Antonio Currà

The clinical diagnostic utility of transcranial magnetic stimulation: Report of an IFCN committee

The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimers disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.

Facilitation of muscle evoked responses after repetitive cortical stimulation in man

Abstract The technique of repetitive transcranial magnetic stimulation (rTMS) allows cortical motor areas to be activated by trains of magnetic stimuli at different frequencies and intensities. In this paper, we studied long-term neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an intensity of 120% of motor threshold. Each stimulus of the train produced muscle-evoked potentials (MEPs) in hand and forearm muscles, which gradually increased in size from the first to the last shock. After the end of the train, the response to a single-test stimulus remained enhanced for 600–900 ms. In contrast, the train had no effect on the size of the MEPs evoked by transcranial electrical stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We conclude that rTMS of these parameters increases the excitability of the motor cortex and that this effect outlasts the train for almost 1 s. At the spinal level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible for the H-reflex.

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia.

To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure‐of‐eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50–100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms. Ann Neurol 2000;48:20–26

Transcranial magnetic stimulation techniques in clinical investigation

Transcranial magnetic stimulation (TMS) is a technique that can activate cortical motor areas and the corticospinal tract without causing the subject discomfort. Since TMS was introduced, numerous applications of the technique have been developed for the evaluation of neurologic diseases. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of motor conduction in the CNS. Conduction studies provide specific information in neurologic conditions characterized by clinical and subclinical upper motor neuron involvement. In addition, they have proved useful in monitoring motor abnormalities and the recovery of motor function. TMS also gives information on the pathophysiology of the processes underlying the various clinical conditions. More complex TMS applications (paired-pulse stimulation, silent period, ipsilateral silent period, input-output curve, and evaluation of central fatigue) allow investigation into the mechanisms of diseases causing changes in the excitability of cortical motor areas. These techniques are also useful in monitoring the effects of neurotrophic drugs on cortical activity. TMS applications have an important place among the investigative tools to study patients with motor disorders.

Pathophysiology of chorea and bradykinesia in Huntington's disease

This article reviews the neurophysiological abnormalities described in Huntingtons disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median‐nerve somatosensory‐evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long‐latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntingtons disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntingtons disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntingtons disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntingtons disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntingtons disease probably reflect the involvement of direct and indirect pathways in the basal ganglia–thalamus–cortical motor circuit.

Ovarian hormones and cortical excitability. An rTMS study in humans

OBJECTIVE Ovarian steroids influence neural excitability. Using repetitive transcranial magnetic stimulation (rTMS) we investigated changes in cortical excitability during the menstrual cycle. METHODS Eight women underwent rTMS on Days 1 and 14 of the menstrual cycle. As a control group, 8 age-matched men were also tested twice, with a 14-day interval between the two experimental sessions. Repetitive magnetic pulses were delivered in trains of 10 stimuli (5 Hz frequency and 120% of the motor threshold calculated at rest) to the left motor area of the first dorsal interosseous muscle. RESULTS In women, the motor evoked potential (MEP) size did not increase on Day 1, but it increased progressively during the train on Day 14. The duration of the silent period progressively lengthened during the train on both days. In men the MEP increased in size, and the silent period lengthened to a similar extent on both days. CONCLUSIONS In women, hormone changes related to the menstrual cycle alter cortical excitability. SIGNIFICANCE Low estrogen levels probably reduce cortical excitability because their diminished action on sodium channels reduces recruitment of excitatory interneurons during rTMS thus abolishing the MEP facilitation.

Central effects of botulinum toxin type A: Evidence and supposition

No convincing evidence exists that botulinum toxin type A (BT‐A) injected intramuscularly at therapeutic doses in humans acts directly on central nervous system (CNS) structures. Nevertheless, several studies, using various approaches, strongly suggest that BT‐A affects the functional organization of the CNS indirectly through peripheral mechanisms. By acting at alpha as well as gamma motor endings, BT‐A could alter spindle afferent inflow directed to spinal motoneurons or to the various cortical areas, thereby altering spinal as well as cortical mechanisms. Muscle afferent input is tightly coupled to motor cortical output, so that the afferents from a stretched muscle go to cortical areas where they can excite neurons capable of contracting the same muscle. The BT‐A–induced reduction in spindle signals could, therefore, alter the balance between afferent input and motor output, thereby changing cortical excitability.

Pathophysiology of tics and Tourette syndrome

Abstract.Tics are involuntary movements that can affect one or more muscles producing simple or complex movements. Blink reflex and startle reflex studies disclose an increased excitability of brainstem interneurons. Analysis of voluntary movement shows that when advance visual information is reduced, patients with tics and Tourette syndrome become progressively slower in completing motor sequences. Sensorimotor integration is abnormally processed. Studies of the contingent negative variation demonstrate abnormalities of movement preparation and the investigation of premotor potentials shows that in some patients tics are not preceded by a normal premotor potential. Magnetic stimulation studies demonstrate an increased excitability of cortical motor cortex. Functional MRI, PET and SPECT studies show abnormal activation of cortical and subcortical areas. Dysfunction of basal ganglia-thalamo-cortical projections affects sensorimotor, language and limbic cortical circuits, and may explain why patients with Tourette syndrome have difficulty in inhibiting unwanted behaviors and impulses.

Effects of repetitive cortical stimulation on the silent period evoked by magnetic stimulation

Abstract The effects of repetitive transcranial stimulation (rTMS) on brain activity remain unknown. In healthy subjects, we studied the effects of rTMS on the duration of the cortical silent period (SP). Repetitive stimuli were delivered with a Cadwell High Speed Magnetic Stimulator and a figure-of-eight coil placed over the hand motor area. rTMS was delivered in trains of 11 or 20 stimuli at frequencies of 3 and 5 Hz and at stimulation intensities of 110 and 120% of motor threshold. The SP was recorded from the forearm muscles during a voluntary contraction (20% of maximum effort). rTMS delivered at a frequency of 3 and 5 Hz and intensities of 110 and 120% motor threshold prolonged the duration of the SP, without modifying either the size or the latency of the muscle-evoked potentials (MEP). A conditioning train of 11 stimuli at 3 Hz had no effect on the duration of the SP evoked by a single magnetic shock delivered 600 ms after the train. These findings show that rTMS increases the duration of the cortical SP, but does so only during the train of stimuli. rTMS probably changes the duration of the SP by facilitating cortical inhibitory interneurons.

Impairment of individual finger movements in Parkinson's disease

By analyzing the kinematics of repetitive, constant‐amplitude, finger oppositions, we compared the impairment of individual and nonindividual finger movements in patients with Parkinsons disease. In one task, subjects tapped only the index finger against the thumb (individual oppositions); in the other task, they tapped all four fingers together against the thumb pad (nonindividual oppositions). We used an optoelectronic motion analysis system to record movements in three‐dimensional space and recorded three 5‐second trials for each task. We counted how many finger oppositions subjects performed during each trial and measured the duration and amplitude of the flexions and extensions. We also calculated the duration of the pauses after flexion and extension. We assessed the deterioration of motor performance in patients by investigating the changes in speed and amplitude with task completion. During both tasks, normal subjects and patients performed finger flexions faster than extensions, and they invariably paused longer after flexion than after extension. Patients performed individual and nonindividual finger movements slowly and with reduced amplitude. Patients were disproportionately slow during flexion and in switching from flexion to extension. Movement slowness increased as finger oppositions progressed but predominantly when patients had to move fingers individually. In conclusion, in patients with Parkinsons disease, the motor performance deteriorated with task completion more during individual than during nonindividual finger movements. Parkinsons disease, therefore, impairs individual finger movements more than gross hand movements. This distinction reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output.