Primary Progressive Form Research Articles

The Prevalence of Multiple Sclerosis, Distribution of Clinical Forms of the Disease and Functional Status of Patients in Csongrád County, Hungary

Objective: The aim of this study was to determine the prevalence of multiple sclerosis (MS) in the population of Csongrád County, Hungary (400,128 inhabitants) and to determine the functional status (based on the Expanded Disability Status Scale; EDSS) of the patients according to the clinical forms of the disease. Methods: The diagnosis was established with the aid of the Poser diagnostic criteria, and the degree of physical disability was determined using the Kurtzke EDSS. Results: In Csongrád County, the prevalence of MS is 62/100,000. The distribution of patients according to the clinical forms of MS was as follows: 15% had the benign form, 54% had relapsing-remitting MS, 20% had secondary chronic progressive MS and 11% had the primary chronic progressive form of MS. Sixty percent of relapsing-remitting MS patients had an EDSS score of 0–4 points and 33% had an EDSS score of 4.5–6.5 points. Conclusion: The distribution of patients according to the clinical forms of the disease in this representative population is comparable to results in other regions of the world.

Increased nitric oxide products in CSF in primary progressive MS may reflect brain atrophy.

Because nitric oxide (NO) is a putative mediator of oligodendrocyte damage in the primary progressive form of MS (PPMS), the authors analyzed the levels of NO oxidation products in CSF and plasma from 25 patients with PPMS and 15 controls. The levels of nitrite + nitrate (NOx) in CSF were fourfold higher in patients with PPMS than in controls (p < 0.001), whereas the concentrations in plasma were similar. These data suggests involvement of NO in nervous tissue damage in PPMS.

Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates.

Autonomic dysfunction has rarely been studied in patients suffering from multiple sclerosis (MS). Some hypotheses have concerned the pathophysiology, especially with regard to a possible spinal cord origin. However, there have been no previous studies on autonomic dysfunction in MS and spinal cord lesions. This study assessed the frequency of autonomic dysfunction (AD) in MS and the correlation to spinal cord magnetic resonance imaging (MRI) findings. We prospectively studied 75 MS patients (25 with relapsing-remitting forms, 25 with secondary progressive forms and 25 with primary progressive forms). We performed sympathetic skin response, R-R interval variability and orthostatic hypotension testing. Spinal cord MRI was performed to detect demyelinating lesions (sagittal and axial plane) or spinal cord atrophy. Clinical and laboratory evidence of AD was found in 84% and 56% of MS patients, respectively. The correlation of the latter with disability was evaluated using the Extended Disability Status Scale. AD was more frequent in primary progressive MS than in the other two forms. AD was correlated with spinal cord cross-sectional area reduction but not with spinal cord hyperintensities. This study confirms that the frequency of AD in MS, especially in primary progressive forms, has until now been underestimated. Furthermore, AD appears to be more closely related to axonal loss, as demonstrated by spinal cord atrophy, than to demyelinating lesions.

Association between the endogenous retrovirus HRES-1 and multiple sclerosis in the United Kingdom--evidence of genetically different disease subsets?

In the present study we determined the frequencies of four haplotypes of the human T-cell lymphotropic virus-related endogenous sequence, HRES-1, in 110 multiple sclerosis (MS) patients and 100 healthy control subjects from the United Kingdom. We found evidence of an association between this endogenous retrovirus and MS (p < 0.01), in particular reflecting an increased frequency of HRES-1 haplotype 1 in the group of patients. There was no significant difference in the distribution of HRES-1 haplotypes between relapsing-remitting MS and the primary progressive form of the disease. The odds ratio for HRES-1 haplotype 1 and MS did not differ significantly between individuals positive for HLA-DR2 and DR2-negative individuals. Comparison of the observations from the present study with previous results implicated HRES-1 as a marker of genetic heterogeneity in MS.

Immunological profile of patients with primary progressive multiple sclerosis. Expression of adhesion molecules.

Adhesion molecules are important in the trafficking of peripheral leucocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis, which is an inflammatory and demyelinating disease. The latest MRI evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of elucidating whether different pathogenic mechanisms are involved in primary progressive multiple sclerosis, we compared membrane expression of the adhesion molecules ICAM-1 (CD54), LFA-1alpha (CD11a), VLA-4 [alpha(4)/beta(1) integrin (CD49d/CD29)], L-selectin (CD62L) and ICAM-3 (CD50) in peripheral blood and the serum-soluble forms ICAM-1, L-selectin, VCAM-1 and ICAM-3 in 89 patients (39 with the primary progressive form, 25 with the secondary progressive form and 25 with the relapsing-remitting form) and 38 healthy controls. We found a significant decrease in leucocyte surface expression of most of the adhesion molecules tested and an increase in soluble ICAM-1 and L-selectin levels in secondary progressive and relapsing-remitting multiple sclerosis compared with primary progressive multiple sclerosis, which gave results similar to those in controls. These results, which are supported by MRI evidence, show that trafficking of autoreactive leucocytes through the blood-brain barrier is crucial to the pathogenesis of secondary progressive and relapsing-remitting forms of multiple sclerosis, whereas other mechanisms leading to progressive axonal damage would account for primary progressive forms of the disease.

Esclerosis múltiple de inicio juvenil

Young onset multiple sclerosis is an infrequent situation which may present with atypical symptoms and uncertain outcome. Our aim was to assess the clinical presentation and course in young onset multiple sclerosis, and analyze eventual data which might be helpful in establishing its prognosis. We have retrospectively reviewed the clinical protocols of 17 patients with young onset multiple sclerosis, defined as presentation of symptoms before 21 years. Diagnosis was made according to Poser's criteria including clinical features, magnetic resonance imaging, cerebrospinal fluid findings, and evoked potentials. The mean age at onset was 16.9 +/- 4.4 and median time to diagnosis was four weeks. The clinical course was relapsing-remitting in 76.5% and secondary progressive in 23.5%. The mean annual exacerbation rate was 1.5 +/- 0.9 and median time to second exacerbation was 12 months. The actual Expanded Disability Status Scale score is 2.6 +/- 2 after a mean disease duration of 11.4 +/- 8.0 years. The correlation between the Expanded Disability Status Scale score and the mean disease duration was the only statistically significant result. These results are similar to other studies, namely, age at onset did not correlate with final neurological disability. However, we must emphasize that any primary progressive form was found in our study. We conclude that in young onset multiple sclerosis, progression is not dependent on the age of onset and does not necessarily lead to an unfavorable outcome.

Evaluación neurofisiológica en pacientes con esclerosis múltiple clínica definida con especial referencia al estudio de la onda P300

In the cognitive sphere, alterations have been found in up to 65% of patients with multiple sclerosis (MS). Study of the P300 wave is a positive component of long latency related to cognitive function: amplitude with attention, and latency with the ability to process information. To assess a study of the P300 wave in a group of patients with MS. The P300 wave was studied in 26 patients, 22 women and 4 men, with definite clinical MS (on criteria of Poser et al), with normal motor and sensory conduction velocity studies. All patients had a battery of multi-modal evoked potentials (MEP), nuclear magnetic resonance imaging and immunological study of the cerebrospinal fluid. Seventeen patients had the exacerbation-remission (ER) and nine the primary progressive (PP) clinical forms of the disorder. The most markedly altered MEP were the visual and somatosensory evoked potentials (SSEP) of the patients with MS. When the types of clinical course were compared, the SSEP were statistically significant in the PP form, which may be explained by the greater spinal involvement of these patients. Comparative analysis of the P300 wave was done for 26 healthy patients of similar age and sex to that of the patients, and significant differences were found in P300 latency and amplitude between the MS and control groups. The patients who had had the disease for longer had significantly greater anomalies in the P300 waves. Study of the evolution of the P300 wave, which is cheap and easy to do, may be valuable in the evolutional assessment of cognitive changes in patients with MS.

Sensibilidad de los potenciales evocados motores en la detección de lesiones corticospinales en pacientes con esclerosis múltiple

Motor evoked potentials (MEP) are very useful for the evaluation of multiple sclerosis patients. To know the sensibility of MEP in a group of patients with diagnosis of multiple sclerosis. A transversal and descriptive study was done in 56 patients with definite multiple sclerosis (MS). MEP using magnetic stimulation were carried out in all of them, with recordings over abductor pollicis brevis and tibialis anterioris. We analyzed the sensibility of MEP and the clinical correlation of this study. In 22 patients the sensibility of MEP and somatosensory, auditory and visual evoked potentials was compared. Abnormalities were detected in the 87% of records, and in 18% with absences of clinical signs of corticospinal lesion. We found statistically significant differences between relapsing-remitting form and primary chronic and progressive form (Wilk's lambda = 0.606, p = 0.00), with a high lineal relation to Kurtzke Scale (p < 0.05). In relation to the other modalities of evoked potentials, MEP were the most sensible study (68.1%), followed by somatosensory (59%), visual (45.4%) and auditory (22.5%) evoked potentials. MEP are a very sensible modality of evoked potentials for the detection of corticospinal lesions in MS patients, with a high degree of clinical correlation.

Combined effect of HLA-DRB1 *1501 and interleukin-1 receptor antagonist gene allele 2 in susceptibility to relapsing/remitting multiple sclerosis

Susceptibility to multiple sclerosis (MS) is associated with HLA-DRB1 *1501. Many reports have suggested associations with other loci but these results remain unconfirmed. We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS). The frequency of DRB1 *1501 and IL-1ra allele 2 were significantly higher in R/R MS. Association was more marked in the female sex and in patients with benign forms of R/R MS. On the other hand DR4 subtypes carrying a Val at position 86 in the DR β chain were increased in PP MS. The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.

Menstrually related worsening of symptoms in multiple sclerosis

The objective of this study was to investigate whether the menstrual cycle influences multiple sclerosis (MS) symptoms. Seventy-two normally menstruating women (aged 20–50 years) with MS were interviewed. Of the 60 patients with a relapsing–remitting form of MS (RR-MS), 26 (43%) regularly experienced worsening of their MS symptoms in the period just before, or at the beginning of, the menstruation. Significantly more patients of the group reporting no influence of the premenstrual period on MS symptoms were using an oral contraceptive ( p=0.041), suggesting a protective effect. There were 12 patients with the primary chronic progressive form of MS (PCP-MS). None of them experienced an influence of the menstrual cycle on their symptoms. Our results suggest that hormonal changes preceding menstruation may worsen symptoms in a subgroup of women with RR-MS.