Krecke, Karl N.

Background and Purpose: The diagnosis of spontaneous spinal cord infarction (SCI) is limited by the lack of diagnostic biomarkers and MRI features that often overlap with those of other myelopathies, especially acute myelitis. We investigated whether the ratio between serum neurofilament light chain levels and MRI T2-lesion area (neurofilament light chain/area ratio—NAR) differentiates SCI from acute myelitis of similar severity. Methods: We retrospectively identified Mayo Clinic patients (January 1, 2000–December 31, 2019) with (1) SCI, (2) AQP4 (aquaporin 4)-IgG or MOG (myelin oligodendrocyte glycoprotein)-IgG-associated myelitis at disease clinical presentation, or (3) idiopathic transverse myelitis from a previously identified population-based cohort of patients seronegative for AQP4-IgG and MOG-IgG. Serum neurofilament light chain levels (pg/mL) were assessed at the Verona University (SIMOA, Quanterix) in a blinded fashion on available stored samples obtained ≤3 months from myelopathy presentation. For each patient, the largest spinal cord lesion area (mm 2 ) was manually outlined by 2 independent raters on sagittal T2-weighted MRI images, and the mean value was used to determine NAR (pg/[mL·mm 2 ]). Results: Forty-eight patients were included SCI, 20 (definite, 11; probable, 6; possible, 3); acute myelitis, 28 (AQP4-IgG-associated, 17; MOG-IgG-associated, 5; idiopathic transverse myelitis, 6). The median expanded disability status scale score (range) at myelopathy nadir were 7.75 (2–8.5) and 5.5 (2–8), respectively. Serum neurofilament light chain levels (median [range] pg/mL) in patients with SCI (188 [14.3–2793.4]) were significantly higher compared with patients with AQP4-IgG-associated myelitis (37 [0.8–6942.9]), MOG-IgG-associated myelitis (45.8 [4–283.8]), and idiopathic transverse myelitis (15.6 [0.9–217.8]); P =0.01. NAR showed the highest accuracy for identification of SCI versus acute myelitis with values ≥0.35 pg/(mL·mm 2 ) yielding 86% specificity and 95% sensitivity (area under the curve=0.93). The positive and negative likelihood ratios were 6.67 and 0.06, respectively. NAR remained independently associated with SCI after adjusting for age, gender, immunotherapy before sampling, and days from myelopathy symptoms onset to sampling ( P =0.0007). Conclusions: NAR is a novel and promising clinical biomarker for differentiation of SCI from acute myelitis.

Abstract Background SMART (stroke‐like migraine attacks after radiation therapy) is a rare, delayed complication of brain radiation. In this study, we wanted to review the spectrum of symptoms, neuroradiological findings, autoimmune status, and outcomes in SMART syndrome patients. Methods We conducted a retrospective cohort study of all consecutive adult patients (≥18 years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018. Results We identified 25 unique patients with SMART syndrome and a total of 31 episodes and 15 (60%) patients were male. The median age at onset was 46 (interquartile range [IQR] 43–55) years and the median latency of onset after the initial radiation was 21.6 (IQR 14.4–28.2) years. Magnetic resonance imaging (MRI) showed gyral edema and enhancement in all cases with the temporal (25, 80.6%) and parietal (23, 74.2%) lobes being the most commonly affected. The median follow‐up of the patients in our cohort was 10 (IQR 6–32) weeks. On univariate analysis, factors associated with an increased risk of recurrent SMART episodes were female gender (odds ratio [OR] 8.1, 95% confidence interval [95% CI] 1.1–52.6, p = 0.019) and absence of electrographic seizure discharges during initial symptoms (OR 7.4, 95% CI 1.1–45.9, p = 0.032). We could not identify an autoimmune etiology. Longer duration of symptoms (>10 weeks) correlated with an older age ( p = 0.049), temporal lobe involvement ( p < 0.001), and diffusion restriction ( p = 0.043). Conclusions SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10 weeks occurred in one‐third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.

Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. Results: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2–39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy ( p = 0.001), seizures ( p = 0.045), and leptomeningeal enhancement ( p = 0.045). Conclusion: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.

Background: Myelitis accompanied by a negative spinal cord MRI may lead to diagnostic uncertainty. Objective and Methods: We retrospectively investigated the frequency of negative spinal cord MRI (performed <6 weeks from onset) in Mayo Clinic patients with myelin oligodendrocyte glycoprotein (MOG)-IgG-associated myelitis (2000–2019). Results: The initial spinal cord MRI was negative in 7/73 (10%) patients, despite severe acute disability (median EDSS, 7 (range, 4.5–8)); myelitis symptoms/signs were frequent (paraparesis, neurogenic bladder, sensory level, Lhermitte’s phenomenon). Myelitis lesions became overt at follow-up MRI in three patients. Conclusions: A negative spinal cord MRI should not dissuade from MOG-IgG testing in patients with acute/subacute myelitis.

Stem cell treatment outside of studied and approved medical indications can have unforeseen adverse consequences. Here, we present a 74-year-old male that underwent such therapy. The patient presented to our institution with progressive lower extremity weakness and urinary incontinence. He had previously undergone intrathecal stem cell therapy in Moscow, Russia for weakness and fatigue. Magnetic resonance imaging of his thoracic and lumbar spine showed marked enlargement of the cauda equina nerve roots and abnormal mass-like soft tissue involving the thoracolumbar thecal sac. Surgical biopsy of the intrathecal soft tissue showed polyclonal lymphocytic and glial cell proliferation. The patient’s symptoms did not improve with medical treatment or radiation, and he is currently under observation after multidisciplinary evaluation. Our patient’s experience illustrates one of the potential risks of “stem cell tourism” and exemplifies the imaging and histopathologic features of this rare entity. We also compare our patient’s treatment with other similar examples of stem cell treatments in our institution and others. These have had a wide spectrum of results. In some instances, intrathecal stem cells have caused abnormal imaging findings without any associated patient symptoms. In extreme examples, however, stem cell treatments have resulted in central nervous system neoplasms. Our patient’s lesion is quite unique, with only one similar lesion having been previously published.