Spasticity, Multiple Sclerosis, Stroke, Trauma Clinical Trial
Official title:
Antispastic Effect of Transcranial Magnetic Stimulation in Patients With Cerebral and Spinal Spasticity
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.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment