Clinical and neurophysiological profile of four German families with spinocerebellar ataxia type 14

Christos Ganos; Simone Zittel; Martina Minnerop; Odette Schunke; Christina Heinbokel; Christian Gerloff; Christine Zühlke; Peter Bauer; Thomas Klockgether; Alexander Münchau; Tobias Bäumer

doi:10.1007/s12311-013-0522-7

Clinical and neurophysiological profile of four German families with spinocerebellar ataxia type 14

Christos Ganos^*, Simone Zittel, Martina Minnerop, Odette Schunke, Christina Heinbokel, Christian Gerloff, Christine Zühlke, Peter Bauer, Thomas Klockgether, Alexander Münchau, Tobias Bäumer

^*Corresponding author for this work

38 Citations (Scopus)

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.

Original language	English
Journal	Cerebellum
Volume	13
Issue number	1
Pages (from-to)	89-96
Number of pages	8
ISSN	1473-4222
DOIs	https://doi.org/10.1007/s12311-013-0522-7
Publication status	Published - 01.01.2014

Funding

Grants by Actelion, Ipsen, Pharm Allergan and Merz Pharmaceuticals Academic research support not attributed in the manuscript: Deutsche Forschungsgemeinschaft (MU1692/2-1). European Science Foundation Simone Zittel Commercial research support: St. Jude Medical, Merz Pharmaceuticals Academic research support not attributed in the manuscript: Wegener Stiftung Martina Minnerop No disclosures Odette Schunke Academic research support not attributed in the manuscript: Deutsche Forschungsgemeinschaft (MU1692/2-1). Christina Heinbokel No disclosures Christian Gerloff Commercial research support: Honoraria for lectures from Boehringer Ingelheim, Glaxo Smith Kline, Sanofi Aventis, ev3 GmbH Academic research support not attributed in the manuscript: DFG (GE844/2-1, GE844/41), SFB (936 Z1, Z2, C1 2011–2015), EU FP7 278276 Christine Zühlke No disclosures Peter Bauer Consulting honoraria from Actelion and Centogene. Honoraria for lectures from Actelion. Research support from the Bundesministerium für Bildung und Forschung (BMBF) and the European Union (EU). Thomas Klockgether Research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF) and the European Union (EU). Editorial board of The Cerebellum. Lecture honorarium from Lundbeck and from Biogen Idec. Royalties for book publications from Thieme, Urban & Schwarzenberg, Kohlhammer, Elsevier, Wissenschaftliche Verlagsgesellschaft Stuttgart and M. Dekker. Alexander Münchau Commercial research support Grants by Pharm Allergan, Ipsen, Merz Pharmaceuticals Honoraria for lectures from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion, GlaxoSmithKline and Desitin Support from non-profit foundations or societies Possehl-Stiftung, Lübeck Dystonia Coalition (USA) Tourette Syndrome Association (Germany) European Huntington Disease Network N.E.MO. Charity supporting the research of paediatric movement disorders Academic research support not attributed in the manuscript Deutsche Forschungsgemeinschaft (MU1692/3-1; SFB 936). European Science Foundation (Euro Veto; CRP Number: 09-ECRP-020) Else Kröner-Fresenius-Stiftung A. Münchau is employed at the University of Lübeck. Tobias Bäumer Honoraria for lectures from Pharm Allergan, Ipsen, Merz Pharmaceuticals No conflicts of interest.

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SDG 10 Reduced Inequalities

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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.",

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AU - Ganos, Christos

AU - Zittel, Simone

AU - Minnerop, Martina

AU - Schunke, Odette

AU - Heinbokel, Christina

AU - Gerloff, Christian

AU - Zühlke, Christine

AU - Bauer, Peter

AU - Klockgether, Thomas

AU - Münchau, Alexander

AU - Bäumer, Tobias

PY - 2014/1/1

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N2 - 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.

AB - 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.

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C2 - 24030789

AN - SCOPUS:84896489548

SN - 1473-4222

VL - 13

SP - 89

EP - 96

JO - Cerebellum

JF - Cerebellum

IS - 1

ER -

Clinical and neurophysiological profile of four German families with spinocerebellar ataxia type 14

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