Alejandro León Betancourt

University Hospital of Bern

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Robert Hoepner

University Hospital of Bern

Andrew Chan

University of Bern

Helly Hammer

University Hospital of Bern

Lara Diem

University of Lucerne

Nicole Kamber

University Hospital of Bern

Anina Schwarzwald

University of Bern

Christoph Friedli

University Hospital of Bern

Anke Salmen

University Hospital of Bern

Fabian Föttinger

Medical University of Vienna

Lídia Sabater

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Cooperative Institutions

Medical University of Vienna

University of Bern

University Hospital of Bern

Universität Innsbruck

Medical University of Graz

Innsbruck Medical University

St. Josef-Hospital

FH Campus Wien

Ruhr University Bochum

Neurology, Inc

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Magnetische Nanopartikel mit therapeutisch wirksamen zellpenetrierenden Peptiden für die zielgerichtete Pharmakotherapie der Dysferlinopathie

Alejandro León Betancourt

10.17169/refubium-29767

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Anti‐kelchlike protein 11 antibody‐associated encephalitis: Two case reports and review of the literature

European Journal of Neurology (2023)

Alejandro León Betancourt Anina Schwarzwald Alban Millonig Michael Oberholzer Lídia Sabater

Kelchlike protein 11 antibodies (KLHL11-IgGs) were first described in 2019 as a marker of paraneoplastic neurological syndromes (PNSs). They have mostly been associated with testicular germ cell tumors (tGCTs).Two patients with KLHL11-IgG encephalitis are reported, and the literature is comprehensively reviewed.Patient 1 had been in remission from a tGCT 10 years prior. He developed episodic vertigo and diplopia progressing over a few days. Treatment with corticosteroids (CSs) was started a few days after symptom onset. Patient 2 had transient diplopia, which resolved spontaneously. Visual problems persisted for 7 months, when he additionally developed a progressive cerebellar syndrome. One year after onset, CS treatment was started. Initial magnetic resonance imaging was unremarkable in both patients, but analysis of cerebrospinal fluid (CSF) revealed chronic inflammation. KLHL11-IgG was positive in both patients (Patient 1 only in CSF, Patient 2 in serum). Neoplastic screening has so far not revealed any signs of active underlying malignancy. We found 15 publications of 112 patients in total with KLHL11-IgG encephalitis. Most patients (n = 82) had a cerebellar syndrome with or without signs of rhombencephalitis. The most common symptoms were ataxia (n = 82) and vertigo (n = 47), followed by oculomotor disturbances (n = 35) and hearing disorders (n = 31). Eighty of 84 patients had a GCT as an underlying tumor.Our cases demonstrate classical symptoms of KLHL11-IgG encephalitis. Early diagnosis and therapy are imperative. As with other PNSs, clinical awareness is needed and further studies are required especially in regard to therapeutic management.

Gait Ataxia

Autoimmune encephalitis

10.1111/ene.15758

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Citations (3)

Fairness in Access to Industry Funded Interventional Phase 1-4 Trials in Epilepsy – How Would a Global Distribution Without Health Inequities Look Like?

Robert Hoepner Alejandro León Betancourt Stefanie Marti Andrea Seiler

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Copy DOI

10.2139/ssrn.4781332

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Switching from natalizumab to antiCD20 monoclonal antibodies: Short transition interval is associated with improved outcome

European Journal of Neurology (2024)

Gabriel Bsteh Robert Hoepner Jonathan A. Gernert Klaus Berek Christiane Gradl

Abstract Objective To investigate the impact of transition interval length when switching from natalizumab (NTZ) to anti‐CD20 monoclonal antibodies (antiCD20) on recurrent disease activity and safety in relapsing multiple sclerosis (RMS). Methods Aggregating data from 8 MS centres in Austria, Switzerland, and Germany, we included RMS patients who (i) continuously received NTZ for ≥3 months, (ii) were switched to antiCD20, and (iii) had ≥12 months follow‐up after switch. The primary endpoint was occurrence of relapse after switch, secondary endpoints included severe infections (CTCAE grade ≥3). Results Overall, 139 RMS patients were included (70.5% females, mean age at switch 38.8 years [SD 9.7], mean disease duration at switch 11.3 years [SD 6.2], median duration on NTZ 4.4 years [range: 0.3–16.4], median transition interval 58 days [0–180]). Relapse occurred in 18 patients (12.9%) after NTZ discontinuation. Of those, 11 (61.1%) patients relapsed during the transition interval. No patient with a transition interval below 30 days experienced a relapse, compared to 11.1% and 16.1% with transition intervals of 30–44 days and ≥ 45 days, respectively. In multivariable Cox regression, a transition interval ≥ 45 days predicted a 4.73‐fold increased risk of relapse. Over approximately 4 years of follow‐up, six severe infections were reported without any noticeable effect of transition interval length. No PML occurred. Conclusions Switching from NTZ to antiCD20 is generally both effective and safe. Keeping the transition interval below 30 days provides the optimal balance between preventing recurrent disease activity and ensuring safety.

Discontinuation

Natalizumab

Clinical endpoint

10.1111/ene.16587

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Anti‐neurochondrin antibody as a biomarker in primary autoimmune cerebellar ataxia—a case report and review of the literature

European Journal of Neurology (2022)

Anina Schwarzwald Anke Salmen Alejandro León Betancourt Lara Diem Helly Hammer

Abstract Background and purpose Neuronal autoantibodies can support the diagnosis of primary autoimmune cerebellar ataxia (PACA). Knowledge of PACA is still sparce. This article aims to highlight the relevance of anti‐neurochondrin antibodies and possible therapeutical consequences in people with PACA. Methods This is a case presentation and literature review of PACA associated with anti‐neurochondrin antibodies. Results A 33‐year‐old man noticed reduced control of the right leg in May 2020. During his first clinic appointment at our institution in September 2021, he complained about gait imbalance, fine motor disorders, tremor, intermittent diplopia and slurred speech. He presented a pancerebellar syndrome with stance, gait and limb ataxia, scanning speech and oculomotor dysfunction. Within 3 months the symptoms progressed. An initial cerebral magnetic resonance imaging, June 2020, was normal, but follow‐up imaging in October 2021 and July 2022 revealed marked cerebellar atrophy (29% volume loss). Cerebrospinal fluid analysis showed lymphocytic pleocytosis of 11 x 10 3 /L (normal range 0–4) and oligoclonal bands type II. Anti‐neurochondrin antibodies (immunoglobulin G) were detected in serum (1:10,000) and cerebrospinal fluid (1:320, by cell‐based indirect immunofluorescence assay and immunoblot, analysed by the EUROIMMUN laboratory). After ruling out alternative causes and neoplasia, diagnosis of PACA was given and immunotherapy (steroids and cyclophosphamide) was started in January 2022. In March 2022 a stabilization of disease was observed. Conclusion Cerebellar ataxia associated with anti‐neurochondrin antibodies has only been described in 19 cases; however, the number of unrecognized PACAs may be higher. As anti‐neurochondrin antibodies target an intracellular antigen and exhibit a mainly cytotoxic T‐cell‐mediated pathogenesis, important therapeutic implications may result. Because of the severe and rapid clinical progression, aggressive immunotherapy was warranted. This case highlights the need for rapid diagnosis and therapy in PACA, as stabilization and even improvement of symptoms are attainable.

Gait Ataxia

Cerebellar ataxia

Pleocytosis

Paraneoplastic cerebellar degeneration

10.1111/ene.15648

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Citations (6)