Laboratory-supported Definite Multiple Sclerosis Research Articles

Multiple sclerosis prevalence and incidence in San Vicente del Raspeig, Spain

BackgroundChanges in the demographic epidemiology of multiple sclerosis (MS) may challenge the view of a latitudinal gradient in the distribution of MS. The objective of this study was to assess the incidence and prevalence of MS in addition to information on MS phenotypes and the use of disease modifying therapies (DMTs) in San Vicente del Raspeig in south eastern Spain. MethodsThis was a prospective epidemiological study of MS in San Vicente del Raspeig (population of 57,175 inhabitants based on the 2017 census) from 2005 to 2018. Multiple sources were used to identify MS cases. We considered as prevalent and incident cases all patients who satisfied either the criteria of Poser for clinically or laboratory-supported definite MS, or McDonald criteria. MS phenotypes were defined according to the 2013 revisions. ResultsFor the prevalence data, 64 patients were identified. The non-adjusted prevalence was 111.9 (95% CI: 87.7–142.9) cases per 100,000 inhabitants; the prevalence was 159.3 cases per 100,000 inhabitants for women and 63.6 cases per 100,000 inhabitants for men. The female-to-male ratio was 2.6:1. The age-adjusted prevalence for the European standard population was 107 cases per 100,000 inhabitants. During the study period, the incidence was 5 cases per 100,000 inhabitants per year. Most patients were being treated with DMTs (81.3%). MS was active in at least 12.5% of patients. ConclusionsThe results are consistent with the increased risk of MS in Spain observed over the last three decades, with growing prevalence rates that place the country in the high-risk prevalence zone.

Prevalence of Multiple Sclerosis in Iceland

Background: In this study, we examined multiple sclerosis (MS) point prevalence in the well-defined island population of Iceland. Methods: This study included all registered residents of Iceland with MS on the prevalence day, December 31, 2007. All included patients met at least one of the following criteria: McDonald criteria; Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS; or criteria for primary progressive MS. The patients’ medical records were reviewed, including all available MRI data acquired prior to the prevalence day. Results: We identified 526 patients, of whom 73% (382) were women. The crude point prevalence of MS was 167.1 per 100,000 population on the prevalence day. With age adjustment made to the 2000 U.S. population, the prevalence was 166.5 per 100,000 population. The mean patient age on the prevalence day was 47 years(range 13–89) for both men and women. The mean age at diagnosis was 36 years (range 13–77): 35 years for women and 36 years for men. Conclusion: MS prevalence was high in Iceland compared to the prevalence mentioned in reports from most of the world, and was similar to prevalence rates in other Nordic countries.

Possible increasing risk of multiple sclerosis in Catania, Sicily

To update prevalence and incidence rates of multiple sclerosis (MS) in Catania, Italy during 1990 to 1999 and evaluate their temporal profiles to assess a possible increase in the MS risk in our study population. We studied the frequency of MS in Catania, Italy (population of 313,110 as reported in the 2001 census). The primary sources for the case ascertainment were the neurologic and motor-rehabilitation departments, the MS centers, the Italian MS Association, private neurologists, and family doctors. We considered as prevalent and incident cases all patients who satisfied Poser's criteria for clinically definite MS (CDMS), laboratory-supported definite MS (LSDMS), clinically probable MS (CPMS), and laboratory-supported probable MS (LSPMS). We found 288 subjects with MS who had onset of disease before December 31, 1999 (prevalence day) in a population of 313,110 inhabitants. The prevalence rate was 92.0/100,000 (95% CI 81.8 to 103.2) and was higher in women (102.4/100,000) than in men (80.4/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 years (208.2/100,000). From 1990 to 1999, 155 patients with MS had the clinical onset of the disease. The mean annual incidence was 4.7/100,000 (95% CI 4.0 to 5.5). Age-specific incidence showed a peak in the group aged 25 to 34 years (11.7/100,000). Mean annual incidence for 5-year intervals increased from 3.9/100,000 during 1990 to 1994 to 5.5/100,000 during 1995 to 1999. Prevalence and incidence rates of multiple sclerosis have further increased during the last decade.

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.

Spinal cord magnetic resonance imaging in suspected multiple sclerosis.

We examined the value of spinal cord magnetic resonance imaging (MRI) in the diagnostic work-up of multiple sclerosis (MS). Forty patients suspected of having MS were examined within 24 months after the start of symptoms. Disability was assessed, and symptoms were categorized as either brain or spinal cord. Work-up further included cerebrospinal fluid analysis and standard proton-density, T2-, and T1-weighted gadolinium-enhanced brain and spinal cord MRI. Patients were categorized as either clinically definite MS (n = 13), laboratory-supported definite MS (n = 14), or clinically probable MS (n = 4); four patients had clinically probable MS, and in nine MS was suspected. Spinal cord abnormalities were found in 35 of 40 patients (87.5 %), consisting of focal lesions in 31, only diffuse abnormalities in two, and both in two. Asymptomatic spinal cord lesions occurred in six patients. All patients with diffuse spinal cord abnormality had clear spinal cord symptoms and a primary progressive disease course. In clinically definite MS, the inclusion of spinal imaging increased the sensitivity of MRI to 100 %. Seven patients without a definite diagnosis had clinically isolated syndromes involving the spinal cord. Brain MRI was inconclusive, while all had focal spinal cord lesions which explained symptoms and ruled out other causes. Two other patients had atypical brain abnormalities suggesting ischemic/vascular disease. No spinal cord abnormalities were found, and during follow-up MS was ruled out. Spinal cord abnormalities are common in suspected MS, and may occur asymptomatic. Although diagnostic classification is seldom changed, spinal cord imaging increases diagnostic sensitivity of MRI in patients with suspected MS. In addition, patients with primary progressive MS may possibly be earlier diagnosed. Finally, differentiation with atypical lesions may be improved.

Risk factors for developing multiple sclerosis after childhood optic neuritis.

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.

Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis

Objective: To examine the efficacy of gabapentin in the treatment of spasticity and painful muscle spasms in patients with multiple sclerosis. Design: Double-blind, placebo-controlled crossover study. Setting: Free-standing, 93-bed, university-affiliated rehabilitation hospital. Participants: There were 15 patients between the ages of 18 and 50 who had laboratory-supported definite multiple sclerosis with spasticity and leg cramps severe enough to interfere with daily activities, including sleep. Intervention: The patients received the placebo or 400mg gabapentin orally three times a day for 48 hours with an 11-day washout period. If the patients were on currently accepted modes of therapy, including oral baclofen, their current medication was not changed. Main Outcome Measures: The outcome measures were Visual Faces Scale rating, Kurtzke Disability Scale, quantitative surface electromyography, Ashworth Scale, presence or absence of clonus in response to rapid ankle dorsiflexion and wrist extension, presence or absence of reflex withdrawal in response to nailbed pressure to the first finger, and assessment of Babinski response. Results: Statistically significant improvements for the gabapentin-treated patients were found in the Ashworth Scale, Visual Faces Scale, and Kurtzke Disability Scale. Conclusions: At a dose of 400mg orally three times a day, gabapentin may be of value in the treatment of the spasticity and painful muscle cramping experienced by patients with multiple sclerosis.

The effectiveness of occupational therapy and physiotherapy in multiple sclerosis patients with ataxia of the upper limb and trunk

Objective: The aim of the study was to evaluate the effectiveness of therapy intervention in reducing impairment and disability due to upper limb and trunk ataxia in chronic multiple sclerosis (MS). Design: The change in performance scores of two patient groups - an inpatient group who received two weeks' therapy intervention and an outpatient 'control' group awaiting a similar admission - were compared. Subjects: Thirty-seven (out of a total of 62) patients with clinically definite or laboratory-supported definite MS, with ataxia of the upper limbs and/or trunk, and who had stable or slowly progressive disease. Intervention: The (inpatient) treatment group (n = 28) received eight half-hour sessions each of occupational therapy and physiotherapy over eight consecutive working days. Treatment approaches used were aimed at improving dynamic posture and appropriate adaptation of the environment. The control group (n = 9) received no intervention. Assessments: Patients were assessed the day before therapy began and the day after it ended: the control group were assessed at the same (two-week) interval. Assessments used included the Jebsen Test of Hand Function (JTHF), the Kurtzke Functional Systems Scale (FSS) and Expanded Disability Status Scale (EDSS), the Northwick Park Index of activities of daily living (NPI), and patient and assessor visual analogue scales. Assessors were independent of patient treatment. Results: There were no significant differences between the two groups at entry to the study with respect to age, sex and scores on the FSS (exception bowel function). The NPI scores were not significantly different except for walking and feeding, whereas the control group was slightly better (Mann-Whitney U-test; p = 0.048; p = 0.037). No significant difference between the change scores of the two groups was found on the JTHF and FSS neurological scores. The treatment group showed significant improvement compared to controls in the NPI scores and on the self and assessor visual analogue scales. Conclusion: The findings support the clinical impression that therapy used to improve dynamic posture and methods of performing functional tasks can result in improvement of functional ability in patients with MS where spontaneous improvement would not otherwise be expected.

Central motor conduction as a measure of disease progression in early multiple sclerosis

We monitored disease progression in 27 patients with clinically or laboratory-supported definite multiple sclerosis by means of clinical assessments [expanded disability status scale (EDSS), and the neurologic rating scale (NRS)] repeated at 6 month intervals for 2 years. Each clinical assessment was accompanied by evoked potentials (EP; visual, brain stem auditory, and somatosensory evoked potentials), motor evoked potentials elicited by magnetic stimulation, and magnetic resonance imaging of the brain and brain stem. Central conduction indices were calculated for each central pathway. According to the EDSS 18 patients deteriorated, eight were unchanged and one improved. The central motor conduction index (CMCI) was the only conduction parameter which correlated significantly with both EDSS and NRS at baseline [rho=0.51 (EDSS); -0.65 (NRS)], at final investigation, and when individual changes from baseline to final investigation were addressed (rho=0.38; -0.38). Individual deteriorations or improvements of the CMCI during the 2 years correlated with changes in both EDSS and NRS (rho = 0.51; -0.38). The MRI parameters did not correlate with the clinical scores. The concordance between MRI and CMCI in detection of disease activity was 63%. We conclude that the CMCI stands out as an objective, accurate and easily obtained outcome parameter.

Korsakoff's syndrome as the initial presentation of multiple sclerosis

A 37-year-old man presented with an acute amnestic syndrome of Korsakoff's type and an upper brain-stem oculomotor syndrome. After a moderate improvement with steroid therapy, he developed progressive behavioural changes due to a frontal lobe syndrome, in addition to motor and visual impairment. Memory performance was investigated on several occasions during an 11-year follow-up. Diagnosis of laboratory-supported definite multiple sclerosis was established and magnetic resonance imaging showed disseminated white matter lesions, especially in both medial temporal lobes. No other cause than multiple sclerosis was found for the amnestic syndrome. Among the rare cases of Korsakoff's syndrome in the course of multiple sclerosis, this is to our knowledge the first case in which a memory deficit was the initial manifestation of the disease.

Magnetic resonance imaging of the head in the diagnosis of multiple sclerosis: A prospective 2‐year follow‐up with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT

We previously compared the diagnostic capabilities of MRI of the head with CT, evoked potentials, and CSF oligoclonal banding (OB) analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). To examine the ability of MRI and other paraclinical tests to predict the diagnosis of clinically definite MS (CDMS), we did a systematic clinical follow-up of 200 patients who were previously reported. In that study, 85 of 200 could be diagnosed as having laboratory-supported definite MS (LSDMS). In follow-up, we excluded one patient diagnosed as LSDMS who in retrospect was considered to have had CDMS at entry and 15 patients who were eventually diagnosed as having other diseases. After a mean follow-up of 2.1 years, 55 of the remaining 184 patients (30%) had developed CDMS. Thirty-eight of 84 patients with an original diagnosis of LSDMS (45%) and 17 of the remaining 100 patients with suspected MS (17%) had become CDMS. Forty-six of the 55 patients who developed CDMS in follow-up (84%) had an initial MRI that was strongly suggestive of MS. Fifty-two of those 55 CDMS patients (95%) had at least one MS-like abnormality on MRI when originally studied. In contrast, 38 of 55 (69%) had CSF OB, 38 of 55 (69%) had an abnormal VEP, 35 of 55 (64%) had an abnormal SEP, and 21 of 55 (38%) had an abnormal CT when first studied. MRI was the most sensitive single paraclinical test for predicting CDMS. CDMS developed during follow-up in 46 of the 94 patients (49%) whose initial MRI was strongly suggestive of MS.(ABSTRACT TRUNCATED AT 250 WORDS)

The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis

To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres. 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1·0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n=55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n=57); or placebo medications and sham plasma exchange (n=56). All patients were followed for at least 12 months (mean 30·4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not. The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1·0 or more on two consecutive 6-monthly assessments). There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo). Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0·81 cyclophosphamide; 0·69 plasma exchange; 0·69 placebo). A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment. This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.

Prevalence of primary Sjögren's syndrome in patients with multiple sclerosis

Sixty-four consecutive patients with clinically or laboratory-supported definite multiple sclerosis (MS) were evaluated prospectively for evidence of primary Sjögren's syndrome (SS). This diagnosis was established when a patient had objective keratoconjunctivitis sicca, xerostomia, or both together with positive labial salivary gland biopsy. We found 2 patients (3.1%) with clinical evidence of primary SS. Whether this association is fortuitous or whether there is pathogenetic linkage between MS and primary SS remains to be established.

CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material.

A prospective study involving 87 patients was carried out to evaluate the necessity for a high dose of contrast material in addition to delayed computed tomographic (CT) scanning for optimal detection of the lesions of multiple sclerosis in the brain. In patients with either clinically definite multiple sclerosis or laboratory-supported definite multiple sclerosis, CT scans were obtained with a uniform protocol. Lesions consistent with multiple sclerosis were demonstrated on the second scan in 54 patients. In 36 of these 54 patients, the high-dose delayed scan added information. These results are quite similar to those of a previous study from this institution using different patients, in whom the second scan was obtained immediately after the bolus injection of contrast material containing 40 g of organically bound iodine. The lack of real difference in the results of the two studies indicates that the increased dose, not just the delay in scanning, is necessary for a proper study.