Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. RESULTS: Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). DISCUSSION: Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

7 T Lesion-Attenuated Magnetization-Prepared Gradient Echo Acquisition for Detection of Posterior Fossa Demyelinating Lesions in Multiple Sclerosis.

OBJECTIVES: Detection of infratentorial demyelinating lesions in multiple sclerosis (MS) presents a challenge in magnetic resonance imaging (MRI), a difficulty that is further heightened in 7 T MRI. This study aimed to assess the efficacy of a novel MRI approach, lesion-attenuated magnetization-prepared gradient echo acquisition (LAMA), for detecting demyelinating lesions within the posterior fossa and upper cervical spine on 7 T MRI and contrast its performance with conventional double-inversion recovery (DIR) and T2-weighted turbo spin echo sequences. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study in 42 patients with a confirmed diagnosis of MS. All patients had 7 T MRI that incorporated LAMA, 3D DIR, and 2D T2-weighted turbo spin echo sequences. Three readers assessed lesion count in the brainstem, cerebellum, and upper cervical spinal cord using both DIR and T2-weighted images in one session. In a separate session, LAMA was analyzed alone. Contrast-to-noise ratio was also compared between LAMA and the conventional sequences. Lesion counts between methods were assessed using nonparametric Wilcoxon signed rank test. Interrater agreement in lesion detection was estimated by intraclass correlation coefficients. RESULTS: LAMA identified a significantly greater number of lesions than DIR + T2 (mean 6.4 vs 3.0; P < 0.001). LAMA also exhibited better interrater agreement (intraclass correlation coefficient [95% confidence interval], 0.75 [0.41-0.88] vs 0.61 [0.35-0.78]). The contrast-to-noise ratio for LAMA (3.7 ± 0.9) significantly exceeded that of DIR (1.94 ± 0.7) and T2 (1.2 ± 0.7) (all P's < 0.001). In cases with no lesions detected using DIR + T2, at least 1 lesion was identified in 83.3% with LAMA. Across all analyzed brain regions, LAMA consistently detected more lesions than DIR + T2. CONCLUSIONS: LAMA significantly improves the detection of infratentorial demyelinating lesions in MS patients compared with traditional methods. Integrating LAMA with standard magnetization-prepared 2 rapid acquisition gradient echo acquisition provides a valuable tool for accurately characterizing the extent of MS disease.

Defining the natural history of tumefactive demyelination: A retrospective cohort of 257 patients.

OBJECTIVE: To describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes. METHODS: Retrospective review of TD cases seen at Mayo Clinic, 1990-2021. RESULTS: Of 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow-up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), 0 had aquaporin-4-IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic. Onset before age 18 was present in 18/257 (7%). Female to male ratio was 1.3:1. Cerebrospinal fluid oligoclonal (CSF) bands were present in 95/153 (62%). TD was the first demyelinating attack in 176/257 (69%). At presentation, 59/126 (47%) fulfilled Barkhof criteria for dissemination in space, 59/100 (59%) had apparent diffusion coefficient (ADC) restriction, and 57/126 (45%) had mass effect. Despite aggressive clinical presentation at onset, 181/257 (70%) of patients remained fully ambulatory (Expanded Disability Status Scale [EDSS] ≤4) after a 3.0-year median follow-up duration. Severe initial attack-related disability (EDSS ≥4) was more common in patients with motor symptoms (81/143 vs. 35/106, p < 0.0001), encephalopathy (20/143 vs. 2/106, p < 0.0001) and ADC restriction on initial MRI (42/63 vs. 15/33, p = 0.04). Poor long-term outcome (EDSS ≥4) was more common in patients with older onset age (41.9 ± 15 vs. 36.8 ± 15.6, p = 0.02) and motor symptoms at onset (49/76 vs. 66/171, p < 0.0001). INTERPRETATION: Most TD patients should be considered part of the MS spectrum after excluding MOGAD and NMOSD. Motor symptoms and older age at presentation portend a poor outcome.

Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies.

OBJECTIVE: Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures. METHODS: Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated. RESULTS: Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p = .04), highest seizure frequency being at least daily (p = .0002), seizures on electroencephalogram (EEG; p = .03), and imaging evidence of limbic encephalitis (LE; p = .03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p = .04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures. SIGNIFICANCE: Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.

Central Vein Sign in Multiple Sclerosis: A Comparison Study of the Diagnostic Performance of 3T versus 7T MRI.

BACKGROUND AND PURPOSE: An early and accurate diagnosis of multiple sclerosis remains challenging in clinical neurology. Established diagnostic methods have less than desirable sensitivity and specificity. An accurate, noninvasive diagnostic test for MS could have a major impact on diagnostic criteria. We compared the frequency of detection of the central vein sign (CVS) in white matter lesions of MS and controls on 7T T2*-weighted and SWI to 3T SWI. Additionally, we assessed the diagnostic performance of 7T T2*, 7T SWI, and 3T SWI for MS. MATERIALS AND METHODS: A retrospective case-control study was performed of patients with MS having both 7T MRI and 3T MRI. A control group of patients without MS was selected. Diagnosis of MS was established by board-certified neurologists with fellowship training in autoimmune neurology in line with the 2017 McDonald criteria. Percentage of lesions with a CVS was blindly measured for each technique. Diagnostic performance was computed by sensitivity, specificity, and positive and negative likelihood ratios (LRs). RESULTS: Sixty-one patients with MS (903 lesions) and 39 controls (1088 lesions) were included. 7T T2* showed significantly more CVS (87%) than both 7T SWI (73%) and 3T SWI (31%) (all P < .001). CVS was identified in the control group in ≤6% of lesions on all sequences. Using a threshold of >40% of lesions with CVS on 7T T2* and >15% on 7T SWI, both sequences had an accuracy = 100%, sensitivity = 100%, specificity = 100%, infinite positive LR, and zero negative LR. Using an optimal threshold of >12%, 3T SWI had an accuracy = 96.0%, sensitivity = 93.4%, specificity = 100%, infinite positive LR, and negative LR = 0.066. CONCLUSIONS: 7T MRI had 100% sensitivity and specificity for the diagnosis of MS and is superior to 3T. Future revisions to MS diagnostic criteria may consider recommendations for 7T MRI and inclusion of CVS as a biomarker.

Utility of MRI Enhancement Pattern in Myelopathies With Longitudinally Extensive T2 Lesions.

OBJECTIVE: To determine whether MRI gadolinium enhancement patterns in myelopathies with longitudinally extensive T2 lesions can be reliably distinguished and assist in diagnosis. METHODS: We retrospectively identified 74 Mayo Clinic patients (January 1, 1996-December 31, 2019) fulfilling the following criteria: (1) clinical myelopathy; (2) MRI spine available; (3) longitudinally extensive T2 hyperintensity (≥3 vertebral segments); and (4) characteristic gadolinium enhancement pattern associated with a specific myelopathy etiology. Thirty-nine cases with alternative myelopathy etiologies, without previously described enhancement patterns, were included as controls. Two independent readers, educated on enhancement patterns, reviewed T2-weighted and postgadolinium T1-weighted images and selected the diagnosis based on this knowledge. These were compared with the true diagnoses, and agreement was measured with Kappa coefficient. RESULTS: Among all cases and controls (n = 113), there was excellent agreement for diagnosis using postgadolinium images (kappa, 0.76) but poor agreement with T2-weighted characteristics alone (kappa, 0.25). A correct diagnosis was more likely when assessing postgadolinium image characteristics than with T2-weighted images alone (rater 1: 100/113 [88%] vs 61/113 [54%] correct, p < 0.0001; rater 2: 95/113 [84%] vs 68/113 [60%] correct, p < 0.0001). Of the 74 with characteristic enhancement patterns, 55 (74%) were assigned an alternative incorrect or nonspecific diagnosis when originally evaluated in clinical practice, 12 (16%) received immunotherapy for noninflammatory myelopathies, and 2 (3%) underwent unnecessary spinal cord biopsy. CONCLUSIONS: Misdiagnosis of myelopathies is common. The gadolinium enhancement patterns characteristic of specific diagnoses can be identified with excellent agreement between raters educated on this topic. This study highlights the potential diagnostic utility of enhancement patterns in myelopathies with longitudinally extensive T2 lesions.

A systematic review of Gamma-aminobutyric Acid Receptor Type B autoimmunity.

OBJECTIVE: To review the available research to describe the clinical characteristics and neoplastic associations of patients with gamma-aminobutyric acid receptor type B (GABAB-R) autoantibodies. METHODS: Literature was reviewed on PubMed, Mendeley literature search, and the American Academy of Neurology database for articles published from June 2008 to October of 2018 using a variety of key words. These key words include: "gamma-aminobutyric acid seizures," "gamma-aminobutyric acid limbic encephalitis", "GABA(B) receptor antibodies," "autoimmune encephalitis," "autoimmune epilepsy," "GABA(B) encephalitis, " and "GABA paraneoplastic." With the results, the papers were reviewed in a systematic manner. RESULTS: A total of 10 studies were reviewed. A summary of the demographic, clinical, and serological findings of the cases detailed in the literature are provided. An additional illustrative case is described. In total, 94 patients were reviewed. CONCLUSIONS: GABAB-R autoimmune disease is characterized by refractory seizures or status epilepticus and frequent association with small cell lung cancer. Additionally, a substantial minority of patients have non-inflammatory CSF.

Trigeminal Neuralgia Following Lightning Injury.

Lightning and other electrical incidents are responsible for more than 300 injuries and 100 deaths per year in the United States alone. Lightning strikes can cause a wide spectrum of neurologic manifestations affecting any part of the neuraxis through direct strikes, side flashes, touch voltage, connecting leaders, or acoustic shock waves. This article describes the first case of trigeminal neuralgia induced by lightning injury to the trigeminal nerve, thereby adding a new syndrome to the list of possible lightning-mediated neurologic injuries.