Non-invasive cerebellar stimulation--a consensus paper.

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

Intracortical inhibition of the motor cortex in Segawa disease (DYT5).

BACKGROUND: Segawa disease (autosomal dominant guanosine triphosphate cyclohydrolase I [GTP-I] deficiency, DYT5) is a hereditary dopa-responsive generalized dystonia. OBJECTIVE: To investigate the pathophysiologic mechanisms for dystonia in Segawa disease, we studied intracortical inhibition of the primary motor cortex in patients with Segawa disease. METHODS: We studied 9 patients with Segawa disease (8 genetically confirmed patients and 1 with abnormally low GTP-I activity) and 12 age-matched normal control subjects. We studied the active motor threshold (AMT) using single pulse transcranial magnetic stimulation (TMS) and the short-interval intracortical inhibition (SICI) of the motor cortex using the previously reported paired pulse TMS method. Responses were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. RESULTS: The AMT was not significantly different between the patients and normal subjects. For both studied muscles, in Segawa disease, normal amount of SICI was evoked at interstimulus intervals (ISIs) of 1 to 4 msec even though they had dystonia in those muscles. CONCLUSION: Normal SICI of the motor cortex in Segawa disease stands in remarkable contrast to the previously reported reduction of SICI in focal dystonia. This suggests that the gamma-aminobutyric acid A system of the motor cortex is intact in Segawa disease. The pathophysiologic mechanisms for dystonia must be partly different between Segawa disease and focal dystonia.

[Transcranial magnetic stimulation (TMS) in movement disorders].

Transcranial magnetic stimulation (TMS) has been used to study several aspects of movement disorders: central motor conduction time (CMCT), electromyographic (EMG) silence evoked by TMS, reset of tremor rhythm by TMS, GABAergic inhibitory interneuronal function of the motor cortex studied with paired-pulse TMS. In this communication, We briefly summarize results of paired-pulse TMS in movement disorders. NORMAL SUBJECTS: A subthreshold conditioning stimulus over the motor cortex reduced the size of EMG responses to a succeeding suprathreshold test stimulus given to the same motor cortex. This inhibition is considered to be an inhibitory effect on the motor cortex because the same conditioning stimulus has no influence on H-reflexes or electrical cortical responses. Pharmacological effects on this inhibition suggested that it is mediated by GABAergic inhibitory systems in the motor cortex. PATIENTS: The cortical inhibition was reduced in cortical myoclonus, which is consistent with the notion that the studied effect is mediated by GABAergic systems. The inhibition was disturbed in focal dystonia, whereas normal inhibition was elicited in Segawa's disease. Reduced inhibition was seen in Parkinson's disease (PD), whereas normal inhibition in essential tremor. Normal inhibition was evoked in all patients with chorea. Abnormal inhibition in basal ganglia disorders must reflect damaged movement selection in the motor cortex secondary to the primary lesion in the basal ganglia. This abnormality occurs in some movement disorders and does not occur in the others, which indicates different pathomechanisms for involuntary movements. It is conspicuous that normal inhibition was evoked in Segawa's disease even though the patients had dystonia.

Magnetic stimulation of the sacral roots for the treatment of stress incontinence: an investigational study and placebo controlled trial.

PURPOSE: We designed an investigational study and placebo controlled trial to evaluate the potential efficacy of magnetic stimulation of the sacral roots for the treatment of stress incontinence. MATERIALS AND METHODS: A total of 75 patients with stress incontinence were studied. A 15 Hz. repetitive magnetic stimulation of the sacral roots with 50% intensity output and duration of 5 seconds per minute was applied for 30 minutes. Urodynamic investigations under magnetic stimulation were performed in 13 patients to evaluate acute effects to lower urinary tract function. There were 62 women (mean age 58 years) enrolled in a placebo controlled study to investigate the short-term efficacy of magnetic stimulation. The number of leaks for 3 days, amount of urine loss on a pad test and quality of life score were evaluated before and 1 week after stimulation. RESULTS: The urodynamic investigations revealed an apparent elevation of urethral closure pressure induced by stimulation (mean 8.2 +/- 3.0 cm H2O, p = 0.0000004) and a significant increase in bladder capacity after stimulation (mean 40.0 +/- 51.0 ml., p = 0.0152). In the placebo controlled study the number of leaks and amount of urine loss on a pad test significantly decreased more in the active than in the sham stimulation group (p = 0.0023 and 0.0377, respectively). The quality of life score significantly improved in the active stimulation group (p = 0.0006) in contrast to no significant improvement in the sham stimulation group. The improvement rate in the active stimulation group was 74%, which was significantly higher than the 32% in the sham stimulation group (p = 0.0009). No adverse effects were noted in any patients. CONCLUSIONS: These results suggest that magnetic stimulation of the sacral roots may be useful for the treatment of stress incontinence. Further studies are needed to evaluate the long-term efficacy of this potential treatment.

The human hand motor area is transiently suppressed by an unexpected auditory stimulus.

OBJECTIVE: To study the effect of a loud auditory stimulus on the excitability of the human motor cortex. METHODS: Ten normal volunteers participated in this study. The size of responses to transcranial magnetic or electrical cortical stimulation (TMS or TES) given at different times (ISIs) after a loud sound were compared with those to TMS or TES alone (control response). Different intensities and durations of sound were used at several intertrial intervals (ITIs). In addition, we examined how the presence of a preceding click modulated the effect of a loud sound (prepulse inhibition). The incidence of startle response evoked by various stimuli was also studied. RESULTS: A loud auditory stimulus suppressed EMG responses to TMS when it preceded the magnetic stimulus by 30-60 ms, whereas it did not affect responses to TES. This suggests that the suppression occurred at a cortical level. Significant suppression was evoked only when the sound was louder than 80 dB and longer than 50 ms in duration. Such stimuli frequently elicited a startle response when given alone. The effect was not evoked if the ITI was 5 s, but was evoked when it was longer than 20 s. A preceding click reduced the suppression elicited by loud sounds. CONCLUSIONS: Auditory stimuli that produced the greatest effect on responses to TMS had the same characteristics as those which yielded the most consistent auditory startle. We suggest that modulation of cortical excitability occurs in parallel with the auditory startle and both may arise from the same region of the brain-stem.

Air-puff-induced facilitation of motor cortical excitability studied in patients with discrete brain lesions.

Air-puff stimulation applied to a fingertip is known to exert a location-specific facilitatory effect on the size of the motor evoked potentials elicited in hand muscles by transcranial magnetic stimulation. In order to clarify its nature and the pathway responsible for its generation, we studied 27 patients with discrete lesions in the brain (16, 9 and 2 patients with lesions in the cerebral cortex, thalamus and brainstem, respectively). Facilitation was absent in patients with lesions affecting the primary sensorimotor area, whereas it was preserved in patients with cortical lesions that spared this area. Facilitation was abolished with thalamic lesions that totally destroyed the nucleus ventralis posterolateralis (VPL), but was preserved with lesions that at least partly spared it. Lesions of the spinothalamic tract did not impair facilitation. The size of the N20-P25 component of the somatosensory evoked potential showed a mild correlation with the amount of facilitation. The facilitation is mainly mediated by sensory inputs that ascend the dorsal column and reach the cortex through VPL. These are fed into the primary motor area via the primary sensory area, especially its anterior portion, corresponding to Brodmann areas 3 and 1 (possibly also area 2), without involving other cortical regions. The spinothalamic tract and direct thalamic inputs into the motor cortex do not contribute much to this effect. Some patients could generate voluntary movements despite the absence of the facilitatory effect. The present method will enable us to investigate in humans the function of one of the somatotopically organized sensory feedback input pathways into the motor cortex, and will be useful in monitoring ongoing finger movements during object manipulation.

Suppression of motor cortical excitability by electrical stimulation over the cerebellum in ataxia.

We studied the effect of electrical stimulation over the cerebellum on electromyographic responses evoked by magnetic stimulation over the cerebral motor cortex in 41 normal volunteers and 32 patients with ataxia due to various disorders. In all the normal subjects, stimulation over the cerebellum significantly reduced the size of electromyographic response in the first dorsal interosseous muscle evoked by magnetic cortical stimulation, when the cerebellar stimulus preceded the cortical stimulus by 5, 6, and 7 msec. This suppression was absent or reduced in ataxic patients who had atrophy of the cerebellar hemispheres as demonstrated by magnetic resonance imaging and in patients with dysfunction of the cerebellothalamocortical pathway who had lesions in the superior cerebellar peduncle or in the motor thalamus. In contrast, suppression was normal in ataxic patients who had pontine lesions that affected the pontocerebellar afferent pathway to the cerebellum. Results were also normal in patients without cerebellar ataxia, such as those with Parkinson's disease, sensory ataxia, and cerebrovascular disease without ataxia. We conclude that electrical stimulation activates cerebellar structures that suppress motor cortical excitability through a cerebellothalamocortical pathway and that the afferent systems to the cerebellum make no or little contribution to the effect. The technique described here would be useful for distinguishing ataxia due to lesions of cerebellar afferent pathway from other types of cerebellar ataxia.

Results of endoscopic management of carpal tunnel syndrome.

This paper is a retrospective study of 27 women with carpal tunnel syndrome (39 hands) who underwent a new endoscopic operative procedure utilizing the Universal Subcutaneous Endoscope system developed by the lead author. Operations on 199 hands were performed under local anesthesia on an outpatient basis. The etiology was considered idiopathic in all cases. Complete preoperative and postoperative clinical and electrophysiologic data were analyzed in 39 hands. The follow-up period ranged from 12 to 45.8 months (mean, 18.3 months). Symptoms of sensory disturbances disappeared in an average of 20 weeks in all patients. Electrophysiologic studies showed definite improvement when compared with preoperative studies. No complications were recorded. Clinical and electrophysiologic results showed that the less-invasive management of carpal tunnel syndrome by endoscopy is safe and effective.

Magneto-electrical stimulation of central motor pathways compared with percutaneous electrical stimulation.

The central motor conduction to the relaxed muscles was studied in 30 normal volunteers using magneto-electrical stimulation (MES) of the central motor pathways. The results were compared with those obtained by the percutaneous electrical stimulation technique (PES) described previously. None of the cortical and spinal latencies (Lcor and Lsp, respectively) and the central motor conduction time were different between MES and PES in the upper limb muscles. In some lower limb muscles, however, the Lsps of MES were significantly shorter than those of PES. This was probably because the magnetic stimulation over the lumbar spinal column activated the motor roots at their exit from the spinal canal rather than the level of conus medullaris, at which activation occurs in the electrical stimulation.