Thérèse Botez-Marquard

Cognitive Behavior in Heredodegenerative Ataxias

Fifteen patients with Friedreichs ataxia (FA) and 15 others with olivopontocerebellar atrophy (OPCA) were evaluated with a comprehensive neuropsychological battery of tests. They were pair-matched with normal controls for age, sex and education. Depressed patients were excluded from the study as were those with extrapyramidal signs. The following results were obtained: (1) the Raven test, untimed block design performance in OPCA and quantitative analysis of Rey figure drawing revealed a visuospatial deficit suggestive of a mild parietal-like syndrome; signs of mild frontal-like syndrome were also found; (2) cognition was slowed in the FA group; (3) simple visual and auditory reaction times were increased in both patient groups. It appears that the cerebellum may interfere indirectly with cognition through various physiological and neurochemical 2-way cerebellocortical loops. Finally, the cerebellum seems to interfere directly also with basic speed of information processing.

Neuropsychological Functioning in Unilateral Cerebellar Damage

A woman had a left superior cerebellar artery infarct associated with reduced hexamethylpropileneamine oxime uptake on SPECT scan of the basal ganglia and frontoparietal areas of the opposite hemisphere performed poorly in some neuropsychological tests indicating right hemisphere dysfunction. There was a lengthening of reaction and movement times with the hand ipsilateral to the lesion. These deficits were temporary. A unilateral cerebellar lesion can produce neuropsychological deficits, possibly because of hypoperfusion in contralateral frontoparietal regions, but spontaneous neuropsychological remissions may occur.

The Neurobiological Basis of Movement Initiation

Simple reaction time (RT) is defined as the elapsed time between presentation of a single stimulus and onset of movement. In choice RT, there are at least two stimuli, requiring two distinct responses. The neurobiological basis of RT in humans has mostly been evaluated in patients with Parkinsons disease or cerebellar disease. Lesion studies in animals have assessed the different contributions of various subregions of the basal ganglia and the cerebellum. There is a prolongation of simple RT and in some cases of choice RT in Parkinsons disease. Both simple and choice RT are susceptible to modulation by brain dopamine levels. However, such is not invariably the case, attesting to the contribution of non-dopaminergic neurons in the sensori-motor slowing found in Parkinsons disease. An increase in simple RT and in choice RT are found in patients with cerebellar atrophy. The initiation of fast ballistic movements is associated with the dentate efferent system. This system is modulated by dopaminergic and glutamatergic pathways to the striatum.

A severe frontal–parietal lobe syndrome following cerebellar damage*

We report a case study of a frontal and parietal lobe syndrome with memory loss after unilateral left‐sided cerebellar damage caused by a stroke in a patient with right cerebellar unusual developmental agenesis. The syndrome consisted of severe deficits in planning an organized sequence of events, in visuo‐constructive abilities and inappropriate jocularity. These changes are ascribed in part to cerebellar‐pontine lesions with resulting frontal lobe diaschisis as documented by single‐photon emission computed tomography in the absence of morphological damage to the neocortex.

Amantadine Hydrochloride Treatment in Olivopontocerebellar Atrophy: A Long-Term Follow-Up Study

The efficacy of amantadine, a dopamine-releasing agent and antagonist of the N-methyl-D-aspartate glutamate receptor, was evaluated in patients with olivopontocerebellar atrophy. By contrast to an untreated control group whose terminal performance deteriorated on 8 of 8 measurements of reaction time and movement time, patients treated with amantadine for a mean duration of over 40 months had improved performances in 1 of 4 reaction time measurements and in 3 of 4 movement time measurements and remained stable on the others. These results demonstrate long-term benefits of amantadine in olivopontocerebellar atrophy-induced deficits of movement initiation and movement completion.

Radiologic Correlates of Reaction Time Measurements in Olivopontocerebellar Atrophy

We measured simple visual and auditory reaction time (RT) and movement time (MT) in 32 patients with olivopontocerebellar atrophy (OPCA) in comparison to 32 control subjects. In addition, we followed 2 approaches to radiologic assessment by computed tomographic scans: subjective (by inspection of films) and objective (by measurement of 4 radiologic ratios at the level of the posterior fossa and 1 ratio at the supratentorial level). All OPCA patients had various degrees of cerebellar atrophy and lengthened RT and MT in comparison to their controls. There were no significant differences in RT and MT performances in patients with mild-moderate versus those with severe cerebellar atrophy as assessed by inspection of their films. OPCA patients with severe versus mild-moderate atrophy evaluated by 3 measures, i.e., brainstem, brachium pontis and fourth ventricle ratios, presented few significantly lengthened RT and MT performances. In contrast, patients with severe atrophy revealed by the midbrain ratio had significantly lengthened RT and MT performances compared to those with mild-moderate atrophy assessed by this ratio on 7 of 8 measures; the 8th measure showed a borderline significant difference. This could be explained by the fact that atrophy at the midbrain level is the only one which involves dopaminergic, noradrenergic and glutamatergic structures and pathways.

Behavioral and biochemical effects of l-tryptophan and buspirone in a model of cerebellar atrophy

The Lurcher mutant mouse can be considered an adequate model of autosomal dominant spinocerebellar atrophy because of the severe degeneration of its cerebellar cortex and inferior olive. The purpose of this study was to determine whether the motor coordination deficits of Lurcher mutants could be improved after chronic administration of the serotonin (5-hydroxytryptamine; 5-HT) precursor, L-tryptophan, or of the 5-HT(1A) agonist, buspirone. During these treatments, the mice were submitted to behavioral evaluations using the coat hanger and the rotorod tests, as well as an inclined screen and a vertical grid test. At the end of treatments, 5-HT and 5-hydroxindole-3-acetic acid (5-HIAA) were measured in six brain regions. On the coat hanger test, administration of L-tryptophan accelerated movements along the horizontal bar by 44%, while buspirone increased the time spent on the apparatus by 11%. Neither drug had an effect on climbing ability or on the time spent on a rotating beam. Administration of L-tryptophan increased 5-HIAA levels in frontal cortex, neostriatum, thalamus, brainstem, cerebellum and spinal cord, but elevated 5-HT only in neostriatum, brainstem and cerebellum. In contrast, buspirone led to 5-HT increases in cerebellum and augmented 5-HIAA in the spinal cord. The modest test-specific improvements are consistent with some of the clinical data concerning 5-HT pharmacotherapy in patients suffering from cerebellar atrophy.

Neuroradiological correlates of neuropsychological disorders in olivopontocerebellar atrophy (OPCA)

Thirty‐two OPCA patients without cortical atrophy were studied. In addition to inspection of films by a neuroradiologist (i.e. “subjective” assessment), five neuroradiological measures were used, namely, the estimation of brainstem ratio, midbrain ratio, fourth ventricular ratio, brachium pontis ratio and bicaudate ratio. The patients were divided into two groups: one with mild and the other with moderate‐severe atrophies. The neuropsychological assessment measures were: global memory quotient, verbal learning capacities, recall and recognition, attention, abstract thinking, visuo‐spatial and visuo‐constructive functioning. Three conclusions emerged: (i) cognitive disturbances in OPCA are related to the degree of cerebellar damage; (ii) these findings are consistent with the concept of anatomic and metabolic neocerebellar → basal ganglia → associative cerebral cortex loops; and (iii) it appears that the role of the neocerebellum in cognition is not exclusive because some other structures (fastigius, vermis) and the fastigial → limbic loops seem to be involved.

Relationship between choice reaction time and the Tower of Hanoi test.

The aim of this study was to examine a possible relation between the speed of information processing, as measured by simple and choice visual RT, and problem-solving, as measured by the Tower of Hanoi test. For 20 normal teenagers, performing all tests, significant correlations were found between choice RT and both measures of performance on the Tower of Hanoi, number of disk moves, and time taken to complete the task. Simple RT was correlated with Completion time but not with the number of moves, while the reverse pattern was discerned for decision time. Choice movement time was also associated with both measures, but simple movement time was not. These results are consistent with the hypothesis of a common neurobiological basis to information-processing speed and executive functions.