Rossana Terlizzi1, Giovanna Calandra-Buonaura1, Stefano Zanigni2, Giorgio Barletta1, Sabina Capellari1, Pietro Guaraldi3, Vincenzo Donadio1, Ernesto Cason4, Manuela Contin1, Roberto Poda5, Caterina Tonon2, Luisa Sambati1, Roberto Gallassi5, Rocco Liguori1, Raffaele Lodi2, Pietro Cortelli6. 1. IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. 2. Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Functional MR Unit, Policlinico S. Orsola-Malpighi, Italy. 3. Neurology outpatient Clinic, Department of Primary Care, Local Health Authority of Modena, Modena, Italy. 4. Unit of Nuclear Medicine, Maggiore Hospital of Bologna, Italy. 5. IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy. 6. 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.
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.
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 ADLDpatients 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 ADLDpatients 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.
Authors: Laura A Adang; Omar Sherbini; Laura Ball; Miriam Bloom; Anil Darbari; Hernan Amartino; Donna DiVito; Florian Eichler; Maria Escolar; Sarah H Evans; Ali Fatemi; Jamie Fraser; Leslie Hollowell; Nicole Jaffe; Christopher Joseph; Mary Karpinski; Stephanie Keller; Ryan Maddock; Edna Mancilla; Bruce McClary; Jana Mertz; Kiley Morgart; Thomas Langan; Richard Leventer; Sumit Parikh; Amy Pizzino; Erin Prange; Deborah L Renaud; William Rizzo; Jay Shapiro; Dean Suhr; Teryn Suhr; Davide Tonduti; Jacque Waggoner; Amy Waldman; Nicole I Wolf; Ayelet Zerem; Joshua L Bonkowsky; Genevieve Bernard; Keith van Haren; Adeline Vanderver Journal: Mol Genet Metab Date: 2017-08-20 Impact factor: 4.797
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