V. Mall

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.

Treatment of adductor spasticity with BTX-A in children with CP: a randomized, double-blind, placebo-controlled study

Adductor spasticity in children with cerebral palsy (CP) impairs motor function and development. In a placebo‐controlled, double‐blind, randomized multicentre study, we evaluated the effects of botulinum toxin A(BTX‐A) in 61 children (37 males, 24 females; mean age 6 years 1 month [SD 3y 1mo]) with CP (leg‐dominated tetraparesis, n=39; tetraparesis, n=22; GMFCS level I, n=3; II, n=6; III, n=17; IV, n=29; V, n=6). Four weeks after treatment, a significant superiority of BTX‐A was observed in the primary outcome measure (knee‐knee distance ‘fast catch’, p=0.002), the Ash worth scale (p=0.001), and the Goal Attainment Scale (p=0.037).

Two types of exercise-induced neuroplasticity in congenital hemiparesis: a transcranial magnetic stimulation, functional MRI, and magnetoencephalography study

Early unilateral brain lesions can lead to a persistence of ipsilateral corticospinal projections from the contralesional hemisphere, which can enable the contralesional hemisphere to exert motor control over the paretic hand. In contrast to the primary motor representation (M1), the primary somatosensory representation (S1) of the paretic hand always remains in the lesioned hemisphere. Here, we report on differences in exercise‐induced neuroplasticity between individuals with such ipsilateral motor projections (ipsi) and individuals with early unilateral lesions but ‘healthy’ contralateral motor projections (contra).

Clinical impact of antibody formation to botulinum toxin A in children

We studied the clinical impact of neutralizing antibodies to botulinum toxin A that occurred during long‐term treatment of children between 1993 and 2001. Antibodies were found in high titers in 35 of 110 (31.8%) samples from individual patients. Antibody formation correlated with secondary nonresponse (p < 0.001). The most significant risk factors for antibody formation were the frequency of treatments (p = 0.0001) and the injection of a higher weight‐adapted maximum dose per treatment (p = 0.001).

Occlusion of bidirectional plasticity by preceding low-frequency stimulation in the human motor cortex.

OBJECTIVE Low-frequency stimulation, which does not induce long-term potentiation (LTP) or long-term potentiation (LTD) by itself, suppresses consecutive LTP or LTD induction in vitro. We tested whether a similar interaction occurs in the human motor cortex. METHODS LTP- or LTD-like plasticity was induced using paired associative stimulation (PAS) with 25 and 10 ms interstimulus interval and conditioned by suprathreshold repetitive transcranial magnetic stimulation (rTMS) at a frequency of 0.1Hz. RESULTS RTMS completely abolished the significant increase of motor-evoked potential (MEP) amplitudes after PAS(25 ms) (PAS(25 ms) only: 1.05+/-0.14 to 1.76+/-0.66 mV, p=0.001; rTMS+PAS(25 ms): 1.08+/-0.18 to 1.02+/-0.44 mV, n.s.) and also abolished the significant decrease of MEP amplitudes after PAS(10 ms) (PAS(10 ms) only: 1.00+/-0.14 to 0.73+/-0.32 mV; rTMS+PAS(10 ms): 1.15+/-0.35 to 1.25+/-0.43 mV, p=0.006). RTMS alone did not significantly alter MEP amplitudes but increased SICI and LICI. CONCLUSIONS Low frequency stimulation increases intracortical inhibition and occludes LTP- and LTD-like plasticity in the human motor cortex. SIGNIFICANCE This finding supports the concept that metaplasticity in the human motor cortex follows similar rules as metaplasticity in in vitro experiments.

Evaluation of botulinum toxin A therapy in children with adductor spasm by gross motor function measure.

Intramuscular injection of botulinum neurotoxin A is a relatively new method for treating spastic movement disorders in children. One major goal of any therapy for patients with movement disorders is to improve gross motor function. In this study, 18 patients with adductor spasm were treated with botulinum neurotoxin A. Treatment effect was determined with the Gross Motor Function Measure, a standardized, validated instrument designed to assist in assessment of gross motor function. Spastic muscle hyperactivity and joint mobility were evaluated by the modified Ashworth Scale and by range of motion, respectively. Compared to pretreatment values, significant improvement in gross motor function ( P < .010), decrease in the modified Ashworth Scale, and increase in the range of motion (P < .010) were achieved. Patients with moderate impairment of gross motor function (classed at level III and level IV in the Gross Motor Function Classification System) benefited most from treatment. In patients with severe handicap (level V), only one of five treated patients showed improvement in gross motor function. Nevertheless, all patients in this subgroup benefited from improved ease in hygienic care. In conclusion, we have demonstrated that for most children with moderate functional impairment, the Gross Motor Function Measure is a useful instrument for objective documentation of improvements of gross motor function following treatment with botulinum neurotoxin A. (J Child Neurol 2000;15:214-217).

Validation of the Gross Motor Function Measure for Use in Children and Adolescents With Traumatic Brain Injuries

OBJECTIVES. Motor function recovery is a key goal during rehabilitation of children and adolescents with traumatic brain injury. To evaluate how well treatment strategies improve motor function, we need validated outcome measures that are responsive to change in pediatric patients with traumatic brain injury. The Gross Motor Function Measure has demonstrated excellent psychometric properties in children with cerebral palsy and Down syndrome, yet its responsiveness in patients with pediatric traumatic brain injury has not been proven irrefutably. Our aim was to validate the Gross Motor Function Measure for this patient group. METHODS. Seventy-three patients (mean age: 11.4 years; range: 0.8–18.9 years) with moderate-to-severe traumatic brain injury were recruited in 12 rehabilitation centers and assessed twice with the Gross Motor Function Measure-88 over 4 to 6 weeks. As an external standard, we used judgements of change made independently by parents, physiotherapists, and 2 video assessors who were not familiar with the patients. We formulated and statistically investigated a priori hypotheses of how Gross Motor Function Measure change scores would correlate with those judgements of change. Both Gross Motor Function Measure versions, the original Gross Motor Function Measure-88 and the more recently developed Gross Motor Function Measure-66, were evaluated. RESULTS. Both Gross Motor Function Measure change scores correlated significantly with all of the clinical judgements of change. The degree of correlation that we postulated, that the Gross Motor Function Measure change score would correlate highest with the video rating followed by physiotherapists and parents, was fully confirmed by the Gross Motor Function Measure-88 and largely confirmed by the Gross Motor Function Measure-66. Both Gross Motor Function Measure versions revealed convincing discriminative capability. Test-retest reliability was excellent. CONCLUSIONS. We demonstrate convincing evidence of responsiveness and validity to support the use of both Gross Motor Function Measure versions as evaluative measures of gross motor function in children and adolescents with traumatic brain injury.

Changes in Soleus H-Reflex Modulation after Treadmill Training in Children with Cerebral Palsy.

In healthy children, short latency leg muscle reflexes are profoundly modulated throughout the step cycle in a functionally meaningful way and contribute to the electromyographic (EMG) pattern observed during gait. With maturation of the corticospinal tract, the reflex amplitudes are depressed via supraspinal inhibitory mechanisms. In the soleus muscle the rhythmic part of the modulation pattern is present in children with cerebral palsy (CP), but the development of tonic depression with increasing age, as seen in healthy children, is disturbed. Treadmill training clinically improves the walking pattern in children with CP. Presuming that short latency reflexes contribute significantly to the walking pattern, a change in the modulation may occur after training. The aim of this study was to assess whether treadmill training also improves the soleus reflex modulation during gait in children with CP. Seven children with CP underwent brief treadmill training for 10 min a day over 10 consecutive days; all of them were functional walkers. Soleus Hoffmann (H-) reflexes were investigated during walking on a treadmill before the first, and one day after the last, training session. Treadmill training led to a considerable clinical improvement in gait velocity. After 10 days of training, soleus H-reflexes during gait were almost completely depressed during the swing phase. The complete suppression of the soleus H-reflex during the swing phase, which is also exhibited by healthy subjects, could reflect an improvement towards a functionally more useful pattern. In conclusion, treadmill training can induce changes in the modulation of short latency reflexes during gait.

Absence of transcallosal inhibition in adolescents with diplegic cerebral palsy.

The role of intracortical organization in the pathophysiology of cerebral palsy (CP) is not clear. We used transcranial magnetic stimulation to investigate the paradigm of transcallosal inhibition (TI) in a group of adolescent patients with diplegic CP (n = 4), hereditary spastic paraplegia (n = 2), and healthy control adolescents (n = 4). None of the patients with CP showed TI, whereas all other subjects had normal TI. These findings indicate a lack of inhibitory control of the motor cortex in CP.

Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option.

Abstract Intramuscular injections of botulinum toxin type A (BTX-A) have increasingly been used to reduce spasticity in specific muscle groups in children with cerebral palsy. Targets of therapeutic efforts are improvement of gross motor function, alleviation of pain or facilitation of hygienic care. Placebo-controlled studies have shown the local and functional effectiveness of BTX-A for the treatment of dynamic pes equinus. Whether long-term treatment with BTX-A improves motor development and delays contractures is still under investigation.