Guillain–Barré syndrome with optic neuritis Andersen, Erik W; Ryan, Monique M; Leventer, Richard J
Journal of paediatrics and child health,
20/May , Letnik:
58, Številka:
5
Journal Article
IMPORTANCE: Using an aquaporin-4 (AQP4) M1-isoform–specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California ...population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay. OBSERVATIONS: Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis reported on at least 1 magnetic resonance imaging spine) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive. CONCLUSIONS AND RELEVANCE: Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.
Optic neuritis (ON), the most common ocular manifestation of multiple sclerosis, is an autoimmune inflammatory demyelinating disease also characterized by degeneration of retinal ganglion cells ...(RGCs) and their axons, which commonly leads to visual impairment despite attempted treatments. Although ON disease etiology is not known, changes in the redox system and exacerbated optic nerve inflammation play a major role in the pathogenesis of the disease. Silent information regulator 1 (sirtuin-1/SIRT1) is a ubiquitously expressed NAD
-dependent deacetylase, which functions to reduce/prevent both oxidative stress and inflammation in various tissues. Non-specific upregulation of SIRT1 by pharmacologic and genetic approaches attenuates RGC loss in experimental ON. Herein, we hypothesized that targeted expression of SIRT1 selectively in RGCs using an adeno-associated virus (AAV) vector as a delivery vehicle is an effective approach to reducing neurodegeneration and preserving vision in ON. We tested this hypothesis through intravitreal injection of AAV7m8.SNCG.SIRT1, an AAV2-derived vector optimized for highly efficient SIRT1 transgene transfer and protein expression into RGCs in mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis that recapitulates optic neuritis RGC loss and axon demyelination. Our data show that EAE mice injected with a control vehicle exhibit progressive alteration of visual function reflected by decreasing optokinetic response (OKR) scores, whereas comparatively, AAV7m8.SNCG.SIRT1-injected EAE mice maintain higher OKR scores, suggesting that SIRT1 reduces the visual deficit imparted by EAE. Consistent with this, RGC survival determined by immunolabeling is increased and axon demyelination is decreased in the AAV7m8.SNCG.SIRT1 RGC-injected group of EAE mice compared to the mouse EAE counterpart injected with a vehicle or with control vector AAV7m8.SNCG.eGFP. However, immune cell infiltration of the optic nerve is not significantly different among all EAE groups of mice injected with either vehicle or AAV7m8.SNCG.SIRT1. We conclude that despite minimally affecting the inflammatory response in the optic nerve, AAV7m8-mediated SIRT1 transfer into RGCs has a neuroprotective potential against RGC loss, axon demyelination and vison deficits associated with EAE. Together, these data suggest that SIRT1 exerts direct effects on RGC survival and function.
The goal was to visualize topographic thickness maps of the intraretinal layers and evaluate their discrimination abilities and relationships with clinical manifestations in patients with multiple ...sclerosis (MS) and a history of optic neuritis (ON).
Thirty patients with relapsing-remitting MS (34 eyes with a history of ON MSON and 26 non-ON fellow eyes MSFE) were recruited together with 63 age- and sex-matched controls (HC). Ultrahigh resolution optical coherence tomography was used to image the macula and the volumetric data set was segmented to yield six intraretinal layers. Topographic thickness maps were aligned and averaged for the visualization. The thickness maps were partitioned using the Early Treatment Diabetic Retinopathy Study (ETDRS) and related to Sloan low-contrast letter acuity (LCLA), Expanded Disability Status Scale (EDSS), and disease duration.
Focal thickness reduction occurred in the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL), with the most profound reduction occurring in MSON eyes (P < 0.05). A horseshoe-like thickness reduction pattern (U Zone) in the GCIPL appeared in MSON. The thickness of the U Zone had better discrimination power than the ETDRS partitions (area under the curve = 0.97) and differentiated 96% of MSON from HC. The thickness of the U Zone was positively correlated to 2.5% LCLA (r = 0.38, P < 0.05) and 1.25% LCLA (r = 0.57, P < 0.05).
The horseshoe-like thickness reduction of the GCIPL appeared to be an ON-specific focal thickness alteration with the highest discrimination power of prior ON.
Optic neuritis is an inflammatory demyelinating disorder that primarily affects the optic nerve and is often associated with multiple sclerosis. While it is rare for optic neuritis to be accompanied ...by autoimmune encephalitis, it can occur in some cases. A 65-year-old woman with bipolar disorder presented with a progressively altered mentality. Magnetic resonance imaging of the brain showed no definite abnormal findings. Electroencephalography revealed nonconvulsive status epilepticus. Cerebrospinal fluid study and autoimmune and paraneoplastic encephalitis antibodies were negative. The patient was diagnosed with seronegative autoimmune encephalitis and treated with methylprednisolone, intravenous immunoglobulin, and rituximab. Her condition gradually improved except for persistent blindness on the left side. This case highlights the importance of considering autoimmune encephalitis even in the absence of identifiable pathogenic antibodies when clinical manifestations and response to immunotherapy support such a diagnosis.
We report a unique presentation of anti-myelin oligodendrocyte (MOG) optic neuritis in a patient with AML in remission. An elderly man presented with diminished vision in the right eye associated ...with headache and jaw pain. Systemic investigations revealed no leukemic recurrence. The presence of anti-MOG antibodies and optic nerve enhancement suggested of unilateral optic neuritis. Steroid therapy resulted in the resolution of disc edema. We faced a diagnostic dilemma in a patient with unilateral disc edema in the background of multiple systemic diseases. A methodical approach to investigations helped us in accurate diagnosis, institution of prompt therapy, and minimizing visual morbidity. We present this case to highlight the importance of differentiating leukemic optic nerve infiltration from other causes of unilateral disc edema, as their therapeutic approaches are different.
Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be ...associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities.
This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS.
Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range IQR: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening.
OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.
To evaluate retinal segmented layer alterations in optic neuritis (ON) in an AQP4-Ab seropositive (AQP4-Ab+/ON) cohort and in neuromyelitis optica (NMO) with ON eyes (NMO-ON) compared with an AQP4-Ab ...seronegative ON (AQP4-Ab-/ON) cohort using optical coherence tomography (OCT).
We recruited 109 patients with ON (161 eyes) and 47 healthy controls. All patients with ON were subdivided into three subcohorts: 37 patients (54 eyes) with AQP4-Ab+/ON, 45 patients (65 eyes) with AQP4-Ab-/ON and 27 patients (42 eyes) with NMO-ON. All subjects were evaluated for their peripapillary retinal nerve fibre layer (pRNFL) and inner macular segmented layer using OCT.
AQP4-Ab+/patients with ON had the same structural injury patterns as patients with NMO-ON, and the injury patterns were distinct from those of AQP4-Ab-/patients with ON. NMO-ON and AQP4-Ab+/ON preferentially damaged the pRNFL (all p=0.000), the macular retinal nerve fibre layer (mRNFL; p=0.000 and 0.032, respectively), and the inner plexiform layer (IPL; p=0.000 and 0.006, respectively) without differences in the retinal ganglion cell layer (p=0.106 and 0.374, respectively) compared with AQP4-Ab-/patients with ON. The thickness of the inner nuclear layer (INL) increased in NMO-ON (p=0.043) compared with that of AQP4-Ab-/ON without a significant difference in AQP4-Ab+/ON versus AQP4-Ab-/ON (p=0.353). When the thickness of the inferior nasal quadrant (NI) of the pRNFL was reduced to ≤46.5 μm (area under the curve 0.772, sensitivity 89.2% and specificity 57.5%) 6 months after ON onset, NMO was considered.
AQP4-Ab+/ON produced similar structural injury patterns as NMO-ON. The pRNFL, mRNFL and IPL in the two types of ON and the INL in NMO-ON suffered more damage than those in AQP4-Ab-/ON, which could be associated with strong aquaporin-4 expression. The thickness of the NI of the pRNFL could be a potential clue for predicting ON progression to definite NMO.
Background:
Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited.
...Objective:
To compare visual and optical coherence tomography (OCT) measures following AQP4-ON, MOG-ON, and multiple sclerosis associated ON (MS-ON).
Methods:
In this cross-sectional study, 48 AQP4-ON, 16 MOG-ON, 40 MS-ON, and 31 healthy control participants underwent monocular letter-acuity assessment and spectral-domain OCT. Eyes with a history of ON >3 months prior to evaluation were analyzed.
Results:
AQP4-ON eyes exhibited worse high-contrast letter acuity (HCLA) compared to MOG-ON (−22.3 ± 3.9 letters; p < 0.001) and MS-ON eyes (−21.7 ± 4.0 letters; p < 0.001). Macular ganglion cell + inner plexiform layer (GCIPL) thickness was lower, as compared to MS-ON, in AQP4-ON (−9.1 ± 2.0 µm; p < 0.001) and MOG-ON (−7.6 ± 2.2 µm; p = 0.001) eyes. Lower GCIPL thickness was associated with worse HCLA in AQP4-ON (−16.5 ± 1.5 letters per 10 µm decrease; p < 0.001) and MS-ON eyes (−8.5 ± 2.3 letters per 10 µm decrease; p < 0.001), but not in MOG-ON eyes (−5.2 ± 3.8 letters per 10 µm decrease; p = 0.17), and these relationships differed between the AQP4-ON and other ON groups (p < 0.01 for interaction).
Conclusion:
AQP4-IgG seropositivity is associated with worse visual outcomes after ON compared with MOG-ON and MS-ON, even with similar severity of macular GCIPL thinning.
In recent years, not only the incidence of brain demyelinating disease has increased, but also it seems that the world is facing new forms of autoimmune diseases of the brain. Distinguishing these ...diseases from each other is very important, since each requires a different treatment. The new criteria that were put forward in 2015 were meant to pave the way for better diagnosis of these diseases called neuromyelitis optica spectrum disease (NMOSD). However, too much emphasis on the criteria based on the convergence and association of radiological findings with the clinical symptoms actually causes confusion in the diagnosis.
Here, the case of a 16-year-old child suffering from optic neuritis has been discussed. Her cervical magnetic resonance imaging (MRI) revealed longitudinal extensive transverse myelitis (LETM); however, the patient had no symptoms of the spinal cord's involvement. According to the 2015 criterion, the diagnosis of NMOSD cannot be accepted for this patient. Therefore, this case report emphasizes on the modification of the existing criterion.
•A case of a 16-year old child suffering from optic neuritis is discussed.•His cervical MRI revealed longitudinal extensive transverse myelitis.•The patient had no symptoms of spinal cord involvement.•According to 2015 criterion, the diagnosis of NMOSD cannot be accepted for this patient.•This case report emphasizes on the modification of the existing criterion.
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