Abnormal locomotor muscle recruitment activity is present in horses with shivering and Purkinje cell distal axonopathy.

BACKGROUND: Cerebellar Purkinje cell axonal degeneration has been identified in horses with shivering but its relationship with abnormal hindlimb movement has not been elucidated. OBJECTIVES: To characterise surface electromyographic (sEMG) hindlimb muscle activity in horses with shivering, correlate with clinical scores and examine horses for Purkinje axonal degeneration. STUDY DESIGN: Descriptive controlled clinical study. METHODS: The hindlimb of seven shivering and six control draught horses were clinically scored. Biceps femoris (BF), vastus lateralis (VL), tensor fasciae latae and extensor digitorum longus were recorded via sEMG during forward/backward walking and trotting. Integrated (iEMG) and peak EMG activity were compared between groups and correlated with clinical locomotor exam scores. Sections of the deep cerebellar nuclei (DCN) of six of the seven shivering horses were examined with calbindin immunohistochemistry. RESULTS: In control horses, backward walking resembled forward walking (right hindlimb peak EMG: backward: 47.5 ± 21.9%, forward: 36.9 ± 15.7%) but displayed significantly higher amplitudes during trotting (76.1 ± 3.4%). However, in shivering horses, backward walking was significantly different from forward (backward: 88.5 ± 21.5%, forward: 49.2 ± 8.9%), and resembled activity during trotting (81.4 ± 4.8%). Specific to backward walking, mean sEMG amplitude fell outside two standard deviations of mean control sEMG for ≥25% of the stride in the BF for all seven and the VL for six of the seven shivering horses. Locomotor exam scores were correlated with peak EMG (r = 0.87) and iEMG (r = 0.87). Calbindin-positive spheroids were present in Purkinje axons in DCN of all shivering horses examined. MAIN LIMITATIONS: The neuropathological examination focused specifically on the DCN and, therefore, we cannot fully exclude additional lesions that may have influenced abnormal sEMG findings in shivering horses. CONCLUSION: Shivering is characterised by abnormally elevated muscle recruitment particularly in BF and VL muscles during backward walking and associated with selective Purkinje cell distal axonal degeneration.

The Equine Movement Disorder "Shivers" Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration.

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus.

Robot-assisted training to improve proprioception does benefit from added vibro-tactile feedback.

Proprioception is central for motor control and its role must also be taken into account when designing motor rehabilitation training protocols. This is particularly important when dealing with motor deficits due to proprioceptive impairment such as peripheral sensory neuropathy. In these cases substituting or augmenting diminished proprioceptive sensory information might be beneficial for improving motor function. However it still remains to be understood how proprioceptive senses can be improved by training, how this would translate into motor improvement and whether additional sensory modalities during motor training contribute to the sensorimotor training process. This preliminary study investigated how proprioceptive/haptic training can be augmented by providing additional sensory information in the form of vibro-tactile feedback. We tested the acuity of the wrist proprioceptive position sense before and after robotic training in two groups of healthy subjects, one trained only with haptic feedback and one with haptic and vibro-tactile feedback. We found that only the group receiving the multimodal feedback significantly improved proprioceptive acuity. This study demonstrates that non-proprioceptive position feedback derived from another somatosensory modality is easily interpretable for humans and can contribute to an increased precision of joint position. The clinical implications of this finding will be outlined.

Location and restoration of function after cerebellar tumor removal-a longitudinal study of children and adolescents.

Sequelae in children following cerebellar tumor removal surgery are well defined, and predictors for poor recovery include lesions of the cerebellar nuclei and the inferior vermis. Dynamic reorganization is thought to promote functional recovery in particular within the first year after surgery. Yet, the time course and mechanisms of recovery within this critical time frame are elusive and longitudinal studies are missing. Thus, a group of children and adolescents (n = 12, range 6-17 years) were followed longitudinally after cerebellar surgery and compared to age- and gender-matched controls (n = 11). Patients were examined (1) within the first days, (2) 3 months, and (3) 1 year after surgery. Each time behavioral tests of balance and upper limb motor function, ataxia rating, and a MRI scan were performed. Data were used for subsequent lesion-symptom mapping of cerebellar function. Behavioral improvements continued beyond 3 months, but were not complete in all patients after 1 year. At that time, remaining deficits were mild. Within the first 3 months, cerebellar lesion volumes were notably reduced by vanishing edema. Reduction in edema affecting the deep cerebellar nuclei but not reduction of total cerebellar lesion volume was a major predictor of early functional recovery. Persistent impairment in balance and upper limb function was linked to permanent lesions of the inferior vermis and the deep cerebellar nuclei.

Current advances in lesion-symptom mapping of the human cerebellum.

While high-resolution structural magnetic resonance imaging (MRI) combined with newer analysis methods has become a powerful tool in human cerebral lesion studies, comparatively few studies have used these advanced imaging techniques to study lesions of the human cerebellum and their associated symptoms. This review will summarize the methodology of MRI-based lesion-symptom mapping of the human cerebellum and discuss its potential for gaining insights into cerebellar function. The investigation of patients with defined focal lesions yields the greatest potential for obtaining meaningful correlations between lesion site and behavioral deficits. In smaller groups of patients overlay plots and subtraction analysis are good options. If larger groups of patients are available, different statistical techniques have been introduced to compare behavior and lesion site on a voxel-by-voxel basis. Although localization in degenerative cerebellar disorders is less accurate because of the diffuse nature of the disease, certain information about the supposed function of larger subdivisions of the cerebellum can be gained. Examples are given which show that lesion-symptom mapping allows to investigate the function of the intermediate zone and cerebellar nuclei. We conclude that meaningful correlations between lesion site and behavioral data can be obtained in patients with degenerative as well as focal cerebellar disorders.

Lesion-symptom mapping of the human cerebellum.

High-resolution structural magnetic resonance imaging (MRI) has become a powerful tool in human cerebellar lesion studies. Structural MRI is helpful to analyse the localisation and extent of cerebellar lesions and to determine possible extracerebellar involvement. Functionally meaningful correlations between a cerebellar lesion site and behavioural data can be obtained both in subjects with degenerative as well as focal cerebellar disorders. In this review, examples are presented which demonstrate that MRI-based lesion-symptom mapping is helpful to study the function of cerebellar cortex and cerebellar nuclei. Behavioural measures were used which represent two main areas of cerebellar function, that is, motor coordination and motor learning. One example are correlations with clinical data which are in good accordance with the known functional compartmentalisation of the cerebellum in three sagittal zones: In patients with cerebellar cortical degeneration ataxia of stance and gait was correlated with atrophy of the medial (and intermediate) cerebellum, oculomotor disorders with the medial, dysarthria with the intermediate and limb ataxia with atrophy of the intermediate and lateral cerebellum. Similar findings were obtained in patients with focal lesions. In addition, in patients with acute focal lesions, a somatotopy in the superior cerebellar cortex was found which is in close relationship to animal data and functional MRI data in healthy control subjects. Finally, comparison of data in patients with acute and chronic focal lesions revealed that lesion site appears to be critical for motor recovery. Recovery after lesions to the nuclei of the cerebellum was less complete. Another example which extended knowledge about functional localisation within the cerebellum is classical conditioning of the eyeblink response, a simple form of motor learning. In healthy subjects, learning rate was related to the volume of the cortex of the posterior cerebellar lobe. In patients with focal cerebellar lesions, acquisition of eyeblink conditioning was significantly reduced in lesions including the cortex of the superior posterior lobe, but not the inferior posterior lobe. Disordered timing of conditioned eyeblink responses correlated with lesions of the anterior lobe. Findings are in good agreement with the animal literature. Different parts of the cerebellar cortex may be involved in acquisition and timing of conditioned eyeblink responses in humans. These examples demonstrate that MRI-based lesion-symptom mapping is helpful to study the contribution of functionally relevant cerebellar compartments in motor control and recovery in patients with cerebellar disease. In addition, information about the function of cerebellar cortex and nuclei can be gained.

Increased basal-ganglia activation performing a non-dystonia-related task in focal dystonia.

BACKGROUND AND PURPOSE: We tried to determine whether altered sensorimotor cortex and basal-ganglia activation in blepharospasm (BSP) and cervical dystonia (CD) are restricted to areas directly responsible for the innervation of dystonic muscles, or whether impairment in focal dystonia reaches beyond these direct associations supporting a more global disturbance of sensory and motor control in focal dystonia. METHODS: Twenty patients with focal dystonia (11 BSP, 9 CD) and 14 healthy controls were investigated with functional magnetic resonance imaging (fMRI) performing a simple grip force forearm contraction task. RESULTS: BSP and CD patients and healthy controls showed similar activation in the pre-motor, primary motor and primary sensory cortex, whilst basal-ganglia activation was increased in BSP and CD with related activation patterns compared with controls. BSP patients had increased activation in the thalamus, caudate nucleus, putamen and lateral globus pallidus, whilst CD patients showed increased activation in the caudate nucleus, putamen and thalamus. No differences in applied grip force were detected between groups. CONCLUSIONS: In both, BSP and CD, increased basal-ganglia activation could be demonstrated in a task not primarily involving the dystonic musculature affected by these disorders. Comparable activation changes may also indicate a common pathway in the pathophysiology in BSP and CD.

Impact of surgery and adjuvant therapy on balance function in children and adolescents with cerebellar tumors.

OBJECTIVES: This study examined the effects of posterior fossa tumor surgery and concomitant irradiation and/or chemotherapy on the long-term recovery of balance function in children and adolescent patients. SUBJECTS AND METHODS: 22 patients, treated during childhood for a benign (n = 14) or malignant cerebellar tumor (n = 8), were examined in chronic state (mean latency between surgery and testing: 7.7 years, range 3 - 17 years). Postural impairments were assessed with static and dynamic posturography. All cerebellar lesions were documented by standardized and normalized MRI data. Healthy age- and gender-matched subjects served as a control group. RESULTS: Comparing the balance function of (i) children with or without affected cerebellar nuclei and (ii) children with and without adjuvant chemotherapy and/or radiotherapy revealed that damage to the cerebellar nuclei had more impact on neurological impairment than concomitant tumor therapy. Balance abnormalities were most pronounced when a lesion affected the fastigial nucleus. Chemotherapy with its neurological side effect was associated with enhanced postural sway in only two children with malignant tumors. CONCLUSIONS: The study results indicate that the sparing of the deep cerebellar nuclei had the greatest impact on the recovery of balance function in pediatric patients treated for both a benign or malignant cerebellar tumor.

The effect of subthalamic nucleus stimulation on kinaesthesia in Parkinson's disease.

BACKGROUND: Parkinson's disease is accompanied by deficits in passive motion and limb position sense. OBJECTIVE: To investigate whether deep brain stimulation of the subthalamic nucleus (STN-DBS) reverses these proprioceptive deficits. METHODS AND RESULTS: A passive movement task was applied to nine patients with Parkinson's disease and bilateral chronic STN-DBS and to seven controls. Thresholds for 75% correct responses were 0.9 degrees for controls, 2.5 degrees for Parkinson's disease patients when stimulation was OFF, and 2.0 degrees when stimulation was ON. CONCLUSIONS: STN-DBS improves kinaesthesic deficits in Parkinson's disease, but does not lead to a full recovery of proprioceptive function.

Predicting children's overarm throw ball velocities from their developmental levels in throwing.

This study examined the movement process-product relationship from a developmental perspective. The authors used multiple regression to investigate the changing relationship between qualitative movement descriptions of the overarm throw and the throwing outcome, horizontal ball velocity. Seventeen girls and 22 boys were filmed longitudinally at ages 6, 7, 8, and 13 years. Their movements were assessed using Roberton's (Roberton & Halverson, 1984) developmental sequences for action of the humerus, forearm, trunk, stepping, and stride length. The sequences accounted for 69-85% (adjusted) of the total velocity variance each year. The components that best predicted ball velocity changed over time, although humerus or forearm action always accounted for considerable variance. Gender was a good predictor of ball velocity, but if the developmental descriptions were entered first in a stepwise regression, gender then explained no more than 2% additional variance.