As there were only regional studies in Hungary about the prevalence of multiple sclerosis (MS), we aimed to estimate its epidemiological features using data of Hungary's single-payer health insurance ...system. Pseudonymized database of claims reported by hospitals and outpatient services between 2004-2016 was analyzed and linked with an independent database of outpatient pharmacy refills between 2010-2016. We established an administrative case definition of MS and validated it on medical records of 309 consecutive patients. A subject was defined as MS-patient if received MS diagnosis (International Classification of Diseases, 10th edition, code G35) on three or more occasions at least in 2 calendar years and at least once documented by a neurologist. Patients were counted as incident cases in the year of the first submitted claim for MS. We allowed a 6-year-long run-in period, so only data between 2010-2015 are discussed. Sensitivity of the administrative case definition turned out to be 99%, while specificity was >99%. Crude prevalence of MS has increased from 109.3/100,000 in 2010 to 130.8/100,000 in 2015 (p-value = 0.000003). Crude incidence declined from 7.1/100,000 (2010) to 5.4/100,000 (2015) (p-value = 0.018). Direct standardization - based on European standard population and results of nationwide Hungarian census of 2011 - revealed that age standardized prevalence was 105.2/100,000 (2010), which has grown to 127.2/100,000 (2015) (p-value = 0.000001). Age standardized incidence rate declined from 6.7/100,000 (2010) to 5.1/100,000 (2015) (p-value = 0.016). The ratio of MS-patients receiving greater than or equal to1 prescription for disease modifying treatment increased from 0.19 (2010) to 0.29 (2015) (p-value = 0.0051). The female/male ratio of prevalent cases remained 2.6. The prevalence of MS in Hungary is higher than previously reported, the incidence rate is moderate. The prevalence is rising, the incidence rate shows decline. The proportion of patients receiving disease modifying treatment grows but was still around 30% in 2015.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative ...to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 95% CI 0·14–0·23 vs 0·53 0·46–0·61, p<0·0001) and fingolimod (0·15 0·10–0·20 vs 0·34 0·26–0·41, p<0·0001), and was associated with a similar annualised relapse rate as natalizumab (0·20 0·14–0·26 vs 0·19 0·15–0·23, p=0·78). For the disability outcomes, alemtuzumab was associated with similar probabilities of disability accumulation as interferon beta (hazard ratio HR 0·66 95% CI 0·36–1·22, p=0·37), fingolimod (1·27 0·60–2·70, p=0·67), and natalizumab (0·81 0·47–1·39, p=0·60). Alemtuzumab was associated with similar probabilities of disability improvement as interferon beta (0·98 0·65–1·49, p=0·93) and fingolimod (0·50 0·25–1·01, p=0·18), and a lower probability of disability improvement than natalizumab (0·35 0·20–0·59, p=0·0006). Interpretation Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles. Funding National Health and Medical Research Council, and the University of Melbourne.
Objective
In patients suffering multiple sclerosis activity despite treatment with interferon β or glatiramer acetate, clinicians often switch therapy to either natalizumab or fingolimod. However, no ...studies have directly compared the outcomes of switching to either of these agents.
Methods
Using MSBase, a large international, observational, prospectively acquired cohort study, we identified patients with relapsing–remitting multiple sclerosis experiencing relapses or disability progression within the 6 months immediately preceding switch to either natalizumab or fingolimod. Quasi‐randomization with propensity score–based matching was used to select subpopulations with comparable baseline characteristics. Relapse and disability outcomes were compared in paired, pairwise‐censored analyses.
Results
Of the 792 included patients, 578 patients were matched (natalizumab, n = 407; fingolimod, n = 171). Mean on‐study follow‐up was 12 months. The annualized relapse rates decreased from 1.5 to 0.2 on natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative postswitch difference in relapse hazard (p = 0.002). A 2.8 times higher rate of sustained disability regression was observed after the switch to natalizumab in comparison to fingolimod (p < 0.001). No difference in the rate of sustained disability progression events was observed between the groups. The change in overall disability burden (quantified as area under the disability–time curve) differed between natalizumab and fingolimod (−0.12 vs 0.04 per year, respectively, p < 0.001).
Interpretation
This study suggests that in active multiple sclerosis during treatment with injectable disease‐modifying therapies, switching to natalizumab is more effective than switching to fingolimod in reducing relapse rate and short‐term disability burden. Ann Neurol 2015;77:425–435
To evaluate macular morphology in the eyes of patients with multiple sclerosis (MS) with or without optic neuritis (ON) in previous history.
Optical coherence tomography (OCT) examination was ...performed in thirty-nine patients with MS and in thirty-three healthy subjects. The raw macular OCT data were processed using OCTRIMA software. The circumpapillary retinal nerve fiber layer (RNFL) thickness and the weighted mean thickness of the total retina and 6 intraretinal layers were obtained for each eye. The eyes of MS patients were divided into a group of 39 ON-affected eyes, and into a group of 34 eyes with no history of ON for the statistical analyses. Receiver operating characteristic (ROC) curves were constructed to determine which parameter can discriminate best between the non-affected group and controls.
The circumpapillary RNFL thickness was significantly decreased in the non-affected eyes compared to controls group only in the temporal quadrant (p = 0.001) while it was decreased in the affected eyes of the MS patients in all quadrants compared to the non-affected eyes (p<0.05 in each comparison). The thickness of the total retina, RNFL, ganglion cell layer and inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, comprising the RNFL and GCL+IPL) in the macula was significantly decreased in the non-affected eyes compared to controls (p<0.05 for each comparison) and in the ON-affected eyes compared to the non-affected eyes (p<0.001 for each comparison). The largest area under the ROC curve (0.892) was obtained for the weighted mean thickness of the GCC. The EDSS score showed the strongest correlation with the GCL+IPL and GCC thickness (p = 0.007, r = 0.43 for both variables).
Thinning of the inner retinal layers is present in eyes of MS patients regardless of previous ON. Macular OCT image segmentation might provide a better insight into the pathology of neuronal loss and could therefore play an important role in the diagnosis and follow-up of patients with MS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the differences in texture descriptors and optical properties of retinal tissue layers in patients with multiple sclerosis (MS) and to evaluate their usefulness in the detection of ...neurodegenerative changes using optical coherence tomography (OCT) image segmentation.
38 patients with MS were examined using Stratus OCT. The raw macular OCT data were exported and processed using OCTRIMA software. The enrolled eyes were divided into two groups, based on the presence of optic neuritis (ON) in the history (MSON+ group, n = 36 and MSON- group, n = 31). Data of 29 eyes of 24 healthy subjects (H) were used as controls. A total of seven intraretinal layers were segmented and thickness as well as optical parameters such as contrast, fractal dimension, layer index and total reflectance were measured. Mixed-model ANOVA analysis was used for statistical comparisons.
Significant thinning of the retinal nerve fiber layer (RNFL), ganglion cell/inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, RNFL+GCL+IPL) was observed between study groups in all comparisons. Significant difference was found in contrast in the RNFL, GCL+IPL, GCC, inner nuclear layer (INL) and outer plexiform layer when comparing MSON+ to the other groups. Higher fractal dimension values were observed in GCL+IPL and INL layers when comparing H vs. MSON+ groups. A significant difference was found in layer index in the RNFL, GCL+IPL and GCC layers in all comparisons. A significant difference was observed in total reflectance in the RNFL, GCL+IPL and GCC layers between the three examination groups.
Texture and optical properties of the retinal tissue undergo pronounced changes in MS even without optic neuritis. Our results may help to further improve the diagnostic efficacy of OCT in MS and neurodegeneration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Using the emerging technique of peripheral nerve ultrasonography, multiple focal nerve swellings corresponding to sites of existing conduction blocks have been described in demyelinating ...polyneuropathies. We report two cases of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). In the first, multiple focal nerve enlargements were detected by ultrasound at sites of previous conduction blocks, well after complete clinical and electrophysiological resolution. In the second case, existing proximal conduction blocks could be localized by ultrasound. Our cases highlight the importance of nerve ultrasound in identifying conduction blocks and demonstrate that ultrasonographic morphological changes may outlast functional recovery in demyelinating neuropathies.
The purpose of our study was to examine how the pathologic type of polyneuropathy affects nerve size as assessed by high-resolution ultrasonography with a 15 MHz transducer. Cross-sectional area ...(CSA) of the C5-C7 nerve roots and several upper and lower limb nerves at multiple sites was measured in 38 patients with acquired diffuse sensorimotor demyelinating or axonal polyneuropathy and in 34 healthy control subjects. Significant differences were found among the groups for all nerve and root segments: Both types of polyneuropathy are characterized by nerve enlargement in comparison to controls, but in different patterns. In demyelinating polyneuropathies, an additional degree of nerve thickening appears in proximal upper limb nerves and cervical nerve roots compared with axonal polyneuropathies. With respect to the other nerves, a similar degree of nerve enlargement was observed in both patient groups. These results highlight that ultrasonography may be a complementary tool in differentiating polyneuropathies.
Highlights ► High-resolution ultrasound shows pronounced focal morphological abnormalities of the ulnar nerve at the elbow in UNE, which may be of significant diagnostic help particularly in nerve ...lesions with non-localizing axonal loss. ► Nerve size parameters, such as the largest cross sectional area (CSAmax ) of the ulnar nerve around the elbow and the cubital-to-humeral nerve area ratio (CHR) show significantly larger nerve swelling in axonal lesions, as compared to predominantly demyelinating lesions. ► The subtype of axonal lesion also affects nerve size parameters: CSAmax values in patients with sensorimotor axonal lesion were significantly higher than in those with pure sensory axonal involvement.
Leber Hereditary Optic Neuropathy (LHON) is the most common inherited mitochondrial disease characterized by bilateral, painless, subacute visual loss with a peak age of onset in the second to third ...decade. Historically, LHON was thought to be exclusively maternally inherited due to mutations in mitochondrial DNA (mtDNA); however, recent studies have identified an autosomal recessive form of LHON (arLHON) caused by point mutations in the nuclear gene,
.
In this study, we report the cases of three Eastern European individuals presenting with bilateral painless visual loss, one of whom was also exhibiting motor symptoms. After a several-year-long diagnostic journey, all three patients were found to carry the homozygous c.152A>G (p.Tyr51Cys) mutation in
. This has been identified as the most common arLHON pathogenic variant and has been shown to exhibit a significant founder effect amongst Eastern European individuals.
This finding adds to the growing cohort of patients with arLHON and demonstrates the importance of
screening in patients with molecularly undiagnosed LHON, particularly in Eastern European individuals. It is of heightened translational significance as patients diagnosed with arLHON exhibit a better prognosis and response to therapeutic treatment with the co-enzyme Q10 analog idebenone.
•Features of BMS patients who were never treated.•Comparison to healthy controls and relapsing-remitting MS patients treated from disease onset.•Cognitive deficit in BMS was similar to RRMS.•BMS ...group was more depressed.•Disease modifying treatment did not improve cognitive deficit in RRMS over two years.
The definition of benign multiple sclerosis (BMS) is still debated. It is mainly based on physical status, however, there is an attempt to involve cognitive functioning or paraclinical factors in order to avoid unnecessary long-term treatment with disease-modifying therapies and to identify these subjects in the early stages of the disease. Therefore the aim of our two-year follow-up study was to investigate the pattern of cognitive functioning and depression in patients with BMS compared to treated relapsing-remitting MS (RRMS) patients and healthy controls.
A group of 22 BMS patients was tested against matched RRMS patients and healthy controls. All individuals underwent neuropsychological evaluation exploring mood and the cognitive domains most frequently impaired in MS. MS patients were retested at two-year follow-up.
In terms of cognitive functions there were no differences between BMS and RRMS patients either at baseline or at two-year follow-up. Compared to healthy controls BMS patients showed poorer performance in long-term visuo-spatial memory and information processing speed, whereas, complex attention, working memory, long-term verbal memory – despite slower verbal learning – and executive function were found to be intact. RRMS patients showed significant difference in complex attention, long-term visual memory and information processing speed. Cognitive impairment differed in the patient groups in terms of severity. Both patient groups were depressed compared to controls, but significant differences were found only between BMS and healthy individuals.
The results of our study confirm that cognitive functions and mood can be affected in MS independent of disease course and disease modifying treatment. The “benign” label should be treated as only a reference to physical status and non-motor symptoms should be routinely monitored. Without receiving therapy it is an existing entity with longstanding minimal disability.
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