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PubMed1981

Relative value of three laboratory methods in the diagnosis of multiple sclerosis.

We compared three methods of analysis for IgG in cerebrospinal fluid, using samples from 158 patients with clinically suspected multiple sclerosis and from 200 neurological controls. The tests were: search for oligoclonal bands, calculation of rate of synthesis of IgG in the cerebrospinal fluid, and determination of the IgG/albumin ratio. Paired cerebrospinal fluid and serum samples were collected and their IgG and albumin concentrations measured. Oligoclonal bands were detected by electrophoresis on agarose. Positive results were obtained in 94, 75, and 67% of patients with probable or definite multiple sclerosis by the three respective methods. In contrast, for patients for whom the clinical diagnosis of multiple sclerosis was considered possible, positive results were obtained in 10, 43, and 13%, respectively. Evidently, detection of oligoclonal bands remains the best single test for the presence of abnormal IgG in suspected multiple sclerosis patients. A combination of the first two tests is most sensitive for both probable and definite multiple sclerosis (97%) and possible multiple sclerosis (50%). Some infectious or immunologic disorders can also produce these IgG abnormalities, but they can usually be distinguished from multiple sclerosis by other clinical and laboratory data.

Diagnosis, Differential↗

PubMed2004

Chlamydophila pneumoniae infection of the central nervous system in patients with multiple sclerosis.

BACKGROUND: Chlamydophila pneumoniae has been postulated as an aetiological agent in the pathophysiology of multiple sclerosis. Previous studies show conflicting results. OBJECTIVE: To investigate patients with multiple sclerosis and other neurological diseases for evidence of past or present infection with C pneumoniae. METHODS: 19 patients with multiple sclerosis and 29 with other neurological diseases were studied. Evidence was sought for past or present infection with C pneumoniae using polymerase chain reaction (PCR) and cell culture of cerebrospinal fluid (CSF), and enzyme linked immunosorbent assay and microimmunofluorescence of serum. RESULTS: C pneumoniae was grown from the CSF of one patient with multiple sclerosis. PCR was negative in all cases. Anti-chlamydial antibodies were detected in the same proportion in each group. CONCLUSIONS: This study does not support the theory of an association between C pneumoniae and multiple sclerosis.

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↗

PubMed2003

Peripheral sensory and motor abnormalities in patients with multiple sclerosis.

OBJECTIVES: Peripheral nerve abnormalities are uncommon in multiple sclerosis (MS). When present, they are usually attributed to factors associated with advanced disease, such as malnutrition or cytotoxic drugs or hereditary factors. However, a combination of MS and neuropathy has been reported. The aim of this study is to evaluate the question of possible peripheral involvement in MS. METHODS: We studied sensory and motor nerve conduction velocities (NCV) and amplitudes values in some sensory and motor nerves in upper and lower extremities in 20 definite multiple sclerosis patients diagnosed according to the criteria of Poser Scale and in 15 healthy subjects. The total number of studied nerves were 91 in patients group and 69 in control group. RESULTS: The most frequent electrophysiological abnormalities noted in patients group were low amplitude of the ulnar and sural nerve and slow NCV of the tibial and sural nerves. Electrophysiological abnormalities were found in 15 of 91 nerves examined (16.5%). The neurological disability was not associated with the presence of electrophysiological abnormalities. The electrophysiological abnormalities in control group subjects were a slight slow conduction of sural nerve in 2 of 69 nerves examined (2.9%). CONCLUSIONS: Our findings indicate a high frequency of sensory-motor electrophysiological nerve abnormalities in a selected group of multiple sclerosis patients. Electromyographers must be aware of these abnormalities when performing routine electromyography examinations in these patients.

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↗

PubMed1984

Pattern electroretinogram in multiple sclerosis.

The pattern electroretinogram obtained in patients affected by multiple sclerosis were compared with those in a normal population. The pattern electroretinogram amplitude in multiple sclerosis optic neuritis frequently appeared normal, but pattern electroretinogram amplitude abnormalities were found in patients suffering from recurrent multiple sclerosis optic neuritis. Pattern electroretinogram examination appears a useful method in the differential diagnosis between axonal and demyelinating optic nerve impairment.

Adult↗

PubMed2001

Definite and suspected multiple sclerosis in children: long-term follow-up and magnetic resonance imaging findings.

Twenty-five children at the ages of 3 to 18 years with an initial diagnosis of acute disseminated encephalomyelitis were followed in the Clinic of Child Neurology for a period of 2 to 8 years. In 10 children, there were data for clinically definite or laboratory-supported definite multiple sclerosis. The other 15 children in our study were considered as having suspected multiple sclerosis. Brain magnetic resonance imaging (MRI) performed in 15 children disclosed multiple hyperintense lesions on T2-weighted imaging in 13 children: 10 with definite multiple sclerosis and 3 with suspected multiple sclerosis. The clinical manifestations did not always correspond to the size and location of the MRI lesions of demyelination. Follow-up revealed normalization of the neurologic examination in 18 patients (72%) and abnormal neurologic findings in 7 patients (28%) (6 children with definite multiple sclerosis and 1 with suspected multiple sclerosis). Magnetic resonance imaging follow-up in children with definite multiple sclerosis disclosed a reduction in the size of the lesions in 3; enlargement or new lesions were established in the other 7 cases, and 2 cases were without clinical signs of new attacks. Correlation was done concerning the findings of the cerebrospinal fluid examination, transcranial magnetic stimulation, evoked potentials, computed tomography, and MRI. The role of MRI for an early diagnosis of multiple sclerosis in children is discussed. The dynamic follow-up of the pathologic changes is of prognostic significance for the course of the disease that could be a definite cessation of the process in acute disseminated encephalomyelitis cases or transition to multiple sclerosis.

Acute Disease↗

PubMed1993

Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis.

T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP-specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant T cell recognitions of distinct MBP regions were present in three patients, all HLA-DR2+, independently of the clinical features of their disease. T cell reactivity was preferentially directed to residues 16-38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86-99 was detected in the two other DR2+ patients. In each of the patients with other HLA-DR haplotypes (DR2-), as well as in three DR2+ non-MS donors, the T cell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA-DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA-DRB1 gene in individuals with the HLA-DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA-DR2 gene products alone do not account for the selection of the dominant MBP T cell epitope.

Adolescent↗

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↗

PubMed2000

Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates.

OBJECTIVES: To explore whether mortality from multiple sclerosis is negatively associated with exposure to sunlight. METHODS: Two case-control studies based on death certificates were conducted for mortality from multiple sclerosis and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from multiple sclerosis between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded cancer and certain neurological deaths. The effects of occupational exposure to sunlight were assessed among subjects with usual occupations requiring substantial activity, so as to exclude those whose indoor jobs resulted from disabilities subsequent to the onset of the disease. Multiple logistic regression analyses were applied, with adjustment for age, sex, race, and socioeconomic status. RESULTS: Unlike mortality from skin cancer, mortality from multiple sclerosis was negatively associated with residential exposure to sunlight (odds ratio (OR)=0.53 (multiple sclerosis) and OR=1.24 (skin cancer)). Odds ratios for the highest occupational exposure to sunlight were 0.74 (95% confidence interval (95% CI) 0.61 to 0.89) for mortality from multiple sclerosis, compared with 1.21 (1.09 to 1.34) for mortality from non-melanoma skin cancer. The OR was 0.24 for the combined effect of the highest levels of residential and occupational exposure to sunlight on multiple sclerosis, compared with an OR of 1.38 for skin cancer. CONCLUSIONS: In this exploratory study, mortality from multiple sclerosis, unlike mortality from skin cancer, was negatively associated with both residential and occupational exposure to sunlight.

Adult↗

PubMed2003

A meta-analysis of whole genome linkage screens in multiple sclerosis.

Linkage studies in complex diseases like multiple sclerosis, where the effects attributable to individual loci are modest, are critically dependent upon the number of families included. We have combined the raw genotyping data from all published genome linkage screens in multiple sclerosis and thereby performed a linkage analysis including 719 families studied with a weighted average of 359 microsatellite markers per family (range 257-453) providing an average marker separation of 10.2 cM. Linkage with genome-wide significance is confirmed in the HLA region on chromosome 6p21. In addition, two novel regions suggestive of linkage are seen (17q21 and 22q13). Our simulations would imply that the number of peaks with NPL scores >/=2.1 exceeds the number expected by chance alone.

Alleles↗

PubMed1998

Viruses and multiple sclerosis.

Animal models illustrate how viruses and host genetic factors may interact to cause immune-mediated demyelination. Similar mechanisms may take place in at least some forms of multiple sclerosis, a disease that is histopathologically heterogeneous. No 'multiple sclerosis virus' has been found yet, although recent data on human herpesvirus-6 antigens in multiple sclerosis brain warrant further investigation. Multiple sclerosis associated retrovirus, a recently described retroviral sequence isolated from multiple sclerosis material, is a member of the endogenous retrovirus-9 family. The association between the expression of this virus associated retrovirus and multiple sclerosis is only tentative.

Animals↗

PubMed1975

Multiple sclerosis and its etiopathogenesis.

Information available about the etiopathogenesis of multiple sclerosis is reviewed. It is concluded that multiple sclerosis is a chronic inflammatory disease, which usually has fluctuating manifestations. Oligoclonal and individual-specific humoral antibody responses suggest the existence of a continuous antigenic stimulus in the CNS tissue, which may vary in intensity from time to time. The best explanation for this antigen suggests, that is has a viral origin, but the available evidence for this hypothesis is, however, only indirect. More sophisticated methods are proclaimed to characterize specifically the humoral and cellular immunity to virus antigens and the interactions between viruses and cells in patients with demyelinating diseases like multiple sclerosis.

Antibodies, Viral↗

PubMedDate not supplied

Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies.

Our work with multiple sclerosis has demonstrated a favorable effect on the course of chronic progressive multiple sclerosis in two-thirds of patients treated with cyclophosphamide/ACTH. However, alternative methods of therapy, or repeated treatments with cyclophosphamide and ACTH are required for longer term control of the illness. We are attempting to assess the efficacy of outpatient maintenance cyclophosphamide, but do not as yet have any data to support the use of this form of treatment. Cyclophosphamide and ACTH can be given to multiple sclerosis patients without significant serious toxicity. Monoclonal antibody therapy of multiple sclerosis is in its beginning stages. The treatment appears to be safe and has produced some interesting data indicating that rapid entry of some labeled lymphocytes into the nervous system can be measured by this technique. Since these are phase one pilot trials designed to assess immune parameters and only small numbers of patients have been treated, no clinical results have been obtained. No adverse effects of monoclonal antibody therapy were observed.

Adrenocorticotropic Hormone↗

PubMed2003

Cognitive presentation of multiple sclerosis: evidence for a cortical variant.

BACKGROUND: Although neuropsychiatric complications are well recognised, the presentation of multiple sclerosis with cognitive or neuropsychiatric symptoms has generally been considered a rare occurrence and to reflect subcortical pathology. OBJECTIVES: To document the clinical, neuropsychological, and radiological features of six cases of cognitive presentation of multiple sclerosis, to review the relevant literature, and to propose a possible cortical basis for this clinical presentation. SUBJECTS: Six patients (five women; age range 38 to 60 years) presented to the memory and cognitive disorders clinic in Cambridge with an initially undiagnosed cognitive/neuropsychiatric syndrome. All underwent neuropsychological evaluation, brain imaging, and ancillary investigations to establish a diagnosis of multiple sclerosis. RESULTS: The six cases all had a progressive dementia syndrome with prominent amnesia, often accompanied by classic cortical features including dysphasia, dysgraphia, or dyslexia. Mood disturbance was ubiquitous and in three patients there was a long history of preceding severe depression. All six developed characteristic physical signs on follow up, with marked disabilities. A review of 17 previously reported cases highlighted the prominence of memory impairment and depression in the early stages. CONCLUSIONS: On clinical, pathological, and radiological grounds, the neuropsychiatric presentation of multiple sclerosis may represent a clinicopathological entity of "cortical multiple sclerosis." Failure to recognise this will delay diagnosis and may expose patients to potentially dangerous and invasive investigation. Because the neuropsychiatric features of cortical multiple sclerosis are a major cause of handicap, their early recognition may be particularly important in view of emerging treatments.

Adult↗

PubMed2003

[A case of childhood multiple sclerosis presented with meningitis and multiple silent plaques].

A 13-year-old girl presented herself with right optic neuritis and pleocytosis in the cerebrospinal fluid (CSF) in May 2000. Although her vision gradually improved after steroid therapy, the right optic neuritis relapsed a month later, and MRIs of the brain showed multiple high-signal intensity areas in the white matter of the right frontal and parietal lobes on T2-weighted and FLAIR images. She developed nuchal pain, low-grade fever, and general malaise in January 2002. Mononuclear pleocytosis and an elevation of myelin basic protein level were noted in CSF (33/microliter, 17.7 ng/ml, respectively). In addition to the plaque-like lesions seen in June 2000, MRI at this time showed an increase in the number of plaques in the medulla, pons, bilateral cerebellar peduncles and cerebellum. We thus considered this case as MS presenting with no focal neurological deficits but meningitis and asymptomatic MRI lesions. The past history of relapsed optic neuritis is supportive and compatible with that diagnosis. One might assume that the case belongs to that of relapsed type acute disseminated encephalomyelitis (ADEM). However, the cardinal pictures of the case are those of relapsing optic neuritis and multiple asymptomatic plaques despite clinical remission. Some atypical features like meningitis may predominate in clinical presentations of child MS, since immune response in child may differ from that of adult.

Adolescent↗

PubMed1984

[Spinal anesthesia and multiple sclerosis].

Spinal anaesthesia was performed in 9 patients with multiple sclerosis for 14 surgical procedures: urological surgery 13 times and plastic surgery once. No complication was observed. except for a transient exacerbation in one case. Spinal anaesthesia appeared to be an innocuous procedure in multiple sclerosis as no neurotoxicity was observed. Exacerbation of multiple sclerosis was similar to that seen with general anaesthesia. Moreover, spinal anaesthesia improved the operating conditions by relieving bladder spasticity; it was also often asked for by patients who feared the loss of consciousness of general anaesthesia.

Adult↗

PubMed2000

Ocular microtremor (OMT): a new neurophysiological approach to multiple sclerosis.

Using a piezoelectric transducer, the frequency and pattern of ocular microtremor (OMT) between 50 normal subjects and 50 patients with multiple sclerosis were compared. Controls were age matched. All records were analysed blindly. The frequency of OMT in the normal group was 86 (SD 6) Hz, which was significantly different from that of the multiple sclerosis group (71 (SD) 10 Hz, p<0.001). Those in the multiple sclerosis group with clinical evidence of brain stem or cerebellar disease (n=36) had an average OMT frequency of 67 (SD 9) Hz (p<0.001) compared with normal (n=86), whereas those with no evidence of brain stem or cerebellar involvement (n=14) had a frequency of 81.2 (SD 6) Hz (p<0.05, n=64). The differences between the two multiple sclerosis groups were also significant (p<0. 001, n=50). At least one abnormality (frequency and pattern) of OMT activity was seen in 78% of patients with multiple sclerosis. In the presence of brain stem or cerebellar disease 89% had abnormal records whereas in the absence of such disease 50% had abnormal records. This is the first report of the application of this technique to patients with multiple sclerosis. The results suggest that OMT activity may be of value in the assessment of multiple sclerosis.

Adult↗