We aimed to evaluate racial differences in the clinical features of neuromyelitis optica spectrum disorder. This retrospective review included 603 patients (304 Asian, 207 Caucasian, and 92 Afro-American/Afro-European), who were... more
We aimed to evaluate racial differences in the clinical features of neuromyelitis optica spectrum disorder. This retrospective review included 603 patients (304 Asian, 207 Caucasian, and 92 Afro-American/Afro-European), who were seropositive for anti-aquaporin-4 antibody, from 6 centers in Denmark, Germany, South Korea, United Kingdom, United States, and Thailand. Median disease duration at last follow-up was 8 years (range 0.3-38.4 years). Asian and Afro-American/Afro-European patients had a younger onset age than Caucasian patients (mean 36, 33, and 44 years, respectively; < 0.001). During the disease course, Caucasian patients (23%) had a lower incidence of brain/brainstem involvement than Asian (42%) and Afro-American/Afro-European patients (38%) ( < 0.001). Severe attacks (visual acuity ≤0.1 in at least one eye or Expanded Disability Status Scale score ≥6.0 at nadir) at onset occurred more frequently in Afro-American/Afro-European (58%) than in Asian (46%) and Caucasian (...
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In the short time since 2014, three pivotal, worldwide studies in neuromyelitis optica spectrum disorders have been launched: eculizumab, SA237 and inebelizumab, each based on a unique mechanism. Areas covered: In this review, we provide... more
In the short time since 2014, three pivotal, worldwide studies in neuromyelitis optica spectrum disorders have been launched: eculizumab, SA237 and inebelizumab, each based on a unique mechanism. Areas covered: In this review, we provide a discussion on the trial data available for each drug, a brief description of the trial design, and our expert opinion on the potential benefits and risks. Expert opinion: Eculizumab, a C5 complement inhibitor, may prove useful in the treatment of intractable cases of NMOSD, but physicians must be aware of the known risk of meningococcal infection. SA237, an interleukin-6 receptor blocker, may be effective at reducing relapse risk, and also has the potential to reduce neuropathic pain in NMOSD. Inebelizumab, a B cell depleting agent, has never been tested in NMOSD, but based on extensive evidence of efficacy with B cell depletion using rituximab, inebelizumab is expected to work at least as well.
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MOG antibody disease is an autoimmune disease of the central nervous system associated with a serological antibody against MOG, myelin oligodendrocyte glycoprotein. MOG is a glycoprotein expressed on the outer membrane of myelin and... more
MOG antibody disease is an autoimmune disease of the central nervous system associated with a serological antibody against MOG, myelin oligodendrocyte glycoprotein. MOG is a glycoprotein expressed on the outer membrane of myelin and solely found within the central nervous system, including in the brain, optic nerves and spinal cord. Clinically, the disease resembles neuromyelitis optica spectrum disorders in the predilection for relapses of optic neuritis and transverse myelitis. In addition, acute disseminated encephalomyelitis (ADEM) is a well-recognized phenotype of MOG antibody disease in children. In recent studies around the world where MOG testing is available, up to 42% of NMOSD patients who test seronegative for the AQP4 antibody test positive for MOG antibodies. MOG antibody disease has thus recently emerged as a distinct entity carved out of the patient population diagnosed with NMOSD. In this review, we examine the history of the MOG antibody and its relevance to demyeli...
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Background: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies... more
Background: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). Objective: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. Methods: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). Results: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p
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Objective: To characterize paramagnetic MRI phase signal abnormalities in neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions in a cross-sectional study. Methods: Ten patients with NMOSD and 10 patients with... more
Objective: To characterize paramagnetic MRI phase signal abnormalities in neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions in a cross-sectional study. Methods: Ten patients with NMOSD and 10 patients with relapsing-remitting MS underwent 7-tesla brain MRI including supratentorial T2*-weighted imaging and supratentorial susceptibility weighted imaging. Next, we analyzed intra-and perilesional paramagnetic phase changes on susceptibility weighted imaging filtered magnetic resonance phase images. Results: We frequently observed paramagnetic rim-like (75 of 232 lesions, 32%) or nodular (32 of 232 lesions, 14%) phase changes in MS lesions, but only rarely in NMOSD lesions (rim-like phase changes: 2 of 112 lesions, 2%, p , 0.001; nodular phase changes: 2 of 112 lesions, 2%, p , 0.001). Conclusions: Rim-like or nodular paramagnetic MRI phase changes are characteristic for MS lesions and not frequently detectable in NMOSD. Future prospective studies should ask whether these imaging findings can be used as a biomarker to distinguish between NMOSD-and MS-related brain lesions. GLOSSARY ICC 5 intraclass correlation; MS 5 multiple sclerosis; NMOSD 5 neuromyelitis optica spectrum disorder; SWI 5 susceptibility weighted imaging; T2*w 5 T2*-weighted. Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are distinct autoimmune CNS diseases with sometimes overlapping clinical phenotypes. 1 Since treatment options for these 2 CNS diseases differ considerably, 1 the distinction between NMOSD and MS is of high clinical relevance. Recently, new international consensus diagnostic criteria were proposed for NMOSD emphasizing the role of MRI and aquaporin-4 immunoglobulin G antibody testing. 2 Notwithstanding this success, the distinction of NMOSD vs MS can still be challenging in current clinical practice. Ultra-high field MRI at 7 tesla (T) has improved the detection and morphologic characterization of brain lesions by visualizing a central intralesional vein and a T2*-weighted (T2*w) hypointense rim around many MS lesions. 3,4 Contrarily, these imaging features are only rarely depictable in NMOSD lesions. 3,4 At 3T, susceptibility-induced MRI phase signal changes were reported to be specific for MS in contrast to other neurologic disorders such as migraine, antiphospholipid syndrome, and Parkinson disease. 5 Inspired by these findings, we rescanned previously reported patients with NMOSD at 7T 3 and included additional NMOSD cases to describe MRI phase signal changes in NMOSD vs MS lesions in a cross-sectional study.
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Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing... more
Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than...
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Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG)... more
Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the "energy" and "emotional" area of the NHP. In addition, OSA patients also s...
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There are few studies describing periodic limb movement syndrome (PLMS) in rapid eye movement (REM) sleep in patients with narcolepsy, restless legs syndrome, REM sleep behavior disorder, and spinal cord injury, and to a lesser extent, in... more
There are few studies describing periodic limb movement syndrome (PLMS) in rapid eye movement (REM) sleep in patients with narcolepsy, restless legs syndrome, REM sleep behavior disorder, and spinal cord injury, and to a lesser extent, in insomnia patients and healthy controls, but no published cases in multiple sclerosis (MS). The aim of this study was to investigate PLMS in REM sleep in MS and to analyze whether it is associated with age, sex, disability, and laboratory findings. From a study of MS patients originally published in 2011, we retrospectively analyzed periodic limb movements (PLMs) during REM sleep by classifying patients into two subgroups: PLM during REM sleep greater than or equal to ten per hour of REM sleep (n=7) vs less than ten per hour of REM sleep (n=59). A univariate analysis between PLM and disability, age, sex, laboratory findings, and polysomnographic data was performed. MS patients with more than ten PLMs per hour of REM sleep showed a significantly high...
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To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field... more
To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field mapped composite IVCM images. This prospective, cross-sectional, and masked study included 110 eyes of 58 patients seen in a neurology clinic who underwent laser-scanning IVCM (Heidelberg Retina Tomograph 3) of the central cornea. Densities of subbasal corneal nerves and DCs were compared between the average of three representative standard images and the wide-field mapped composite images, which were reconstructed by automated mapping. There were no statistically significant differences between the average of three representative standard images (0.16 mm2 each) and the wide-field composite images (1.29 ± 0.64 mm2) in terms of mean subbasal nerve density (17.10 ± 6.10 vs. 17.17 ± 5.60 mm/mm2, respectively, P = 0.87) and mean subbasal DC density (53.2 ± 67.8 vs. 49.0 ± 54.3 cells/mm2, respectively, P = 0.43). However, there were notable differences in subbasal nerve and DC densities between these two methods in eyes with very low nerve density or very high DC density. There are no significant differences in the mean subbasal nerve and DC densities between the average values of three representative standard IVCM images and wide-field mapped composite images. Therefore, these standard images can be used in clinical studies to accurately measure cellular structures in the subbasal layer.
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Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) have a similar clinical phenotype but represent distinct diseases, requiring different therapies. MicroRNAs (miRNAs) are short non-coding RNAs whose expression... more
Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) have a similar clinical phenotype but represent distinct diseases, requiring different therapies. MicroRNAs (miRNAs) are short non-coding RNAs whose expression profiles can serve as diagnostic biomarkers and which may be involved in the pathophysiology of neuroinflammatory diseases. Here, we analyzed miRNA profiles in serum and whole blood of patients with NMOSD and clinically isolated syndrome (CIS)/relapsing-remitting MS (RRMS) as well as healthy controls by next-generation sequencing (NGS). MiRNA expression profiles were determined by NGS in sera of patients with aquaporin-4 antibody-positive NMOSD (n = 20), CIS/RRMS (n = 20), and healthy controls (n = 20) and in whole blood of patients with NMOSD (n = 11), CIS/RRMS (n = 60), and healthy controls (n = 43). Differentially expressed miRNAs were calculated by analysis of variance and t tests. All significance values were corrected for multiple testing. Select...
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The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to... more
The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an &quot;oxidative stress memory&quot; both in the periphery and CNS compartments, in chronic neuroinflammation.
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Conventional magnetic resonance imaging (MRI) at 1.5 Tesla (T) is limited by modest spatial resolution and signal-to-noise ratio (SNR), impeding the identification and classification of inflammatory central nervous system changes in... more
Conventional magnetic resonance imaging (MRI) at 1.5 Tesla (T) is limited by modest spatial resolution and signal-to-noise ratio (SNR), impeding the identification and classification of inflammatory central nervous system changes in current clinical practice. Gaining from enhanced susceptibility effects and improved SNR, ultrahigh field MRI at 7 T depicts inflammatory brain lesions in great detail. This review summarises recent reports on 7 T MRI in neuroinflammatory diseases and addresses the question as to whether ultrahigh field MRI may eventually improve clinical decision-making and personalised disease management.
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Genome-wide association studies (GWAS) successfully identified various chromosomal regions to be associated with multiple sclerosis (MS). The primary aim of this study was to replicate reported associations from GWAS using an exome array... more
Genome-wide association studies (GWAS) successfully identified various chromosomal regions to be associated with multiple sclerosis (MS). The primary aim of this study was to replicate reported associations from GWAS using an exome array in a large German study. German MS cases (n = 4,476) and German controls (n = 5,714) were genotyped using the Illumina HumanExome v1-Chip. Genotype calling was performed with the Illumina Genome Studio(TM) Genotyping Module, followed by zCall. Single-nucleotide polymorphisms (SNPs) in seven regions outside the human leukocyte antigen (HLA) region showed genome-wide significant associations with MS (P values < 5 × 10(-8) ). These associations have been reported previously. In addition, SNPs in three previously reported regions outside the HLA region yielded P values < 10(-5) . The effect of nine SNPs in the HLA region remained (P < 10(-5) ) after adjustment for other significant SNPs in the HLA region. All of these findings have been reporte...
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Autoantibodies to neuronal tissue are becoming increasingly more important in the evaluation and classification of several neurological diseases, e.g. neuromyelitis optica, paraneoplastic syndromes of the central nervous system (CNS),... more
Autoantibodies to neuronal tissue are becoming increasingly more important in the evaluation and classification of several neurological diseases, e.g. neuromyelitis optica, paraneoplastic syndromes of the central nervous system (CNS), stiff person syndrome or autoimmune epilepsy. As these disorders are rare, no evidence-based recommendations for therapy are available. Currently, immunomodulating or immunosuppressive drugs are administered in most cases. In paraneoplastic syndromes treatment of the underlying cancer is of considerable importance. This overview summarizes current experiences and recommendations in the treatment of autoimmune neurological disorders.
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The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). In this multicenter, randomized, placebo-controlled, double-blind trial... more
The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). In this multicenter, randomized, placebo-controlled, double-blind trial (treatment allocation was concealed), 102 patients with RRMS were randomized to receive a daily oral dose of diazoxide (0.3 and 4 mg/d) or placebo for 24 weeks (NCT01428726). The primary endpoint was the cumulative number of new T1 gadolinium-enhancing lesions per patient, recorded every 4 weeks from week 4 to week 24. Secondary endpoints included brain MRI variables such as the number of new/enlarging T2 lesions and the percentage brain volume change (PBVC); clinical variables such as the percentage of relapse-free patients, relapse rate, and change in the Expanded Disability Status Scale score; and safety and tolerability. Diazoxide was well-tolerated and it produced no serious adverse events other than 1 case of Hashimoto disease. At the 2 doses tested, diazoxide did not improve the primary endpoint or the MRI and clinical variables related to the presence of new lesions or relapses. Patients treated with diazoxide showed reduced PBVC compared with the placebo group, although such changes could be confounded by the higher disease activity of the treated group and the vascular effects of diazoxide. At the doses tested, oral diazoxide did not decrease the appearance of new lesions evident by MRI. The effects in slowing the progression of brain atrophy require further validation. This study provides Class I evidence that for patients with RRMS, diazoxide (0.3 and 4 mg/d) does not significantly change the number of new MRI T1 gadolinium-enhancing lesions.
Low 25-hydroxyvitamin D [25(OH)D] levels correlate with higher disease activity in patients with multiple sclerosis (MS). However, it is not clear whether low 25(OH)D levels directly contribute to increased disease activity or merely... more
Low 25-hydroxyvitamin D [25(OH)D] levels correlate with higher disease activity in patients with multiple sclerosis (MS). However, it is not clear whether low 25(OH)D levels directly contribute to increased disease activity or merely represent a consequence of reduced endogenous vitamin D synthesis in more disabled MS patients. Furthermore, recent data suggest that bioavailable vitamin D, which also integrates the levels of vitamin D binding proteins and albumin, could be a biologically more relevant parameter than 25(OH)D. Measured de-seasonalized 25(OH)D3 and vitamin D binding protein and calculated bioavailable and free vitamin D were compared in the baseline serum samples of 76 patients with clinically isolated syndrome enrolled in a longitudinal observational study and in 76 age- and sex-matched healthy controls (HC). 25(OH)D3 levels were lower in patients with clinically isolated syndrome (P = 0.002) than in HC, and more patients (8/76, 10.5%) than HC (1/76, 1.3%) had 25(OH)D3 levels &lt;25 nmol/l (P = 0.03). In contrast, levels of 25(OH)D2, vitamin D binding protein and calculated levels of free and bioavailable vitamin D did not differ between the two groups. Lower 25(OH)D3 levels already in the earliest phase of disease and in clinically hardly affected patients suggest that low 25(OH)D3 levels are rather a risk factor for than a consequence of MS. Nevertheless, because bioavailable vitamin D levels did not differ between the two groups, the mechanism underlying the association of 25(OH)D3 and MS does not appear to be related to reduced bioavailability of vitamin D.
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Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection. A characteristic feature of MS is an intrathecal synthesis of immunoglobulin (Ig)G. In 90 patients with clinically isolated syndromes/early relapsing-remitting... more
Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection. A characteristic feature of MS is an intrathecal synthesis of immunoglobulin (Ig)G. In 90 patients with clinically isolated syndromes/early relapsing-remitting MS, serum antibodies to Epstein-Barr nuclear antigen-1, but not to EBV viral capsid antigen, rubella, or varicella zoster virus, were higher (p=0.03) in those with than those without a calculated intrathecal IgG synthesis >0% and correlated with the percentage (r=0.27, p=0.009) and concentration (r=0.27, p=0.012) of intrathecally produced IgG. These findings suggest a link between EBV infection and the events leading to intrathecal IgG synthesis in patients with MS.
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The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology... more
The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T). 17 MS or clinically isolated syndrome patients with short (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;60 months) and 11 with long (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;60 months) disease duration underwent 7T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images. 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean±SD 51±37%, range 0-100%) compared to patients with short disease duration (mean±SD 90±19.5%, range 50-100%, p = 0.003). This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques.
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To investigate whether patients with moyamoya angiopathy without obvious retinal pathologies such as retinal infarctions or the congenital morning glory anomaly may have subtle subclinical retinal changes. In this cross-sectional study,... more
To investigate whether patients with moyamoya angiopathy without obvious retinal pathologies such as retinal infarctions or the congenital morning glory anomaly may have subtle subclinical retinal changes. In this cross-sectional study, spectral domain optical coherence tomography was used to analyze the retinal morphology of 25 patients with idiopathic moyamoya angiopathy and 25 age- and sex-matched healthy controls. We analyzed the retinal vasculature with blue laser autofluorescence, lipofuscin deposits with MultiColor confocal scanning laser ophthalmoscopy, and the optic nerve head (ONH) volume with a custom postprocessing algorithm. In addition to the total retinal thickness, semiautomated segmentation was used for segmentation of retinal layers in macular cross scans, macular volume scans, and peripapillary ring scans. The main finding was a pronounced reduction of the ONH volume in moyamoya angiopathy compared with controls (0.76 ± 0.45 mm(3) and 1.47 ± 0.50 mm(3), respective...
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Neben seinen wichtigen Funktionen in Knochenstoffwechsel und Kalziumhomöostase werden Vitamin D weitere positive Effekte bei verschiedenen Erkrankungen zugeschrieben. Aufgrund seiner immunmodulatorischen Eigenschaften könnten... more
Neben seinen wichtigen Funktionen in Knochenstoffwechsel und Kalziumhomöostase werden Vitamin D weitere positive Effekte bei verschiedenen Erkrankungen zugeschrieben. Aufgrund seiner immunmodulatorischen Eigenschaften könnten beispielsweise ein Mangel an Vitamin D oder Veränderungen im Vitamin-D-Metabolismus Risikofaktoren für die Entstehung von Autoimmunerkrankungen wie der Multiplen Sklerose und eine Vitamin-D-Supplementation eine Option für deren Behandlung sein. Tatsächlich gibt es inzwischen zahlreiche Untersuchungen, die einen Zusammenhang zwischen dem Vitamin-D-Haushalt und dem Erkrankungsrisiko einer Multiplen Sklerose nahelegen, sodass Vitamin D einer der lange gesuchten Umweltfaktoren für die multifaktorielle Entstehung dieser häufigsten chronisch-entzündlichen Erkrankung des Zentralnervensystems sein könnte. Weniger aussagekräftig sind die bislang vorhandenen Daten zur Verlaufsmodifikation einer bereits manifesten Multiplen Sklerose durch Vitamin D.Diese Übersichtsarbeit ...
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Background Neuromyelitis optica (NMO, Devic syndrome) is associated with antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO-IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has important... more
Background Neuromyelitis optica (NMO, Devic syndrome) is associated with antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO-IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has important differential diagnostic, prognostic and therapeutic implications. So-called cell-based assays (CBA) are thought to provide the best AQP4-Ab detection rates. Objective To compare directly the AQP4-IgG detection rates of the currently most widely used commercial CBA, which employs cells transfected with a full-length (M1)-human AQP4 DNA in a fashion that allows leaky scanning (LS) and thus expression of M23-AQP4 in addition to M1-AQP, to that of a newly developed CBA from the same manufacturer employing cells transfected with human M23-AQP4-DNA. Methods Results from 368 serum samples that had been referred for routine AQP4-IgG determination and had been tested in parallel in the two assays were compared. Results Seventy-seven out of 368 samples (20.9%) ...
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Neben der Schubaktivität und dem neurologischen Untersuchungsbefund spielt die magnetresonanztomographische (MRT-)Bildgebung bei der Verlaufsbeurteilung der Multiplen Sklerose (MS) derzeit eine Schlüsselrolle. Letztere ist jedoch zeit-... more
Neben der Schubaktivität und dem neurologischen Untersuchungsbefund spielt die magnetresonanztomographische (MRT-)Bildgebung bei der Verlaufsbeurteilung der Multiplen Sklerose (MS) derzeit eine Schlüsselrolle. Letztere ist jedoch zeit- und kostenintensiv und selbst in Deutschland nicht immer kurzfristig verfügbar. Vor allem diskriminiert das Routine-MRT aber nur unzureichend zwischen Demyelinisierung und Neurodegeneration und weist eine Diskrepanz zwischen Läsionslast und Behinderungsgrad auf. Die optische Kohärenztomographie (OCT) ist eine in der Ophthalmologie inzwischen gut validierte, nichtinvasive Methode zur Darstellung und Quantifizierung neurodegenerativer Prozesse der Retina, wie sie auch bei der MS und zahlreichen anderen neurologischen Erkrankungen auftreten. Darüber hinaus ist die OCT-Untersuchung im klinisch-ophthalmologischen Einsatz kostengünstig, mit geringem Zeitaufwand durchführbar, gut reproduzierbar und für den Patienten nicht belastend, mithin ideale Voraussetzu...
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Besides the relapse rate and neurological examination, magnetic resonance imaging (MRI) plays a key role in multiple sclerosis (MS) monitoring. However, MRI is costly and even in Germany not always readily available. Additionally, routine... more
Besides the relapse rate and neurological examination, magnetic resonance imaging (MRI) plays a key role in multiple sclerosis (MS) monitoring. However, MRI is costly and even in Germany not always readily available. Additionally, routine MRI scans are not sensitive enough regarding differentiation between demyelination and neurodegeneration and show a discrepancy between lesion load and the degree of disability. In contrast, optical coherence tomography (OCT) is a validated non-invasive method for the quantification of neurodegenerative processes in the retina, as they appear in MS and other neurological diseases. The OCT is inexpensive, easy to handle and highly reproducible. Additionally, it is well tolerated and thus represents a promising tool for monitoring of neurodegenerative disorders. This article describes in detail the OCT technique and its usefulness for both diagnosis and monitoring of MS.
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ABSTRACT The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Typical clinical presentations include cognitive deficits,... more
ABSTRACT The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Typical clinical presentations include cognitive deficits, psychiatric symptoms, movement disorders and seizures and the majority of patients responds well to immunotherapy. Pathophysiological mechanisms and clinical features are increasingly recognized and indicate hippocampal dysfunction in most of these syndromes. Here, we review the neuroimaging characteristics of autoimmune encephalitides, including N-methyl-D-aspartate (NMDA) receptor, leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2) encephalitis as well as more recently discovered and less frequent forms such as dipeptidyl-peptidase-like protein 6 (DPPX) or glycine receptor encephalitis. We summarize findings of routine MRI investigations as well as FDG-PET and SPECT imaging and relate these observations to clinical features and disease outcome. We furthermore review results of advanced imaging analyses such as diffusion tensor imaging, volumetric analyses and resting state functional MRI. Finally, we discuss contributions of these neuroimaging observations to the understanding of the pathophysiology of autoimmune encephalitides. Copyright © 2015. Published by Elsevier Ltd.
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Aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare but often severe autoimmune disease with median onset around 40 years of age. We report characteristics of three very-late-onset NMOSD... more
Aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare but often severe autoimmune disease with median onset around 40 years of age. We report characteristics of three very-late-onset NMOSD (including complete NMO) patients &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;75 years of age, in whom this diagnosis initially seemed unlikely because of their age and age-associated concomitant diseases, and briefly review the literature. All three patients, aged 79, 82 and 88 years, presented with a spinal cord syndrome as the first clinical manifestation of AQP4-Ab-positive NMOSD. They all had severe relapses unless immunosuppressive therapy was initiated, and one untreated patient died of a fatal NMOSD course. Two patients developed side effects of immunosuppression. We conclude that a first manifestation of NMOSD should be considered even in patients beyond the age of 75 years with a compatible syndrome, especially longitudinally extensive myelitis. Early diagnosis and treatment are feasible and highly relevant. Special attention is warranted in the elderly to recognize adverse effects of immunosuppressive therapies as early as possible.