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The Cerebellum

, Volume 13, Issue 1, pp 89–96 | Cite as

Clinical and Neurophysiological Profile of Four German Families with Spinocerebellar Ataxia Type 14

  • Christos GanosEmail author
  • Simone Zittel
  • Martina Minnerop
  • Odette Schunke
  • Christina Heinbokel
  • Christian Gerloff
  • Christine Zühlke
  • Peter Bauer
  • Thomas Klockgether
  • Alexander Münchau
  • Tobias Bäumer
Original Paper

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.

Keywords

Spinocerebellar ataxia 14 Transcranial magnetic stimulation Dystonia Intracortical inhibition 

Notes

Financial Disclosures

Christos Ganos

Commercial research support:

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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Christos Ganos
    • 1
    • 2
    • 8
    Email author
  • Simone Zittel
    • 1
    • 2
  • Martina Minnerop
    • 3
    • 4
  • Odette Schunke
    • 1
  • Christina Heinbokel
    • 1
  • Christian Gerloff
    • 1
  • Christine Zühlke
    • 5
  • Peter Bauer
    • 6
  • Thomas Klockgether
    • 4
    • 7
  • Alexander Münchau
    • 2
  • Tobias Bäumer
    • 2
  1. 1.Department of NeurologyUniversity Medical Centre Hamburg-EppendorfHamburgGermany
  2. 2.Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Institute of NeurogeneticsUniversity of LübeckLübeckGermany
  3. 3.Institute of Neuroscience and Medicine (INM-1)Research Centre JuelichJuelichGermany
  4. 4.Department of NeurologyUniversity Hospital of BonnBonnGermany
  5. 5.Institute of Human GeneticsUniversity of LübeckLübeckGermany
  6. 6.Institute of Medical Genetics and Applied GenomicsUniversity of TübingenTübingenGermany
  7. 7.German Center for Neurodegenerative Diseases (DZNE)BonnGermany
  8. 8.Movement Disorders Group, Department of NeurologyUniversity Medical Center Hamburg-EppendorfHamburgGermany

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