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This case study investigates low-energy alternatives to distillation for the recovery of N-methyl-2-pyrrolidone (NMP) from solvent waste in the manufacture of resin precursors. Evaluation includes environmental and economic life cycle assessment of solvent recovery and reuse using batch distillation, solvent extraction, and solvent extraction at a sister plant. Solvent extraction at the sister plant involved shipment of hazardous waste to a facility with existing solvent recovery equipment and lower purity standards for NMP. The amount of processing required to recover useful NMP is reduced, increasing reductions in life cycle emissions and damages to the environment. Extraction at the sister plant recovered 98% of the NMP at a purity of 97.1 wt% from aqueous waste containing 17 wt% NMP. Extraction at the sister plant reduced total and CO2 life cycle emissions by 61% and 59%, respectively. Compared to the distillation recovery alternative, extraction at the sister plant results in reductions of 32% and 33% for total and CO2 life cycle emissions, respectively. Annual operating costs were reduced by 80%, with no capital investment, due to utilization of existing equipment. This resulted in a 10-year net present value (NPV) of $4.20 million, whereas distillation resulted in a 10-year NPV of $3.12 million.

Background and Objectives: To assess the clinical practice applicability of autoimmune encephalitis (AE) criteria (2016)., Methods: Medical records of 538 adults diagnosed with AE or related autoimmune encephalopathy at Mayo Clinic (not including pure movement disorders) were reviewed and AE guideline criteria applied., Results: Of 538 patients, 288 were male (52%). The median symptom onset age was 55 years (range, 11-97 years; 16 had onset as children). All had other non-AE diagnoses reasonably excluded. Of 538 patients, 361 (67%) met at least possible criteria, having all 3 of subacute onset; memory deficits, altered mental status or psychiatric symptoms, and ≥1 supportive feature (new focal objective CNS finding, N = 285; new-onset seizures, N = 283; supportive MRI findings, N = 251; or CSF pleocytosis, N = 160). Of 361 patients, AE subgroups were as follows: definite AE (N = 221, 61%, [87% AE-specific IgG positive]), probable seronegative AE (N = 18, 5%), Hashimoto encephalopathy (N = 20, 6%), or possible AE not otherwise categorizable (N = 102, 28%). The 221 patients with definite AE had limbic encephalitis (N = 127, 57%), anti-NMDA-R encephalitis (N = 32, 15%), ADEM (N = 8, 4%), or other AE-specific IgG defined (N = 54, 24%). The 3 most common definite AE-IgGs detected were as follows: LGI1 (76, 34%), NMDA-R (32, 16%), and high-titer GAD65 (23, 12%). The remaining 177 patients (33%) not meeting possible AE criteria had the following: seizures only (65, 12% of all 538 patients), brainstem encephalitis without supratentorial findings (55, 10%; none had Bickerstaff encephalitis), or other (57, 11%). Those 57 "others" lacked sufficient supportive clinical, radiologic, or CSF findings (N = 26), had insidious or initially episodic onset of otherwise typical disorders (N = 21), or had atypical syndromes without clearcut memory deficits, altered mental status, or psychiatric symptoms (N = 10). Fifteen of 57 were AE-specific IgG positive (26%). Among the remaining 42, evidence of other organ-specific autoimmunity (mostly thyroid) was encountered in 31 (74%, ≥1 coexisting autoimmune disease [21, 50%] or ≥1 non-AE-specific antibodies detected [23, 53%]), and all but 1 had an objective immunotherapy response (97%)., Discussion: The 2016 AE guidelines permit autoimmune causation assessment in subacute encephalopathy and are highly specific. Inclusion could be improved by incorporating AE-IgG-positive patients with isolated seizures or brainstem disorders. Some patients with atypical presentations but with findings supportive of autoimmunity may be immune therapy responsive., Competing Interests: E. Orozco and C. Valencia-Sanchez report no disclosures relevant to the manuscript; J.W. Britton has consulted for UCB pharmaceuticals; D. Dubey has research support from the Department of Defence (CA210208), Centers of Multiple Sclerosis and Autoimmune Neurology and Clinical and Translational Science, Mayo Clinic, and Grifols pharmaceuticals, has consulted for UCB, Immunovant, Argenx, and Astellas pharmaceuticals (compensation for consulting activities paid directly to Mayo Clinic), and has patents pending for KLHL11-IgG, LUZP4-IgG, and cavin-4-IgG as markers of neurologic autoimmunity; E.P. Flanagan has funding from NIH (R01NS113828), has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB, has received honoraria from Pharmacy Times and UpToDate, and has a patent pending for DACH1-IgG as a biomarker of paraneoplastic autoimmunity; A.S. Lopez-Chiriboga has consulted for Horizon Therapeutics and Genentech; N. Zalewski reports no disclosures relevant to the manuscript. A. Zekeridou has patent applications pending on PDE10A-IgG and DACH1-IgG as biomarkers of paraneoplastic neurologic autoimmunity and has received research funding from Genentech; S.J. Pittock is a named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker, has patents pending for KLHL11-IgG and Septin-5-IgG and issued for MAP1B-IgG as markers of neurologic autoimmunity and paraneoplastic disorders, has consulted for Alexion and Medimmune, and has received research support from Genentech, Grifols, Medimmune, and Alexion; A. McKeon reports research funding from the NIH (NIH: RO1NS126227, U01NS120901), patents issued for GFAP and MAP1B-IgGs and patents pending for PDE10A, Septins-5 and Septins-7, and KLCHL11-IgGs, and has consulted for Janssen and Roche pharmaceuticals, without personal compensation. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background and Objectives: Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD)., Methods: We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD., Results: We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD ( p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R 2 = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance., Discussion: Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD., (© 2023 American Academy of Neurology.)

Background and Objective: To determine the frequency of new or enlarging T2-hyperintense or enhancing lesions outside of clinical attacks in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (AQP4+NMOSD)., Methods: We retrospectively included Mayo Clinic patients with MOGAD with: (1) MOG-Immunoglobulin-G positivity by live cell-based assay, (2) fulfilling proposed MOGAD diagnostic criteria, and (3) baseline and follow-up paired MRIs without interval attacks. A neurologist and neuroradiologist reviewed MRIs (T2-fluid attenuated inversion recovery brain, T2 spine, and T1-postgadolinium brain and spine) to identify new or enlarging lesions. A MOGAD subset was then compared to patients with MS and AQP4+NMOSD, based on broadly similar interscan intervals., Results: We included 105 patients with MOGAD (median age, 31 years [range, 2-80]; 60% female) with 373 paired MRIs. In total, 10/105 (9.5%) patients and 13/373 (3%) scans had one or more new T2 lesions (brain, 12/213 [6%]; spine, 1/160 [0.6%]); and 8/367 (2%) had enhancing lesions. New brain lesions were less in MOGAD (1/25 [4%]) than MS (14/26 [54%], p < 0.0001) but did not differ from AQP4+NMOSD (1/13 [8%], p = 1.0) in subgroup analysis. New spinal lesions were rare across groups (0%-4%)., Discussion: New or enlarging MRI lesions rarely develop outside of clinical attacks in MOGAD differing from MS. Surveillance MRIs in MOGAD have limited utility with implications for clinical practice and trial design., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To describe paraneoplastic neuronal intermediate filament (NIF) autoimmunity., Methods: Archived patient and control serum and CSF specimens were evaluated by tissue-based indirect immunofluorescence assay (IFA). Autoantigens were identified by Western blot and mass spectrometry. NIF specificity was confirmed by dual tissue section staining and 5 recombinant NIF-specific HEK293 cell-based assays (CBAs, for α-internexin, neurofilament light [NfL], neurofilament medium, or neurofilament heavy chain, and peripherin). NIF-immunoglobulin Gs (IgGs) were correlated with neurologic syndromes and cancers., Results: Among 65 patients, NIF-IgG-positive by IFA and CBAs, 33 were female (51%). Median symptom onset age was 62 years (range 18-88). Patients fell into 2 groups, defined by the presence of NfL-IgG (21 patients, who mostly had ≥4 NIF-IgGs detected) or its absence (44 patients, who mostly had ≤2 NIF-IgGs detected). Among NfL-IgG-positive patients, 19/21 had ≥1 subacute onset CNS disorders: cerebellar ataxia (11), encephalopathy (11), or myelopathy (2). Cancers were detected in 16 of 21 patients (77%): carcinomas of neuroendocrine lineage (10) being most common (small cell [5], Merkel cell [3], other neuroendocrine [2]). Two of 257 controls (0.8%, both with small cell carcinoma) were positive by both IFA and CBA. Five of 7 patients with immunotherapy data improved. By comparison, the 44 NfL-IgG-negative patients had findings of unclear significance: diverse nervous system disorders ( p = 0.006), as well as limited ( p = 0.003) and more diverse ( p < 0.0001) cancer accompaniments., Conclusions: NIF-IgG detection by IFA, with confirmatory CBA testing that yields a profile including NfL-IgG, defines a paraneoplastic CNS disorder (usually ataxia or encephalopathy) accompanying neuroendocrine lineage neoplasia., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Neuronal calcium channel antibodies are a biomarker of Lambert-Eaton syndrome (LES) and cerebellar ataxia. We have encountered several patients with LES and cerebellar ataxia coexisting, and we sought to further define this association., Methods: We reviewed records of patients at our institution with a diagnosis of "Lambert-Eaton syndrome" and "cerebellar ataxia.", Results: Seventeen patients were identified with LES and ataxia. Presenting symptoms were weakness (8), concurrent weakness and ataxia (4), ataxia (4), and other (1). Nine patients had small-cell lung carcinoma, 3 of whom had survival greater than 100 months. Immunotherapy responses were best among patients without cancer. Nine of 17 (53%) patients were alive at last follow-up (median survival 62 months; range, 8-240)., Discussion: Calcium channel autoimmunity should be considered in patients with coexisting cerebellar ataxia and myasthenic weakness. Affected patients may survive small-cell carcinoma or have immunotherapy-responsive neurological symptoms. Muscle Nerve, 2018., (© 2017 Wiley Periodicals, Inc.)

The 4-repeat (4R)-tauopathies can be clinically heterogeneous and difficult to diagnose. An FDG-PET pattern of hypometabolism has been previously reported in clinically suspected 4R-tauopathies. Considering that pathological confirmation has not been used as inclusion criteria in these studies, however, the possibility exists that atypical cases were excluded. We studied pathologically confirmed cases of 4R-tauopathies to determine if FDG-PET patterns of hypometabolism different than those previously described exist. We identified all autopsy confirmed 4R-tauopathies with FDG-PET imaging performed between 2010 and 2013 within the Mayo Clinic database. Clinical features and FDG-PET imaging were compared to a group of normal controls. Ten patients, seven of which had autopsy-confirmed progressive supranuclear palsy (PSP), were identified. We also identified two cases with globular glial tauopathy (GGT) and one case of corticobasal degeneration (CBD). The overall predominant imaging findings included bilateral caudate hypometabolism in nine cases, mild asymmetric thalamic hypometabolism in eight, midbrain hypometabolism in seven, and bilateral hypometabolism in the supplementary motor area in seven. No differences were observed between PSP and GGT. The one CBD case had asymmetric parietal hypometabolism that was not seen in the PSP and GGT cases. As previously described, 4R-tauopathies are associated with frontal, caudate, midbrain and thalamic hypometabolism on FDG-PET. This is the first report of FDG-PET in GGT, and although our series was limited, no features distinguish GGT from PSP. There was some evidence that parietal hypometabolism may be suggestive of CBD.