title: LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course.
abstract: OBJECTIVE
  Duplication of the LMNB1 gene encoding lamin B1 causes adult-onset autosomal-dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia. Magnetic resonance imaging (MRI) of the brain reveals characteristic findings. This is the first longitudinal study on this disease. Our objective is to describe the natural clinical and radiological course of LMNB1-related ADLD.
  
  
  METHODS
  Twenty-three subjects in two families with LMNB1 duplications were studied over two decades with clinical assessment and MRI of the brain and spinal cord. They were 29 to 70 years old at their first MRI. Repeated MRIs were performed in 14 subjects over a time period of up to 17 years.
  
  
  RESULTS
  Pathological MRI findings were found in the brain and spinal cord in all examinations (i.e., even preceding clinical symptoms). MRI changes and clinical symptoms progressed in a definite order. Autonomic dysfunction appeared in the fifth to sixth decade, preceding or together with gait and coordination difficulties. Motor signs developed ascending from spastic paraplegia to tetraplegia and pseudobulbar palsy in the seventh decade. There were clinical, radiological, and neurophysiological signs of myelopathy. Survival lasted more than two decades after clinical onset.
  
  
  CONCLUSIONS
  LMNB1-related ADLD is a slowly progressive neurological disease. MRI abnormalities of the brain and spinal cord can precede clinical symptoms by more than a decade and are extensive in all symptomatic patients. Spinal cord involvement is a likely contributing factor to early autonomic symptoms and spastic paraplegia.
authors.affiliation: Department of Radiology, Uppsala University, Uppsala, Sweden.
authors.forename: Johannes
authors.initials: J
authors.lastname: Finnsson
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Sundblom
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Atle
authors.initials: A
authors.lastname: Melberg
authors.affiliation: Department of Radiology, Uppsala University, Uppsala, Sweden.
authors.forename: Raili
authors.initials: R
authors.lastname: Raininko
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D034921:Lamin Type B / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020371:Pelizaeus-Merzbacher Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000401:mortality; D011859:Radiography; D013116:Spinal Cord / Q000000981:diagnostic imaging*; D015996:Survival Rate / Q000639:trends
chemical_list: D034921:Lamin Type B