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Mitochondrial diseases mimicking autoimmune diseases of the CNS and good response to steroids initially

  • Author Footnotes
    1 Contributed equally, first author.
    Adela Della Marina
    Footnotes
    1 Contributed equally, first author.
    Affiliations
    Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany
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  • Author Footnotes
    1 Contributed equally, first author.
    Annikki Bertolini
    Footnotes
    1 Contributed equally, first author.
    Affiliations
    Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany
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  • Andreas Wegener-Panzer
    Affiliations
    Department of Pediatric Radiology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany
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  • Marina Flotats-Bastardas
    Affiliations
    Department of Pediatric Neurology, Saarland University Medical Center, Homburg, Germany
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  • Tabea Reinhardt
    Affiliations
    Department of Pediatric Neurology, Saarland University Medical Center, Homburg, Germany
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  • Ines El Naggar
    Affiliations
    Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany
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  • Felix Distelmaier
    Affiliations
    Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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  • Astrid Blaschek
    Affiliations
    Department of Pediatric Neurology and Development Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
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  • Ulrike Schara-Schmidt
    Affiliations
    Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany
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  • Theresa Brunet
    Affiliations
    School of Medicine, Institute of Human Genetics, Technical University of Munich, Munich, Germany
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  • Matias Wagner
    Affiliations
    Department of Pediatric Neurology and Development Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany

    School of Medicine, Institute of Human Genetics, Technical University of Munich, Munich, Germany

    Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg, Germany
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  • Dimitri Smirnov
    Affiliations
    School of Medicine, Institute of Human Genetics, Technical University of Munich, Munich, Germany

    Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg, Germany
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  • Holger Prokisch
    Affiliations
    School of Medicine, Institute of Human Genetics, Technical University of Munich, Munich, Germany

    Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg, Germany
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  • Author Footnotes
    2 Contributed equally, senior author.
    Saskia B. Wortmann
    Footnotes
    2 Contributed equally, senior author.
    Affiliations
    University Children's Hospital, Paracelsus Medical University (PMU), Salzburg, Austria

    Amalia Children's Hospital, Radboudumc, Nijmegen, the Netherlands
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  • Author Footnotes
    2 Contributed equally, senior author.
    Kevin Rostasy
    Correspondence
    Corresponding author. Pediatric Neurology, Witten/Herdecke University, Children's Hospital Datteln, Dr. Friedrich-Steiner Str. 5, D-45711, Datteln, Germany.
    Footnotes
    2 Contributed equally, senior author.
    Affiliations
    Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally, first author.
    2 Contributed equally, senior author.
Published:September 20, 2022DOI:https://doi.org/10.1016/j.ejpn.2022.09.003

      Highlights

      • Mitochondrial diseases can mimic disorders such as autoimmune encephalitis (AE).
      • Mitochondrial diseases can show a good response to steroids in the acute event.
      • Genetic testing for mitochondrial disorders should be performed in uncertain cases.
      • In possible AE elevated lactate or consanguinity may indicate alternative diagnoses.

      Abstract

      Introduction

      Neuroimmunological diseases such as autoimmune encephalitis (AE) or acquired demyelinating syndromes (ADS), can present with neurological symptoms and imaging features that are indistinguishable from mitochondrial diseases (MD) in particular at initial presentation.

      Methods

      Retrospective analysis of the clinical, laboratory and neuroimaging features of five patients who presented with signs of a neuroimmunological disease but all had pathological pathogenic variants in genes related to mitochondrial energy metabolism.

      Results

      Four patients presented with an acute neurological episode reminiscent of a possible AE and one patient with a suspected ADS at initial presentation. MRI findings were compatible with neuroimmunological diseases in all patients. In two children cerebrospinal fluid (CSF) studies revealed a mildly elevated cell count, two had elevated CSF lactate, none had oligoclonal bands (OCBs). All patients improved rapidly with intravenous steroids or immunoglobulins. Four patients had one or more relapses. Three patients showed worsening of their neurological symptoms with subsequent episodes and one patient died. Relapses in conjunction with new and progressive neurological symptoms, led to additional work-up which finally resulted in different genetic diagnosis of MD in all patients (MT-TL1, MT-ND5, APOA1-BP, HPDL, POLG).

      Discussion

      We would like to draw attention to a subset of patients with MD initially presenting with signs and symptoms mimicking neuroimmunological. Absence of CSF pleocytosis, elevated CSF lactate and progressive, relapsing course should trigger further (genetic) investigations in search of a MD even in patients with good response initially to immunomodulating therapies.

      Keywords

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