13401
2012
eng
e38741
6
7
article
1
2016-05-27
--
--
Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS
Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.
PLoS One
10.1371/journal.pone.0038741
urn:nbn:de:bvb:20-opus-134013
PLoS ONE 7(6): e38741. doi:10.1371/journal.pone.0038741
Alexander U. Brandt
Hanna Zimmermann
Falko Kaufhold
Julia Promesberger
Sven Schippling
David Finis
Orhan Aktas
Christian Geis
Marius Ringelstein
E. Bernd Ringelstein
Hans-Peter Hartung
Friedemann Paul
Ilka Kleffner
Jan Dörr
eng
uncontrolled
optical coherence tomography
eng
uncontrolled
vasculopathy
eng
uncontrolled
artery occlusion
eng
uncontrolled
hearing loss
eng
uncontrolled
microangiopathy
eng
uncontrolled
brain
eng
uncontrolled
endotheliopathy
eng
uncontrolled
antibodies
eng
uncontrolled
multiple-sclerosis
eng
uncontrolled
retinocochleocerebral
Krankheiten
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13401/Brandt_PLoS_One_2012.pdf
13363
2012
eng
14
9
article
1
2016-05-17
--
--
Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of <= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades <= 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions >= 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Journal of Neuroinflammation
10.1186/1742-2094-9-14
urn:nbn:de:bvb:20-opus-133636
Journal of Neuroinflammation 2012, 9:14. doi:10.1186/1742-2094-9-14
Sven Jarius
Klemens Ruprecht
Brigitte Wildemann
Tania Kuempfel
Marius Ringelstein
Christian Geis
Ingo Kleiter
Christoph Kleinschnitz
Achim Berthele
Johannes Brettschneider
Kerstin Hellwig
Bernhard Hemmer
Ralf A. Linker
Florian Lauda
Christoph A. Hayrettin
Hayrettin Tumani
Arthur Melms
Corinna Trebst
Martin Stangel
Martin Marziniak
Frank Hoffmann
Sven Schippling
Jürgen H. Faiss
Oliver Neuhaus
Barbara Ettrich
Christian Zentner
Kersten Guthke
Ulrich Hofstadt-van Oy
Reinhard Reuss
Hannah Pellkofer
Ulf Ziemann
Peter Kern
Klaus P. Wandinger
Florian Then Bergh
Tobias Boettcher
Stefan Langel
Martin Liebetrau
Paulus S. Rommer
Sabine Niehaus
Christoph Münch
Alexander Winkelmann
Uwe K Zettl
Imke Metz
Christian Veauthier
Jörn P. Sieb
Christian Wilke
Hans P. Hartung
Orhan Aktas
Friedemann Paul
eng
uncontrolled
cerebrospinal-fluid
eng
uncontrolled
intractable hiccup
eng
uncontrolled
extensiv transverse myelitis
eng
uncontrolled
multiple sclerosis
eng
uncontrolled
anti-aquaporin-4 antibody
eng
uncontrolled
NMO-IGG
eng
uncontrolled
aquaporin-4 autoantibodies
eng
uncontrolled
immune-response
eng
uncontrolled
myasthenia gravis
eng
uncontrolled
immunoglobulin-G
Krankheiten
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13363/Jarius_1742-2094-9-14.pdf
16555
2016
eng
282
13
article
in cooperation with the Neuromyelitis Optica Study Group (NEMOS)
1
2018-07-24
--
--
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients
Background
Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in the retina of MOG-IgG-positive patients in comparison with AQP4-IgG-positive NMOSD patients.
Methods
Afferent visual system damage following ON was bilaterally assessed in 16 MOG-IgG-positive patients with a history of ON and compared with that in 16 AQP4-IgG-positive NMOSD patients. In addition, 16 healthy controls matched for age, sex, and disease duration were analyzed. Study data included ON history, retinal optical coherence tomography, visual acuity, and visual evoked potentials.
Results
Eight MOG-IgG-positive patients had a previous diagnosis of AQP4-IgG-negative NMOSD with ON and myelitis, and eight of (mainly recurrent) ON. Twenty-nine of the 32 eyes of the MOG-IgG-positive patients had been affected by at least one episode of ON. Peripapillary retinal nerve fiber layer thickness (pRNFL) and ganglion cell and inner plexiform layer volume (GCIP) were significantly reduced in ON eyes of MOG-IgG-positive patients (pRNFL = 59 ± 23 μm; GCIP = 1.50 ± 0.34 mm3) compared with healthy controls (pRNFL = 99 ± 6 μm, p < 0.001; GCIP = 1.97 ± 0.11 mm3, p < 0.001). Visual acuity was impaired in eyes after ON in MOG-IgG-positive patients (0.35 ± 0.88 logMAR). There were no significant differences in any structural or functional visual parameters between MOG-IgG-positive and AQP4-IgG-positive patients (pRNFL: 59 ± 21 μm; GCIP: 1.41 ± 0.27 mm3; Visual acuity = 0.72 ± 1.09 logMAR). Importantly, MOG-IgG-positive patients had a significantly higher annual ON relapse rate than AQP4-IgG-positive patients (median 0.69 vs. 0.29 attacks/year, p = 0.004), meaning that on average a single ON episode caused less damage in MOG-IgG-positive than in AQP4-IgG-positive patients. pRNFL and GCIP loss correlated with the number of ON episodes in MOG-IgG-positive patients (p < 0.001), but not in AQP4-IgG-positive patients.
Conclusions
Retinal neuro-axonal damage and visual impairment after ON in MOG-IgG-positive patients are as severe as in AQP4-IgG-positive NMOSD patients. In MOG-IgG-positive patients, damage accrual may be driven by higher relapse rates, whereas AQP4-IgG-positive patients showed fewer but more severe episodes of ON. Given the marked damage in some of our MOG-IgG-positive patients, early diagnosis and timely initiation and close monitoring of immunosuppressive therapy are important.
Journal of Neuroinflammation
10.1186/s12974-016-0720-6
urn:nbn:de:bvb:20-opus-165551
Journal of Neuroinflammation (2016) 13:282
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Florence Pache
Hanna Zimmermann
Janine Mikolajczak
Sophie Schumacher
Anna Lacheta
Frederike C. Oertel
Judith Bellmann-Strobl
Sven Jarius
Brigitte Wildemann
Markus Reindl
Amy Waldman
Kerstin Soelberg
Nasrin Asgari
Marius Ringelstein
Orhan Aktas
Nikolai Gross
Mathias Buttmann
Thomas Ach
Klemens Ruprecht
Friedemann Paul
Alexander U. Brandt
eng
uncontrolled
Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)
eng
uncontrolled
aquaporin-4 antibodies (AQP4-IgG)
eng
uncontrolled
NMO-IgG
eng
uncontrolled
neuromyelitis optica
eng
uncontrolled
Devic syndrome
eng
uncontrolled
neuromyelitis optica spectrum disorders (NMOSD)
eng
uncontrolled
optic neuritis
eng
uncontrolled
optical coherence tomography
eng
uncontrolled
visual evoked potentials
eng
uncontrolled
visual acuity
eng
uncontrolled
retinal neuro-axonal damage
Medizin und Gesundheit
open_access
Augenklinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16555/077_Pache_Journal of Neuroinflammation.pdf
16557
2016
eng
280
13
article
in cooperation with the Neuromyelitis Optica Study Group (NEMOS)
1
2018-07-24
--
--
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome
Background
A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).
Objective
To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes.
Methods
Retrospective multicenter study.
Results
The sex ratio was 1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease followed a multiphasic course in 80% (median time-to-first-relapse 5 months; annualized relapse rate 0.92) and resulted in significant disability in 40% (mean follow-up 75 ± 46.5 months), with severe visual impairment or functional blindness (36%) and markedly impaired ambulation due to paresis or ataxia (25%) as the most common long-term sequelae. Functional blindness in one or both eyes was noted during at least one ON attack in around 70%. Perioptic enhancement was present in several patients. Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70%). Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44%. Fourty-one percent had a history of simultaneous ON and myelitis. Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50%; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one). CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in only 13%, and blood-CSF-barrier dysfunction in 32%. Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was associated with ongoing or increasing disease activity. Rituximab and ofatumumab were effective in some patients. However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9%). Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%, respectively; MS had been suspected in 36%. Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases.
Conclusion
Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD. The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis.
Journal of Neuroinflammation
10.1186/s12974-016-0718-0
urn:nbn:de:bvb:20-opus-165570
Journal of Neuroinflammation (2016) 13:280
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sven Jarius
Klemens Ruprecht
Ingo Kleiter
Nadja Borisow
Nasrin Asgari
Kalliopi Pitarokoili
Florence Pache
Oliver Stich
Lena-Alexandra Beume
Martin W. Hümmert
Marius Ringelstein
Corinna Trebst
Alexander Winkelmann
Alexander Schwarz
Mathias Buttmann
Hanna Zimmermann
Joseph Kuchling
Diego Franciotta
Marco Capobianco
Eberhard Siebert
Carsten Lukas
Mirjam Korporal-Kuhnke
Jürgen Haas
Kai Fechner
Alexander U. Brandt
Kathrin Schanda
Orhan Aktas
Friedemann Paul
Markus Reindl
Brigitte Wildemann
eng
uncontrolled
Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)
eng
uncontrolled
Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG)
eng
uncontrolled
Optic neuritis
eng
uncontrolled
Transverse myelitis
eng
uncontrolled
Longitudinally extensive transverse myelitis
eng
uncontrolled
Magnetic resonance imaging
eng
uncontrolled
Autoantibodies
eng
uncontrolled
Neuromyelitis optica spectrum disorders (NMOSD)
eng
uncontrolled
Cerebrospinal fluid
eng
uncontrolled
Oligoclonal bands
eng
uncontrolled
Electrophysiology
eng
uncontrolled
Evoked potentials
eng
uncontrolled
Treatment
eng
uncontrolled
Therapy
eng
uncontrolled
Methotrexate
eng
uncontrolled
Azathioprine
eng
uncontrolled
Rituximab
eng
uncontrolled
Ofatumumab
eng
uncontrolled
Interferon beta
eng
uncontrolled
Glatiramer acetate
eng
uncontrolled
Natalizumab
eng
uncontrolled
Outcome
eng
uncontrolled
Pregnancy
eng
uncontrolled
Infections
eng
uncontrolled
Vaccination
eng
uncontrolled
Multiple sclerosis
eng
uncontrolled
Barkhof criteria
eng
uncontrolled
McDonald criteria
eng
uncontrolled
Wingerchuk criteria 2006 and 2015
eng
uncontrolled
IPND criteria
eng
uncontrolled
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16557/078_Jarius_Journal of Neuroinflammation.pdf
16565
2016
eng
1-16
279
13
article
in cooperation with the Neuromyelitis Optica Study Group (NEMOS)
1
2018-07-25
--
--
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin
Background
Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders.
Objective
To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers.
Methods
614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells.
Results
MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7%) patients with a history of both ON and myelitis, 22/103 (21.4%) with a history of ON but no myelitis and 6/45 (13.3%) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67%) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89%) follow-up samples obtained over a median period of 16.5 months (range 0–123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment.
Conclusions
To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.
Journal of Neuroinflammation
10.1186/s12974-016-0717-1
urn:nbn:de:bvb:20-opus-165659
Journal of Neuroinflammation (2016) 13:279
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sven Jarius
Klemens Ruprecht
Ingo Kleiter
Nadja Borisow
Nasrin Asgari
Kalliopi Pitarokoili
Florence Pache
Oliver Stich
Lena-Alexandra Beume
Martin W. Hümmert
Corinna Trebst
Marius Ringelstein
Orhan Aktas
Alexander Winkelmann
Mathias Buttmann
Alexander Schwarz
Hanna Zimmermann
Alexander U. Brandt
Diego Franciotta
Marco Capobianco
Joseph Kuchling
Jürgen Haas
Mirjam Korporal-Kuhnke
Soeren Thue Lillevang
Kai Fechner
Kathrin Schanda
Friedemann Paul
Brigitte Wildemann
Markus Reindl
eng
uncontrolled
Neuromyelitis optica (NMO)
eng
uncontrolled
Devic’s syndrome
eng
uncontrolled
Optic neuritis
eng
uncontrolled
Transverse Myelitis
eng
uncontrolled
Longitudinally extensive transverse myelitis (LETM)
eng
uncontrolled
Neuromyelitis optica spectrum disorders (NMOSD)
eng
uncontrolled
Multiple sclerosis
eng
uncontrolled
Autoantibodies
eng
uncontrolled
Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)
eng
uncontrolled
Neuromyelitis optica antibodies (NMO-IgG)
eng
uncontrolled
Aquaporin-4 antibodies (AQP4-IgG)
eng
uncontrolled
Cell-based assays
eng
uncontrolled
Cerebrospinal fluid
eng
uncontrolled
Antibody index
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16565/079_Jarius_JOURNAL OF NEUROINFLAMMATION.pdf
16554
2016
eng
1-23
281
13
article
Optica Study Group (NEMOS)
1
2018-07-24
--
--
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome
Background
Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients.
Objective
To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis.
Methods
Retrospective case study.
Results
Among 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up).
Conclusions
Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.
Journal of Neuroinflammation
10.1186/s12974-016-0719-z
urn:nbn:de:bvb:20-opus-165543
Journal of Neuroinflammation (2016) 13:281
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sven Jarius
Ingo Kleiter
Klemens Ruprecht
Nasrin Asgari
Kalliopi Pitarokoili
Nadja Borisow
Martin W. Hümmert
Corinna Trebst
Florence Pache
Alexander Winkelmann
Lena-Alexandra Beume
Marius Ringelstein
Oliver Stich
Orhan Aktas
Mirjam Korporal-Kuhnke
Alexander Schwarz
Carsten Lukas
Jürgen Haas
Kai Fechner
Mathias Buttmann
Judith Bellmann-Strobl
Hanna Zimmermann
Alexander U. Brandt
Diego Franciotta
Kathrin Schanda
Friedemann Paul
Markus Reindl
Brigitte Wildemann
eng
uncontrolled
Myelin oligodendrocyte glycoprotein (MOG) antibodies
eng
uncontrolled
MOG-IgG
eng
uncontrolled
Neuromyelitis optica spectrum disorders (NMOSD)
eng
uncontrolled
Brainstem encephalitis
eng
uncontrolled
Rhombencephalitis
eng
uncontrolled
Optic neuritis
eng
uncontrolled
Myelitis
eng
uncontrolled
Longitudinally extensive transverse myelitis (LETM)
eng
uncontrolled
Cerebellitis
eng
uncontrolled
Ataxia
eng
uncontrolled
Respiratory insufficiency
eng
uncontrolled
Intractable nausea and vomiting
eng
uncontrolled
Facial nerve palsy
eng
uncontrolled
Diplopia Internuclear ophthalmoplegia (INO)
eng
uncontrolled
Hearing loss
eng
uncontrolled
Aquaporin-4 antibodies (AQP4-Ig, NMO-IgG)G
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16554/076_Jarius_Journal of Neuroinflammation.pdf
16540
2016
eng
2073-2079
7
6
article
1
2018-07-23
--
--
Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients
Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.
G3: Genes Genomes Genetics
10.1534/g3.116.030841
urn:nbn:de:bvb:20-opus-165405
G3: Genes Genomes Genetics, 2016, Vol. 6(7), p 2073-2079
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
A. Dessa Sadovnick
Anthony L. Traboulsee
Cecily Q. Bernales
Jay P. Ross
Amanda L. Forwell
Irene M. Yee
Lena Guillot-Noel
Bertrand Fontaine
Isabelle Cournu-Rebeix
Antonio Alcina
Maria Fedetz
Guillermo Izquierdo
Fuencisla Matesanz
Kelly Hilven
Bénédicte Dubois
An Goris
Ianire Astobiza
Iraide Alloza
Alfredo Antigüedad
Koen Vandenbroeck
Denis A. Akkad
Orhan Aktas
Paul Blaschke
Mathias Buttmann
Andrew Chan
Joerg T. Epplen
Lisa-Ann Gerdes
Antje Kroner
Christian Kubisch
Tania Kümpfel
Peter Lohse
Peter Rieckmann
Uwe K. Zettl
Frauke Zipp
Lars Bertram
Christina M. Lill
Oscar Fernandez
Patricia Urbaneja
Laura Leyva
Jose Carlos Alvarez-Cermeño
Rafael Arroyo
Aroa M. Garagorri
Angel García-Martínez
Luisa M. Villar
Elena Urcelay
Sunny Malhotra
Xavier Montalban
Manuel Comabella
Thomas Berger
Franz Fazekas
Markus Reindl
Mascha C. Schmied
Alexander Zimprich
Carles Vilariño-Güell
eng
uncontrolled
multiple sclerosis
eng
uncontrolled
genetics
eng
uncontrolled
linkage
eng
uncontrolled
association
eng
uncontrolled
plasminogen
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16540/068_Sadovnick_G3-GENES GENOMES GENETICS.pdf
20076
2020
eng
1
9
article
1
--
2020-01-10
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The rare IL22RA2 signal peptide coding variant rs28385692 decreases secretion of IL-22BP isoform-1, -2 and -3 and is associated with risk for multiple sclerosis
The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10\(^{-4}\)). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%–60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS.
Cells
2073-4409
10.3390/cells9010175
urn:nbn:de:bvb:20-opus-200769
swordwue
2020-03-06T10:40:13+00:00
attachment; filename=deposit.zip
ff20d7328934edf1e9a10066b8440b2b
Cells (2020) 9:1, 175. https://doi.org/10.3390/cells9010175
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Paloma Gómez-Fernández
Aitzkoa Lopez de Lapuente Portilla
Ianire Astobiza
Jorge Mena
Andoni Urtasun
Vivian Altmann
Fuencisla Matesanz
David Otaegui
Elena Urcelay
Alfredo Antigüedad
Sunny Malhotra
Xavier Montalban
Tamara Castillo-Triviño
Laura Espino-Paisán
Orhan Aktas
Mathias Buttmann
Andrew Chan
Bertrand Fontaine
Pierre-Antoine Gourraud
Michael Hecker
Sabine Hoffjan
Christian Kubisch
Tania Kümpfel
Felix Luessi
Uwe K. Zettl
Frauke Zipp
Iraide Alloza
Manuel Comabella
Christina M. Lill
Koen Vandenbroeck
eng
uncontrolled
IL22RA2
eng
uncontrolled
IL-22 binding protein isoform
eng
uncontrolled
mutation
eng
uncontrolled
signal peptide
eng
uncontrolled
multiple sclerosis
eng
uncontrolled
autoimmune
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/20076/cells-09-00175.pdf