A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings

Rossana Terlizzi, Giovanna Calandra-Buonaura, Stefano Zanigni, Giorgio Barletta, Sabina Capellari, Pietro Guaraldi, Vincenzo Donadio, Ernesto Cason, Manuela Contin, Roberto Poda, Caterina Tonon, Luisa Sambati, Roberto Gallassi, Rocco Liguori, Raffaele Lodi, Pietro Cortelli

Research output: Contribution to journalArticle

Abstract

Background and purpose: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)20-26
Number of pages7
JournalAutonomic Neuroscience: Basic and Clinical
Volume195
DOIs
Publication statusPublished - Feb 1 2016

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Keywords

  • Adult onset
  • Autonomic nervous system disease
  • Lamin B1
  • Leukodystrophy

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems

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