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Background and Objectives: Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies., Methods: European Academy of Neurology/Peripheral Nerve Society 2021 guidelines were used to assess patients with neuropathy using anti-MAG Bühlmann titration units (BTU) and IgM-gammopathy with Mass-Fix (mass spectrophotometry) and serum protein immunofixation electrophoresis (SPIEP). The immunotherapy outcome was reviewed by inflammatory neuropathy cause and treatment (INCAT) and summated compound muscle action potential (CMAP) nerve conduction changes., Results: Seven hundred and fifty-two patients (average age: 63.8 years, female: 31%) were identified over 30 months: (1) typical anti-MAG neuropathy (n = 104); (2) atypical anti-MAG neuropathy (n = 13); (3) distal or sensory-predominant CIDP (n = 25), including 7 without IgM-gammopathy; (4) typical CIDP (n = 47), including 36 without IgM-gammopathy; (5) axonal IgM-gammopathy-associated neuropathy (n = 104); and (6) IgM-gammopathy-negative, anti-MAG-negative axonal neuropathies (n = 426); and (7) without neuropathy (n = 33) anti-MAG negative. IgM-gammopathy was evaluated by Mass-Fix (n = 493), SPIEP (n = 355), or both (n = 96). Mass-Fix detected 4 additional IgM-gammopathies (3%, 4/117) among patients with anti-MAG antibodies and 7 additional patients (2%, 7/376) without anti-MAG not detected by SPIEP testing. Immunotherapy follow-up was available in 123 (mean: 23 months, range: 3-120 months) including 47 with CIDP (28 without IgM-gammopathy) and 76 non-CIDP (5 without IgM-gammopathy, 45 anti-MAG positive). Treatments included IVIG (n = 89), rituximab (n = 80), and ibrutinib or zanubrutinib (n = 24). An optimal anti-MAG-positive cutoff was identified at ≥1,500 BTU (78% sensitivity, 96% specificity) and at ≥10,000 BTU (74% sensitivity, 100% specificity) for typical anti-MAG neuropathy. Improvements in INCAT scores ( p < 0.0001) and summated CMAP ( p = 0.0028) were associated with negative anti-MAG (<1,500 BTU, n = 78) and absence of IgM-gammopathy (n = 34). Among 47 patients with electrodiagnostically confirmed CIDP, all anti-MAG negative, the presence of IgM-gammopathy (n = 19) also correlated with a worse treatment response (INCAT scores p = 0.035, summated CMAP p = 0.049)., Discussion: A cutoff of 10,000 BTU seems optimal for typical anti-MAG neuropathy while ≥1,500 BTU reduces the likelihood of immune-treatable CIDP. Mass-Fix improves IgM-gammopathy detection in anti-MAG and other IgM-gammopathy neuropathies. Patients with IgM-gammopathy lacking MAG antibodies show reduced treatment response.

Introduction/aims: Hypogammaglobulinemia is a common yet under-recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine-thymine-guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients., Methods: We conducted a single-center, retrospective cross-sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results., Results: Forty-one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p = .02). There was no association between IgG deficiency and frequency of infection in this group (p = .428)., Discussion: IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. HID-1 is a trans-Golgi network (TGN) localized peripheral membrane protein contributing to LDCV formation. There is no information about HID-1 structure or domain architecture, and thus it remains unknown how HID-1 binds to the TGN and performs its function. We report that the N-terminus of HID-1 mediates membrane binding through a myristoyl group with a polybasic amino acid patch but lacks specificity for the TGN. In addition, we show that the C-terminus serves as the functional domain. Indeed, this isolated domain, when tethered to the TGN, can rescue the neuroendocrine secretion and sorting defects observed in HID-1 KO cells. Finally, we report that a point mutation within that domain, identified in patients with endocrine and neurological deficits, leads to loss of function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hummer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although median nerve somatosensory evoked potentials are routinely used for prognostication in comatose cardiac arrest survivors, myogenic artifact can reduce inter-rater reliability, leading to unreliable or inaccurate results. To minimize this risk, we determined the benefit of neuromuscular blockade agents in improving the inter-rater reliability and signal-to-noise ratio of SSEPs in the context of prognostication., Methods: Thirty comatose survivors of cardiac arrest were enrolled in the study, following the request from an intensivist to complete an SSEP for prognostication. Right and left median nerve SSEPs were obtained from each patient, before and after administration of an NMB agent. Clinical histories and outcomes were retrospectively reviewed. The SSEP recordings before and after NMB were randomized and reviewed by five blinded raters, who assessed the latency and amplitude of cortical and noncortical potentials (vs. absence of response) as well as the diagnostic quality of cortical recordings. The inter-rater reliability of SSEP interpretation before and after NMB was compared via Fleiss' κ score., Results: Following NMB administration, Fleiss' κ score for cortical SSEP interpretation significantly improved from 0.37 to 0.60, corresponding to greater agreement among raters. The raters were also less likely to report the cortical recordings as nondiagnostic following NMB (40.7% nondiagnostic SSEPs pre-NMB; 17% post-NMB). The SNR significantly improved following NMB, especially when the pre-NMB SNR was low (< 10 dB). Across the raters, there were three patients whose SSEP interpretation changed from bilaterally absent to bilaterally present after NMB was administered (potential false positives without NMB)., Conclusions: NMB significantly improves the inter-rater reliability and SNR of median SSEPs for prognostication among comatose cardiac arrest survivors. To ensure the most reliable prognostic information in comatose post-cardiac arrest survivors, pharmacologic paralysis should be consistently used before recording SSEPs., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Posterior reversible encephalopathy syndrome (PRES) may present with diverse clinical symptoms including visual disturbance, headache, seizures and impaired consciousness. MRI shows oedema, usually involving the posterior subcortical regions. Triggering factors include hypertension, pre-eclampsia/eclampsia, renal failure, cytotoxic agents and autoimmune conditions. The mechanism underlying PRES is not certain, but endothelial dysfunction is implicated. Treatment is supportive and involves correcting the underlying cause and managing associated complications, such as seizures. Although most patients recover, PRES is not always reversible and may be associated with considerable morbidity and even mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Susac syndrome (SuS) is an inflammatory condition of the brain, eye and ear. Diagnosis can be challenging, and misdiagnosis is common., Methods: This is a retrospective review of the medical records of 32 adult patients from an Australasian cohort of SuS patients., Results: An alternative diagnosis prior to SuS was made in 30 patients (94%) with seven patients receiving two or more diagnoses. The median time to diagnosis of SuS was 3 months (range 0.5-100 months). The commonest misdiagnoses were migraine in 10 patients (31%), cerebral vasculitis in six (19%), multiple sclerosis in five (16%) and stroke in five (16%). Twenty-two patients were treated for alternative diagnoses, 10 of whom had further clinical manifestations prior to SuS diagnosis. At presentation seven patients (22%) met criteria for definite SuS, 19 (59%) for probable SuS and six (19%) for possible SuS. Six patients (19%) presented with brain-eye-ear involvement, 14 with brain-ear (44%), six with brain-eye (19%) and six (19%) with only brain involvement. In patients with the complete triad of symptoms the median delay to diagnosis was 3 months (range 1-9 months) compared to 5.25 months (range 0.5-100 months) for patients with encephalopathy and ocular symptoms at presentation., Conclusions: Susac syndrome patients are frequently misdiagnosed at initial presentation, despite many having symptoms or radiological features that are red flags for the diagnosis. Delayed diagnosis can lead to patient morbidity. The varied ways in which SuS can present, and clinician failure to consider or recognize SuS, appear to be the main factors leading to misdiagnosis., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction/aims: Immune-mediated necrotizing myopathy (IMNM) is an immune-mediated myopathy typically presenting with progressive subacute weakness and characteristic, but nonspecific, myopathological findings. Atypical cases however can mimic other inherited or acquired myopathies, depriving patients of treatment. We describe a cohort of such patients., Methods: We retrospectively identified IMNM patients who either previously carried a diagnosis of an inherited myopathy established on clinicopathological grounds or whose muscle biopsies displayed atypical features suggestive of a different myopathy., Results: Among 131 IMNM patients, seven previously unreported patients (5%) met one of the above criteria. Three patients were diagnosed with limb-girdle muscular dystrophy on the basis of a chronic progressive course of weakness and family history of myopathy or cardiomyopathy. The other four patients displayed atypical histological features (two prominent mitochondrial abnormalities, one myofibrillar pathology, and one granulomatous inflammation). Immunostaining of biopsies from 12 additional IMNM patients did not identify myofibrillar pathology. The patient with granulomatous inflammation was known to have pulmonary sarcoidosis. Genetic testing for inherited myopathies was unrevealing. Antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle were identified in 5 and 1 patients, respectively. Four patients presented with slowly progressive weakness over 3-13 y, while weakness was subacute over ≤6 mo in three patients. All patients responded to immunomodulatory therapy., Discussion: Atypical clinical and histological features can occur in IMNM patients, causing delays in diagnosis and treatment. Clinicians should, therefore, consider IMNM in the differential diagnosis of unexplained proximal myopathies in spite of atypical clinical and myopathological findings., (© 2021 Wiley Periodicals LLC.)

Background: Bariatric surgery is an increasingly utilized procedure among patients with obesity-related medical complications. The impact of bariatric surgery on seizure frequency and antiseizure drug (ASD) levels are not well described., Methods: We conducted a retrospective chart review of adult patients with a history of epilepsy or seizures undergoing bariatric surgery for morbid obesity from September 1997-September 2019. The median follow-up was 60 months [range 9-220 months]., Results: Forty-six patients with a history of seizures were identified (38 female); 44 patients had recurrent and unprovoked seizures. Seventeen sets of pre- and post-surgery drug concentrations from 14 patients were reviewed. The median age at surgery was 44 years (range, 19-68). Thirty-three patients were prescribed ASDs at the time of bariatric surgery (median 1 drug [range, 1-3]). Laparoscopic Roux-en-Y was performed in 40 patients, and sleeve gastrectomy in 6 patients. Median pre-surgery weight was 120.75 kg (range, 71-230) and BMI 44.4 kg/m 2 (range, 34-77.6). Six months following surgery the median weight was 89.5 kg (range, 58.2-202) and BMI 34.2 kg/m 2 (range, 24.5-61.9). Nine patients (19.6%) had a worsening of seizure control on long-term follow-up (median 60, range 9-220 months) following bariatric surgery, including five (10.8%) who suffered seizures within 6 months of bariatric surgery. Five patients developed ASD-associated side effects following bariatric surgery including irritability in two patients (levetiracetam and phenytoin) and one patient each suffering from somnolence (phenytoin), hyperammonemic encephalopathy (sodium valproate), and nausea and vomiting (carbamazepine). Subtherapeutic post-surgery drug concentrations were identified in 5 patients and supratherapeutic concentrations in one patient. In the initial 6 months following surgery, ASD doses were increased in five patients and reduced in five., Conclusions: The majority of patients with epilepsy who undergo bariatric surgery have no change in seizure frequency. However, a significant minority of patients may experience medication side effects or an increase in seizure tendency due to the impact of bariatric surgery on ASD drug absorption and metabolism leading. Pre- and post-surgical serum concentrations should be measured in patients with seizures or epilepsy receiving ASDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Acute focal demyelination is the characteristic feature of multiple sclerosis, with the majority of damaged axons undergoing limited remyelination and forming chronic lesions. Potential remyelinating agents are currently under development and there is therefore an urgent need for reliable in vivo biomarkers of remyelination. This study aimed to investigate potential changes in multifocal visual evoked potentials' (mfVEPs) latency in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients. The potential sample size required for a remyelination-based clinical trial using different treatment effect sizes and the mfVEP latency as an outcome measure was also estimated., Methods: A total of 50 RRMS consecutive patients with no previous history of optic neuritis in at least one eye and 15 normal controls of similar age and gender composition were prospectively enrolled. Fifteen patients had a history of unilateral ON more than 12 months earlier, whereas 41 patients demonstrated optic radiations lesions on MRI at baseline. Most patients were on disease modifying therapy. A mfVEP was recorded at baseline and 12 months later., Results: At baseline, the mfVEP latency in RRMS patients was delayed compared with normal controls in both optic neuritis and nonoptic neuritis eyes. Latency delay was significantly correlated to optic radiation lesion volume (R2 = 0.38, P < 0.001). There was no significant latency change in multiple sclerosis patients' eyes or optic neuritis and nonoptic neuritis eyes over the follow-up period with latency remaining remarkably constant. This was despite the fact that 46 of 50 patients were on disease-modifying therapies, implying current treatments do not affect myelination in chronic RRMS cases. Sample size calculations to evaluate an additional or alternative remyelinating agent, based on a 40% treatment effect, revealed that a relatively small sample size (78 patients) would be required to demonstrate efficacy in future trials of remyelination therapies., Conclusions: Given its known sensitivity for latency changes and the stability found in this RRMS population, the mfVEP represents an ideal biomarker to assess the degree of latency recovery that may be achieved by remyelination in multiple sclerosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Delayed diagnosis of immune - mediated necrotizing myopathy leads to increased morbidity. Patients with the chronic course without 3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG or signal recognition particle-IgG are often challenging to diagnose. Immunotherapy response can also be difficult to assess. We created a statistical model to assist immune - mediated necrotizing myopathy diagnosis. Electrical myotonia versus fibrillations were reviewed as biomarkers for immunotherapy treatment response. Identified were 119 immune - mediated necrotizing myopathy cases and 938 other myopathy patients. Inclusion criteria included all having electrophysiological evaluations, muscle biopsies showing inflammatory/necrotizing myopathies, comprehensively recorded neurological examinations, and creatine kinase values. Electrical myotonia was recorded in 56% (67/119) of retrospective and 67% (20/30) of our validation immune - mediated necrotizing myopathy cohorts, and significantly ( P  < 0.001) favoured immune - mediated necrotizing myopathy over other myopathies: sporadic inclusion body myositis (odds ratio = 4.78); dermatomyositis (odds ratio = 10.61); non-specific inflammatory myopathies (odds ratio = 8.46); limb-girdle muscular dystrophies (odds ratio = 5.34) or mitochondrial myopathies (odds ratio = 14.17). Electrical myotonia occurred in immune - mediated necrotizing myopathy seropositive (3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG 70%, 37/53; signal recognition particle-IgG 29%, 5/17) and seronegative (51%, 25/49). Multivariate regression analysis of 20 variables identified 8 (including electrical myotonia) in combination accurately predicted immune - mediated necrotizing myopathy (97.1% area-under-curve). The model was validated in a separate cohort of 30 immune - mediated necrotizing myopathy cases. Delayed diagnosis of cases with electrical myotonia occurred in 24% (16/67, mean 8 months; range 0-194). Half (8/19) had a chronic course and were seronegative, with high model prediction (>86%) at the first visit. Inherited myopathies were commonly first suspected in them. Follow-up evaluation in patients with electrical myotonia on immunotherapy was available in 19 (median 21 months, range 2-124) which reduced from 36% (58/162) of muscles to 7% (8/121; P  < 0.001). Reduced myotonia correlated with immunotherapy response in 64% (9/14) as well as with median creatine kinase reduction of 1779 U/l (range 401-9238, P  < 0.001). Modelling clinical features with electrical myotonia is especially helpful in immune - mediated necrotizing myopathy diagnostic suspicion among chronic indolent and seronegative cases. Electrical myotonia favours immune - mediated necrotizing myopathy diagnosis and can serve as an adjuvant immunotherapy biomarker., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Immune checkpoint inhibitors have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy, which potentially result in substantial morbidity if not recognized and treated promptly. Current knowledge of immune checkpoint inhibitor-associated myopathy is limited. We conducted a 5-year retrospective study of patients with immune checkpoint inhibitor-associated myopathy. Clinical features, survival and ancillary test findings were analysed and compared with those of immune-mediated necrotizing myopathy patients without immune checkpoint inhibitor exposure seen during the same time period. We identified 24 patients with immune checkpoint inhibitor-associated myopathy (median age 69 years; range 28-86) and 38 patients with immune-mediated necrotizing myopathy. Ocular involvement occurred in 9/24 patients with immune checkpoint inhibitor exposure, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of the immune-mediated necrotizing myopathy patients ( P  < 0.001). Myocarditis occurred in eight immune checkpoint inhibitor-associated myopathy patients and in none of the immune-mediated necrotizing myopathy patients ( P  < 0.001). Median creatine kinase was 686 IU/l in the immune checkpoint inhibitor cohort (seven with normal creatine kinase) compared to 6456 IU/l in immune-mediated necrotizing myopathy cohort ( P  < 0.001). Lymphopenia was observed in 18 and 7 patients with and without immune checkpoint inhibitor exposure, respectively ( P  < 0.001). Myopathological findings were similar between patients with and without immune checkpoint inhibitor exposure, consisting of necrotic fibres with no or subtle inflammation. Necrotic fibres however arranged in clusters in 10/11 immune checkpoint inhibitor-associated myopathy patients but in none of the immune checkpoint inhibitor-naïve patients ( P  < 0.001). Despite the lower creatine kinase levels in immune checkpoint inhibitor-exposed patients, the number of necrotic fibres was similar in both groups. Immune checkpoint inhibitor-associated myopathy patients had a higher frequency of mitochondrial abnormalities and less number of regenerating fibres than immune-mediated necrotizing myopathy patients ( P  < 0.001). Anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies were absent in patients with immune checkpoint inhibitor exposure but positive in two-thirds of immune checkpoint inhibitor-naïve patients. Most patients with immune checkpoint inhibitor-associated myopathy responded favourably to immunomodulatory treatments, but four died from myopathy-related complications and one from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P  = 0.004). In summary, immune checkpoint inhibitor-associated myopathy is a distinct, treatable immune-mediated myopathy with common ocular involvement, frequent lymphopenia and necrotizing histopathology, which contrary to immune-mediated necrotizing myopathy, is featured by clusters of necrotic fibres and not accompanied by anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies. Normal or mildly elevated creatine kinase level does not exclude the diagnosis., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Limited data exist regarding myopathies with early or prominent dysphagia., Methods: A retrospective study was performed (January 2003 to August 2019) to identify myopathy patients in whom dysphagia was the initial symptom or was disproportionately severe compared with limb weakness., Results: Thirty-two patients were identified. The median age at diagnosis was 65 y (range, 36-80 y). Inclusion body myositis (IBM) (n = 15), immune-mediated necrotizing myopathy (IMNM) (n = 5), and oculopharyngeal muscular dystrophy (n = 4), were the most common diagnoses. In 4 patients (3 IMNM and 1 nonspecific myositis) dysphagia evolved rapidly. At evaluation, 21 patients required diet alterations, 5 required feeding tubes, and 8 had aspiration pneumonia. Follow-up data were available for 20 patients (median, 24 mo). Eight patients received immunosuppressive therapies with improvement in 7, including 3 of 4 with rapidly progressive dysphagia., Conclusions: IBM and IMNM accounted for approximately two-thirds of patients with early or prominent dysphagia at our institution. Rapidly progressive dysphagia may predict immunotherapy responsiveness., (© 2020 Wiley Periodicals, Inc.)

Background: Natalizumab, a monoclonal antibody directed against alpha-4-integrin, is an efficacious treatment used in Multiple Sclerosis (MS). Use in early pregnancy is safe but information in the third trimester is limited. Ceasing natalizumab is often associated with an increased risk in MS relapse and in some instances natalizumab continuation during pregnancy may be required. However natalizumab crosses the placenta in late pregnancy and has been associated with hematological abnormalities. We present clinical and hematological outcome data of newborns from a series of MS patients who received natalizumab during their second and third pregnancy trimesters. We describe possible methods to mitigate risks to the fetus., Methods: Retrospective chart review of 15 births from mothers receiving natalizumab throughout pregnancy., Results: Thirteen mothers with third-trimester exposure to natalizumab were identified. Median age at conception was 34 years (26-40) and median disease duration was 53.5 months (11-204). The 13 mothers gave birth to 15 newborns (2 mothers each with 2 individual births), median (SD) birth weight was 2778 gs (2100 - 3790). Congenital or laboratory abnormalities were identified in 5 which included anemia (n = 2) and thrombocytopenia (n = 3)., Conclusions: Complications following natalizumab administration during the second and third trimester of pregnancy occurred in 33% of newborns. However, did not result in mortality or morbidity. Dose alterations during the third trimester, pre-delivery umbilical cord sampling and IVIG administration may reduce hematological effects on newborns. Prospective studies with larger numbers of patients are required to provide further evidence regarding the safety of Natalizumab use in pregnancy., Competing Interests: Declaration of Competing Interest James Triplett, Srimathy Vijayan, SIvaajani Rajanayagam and Phillip Tuch have no disclosures. Allan Kermode has received speaker honoraria and Scientific Advisory Board fees from Bayer, BioCSL, Biogen-Idec, Lgpharma, Merck, Novartis, Roche, Sanofi-Aventis, Sanofi-Genzyme, Teva, NeuroScientific Biopharmaceuticals and Innate Immunotherapeutics. He is currently an investigator in pharmaceutical trials sponsored by Biogen-Idec, Novartis, and Innate Immunotherapeutics., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Metabolic encephalopathy and Non-Convulsive Status Epilepticus (NCSE) have been reported with cephalosporin use, particularly cefepime. We aimed to analyze the clinical and EEG findings in patients with cephalosporin-related neurotoxicity (CRN) at our hospital identified via the hospital EEG database, and to critically review CRN case reports in the literature. A Medline search was performed to identify CRN cases where a representative sample of EEG was provided. EEGs were analyzed using published criteria differentiating NCSE from triphasic waves (TW). Eleven patients at our hospital were identified with CRN (9 cefepime, 2 ceftriaxone): all had an encephalopathy with decreased consciousness and/or confusion. One patient had clinical seizures and 6 had multifocal myoclonus. All patients had abnormal EEGs, all with moderate to severe generalized slowing and 10 also with TW. Recovery was related to cephalosporin withdrawal rather than antiepileptic therapy. Analysis of 37 EEG samples of CRN patients reported in the literature as NCSE (30) or TW (7) revealed that most did not meet criteria for NCSE, with 33 showing TW, 1 showing generalised epileptiform discharges and 3 being uninterpretable. CRN usually produces a toxic encephalopathy rather than NCSE, and is commonly associated with triphasic waves on EEG. In most patients anti-epileptic and/or sedative drugs do not hasten clinical improvement., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pure autonomic failure (PAF) is a progressive syndrome of neurogenic orthostatic hypotension, widespread anhidrosis, urinary retention, and constipation without other neurologic manifestations. It is generally considered a peripheral ganglionic synucleinopathy. Natural history studies have described risk factors for the conversion of PAF to Parkinson's disease, multiple system atrophy, or dementia with Lewy bodies, yet the early stages of PAF are not well characterized. We present a patient with unilateral anhidrosis, contralateral facial flushing and hyperhidrosis consistent with Harlequin syndrome that, over 6 years, progressed to PAF, suggesting that PAF may present with focal autonomic impairment prior to generalized autonomic failure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Muscle-specific tyrosine kinase (MuSK) autoantibody related myasthenia gravis is characterized by bulbar and respiratory manifestations, a poor response to anticholinergics, and a generally good response to plasma exchange and rituximab. It is not known if MuSK-antibody (Ab) levels could be used to predict the clinical course Methods: Three patients for whom frequent long-term monitoring of MuSK-Ab levels and the Myasthenia Gravis Composite (MGC) scores were performed are described., Results: A close relationship existed between the MuSK-Ab concentrations and the MGC score. Furthermore, a rise in Ab concentration preceded a more serious clinical relapse in all patients Conclusions: These findings suggest that MuSK-Ab concentrations may be a useful biomarker for the long-term monitoring of MuSK myasthenia gravis, particularly while in clinical remission. This may allow preemptive escalation of therapy to prevent clinical relapse, and conversely permitting greater weaning of unnecessary immunosuppression. Muscle Nerve, 2019., (© 2019 Wiley Periodicals, Inc.)

The triad of central nervous system symptoms, visual disturbance and hearing impairment is an oft-encountered clinical scenario. A number of immune-mediated diseases should be considered among the differential diagnoses including: Susac syndrome, Cogan syndrome or Vogt-Koyanagi-Harada disease; demyelinating conditions such as multiple sclerosis or neuromyelitis optica spectrum disorder; systemic diseases such as systemic lupus erythematosus, Sjögren syndrome or Behcet disease and granulomatous diseases such as sarcoidosis. In this article, we coin the term 'BEE syndromes' to draw attention to the various immune-mediated diseases that affect the brain, eye and ear. We present common disease manifestations and identify key clinical and investigation features., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Baclofen has been reported to cause both a metabolic encephalopathy and nonconvulsive status epilepticus. Baclofen is typically used in the management of muscle spasticity but is being increasingly used to manage alcohol withdrawal and opiate dependency. Given the increasing use of baclofen we describe the clinical and electrographical features of baclofen neurotoxicity seen at our institution., Methods: The clinical and EEG features of patients with an encephalopathy in the setting of baclofen therapy were analyzed. Patients were identified via our hospital EEG database., Results: Fourteen patients were identified having presented with an acute confusional state without identifiable cause other than baclofen use. Five patients took a deliberate overdose, three of whom were baclofen naive, two patients presented after medication prescription error, and seven patients were on stable doses (30-140 mg daily). All patients presented with an encephalopathy, one patient was reported to have clinical seizures, and seven had multifocal myoclonus. EEGs were abnormal in all patients and showed moderate to severe generalized slowing. Generalized triphasic waves occurring at 1 to 2 Hz, sometimes with an anterior to posterior phase lag, were present in 10 patients (71%), and intermittent generalized suppression of the background was seen in three patients. Three patients received small doses of intravenous benzodiazepines, resulting in a marked depression of consciousness and respiration. All patients recovered within 48 hours of baclofen discontinuation., Conclusions: Baclofen toxicity can produce an acute encephalopathy even at modest doses, with the EEG showing generalized slowing and triphasic waves consistent with a toxic encephalopathy. Management consists of supportive care and cessation of baclofen. Patients with baclofen neurotoxicity exhibit a marked vulnerability to the depressant effects of benzodiazepines.

Objective: There is currently an urgent need for reliable clinical biomarkers of remyelination to be used in Phase 2 and Phase 3 clinical trials. Low contrast visual acuity (LCVA) has been suggested as a functional measure of the integrity of the visual pathway. Therefore, the aim of this study was to elucidate the potential contribution of axonal loss and demyelination to LCVA loss in MS patients., Method: In this study, 50 consecutive relapsing remitting MS patients with a previous history of unilateral optic neuritis were enrolled. Using the linear regression model, we assessed the relative contribution of multifocal Visual Evoked Potentials (mfVEP) latency and Retinal Nerve Fiber Layer (RNFL) thickness to LCVA deficit., Results: Intereye asymmetry of mfVEP latency and RNFL thickness correlated significantly with intereye asymmetry of LCVA ( P  < 0.001). A linear regression model demonstrated increased predictive power of LCVA when mfVEP latency and RNFL thinning were combined (reaching R 2  = 0.67) and confirmed a higher predictive value of RNFL thinning compared to mfVEP latency delay for both contrast levels. However, elimination of subjects with severe axonal loss dramatically increased the relative contribution of mfVEP latency, with contribution of RNFL thickness losing significance for both 1.25% and 2.5% LCVA., Interpretation: While retinal ganglion cell axonal loss is a superior predictor of LCVA, the degree of demyelination contributes significantly to worsening of LCVA, particularly when patients with severe axonal loss are excluded. These results support the feasibility of using LCVA as a functional biomarker in remyelination therapy trials, providing appropriate patient's selection criteria are implemented.