MS-taudin diagnoosi, lääkehoito ja kuntoutus

Mitä uutta päivityksessä? MS-taudin lääkehoito aloitetaan heti McDonaldin diagnostisten kriteereiden täytyttyä. Henkilöitä, joilla todetaan kliinisesti eriytynyt oireyhtymä (KEO) ja suurentunut riski saada MS-tauti (MS-tautiin sopivia muutoksia magneettikuvauksissa (MK) ja selkäydinnesteessä), seurataan MK:lla 3-6 kuukauden välein vuoden ajan ensimmäisestä kuvauksesta. Akuutti pahenemisvaihe hoidetaan suonensisäisellä tai suun kautta otettavalla jättiannoksisella kortikosteroidilla. Ensisijainen lääkehoito on beetainterferoni tai glatirameeriasetaatti. Beetainterferonihoidossa olevilta mitataan 12 ja 24 kuukauden kuluttua hoidon aloituksesta MxA-vaste. Jos vaste puuttuu toistetuissa määrityksissä, hoitoa on vaihdettava, ja mikäli vaste on vähäinen, mittaus toistetaan. Beetainterferoni- tai glatirameeriasetaattihoidosta huolimatta aktiivisen MS-taudin toissijainen lääkehoito on natalitsumabi. Immunomoduloiva hoito lopetetaan, mikäli tauti muuttuu toissijaisesti eteneväksi eikä ole enää immunologisesti aktiivinen. English summary: Update on Current Care guidelines: Diagnostics, treatment and rehabilitation of multiple sclerosis Treatment is initiated when the McDonald criteria for relapsing-remitting multiple sclerosis (RRMS) are fulfilled. High-risk patients with clinically isolated syndrome are followed using magnetic resonance imaging for one year after the first imaging. Interferon-β or glatiramer acetate are the first-line immunomodulating drugs (IMD) for RRMS. MxA protein is measured 12 and 24 months after initiation of Interferon-β to evaluate possible development of neutralizing antibodies. If MxA protein may not be detected repeatedly interferon-β treatment is discontinued. If the disease is active in spite of treatment with first-line IMD, natalizumab may be considered as a second-line therapy. IMD is stopped when the transition to secondary progressive phase has occurred (or upon transition to secondary progressive phase)

Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance

In Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) α-synuclein (αS) pathology is seen that displays a predictable topographic distribution. There are two staging/categorization systems, i.e. Braak’s and McKeith’s, currently in use for the assessment of αS pathology. The aim of these diagnostic strategies in pathology is, in addition to assess the stage/severity of pathology, to assess the probabilities of the related clinical symptomatology i.e. dementia and extrapyramidal symptoms (EPS). Herein, we assessed the applicability of these two staging/categorization systems and the frequency of dementia and EPS in a cohort of 226 αS-positive-subjects. These subject were selected from a large autopsy sample (n = 1,720), irrespective of the clinical presentation, based on the detection of αS-immunoreactivity (IR) in one of the most vulnerable nuclei; in the dorsal motor nucleus of vagus, substantia nigra and basal forebrain. The frequency of αS-IR lesions in this large cohort was 14% (248 out of 1,720). If applicable, each of the 226 subjects with all required material available was assigned a neuropathological stage/category of PD/DLB and finally the neuropathological data was analyzed in relation to dementia and EPS. 83% of subjects showed a distribution pattern of αS-IR that was compatible with the current staging/categorization systems. Around 55% of subjects with widespread αS pathology (Braak’s PD stages 5–6) lacked clinical signs of dementia or EPS. Similarly, in respect to those subjects that fulfilled the McKeith criteria for diffuse neocortical category and displaying only mild concomitant Alzheimer’s disease-related pathology, only 48% were demented and 54% displayed EPS. It is noteworthy that some subjects (17%) deviated from the suggested caudo-rostral propagation suggesting alternative routes of progression, perhaps due to concomitant diseases and genetic predisposition. In conclusion, our results do indeed confirm that current staging/categorization systems can readily be applied to most of the subjects with αS pathology. However, finding that around half of the subjects with abundant αS pathology remain neurologically intact is intriguing and raises the question whether we do assess the actual disease process

MYO9B polymorphisms in multiple sclerosis

"Single-nucleotide polymorphisms (SNPs) in the 30 region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS. European Journal of Human Genetics (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009""Single-nucleotide polymorphisms (SNPs) in the 30 region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS. European Journal of Human Genetics (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009""Single-nucleotide polymorphisms (SNPs) in the 30 region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS. European Journal of Human Genetics (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009"Peer reviewe

Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects

Background/Aims: Abnormal processing of hyperphosphorylated τ (HPτ), amyloid-β (Aβ) and α-synuclein (αS) proteins is considered as causative with regard to the clinical symptoms in age-related neurodegenerative diseases.Methods: In this retrospective, postmortem study applying immunohistochemical methodology, we assessed Alzheimer’s-disease (AD)-related HPτ and Aβ pathology in 178 subjects with αS pathology.Results: These pathologies were frequently seen concomitantly, i.e. HPτ in 83% and Aβ in 62% of the αS-positive cases. Furthermore, the striatum was frequently involved, particularly in subjects with cognitive impairment (65%). The predictive value of widespread HPτ pathology, i.e. stages V–VI, with respect to cognitive impairment was high, since all 18 subjects presenting with this stage were demented. In contrast, the predictive value of widespread αS pathology, i.e. stages 5–6 according to Braak’s Parkinson disease staging, was debatable. Fifty-three percent of the subjects with widespread αS pathology and no or mild AD-related HPτ pathology were cognitively unimpaired. It is noteworthy that striatal Aβ pathology was more often seen in demented subjects independently of HPτ and/or αS status.Conclusion: The causative pathology in subjects with clinically diagnosed dementia with Lewy bodies needs to be clarified in future studies