Antonio Caronni

Botulinum toxin injections reduce associative plasticity in patients with primary dystonia.

Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long‐term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation‐evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short‐interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity.

Practice-related reduction of electromyographic mirroring activity depends on basal levels of interhemispheric inhibition

Paired‐pulse transcranial magnetic stimulation (TMS) is used to measure the excitability of interhemispheric inhibition (IHI) between the hand areas of the two motor cortices. It varies from person to person, and is highly predictive of individual differences in callosal anatomy (fractional anisotropy) and even motor behaviour, e.g. the amount of involuntary electromyographic (EMG) ‘mirroring’ in one hand during rapid contraction of the other. The present experiments tested whether it also predicts how well individuals can improve motor performance in a task involving the two hands. Healthy participants were given 100 trials to maximize the initial acceleration of a ballistic finger movement made with one hand while trying to maintain a tonic low level of EMG activity in the other hand. Initially, each movement was accompanied by additional unwanted EMG mirroring in the other hand. However, after practice, participants had on average increased acceleration by approximately one‐third without changing the amount of EMG mirroring in the contralateral hand; indeed, in some individuals EMG mirroring activity declined. TMS measures showed that there was an increase in corticospinal excitability in the trained hemisphere, but there was no change in the excitability of short‐ or long‐latency IHI from the trained to non‐trained hemisphere. Nevertheless, in each individual, the baseline (pre‐practice) excitability of short‐latency IHI was highly predictive (r = 0.65; P = 0.0019) of the change in EMG mirroring. The implication is that a physiological measure of brain excitability at rest can predict behaviour in response to training.

An unavoidable modulation? Sensory attention and human primary motor cortex excitability

The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task‐specific dystonia, widely lack laboratory‐based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation‐induced GABA‐related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use‐dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition.

Changes in cortical excitability and blood lactate after a fatiguing hand-grip exercise

Abstract Excitability of primary hand motor cortex (PHMC), evaluated with transcranial magnetic stimulation by using the “1 mV resting motor threshold” method, and capillary blood lactate were measured at the end, as well as 5 and 10 min after a fatiguing hand-grip exercise. The relation between blood lactate and the amplitudes of motor-evoked potentials showed a significant direct proportionality. Blood lactate seems to exert a protective role on PHMC against fatigue reduction during extremely intensive isometric exercises.

Mechanical and focal electrical stimuli applied to the skin of the index fingertip induce both inhibition and excitation in low-threshold flexor carpi radialis motor units.

It has been observed that mechanical stimulation of the skin of the index fingertip causes a weak short‐latency inhibition followed by a strong long‐lasting facilitation of the flexor carpi radialis (FCR) H‐reflex. Based on threshold and latency, these cutaneous reflexes are thought to be routed to motoneurons by parallel pathways. As recent studies have shown predominant inhibitory potentials in slow motoneurons and predominant excitatory potentials in faster ones, the question arises as to whether or not the two cutaneous pathways converge onto the same motoneuron. The poststimulus time histogram technique was used to investigate the changes in firing frequency of low‐threshold FCR motor units (MUs), induced by passive mechanical or focal electrical stimuli to the index skin. After gently tapping the finger pulp a small sharp inhibition appeared in 20 MUs. On average, inhibition started 10.2 ± 1.6 ms from the homonymous Ia monosynaptic effect, and its central delay was estimated to be 1.2 ± 1.6 ms. The subsequent facilitation, more consistent, had a mean latency of 13.5 ± 1.7 ms. Inhibition and excitation were statistically significant (P < 0.05). A similar biphasic effect was observed in seven other FCR‐MUs, also after focal electrical stimulation of the same skin area. Comparison with the time course of the H‐reflex, representing the whole population of MUs, showed striking similarities in time course and latency to the present MU effect. It is thus suggested that cutaneous spinal pathways may have a homogeneous distribution within the FCR motoneuron pool, and that the skewed distribution of cutaneous afferents onto motoneurons should be not taken as a rule.

ISYQOL: a rasch-consistent questionnaire for measuring health-related quality of life in adolescents with spinal deformities

BACKGROUND CONTEXT Spinal deformities are commonly associated with poor health-related quality of life (HRQOL). Several questionnaires (eg, Scoliosis Research Society-24 [SRS-24] and Scoliosis Research Society-22 [SRS-22]) have been developed to evaluate HRQOL in these conditions. In adults as well as during growth, the HRQOL is considered one of the most relevant outcomes of both conservative and surgical treatments. Rasch analysis is a powerful statistical technique for developing high-quality and valid questionnaires. The SRS-24 and SRS-22 have been evaluated using the Rasch analysis but showed poor measurement properties. Thus, a proper measure of HRQOL in people with a spine condition is still missing. PURPOSE This study aimed to develop a new questionnaire that is totally Rasch consistent for measuring the HRQOL in young people with a spine condition. STUDY DESIGN This is a cross-sectional study for developing a new HRQOL measure. PATIENT SAMPLE A total of 402 participants with adolescent idiopathic scoliosis or Scheuermann juvenile kyphosis were included in the study. OUTCOME MEASURE The outcome measure used was the Italian Spine Youth Quality of Life (ISYQOL) questionnaire. MATERIALS AND METHODS The study consisted of different stages: a conventional approach content analysis, an opinion poll among clinicians trained in spine deformities, and the Rasch analysis (partial credit model). RESULTS The Rasch analysis showed that all items of the ISYQOL questionnaire had ordered thresholds and a good fit to the model. Differential item functioning was present for Item 1, with bracing only, and was solved with a conventional items splitting procedure. The ISYQOL item map spans an adequate range of HRQOL. The principal component analysis for Rasch residuals showed, in practical terms, the ISYQOL unidimensionality. The reliability of ISYQOL was high enough so that approximately three significantly different levels of HRQOL could be discerned. Two questionnaire versions were provided for patients with and without the brace, respectively. CONCLUSIONS ISYQOL is the first HRQOL questionnaire developed according to the Rasch analysis. It was developed in a conservative treatment setting for all types of spinal deformities, including also patients with surgical curves. Validation in many languages is already under way.

Is my patient actually getting better? Application of the McNemar test for demonstrating the change at a single subject level

Abstract Purpose: The aim of the current work is to provide a novel method for demonstrating the modification of a single patient’s performance on questionnaires and scales. The minimal detectable change (MDC), a statistics indicating the minimal change in measure not attributable to random variation, is commonly used in rehabilitation for this purpose. However, the MDC has some important drawbacks (e.g. it cannot be calculated on scores from ordinal tests and it can be only used for full questionnaire). Method: Review of the MDC and its limitations and application of the McNemar test on simulated data from single subjects. Results: We propose to use the McNemar test to check if the proportion of test items affirmed by a patient after rehabilitation is significantly different from the same proportion before rehabilitation. A significant McNemar test would indicate a non-random modification of the patient’s score and thus a true modification of his/her performance. Conclusions: The application of the McNemar test to questionnaires and scales offers a simple method for demonstrating the modification of a single patient’s performance. This use of the McNemar test overcomes the weaknesses of the MDC and gives support to the clinician in assisting him/her to convincingly communicate a non-negligible modification of the patient’s status. IMPLICATIONS FOR REHABILITATION Measuring the change in patients’ status is of paramount importance in medicine and rehabilitation. However, tracking the change in rehabilitation is difficult. For example, the minimal detectable change cannot be calculated on scores from ordinal questionnaires and tests, which are widely used as rehabilitative outcome measures. We propose here to use a McNemar test to check if the proportion of test items affirmed or passed by is significantly different between two conditions (e.g. before vs. after rehabilitation). Similar to the minimal detectable change, the significant McNemar test would indicate a non-random modification of the patient’s test score. In addition, the McNemar test can be calculated on ordinal data, thus overcoming some of the minimal detectable change weaknesses.

Criterion validity of the instrumented timed up and go test: a partial least square regression study

The Timed Up and Go (TUG) test is a common mobility measure in rehabilitation. With the instrumental TUG test (ITUG; i.e. the TUG measured by inertial measurement units, IMUs), several movement measures are newly available. However, the clinical meaning of these new measures is not totally clear. Aim of the current work is to evaluate the validity of different ITUG parameters as a measure of balance. Neurological patients (n = 122; 52 females; 89 older than 65 years) completed the TUG test with IMUs secured to their back. IMUs signals were used to split the TUG test in five phases (sit-to-stand, walk1, turn1, walk2 and turn-and-sit) and twelve movement parameters were obtained. Experienced clinicians administered the Mini-BESTest (MB) scale, a sound balance measure. The partial least square regression (PLSR) was used to explore the association between the ITUG variables and the MB measure. A PLSR model with twelve ITUG variables had satisfactory fit parameters (RMSEP: 11%; R2: 0.41, 95% CI: 0.28-0.54; regression line: 1, 95% CI: 0.78-1.22). Three ITUG variables (i.e. turn1 vertical angular velocity, turn1 duration and turn2 vertical angular velocity) were found to be the most important predictors of the MB measure. A PLSR model with the turning variables only had fit parameters comparable to that of the twelve variables model. Turning parameters from the TUG test are good predictors of the MB scale. The mean angular velocity during turning and the duration of the turning phase are thus proposed as a valid, ratio-level measures of balance in neurological patients.