title: Stroke-like onset of brain stem degeneration presents with unique MRI sign and heterozygousNMNAT2variant: a case report.
abstract: BACKGROUND
  Acute-onset neurodegenerative diseases in older patients are rare clinical cases, especially when the degeneration only affects specific regions of the nervous system. Several neurological disorders have been described in which the degeneration of brain parenchyma originates from and/or primarily affects the brain stem. Clinical diagnosis in these patients, however, is often complicated due to a poor understanding of these diseases and their underlying mechanisms.
  
  
  METHODS
  In this manuscript we report on a 73-year-old female who had experienced a sudden onset of complex neurological symptoms that progressively worsened over a period of 2 years. Original evaluation had suggested a MRI-negative stroke as underlying pathogenesis. The combination of patient's medical history, clinical examination and exceptional pattern of brain stem degeneration presenting as "kissing swan sign" in MR imaging was strongly suggestive of acute onset of Alexander's disease. This leukoencephalopathy is caused byGFAP(glial fibrilary acidic protein) gene mutations and may present with brain stem atrophy and stroke-like onset of symptoms in elderly individuals. However, a pathognomonicGFAPgene mutation could not be identified by Sanger sequencing.
  
  
  CONCLUSIONS
  After an extended differential diagnosis and exclusion of other diseases, a definite diagnosis of the patient's condition presently remains elusive. However, whole-exome sequencing performed from patient's blood revealed 12 potentially disease-causative heterozygous variants, amongst which several have been associated with neurological disorders in vitro and in vivo - in particular the axon degeneration-relatedNMNAT2gene.
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University Jena, Jena, 07747 Germany.|Present address: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510 USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University Jena, Jena, 07747 Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wagner
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, 07743 Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ungelenk
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, 07743 Germany.|Present address: Institute of Human Genetics, Uniklinik RWTH Aachen, Aachen, 52074 Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kurth
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University Jena, Jena, 07747 Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Redecker
keywords: Alexander’s disease; Axon degeneration; Brain stem atrophy; Dementia; Kissing swan sign; NMNAT2; Whole-exome sequencing