Introduction
Late‐onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α‐glucosidase enzyme activity. Enzyme replacement therapy has been shown to ...be effective, but long‐term treatment results vary. Avalglucosidase alfa demonstrated non‐inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.
Methods
Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow‐up. Respiratory (forced vital capacity FVC) and motor functions (Six‐Minute Walk Test 6MWT) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.
Results
Twenty‐nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.
Discussion
At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.
Conclusion
Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.
Platinum‐based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain‐Barré syndrome (GBS). We describe five patients who developed GBS while ...receiving platinum‐based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non–dose‐dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life‐threatening complication of platinum chemotherapy.
Implications for Practice
Many patients on platinum‐based chemotherapy for solid tumors develop sensory neuropathy, a common dose‐dependent side effect. The authors propose that Guillain‐Barré syndrome may constitute an immune‐mediated, non‐dose‐related side effect of platinum‐based chemotherapy. Prompt diagnosis of Guillain‐Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.
To increase awareness of a potentially life‐threatening complication of platinum chemotherapy, this brief communication describes five patients who developed GBS while receiving platinum‐based chemotherapy for a solid tumor and reports the results of a review of the literature on this topic.
Recent studies suggest that sleep disorders are present in two-thirds of patients with autoimmune encephalitis. In anti-Ma2 encephalitis, hypersomnia appears to be frequent. However, only few cases ...of type 1 narcolepsy have been reported to date with anti-Ma2 encephalitis. We report 2 new cases of patients with narcolepsy secondary to anti-Ma2 encephalitis. Patient 1, a 68-year-old man, had narcolepsy type 1, including sleep attacks, cataplexy, abnormal Multiple Sleep Latency Tests and hypocretin-1 deficiency (< 50 ng/L) in the cerebrospinal fluid (CSF), associated with a cerebellar syndrome. Anti-Ma2 antibodies were present in the serum and CSF and antivoltage-gated potassium channel antibodies in the serum. He benefited from a treatment with pitolisant. Patient 2, a 42-year-old man, had narcolepsy type 2, including hypersomnolence, no cataplexy, intermediate CSF levels of hypocretin-1 (138 ng/L), abnormal Multiple Sleep Latency Tests, and a limbic encephalitis presentation. Anti-Ma2 antibodies were present in the serum and CSF, and anti-Ma1 antibodies were in the CSF. For both, repeated polysomnographies were necessary to establish the precise diagnosis of central hypersomnia, emphasizing the importance of carrying out sleep investigations in a tertiary neurology center with sleep medicine expertise in patients with anti-Ma2 encephalitis.
Brunet de Courssou J-B, Testard P, Sallansonnet-Froment M, et al. Narcolepsy secondary to anti-Ma2 encephalitis: two case reports.
. 2023;19(4):837-841.
Abstract
Bioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses ...many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To overcome these difficulties, we initiated BioConvert, a collaborative project to facilitate the conversion of life science data from one format to another. BioConvert aggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently, BioConvert supports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users, BioConvert can also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface to BioConvert, hence allowing direct use for the community.
Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively characterise ...ICI-encephalitis and identify diagnostic biomarkers and outcome predictors.
This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015–2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade < 3 at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. Neurofilament light chain (NfL) was measured by enzyme-linked immunosorbent assay.
Sixty-seven patients with definite encephalitis were identified (median age, 69 years; 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), while 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24 patients, 92%) and pleocytosis (24/24 patients, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62% versus 8/24, 33%, p = 0.025), PNS-related antibodies (36/43, 84% versus 1/24, 4%, p < 0.001), and neuroendocrine cancers (22/43, 51% versus 1/24, 4%; p < 0.001) than patients with meningoencephalitis. Focal encephalitis patients had a lower rate of irAE treatment response (7/39, 18%) and higher mortality (27/43, 63%) compared to meningoencephalitis patients (12/22, 77% and 5/24, 21%, respectively, p < 0.001 each). PNS-related antibodies were associated with less irAE treatment response, independently of age, sex, and baseline severity (adjusted OR 0.05; 95%CI 0.01; 0.19; p < 0.001) as well as higher mortality, independently of age and cancer type (adjusted HR 5.07; 95% CI 2.12; 12.12; p < 0.001). Serum NfL discriminated patients with definite ICI-encephalitis (n = 27) from cancer-matched controls (n = 16; optimal cut-off >273.5 pg/mL, sensitivity 81%, specificity 88%, AUC 0.87, 95% CI 0.76; 0.98) and irAE treatment responders (n = 10) from non-responders (n = 17, optimal cut-off >645 pg/mL, sensitivity 90%, specificity 65%; AUC 0.75, 95% CI 0.55; 0.94).
ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations.
Agence Nationale de la Recherche.
Background: Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively ...characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors. Methods: This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015–2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade < 3 at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. Neurofilament light chain (NfL) was measured by enzyme-linked immunosorbent assay. Findings: Sixty-seven patients with definite encephalitis were identified (median age, 69 years; 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), while 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24 patients, 92%) and pleocytosis (24/24 patients, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62% versus 8/24, 33%, p = 0.025), PNS-related antibodies (36/43, 84% versus 1/24, 4%, p < 0.001), and neuroendocrine cancers (22/43, 51% versus 1/24, 4%; p < 0.001) than patients with meningoencephalitis. Focal encephalitis patients had a lower rate of irAE treatment response (7/39, 18%) and higher mortality (27/43, 63%) compared to meningoencephalitis patients (12/22, 77% and 5/24, 21%, respectively, p < 0.001 each). PNS-related antibodies were associated with less irAE treatment response, independently of age, sex, and baseline severity (adjusted OR 0.05; 95%CI 0.01; 0.19; p < 0.001) as well as higher mortality, independently of age and cancer type (adjusted HR 5.07; 95% CI 2.12; 12.12; p < 0.001). Serum NfL discriminated patients with definite ICI-encephalitis (n = 27) from cancer-matched controls (n = 16; optimal cut-off >273.5 pg/mL, sensitivity 81%, specificity 88%, AUC 0.87, 95% CI 0.76; 0.98) and irAE treatment responders (n = 10) from non-responders (n = 17, optimal cut-off >645 pg/mL, sensitivity 90%, specificity 65%; AUC 0.75, 95% CI 0.55; 0.94). Interpretation: ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations. Funding: Agence Nationale de la Recherche.
Narcolepsy secondary to anti-Ma2 encephalitis: two case reports Brunet de Courssou, Jean-Baptiste; Testard, Pauline; Sallansonnet-Froment, Magali ...
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine,
04/2023, Letnik:
19, Številka:
4
Report
Recent studies suggest that sleep disorders are present in two-thirds of patients with autoimmune encephalitis. In anti-Ma2 encephalitis, hypersomnia appears to be frequent. However, only few cases ...of type 1 narcolepsy have been reported to date with anti-Ma2 encephalitis. We report 2 new cases of patients with narcolepsy secondary to anti-Ma2 encephalitis. Patient 1, a 68-year-old man, had narcolepsy type 1, including sleep attacks, cataplexy, abnormal Multiple Sleep Latency Tests and hypocretin-1 deficiency (< 50 ng/L) in the cerebrospinal fluid (CSF), associated with a cerebellar syndrome. Anti-Ma2 antibodies were present in the serum and CSF and antivoltage-gated potassium channel antibodies in the serum. He benefited from a treatment with pitolisant. Patient 2, a 42-year-old man, had narcolepsy type 2, including hypersomnolence, no cataplexy, intermediate CSF levels of hypocretin-1 (138 ng/L), abnormal Multiple Sleep Latency Tests, and a limbic encephalitis presentation. Anti-Ma2 antibodies were present in the serum and CSF, and anti-Ma1 antibodies were in the CSF. For both, repeated polysomnographies were necessary to establish the precise diagnosis of central hypersomnia, emphasizing the importance of carrying out sleep investigations in a tertiary neurology center with sleep medicine expertise in patients with anti-Ma2 encephalitis.CITATIONBrunet de Courssou J-B, Testard P, Sallansonnet-Froment M, et al. Narcolepsy secondary to anti-Ma2 encephalitis: two case reports. J Clin Sleep Med. 2023;19(4):837-841.
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