Antispastic Effect of Transcranial Magnetic Stimulation in Patients With Cerebral and Spinal Spasticity (ANTMS)
|First Received Date ICMJE||February 5, 2013|
|Last Updated Date||November 5, 2014|
|Start Date ICMJE||February 2013|
|Estimated Primary Completion Date||September 2015 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01786005 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||The patient is discharged from clinic [ Time Frame: 20 days ] [ Designated as safety issue: No ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE
||Pregnancy [ Time Frame: 20 days ] [ Designated as safety issue: No ]|
|Original Other Outcome Measures ICMJE||Same as current|
|Brief Title ICMJE||Antispastic Effect of Transcranial Magnetic Stimulation in Patients With Cerebral and Spinal Spasticity|
|Official Title ICMJE||Antispastic Effect of Transcranial Magnetic Stimulation in Patients With Cerebral and Spinal Spasticity|
|Brief Summary||Spasticity - movement disorder, which is part of the syndrome of defeat top motor-neuron, characterized by the rate-dependent increase in muscle tone and increased dry-core reflections from hyperexcitability of stretch receptors (Lance, 1980). Spasticity - a frequent symptom of neurological diseases (Valero-Cabre, Pascual-Leone, 2005) and may be accompanied by such a disorders consequences of stroke, multiple sclerosis, head trauma and spinal cord, cerebral palsy, etc. The magnitude and severity of spasticity depends on the level of the lesion, the duration of its existence from the time before the disease, and possible plastic changes in axons and synapses on the affected level. There are two basic models of spasticity: cerebral (hemiplegic) and spinal (paraplegicheskaya) (Nikitin, 2005). Cerebral model appears with the direct injury of the brain and is characterized by increased excitability of monosynaptic reflexes with the rapid development of pathological ref-plexes and characteristic hemiplegic posture. Model is characterized by spinal spasticity opposite lower segmental inhibition polysynaptic reflexes slow increase of nervous excitability due to the mechanism of cumulative excitation perevozbuzhdeniem flexor and razgibate-ing, as well as expansion of the area of segmental responses (Nikitin, 2005). As spinal and cerebral spasticity are extremely difficult corrected by standard medical clinic and physiotherapy methods. In this regard, in the world literature actively searched for addi-tional search correct this symptom. A new modern methods that could affect the syndrome of spasticity is rhythmic transcranial magnetic stimulation (Mori et al., 2009).|
Spasticity associated with excessive activation of the stretch reflex, the second occurs when the upper motor neuron injury (Young, 1994), which leads to a reduction of spinal inhibition, manifested in the reduction of presynaptic inhibition of Ia afferents coming from muscle spindles flexor (Nielsen et al., 1995 ) and disinapticheskogo reciprocal Ia inhibition of antagonist muscle afferents (Meunier and Pierrot-Deseilligny, 1998; Nielsen et al., 2007), abnormal activity of Ib afferents from tendon Golgi complex (autogenous Ib inhibition), resulting in relief instead of inhibiting alpha-motoneurons ( Delwaide and Olivier, 1988), the deterioration of motor neurons inhibit rekkurentnogo Renshaw cells (Katz and Pier-rot-Deseilligny, 1982, 1999).
There are two basic models of spasticity: cerebral (hemiplegic) and spinal (paraplegicheskaya) (Nikitin, 2005). Cerebral model shines through direct injury of the brain and is characterized by increased excitability of the monosynaptic reflexes with quick reflexes and the development of pathological characteristic hemiplegic posture. Model is characterized by spinal spasticity opposite lower segmental inhibition polysynaptic reflexes slow increase of nervous excitability due to the mechanism of cumulative excitation overexcitation of the flexor and extensor muscles, as well as expansion of the area of segmental responses (Nikitin, 2005). According to recent studies the mechanisms of cerebral and spinal spasticity are different.
According to most researchers increased activity (excitability) of the motor cortex can increase the inhibitory effect of the corticospinal tract and reduce hyperactivity gamma and alpha motor neurons (Valero-Cabre, Pascual-Leone, 2005; Valero-Cabre et al., 2001; Valle et al. , 2007). According to this statement is a special place in the methods of correction of spasticity can take neuromodulation techniques, one of which is a rhythmic transcranial magnetic stimulation (RTMS). In the widely discussed mechanisms of action RTMS to reduce spasticity, explaining its efficacy in MS, spinal cord injury, stroke and cerebral palsy (Nielsen et al., 1996; Kumru et al., 2010; Mori et al., 2011). However, to date, conclusive evidence explaining the mechanisms reduce both spinal and cerebral spasticity under the RTMS not.
From this point of view, it is particularly interesting to study the excitability of the motor cortex by paired TMS to the study of phenomena vnutrikorkovogo inhibition of motor response (SISI in English literature) and vnutrikorkovogo facilitate induced motor response (ICF in the English language), which allow to study the mechanisms of differentiated inhibition and excitation in central nervous system at different levels (Chen et al., 1998).
Transcranial magnetic stimulation (TMS) is a technique that, on the one hand, it can be considered as a way to assess neyroplasticheskih processes, and on the other, the special modes, as neyromoduliruyuschego impact.
In assessing neyroplasticheskih processes using the TMS plays a major role TMS mapping. Since patients undergoing stroke, showed a significant decrease of cortical projection (map) muscles of the hand on the side of the affected hemisphere (Nikitin, Kurenkov, 2003), also points to a change of cortical excitability. A special role in the evaluation of the excitability of the cortical representation of muscles play doubles TMS at different intervals between stimuli. This technique allows to assess the processes intracrustal relationships: inhibition and facilitation.
RTMS, as a method of neuromodulation, is used in a large number of neurological diseases: consequences of stroke, Parkinson's disease, epilepsy, pain, etc. With the success of this technique is applied in spasticity (eg, Mori et al., 2009).
The mechanism of modulating influence of TMS is considered from two perspectives: the impact on the excitability of cortical and spinal centers.
RTMS low frequency (1 Hz) is used to decrease the excitability of the motor cortex, as demonstrated by reduced amplitude of motor responses (WMO) (Chen et al., 1997). High-frequency stimulation (5 Hz) is used to increase cortical excitability - increasing the amplitude of the WMO (Berardelli et al., 1998). Continuous stimulation at 5 Hz leads to prolongation of the effect.
It is believed that the application of TMS to the motor cortex is excited corticospinal neurons. These neurons, the founders corticospinal tract affect the alpha and gamma motor neurons of the spinal cord, Ia afferents, interneurons. Thus, the use of TMS and should lead to changes in the excitability of neurons in the spinal level. The main parameter of the study electrophysiological spinal excitability is an H-reflex (similar stretch reflex) (Mori et al., 2009). It is shown that TMS can change the parameters of H-reflex induced from soleus muscle. TMS single stimuli lead to changes in the muscles of the lower extremities, a decrease in the frequency of presynaptic inhibition of Ia afferents (Meunier and Pierrot-Deseilligny, 1998). Moreover, the above-threshold magnetic stimulation of the motor cortex with a frequency of 5 Hz results in reducing the H-reflex for 900 ms in the muscles of the forearm (Berardelli et al., 1998). In contrast, TMS of the motor cortex at 1 Hz decreased the amplitude of the WMO (Touge et al., 2001), or increase the effect on the H-reflex (Valero-Cabre et al., 2001). It also shows that the stimulation did not change the M & A in the stimulation of peripheral nerves, so that the amplitude ratio H / M was increased (Valero-Cabre et al., 2001). This fact indicates that low-frequency stimulation can facilitate monosynaptic spinal reflexes by inhibiting effects on corticospinal excitability of the spinal cord.
More recent studies have examined the effect of short sessions of 20-pulse stimulation of the cortical representation feet at 5 Hz at the spinal level. Found that the WMO soleus and tibialis anterior muscles rose alone, while the H-reflex was reduced by 1 second. RTMS 5 Hz also caused an increase in long-term depression of H-reflex from the soleus muscle caused by stimulation of the common peroneal nerve and reduce the H-reflex facilitation during stimulation of the femoral nerve. Reduction of the H-reflex at high-frequency TMS can partially be explained by increasing presynaptic inhibition of Ia-afferents (Perez et al., 2005). This mechanism can be considered as one of the possible effects of antispastic TMS. However, to date, the question of the mechanisms underlying the effects of TMS neyromodulyatsionnyh with spasticity, remains open.
In addition, at the present time for the study of motor areas of the brain by the method of transcranial magnetic stimulation (TMS) in addition to stimulation of one-off incentives also apply paired stimulation technique that allows to study the local changes in cortical excitability. The essence of paired stimulation is that consistently served two magnetic stimulus, first on any area of the brain is supplied conditioning, and then on the motor cortex - testing stimulus. Changes in cortical excitability measured by change in the amplitude of motor response (WMO) for steam stimulation compared with the amplitude of the WMO in response to isolated testing stimulus.
The most widely used kind of paired stimulation is stimulation with subthreshold and above-threshold conditioning testing stimulus, consistently applied to the same area of the motor cortex. In this case, using interpulse intervals of 1 to 5 ms observed phenomenon of the so-called braking vnutrikorkovogo WMO, with interpulse intervals of 7 to 20 milliseconds - a phenomenon vnutrikorkovogo facilitate WMO (respectively, SICI and ICF in the English language) (Conte A. et al ., 2008). Many studies show the different nature of phenomena SICI and ICF and the absence of direct communication between them (V. Di Lazzaro et al., 2006). The high localization phenomena SICI and ICF, their dependence on the position of the magnetic coil (Cathrin M. Butefisch et al., 2005, Liepert J. et al., 1998). This suggests that subtle changes in the study of local cortical excitability using the paired stimulation is preferable to use TMS with the possibility of precise navigation, for example, systems for nTMS - NBS Eximia Nexstim. The study of the excitability of the motor cortex by paired TMS to the study of phenomena and SISI ICF might be interesting to study the pathogenesis of spasticity as in brain damage, and with the defeat of the spinal cord. The phenomena studied paired TMS stimulation, will approach the study of mechanisms of differential inhibition and excitation in the central nervous system at different levels.
In the literature, there is no conclusive data on the effect of various parameters on RTMS vnutrikorkogo phenomena of inhibition and facilitation in different models of spasticity.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Condition ICMJE||Spasticity, Multiple Sclerosis, Stroke, Trauma|
|Intervention ICMJE||Device: Transcranial magnetic stimulation|
|Study Arm (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||60|
|Estimated Completion Date||December 2015|
|Estimated Primary Completion Date||September 2015 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
The age of the patients and healthy volunteers from 18 to 70 years
The criteria included:
|Ages||18 Years to 70 Years|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||Russian Federation|
|Removed Location Countries|
|NCT Number ICMJE||NCT01786005|
|Other Study ID Numbers ICMJE||TMS-002, TMS-002|
|Has Data Monitoring Committee||Yes|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Chervyakov Alexander, Russian Academy of Medical Sciences|
|Study Sponsor ICMJE||Russian Academy of Medical Sciences|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||Russian Academy of Medical Sciences|
|Verification Date||November 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP