Neuropsychological deficits of patients with chronic or acute cerebellar lesions
Introduction
The role of the cerebellum in cognitive processes was first proposed following evidence of specific neuropsychological deficits in two epileptic patients with phenytoin-induced ataxia [1]. These deficits were explained by cerebellar modulation of higher brain regions, including frontal and parietal association cortex. Afterwards, on the basis of neuroimagery findings, cerebello–prefrontal interactions were hypothesized as the physiological basis of various cognitive and language skills in normal subjects [2]; the importance of the dentate nucleus was particularly emphasized as a result of its evolutionary expansion [3]. The frontal-like and the parietal-like symptoms seen in patients with acute or chronic cerebellar lesions [4], [5] have been designated the cerebellar cognitive affective syndrome [6], dysmetria of thought [6], [7] and ataxic hindbrain thinking [8]. The latter is defined as an inability to render automatic those mental subroutines implicated in problem solving.
Section snippets
Patient selection
Among the many variants of inherited ataxia, olivopontocerebellar atrophy (OPCA), Friedreich’s ataxia and cerebellar cortical atrophy (CCA) represent the most common diseases and the most widely studied. OPCA is caused by CAG (cytosine–adenine–guanine) repeat expansions of SCA-1 or SCA-2 genes, and CCA by CAG repeat expansions of the SC6 gene [9], [10]. The number of nucleotide repeat expansions has been shown to be correlated with disease onset and the severity of clinical signs. GAA repeat
Visuospatial organization
Appropriate testing methods must be devised during the neuropsychological evaluation of patients with severe cerebellar disease because of their upper limb ataxia. Visuospatial organization can be evaluated by means of tests requiring no movement on the part of patients, such as the Raven Standard Progressive Matrices (or its simpler version, the Raven Colored Progressive Matrices) and the mental folding test. Block design and object assembly subtests of Wechsler’s Adult Intelligence Scale
Short-term or working memory
Short-term or working memory has been examined by means of the digit span subtest of the WAIS or its revised version (WAIS-R). This test is subdivided into forward span, requiring passive repetition of a string of digits (short-term memory) and backward span, requiring repetition and online manipulation of digits (working memory). No digit span deficit was observed in patients with OPCA [14], [20], Friedreich’s ataxia [4] or either cerebellar or brainstem infarcts [27]. Moreover, no deleterious
Long-term memory
Patients with cerebellar atrophy have been examined in various declarative memory tasks. OPCA patients were impaired in the Wechsler Memory Scale story recall [20], [32]. Moreover, immediate recall of the Benton figures was impaired in a group with combined cerebellar and brainstem damage [13].
Free recall in Hasher’s frequency monitoring task and in paired-associate learning was impaired in a group with either CCA or OPCA, but not in the standard cued recall version of paired-associate
Associative learning
The role of the cerebellum in associative learning has been examined by means of classical conditioning of the eyeblink response and in conceptual stimulus-response tasks such as paired associates. Eyeblink conditioning is a form of procedural learning and paired-associate learning a form of declarative learning. In confirmation of studies using cerebellar-lesioned animals, deficits in the acquisition of eyeblink conditioning were found in patients with cerebellar damage [34], [35]. That result
Selective attention
Deficits of selective attention but not of memory were found in SCA3/Machado–Joseph disease [41], characterized by combined damage to the cerebellum and the substantia nigra [9], [42]. However, no deficit on selective attention tasks requiring either stimulus detection or shifts in spatial attention was seen in two groups of patients with heredodegenerative ataxia [24]. On the other hand, deficits of rapid intermodality shifts in attention [43] were reported in a group of patients with
Frontal lobe-sensitive behaviors
The above-cited poor performances in the Raven Standard Progressive Matrices by patients with OPCA or Friedreich’s ataxia may be ascribed to difficulties in planning and organizing a series of logical steps [4]. Additional evidence for a role of the cerebellum in frontal-lobe sensitive behaviors [33], [46] includes impaired Luria hand sequences, the Trail Making B-A differential, arithmetic problem solving, proverb interpretation and verbal reasoning on nonsense sentences observed in patients
Influence of the brainstem
The influence of the brainstem in cerebellar-related disorders has been discussed in a syndrome consisting of transitory mutism and subsequent dysarthia, seen in children [51] and adults [52], [53] after removal of midline cerebellar tumors. The absence of cranial nerve dysfunction is an indication that the mutism is directly caused by the cerebellar damage. On the other hand, since hydrocephalus and postsurgical edema in the pontine tegmentum are precipitating factors, it has been suggested
Subcortical dementia
It has been proposed [21] that the neuropsychological profile of patients with cerebellar damage be classified as a mild form of subcortical dementia. The hallmarks of subcortical dementia are the following.
Conclusion
The most prevalent neuropsychologic deficits after cerebellar lesions include visuospatial processing, organizing a logical sequence of events and certain forms of associative learning. The significant correlation between RT and visuospatial performance in patients with OPCA emphasizes the role of slowed information processing speed in neuropsychologic functions. Future studies must determine in greater detail the contribution of cerebello–cerebral interactions in these neuropsychologic
Acknowledgements
This work was supported by a grant from the Canadian Association of Friedreich’s ataxia. This article is dedicated to the memory of Dr. M.I. Botez.
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