The direct costs of multiple sclerosis—study in the Czech Republic

Background

Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system that is often disabling and for which there is currently no cure, though disease-modifying treatment is now available. The aim of this study is to describe the current values of the direct costs of multiple sclerosis (MS) in the Czech Republic.

Methods

Attention is focused on direct medical costs. The costs were monitored in the Czech Republic among 5673 patients in the period between 2011 and 2015. These costs included complex, special and targeted visits at the neurologist, blood collection and the costs of hospitalisation. The results refer to the diagnoses according to the International Statistical Classification of Diseases and Related Health Problems. The attention is focused on MS G35 (NS; brain stem; spinal cord; disseminated; generalised).

Results

The average total direct costs per patient per year are 4838.1 €. Not every patient has to be hospitalised during the year, and not every patient has prescribed medication. According to the above data, 12% of patients are hospitalised and 55% of patients are prescribed medication. The minimum average cost per patient without medication and hospitalisation is 54.1 €.

Conclusion

Cost evaluation across countries is difficult due to the different evidence. If only selected direct costs considered in this study are compared, the absolute economics burden increases over time. The only statistically significant difference in the average price and the time spent is between 2012 and 2013, where the correlation value is 0.597.

     

Neurophysiological impairments in multiple sclerosis—Central and peripheral motor pathways

A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS.     

Amyloid in a multiple sclerosis lesion is clearly of Aλ type

In rare multiple sclerosis cases amyloid is deposited in demyelinated plaques. In one such case amyloid was examined immunohistochemically with a panel of antibodies directed against different amyloid types. The amyloid was classified as the Aλ type produced by a local monoclonal B cell population. Received: 28 September 1999 / Revised: 17 March 2000 / Accepted: 20 March 2000     

A longitudinal study of cognitive function in multiple sclerosis: is decline inevitable?

Journal of Neurology - Numerous cross-sectional studies report cognitive impairment in multiple sclerosis (MS), but longitudinal studies with sufficiently long-term follow-up are scarce. We aimed...     

The effects of transcranial direct current stimulation on sleep in patients with multiple sclerosis–A pilot study

BackgroundSleep complaints are commonly reported by patients with multiple sclerosis (PwMS). Several pharmacological and alternative interventions have been tried, but are usually faced by limited efficacy. Hence, exploring other methods such as transcranial direct current stimulation (tDCS), might be of interest. The aim of this study was to assess the effects of bifrontal tDCS on subjective (i.e., Epworth Sleepiness Scale (ESS)) and objective sleep measures (i.e., actigraphy).MethodsSeven patients completed the study. Patients randomly received two blocks of five daily sessions each in a crossover design (active and sham, with a washout interval of three weeks). The anode and cathode were placed over the left and right dorsolateral prefrontal cortices, respectively. Sleep assessment included ESS, sleep onset latency, total sleep duration, time in bed, sleep efficiency, waking after sleep onset, and number of awakenings.ResultsCompared to baseline scores (11.14 ± 4.06), significant decrease in ESS was obtained after active intervention (7.86 ± 4.18; p = 0.011), but not after sham intervention (9.57 ± 5.62; p = 0.142). No significant changes were observed with regards to actigraphy measures. Sessions were well tolerated, and no serious side-effects were reported at any time.ConclusionBifrontal tDCS resulted in significant improvement in daytime sleepiness, but did not yield any effect on objective sleep measures in PwMS. This discrepency might be explained by the modest association that could exist between objective and subjective sleep measures. In addition, it could be assumed that modulating objective sleep measures would require a larger sample size, more stimulation sessions, or modulation of other cortical areas.     

Congenital adrenal hyperplasia and multiple sclerosis: is there an increased risk of multiple sclerosis in individuals with congenital adrenal hyperplasia?

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis, generally caused by a total or partial deficiency in 21-hydroxylase, due to a deletion of or mutations in the CYP21 gene (the gene that codes for 21-hydroxylase). Impaired cortisol biosynthesis results in corticotropin hypersecretion, which leads to overproduction of intermediate metabolites and androgens. OBJECTIVE: To describe for the first time, to our knowledge, a patient with CAH and multiple sclerosis (MS). DESIGN: Case report. PATIENT: A 22-year-old woman, diagnosed at birth as having a salt-losing 21-hydroxylase deficiency, had sudden visual loss in the right eye and pyramidal, sensory, and cerebellar signs. Repeated brain magnetic resonance images showed focal white matter lesions in periventricular areas, the corpus callosum, the cerebellum, and the brainstem. A cerebrospinal fluid examination revealed several oligoclonal bands. Thereafter, she had 2 relapses, characterized by ataxia and diplopia, and recovered after corticosteroid treatment. RESULTS: The reported case fulfills the diagnostic criteria for CAH and MS. CONCLUSIONS: Some clues suggest that the association between CAH and MS could be nonincidental: a possible MS susceptibility locus is on chromosome 6p21, on which the CYP21 gene is located; the CYP21 gene and the CYP21P pseudogene alternate in tandem with the C4 genes (the genes that code for the homonym complement protein) (C4AQ0 is particularly frequent in patients with relapsing-remitting MS); and, in previous studies, brain magnetic resonance imaging showed T2-hyperintense focal areas in the white matter of CAH patients. Our observation should alert neurologists to the presence of signs and symptoms suggestive of late-onset CAH in MS patients and, in turn, endocrinologists to the appearance of neurological signs and symptoms in CAH patients.     

TNF-α-mediated anxiety in a mouse model of multiple sclerosis

Multiple sclerosis (MS) causes a variety of motor and sensory deficits and it is also associated with mood disturbances. It is unclear if anxiety and depression in MS entirely reflect a subjective reaction to a chronic disease causing motor disability or rather depend on specific effects of neuroinflammation in neuronal circuits. To answer this question, behavioral, electrophysiological, and immunofluorescence experiments were performed in mice with experimental autoimmune encephalomyelitis (EAE), which models MS in mice. First, we observed high anxiety indexes in EAE mice, preceding the appearance of motor defects. Then, we demonstrated that tumor necrosis factor α (TNF-α) has a crucial role in anxiety associated with neuroinflammation. In fact, intracerebroventricular (icv) administration of etanercept, an inhibitor of TNF-α signaling, resulted in anxiolytic-like effects in EAE-mice. Accordingly, icv injection of TNF-α induced per se overt anxious behavior in control mice. Moreover, we propose the striatum as one of the brain regions potentially involved in EAE anxious behavior. We observed that before disease onset EAE striatum presents elevated TNF-α levels and strong activated microglia, early signs of inflammation associated with alterations of striatal excitatory postsynaptic currents (EPSCs). Interestingly, etanercept corrected the synaptic defects of pre-symptomatic EAE mice while icv injection of TNF-α in non-EAE mice altered EPSCs, thus mimicking the synaptic effects of EAE. In conclusion, anxiety characterizes EAE course since the very early phases of the disease. TNF-α released from activated microglia mediates this effect likely through the modulation of striatal excitatory synaptic transmission.     

The processing of compounds in bilingual aphasia: A multiple‐case study

Background: While converging evidence has led to the view that people with aphasia exploit compositional procedures when producing compound words, the issue of what compound‐internal characteristics are at play during these procedures is still under debate. It has been argued that constituent position and/or morphosyntactic prominence, i.e., being the head constituent of a compound, may influence the manner in which compounds are accessed. However, findings obtained from patient performances are thus far inconclusive, because positional and headedness effects are frequently confounded in a language.

Aims: In order to disentangle position‐in‐the‐string and headedness effects in compound production in aphasia, the main objective of this study is to investigate the performance of bilingual patients speaking languages in which these effects can be teased apart. Our secondary goal is to probe the roles of grammatical category (adjectives vs nouns) and of between‐language phonological similarity, as both these factors have been demonstrated to influence compound processing.

Methods & Procedures: Three English–French bilingual persons with aphasia participated in the study. Three experimental tasks, reading, repetition, and translation of isolated compound words, were administrated in each language. We contrasted French and English compounds that differ in the position of the head constituent: left for French and right for English.

Outcomes & Results: Two participants showed a similar pattern—a significantly reduced number of errors for the head (or first) constituent as compared to the non‐head (or second) constituent in French and an equivalent number of errors for both constituents in English—pointing to the cumulative effects of headedness and first‐position‐in‐the‐string in French, and to the mutual cancelling out of these effects in English. The third participant exhibited a non‐head constituent advantage in both languages, indicating that semantic modification of the head constituent by the non‐head constituent plays a prominent role in her accessing procedures. For all three participants phonological similarity influenced production, while grammatical category did not.

Conclusions: Our results reveal that headedness and position interact in the processing of compounds. They also demonstrate that compound constituents are processed asymmetrically across and within languages, thus confirming that people with aphasia are sensitive to compound‐internal structure. Moreover, they show that patients rely on varying structural information when accessing compounds.     

The role of osteopontin: A shared pathway in the pathogenesis of multiple sclerosis and osteoporosis?

Osteopontin (OPN) was suggested to have a role in the pathophysiology of MS and in bone metabolism. However, we formerly reported increased presence of osteoporosis in MS patients independent of corticosteroid treatment, there is only limited information about the mechanism of bone loss. In this study, we investigated the role of OPN on bone mineral density in MS patients. Thirty-three relapsing-remitting (RR), 12 secondary progressive (SP), and 5 primary progressive (PP) MS patients and 30 healthy controls were prospectively enrolled. Students' t test, chi-square test, and Pearson correlations were used. The mean OPN level was 155.4+/-81.8 ng/ml in controls, and 15.9+/-36.2 ng/ml in MS patients (p<0.001).No statistical difference was observed among RR, SP and PPMS patients (p=0.162). No relationship was found between OPN levels and age at onset of disease (p=0.830), gender (p=0.785), MS subtypes (p=0.330), disease duration (p=0.744), or EDSS scores (p=0.633).About 34% of MS patients versus 10.3% of controls had osteoporosis (p=0.017).Osteopontin levels showed no significant correlation with osteoporosis in controls, but were lower in MS patients with osteoporosis in femur neck (r=0.85, p=0.010).The cumulative dose of corticosteroid treatment did not correlate with OPN levels (p=0.285).In conclusion, our results suggest that OPN may have a role as a shared cytokine in pathogenesis of MS and osteoporosis.     

The Rao’s Brief Repeatable Battery in the study of cognition in different multiple sclerosis phenotypes: application of normative data in a Serbian population

Cognitive impairment is prevalent in multiple sclerosis (MS) occurring in 43–72 % of patients with all MS phenotypes. The aim of our study was to assess cognitive performance in different MS subtypes in Serbian population. Rao’s Brief Repeatable Battery of neuropsychological tests (BRB-N) was administered to 168 MS patients [37 patients with clinically isolated syndrome (CIS) suggestive of MS, 65 with relapsing-remitting MS (RRMS), 31 with secondary progressive MS (SPMS) and 35 patients with primary progressive MS (PPMS)]. The percentage of cognitively impaired patients in our total MS cohort was 58.9 %. Prevalence of cognitive dysfunction was 40.5 % in CIS group, 36.9 % in RRMS, 96.8 % in SPMS, and 85.7 % in PPMS group. Patients in CIS and RRMS groups performed consistently better all tests of the Rao’s battery than patients in SPMS and PPMS cohort. CIS and RRMS groups performed consistently better in all tests of the Rao’s battery than SPMS and PPMS cohort. Additionally, difference in the performance of any of the BRB-N tests was not found between CIS and RRMS. However, there was a significant difference between SPMS and PPMS patients in the performance on five tests of Rao’s battery. Statistical significance (p < 0.05) in favor of PPMS patients was demonstrated for the following tasks: SRT_lts, SRT_cltr, SDMT, SRT_D, SPART_D. Our study demonstrates that cognitive impairment is frequent in all MS phenotypes. Furthermore, we have found that cognitive deficit is most severe and most frequent in SPMS patients, followed by PPMS subjects and then CIS and RRMS patients.     

The use of ID migraine™ questionnaire in patients with multiple sclerosis

Primary headaches are underdiagnosed and undertreated in patients with multiple sclerosis (MS). The aim of our study was to investigate the possibility of using the ID migraine™ (ID-M) questionnaire to make a first-line diagnosis of migraine in subjects affected by MS. We consecutively recruited 144 patients regularly attending the MS Centre of S. Andrea Hospital in Rome. Results from ID-M were matched with diagnoses of a blind neurologist. According to the ICHD-II criteria, 77 (53.5%) patients were diagnosed as suffering from migraine. ID-M showed high sensitivity (91%) and specificity (94%) in identifying patients with migraine. ID-M was also able to discriminate patients affected by headache following interferon beta therapy, having only the 10% out of these patients a positive ID-M. The use of the ID-M as a screening test is warranted not only in the epidemiological research, but also to ensure a better clinical management of patients with MS.     

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two pathologies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentation, laboratory findings (MRI and CSF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. CSF and MRI data were clearly different: oligoclonal bands (OCB) were found in 23% of NMO cases and 88% of MS (P < 0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P < 0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P < 0.001). Clinical outcome was evaluated as more severe in the NMO group (P < 0.001). On the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. Our study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two pathologies but only when MRI data were applied. This finding could have implications for future therapeutic trials.     

Efficacy and tolerability of natalizumab in relapsing–remitting multiple sclerosis patients: a post-marketing observational study

The X-linked genetic Fabry disease causes multiorgan lesions due to intracellular storage of the substrate globotriaosylceramide. Neurological involvement ranges from painful, small fiber neuropathy to cerebrovascular disorders to multifocal aggressive forms. Disease identification through proper differential diagnosis and timely assessment of organ damage should guide a careful treatment planning. Mainstay treatment, include enzyme replacement and support therapy. Neurologists have a pivotal role in early instrumental and clinical detection of organ damage. A panel of experts has developed a set of consensus recommendations to guide the approach of neurologists to Fabry disease.     

The prevalence of multiple sclerosis in the District of Santarém, Portugal

The prevalence of multiple sclerosis (MS) in Portugal is still unknown. Recent studies conducted in southern European countries showed higher than expected rates of MS prevalence.In an attempt to evaluate the MS prevalence in Santarém--a district with 62621 inhabitants (1991 census) located in the centre of Portugal--we have conducted a population survey in this district for five years. The crude prevalence rate found was 46.3/100,000. This figure is not different from findings recently reported in studies conducted at similar latitudes in neighbour southern European countries. This was the first population survey conducted in Portugal, and it is the first accurate contribution to the knowledge of the MS prevalence in this country.     

Is central fatigue in multiple sclerosis a disorder of movement preparation?

We tested the hypothesis that fatigue in MS is related to a dysfunction in cortical areas involved in movement preparation. Thirty-three patients with clinically definite MS (16 with fatigue MS-F, 17 without fatigue MS-NF) and a relapsing-remitting course, matched for disease severity and duration, disability scores and level of depression were enrolled. They underwent a combined assessment with magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS) and, for the electrophysiological study, were compared with 12 healthy controls. MRI was used to assess regional and total lesion-load volume (LL) on T1- and T2-weighted sequences and total brain volume on T1-weighted sequences. With TMS we tested central motor conduction time, short intracortical inhibition (SICI) and facilitation (ICF), pre-movement facilitation related to a simple reaction time paradigm and the effect of short trains of 5-Hz repetitive TMS (rTMS). No significant differences were found in total and regional LL between MS-F and MS-NF, except for a significant increase in frontal lobe LL in MS-F. Neurophysiological assessment did not disclose any difference of SICI and ICF among the three groups. The significant increase of MEP size produced by 5 Hz rTMS in controls was absent in both MS-NF and MS-F. MS-F lacked pre-movement facilitation compared with MS-NF and controls. The lack of pre-movement facilitation and the increased frontal lobe lesion load were significantly correlated to the FSS score, suggesting that central fatigue in MS is probably due to a dysfunction of cortical motor areas involved in movement preparation.     

The prevalence of multiple sclerosis in the north–west Italian province of Genoa

The objective of this study was to assess the prevalence of multiple sclerosis (MS), calculated as point prevalence on 31 December 1997, in the province of Genoa, North–western Italy. Methods The province of Genoa is located in North–western Italy, an area of 1835 km². On the point prevalence day the population consisted of 913,218 inhabitants. MS cases were identified by analysing archives of the hospitals with neurological or rehabilitation wards, neurologists serving the community, files of local chapters of the Italian MS society, all requests for oligoclonal bands analysis on CSF in the studied area. Patients included in the study were MS cases diagnosed before 31 December 1997 according to the Poser criteria resident in the province under study. Results A total of 857 subjects were alive and residing in the province of Genoa on the prevalence day. The overall crude prevalence rate was 94 per 100,000 (95% CI 88–100); 291 were males (34%) with a crude prevalence of 67 per 100,000 (95 % CI 60–76) and 566 were females (66%) with a prevalence of 118 per 100,000 (95% CI 108–128). The female/male ratio was 1.9. When age and sex were adjusted to the Italian standard population of 1991 prevalence was 85 per 100,000. Five hundred and thirty two out of the 857 patients agreed to be interviewed. The interviewed sample was representative of the prevalence sample: sex and gender distributions were identical in the two samples. The overall mean age was 48 (± 13) years (48 ± 12 years in males; 48 ± 14 years in females). Mean disease duration was 15 (± 10) years for males and 16 (± 11) years for females. Two hundred and ninety one (55 %) subjects had a relapsing remitting (RR) clinical course, 150 (28%) were secondary progressive (SP) and 91 (17%) were primary progressive (PP). Mean EDSS score was 5 (± 2; median 5). The mean age at time of onset was 33 (±10) years for males and 32 (± 11) years for females. The disease onset was monosymptomatic in 76% (n = 407) patients and polysymptomatic in 24% (n = 125). The mean length of time between clinical onset and diagnosis was 5 (± 6) years. Conclusion We confirmed that the province of Genoa is a very high risk area for MS. We found a high rate of patients with a PP course; also the proportion of patients with high disability scores is greater compared to previous studies.