Calprotectin levels in the cerebrospinal fluid reflect disease activity in multiple sclerosis.

Calprotectin is produced by activated monocytes and microglia, and cerebrospinal fluid (CSF) levels could be a marker of neuroinflammation. Calprotectin was detectable in CSF from 13.8% of normal controls, compared to 90.

MS and clinically isolated syndromes: shared specificity but diverging clonal patterns of virus-specific IgG antibodies produced in vivo and by CSF B cells in vitro.

Background: Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type-1 (HSV-1) is a characteristic feature multiple sclerosis (MS).

Methods: We have used isoelectric focusing-immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV-1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease.

Results: In vitro synthesis of IgG by PBL was not detected in any patient.

GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence.

Background And Purpose: Persistent intrathecal production of IgG autoantibodies against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of undetermined specificity has been reported in stiff person syndrome (SPS).

Methods: To chart the avidity and clonal patterns of GAD65 IgG, we performed scatchard plot of binding characteristics and isoelectric focusing-immunoblot of cerebrospinal fluid (CSF) and serum from five SPS patients.

Results: Oligoclonal GAD65 IgG bands, predominantly restricted to the IgG1 subclass, were detected in CSF and serum in all patients.

[A stiff-legged man with a bizarre gait].

Background: Stiff person syndrome (SPS) is a rare neurological disorder characterized by simultaneous contraction of agonistic and antagonistic muscles. SPS can easily be confused with a psychogenic movement disorder, but the frequent finding of autoantibodies against glutamic acid decarboxylase (GAD65), positive response to immunomodulatory treatment and association with other autoimmune diseases strongly suggests an immununological pathogenesis.

Case Report: A 43-year-old man was admitted with a three-year history of stiffness and painful spasms in the left leg, causing walking problems and frequent falls.

T cells from multiple sclerosis patients recognize immunoglobulin G from cerebrospinal fluid.

Idiotopic sequences are created after V, D and J recombinations and by somatic mutations during affinity maturation of immunoglobulin (Ig) molecules, and may therefore be potential immunogenic epitopes. Idiotope-specific T cells are able to activate and sustain the B cells producing such idiotopes. It is therefore possible that idiotope-specific intrathecal T cells could help maintain the persisting intrathecal synthesis of oligoclonal IgG observed in patients with multiple sclerosis (MS).

Diagnostic validity of somatosensory evoked potentials in subgroups of patients with sciatica.

The diagnostic utility of scalp-recorded somatosensory evoked potentials (SEP) in patients with sciatica has generally been regarded as low. The purpose of the present study was to determine the validity of sensory nerve SEP in different subgroups of sciatic patients. A total of 65 consecutive patients with sciatica showing disc pathology and/or facet joint hypertrophy on lumbar computed tomography (CT) and/or myelography were studied.

Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period.

The Oslo Multiple Sclerosis (MS) Registry was established in 1990, and this is the first report on the prevalence and incidence of MS in the city of Oslo, Norway. The prevalence rate of definite MS on 1 January 1995 was 120.4/10(5).

Sex and age at diagnosis are correlated with the HLA-DR2, DQ6 haplotype in multiple sclerosis.

The HLA-DR2, DQ6 (i.e., HLA-DRB1*1501, DQA1*0102, DQB1*0602) haplotype contributes to the risk of developing multiple sclerosis (MS) in Caucasoids of Northern European heritage.

[Lumbar disk prolapses and radiological spinal intervention. What do the randomized controlled trials say?].

We searched the Medline database and examined 11 randomized controlled trials to evaluate the efficacy of treating lumbar herniated discs by injection with chymopapain or by automated percutaneous discectomy. Our findings show that chemonucleolysis with chymopapain is a documented treatment which is better than placebo, but consistently inferior to surgical discectomy. The two randomized controlled trials to evaluate automated percutaneous discectomy fail to show efficacy that is any better than would be expected from a placebo response.

Intrathecal immune response in neonatal Flavobacterium meningosepticum meningitis.

Neonates are predisposed to serious infections such as meningitis, probably due to their immature host reaction to the pathogens. We have studied the intrathecal immune response in 2 newborns with Flavobacterium meningosepticum meningitis. They showed a significant elevation of immunoglobulin indices ( >1.

HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients.

Japanese MS patients and controls were examined for the distribution of HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 alleles using in vitro amplification of genomic DNA and probing with sequence-specific oligonucleotides. No significant difference in frequency of the examined alleles was observed among the two groups. This is in contrast to Norwegian MS patients, where an association to a combination of certain DQA1 and DQB1 alleles has previously been demonstrated.

HLA-DQA1 and HLA-DQB1 genes may jointly determine susceptibility to develop multiple sclerosis.

Serologic DR typing and genomic DRB1, DQA1, DQB1, DPA1, and DPB1 typing using sequence-specific oligonucleotides were performed in 69 multiple sclerosis (MS) patients and 181 healthy controls on in vitro amplified DNA. The frequencies of DR2 as well as the DR2-associated DQA1*0102 and DQB1*0602 alleles were increased whereas DR7 was decreased among MS patients. The distribution of DR4 subtypes as well as DP alleles were similar in patients and healthy controls.

Cerebral vasculopathy associated with primary varicella infection.

A previously healthy 5-year-old boy developed cerebral vasculopathy, presenting as two episodes of acute hemiparesis 3 and 9 months, respectively, after a primary varicella infection (chickenpox). This association has not been reported before, to our knowledge, although cerebral vasculopathy is a well-known complication of herpes zoster ophthalmicus. The diagnosis was based on the presence of oligoclonal varicella-specific IgG in the cerebrospinal fluid and angiographic findings.

Quantitation of immunoglobulins produced by donor lymphocytes in transplant patients and the possible identification of donor cell-produced antiviral antibodies by imprint immunofixation.

In the present study two patients were studied in detail to estimate the quantity of IgG of donor lymphocyte origin. Using IgG subclass quantitation and Gm haemagglutination inhibition titre, we estimated that up to 3% of IgG found after transplantation may be of donor lymphocyte origin. Analysis of viral antibody patterns by imprint immunofixation suggested polyclonal production of donor-derived antibodies.

Patients with multiple sclerosis carry DQB1 genes which encode shared polymorphic amino acid sequences.

Of 61 Norwegian multiple sclerosis patients tested, 59, i.e., 97%, were positive for at least one of the HLA specificities DR2, DR4, or DRw6.

Multiple sclerosis patients have a high frequency of an HLA-DQ beta epitope defined by a human-human hybridoma antibody.

Epstein-Barr virus (EBV) transformed B-cells from patients with multiple sclerosis (MS) and healthy controls were analysed for reactivity with the HLA-DQ-specific human-human hybridoma Ab TrB12 (anti-DQw6 + DQw8 + DQw9) by indirect immunofluorescence (IIF). Positive results were obtained with 34 out of 35 MS patients (97.1%) and 79 out of 106 controls (74.

Paramyxovirus SV5 and multiple sclerosis.

Multiple sclerosis is commonly associated with a local humoral immune response within the central nervous system. A hallmark of this intrathecal response is the presence of electrophoretically demonstrable oligoclonal bands of IgG in the cerebrospinal fluid (CSF) of up to 95% of patients. Observations indicating that a major part of the CSF IgG in some patients may represent antibodies to SV5, a simian virus closely related to human parainfluenza type 2 virus, were recently reported by Goswami et al.

Human immunodeficiency virus infection of the brain. II. Detection of intrathecally synthesized antibodies by enzyme linked immunosorbent assay and imprint immunofixation.

Sera and CSF from 29 patients in early and late stages of HIV infection were analysed for intrathecal antibody production. Elevated CSF-IgG indices indicating intrathecal IgG synthesis were demonstrated in 9 patients while 4 of 18 patients tested had oligoclonal IgG bands in the CSF. Analysis of HIV-specific antibodies by enzyme-linked immunosorbent assay (whole antigen and site-directed ELISA) and calculation of "antibody indices" (CSF/serum antibody quotient divided by CSF/serum albumin quotient) indicated intrathecal HIV antibody synthesis in 19 patients.

The intrathecal immune response in the early stage of multiple sclerosis.

Sequential pairs of cerebrospinal fluid (CSF) and serum samples from 10 patients followed for 2.5-12 years after onset of unilateral optic neuritis (ON) were studied. Eight patients developed definite multiple sclerosis (MS) during the observation period.

Intrathecal complement activation in neurological diseases evaluated by analysis of the terminal complement complex.

The terminal complement complex (TCC) was determined in plasma and cerebrospinal fluid (CSF) from 208 neurological patients. Elevated CSF TCC levels were observed in higher frequencies in patients with infectious diseases (80%), radiculoneuritis (62%), multiple sclerosis (30%), and miscellaneous autoimmune diseases (27%) than in patients with miscellaneous non-inflammatory diseases (2-13%). The plasma level of TCC was significantly increased only in the infectious group.

Immunofluorescence staining of agarose-embedded cells. A new technique developed for immunological characterization of markers on a small number of cells.

A simple new method for the immunofluorescence staining of small numbers of cells is described: cell suspensions are mixed with low-temperature-gelling agarose at 37 degrees C and 2 microliter samples of agarose containing cells are dispensed onto multitest microslides precoated with agarose. The cells are subsequently stained by immunofluorescence techniques. Alternatively, the cell slides can be stored in liquid nitrogen until immunofluorescence staining is carried out.

Multimodal evoked responses and cerebrospinal fluid oligoclonal immunoglobulins in patients with multiple sclerosis.

One hundred patients with possible, probable and definite multiple sclerosis (MS) were examined with somatosensory (SER), visual (VER) and brain stem auditory (BAER) evoked responses. Paired samples of cerebrospinal fluid (CSF) and serum were examined with agarose gel electrophoresis to detect intrathecally synthesized oligoclonal immunoglobin bands. Comparison of the number of abnormal CSF and evoked response tests showed that the CSF examination was slightly more sensitive in all diagnostic groups when compared to the results of multimodal evoked responses but that the two sets of test were in part supplementary.

Long-term persistence of intrathecal virus-specific antibody responses after herpes simplex virus encephalitis.

Paired sera and cerebrospinal fluids (CSF) from nine surviving patients were collected 4.5 to 8 years after acute herpes simplex (HS) virus encephalitis. Oligoclonal bands of IgG were detected in the CSF of all, and seven patients had an elevated CSF IgG index.

Late sequelae after meningococcal disease as related to anamnestic and clinical factors recorded during the acute illness.

In 71 males who survived acute meningococcal disease 3 to 15 years ago at an age of about 20, associations between acute clinical conditions (including a few pre- and post-admission variables) and late sequelae have been studied. There was a higher rate of sequelae symptoms (mainly light neurological and mental disturbances) among survivors from meningitis (76%) than among those who had had both meningitis and septicemia (58%) or pure septicemia (50%). Twenty percent of control persons experienced such symptoms.