title: A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings.
abstract: OBJECTIVE
  Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare progressive neurological disorder caused by Lamin B1 duplication (LMNB1). Our aim was to investigate longitudinally the pattern of the autonomic dysfunction and the degree of neuropsychological involvement.
  
  
  METHODS
  Three related ADLD patients and one asymptomatic carrier of LMNB1 duplication underwent a standardized evaluation of autonomic nervous system, including cardiovascular reflexes, pharmacological testing, microneurography, skin biopsy, Metaiodobenzylguanidine scintigraphy and a complete neuropsychological battery.
  
  
  RESULTS
  An early neurogenic orthostatic hypotension was detected in all patients and confirmed by a low rise in noradrenaline levels on Tilt Test. However infusion of noradrenaline resulted in normal blood pressure rise as well as the infusion of clonidine. At the insulin tolerance test the increase in adrenaline resulted pathological in two out three patients. Microneurography failed to detect muscle sympathetic nerve activity bursts. Skin biopsy revealed a poor adrenergic innervation, while cardiac sympathetic nerves were normal. None of ADLD patients showed a global cognitive deficit but a selective impairment in the executive functions.
  
  
  CONCLUSIONS
  Autonomic disorder in ADLD involves selectively the postganglionic sympathetic system including the sympatho-adrenal response. Cognitive involvement consisting in an early impairment of executive tasks that might precede brain MR abnormalities.
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Terlizzi
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Calandra-Buonaura
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Functional MR Unit, Policlinico S. Orsola-Malpighi, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zanigni
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Barletta
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.affiliation: Neurology outpatient Clinic, Department of Primary Care, Local Health Authority of Modena, Modena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Guaraldi
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Donadio
authors.affiliation: Unit of Nuclear Medicine, Maggiore Hospital of Bologna, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cason
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Contin
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Poda
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Functional MR Unit, Policlinico S. Orsola-Malpighi, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Tonon
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sambati
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gallassi
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Functional MR Unit, Policlinico S. Orsola-Malpighi, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Lodi
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. Electronic address: pietro.cortelli@unibo.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D056344:Executive Function; D005260:Female; D020440:Gene Duplication; D006801:Humans; D034921:Lamin Type B / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*
chemical_list: D034921:Lamin Type B
keywords: Adult onset; Autonomic nervous system disease; Lamin B1; Leukodystrophy