Different cortical excitability profiles in hereditary brain iron and copper accumulation.
Adult
Ceruloplasmin
/ deficiency
Cortical Excitability
/ physiology
Female
Hepatolenticular Degeneration
/ physiopathology
Humans
Iron Metabolism Disorders
/ physiopathology
Male
Middle Aged
Neuroaxonal Dystrophies
/ physiopathology
Neurodegenerative Diseases
/ physiopathology
Parkinsonian Disorders
/ physiopathology
Transcranial Magnetic Stimulation
Young Adult
GABA
Metals
NBIA
Neurodegeneration
TMS
Wilson’s disease
Journal
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
18
05
2019
accepted:
08
11
2019
pubmed:
28
11
2019
medline:
1
12
2020
entrez:
28
11
2019
Statut:
ppublish
Résumé
Neurodegeneration with brain iron accumulation (NBIA) and Wilson's disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload. Three patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF). Patients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI. Hereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.
Sections du résumé
BACKGROUND AND AIM
OBJECTIVE
Neurodegeneration with brain iron accumulation (NBIA) and Wilson's disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload.
METHODS
METHODS
Three patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF).
RESULTS
RESULTS
Patients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI.
CONCLUSION
CONCLUSIONS
Hereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.
Identifiants
pubmed: 31773358
doi: 10.1007/s10072-019-04147-0
pii: 10.1007/s10072-019-04147-0
doi:
Substances chimiques
Ceruloplasmin
EC 1.16.3.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
679-685Références
Neurology. 2008 Apr 29;70(18):1614-9
pubmed: 18443312
J Neural Transm (Vienna). 2015 Nov;122(11):1533-40
pubmed: 26228625
Neurology. 1991 Sep;41(9):1449-56
pubmed: 1891097
Clin Neurophysiol. 2015 Oct;126(10):1847-68
pubmed: 25534482
J Neurol. 2012 May;259(5):833-7
pubmed: 21956377
Funct Neurol. 2004 Jan-Mar;19(1):37-41
pubmed: 15212115
Mov Disord. 2006 Sep;21(9):1350-4
pubmed: 16721731
Int J Alzheimers Dis. 2011;2011:292593
pubmed: 22145081
Parkinsonism Relat Disord. 2012 Jun;18(5):590-4
pubmed: 22104014
Clin Neurophysiol. 2011 Apr;122(4):819-22
pubmed: 21111673
F1000Res. 2016 Mar 17;5:
pubmed: 27006759
Neuroimage. 2017 Sep;158:37-47
pubmed: 28669907
Funct Neurol. 2012 Jul-Sep;27(3):131-45
pubmed: 23402674
Parkinsonism Relat Disord. 2018 Jun;51:36-42
pubmed: 29503155
Neurogenetics. 2011 Feb;12(1):33-9
pubmed: 20853184
FASEB J. 2019 Feb;33(2):2460-2471
pubmed: 30277817
Brain Stimul. 2015 Nov-Dec;8(6):1144-50
pubmed: 26140957
J Neurol. 2014 Apr;261(4):804-8
pubmed: 24570279
Parkinsonism Relat Disord. 2016 Mar;24:15-9
pubmed: 26851839
Mov Disord. 2010 Jun 15;25(8):979-84
pubmed: 20310007
J Neurol Sci. 2015 Jan 15;348(1-2):262-5
pubmed: 25537619
Electroencephalogr Clin Neurophysiol. 1992 Apr;85(2):158-60
pubmed: 1373368
Clin Neurophysiol. 2015 Jun;126(6):1071-1107
pubmed: 25797650
Arch Neurol. 2010 Nov;67(11):1357-63
pubmed: 21060012
J Neurosci. 2013 Aug 14;33(33):13431-5
pubmed: 23946400
J Neurol Sci. 2013 Nov 15;334(1-2):180-2
pubmed: 23988229
Neurosci Lett. 2017 Jul 27;654:107-110
pubmed: 28645789
J Neural Transm (Vienna). 2012 Dec;119(12):1499-506
pubmed: 22711234
Front Hum Neurosci. 2019 Apr 08;13:111
pubmed: 31024277
Environ Toxicol Pharmacol. 2009 May;27(3):314-20
pubmed: 21783959
Brain Res Brain Res Rev. 2002 Feb;38(3):309-27
pubmed: 11890979