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PubMed1991

[Laboratory diagnosis of multiple sclerosis].

In 26 patients with multiple sclerosis 100% responded abnormally to magnetic resonance imaging of the brain. Lesions in the posterior fossa were observed in 18 patients. The auditory brain stem response was abnormal in 15 patients, and 22 had abnormal immunoglobulins in the cerebrospinal fluid. The correlation between abnormalities of the auditory brain stem response and the magnetic resonance images was greatest in a subgroup where the two investigations were performed within a ten day interval. Results from magnetic resonance imaging, evoked potentials and cerebrospinal fluid investigations were used to reclassify 13 of 15 patients with clinically "possible" or "probable" multiple sclerosis to a higher level using Poser's criteria. Evoked potentials (the auditory brain stem response in particular) correlated best with clinical multiple sclerosis category. We recommend that magnetic resonance imaging is established as a first-hand investigation in evaluations of multiple sclerosis. Evoked potentials and cerebrospinal fluid investigations may prove to be more specific, however, and these investigations should also be performed as a routine.

Adult↗
PubMed1999

Value of sympathetic skin response in multiple sclerosis.

Thirty patients with definite multiple sclerosis along with fourteen healthy volunteers as control group were studied. Mean SSR latencies in the control group was 1,467 ms for upper extremities and 1,915 ms for lower extremities while 1,655 and 2,170 ms respectively in the patients with multiple sclerosis. Mean SSR amplitudes in the control group was 2.22 mV for upper extremities and 1.21 mV for lower extremities while 1.24 and 0.64 mV respectively in the patients with multiple sclerosis. All the differences between the patients and the control group was significant using T test (P = 0.001). Using Roc-curve, limits with highest sensitivity specificity products for SSR latency were calculated to be 1,700 ms for upper and 2,400 ms for lower extremities. For SSR amplitude they were 1.2 mV for upper and 0.5 mV for lower extremities. Considering absent SSR and/or at least 3 abnormal amplitudes or latencies as the criteria of abnormality, the specificity of the test was 100% and the sensitivity was 80% among our patients. Using the following criteria for abnormality, SSR study in the patients with multiple sclerosis is a test with high specificity and sensitivity: 1--Absent SSR, and/or 2--At least 3 abnormal out of the eight recordings (amplitudes and latencies of four extremities) with normal limits for SSR latency being defined as < or = 1,700 ms for upper and < or = 2,400 ms for lower extremities and for SSR amplitude as > or = 1.2 mV for upper and > or = 0.5 mV for lower extremities.

Adolescent↗
PubMed2003

TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis.

BACKGROUND: Many patients with multiple sclerosis do not respond to interferon beta, which is widely used as an immunomodulatory treatment in this disease. We aimed to assess the functional relevance of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), which is upregulated on incubation with interferon beta, for clinical treatment response. METHODS: We quantified gene expression longitudinally by realtime-PCR of the peripheral immune cells of 82 patients with multiple sclerosis. In a first cohort of 62 patients, 20 were classified as first-year responders since they did not have relapses during treatment with interferon beta 1a; 19 were classified as first-year non-responders; and 23 developed neutralising antibodies to interferon beta. A second cohort, also characterised by MRI, consisted of 11 patients on interferon beta 1a and nine patients who were not treated. Concentrations of soluble TRAIL were determined by ELISA in serum samples of nine non-treated patients, 49 patients before treatment (29 responders, 20 non-responders), as well as longitudinally in a subset of 23 patients. FINDINGS: In both patient cohorts, drug-responders could be distinguished from non-responders by early and sustained induction of TRAIL (p<0.0001, each). In the presence of neutralising antibodies, initial upregulation of TRAIL expression was subsequently abrogated. Raised concentrations of soluble TRAIL in patients' serum samples before the start of treatment allowed prediction of the treatment response in the first year (ROC analysis with area under the curve 0.879 [0.785-0.974]). INTERPRETATION: Our data suggest that TRAIL expression is a candidate for pretreatment assessment and might thus be used as a prognostic marker of treatment response to interferon beta in multiple sclerosis. Furthermore, our observations have implications for the development of future immunoregulatory strategies in multiple sclerosis therapy.

Adjuvants, Immunologic↗
PubMed2005

A longitudinal fMRI study on motor activity in patients with multiple sclerosis.

Using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of motor activation than controls. Although functional changes are often interpreted as adaptive and as a contributing factor in limiting the clinical deficit, no longitudinal studies have yet been performed for multiple sclerosis. Sixteen patients with multiple sclerosis, two patients with possible multiple sclerosis and nine age-matched controls underwent two fMRI studies with a time interval of 15-26 months. The motor task consisted of a self-paced sequential finger opposition movement with the right hand. Patients with multiple sclerosis exhibited greater bilateral activation than controls in both fMRI studies. At follow-up, patients showed a reduction in functional activity in the ipsilateral sensorimotor cortex and in the contralateral cerebellum. No significant differences between the two fMRI studies were observed in controls. Activation changes in ipsilateral motor areas correlated inversely with age, extent and progression of T1 lesion load, and occurrence of a new relapse. This study may help the understanding of the evolution of brain plastic changes in multiple sclerosis indicating that, in younger patients with a less structural brain damage and benign clinical course, the brain reorganizes its functional activity towards a more lateralized pattern of brain activation. The tendency towards a normalization of brain functional activity is hampered in older patients and in those developing relapses or new irreversible brain damage.

Adult↗
PubMedDate not supplied

[Magnetic resonance in the diagnosis and treatment of multiple sclerosis].

Although the diagnosis of multiple sclerosis is still based on clinical criteria, confirmation by magnetic resonance imaging (MRI) is considered to be essential, thank to its high sensitivity in demonstrating the spatial dissemination of the demyelinating plaques in the brain and spinal cord. Additionally, MRI can establish an approximation of the pathological substrate of the multiple sclerosis plaques and it has proven useful for studying the natural history of the disease and monitoring the effects of new treatments. This capacity of MRI is based on its ability to estimate the degree of demyelination, gliosis, edema, inflammation and axonal damage and to detect diffuse involvement of the normal appearing white matter. The selective identification of the lesions that contribute most to the patient's disability and clinical progression, such as severe demyelination and axonal damage, improves the MRI correlation with the neurological impairment scales. However, a correct application of MRI in the study of multiple sclerosis requires standardization of the techniques and sequences used in the different clinical forms of the disease and of the systems for measuring the lesion load. In this way multiple sclerosis can serve as a true biological marker of the severity of the disease.

Atrophy↗
PubMed2004

Marburg type and Balò's concentric sclerosis: rare and acute variants of multiple sclerosis.

Marburg type and Balò's concentric sclerosis are considered particular variants of multiple sclerosis, clinically characterized by a severe, rapidly evolving clinical course, and by unusual neuropathological changes, often large tumor-like demyelinating plaques in Marburg type and concentric layers of partial demyelination alternating with demyelinating bands in Balò's concentric sclerosis. These forms now can be diagnosed in vivo, with complete clinical and laboratory examination and MRI follow up. Although in some patients a favourable clinical course has been described, the poor prognosis of the majority of these cases justifies a treatment with intense immunosuppression.

Brain↗
PubMed1985

Multiple sclerosis. Current concepts in management.

Multiple sclerosis is a chronic, often progressive disease of the central nervous system which can produce visual, sensory, motor, and genitourinary dysfunction. Although there is no cure, many disabling symptoms can be ameliorated. Baclofen is the treatment of choice for spasticity and is usually given in doses of 30 to 80 mg/day, although higher doses may be used. Bladder symptoms in multiple sclerosis generally fall into the categories of failure to store, failure to empty, and mixed types. Most patients can be managed after obtaining a urine culture and sensitivity and post-voiding residual. A variety of anticholinergic agents plus intermittent self-catheterisation is usually the most effective treatment for bladder dysfunction. Prevention of infection is accomplished by urinary acidifiers or low-dose antibiotics. There is no evidence that long term use of corticosteroids has a beneficial effect on the outcome of multiple sclerosis, although they appear to be useful in hastening the recovery time from an acute exacerbation. There are a number of experimental therapeutic agents which are used to modulate the immune response, which may prove to be of use in slowing or arresting the progression of multiple sclerosis.

Adrenal Cortex Hormones↗
PubMed1984

Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis.

In 21 patients with multiple sclerosis and 20 healthy controls, the following tests of autonomic function were examined: (1) variation in heart rate during deep breathing, (2) the variations in heart rate and systolic blood pressure during a standardised Valsalva manoeuvre, (3) the changes in heart rate and systolic blood pressure during arm ergometry starting at 30 W with increments of 20 W every 3 min. In the control subjects the maximum variation in heart rate from inspiration to expiration was greater than 16 beat/min (range 17-43). In patients with multiple sclerosis, five had a maximum variation in heart rate of less than 13 beat/min which was considered as the lower limit of normal. The Valsalva ratio in the control subjects ranged from 1.33-3.24. Four patients had Valsalva ratios of less than 1.30. In patients with multiple sclerosis the heart rate and systolic blood pressure responses to exercise were attenuated significantly in four and seven subjects respectively. It is concluded that a significant number of patients with multiple sclerosis show evidence of autonomic dysfunction involving the cardiovascular system.

Adult↗
PubMed2000

Susceptibility to multiple sclerosis: interplay between genes and environment.

Multiple sclerosis is a complex trait of unknown etiology. Epidemiological data have shown that susceptibility to multiple sclerosis is determined by both genetic and environmental factors. It is unknown whether the clinical subcategories of multiple sclerosis are separate diseases with separate etiologies and causes. Recent theories of the pathogenesis of multiple sclerosis and candidate genes are discussed. Other potential nonchromosomal factors involved in multiple sclerosis susceptibility such as mitochondrial DNA and viral factors such as Chlamydia pneumoniae are reviewed.

Environmental Exposure↗
PubMed1994

Role of limited evaluation and aggressive medical management in multiple sclerosis: a review of 113 patients.

Multiple sclerosis has frequent urological manifestations. Medical management, based on clinical symptoms and urodynamic findings, incorporates clean intermittent catheterization, oral pharmacological agents (that is oral oxybutynin) or their combination (the desired end point of treatment being complete retention with clean intermittent catheterization). Our objectives were to evaluate the efficacy of medical management in multiple sclerosis patients, determine the incidence of hydronephrosis at presentation and during treatment, and evaluate the impact of electromyography on patient management. We reviewed retrospectively 113 patients with documented multiple sclerosis (mean age 45 years, range 20 to 75 years and mean followup 41 months, range 6 to 136 months). Presenting symptoms were irritative alone or combined with obstructive symptoms in 94 patients (83%). On cystometrography 79 patients (70%) had detrusor hyperreflexia and 17 (15%) had an areflexic bladder. Coaxial needle electromyography was performed on 54 patients and 15 (28%) had detrusor-sphincter dyssynergia. Patients with detrusor-sphincter dyssynergia had more advanced neurological disease. A total of 105 patients had radiological imaging of the upper tracts. Only 7 patients (6.6%) had hydronephrosis at presentation and all were stable or improved with medical management. No patient had hydronephrosis with aggressive medical management. No patient with detrusor-sphincter dyssynergia had hydronephrosis or elevated creatinine levels at presentation or during treatment. Medical management failed in 8 patients (7%) who required surgical intervention. Limited evaluation (voiding symptoms, post-void residual and cystometrography) of multiple sclerosis patients is sufficient to formulate an effective treatment program. Electromyography is not necessary in the routine evaluation of patients with documented multiple sclerosis. After baseline upper tract imaging, routine yearly evaluations are unnecessary (unless initially abnormal or indicated by a change in clinical status). Medical management of patients with multiple sclerosis is safe and effective. In this series, no patient had hydronephrosis on therapy, and only 7% of the patients failed aggressive medical management and required surgical intervention.

Adult↗
PubMed2000

Community services in multiple sclerosis: still a matter of chance.

OBJECTIVES: People with multiple sclerosis often have multiple complex needs that require input from a wide range of services. Many complain that services are inadequate and poorly coordinated. Few studies have been undertaken to support this contention and objective data are scarce. The level of services and home modifications received by people with multiple sclerosis across a broad range of disease severity has been investigated. METHODS: As part of a quality of life study, 150 adults with clinically definite multiple sclerosis were interviewed, using a structured questionnaire, to determine their current use of outpatient and community services and the home modifications in place. Disability, handicap, and emotional status were also measured. RESULTS: Forty five per cent of people did not receive any community services other than contact with their general practitioner. Thirty nine per cent of people with moderate and 12% with severe disability failed to receive community services. For the services received: 17% had contact with a community nurse; 33% with a care attendant or home help; 23% with a physiotherapist, 21% with an occupational therapist, and 10% with a social worker. Fifty eight per cent of people had modifications to their home as a direct result of multiple sclerosis. The relation between level of disability and number of services and adaptations received was moderate (r=0.58 and 0.54 respectively) and the relation between level of services and age (r=0.12), living alone (r=0.16), and emotional status (r=0.10) was negligible. CONCLUSIONS: Despite a shift of emphasis from hospital to community care, and the establishment of standards of care for multiple sclerosis, many people with moderate or severe disability fail to receive assistance. These results provide evidence to support the dissatisfaction felt by people with multiple sclerosis in relation to the services they receive. It raises questions about equitable allocation of resources and highlights the urgent need for a review of community services.

Adult↗
PubMed1998

Heart rate variability in multiple sclerosis during a stable phase.

OBJECTIVES: Multiple sclerosis (MS) frequently causes disturbances of autonomic functions. Cardiovascular dysautonomia has been studied by classic autonomic tests and, recently, by heart rate variability analysis in some isolated periods. Multiple authors recommended performing heart rate variability analysis with a 24 h ECG recording to increase its sensitivity. MATERIAL AND METHODS: We analyzed the heart rate variability in time and frequency domains in 34 MS patients and 24 age and sex-matched healthy control subjects, in order to evaluate the effects of MS on sympathetic and parasympathetic cardiovascular regulatory functions measured from 24-h electrocardiogram. RESULTS: Low frequency power (0.01) and low frequency/high frequency power (0.01) were significantly higher in multiple sclerosis patients independently, all together or in subgroups. Very low frequency (0.01) and high frequency (0.001) power were higher in less affected multiple sclerosis patients. Variability in time domain (0.05) were lower in most affected multiple sclerosis patients. CONCLUSIONS: These results suggest that multiple sclerosis causes cardiovascular autonomic dysregulation manifesting as impaired heart rate variability. This illness seems to cause an increase in sympathetic cardiovascular tone; the parasympathetic tone is most variable and depends on clinical and paraclinical findings, but the illness progression seems to provoke a decrease in it.

Adult↗
PubMed2001

Upregulation of the inhibitor of apoptosis proteins in activated T lymphocytes from patients with multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) may involve failure of programmed cell death (apoptosis) to eliminate potentially pathogenic, autoreactive T lymphocytes. This failure may be caused by multiple abnormalities of the cell death machinery. In this study, we investigated the expression of the inhibitors of apoptosis (IAP) proteins, cellular IAP-1, IAP-2, and X-linked IAP (XIAP), in T lymphocytes from patients with active relapsing-remitting MS and appropriate controls. The expression of IAP proteins was significantly higher in mitogen-stimulated intrathecal and peripheral T lymphocytes from MS patients when compared to corresponding expressions from inflammatory and non-inflammatory neurologic controls, and healthy individuals. IAP proteins were also expressed in resting (unstimulated) T lymphocytes predominantly from MS patients. The heightened expression of IAP proteins in MS patients correlated with T lymphocyte resistance to apoptosis, and was independent of cellular expression of the death receptor protein Fas. In contrast, cellular expression of the anti-apoptosis protein Bcl-2 was relatively similar between MS patients and the control groups. These findings suggest that over-expression of IAP proteins in mitogen-stimulated T lymphocytes is a feature of multiple sclerosis.

Apoptosis↗
PubMed2006

[Spanish adaptation of the disease-specific questionnaire MSQOL-54 in multiple sclerosis patients].

INTRODUCTION: The Multiple Sclerosis Quality of Life 54 (MSQOL-54) is a health-related quality of life specific questionnaire for multiple sclerosis (MS) patients. The objective of this study was to develop the Spanish version of the MSQOL-54 and to obtain a conceptually equivalent version to the original one for its use in patients with MS in the first phase of the project. METHODS: A transcultural adaptation procedure was designed according to the following phases: a) two independent translations made by bilingual native Spanish speaking translators (forward translation); b) a revision of the items by an expert panel; c) a back translation by a bilingual native English speaking person; d) comparison with the original version (expert panel and advise by the original authors), and e) cognitive debriefing (interviews with subjects with MS) to test the comprehension and feasibility of the instrument. RESULTS: Ten interviews were carried out with 5 men and 5 women with MS, aged 21 to 54 years, with different education levels and EDSS scores ranging from 1,0 to 8,0. Most of the patients found the questionnaire easy to fill out and the understanding favorable. Only one item (item 51) was modified after the cognitive debriefing to improve its comprehension. Finally, a final pretest version was obtained. CONCLUSIONS: The procedure carried out maximizes the conceptual equivalence between the original MSQOL-54 and the translated version and shows that the Spanish pre-test version is comprehensible and its administration feasible in patients with MS. The psychometric properties must be evaluated in the next phase of the project.

Activities of Daily Living↗
PubMedDate not supplied

Membranous nephropathy associated with multiple sclerosis.

Membranous nephropathy and multiple sclerosis are believed to be mediated by immune mechanisms. A patient is reported with the first described association of membranous nephropathy and multiple sclerosis. Its significance and possible pathogenetic mechanisms are discussed.

Adolescent↗
PubMed1985

[Micturition disorders in multiple sclerosis].

103 patients with multiple sclerosis (MS) were investigated, of which 53% complained of micturition difficulties. Since these symptoms frequently are the main cause for social withdrawal of the multiple sclerosis patient, the investigation and therapy of micturition dysfunction should play a central role in the management of these patients.

Adult↗
PubMed1980

Haemorrhagic complications of multiple sclerosis.

Neurological exacerbations in multiple sclerosis patients are usually attributed to relapses of the disease. This report emphasises that other conditions, such as spontaneous CNS haemorrhage, may be responsible for the clinical deterioration. We describe two patients appropriately diagnosed as having multiple sclerosis who developed spontaneous CNS haemorrhage.

Adult↗
PubMed1999

Reporting delay and corrected incidence of multiple sclerosis.

The incidence of multiple sclerosis can be adjusted for reporting delay in a way similar to that for AIDS incidence as described in this paper. Two models are applied to data from the Danish Multiple Sclerosis Registry. The first simply describes the delay distribution, the second is a regression model. For the latter it is shown how goodness-of-fit assessment for both time-dependent and time-independent covariates can be handled using ideas from the Cox proportional hazards model. The goodness-of-fit analysis shows that people with onset age below 40 years and people with onset age from 40 years and above should be analysed separately and this is done throughout the paper. The incidences are adjusted with the two estimated delays and an estimate of the variance for the adjusted incidence is given. Finally the crude incidences are compared with the adjusted ones. We find that the incidence has been increasing since 1965 but mostly for people with onset age below 40 years.

Adult↗