L A N G U A G E
approximately 50% of participants.16 We hypothesize that the response to PAS25 is, as in healthy people, highly variable in patients with dystonia. Previous studies on healthy participants have circumvented the variability of PAS by preselecting individuals who have a facilitatory response.14 When we followed the same logic and separated the patients into “responders” who showed facilitation after PAS25 and “nonresponders” or inhibitors, we found that cDC reduced facilitation in “responders,” as described previously in healthy individuals. Indeed, there was a weak tendency for cDC to reduce the amount of suppression in “inhibitors” to PAS25, suggesting that cDC might stabilize the response to PAS25. Clinically we did not see any behaviorally relevant improvement in measures of WD severity. Possibly the WD scores we employed were insensitive to clinical changes; however, subjective change was also negative, and thus we do not think we have missed subtle changes in writing kinematics. In addition, the negative electrophysiological data, which motivated our study design, are also against this. Will the exciting work in animal models of dystonia translate into new therapeutic avenues in humans with dystonia? In rodent models, modulating cerebellar function (i.e., cerebellectomy, functional block of output) is sufficient to abolish dystonia. In humans, noninvasive stimulation techniques have been unable to achieve this. Clearly, cDC and TBS paradigms are by necessity weaker modulators. Furthermore, any study employing a single session of stimulation is ambitious, because one is attempting to undo dystonic processes within the brain, which have presumably been strongly consolidated through many years of symptoms. Repeated sessions of stimulation (as used in the treatment of depression,17), phasic cDC, or more invasive cerebellar stimulation sites are just a few of the potential tools that could be employed in future work. Our view is that cerebellar stimulation with the aim of modulating plasticity responses of the motor cortex in focal hand dystonia is not a useful avenue of research, because not all patients have increased plasticity. However, further characterization of pathophysiological changes in dystonia and characterization of cerebellar dysfunction in humans may well yield the development of new therapeutic options using cerebellar modulation, via different underlying mechanisms. Based on the results of this study, cerebellar stimulation may have a role in regulating the responsiveness of the motor cortex to plasticity-inducing protocols. Aside from dystonia, other important conditions such as brain recovery after stroke would greatly benefit from a noninvasive brain stimulation method that regulates plasticity response. In other conditions, if exaggerated plasticity is more consistently seen, a therapeutic effect may be possible, especially if stimulation is repeated and given alongside targeted physical rehabilitation.
I M P A I R M E N T
I N
S C A 6
Acknowledgment: We thank the patients for their participation in this study.
References 1.
Neychev VK, Gross RE, Lehericy S, Hess EJ, Jinnah HA. The functional neuroanatomy of dystonia. Neurobiol Dis 2011;42:185-201.
2.
Bostan AC, Strick PL. The cerebellum and basal ganglia are interconnected. Neuropsychol Rev 2010;20:261-270.
3.
Bostan AC, Dum RP, Strick PL. The basal ganglia communicate with the cerebellum. Proc Natl Acad Sci U S A 2010;107:8452-8456.
4.
Campbell DB, North JB, Hess EJ. Tottering mouse motor dysfunction is abolished on the Purkinje cell degeneration (pcd) mutant background. Exp Neurol 1999;160:268-278.
5.
LeDoux MS, Lorden JF, Ervin JM. Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat. Exp Neurol 1993;120:302-310.
6.
Fan X, Hughes KE, Jinnah HA, Hess EJ. Selective and sustained alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation in cerebellum induces dystonia in mice. J Pharmacol Exp Ther 2012;340:733-741.
7.
Sadnicka A, Hoffland BS, Bhatia KP, van de Warrenburg BP, Edwards MJ. The cerebellum in dystonia: Help or hindrance? Clin Neurophysiol 2012;123:65-70.
8.
Brighina F, Romano M, Giglia G, Saia V, Puma A, Giglia F, Fierro B. Effects of cerebellar TMS on motor cortex of patients with focal dystonia: A preliminary report. Exp Brain Res 2009;192:651-656.
9.
Quartarone A, Pisani A. Abnormal plasticity in dystonia: Disruption of synaptic homeostasis. Neurobiol Dis 2011;42:162-170.
10.
Hamada M, Strigaro G, Murase N, Sadnicka A, Galea JM, Edwards MJ, Rothwell JC. Cerebellar modulation of human associative plasticity. J Physiol 2012;590:2365-2374.
11.
Popa T, Velayudhan B, Hubsch C, et al. Cerebellar processing of sensory inputs primes motor cortex plasticity. Cereb Cortex 2013;23:305-314.
12.
Cirillo J, Lavender AP, Ridding MC, Semmler JG. Motor cortex plasticity induced by paired associative stimulation is enhanced in physically active individuals. J Physiol 2009;587:5831-5842.
13.
Wissel J, Kabus C, Wenzel R, et al. Botulinum toxin in writer’s cramp: objective response evaluation in 31 patients. J Neurol Neurosurg Psychiatry 1996;61:172-175.
14.
Korchounov A, Ziemann U. Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex: a pharmaco-TMS study. Neuropsychopharmacology 2011;36:1894-1902.
15.
Hubsch H, Roze E, Popa T, et al. Defective cerebellar control of cortical plasticity in writer’s cramp. Brain 2013;136:13.
16.
Muller-Dahlhaus JF, Orekhov Y, Liu Y, Ziemann U. Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation. Exp Brain Res 2008;187:467-475.
17.
George MS, Taylor JJ, Short EB. The expanding evidence base for rTMS treatment of depression. Curr Opin Psychiatry 2013;26:13-18.
Supporting Data Additional Supporting Information may be found in the online version of this article at the publisher’s web-site.
Language Impairment in Cerebellar Ataxia Judith van Gaalen, MD,1* Bert J.M. de Swart, PhD,2 Judith Oostveen,2 Simone Knuijt, MA,2 Bart P.C. van de Warrenburg, MD, PhD1 and Berry (H.) P.H Kremer, MD, PhD3 Departments of 1Neurology and 2Rehabilitation, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen
Movement Disorders, Vol. 29, No. 10, 2014
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V A N
G A A L E N
E T
A L
Medical Center, Nijmegen, The Netherlands 3Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands
ABSTRACT Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients with standardized linquistic tests and correlated this with the severity of ataxia, as quantified by the Scale of Assessment and Rating of Ataxia. Results: Individual patients show mild-to-moderate linguistic impairment. Linguistic abnormalities were most distinct on the writing and comprehension subtests. A strong correlation between severity of ataxia and linguistic performance was consistently found. Conclusions: This study confirms the occurrence of linguistic impairments in patients with cerebellar degenerative diseases, such as SCA6. The relation between linguistic abnormalities and severity of ataxia provides further evidence for a role of the cerebellum C 2014 International Parkinson in linguistic processing. V and Movement Disorder Society Key Words: cerebellar ataxia; aphasia; language impairment
The cerebellum has an important role in motor function.1 In the past few decades, studies have suggested an additional role for the cerebellum in cognition, including linguistic processing.2 In some of these studies, linguistic impairment was classified as aphasia.3-5 Data from PET studies also consistently illustrate involvement of the cerebellum in language processing.6-8 However, dysarthria may confound performance on linguistic tasks. We hypothesized that if the cerebellum plays a role in linguistic processing, language comprehension should also be affected, and a correlation between
------------------------------------------------------------
*Correspondence to: Dr. J. van Gaalen, Department of Neurology, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; [email protected] Relevant conflicts of interest/financial disclosures: B.v.d.W. is supported by grants from the Netherlands Brain Foundation, the Prinses Beatrix Fonds, the Royal Dutch Society for Physical Therapy, the Radboud University Nijmegen Medical Center, the Gossweiler Foundation, and Biobanking and Biomolecular Research Infrastructure (BBMRI-NL). J.v.G. is supported by the Gossweiler Foundation. Full financial disclosures and author roles may be found in the online version of this article. Received: 10 June 2013; Revised: 8 January 2014; Accepted: 27 January 2014 Published online 6 March 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25854
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the actual performance of various language tests and the severity of cerebellar ataxia should be detectable. We studied patients with spinocerebellar ataxia type 6 (SCA6), which is associated with a more or less “pure” cerebellar ataxia.9 We applied standardized linguistic tests to assess the whole spectrum of speech and language production and comprehension.
Patients and Methods Patients Participants with SCA6 and clinical symptoms of ataxia were included. Exclusion criteria were a medical history of stroke, malignancy of the central nervous system, and significant visual impairment. Available MRI or CT scans were reviewed. Written informed consent was obtained from all patients.
Experimental Procedures To quantify the severity of ataxia, the Scale for Assessment and Rating of Ataxia (SARA) was administered to all patients. Total SARA scores range from 0 (no ataxia) to 40 (most severe ataxia).10 General cognitive functions were assessed with the Mini–Mental State Examination (MMSE). Two experienced speech therapists (B.J.M.d.S. and S.K.) scored severity of dysarthria on the Nijmegen Dysarthria Scale (NDS).11 Linguistic tests administered to assess the various language functions included the Aachen Aphasia Test (AAT),12 the Boston Naming Test (BNT),13 the Semantic Verbal Association Test (SVeAT),14 and the Semantic Visual Association Test (SViAT).14 (see the Supporting Information). All tests were administered in their validated Dutch versions, and results of the various language tests were compared to normative data (age and education matched) that are available for all of these. Established normative data were used, rather than an adhoc control sample of subjects, in order to strictly define the limits of what should be considered normal and circumvent the issue of which of many potential variables to match for. This approach has been used in previous comparable studies.16,19,20 A score outside the range of the normative data is indicative of language impairment on the specific task.
Statistical Analysis First, the performance of the patient group was compared to the normative data. Results of the AAT are reflected in t values. Pearson’s correlation coefficients were calculated to assess the correlation between the SARA score and the scores on the linguistic tests. To study the contribution of age, separate from ataxia severity, to the results of the linguistic tests, a step-wise multiple regression analysis was performed in which age and then SARA score were added.
L A N G U A G E
Results A total of 29 patients (with a mean SARA score of 15.8) with SCA6 were enrolled into this study. Mean time from disease onset to linguistic testing was 8.9 years (Supporting Table 1). No focal neurological deficits, such as hemiparesis, were present. Mean MMSE score was 28.2 6 2.0. Previously obtained neuroimaging scans were available for 21 patients. In 16 patients, varying degrees of cerebellar atrophy was found; no relevant supratentorial lesions were found. On the NDS, 5 patients (17%) showed no signs of dysarthria, 7 (24%) had severe dysarthria, and the others had mild-to-moderate dysarthria. The results of all linguistic tests are shown in Table 1 and can be summarized as follows.
AAT All patients performed within the range of normative data on the AAT. Some individual patients, however, did show mild impairment (scores below cutoff for normal range), with a distribution of the scores suggestive of more impairment with more severe ataxia (Fig. 1).
BNT When the Dutch scoring system was applied, three (10%) patients had a score below the first percentile, indicating a severe naming defect.
SVeAT and SViAT On the verbal association test, 14 (48%) patients had scores at or below the 25th percentile, of whom 5 (17%) had scores at or below the 5th percentile. On the visual association test, no significant impairment could be established. Pearson’s correlation analysis showed a significant negative correlation between the SARA scores and the score on the AAT, BNT, and SVeAT and SViAT. Those with more-severe ataxia performed worse on these language tests. When the dysarthria item was left out of the SARA score (because this, in itself, correlates with performance on some of the verbal language production tests), significant negative correlations remained for all linguistic tests. These results show that, with progression of cerebellar ataxia, linguistic impairment becomes more evident (Supporting Table 2). A significant correlation between SARA score and age, as well as disease duration, was found (r 5 0.684, P < 0.01 and r 5 0.710, P < 0.01, respectively). Because age could be a possible confounder, the variance inflation factor (VIF), was calculated. This showed minor collinearity (VIF 5 1.878; tolerance 5 0.532) between
I M P A I R M E N T
I N
S C A 6
TABLE 1. Results of MMSE and the linguistic tests Function and Test Cognitve function a
MMSE (N 5 30) Dysarthria Functional level (N 5 5) Activity level (N 5 5) Linguistic function AAT Spontaneous speech (N 5 30) Communicative behavior (N 5 5) Articulation and prosody (N 5 5) Automized language (N 5 5) Semantic structure (N 5 5) Phonological structure (N 5 5) Syntactical structure (N 5 5) Token Test (range, 50-0) Repetition (N 5 150) Writing (N 5 90) Naming (N 5 120) Comprehension (N 5 120) Auditory comprehension (N 5 60) Reading comprehension (N 5 60) BNT English scoring system (N 5 60) Dutch scoring system(score
approximately 50% of participants.16 We hypothesize that the response to PAS25 is, as in healthy people, highly variable in patients with dystonia. Previous studies on healthy participants have circumvented the variability of PAS by preselecting individuals who have a facilitatory response.14 When we followed the same logic and separated the patients into “responders” who showed facilitation after PAS25 and “nonresponders” or inhibitors, we found that cDC reduced facilitation in “responders,” as described previously in healthy individuals. Indeed, there was a weak tendency for cDC to reduce the amount of suppression in “inhibitors” to PAS25, suggesting that cDC might stabilize the response to PAS25. Clinically we did not see any behaviorally relevant improvement in measures of WD severity. Possibly the WD scores we employed were insensitive to clinical changes; however, subjective change was also negative, and thus we do not think we have missed subtle changes in writing kinematics. In addition, the negative electrophysiological data, which motivated our study design, are also against this. Will the exciting work in animal models of dystonia translate into new therapeutic avenues in humans with dystonia? In rodent models, modulating cerebellar function (i.e., cerebellectomy, functional block of output) is sufficient to abolish dystonia. In humans, noninvasive stimulation techniques have been unable to achieve this. Clearly, cDC and TBS paradigms are by necessity weaker modulators. Furthermore, any study employing a single session of stimulation is ambitious, because one is attempting to undo dystonic processes within the brain, which have presumably been strongly consolidated through many years of symptoms. Repeated sessions of stimulation (as used in the treatment of depression,17), phasic cDC, or more invasive cerebellar stimulation sites are just a few of the potential tools that could be employed in future work. Our view is that cerebellar stimulation with the aim of modulating plasticity responses of the motor cortex in focal hand dystonia is not a useful avenue of research, because not all patients have increased plasticity. However, further characterization of pathophysiological changes in dystonia and characterization of cerebellar dysfunction in humans may well yield the development of new therapeutic options using cerebellar modulation, via different underlying mechanisms. Based on the results of this study, cerebellar stimulation may have a role in regulating the responsiveness of the motor cortex to plasticity-inducing protocols. Aside from dystonia, other important conditions such as brain recovery after stroke would greatly benefit from a noninvasive brain stimulation method that regulates plasticity response. In other conditions, if exaggerated plasticity is more consistently seen, a therapeutic effect may be possible, especially if stimulation is repeated and given alongside targeted physical rehabilitation.
I M P A I R M E N T
I N
S C A 6
Acknowledgment: We thank the patients for their participation in this study.
References 1.
Neychev VK, Gross RE, Lehericy S, Hess EJ, Jinnah HA. The functional neuroanatomy of dystonia. Neurobiol Dis 2011;42:185-201.
2.
Bostan AC, Strick PL. The cerebellum and basal ganglia are interconnected. Neuropsychol Rev 2010;20:261-270.
3.
Bostan AC, Dum RP, Strick PL. The basal ganglia communicate with the cerebellum. Proc Natl Acad Sci U S A 2010;107:8452-8456.
4.
Campbell DB, North JB, Hess EJ. Tottering mouse motor dysfunction is abolished on the Purkinje cell degeneration (pcd) mutant background. Exp Neurol 1999;160:268-278.
5.
LeDoux MS, Lorden JF, Ervin JM. Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat. Exp Neurol 1993;120:302-310.
6.
Fan X, Hughes KE, Jinnah HA, Hess EJ. Selective and sustained alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation in cerebellum induces dystonia in mice. J Pharmacol Exp Ther 2012;340:733-741.
7.
Sadnicka A, Hoffland BS, Bhatia KP, van de Warrenburg BP, Edwards MJ. The cerebellum in dystonia: Help or hindrance? Clin Neurophysiol 2012;123:65-70.
8.
Brighina F, Romano M, Giglia G, Saia V, Puma A, Giglia F, Fierro B. Effects of cerebellar TMS on motor cortex of patients with focal dystonia: A preliminary report. Exp Brain Res 2009;192:651-656.
9.
Quartarone A, Pisani A. Abnormal plasticity in dystonia: Disruption of synaptic homeostasis. Neurobiol Dis 2011;42:162-170.
10.
Hamada M, Strigaro G, Murase N, Sadnicka A, Galea JM, Edwards MJ, Rothwell JC. Cerebellar modulation of human associative plasticity. J Physiol 2012;590:2365-2374.
11.
Popa T, Velayudhan B, Hubsch C, et al. Cerebellar processing of sensory inputs primes motor cortex plasticity. Cereb Cortex 2013;23:305-314.
12.
Cirillo J, Lavender AP, Ridding MC, Semmler JG. Motor cortex plasticity induced by paired associative stimulation is enhanced in physically active individuals. J Physiol 2009;587:5831-5842.
13.
Wissel J, Kabus C, Wenzel R, et al. Botulinum toxin in writer’s cramp: objective response evaluation in 31 patients. J Neurol Neurosurg Psychiatry 1996;61:172-175.
14.
Korchounov A, Ziemann U. Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex: a pharmaco-TMS study. Neuropsychopharmacology 2011;36:1894-1902.
15.
Hubsch H, Roze E, Popa T, et al. Defective cerebellar control of cortical plasticity in writer’s cramp. Brain 2013;136:13.
16.
Muller-Dahlhaus JF, Orekhov Y, Liu Y, Ziemann U. Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation. Exp Brain Res 2008;187:467-475.
17.
George MS, Taylor JJ, Short EB. The expanding evidence base for rTMS treatment of depression. Curr Opin Psychiatry 2013;26:13-18.
Supporting Data Additional Supporting Information may be found in the online version of this article at the publisher’s web-site.
Language Impairment in Cerebellar Ataxia Judith van Gaalen, MD,1* Bert J.M. de Swart, PhD,2 Judith Oostveen,2 Simone Knuijt, MA,2 Bart P.C. van de Warrenburg, MD, PhD1 and Berry (H.) P.H Kremer, MD, PhD3 Departments of 1Neurology and 2Rehabilitation, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen
Movement Disorders, Vol. 29, No. 10, 2014
1307
V A N
G A A L E N
E T
A L
Medical Center, Nijmegen, The Netherlands 3Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands
ABSTRACT Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients with standardized linquistic tests and correlated this with the severity of ataxia, as quantified by the Scale of Assessment and Rating of Ataxia. Results: Individual patients show mild-to-moderate linguistic impairment. Linguistic abnormalities were most distinct on the writing and comprehension subtests. A strong correlation between severity of ataxia and linguistic performance was consistently found. Conclusions: This study confirms the occurrence of linguistic impairments in patients with cerebellar degenerative diseases, such as SCA6. The relation between linguistic abnormalities and severity of ataxia provides further evidence for a role of the cerebellum C 2014 International Parkinson in linguistic processing. V and Movement Disorder Society Key Words: cerebellar ataxia; aphasia; language impairment
The cerebellum has an important role in motor function.1 In the past few decades, studies have suggested an additional role for the cerebellum in cognition, including linguistic processing.2 In some of these studies, linguistic impairment was classified as aphasia.3-5 Data from PET studies also consistently illustrate involvement of the cerebellum in language processing.6-8 However, dysarthria may confound performance on linguistic tasks. We hypothesized that if the cerebellum plays a role in linguistic processing, language comprehension should also be affected, and a correlation between
------------------------------------------------------------
*Correspondence to: Dr. J. van Gaalen, Department of Neurology, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; [email protected] Relevant conflicts of interest/financial disclosures: B.v.d.W. is supported by grants from the Netherlands Brain Foundation, the Prinses Beatrix Fonds, the Royal Dutch Society for Physical Therapy, the Radboud University Nijmegen Medical Center, the Gossweiler Foundation, and Biobanking and Biomolecular Research Infrastructure (BBMRI-NL). J.v.G. is supported by the Gossweiler Foundation. Full financial disclosures and author roles may be found in the online version of this article. Received: 10 June 2013; Revised: 8 January 2014; Accepted: 27 January 2014 Published online 6 March 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25854
1308
Movement Disorders, Vol. 29, No. 10, 2014
the actual performance of various language tests and the severity of cerebellar ataxia should be detectable. We studied patients with spinocerebellar ataxia type 6 (SCA6), which is associated with a more or less “pure” cerebellar ataxia.9 We applied standardized linguistic tests to assess the whole spectrum of speech and language production and comprehension.
Patients and Methods Patients Participants with SCA6 and clinical symptoms of ataxia were included. Exclusion criteria were a medical history of stroke, malignancy of the central nervous system, and significant visual impairment. Available MRI or CT scans were reviewed. Written informed consent was obtained from all patients.
Experimental Procedures To quantify the severity of ataxia, the Scale for Assessment and Rating of Ataxia (SARA) was administered to all patients. Total SARA scores range from 0 (no ataxia) to 40 (most severe ataxia).10 General cognitive functions were assessed with the Mini–Mental State Examination (MMSE). Two experienced speech therapists (B.J.M.d.S. and S.K.) scored severity of dysarthria on the Nijmegen Dysarthria Scale (NDS).11 Linguistic tests administered to assess the various language functions included the Aachen Aphasia Test (AAT),12 the Boston Naming Test (BNT),13 the Semantic Verbal Association Test (SVeAT),14 and the Semantic Visual Association Test (SViAT).14 (see the Supporting Information). All tests were administered in their validated Dutch versions, and results of the various language tests were compared to normative data (age and education matched) that are available for all of these. Established normative data were used, rather than an adhoc control sample of subjects, in order to strictly define the limits of what should be considered normal and circumvent the issue of which of many potential variables to match for. This approach has been used in previous comparable studies.16,19,20 A score outside the range of the normative data is indicative of language impairment on the specific task.
Statistical Analysis First, the performance of the patient group was compared to the normative data. Results of the AAT are reflected in t values. Pearson’s correlation coefficients were calculated to assess the correlation between the SARA score and the scores on the linguistic tests. To study the contribution of age, separate from ataxia severity, to the results of the linguistic tests, a step-wise multiple regression analysis was performed in which age and then SARA score were added.
L A N G U A G E
Results A total of 29 patients (with a mean SARA score of 15.8) with SCA6 were enrolled into this study. Mean time from disease onset to linguistic testing was 8.9 years (Supporting Table 1). No focal neurological deficits, such as hemiparesis, were present. Mean MMSE score was 28.2 6 2.0. Previously obtained neuroimaging scans were available for 21 patients. In 16 patients, varying degrees of cerebellar atrophy was found; no relevant supratentorial lesions were found. On the NDS, 5 patients (17%) showed no signs of dysarthria, 7 (24%) had severe dysarthria, and the others had mild-to-moderate dysarthria. The results of all linguistic tests are shown in Table 1 and can be summarized as follows.
AAT All patients performed within the range of normative data on the AAT. Some individual patients, however, did show mild impairment (scores below cutoff for normal range), with a distribution of the scores suggestive of more impairment with more severe ataxia (Fig. 1).
BNT When the Dutch scoring system was applied, three (10%) patients had a score below the first percentile, indicating a severe naming defect.
SVeAT and SViAT On the verbal association test, 14 (48%) patients had scores at or below the 25th percentile, of whom 5 (17%) had scores at or below the 5th percentile. On the visual association test, no significant impairment could be established. Pearson’s correlation analysis showed a significant negative correlation between the SARA scores and the score on the AAT, BNT, and SVeAT and SViAT. Those with more-severe ataxia performed worse on these language tests. When the dysarthria item was left out of the SARA score (because this, in itself, correlates with performance on some of the verbal language production tests), significant negative correlations remained for all linguistic tests. These results show that, with progression of cerebellar ataxia, linguistic impairment becomes more evident (Supporting Table 2). A significant correlation between SARA score and age, as well as disease duration, was found (r 5 0.684, P < 0.01 and r 5 0.710, P < 0.01, respectively). Because age could be a possible confounder, the variance inflation factor (VIF), was calculated. This showed minor collinearity (VIF 5 1.878; tolerance 5 0.532) between
I M P A I R M E N T
I N
S C A 6
TABLE 1. Results of MMSE and the linguistic tests Function and Test Cognitve function a
MMSE (N 5 30) Dysarthria Functional level (N 5 5) Activity level (N 5 5) Linguistic function AAT Spontaneous speech (N 5 30) Communicative behavior (N 5 5) Articulation and prosody (N 5 5) Automized language (N 5 5) Semantic structure (N 5 5) Phonological structure (N 5 5) Syntactical structure (N 5 5) Token Test (range, 50-0) Repetition (N 5 150) Writing (N 5 90) Naming (N 5 120) Comprehension (N 5 120) Auditory comprehension (N 5 60) Reading comprehension (N 5 60) BNT English scoring system (N 5 60) Dutch scoring system(score
