Deficits of thermal sensation in patients with unilateral cerebral lesions

Using a quantitative psychophysical test, the thresholds for detection of heat and cold were determined at both wrists in 16 hemiparetic patients with unilateral cerebral lesions and 1 patient with a unilateral frontal lesion but no hemiparesis. These data were compared with normal values for the absolute thermal thresholds and the symmetry of thermal thresholds in 25 age-matched control subjects. Significant elevation of thermal thresholds was found in all patients with clinically detectable deficits of nociceptive or thermal sensations. Thresholds were also elevated in 3 of 10 hemiparetic patients with no clinical evidence of impairment of nociceptive or thermal sensations. Deficits were found in patients with superficial cortical lesions as well as in those with extensive lesions involving deep structures, including thalamus. In patients with superficial lesions, the elevation of thermal threshold was slight (less than 1 degree C) and there was often little or no sensory deficit to clinical testing. In patients with very high thermal thresholds (greater than 6 degrees C), the lesions involved deep structures and there were clinically obvious deficits of thermal and nociceptive sensations.     

Impairments of prehension kinematics and grasping forces in patients with cerebellar degeneration and the relationship to cerebellar atrophy

OBJECTIVE: This study established the relationship between kinematic and grip force parameters in prehension tasks, disease severity and cerebellar atrophy in patients with cerebellar degeneration. METHODS: Prehension was tested in a condition during which the hand reached out, grasped, and lifted an object. Task complexity was modified by limiting the transport component to a single-joint movement, and introducing a bimanual condition. RESULTS: Compared to controls the cerebellar patients showed disturbances in hand transport, in hand shaping and the most pronounced in time to peak grip force and the grip/load force coupling. Task-dependent changes did not differ between groups. Ataxia scores revealed significant correlations with hand transport and shaping measures only. Ataxia subscores correlated with volume reduction of appropriate longitudinal cerebellar zones. Volume reduction of the intermediate zone was associated with grip force coordination deficits. CONCLUSIONS: Results indicate that the cerebellum may have a more general role in motor control of grasping independent of task complexity. Temporal and coordinative measures of grip force appear to be most useful to assess the severity of grasping deficits in patients with cerebellar degeneration not detectable by clinical ataxia scales. SIGNIFICANCE: To assess the severity and course of cerebellar disease grip force control in a standard prehension task is a sensitive quantitative measure.     

Reduced skilfulness of arm motor behaviour among motor stroke patients with good clinical recovery: does it indicate reduced automaticity? Can it be improved by unilateral or bilateral training? A kinematic motion analysis study

Functional cortical reorganisation had been demonstrated to accompany recovery from motor stroke. In agreement with a previous study, quantitative kinematic analysis of aimed movements in 14 almost completely recovered hemiparetic stroke patients and 14 healthy control subjects indicated a reduced skilfulness of both the more ballistic initial movement phase and the more feedback-guided late homing-in phase of aimed movements. By means of two dual motor tasks it was further investigated whether the reduced skilfulness of patients was due to an increased attentional demand and thus a reduced automaticity of motor control. Interference effects by dual tasks, however, were similar for patients and control subjects. Thus, the notion of reduced automaticity could not be supported empirically, and reduced skilfulness seemed rather related to residual pyramidal motor deficits. By means of a repetitive daily training for 1 week based on the Arm Ability Training approach, patients were able to reduce their performance deficits in both movement phases significantly. Whether patients practised with the affected arm or simultaneously with both the affected and non-affected arm only marginally modified outcome, unilateral training being slightly more efficacious. These findings demonstrate that even clinically minor residual motor deficits can be improved by a structured training for the affected arm.     

Stance control is not affected by paresis and reflex hyperexcitability: the case of spastic patients

OBJECTIVES: Spastic patients were studied to understand whether stance unsteadiness is associated with changes in the control of voluntary force, muscle tone, or reflex excitability, rather than to abnormal posture connected to the motor deficit itself. METHODS: Twenty four normal subjects, 12 patients affected by amyotrophic lateral sclerosis (ALS), seven by spastic paraparesis, and 14 by hemiparesis were studied. All patients featured various degrees of spasticity and paresis but were free from clinically evident sensory deficits. Body sway during quiet upright stance was assessed through a stabilometric platform under both eyes open (EO) and eyes closed (EC) conditions. The sudden rotation of a supporting platform, in a toe up and toe down direction respectively, evoked short (SLR) and medium latency (MLR) reflex responses to stretch of the soleus or the tibialis anterior (TA) muscle. RESULTS: No relation was found between clinical findings (tone, muscle strength, tendon reflexes, plantar response, and duration of disease) and body sway. On average, all patient groups exhibited a forward shift of the centre of foot pressure (CFP) with respect to normal subjects; in addition, paraparetic and to a much larger extent hemiparetic patients showed a lateral shift of CFP. Body sway area was significantly increased only in the hemiparetic patients. No relation was found between position of the CFP and sway within any patient group. Soleus SLR was increased in all patients with respect to normal subjects. TA SLR was often seen in both patients with ALS and paraparetic patients, but only rarely in normal subjects and hemiparetic patients. However, no relation was found between amplitude of soleus or TA SLRs and stabilometric variables. The frequency and size of soleus MLR and TA MLR were decreased in all patients. These responses were decreased in size and not modulated by background EMG in the affected leg of hemiparetic patients, suggesting a disturbed control of spinal reflexes fed by spindle group II afferent fibres. CONCLUSIONS: It is proposed that body posture, paresis, or monosynaptic reflex hyperexcitability do not affect the control of equilibrium during quiet upright stance. In hemiparetic patients, the decreased amplitude of MLRs might be the main cause of the large postural instability. The results are congruent with the hypothesis of a role for group II afferent input in the reflex control of equilibrium.     

Prehension Kinematics,Grasping Forces,and Independent Finger Control in Mildly Affected Patients with Essential Tremor

Although the pathophysiology of essential tremor (ET), one of the most common movement disorders, is not fully understood, evidence increasingly points to cerebellar involvement. To confirm this connection, we assessed the everyday hand and finger movements of patients with ET, as these movements are known to be affected in cerebellar diseases. In 26 mildly affected patients with ET (compared to age- and gender-matched controls), kinematic and finger force parameters were assessed in a precision grip. In a second task, independent finger movements were recorded. The active finger had to press and release against a force-sensitive keypad while the other fingers stayed inactive. Finally, control of grip force to movement-induced, self-generated load changes was studied. Transport and shaping components during prehension were significantly impaired in patients with ET compared to controls. No significant group differences were observed in independent finger movements and grip force adjustments to self-generated load force changes. However, in the latter two tasks, more severely affected ET patients performed worse than less affected. Although observed deficits in hand and finger movement tasks were small, they are consistent with cerebellar dysfunction in ET. Findings need to be confirmed in future studies examining more severely affected ET patients.     

Biomechanical changes at the ankle joint after stroke.

The resistance of the relaxed ankle to slow displacement over the joint movement range was measured on both sides of a group of hemiparetic stroke patients, in whom spasticity had been established for at least one year and who showed no clinical signs of contractures. The ankle joints of the age-matched normal subjects were flexible over most of the movement range, showing dramatically increasing stiffness only when the foot was dorsiflexed beyond 70 degrees, with a neutral range between 90-100 degrees, and a less dramatic increase in stiffness during plantarflexion. Hemiparetic patients showed identical curves to the normal subjects on the "healthy" side, ipsilateral to the causative cerebral lesion, but were significantly stiffer in dorsiflexion on the contralateral side, without change in the minimum stiffness range or during plantarflexion. Therefore significant changes in passive biomechanical properties occur at the affected ankle of hemiparetic subjects, predominantly as the result of a loss of compliance in the Achilles tendon, although an increase in the passive stiffness of the triceps surae may also occur. The contribution of these changes to the locomotor disability of hemiparetic patients is discussed.     

Reorganization of multi-muscle and joint withdrawal reflex during arm movements in post-stroke hemiparetic patients

ObjectivesTo investigate the behavior of the nociceptive withdrawal reflex (NWR) in the upper limb during reaching and grasping movements in post-stroke hemiparetic patients.MethodsEight patients with chronic stroke and moderate motor deficits were included. An optoelectronic motion analysis system integrated with a surface EMG machine was used to record the kinematic and EMG data. The NWR was evoked through a painful electrical stimulation of the index finger during a movement which consisted of reaching out, picking up a cylinder, and returning it to the starting position.ResultsWe found that: (i) the NWR is extensively rearranged in hemiparetic patients, who were found to present different kinematic and EMG reflex patterns with respect to controls; (ii) patients partially lose the ability to modulate the reflex in the different movement phases; (iii) the impairment of the reflex modulation occurs at single-muscle, single-joint and multi-joint level.ConclusionsPatients with chronic and mild-moderate post-stroke motor deficits lose the ability to modulate the NWR dynamically according to the movement variables at individual as well as at multi-muscle and joint levels.SignificanceThe central nervous system is unable to use the NWR substrate dynamically and flexibly in order to select the muscle synergies needed to govern the spatio–temporal interaction among joints.     

Resection of cerebellar tumours causes widespread and functionally relevant white matter impairments

Several diffusion tensor imaging studies reveal that white matter (WM) lesions are common in children suffering from benign cerebellar tumours who are treated with surgery only. The clinical implications of WM alterations that occur as a direct consequence of cerebellar disease have not been thoroughly studied. Here, we analysed structural and diffusion imaging data from cerebellar patients with chronic surgical lesions after resection for benign cerebellar tumours. We aimed to elucidate the impact of focal lesions of the cerebellum on WM integrity across the entire brain, and to investigate whether WM deficits were associated with behavioural impairment in three different motor tasks. Lesion symptom mapping analysis suggested that lesions in critical cerebellar regions were related to deficits in savings during an eyeblink conditioning task, as well as to deficits in motor action timing. Diffusion imaging analysis of cerebellar WM indicated that better behavioural performance was associated with higher fractional anisotropy (FA) in the superior cerebellar peduncle, cerebellum''s main outflow path. Moreover, voxel‐wise analysis revealed a global pattern of WM deficits in patients within many cerebral WM tracts critical for motor and non‐motor function. Finally, we observed a positive correlation between FA and savings within cerebello‐thalamo‐cortical pathways in patients but not in controls, showing that saving effects partly depend on extracerebellar areas, and may be recruited for compensation. These results confirm that the cerebellum has extended connections with many cerebral areas involved in motor/cognitive functions, and the observed WM changes likely contribute to long‐term clinical deficits of posterior fossa tumour survivors.     

Electrophysiological signs of changes in motor units after ischaemic stroke.

OBJECTIVE: To study changes in motor units on the hemiparetic side, and the relationship between these changes and time after stroke onset and hemiparetic severity. METHODS: Neurography and concentric needle EMG were performed, and hemiparetic side mean and extreme parameter values were compared with the unaffected side mean and extreme parameter values using non-parametric tests. RESULTS: The mean M wave amplitude was significantly lower, while the spontaneous activity and the mean number of motor unit potential (MUAP) phases and turns were significantly higher on the hemiparetic side. The outliers above maximum for MUAP duration and amplitude on the hemiparetic side were significantly higher than those on the unaffected side. Correlations were found between the hemiparetic side parameter values and time after stroke onset and hemiparetic severity. CONCLUSIONS: Axonal or neuronal lesion occurs and collateral reinnervation starts in the acute phase after stroke, while enlarged motor units are found in the chronic state. These changes correlate with hemiparetic severity. SIGNIFICANCE: This work confirms the controversial concept about lower motor neuron injury with stroke, and provides some information about its time course.     

Comparison of the basal ganglia and cerebellum in shifting attention

The basal ganglia and cerebellum have traditionally been associated with motor performance. Recently, there has been considerable interest regarding the contributions of these subcortical structures to aspects of cognition. In particular, both the basal ganglia and cerebellum have been hypothesized to be involved in the control of attentional set. To date, no neuropsychological studies have directly compared the effects of basal ganglia and cerebellar dysfunction on the same attention shifting tasks. To this end, we employed an alternating attention task that has been used to demonstrate putative attentional control deficits in children with cerebellar pathology, either related to autism or neurological insult. When adult patients with either Parkinson's disease or cerebellar lesions were tested on this task, a similar pattern of deficits was observed for both groups. However, when the motor demands were reduced, cerebellar patients showed a significant improvement on the alternating attention task, whereas the Parkinson patients continued to exhibit an impairment. This dissociation suggests that attentional deficits reported previously as being due to cerebellar dysfunction may be, at least in part, secondary to problems related to coordinating successive responses. In contrast, attention-shifting deficits associated with basal ganglia impairment cannot be explained by recourse to the motor demands of the task.     

Cerebellar alterations and gait defects as therapeutic outcome measures for enzyme replacement therapy in α-mannosidosis

α-Mannosidosis is a rare lysosomal storage disease with accumulation of undegraded mannosyl-linked oligosaccharides in cells throughout the body, most notably in the CNS. This leads to a broad spectrum of neurological manifestations, including progressive intellectual impairment, disturbed motor functions, and cerebellar atrophy. To develop therapeutic outcome measures for enzyme replacement therapy that could be used for human patients, a gene knockout model of α-mannosidosis in mice was analyzed for CNS pathology and motor deficits. In the cerebellar molecular layer, α-mannosidosis mice display clusters of activated Bergman glia, infiltration of phagocytic macrophages, and accumulation of free cholesterol and gangliosides (GM1), notably in regions lacking Purkinje cells. α-Mannosidosis brain lysates also displayed increased expression of Lamp1 and hyperglycosylation of the cholesterol binding protein NPC2. Detailed assessment of motor function revealed age-dependent gait defects in the mice that resemble the disturbed motor function in human patients. Short-term enzyme replacement therapy partially reversed the observed cerebellar pathology with fewer activated macrophages and astrocytes but unchanged levels of hyperglycosylated NPC2, gangliosides, and cholesterol. The present study demonstrates cerebellar alterations in α-mannosidosis mice that relate to the motor deficits and pathological changes seen in human patients and can be used as therapeutic outcome measures.     

Cerebellar metabolic involvement and its correlations with clinical parameters in vestibular neuritis

Although vestibular neuritis (VN) cortical models are described in the literature, there is lack of knowledge regarding the exclusive cerebellar involvement. The aim of the present study was to analyze, by [18F] fluorodeoxyglucose-positron emission tomography (FDG-PET)/computer tomography, regional cerebellar FDG uptake in eight right-handed VN patients (five females; three males; mean age 48 ± 7 years) during the first few days (PET0) and after 1 month (PET1) since symptoms onset. At both phases, patients underwent otoneurological examination and filled in a battery of validated questionnaires. Twenty-six cerebellar volumes of interest (VOI) were identified by the automated anatomical labeling library and normalized to thalamus FDG-PET uptake. Mean intensity within VOIs was calculated in both phases and processed by within-subjects ANOVA. A significantly lower (p < 0.005) FDG uptake distribution was found in bilateral lobules III, VI and X and in vermis 1–2, 3, 6 and 10 at PET0 as compared to PET1 and a significant higher FDG uptake distribution was found in right crus I in the same comparison. Significant (p < 0.05) positive correlations were found between Anxiety and Bucket test scores, and normalized metabolism in right crus I (at PET0) and vermis 10 (at PET1), respectively. A negative correlation was found at PET0 between slow-phase velocity scores and normalized metabolism in right lobule X. These data show relevant changes in the pattern of cerebellar metabolism that might unravel additional central aspects of early and late VN associated to bilateral cortical responses to sensory conflict during the acute VN-related controversial inflow.     

Grip force control during object manipulation in cerebral stroke.

OBJECTIVE: To analyze impairments of manipulative grip force control in patients with chronic cerebral stroke and relate deficits to more elementary aspects of force and grip control. METHODS: Nineteen chronic stroke patients with fine motor deficits after unilateral cerebral lesions were examined when performing 3 manipulative tasks consisting of stationary holding, transport, and vertical cyclic movements of an instrumented object. Technical sensors measured the grip force used to stabilize the object in the hand and the object accelerations, from which the dynamic loads were calculated. RESULTS: Many patients produced exaggerated grip forces with their affected hand in all types of manipulations. The amount of finger displacement in a grip perturbation task emerged as a highly sensitive measure for predicting the force increases. Measures of grip strength and maximum speed of force changes could not account for the impairments with comparable accuracy. In addition to force economy, the precision of the coupling between grip and load forces was impaired. However, no temporal delays were typically observed between the grip and load force profiles during cyclic movements. CONCLUSIONS: Impaired sensibility and sensorimotor processing, evident by delayed reactions in the perturbation task, lead to an excessive increase of the safety margin between the actual grip force and the minimum force necessary to prevent object slipping. In addition to grip force scaling, cortical sensorimotor areas are responsible for smoothly and precisely adjusting grip forces to loads according to predictions about movement-induced loads and sensory experiences. However, the basic feedforward mechanism of grip force control by internal models appears to be preserved, and thus may not be a cortical but rather a subcortical or cerebellar function, as has been suggested previously.     

Making Sense of Cerebellar Contributions to Perceptual and Motor Adaptation

The cerebellum is thought to adapt movements to changes in the environment in order to update an implicit understanding of the association between our motor commands and their sensory consequences. This trial-by-trial motor recalibration in response to external perturbations is frequently impaired in people with cerebellar damage. In healthy people, adaptation to motor perturbations is also known to induce a form of sensory perceptual recalibration. For instance, hand-reaching adaptation tasks produce transient changes in the sense of hand position, and walking adaptation tasks can lead to changes in perceived leg speed. Though such motor adaptation tasks are heavily dependent on the cerebellum, it is not yet understood how the cerebellum is associated with these accompanying sensory recalibration processes. Here we asked if the cerebellum is required for the recalibration of leg-speed perception that normally occurs alongside locomotor adaptation, as well as how ataxia severity is related to sensorimotor recalibration deficits in patients with cerebellar damage. Cerebellar patients performed a speed-matching task to assess perception of leg speed before and after walking on a split-belt treadmill, which has two belts driving each leg at a different speed. Healthy participants update their perception of leg speed following split-belt walking such that the “fast” leg during adaptation feels slower afterwards, whereas cerebellar patients have significant deficits in this sensory perceptual recalibration. Furthermore, our analysis demonstrates that ataxia severity is a crucial factor for both the sensory and motor adaptation impairments that affect patients with cerebellar damage.     

Facilitation of motor evoked potentials in hand extensor muscles of stroke patients: correlation to the level of voluntary contraction

The influence of ongoing voluntary isometric contractions (ranging from 2.5% to 100% of maximum force production) on motor evoked potentials in the extensor carpi radialis muscle was investigated in 20 healthy subjects and 25 hemiparetic stroke patients using transcranial magnetic stimulation at threshold and at 90% of maximum stimulus intensity. In healthy subjects and in stroke patients, an initial sharp decay in response latencies was observed at low contraction levels. In hemiparetic patients, however, no significant further reduction of response latencies with increasing contraction levels was observed irrespective of whether threshold or 90% stimulus intensities were applied. The continuous decrease in latency in the healthy subjects is supposed to result from an enhanced involvement of rapidly conducting corticospinal neurones that are preferentially damaged in the patient group. In healthy subjects and in hemiparetic patients, however, the increase in response amplitudes runs in parallel with increasing force production, at least with threshold stimulus intensity. Contrary to response latencies, amplitude facilitation appears to be less dependent on the involved corticospinal fibre spectrum but to be predominantly based on temporal and spatial summation effects. The relevance of the latency and amplitude data obtained in healthy subjects and in stroke patients for physiology and localization of facilitatory processes, i.e. whether cortical or spinal, is discussed. For the rehabilitation of stroke patients it is concluded that the effect of slight voluntary contractions is indeed superior to most other facilitatory approaches. The functional relevance is discussed.     

Reduced cerebellar inhibition in schizophrenia: a preliminary study

OBJECTIVE: Postmortem and structural imaging studies suggest that patients with schizophrenia have disrupted cerebellar activity. It has been speculated that these abnormalities mediate disorganized thought processes and psychosis. The authors' goal was to use transcranial magnetic stimulation to measure cerebellar inhibition, a proxy of cerebellar activity, as the principal output of the cerebellum is inhibitory. METHOD: Cerebellar inhibition was accomplished by delivering a magnetic cerebellar conditioning stimulus 5-15 msec before a magnetic test stimulus to the motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor evoked potential produced by the test stimulus by approximately 50%. Ten patients with schizophrenia and 10 healthy comparison subjects completed the cerebellar inhibition protocol. RESULTS: Patients with schizophrenia demonstrated significant deficits in cerebellar inhibition compared with healthy subjects. CONCLUSIONS: The authors conclude that deficits in cerebellar inhibitory activity in schizophrenia may be the result of an abnormality in the cerebellum or disrupted cerebellar-thalamic-cortical connectivity.     

Cognitive Impairment in ARCA-1, a Newly Discovered Pure Cerebellar Ataxia Syndrome

Cerebellar contribution to non-motor functions has been supported by several animal, human and functional neuroimaging studies. Which cognitive skills and to what extent the cerebrocerebellar loops contribute remain unclear, however. Among other reasons, this may be explained by the fact that authors have studied patients with extracerebellar lesions. The goal of this study was to explore the role of the cerebellum in cognition and affect in patients with autosomal recessive cerebellar ataxia type 1 (ARCA-1), a newly described inherited cerebellar disease characterised by middle-age onset of ataxia as well as pure, severe and diffuse cerebellar atrophy. To this end, the performance of 21 ARCA-1 patients was compared to that of 21 normal controls paired for age and education on a 3-h battery of attention, executive, visuospatial and memory skills. Results indicated similar IQ, naming and declarative memory abilities between groups. ARCA-1 patients showed significant deficits in attention (attention span, speed of information processing, sustained attention), verbal working memory and visuospatial/visuoconstructional skills (3-D drawings, copy of a complex figure). Functional brain imaging in a subset of patients showed diffuse severe cerebellar hypometabolism associated with a small area of right parietal hypometabolism. None of the patients presented a significant affective syndrome. Correlational analyses suggested that cognitive deficits could not be explained by the severity of motor deficits, duration of disease or mood. Altogether, this study confirms that pure cerebellar damage as seen in ARCA-1 is associated with significant cognitive impairments but not with psychiatric comorbidity. These deficits are correlated with an overall moderate impact on patient’s autonomy. Our data favour an indirect participation of the dorsolateral prefrontal and posterior parietal cortical areas to the cerebrocerebellar circuit.     

Cerebellar Contribution to Anger Recognition Deficits in Huntington’s Disease

Although there is increasing evidence that cerebellar loss of grey matter volume (GMV) is associated with affective deficits, this has not been tested for patients suffering from Huntington’s disease (HD), who show a pronounced impairment in the recognition of anger. We assessed GMV in 18 symptomatic HD patients and 18 healthy controls using voxel-based morphometry. The GMV of cerebellar subregions was correlated with participants’ intensity and accuracy ratings for facial expressions of basic emotions from the Karolinska Directed Emotional Faces (Lundqvist et al. 1998). The patients gave lower and less accurate anger ratings for angry faces than controls. This anger recognition deficit was correlated with atrophy of selected hemispheric and vermal regions of the cerebellum. Furthermore, cerebellar volume reductions of the HD patients were associated with longer disease duration and greater functional impairment. The data imply that anger recognition deficits could potentially serve as indicators of disease onset and progression in HD. Furthermore, the patients might profit from specific affect trainings.     

Changes of neurotransmitters in the brainstem of patients with respiratory-pattern disorders during childhood.

We examined neuropathologically and immunohistochemically the respiratory centers in the brainstem of two patients with Joubert syndrome (JS), three patients with congenital central hypoventilation syndrome (CCHS) and a patient with apneustic breathing (prolonged inspiratory pause) due to unknown etiology. Immunoreactivity (IR) of tryptophan hydroxylase (TPH) was decreased in the dorsal raphe nuclei of two patients with JS compared with age-matched controls, as well as in two patients with Dandy-Walker malformation. The two JS patients showed vermian defect and elongated cerebellar peduncles, and peculiar vascularities in the midline of the whole brainstem were also noted in one of these patients. These findings, as a whole, confirm that the midline structures of brainstem are disordered both structurally and functionally in JS, conceivably resulting in respiratory patterns and psychomotor deficits. IR of serotonin 1A receptor showed no significant changes in the medulla oblongata of these patients, however. In the parabrachial complex, IR of substance P was increased in two patients with CCHS, and one with apneustic breathing. IR of tyrosine hydroxylase was also increased in the latter. The brainstem of these patients showed reactive astrogliosis. These findings suggest preceding hypoxic episodes as well as an increased activity in the parabrachial complex which plays an important role in conducting the driving force to the medullary respiratory neurons from ascending sensory pathways.