Neuropsychological deficits in cerebellar syndromes

Interest in the role of the cerebellum in cognitive functioning has been increasing in recent years, based on both theoretical considerations and empirical evidence. This review attempts to critically evaluate neuropsychological studies based on standardized testing of patients with selective cerebellar dysfunction. Findings are considered which address possible cerebellar influence on motor adaptation and habituation, motor skill acquisition, classical conditioning of motor responses, temporal processing, general intellectual abilities, frontal lobe functions, visuospatial abilities, memory and non-motor skill learning, and language. Deficits in motor learning and temporal processing are consistently observed in patients with cerebellar syndromes, while deficits in frontal lobe functions, visuospatial processing, memory, non-motor skill learning and language dysfunction have been reported in several studies, but have not been replicated in others. Methodological factors which may account for such discrepancies are discussed.     

EMG analysis of patients with cerebellar deficits.

EMGs from biceps and triceps were recorded during stereotyped elbow flexion tasks performed by 20 patients fulfilling clinical criteria for 'cerebellar deficits' and the data were compared with previously established normal standards. In a fast flexion task, 15 of 18 patients showed prolongation of the initial biceps and/or triceps components, and it is suggested that this abnormality might be an elemental feature of dysmetria. Ten of 14 patients showed the normal pattern of smooth flexion indicating that, with cerebellar deficits, smooth movements are better preserved than fast movements. The timing of the cessation of triceps activity before the initiation of biceps activity in an alternating movement was abnormal in 12 of 16 patients; this abnormality might be an elemental feature of dysdiadochokinesia.     

Speech deficits in ischaemic cerebellar lesions

Summary Twelve patients with cerebellar infarction, 8 in the region supplied by the posterior inferior cerebellar artery (PICA) and 4 in the territory of the superior cerebellar artery, underwent formal perceptual examination for speech deficits. With respect to topography the results firstly underline the significance of the paravermal region of the superior cerebellar portion for speech functions. In all patients with dysarthric impairment the lesion extended to this area, whereas patients with PICA infarction sparing the superior portion of the cerebellum showed no speech deficits. Secondly the findings do not corroborate the notion of an exclusively left-sided cerebellar speech motor control, since 3 of the 4 dysarthric subjects had unilateral right-sided ischaemia. This study thirdly demonstrates that lesions of the cerebellar cortex without involvement of the dentate nucleus can cause dysarthric impairment. Phonetic analysis revealed irregularly distributed articulatory deficits and slowed speech tempo as the most common dysarthric features.     

Some neurophysiological effects of cerebellar stimulation in man.

This paper presents the results of neurophysiological studies of the effects of cerebellar stimulation on H reflexes, late reflexes, blink reflexes, evoked potentials and EEG patterns in 18 human subjects (Male 13, Female 5, Age 25.8+/-10.0, Epileptic 9, Cerebral Palsy 9). In addition to the effects of cerebellar stimulation on the H reflex studies on soleus we assessed V1 and V2, "late" responses (Upton et al., 1971), cortical somatosensory evoked potentials (SSEP) after median nerve stimulation, and visual evoked responses (VER) after flash stimulation. Experiments were extended to assess recovery curves of all the potentials and we examined the effects of changes on the rate or voltage of cerebellar stimulation. Cerebellar stimulation was inhibitory to all the responses except the visual evoked potentials. Serial studies in five patients produced consistent results. Preoperative and postoperative results were compared in two patients with no significant difference in the results in the absence of cerebellar stimulation. Ipsilateral cerebellar stimulation (CS) had the greatest inhibitory effects on H, V1 and V2 responses in the arm and leg whereas contralateral CS produced the greatest effects on cortical SSEPs. There was a greater bilateral effect on SSEPs and reflex responses after right CS than left CS and this may be the first indication of "dominance" in the cerebellar hemispheres. Cerebellar stimulation in patients on diphenylhydantoin produced minimal effects on SSEP's and this observation has led to further studies in patients taking diphenylhydantoin. Recovery of amplitude of the reflex and cortical responses took eight to 30 minutes after one minute of cerebellar stimulation. Serial CS of one minute on and one minute off produced increasing inhibition of SSEP's and reflexes for up to five stimulations. Recovery after cessation of cerebellar stimultion was associated with rebound excitation in six patients, the rebound being noted in the amplitude of H reflexes and SSEP's as well as in the frequency of paroxysmal spike and wave discharges in the EEG. The correlation of the results of such quantitative neurophysiological tests with clinical improvement may allow prediction of clinical improvement may allow prediction of clinical results after cerebellar stimulation. These techniques have already been used to measure the threshold of stimulation and may allow optimal stimulation characteristics to be assessed. The prolonged neurophysiological effects of stimulation may allow the use of maximum effective intervals between optimal epochs of stimulation so that any cerebellar damage can be minimized.     

Subtle cognitive deficits after cerebellar infarcts

The role of the cerebellum in cognitive functions has been under debate. We investigated the neuropsychological functioning of patients with cerebellar lesions (infarcts) and evaluated the significance of laterality in cognitive symptoms. Twenty-six patients with exclusive cerebellar lesions as verified by clinical and neuroradiological findings underwent a neuropsychological assessment at the acute stage and at 3 months. Their performance was compared with 14 controls, also assessed twice. The focus was on four domains: visuospatial/motor functions, episodic memory, working memory and attentional shifting/execution. Both groups improved over time. Statistical differences emerged in tests in the visuomotor domain as well as in the episodic and working memory domains. Patients with left cerebellar lesion were slow in a visuospatial task, whereas those with right cerebellar lesions had verbal memory difficulty compared with controls. By 3 months, 77% of the patients had returned to work, and only one had cognitive impairment and did not return to work. Our results indicate that cerebellar infarcts may result in subtle cognitive changes perhaps primarily related to working memory deficit. The symptoms may be mediated by the contralateral cortical hemisphere, left cerebellar infarcts producing mild right hemispheral dysfunction and right cerebellar infarct producing mild left hemispheral dysfunction.     

Lacunar thalamic stroke with pure cerebellar and proprioceptive deficits.

Case reports of two patients with cerebellar ataxia and proprioceptive sensory loss are presented. MRI of the brain revealed lesions of the ventroposterior part of the thalamus. These patients illustrate clinically the anatomical independence of cerebellar and sensory pathways in the thalamus. We suggest that the ataxic deficit is caused by interruption of cerebellar outflow pathways in the thalamus and not secondary to sensory deafferentation.     

Neuropsychological deficits in depressive disorders

Neuropsychological deficits are considered a significant feature of depression both for their differential value in the diagnostics and the underlying pathophysiology of depressive disorders. The studies reviewed in the present paper predominantly focus on memory disorders as well as frontal-lobe associated dysfunctions such as deficits of attentional performance and executive functions. Despite heterogeneous results in the literature, there is emerging evidence that executive functions and anterograde memory performance are those domains predominantly affected in depressive disorders. The fact that not all depressive patients display neuropsychological deficits rather indicates a dominant role of moderating variables. We discuss the following variables possibly intervening with type and degree of neuropsychological dysfunction: [1] severity and remission of depressive disorders, [2] age of patients and age at the first manifestation of a depressive disorder, [3] psychological factors such as motivation and coping with failure, [4] type and efficacy of antidepressive drug treatment, [5] duration of the stay as inpatients, [6] number of depressive episodes, and [7] gender. Furthermore, we discuss the theory of a dysfunction of fronto-striatal circuits as an underlying mechanism of depressive disorders. The majority of neuropsychological findings seem to support this theory.     

Lateralized cognitive deficits in children following cerebellar lesions

The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.     

Spatial attention deficits in patients with acquired or developmental cerebellar abnormality.

Recent imaging and clinical studies have challenged the concept that the functional role of the cerebellum is exclusively in the motor domain. We present evidence of slowed covert orienting of visuospatial attention in patients with developmental cerebellar abnormality (patients with autism, a disorder in which at least 90% of all postmortem cases reported to date have Purkinje neuron loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial cuing tasks, normal control subjects across a wide age range were able to orient attention within 100 msec of an attention-directing cue. Patients with cerebellar damage showed little evidence of having oriented attention after 100 msec but did show the effects of attention orienting after 800-1200 msec. These effects were demonstrated in a task in which results were independent of the motor response. In this task, smaller cerebellar vermal lobules VI-VII (from magnetic resonance imaging) were associated with greater attention-orienting deficits. Although eye movements may also be disrupted in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing and nature of the attention-orienting deficits reported here. These data may be consistent with evidence from animal models that suggest damage to the cerebellum disrupts both the spatial encoding of a location for an attentional shift and the subsequent gaze shift. These data are also consistent with a model of cerebellar function in which the cerebellum supports a broad spectrum of brain systems involved in both nonmotor and motor function.     

Physiological analysis of simple rapid movements in patients with cerebellar deficits.

Patients with cerebellar deficits made elbow flexion movements as rapidly as possible for three different angular distances. Electromyographic activity of biceps and triceps and the kinematics of the movements were analysed. Results were compared with those of normal subjects making both rapid and slow movements. In the patients, the first agonist burst of the biceps was frequently prolonged regardless of the distance or speed of the movement. The most striking kinematic abnormality was prolonged acceleration time. The pattern of acceleration time exceeding deceleration time was common in patients but uncommon in normal subjects. The best kinematic correlate of the duration of the first agonist burst was acceleration time. Altered production of appropriate acceleration may therefore be an important abnormality in cerebellar dysfunction for attempted rapid voluntary movements.     

Visuospatial abilities in cerebellar disorders

BACKGROUND: Cerebellar involvement in spatial data management has been suggested on experimental and clinical grounds. OBJECTIVE: To attempt a specific analysis of visuospatial abilities in a group of subjects with focal or atrophic cerebellar damage. METHODS: Visuospatial performance was tested using the spatial subtests of the WAIS, the Benton line orientation test, and two tests of mental rotation of objects-the Minnesota paper form board test (MIN) and the differential aptitude test (DAT). RESULTS: In the Benton line orientation test, a test of sensory analysis and elementary perception, no deficits were present in subjects with cerebellar damage. In MIN, which analyses the capacity to process bidimensional complex figures mentally, and in the DAT, which is based on mental folding and manipulation of tridimensional stimuli, subjects with cerebellar damage were impaired. CONCLUSIONS: The results indicate that lesions of the cerebellar circuits affect visuospatial ability. The ability to rotate objects mentally is a possible functional substrate of the observed deficits. A comparison between visuospatial performance of subjects with focal right and left cerebellar lesions shows side differences in the characteristics of the visuospatial syndrome. Thus cerebellar influences on spatial cognition appear to act on multiple cognitive modules.     

Sodium valproate in the treatment of cerebellar disorders.

Because of the high concentrations of gamma-aminobutyric acid (GABA) in the cerebellar cortex and nuclei, an attempt was made to enhance GABAergic transmission in patients with cerebellar disease. Maximum tolerated doses of sodium valproate, a drug which inhibits the degradation of GABA, failed to influence cerebellar deficits in a double blind crossover study on six patients.     

Affective communication deficits associated with cerebellar degeneration

The cerebellum has extensive connections with the frontal lobes. Cerebellar injury has been reported to induce frontal-executive cognitive dysfunction and blunting of affect. We examined a patient with idiopathic cerebellar degeneration with impaired family relationships attributed to an “emotional disconnection.” Examination revealed ataxia, dysmetria, and adiadochokinesia more severe on the left and frontal-executive dysfunction; memory and cognitive functions were otherwise normal. Testing of emotional communication included assessments of emotional semantic knowledge, emotional prosody, and emotional facial expressions. Comprehension was normal but expression was severely impaired. Cerebellar dysfunction can cause a defect in facial and prosodic emotional communication.     

Stability and tremor in the fingers associated with cerebellar hemisphere and cerebellar tract lesions in man.

Stability and tremor in the fingers were assessed by a new technique in patients with unilateral cerebellar syndromes. In 11 patients with unilateral cerebellar hemisphere lesions tremor was observed with either clear tremor at 5-7 Hz or prolongation of the tremor profile out to 11 Hz. In 10 patients with unilateral cerebellar lesions associated with ipsilateral past-pointing there was an asymmetry in finger stability. Compared with normal subjects there was a significant decrease in stability contralateral to the lesion, while the ipsilateral side's stability was not different from normal. In patients with high brain stem lesions at the level of cranial nerves VII and above, tremor had frequencies of 5-7 Hz. In those with lower brain stem lesions, often with long tract signs as well, the frequencies of tremor were faster, 8-11 Hz, which may reflect damage to cerebellar inflow tracts. A broad if not specific correlation was found between clinical condition, site of lesion and finger stability and tremor.