title: Clinical and neurophysiological profile of four German families with spinocerebellar ataxia type 14.
abstract: Spinocerebellar ataxia type 14 (SCA14) is an autosomal-dominant ataxia caused by point mutations of the Protein Kinase C Gamma gene. In addition to slowly progressive cerebellar ataxia, it is characterised by dystonia and myoclonus. With scant neuropathological data and no detailed neurophysiological examinations little is known on extracerebellar consequences of SCA14 related cerebellar pathology. To this end, we here delineate clinical phenomenology and neurophysiology of four German SCA14 families. Detailed clinical examination including ataxia severity evaluation by means of the Scale for the Assessment and Rating of Ataxia (SARA) was carried out in 9 affected family members (mean age 49.8 years ± 14.4 SD). Motor thresholds (MT), the contralateral silent period (CSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), interhemispheric inhibition (IHI) and short afferent inhibition (SAI) were determined using transcranial magnetic stimulation (TMS). Somatosensory evoked potentials (SEP) of the median nerve, and acoustic and visual evoked potentials (AEP, VEP) were also performed. Most patients reported symptoms since early childhood. There was a positive correlation between age and SARA scores (r = .721, P < 0.05). Patients had cerebellar ataxia, mild dystonia (focal, task-specific or segmental), subtle pyramidal signs and myoclonus. SICI increased with increasing conditioning pulse intensities in healthy controls but not in patients. Other neurophysiological parameters did not differ between groups. SCA14 is a slowly progressive ataxia associated with mild dystonia and myoclonus. Reduced SICI reflects abnormalities of intracortical inhibitory circuits.
authors.affiliation: Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, cganos@gmail.com.
authors.forename: Christos
authors.initials: C
authors.lastname: Ganos
authors.forename: Simone
authors.initials: S
authors.lastname: Zittel
authors.forename: Martina
authors.initials: M
authors.lastname: Minnerop
authors.forename: Odette
authors.initials: O
authors.lastname: Schunke
authors.forename: Christina
authors.initials: C
authors.lastname: Heinbokel
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
authors.forename: Christine
authors.initials: C
authors.lastname: Zühlke
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.forename: Alexander
authors.initials: A
authors.lastname: Münchau
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäumer
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D004421:Dystonia / Q000235:genetics / Q000503:physiopathology; D005072:Evoked Potentials, Auditory; D005073:Evoked Potentials, Somatosensory; D005074:Evoked Potentials, Visual; D005190:Family; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009207:Myoclonus / Q000235:genetics / Q000503:physiopathology; D009460:Neurologic Examination; D011493:Protein Kinase C / Q000235:genetics; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C
references.citation: J Neurol Sci. 2002 Jun 15;198(1-2):87-92
references.pmid: 12039668
references.citation: Am J Hum Genet. 2003 Apr;72(4):839-49
references.pmid: 12644968
references.citation: Funct Neurol. 2004 Jan-Mar;19(1):37-41
references.pmid: 15212115
references.citation: Ann Neurol. 2005 Nov;58(5):720-9
references.pmid: 16193476
references.citation: J Neurol Sci. 2004 Feb 15;217(2):205-10
references.pmid: 14706225
references.citation: Ann Neurol. 1995 Feb;37(2):181-8
references.pmid: 7847860
references.citation: Mov Disord. 2006 Jul;21(7):1025-8
references.pmid: 16547918
references.citation: Clin Neurophysiol. 2008 Jun;119(6):1400-7
references.pmid: 18387338
references.citation: J Physiol. 1993 Nov;471:501-19
references.pmid: 8120818
references.citation: J Neurol Sci. 1999 Oct 15;168(2):107-11
references.pmid: 10526191
references.citation: Lancet Neurol. 2010 Sep;9(9):885-94
references.pmid: 20723845
references.citation: Neurology. 2003 Dec 23;61(12):1760-5
references.pmid: 14694043
references.citation: Neurology. 2006 Jun 13;66(11):1717-20
references.pmid: 16769946
references.citation: Ann Neurol. 2000 Jul;48(1):20-6
references.pmid: 10894212
references.citation: J Neurosci. 1988 Feb;8(2):369-82
references.pmid: 3276831
references.citation: J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):530-4
references.pmid: 9771779
references.citation: Electroencephalogr Clin Neurophysiol. 1996 Aug;101(4):273-80
references.pmid: 8761036
references.citation: J Neurol Neurosurg Psychiatry. 1995 Nov;59(5):493-8
references.pmid: 8530933
references.citation: J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1720-2
references.pmid: 16291902
references.citation: Ann Neurol. 1996 Sep;40(3):367-78
references.pmid: 8797526
references.citation: Brain. 2003 Sep;126(Pt 9):2074-80
references.pmid: 12821514
references.citation: Curr Opin Neurol. 2011 Aug;24(4):339-45
references.pmid: 21734495
references.citation: Brain. 1996 Feb;119 ( Pt 1):309-317
references.pmid: 8624691
references.citation: Ther Adv Neurol Disord. 2011 Jan;4(1):47-62
references.pmid: 21339907
references.citation: Mov Disord. 2008 Apr 15;23(5):761-4
references.pmid: 18265016
references.citation: Mov Disord. 2007 Jan 15;22(2):265-7
references.pmid: 17149711
references.citation: Acta Neurol Scand. 1998 Nov;98(5):318-23
references.pmid: 9858101
references.citation: Adv Neurol. 2004;94:37-44
references.pmid: 14509652
references.citation: Parkinsonism Relat Disord. 2010 May;16(4):288-9
references.pmid: 19913450
references.citation: Hum Genet. 2005 Jun;117(1):88-91
references.pmid: 15841389
references.citation: Brain. 2002 Feb;125(Pt 2):301-9
references.pmid: 11844730
references.citation: Mov Disord. 2008 Feb 15;23(3):378-85
references.pmid: 18074367
references.citation: Electroencephalogr Clin Neurophysiol. 1994 Jun;93(3):225-9
references.pmid: 7515799
references.citation: Clin Neurol Neurosurg. 2009 Feb;111(2):211-5
references.pmid: 18986758
references.citation: Ann Neurol. 2000 Aug;48(2):156-63
references.pmid: 10939565
references.citation: J Neurol Neurosurg Psychiatry. 2010 Jan;81(1):97-100
references.pmid: 20019225
references.citation: Adv Neurol. 1998;78:33-40
references.pmid: 9750901
references.citation: Mov Disord. 2007 May 15;22(7):1024-6
references.pmid: 17343273
references.citation: Brain Stimul. 2008 Jul;1(3):183-91
references.pmid: 20633384
references.citation: Exp Neurol. 2009 Apr;216(2):300-5
references.pmid: 19118553
references.citation: Arch Neurol. 2002 Aug;59(8):1291-5
references.pmid: 12164726
references.citation: Arch Neurol. 2004 Aug;61(8):1242-8
references.pmid: 15313841
references.citation: Mov Disord. 2011 Apr;26(5):792-800
references.pmid: 21370272
references.citation: Brain. 2007 May;130(Pt 5):1183-93
references.pmid: 17242025
references.citation: Neurology. 2005 Apr 12;64(7):1258-60
references.pmid: 15824357