Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis.

BACKGROUND AND OBJECTIVES: This [18F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich, glioma-inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined. METHODS: FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non-LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses. RESULTS: P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non-LGI1-AE group, AD group, and NCs (all p < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84-0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non-LGI1-AE groups when compared with NCs (both p < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all p < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up. DISCUSSION: Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.

Comparative analysis of clinical and imaging data between patients with myelin oligodendrocyte glycoprotein antibody disease and patients with aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder.

BACKGROUND: We aimed to compare the clinical data, laboratory findings, and imaging characteristics of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin 4 antibody (AQP4)-positive neuromyelitis optica spectrum disorder (NMOSD), as detailed comparative analyses of laboratory data for both diseases are rare. METHODS: Our retrospective study compared the clinical data, laboratory findings, and imaging characteristics of 118 AQP4-positive patients with first-episode NMOSD and 25 patients with first-episode MOGAD. Logistic regression was used to determine the factors that differentiated MOGAD and AQP4-positive NMOSD. RESULTS: There were significant differences in age, symptoms, recurrence rate, laboratory indicators, and imaging examinations between patients with MOGAD and patients with AQP4-positive NMOSD. Patients with MOGAD were younger and had higher levels of uric acid than those with AQP4-positive NMOSD. The proportion of cortical gray matter/juxtacortical white matter lesions was significantly higher in the MOGAD group than in the NMOSD group. Logistic regression revealed that young age [odds ratio (OR) = 0.947, 95% confidence interval (CI) = 0.905-0.99], high uric acid level (OR = 1.016, 95% CI = 1.006-1.027), and cortical gray matter/juxtacortical white matter involvement (OR = 3.889, 95% CI = 1.048-14.442) were significantly related to MOGAD. CONCLUSION: The multivariate analysis of the present study demonstrated that age, uric acid level, and the presence of lesions in the cortical gray matter/juxtacortical white matter can aid in distinguishing patients with AQP4-positive NMOSD from those with MOGAD. These factors may also aid in determining which patients should be tested for antibodies.

Clinicoradiological comparative study of Aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody associated disease (MOGAD): A prospective observational study and review of literature.

Neuromyelitis Optica spectrum disorders (NMOSD) are autoimmune inflammatory central nervous system diseases. NMOSD patients typically have recurrent attacks of severe optic neuritis or/and myelitis with majority of them having autoantibodies against the aquaporin-4 (AQP4). In the recent past, a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations had been demonstrated. MOG-IgG antibody associated disease (MOGAD) is now considered as a disease entity in its own right, distinct from classic MS and from AQP4-IgG-positive NMOSD. Here, we compared the clinical, laboratory, radiological features and treatment outcomes of patients with Aquaporin-4-IgG seropositive NMOSD and MOGAD. Relatively younger age at onset, lesser number of relapses, better response to treatment and favorable clinical outcomes were found in MOGAD group in comparison to AQP4-IgG-positive NMOSD group.

Evidence for and against subclinical disease activity and progressive disease in MOG antibody disease and neuromyelitis optica spectrum disorder.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) are generally considered to be relapsing disorders, without clinical progression or subclinical disease activity outside of clinical relapses, in contrast to multiple sclerosis (MS). With advances in the diagnosis and treatment of these conditions, prolonged periods of remission without relapses can be achieved, and the question of whether progressive disease courses can occur has re-emerged. In this review, we focus on studies exploring evidence for and against relapse-independent clinical progression and/or subclinical disease activity in patients with MOGAD and AQP4-IgG+ NMOSD.

Aseptic meningitis and leptomeningeal enhancement associated with anti-MOG antibodies: A review.

BACKGROUND: Aseptic meningitis can be caused by autoimmune diseases, such as lupus and sarcoidosis. Aseptic meningitis with leptomeningeal enhancement can be the initial presentation of a neuroinflammatory syndrome associated with antibodies to myelin oligodendrocyte glycoprotein (MOG-abs). MOG-abs is a serum biomarker for MOG-associated disorder (MOG-AD), an acquired demyelinating syndrome that includes features of neuromyelitis optica, multiple sclerosis, optic neuritis, and acute disseminated encephalomyelitis. The purpose of this study is to review cases of aseptic meningitis and leptomeningeal enhancement associated with MOG-abs. METHODS: Systematic review using PubMed, Embase, Ovid MEDLINE, Web of Science Core Collection, and Google Scholar up to December 2020 was performed. Cases of MOG-AD were included if they met the following criteria: 1) Initial clinical presentation of aseptic meningitis; 2) positive leptomeningeal enhancement and 3) MOG-Ab seropositivity. Descriptive statistics were used. This analysis was limited to the cases available in the literature. RESULTS: 11 total cases of aseptic meningitis and leptomeningeal enhancement in setting of MOG-ab were identified. Demyelinating type T2 lesions were also present at time of presentation in 6/11; however, 5/11 of patients had leptomeningeal enhancement alone without demyelinating lesions. All 5 patients required immunotherapy for improvement, including one patient with symptoms for 28 days, with 4/5 receiving steroids and 1/5 receiving intravenous immunoglobulin (IVIG). CONCLUSIONS: Aseptic meningitis with leptomeningeal enhancement can be the initial presenting symptom of MOG-AD. MOG-ab testing should be considered in a patient presenting with aseptic meningitis and leptomeningeal enhancement of unknown etiology.

Clinical analysis of a patient simultaneously positive for antibodies of myelin oligodendrocyte glycoprotein and anti-N-methyl-D-aspartate receptor: A case report.

RATIONALE: Myelin oligodendrocyte glycoprotein (MOG) antibody (MOG-Ab) disease (MOG-AD) is a type of demyelinating disease of the central nervous system characterized by a high frequency of optic neuritis (ON) attacks. anti-Nmethyl-D-aspartate receptor (NMDAR) encephalitis (anti-NMDARe) is an autoimmune disorder characterized by memory deficits, conscious disturbance, and seizures. Cases of simultaneous occurrence of MOG-Ab and anti-NMDARe antibody (anti-NMDARe-Ab) are rarely reported and could be mistaken for overlapping MOG-antibody disease (MOG-AD) and NMDARe. The diagnosis of such patients is challenging. PATIENT CONCERNS: We report the case of a 37-year-old man who presented with recurrent headaches for 3 months and worsening symptoms over 2 weeks. He had a history of ON. He had a generalized seizure after 7 days in the hospital. DIAGNOSIS: Brain magnetic resonance imaging (MRI) and cerebrospinal fluid tests showed no apparent abnormalities. Repeat MRI showed slight lesions 7 days later, and cerebrospinal fluid tests showed the simultaneous occurrence of MOG-Ab and anti-NMDARe-Ab. INTERVENTIONS: He completely recovered after treatment with low doses of oral corticosteroids. OUTCOMES: Two months and 2 years follow-up showed that his condition was stable. LESSONS: The co-occurrence of MOG-Ab and anti-NMDAR-Ab does not indicate the co-occurrence of MOG-AD and anti-NMDARe. Laboratory findings should be combined with the clinical features to achieve an accurate and suitable diagnosis.

Silent New Brain MRI Lesions in Children with MOG-Antibody Associated Disease.

Anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies are associated clinically with either a monophasic or relapsing disease course. We investigated the frequency and clinical importance of acquired asymptomatic brain magnetic resonance imaging (MRI) lesions in a prospective incident cohort of 74 MOG-IgG positive children with serial MRI scans over a median of 5 years from presentation. Silent new lesions were detected in 14% of MOG-IgG positive participants, most commonly within the first months post-onset, with a positive predictive value for clinically relapsing disease of only 20%. Detection of asymptomatic lesions alone need not prompt initiation of chronic immunotherapy. ANN NEUROL 2021;89:408-413.

E.U. paediatric MOG consortium consensus: Part 2 - Neuroimaging features of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

Imaging plays a crucial role in differentiating the spectrum of paediatric acquired demyelinating syndromes (ADS), which apart from myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) includes paediatric multiple sclerosis (MS), aquaporin-4 antibody neuromyelitis optica spectrum disorders (NMOSD) and unclassified patients with both monophasic and relapsing ADS. In contrast to the imaging characteristics of children with MS, children with MOGAD present with diverse imaging patterns which correlate with the main demyelinating phenotypes as well as age at presentation. In this review we describe the common neuroradiological features of children with MOGAD such as acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, AQP4 negative NMOSD. In addition, we report newly recognized presentations also associated with MOG-ab such as the 'leukodystophy-like' phenotype and autoimmune encephalitis with predominant involvement of cortical and deep grey matter structures. We further delineate the features, which may help to distinguish MOGAD from other ADS and discuss the future role of MR-imaging in regards to treatment decisions and prognosis in children with MOGAD. Finally, we propose an MRI protocol for routine examination and discuss new imaging techniques, which may help to better understand the neurobiology of MOGAD.

[Isolated area postrema syndrome with anti-MOG antibodies, a rare association]. / Síndrome del área postrema aislado con anticuerpos anti-MOG, una asociación poco frecuente.

TITLE: Síndrome del área postrema aislado con anticuerpos anti-MOG, una asociación poco frecuente.

PRES-like presentation in MOG antibody-related demyelination (MARD).

A 33-year-old male presented with a progressive four-week history of frontal headache and left visual field impairment. MRI brain confirmed bilateral, asymmetric, occipital vasogenic oedema, suggestive of posterior reversible encephalopathy syndrome (PRES). Serum testing for MOG antibodies was positive, confirming a diagnosis of MOG antibody-related demyelination (MARD). A similar PRES-like pattern of white matter inflammation has been reported previously in neuromyelitis optica spectrum disorder but has not previously been reported in MARD.

CNS inflammatory demyelinating disorders: MS, NMOSD and MOG antibody associated disease.

Although Multiple Sclerosis is the most common central nervous system (CNS) inflammatory demyelinating disorder, other CNS inflammatory disorders should be included as diagnostic considerations. Neuromyelitis Optica Spectrum Disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease are less common but share some clinical characteristics, such as optic neuritis and myelitis, which can make a specific diagnosis challenging. However, these disorders have distinctive and generally different clinical phenotypes, prognosis and management. It is imperative to distinguish each from one another, especially since the treatments (not discussed in this review) can be different. The advent of reliable testing for anti-aquaporin-4 for NMOSD and anti-MOG antibodies has helped significantly; however, diagnosis can remain challenging, especially in sero-negative cases. Clinical indicators are important to guide diagnostic work-up. Careful review of the history, neurological exam, imaging, and/or spinal fluid results are essential to making an accurate diagnosis. In this review, we will examine the clinical presentation, diagnosis, and natural history of these inflammatory CNS disorders.

Deep learning segmentation of orbital fat to calibrate conventional MRI for longitudinal studies.

In conventional non-quantitative magnetic resonance imaging, image contrast is consistent within images, but absolute intensity can vary arbitrarily between scans. For quantitative analysis of intensity data, images are typically normalized to a consistent reference. The most convenient reference is a tissue that is always present in the image, and is unlikely to be affected by pathological processes. In multiple sclerosis neuroimaging, both the white and gray matter are affected, so normalization techniques that depend on brain tissue may introduce bias or remove biological changes of interest. We introduce a complementary procedure, image "calibration," the goal of which is to remove technical intensity artifacts while preserving biological differences. We demonstrate a deep learning approach to segmenting fat from within the orbit of the eyes on T1-weighted images at 1.5 and 3 â€‹T to use as a reference tissue, and use it to calibrate 1018 scans from 256 participants in a study of pediatric-onset multiple sclerosis. The machine segmentations agreed with the adjudicating expert (DF) segmentations better than did those of other expert humans, and calibration resulted in better agreement with semi-quantitative magnetization transfer ratio imaging than did normalization with the WhiteStripe1 algorithm. We suggest that our method addresses two key priorities in the field: (1) it provides a robust option for serial calibration of conventional scans, allowing comparison of disease change in persons imaged at multiple time points in their disease; and (ii) the technique is fast, as the deep learning segmentation takes only 0.5 â€‹s/scan, which is feasible for both large and small datasets.

Brain lesion distribution criteria distinguish demyelinating diseases in China.

OBJECTIVE: To verify the utility of brain lesion distribution criteria in distinguishing multiple sclerosis (MS) from aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive/-negative neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated encephalomyelitis (MOG-EM) in the Chinese population. METHODS: A total of 253 patients with MS (80), NMOSD (129 AQP4-IgG positive, 34 AQP4-IgG negative), and MOG-EM (10) were enrolled. Anonymized magnetic resonance imaging results were scored on the previous reported criteria of "at least one lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion; or a Dawson's finger-type lesion." Chi-squared test (or Fisher's exact test) was used to analyze the data. RESULTS: The distribution criteria were able to distinguish MS with a same sensitivity of 93.8% from all type of NMOSD and MOG-EM, with a specificity of 89.7% from the whole NMOSD cohort, 89.1% from AQP4-IgG-positive NMOSD 91.2% from AQP4-IgG-negative NMOSD, and 70.0% from MOG-EM. Dawson's finger-type lesion was the most sensitive and specific feature, whereas the U-fiber lesion was the least. CONCLUSION: The brain lesion distribution criteria were helpful in distinguishing MS from NMOSD and MOG-EM in the Chinese population. Dawson's finger-type lesion was highly suggestive of MS.

Enlarged and Enhancing Optic Nerves in Advanced Glial Fibrillary Acidic Protein Meningoencephalomyelitis.

A 36-year-old woman presented with intermittent fever, nausea and vomiting, generalized polyarthralgias, and bilateral optic disc swelling. She had a history of difficult-to-control myasthenia gravis since the age of 18 years. Lumbar puncture demonstrated a normal opening pressure; cerebrospinal fluid (CSF) was remarkable for high protein, low glucose, and a mononuclear pleocytosis. Although initial MRI of the brain was normal, a repeat study 8 weeks later revealed enlarged and enhancing bilateral intraorbital and intracranial optic nerves. After a nondiagnostic brain biopsy, a CSF sample tested positive for antibodies to glial fibrillary acidic protein (GFAP). Findings in this case indicate that optic nerve swelling encountered in GFAP meningoencephalomyelitis is more likely due to optic nerve inflammation rather than elevated intracranial pressure.

A surface-in gradient of thalamic damage evolves in pediatric multiple sclerosis.

OBJECTIVE: Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis course a "surface-in" process of injury suggesting progressive biology may begin. METHODS: We focused on the thalamus, which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface. Thalamic volume trajectories were assessed in a prospectively followed cohort of children from initial presentation with either multiple sclerosis or monophasic acquired demyelination, and healthy controls. Voxelwise volume changes were calculated using deformation-based morphometry, and analyzed in relation to distance from the CSF interface by mixed effects modeling and semiparametric smoothing methods. RESULTS: Twenty-seven children with multiple sclerosis and 73 children with monophasic demyelination were prospectively followed with yearly brain scans (mean follow-up = 4.6 years, standard deviation = 1.9). A total of 282 healthy children with serial scans were included as controls. Relative to healthy controls, children with multiple sclerosis and children with monophasic demyelination demonstrated volume loss in thalamic regions adjacent to the white matter. However, only children with multiple sclerosis exhibited an additional surface-in gradient of thalamic injury on the ventricular side, which was already notable in the first year of clinical disease (asymptote estimate = 3.01, 95% confidence interval [CI] = 1.44-4.58, p = 0.0002) and worsened over time (asymptote:time estimate = 0.33, 95% CI = 0.12-0.54, p = 0.0021). INTERPRETATION: Our results suggest that a multiple sclerosis disease-specific surface-in process of damage can manifest at the earliest stages of the disease. ANN NEUROL 2019;85:340-351.

Bilateral cingulate cortices lesions in two autoantibodies directed against MOG (MOG-Ab)-positive patients.

There are no specific radiologic features in MOG-Ab (autoantibodies directed against myelin oligodendrocyte glycoprotein)-associated diseases. We present two MOG-Ab-positive patients with symmetrical lesions in the bilateral cingulate cortex of the frontal and parietal lobes. Those lesions showed hyperperfusion in acute phase and hypoperfusion in chronic phase on brain SPECT. In both patients, steroid therapy was effective in acute phase and for prevention of recurrence. High signal in the bilateral cingulate cortex on MR T2-weighted and FLAIR images might to be one of the unique findings considered MOG-Ab associated diseases.

Radiological characteristics of myelin oligodendrocyte glycoprotein antibody disease.

BACKGROUND: MOG antibody disease is an autoimmune disease of the central nervous system (CNS) characterized by the presence of a serological antibody against myelin oligodendrocyte glycoprotein (MOG). MRI is instrumental in distinguishing neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS), but MRI features of MOG disease appear to overlap with NMOSD and MS. OBJECTIVES: In this study we aim to characterize the radiological features of MOG antibody disease and compare the findings with those previously described. METHODS: This is a retrospective study of 26 MOG positive patients. We aim to describe their brain, spinal and orbital MRI features and compare our findings with those previously reported in the literature. RESULTS: The majority of the abnormal findings was located on orbital MRIs, with more involvement of the anterior structures and bilateral involvement of the optic nerves. Brain abnormalities were distinct from both NMOSD and MS lesions. Spinal cord was the least affected. CONCLUSIONS: This is a dedicated radiological study aiming to characterize the features of MOG antibody disease which might aid in the proper investigation of cases presenting with acquired demyelinating disorders.

Follow-up study on Chinese children with relapsing MOG-IgG-associated central nervous system demyelination.

BACKGROUND: Some studies have reported clinical features of relapsing MOG-IgG-associated CNS demyelination principally in Caucasians children. It is not clear whether Chinese children share the same phenotype. OBJECTIVE: To delineate the clinical characteristics in Chinese children with relapsing MOG-IgG-associated demyelination. METHODS: A follow-up study on 23 Children with relapsing MOG-IgG-associated demyelination from two Chinese tertiary hospitals was performed. Phenotypic features at each demyelinating attacks, neuroimaging characteristics, autoimmune antibodies in CSF/serum, response to disease modifying drugs and functional deficits during the disease course were analyzed. RESULTS: The median age at disease onset was 5.38 (2.33-12.75) years. The male to female ratio was 1:1.30. The disease duration was 2.33(1.00-8.92) years at the last follow-up. (1) Clinical phenotypes: ADEM was the most common initial presentation (12/23, 52.17%). In 82 attacks during disease course, ADEM was also the most common phenotype (30/82, 36.59%), followed by ON (24/82, 29.27%). (2) Imaging findings: 57/70 (81.43%) brain MRI scans during acute attacks showed new lesions. The most common location of new lesions in brain was the juxtacortical white matter (45/57, 78.95%). In 46 brain MRI scans with supratentorial white matter lesions, ADEM-like patterns were most common (25/46, 54.35%), and 5/46 (10.87%) scans exhibited leukodystrophy-like patterns. (3) Laboratory examinations: Anti-NMDA receptor IgG in CSF was detected in two patients (2/12, 16.67%), with one patient presented with anti-NMDAR encephalitis associated symptoms. (4) Therapeutic responses and outcomes: In 19 patients treated with disease-modifying drugs (including rituximab, mycophenolate mofetil, azathioprine and so on) longer than 6 months, median annualised relapse rates decreased from 1.71 before treatment to 0.44 during treatment (P < 0.05), with eleven patients (11/19, 57.89%) having no relapses. Median EDSS score at the last follow-up was 1.0(0-3.5). Visual dysfunction (12/23, 52.17%) was the most common neurological sequela, with cognitive dysfunction and epilepsy in some of patients. CONCLUSIONS: The phenotypic features of Chinese children with relapsing MOG-IgG-associated CNS demyelination were similar to that in Caucasian children. ADEM was the most common phenotype in all demyelinating attacks, followed by ON. Cerebral lesions were common and extensive, manifested as ADEM-like or even leukodystrophy-like patterns. Visual dysfunction was the most common neurological sequela. Although some disease-modifying drugs could reduce ARR, optimal treatment needs future study.