Neuropsychological Testing in Autoimmune Encephalitis:A Scoping Review

BACKGROUND AND OBJECTIVES: Identifying optimal methods for evaluation and monitoring of cognitive outcomes in AE is important for clinical care and research. This scoping review aimed to evaluate neuropsychological tests (NPT) that are most frequently impaired in AE cohorts to provide recommendations for a standardized NPT battery for AE outcome. METHODS: PubMed search for studies examining NPT in patients with AE was conducted on June 9, 2023. Studies were screened for inclusion/exclusion criteria as follows: at least 1 NPT, individual NPT test scores with comparison with healthy controls or normative data and neural-IgG status, total sample size ≥5, and English manuscript available. RESULTS: The search yielded 5,393 studies, of which 3,359 were screened, 107 were full text reviewed, and 32 met inclusion/exclusion criteria, anti-NMDA-R (k = 18), anti-LGI1 (k = 10), anti-GABAB-R (k = 2), anti-GAD-65 (k = 4), and anti-CASPR2 (k = 3). The cognitive domains most frequently impaired were visual and verbal episodic memory, attention/working memory, processing speed, and aspects of executive functions. DISCUSSION: Given the dearth of literature examining NPT in AE in combination with small sample sizes and methodological differences, more research in this area is needed. However, we provide recommendations for a test battery to be used in future studies, with the aim of standardizing research in this area. Based on the available literature, we recommend the use of comprehensive NPT batteries, spanning all cognitive domains. The highest yield measures may include the tests of (1) visual and verbal learning/memory, (2) basic and sustained attention, (3) processing speed, and (4) executive functions.</p

Comparison of MRI lesion evolution in different central nervous system demyelinating disorders

Background and Objective: There are few studies that compare lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2-lesion evolution in myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS). Methods: In this descriptive study, we retrospectively identified Mayo Clinic patients with MOGAD, AQP4-IgG-NMOSD, or MS and: 1) brain or myelitis attack; 2) available attack MRI within 6 weeks; and 3) follow-up MRI beyond 6 months without interval relapses in that region. Two neurologists identified the symptomatic or largest T2-lesion for each patient (index lesion). MRIs were then independently reviewed by two neuroradiologists blinded to diagnosis to determine resolution of T2-lesions by consensus. The index T2-lesion area was manually outlined acutely and at follow-up to assess variation in size. Results: We included 156 patients (MOGAD, 38; AQP4-IgG-NMOSD, 51; MS, 67) with 172 attacks (brain, 81; myelitis, 91). The age (median [range]) differed between MOGAD (25 [2-74]), AQP4-IgG-NMOSD (53 [10-78]) and MS (37 [16-61]) (p&lt;0.01) and female sex predominated in the AQP4-IgG-NMOSD (41/51 [80%]) and MS (51/67 [76%]) groups but not among those with MOGAD (17/38 [45%]). Complete resolution of the index T2-lesion was more frequent in MOGAD (brain, 13/18[72%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 3/21[14%]; spine, 0/34[0%]) and MS (brain, 7/42[17%]; spine, 0/29[0%]), p&lt;0.001. Resolution of all T2-Lesions occurred most often in MOGAD (brain, 7/18[39%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 2/21[10%]; spine, 0/34[0%]), and MS (brain, 2/42[5%]; spine, 0/29[0%]), p&lt; 0.01. There was a larger median (range) reduction in T2-lesion area in mm2 on follow-up axial brain MRI with MOGAD (213[55-873]) than AQP4-IgG-NMOSD (104[0.7-597]) (p=0.02) and MS, 36[0-506]) (p&lt; 0.001) and the reductions in size on sagittal spine MRI follow-up in MOGAD (262[0-888]) and AQP4-IgG-NMOSD (309[0-1885]) were similar (p=0.4) and greater than MS (23[0-152]) (p&lt;0.001)

Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks.

PURPOSE: To evaluate the effectiveness of plasma exchange (PLEX) for optic neuritis (ON). METHODS: We conducted an international multicenter retrospective study evaluating the outcomes of ON following PLEX. Outcomes were compared to raw data from the Optic Neuritis Treatment Trial (ONTT) using a matched subset. RESULTS: A total of 395 ON attack treated with PLEX from 317 patients were evaluated. The median age was 37 years (range 9-75), and 71% were female. Causes of ON included multiple sclerosis (108), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) (92), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (75), seronegative-NMOSD (34), idiopathic (83), and other (3). Median time from onset of vision loss to PLEX was 2.6 weeks (interquartile range [IQR], 1.4-4.0). Median visual acuity (VA) at the time of PLEX was count fingers (IQR, 20/200-hand motion), and median final VA was 20/25 (IQR, 20/20-20/60) with no differences among etiologies except MOGAD-ON, which had better outcomes. In 81 (20.5%) ON attacks, the final VA was 20/200 or worse. Patients with poor outcomes were older (P&nbsp;=&nbsp;.002), had worse VA at the time of PLEX (P &lt; .001), and longer delay to PLEX (P &lt; .001). In comparison with the ONTT subset with severe corticosteroid-unresponsive ON, a final VA of worse than 20/40 occurred in 6 of 50 (12%) PLEX-treated ON vs 7 of 19 (37%) from the ONTT treated with intravenous methylprednisolone without PLEX (P&nbsp;=&nbsp;.04). CONCLUSION: Most ON attacks improved with PLEX, and outcomes were better than attacks with similar severity in the ONTT. The presence of severe vision loss at nadir, older age, and longer delay to PLEX predicted a worse outcome whereas MOGAD-ON had a more favorable prognosis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Neural autoantibody biomarkers of central nervous system autoimmunity and their clinical and serological accompaniments

Several clinical syndromes or phenotypes which arise from central nervous system (CNS) pathology are associated with distinct autoantibodies. The extent to which these phenotypes overlap and the significance of the autoantibodies either as the cause or as biomarkers of disease is important. This thesis aims to evaluate clinical and serological associations of neural autoantibody biomarkers of the CNS with a focus on aquaporin-4 IgG associated neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), myelin oligodendrocyte glycoprotein IgG associated demyelination (MOGAD) and the autoimmune and paraneoplastic encephalitides. Methods These studies were conducted at the Mayo Clinic Neuroimmunology laboratory in Minnesota while a doctoral student at the University of Sydney. Clinical and laboratory data were obtained from a clinical laboratory service. Results Part A: Demonstrates key serological features of MOGAD and AQP4-IgG NMOSD, highlighting that these are distinct disorders. Chapters 1 and 2 identify distinguishing features including different demographics, lack of antibody co-existence, and a lack of co-existent humoral autoimmunity in MOGAD. Chapter 3 demonstrates the unique neural autoantibody association of N-Methyl-D-aspartate receptor antibody with MOG-IgG in patients with autoimmune encephalitis and MOGAD. Chapter 4 examines factors influencing the change in serostatus of AQP4-IgG. Part B: Chapters 5 and 6 demonstrates clinical distinctions between MOGAD and AQP4-IgG NMOSD; namely that MOGAD patients do not fulfill the NMOSD seronegative diagnostic criteria and lack the characteristic clinical and radiological features of area postrema syndrome observed in NMOSD. Part C: Chapter 7 examines the frequency, age and sex associations of autoimmune/paraneoplastic encephalitis autoantibodies. Conclusions Together these studies characterize the demographic, clinical and serological associations of neural antibody biomarkers of CNS autoimmunity

Optic Chiasm Involvement Associated with Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies (Slides)

To describe and compare the pattern of optic chiasm involvement in patients with myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON) with aquaporin-4 antibody associated optic neuritis (AQP4-ON). MOG-IgG associated disease (MOGAD) has been demonstrated to be a distinct entity from AQP4-IgG positive neuromyelitis optica spectrum disorder (NMOSD). Optic neuritis is often the presenting symptom in NMOSD. It has been previously reported that chiasmal involvement is seen in at least 50% of AQP4-ON compared to a minority of patients with MOG-ON

Visual Outcome Following Plasma Exchange for Optic Neuritis

Plasma exchange (PLEX) is routinely utilized in the setting of optic neuritis (ON) from neuromyelitis optica spectrum disorders (NMOSD), however there are few studies evaluating PLEX in other forms of ON. This study retrospectively evaluated the visual outcomes of PLEX for ON from various etiologies and investigated variables that influenced those outcomes

Optic Chiasm Involvement Associated with Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies (Video)

To describe and compare the pattern of optic chiasm involvement in patients with myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON) with aquaporin-4 antibody associated optic neuritis (AQP4-ON). MOG-IgG associated disease (MOGAD) has been demonstrated to be a distinct entity from AQP4-IgG positive neuromyelitis optica spectrum disorder (NMOSD). Optic neuritis is often the presenting symptom in NMOSD. It has been previously reported that chiasmal involvement is seen in at least 50% of AQP4-ON compared to a minority of patients with MOG-ON

Optic Chiasm Involvement Associated with Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies(PDF)

To describe and compare the pattern of optic chiasm involvement in patients with myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON) with aquaporin-4 antibody associated optic neuritis (AQP4-ON). MOG-IgG associated disease (MOGAD) has been demonstrated to be a distinct entity from AQP4-IgG positive neuromyelitis optica spectrum disorder (NMOSD). Optic neuritis is often the presenting symptom in NMOSD. It has been previously reported that chiasmal involvement is seen in at least 50% of AQP4-ON compared to a minority of patients with MOG-ON.vbchiasmalopticneuriti