiple sclerosis and control subjects were 3647 mm3, 3515 mm3, and 4517 mm3, respectively. Mean number of plaques in the right-left occipital lobe was found to be 2.7-3.4 in RR-MS and 5.2-2.8 in SP-MS. Mean plaque surface area in the right-left occipital lobe was determined to be 58.52-88.24 mm2 in RR MS and 124.3-64.82 mm2 in SP MS. Brainstem volumes were significantly reduced in both groups of patients with MS compared to controls (P < 0.01). CONCLUSION: Magnetic-resonance-estimated volume and surface area values in multiple sclerosis may facilitate our understanding of the clinical situation of patients and provide a simple index for evaluating therapeutic efficiency.

Adult↗
PubMed1998

White matter abnormalities in tuberous sclerosis complex.

PURPOSE: The aim of this study was to investigate and describe the range of white matter abnormalities in children with tuberous sclerosis complex by means of MR imaging. MATERIAL AND METHODS: A retrospective cross-sectional study was performed on the basis of MR imaging findings in 20 cases of tuberous sclerosis complex in children aged 17 years or younger. RESULTS: White matter abnormalities were present in 19/20 (95%) cases of tuberous sclerosis complex. These were most frequently (19/20 cases) found in relation to cortical tubers in the supratentorial compartment. White matter abnormalities related to tubers were found in the cerebellum in 3/20 (15%) cases. White matter abnormalities described as radial migration lines were found in relation to 5 tubers in 3 (15%) children. In 4/20 (20%) cases, white matter abnormalities were found that were not related to cortical tubers. These areas had the appearance of white matter cysts in 3 cases and infarction in the fourth. In the latter case there was a definable event in the clinical history, supporting the diagnosis of stroke. CONCLUSION: A range of white matter abnormalities were found by MR imaging in tuberous sclerosis complex, the commonest being gliosis and hypomyelination related to cortical tubers. Radial migration lines were seen infrequently in relation to cortical tubers and these are thought to represent heterotopic glia and neurons along the expected path of cortical migration.

Adolescent↗