Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder caused by mutations in the SACS gene (13q12) encoding the protein sacsin. It is characterized by early-onset cerebellar ataxia, lower limb spasticity, sensorimotor axonal polyneuropathy, and atrophy of the superior cerebellar vermis. Cerebellar disorders in general may be accompanied by the cerebellar cognitive affective syndrome (CCAS) which presents with disturbances of executive functioning, spatial cognition, linguistic capacities, and affect. Sampling and Methods: Two middle-aged brothers with ARSACS, one of whom was referred for behavioral disinhibition, are described. A detailed neuropsychiatric and neuropsychological assessment was performed. Results: Apart from motor symptoms, motivational deficits along with cognitive and behavioral dysfunctions were present; these were much more pronounced in the older sib. Conclusions: These observations add to the literature which suggests that the cerebellum, apart from its significance for motor behavior, plays a functional role in human cognition and affect. The nonmotor symptoms of ARSACS are discussed in terms of the CCAS.

Keywords:
Apathy, Autosomal recessive spastic ataxia of Charlevoix-Saguenay, Cerebellar cognitive affective syndrome
1.
Bouchard JP, Barbeau A, Bouchard R, Bouchard RW: Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci 1978;5:61–69.
2.
Bouchard RW, Bouchard JP, Bouchard R, Barbeau A: Electroencephalographic findings in Friedreich’s ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Can J Neurol Sci 1979;6:191–194.
3.
Schmahmann JD, Sherman JC: The cerebellar cognitive affective syndrome. Brain 1998;121:561–579.
4.
Schmahmann JD: Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2004;16:367–378.
5.
Bouchard JP, Richter A, Mathieu J, Brunet D, Hudson TJ, Morgan K, Melançon SB: Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Neuromuscul Disord 1998;8:474–479.
6.
Martin MH, Bouchard JP, Sylvain M, St-Onge O, Truchon S: Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a report on MR imaging in 5 patients. AJNR Am J Neuroradiol 2007;28:1606–1608.
7.
Engert JC, Bérubé P, Mercier J, Doré C, Lepage P, Ge B, Bouchard JP, Mathieu J, Melançon SB, Schalling M, Lander ES, Morgan K, Hudson T, Richter A: ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet 2000;24:120–125.
8.
Van de Warrenburg BPC, Sinke RJ, Kremer B: Recent advances in hereditary spinocerebellar ataxias. J Neuropathol Exp Neurol 2005;64:171–180.
9.
Palau F, Espinós C: Autosomal recessive cerebellar ataxias. Orphanet J Rare Dis 2006;1:47.
10.
Fogel BI, Perlman S: Clinical features and molecular genetics of autosomal recessive cerebellar ataxias. Lancet Neurol 2007;6:245–257.
11.
Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, Van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B; ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia. Neurogenetics 2008;9:207–214.
12.
Marin RS: Differential diagnosis and classification of apathy. Am J Psychiatry 1990;147:22–30.
13.
Marin RS: Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 1991;3:243–254.
14.
Tavano A, Grasso R, Gagliardi C, Triulzi F, Brezolin N, Fabbro F, Borgatti R: Disorders of cognitive and affective development in cerebellar malformations. Brain 2007;130:2646–2660.
15.
Schmahmann JD, Weilburg JB, Sherman JC: The neuropsychiatry of the cerebellum: insights from the clinic. Cerebellum 2007;6:254–267.
16.
Hoppenbrouwers SS, Schutter DJ, Fitzgerald PB, Chen R, Daskalakis ZJ: The role of the cerebellum in the pathophysiology and treatment of neuropsychiatric disorders: a review. Brain Res Rev 2008;59:185–220.
17.
Wolf U, Rapoport MJ, Schweiter TA: Evaluation of the affective component of cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2009;21:245–253.
18.
Bürk K: Cognition in hereditary ataxia. Cerebellum 2007;6:280–286.
19.
Kawai Y, Suenega M, Watanabe H, Sobue G: Cogitive impairment in spinocerebellar degeneration. Eur Neurol 2009;61:257–268.
20.
Kaufman S, Kaufman NL, Mulder JL, Dekker R, Dekker PH: Dutch Adaptation of the Kaufman Adolescent and Adult Intelligence Test. Amsterdam, Pearson, 2004.
21.
Nelson HE: National Adult Reading Test (NART): Test Manual. Windsor, NFER-Nelson, 1982.
22.
Schmitz-Hübsch T, du Montcel T, Baliko L, Berciano J, Boesch S, Depondt C, et al: Scale for the assessment and rating of ataxia. Neurology 2006;66:1717–1720.
23.
Janssen GT, De Mey HR, Egger JI: Executive functioning in college students: evaluation of the Dutch Executive Function Index (EF-NL). Int J Neurosci 2009;119:792–805.
24.
Krabbendam L, Kalff AC: BADS: Behavioural Assessment of the Dysexecutive Syndrome. Bury St. Edmonds, Thames Valley Test Company, 1997.
25.
Wilson BA, Cockburn J, Baddeley A: The Rivermead Behavioural Memory Test. Bury St. Edmonds, Thames Valley Test Company, 1985.
26.
Bagby RM, Taylor GJ, Parker JD: The twenty-item Toronto Alexithymia Scale-II: convergent, discriminant, and concurrent validity. J Psychosom Res 1994;38:33–40.
27.
Vorst HC, Bermond B: Validity and reliability of the Bermond-Vorst alexithymia questionnaire. J Pers Individ Differ 2001;30:413–434.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.