PM R 9 (2017) 1020-1029

www.pmrjournal.org

Narrative ReviewdCME

Spasticity Management: The Current State of Transcranial

Neuromodulation
Antonino Leo, PT, Antonino Naro, MD, PhD, Francesco Molonia, MS,
Provvidenza Tomasello, MS, Ileana Saccà, MS, Alessia Bramanti, PhD,
Margherita Russo, MD, PhD, Placido Bramanti, MD, Angelo Quartarone, MD, PhD,
Rocco Salvatore Calabrò, MD, PhD

Abstract

This narrative review aims to provide an objective view of the noninvasive neuromodulation (NINM) protocols available for
treating spasticity, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation
(tDCS). On the basis of the relevant randomized controlled trials, we infer that NINM is more effective in reducing spasticity when
combined with the conventional therapies than used as a stand-alone treatment. However, the magnitude of NINM after-effects
depends significantly on the applied hemisphere and the underlying pathology. Being in line with these arguments, low-frequency
rTMS and cathodal-tDCS over the unaffected hemisphere are more effective in reducing spasticity than high-frequency rTMS and
anodal-tDCS over the affected hemisphere in chronic poststroke. However, most of the studies are heterogeneous in the stim-
ulation setup, patient selection, follow-up duration, and the availability of the sham operation. Therefore, the available data on
the usefulness of NINM in reducing spasticity need to be confirmed by larger and multicentric randomized controlled trials to
gather evidence on the efficiency of NINM regimens in reducing spasticity in various neurologic conditions.
Level of Evidence: V

Introduction the dissociation of the motor and sensory components of

Spasticity is defined as a motor disorder character-
ized by a velocity-dependent increase in tonic stretch
reflex, and can be associated with a variety of signs and
symptoms of the upper motor neuron syndrome. These
symptoms include clonus, dystonia (involuntary muscle
contraction resulting in abnormal posturing of a joint or
limb), extensor or flexor spasms, spastic co-contraction
(contraction of both the agonist and antagonist muscles
caused by an abnormal pattern of commands in the
descending supraspinal pathway), abnormal reflex
responses (exaggerated deep tendon reflexes and asso-
ciated reaction), the loss of dexterity, muscle fatigue,
weakness, stiffness, fibrosis, and atrophy [1-7]. Many
disease conditions of the central nervous system,
including stroke, cerebral palsy, multiple sclerosis, and
spinal cord injury, can provoke spasticity.
Fundamentally, spasticity results from an abnormal
intraspinal processing of primary afferent inputs due to
the diastaltic arch [8]. This dissociation is caused by
lesions in the brainstem, the cerebral cortex (in the
primary, secondary, and supplementary motor areas) or
the spinal cord (pyramidal tract), which leads to an
inhibitory/excitatory imbalance in the spinal network
with a consequent segmental hyperexcitability,
including increased muscle activity and exaggerated
spinal reflex responses to a peripheral stimulation
[9-16]. Furthermore, multiple sclerosis
induced spas-
ticity is believed to be due to the occurrence of either
axonal degeneration or demyelination within the spe-
cific descending tracts in the central nervous system.
The inhibitory/excitatory imbalance results from
damage-induced dysfunction and maladaptive connec-
tivity among several brain structures such as the sup-
plementary motor, cingulate motor, premotor, posterior
and inferior parietal areas, and the cerebellum [9].
The spasticity treatment options available so far can be
categorized as pharmacological and nonpharmacological

1934-1482/$ - see front matter ª 2017 by the American Academy of Physical Medicine and Rehabilitation
http://dx.doi.org/10.1016/j.pmrj.2017.03.014

Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
 A. Leo et al. / PM R 9 (2017) 1020-1029 1021

Table 1 Both LTP and LTD abnormalities contribute to spas-

Main pharmacologic and nonpharmacologic therapeutic options for
spasticity management
Pharmacologic Nonpharmacologic
Noninjectable Injectable Instrumental Noninstrumental
Baclofen ITB Thermotherapy Neurosurgery
Tizanidine BoNT Cryotherapy Orthopedic
Dantrolene Neurolysis Neurorobotic PT
Diazepam ESWT OT
Gabapentin NMES
Nabiximols TENS
Eperisone UST
NINM
rTMS
tDCS
MV
WBV
FMV
BoNT ¼ botulinum neurotoxin; ESWT ¼ extracorporeal shock wave
therapy; FES ¼ functional electric stimulation; FMV ¼ focal muscle
vibration; ITB ¼ intrathecal baclofen; MV ¼ muscle vibration;
NINM ¼ noninvasive neuromodulation; OT ¼ occupational therapy;
PT ¼ physiotherapy; rTMS ¼ repetitive transcranial magnetic
stimulation; tDCS ¼ transcranial direct current stimulation;
TENS ¼ transcutaneous electric nerve stimulation; UST ¼ ultrasound
therapy; WBV ¼ whole-body vibration.
(Table 1). The former includes oral (eg, baclofen and
dantrolene) and injectable (eg, botulinum toxins and
phenol) drugs [17], whereas the latter encompasses sur-
gical, physical (eg, physiotherapy, occupational therapy,
positioning/orthotics), and instrumental approaches (eg,
physical and electric-current modalities, including repet-
itive transcranial magnetic stimulation [rTMS] and trans-
cranial direct current stimulation [tDCS]).
In practice, these categories can be implemented in a
neurorehabilitation program, either as a stand-alone
therapy (eg, physiotherapy or occupational therapy
only) or in a combination of 2 or more treatment
modalities [18].
Noninvasive neuromodulation (NINM) uses weak elec-
tric current or neurochemical agents, such as dopami-
nergic and benzodiazepines, to modify neuronal activity
by modulating synaptic plasticity properties [19]. The
electric current can be delivered either directly, by
applying scalp electrodes wired to electric stimulators
using the direct (tDCS) or alternating current, or indi-
rectly, by applying a focal magnetic field to induce an
electric current in the brain itself (rTMS). In both cases,
the current can affect synaptic and nonsynaptic plas-
ticity by modifying the polarity of the neuronal mem-
brane, which in turn, can induce either long-term
potentiation (LTP)
like and long-term depression
(LTD)
like plasticity or spike-time
dependent plasticity
phenomena. Several mechanisms have been proposed to
explain these plasticity phenomena, which include
axonal or depolarizing blockade, stochastic normaliza-
tion/reduction of neural firing, and modulation of neural
network oscillations [20,21].
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
ticity generation. Indeed, there could be a lack of
adaptive LTP compensation to neuronal damage. At the
same time, there could be a strengthening of perile-
sional LTD due the increase in interhemispheric inhibi-
tion (IHI) (ie, the activity of inhibitory interneurons
within motor cortex, which changes the activity of the
homologus interneurons in the contralateral hemi-
sphere, largely through transcallosal pathways) from
the affectecd to the unaffected hemispehere (Figure 1).
Given that NINM can reshape LTP/LTD processes [19-21],
specific paradimgs aimed at stimulating LTP and/or
reducing LTD would decrease spasticity.
At present, rTMS is used to investigate several
neurophysiological processes and to treat some neuro-
logic and psychiatric conditions such as stroke, depres-
sion, and schizophrenia [22-24]. rTMS is based on
Faraday’s principle of electromagnetic induction by an
electric field in a discrete region of the brain [22-24]
inducing focal and distal changes in cortical plasticity.
Single-pulse stimulation techniques are used to measure
cortical inhibition, facilitation, reactivity, and plas-
ticity, which provide valuable insights into the physi-
ology of the cortex. The rTMS induces changes in
cortical excitability at the site of stimulation and distal
sites (trans-synaptic). The direction of rTMS effects
depends mainly on the frequency of stimulation, where
low frequencies yield inhibitory effects and the high
frequencies exert facilitatory effects. The inhibitory
and facilitatory after-effects in the corticospinal motor
output are probably due to LTD- and LTP-like mecha-
nisms, besides changes in network excitability,
activation of feedback loops, and activity-dependent
meta-plasticity phenomena [25-28]. Nonetheless, many
other factors can also influence the results of an rTMS
application, such as the number of stimuli, the number
and duration of rTMS sessions, and the coil configuration
[25-28]. Moreover, the effects of rTMS depend on the
stimulated hemisphere, which in turn influences the
specific patterns of IHI and intracortical inhibition and
facilitation. It is noteworthy that synaptic plasticity is
influenced by the pre-existing levels of cortical excit-
ability, implying that the observed changes in plasticity
could be due to the cumulative or amplified effects of
each session. Specifically, an actual postsynaptic high
firing would elevate the threshold for LTP induction and
lower the threshold for LTD; on the other hand, a low
postsynaptic firing would promote the opposite effects
[25-28]. Therefore, priming (ie, an intervention to
modify synaptic strength, in which NINM constitutes a
pretreatment or pre-protocol stimulation that enhances
the effect of a subsequent protocol) may change several
synaptic properties that can alter the effects of a sub-
sequent plasticity-inducing event (conditioning). Prim-
ing and conditioning can be used in the form of
behavioral, environmental, pharmacological, and elec-
trophysiological inputs [25-28], and then, rTMS and tDCS
1022 Spasticity Management

Figure 1. Schematic depiction of the theoretical effects of excitatory (high-frequency repetitive transcranial magnetic stimulation [rTMS],
intermittent theta-burst [iTBS], anodal tDCS) and inhibitory (low-frequency rTMS, cathodal transcranial direct current stimulation [tDCS])
noninvasive neuromodulation (NINM) paradigms over the ipsilesional and contralesional cortex, respectively. Following a brain lesion, there is
usually a decreased ipsilesional excitability, an increased contralesional excitability, and a reduced ipsi-to-contralesional interhemispheric
inhibition (IHI) (white arrow), whereas the contra-to-ipsilesional IHI (black arrow) does not significantly change. Altogether, these changes reduce
the corticospinal output, with an impairment in motor function (MF) and a Modified Ashworth Scale (MAS) score increase. Ipsilesional excitatory
NINM may enhance the excitability of the damaged cortex, with a consequent enhancement of the corticospinal transmission, and thus, a better
MF of the paretic limb and a lower MAS score. These effects seem to be independent of the IHI. Contralesional inhibitory NINM may instead
suppress the high contra-to-ipsilesional IHI (2 white arrows), thus increasing ipsilesional excitability, improving ipsilesional corticospinal trans-
mission and, potentially, resulting in a better MF of the paretic limb and a lower MAS score.

are applied in neurorehabilitation settings in association method can induce a sustained increase or decrease in
with other approaches, including neurorobotic, physio- cortical excitability of the underlying brain area
therapy, occupational therapy, and drugs. Such associ- (depending on the orientation of the dendrites and the
ations between NINM and other approaches are related axons in the electrical field), which is typically longer
to the associative plasticity (which is generated by a than the period of stimulation [33-35]. Notably, tDCS
timely coupling of 2 different synaptic inputs), leading modulates the spontaneous neuronal firing rates and
to the potentiation of a single approach [29-31]. In most both synaptic and nonsynaptic plasticity, thus bringing
cases, rTMS is safe and well tolerated, except for the changes in the resting polarity of the neurons. However,
potential risk of seizures when a high-frequency stimu- tDCS does not trigger an action potential, due to the low
lation is used [32]. current density delivered [36]. Analogous to how rTMS
tDCS involves the application of a low-amplitude, frequency determines its after-effects, the polarity of
direct electrical current (1-2 mA) through rubber scalp tDCS can influence its effects on spasticity depending on
electrodes placed in saline-soaked sponges. The term whether it is applied to the affected or the unaffected
“direct” implies that the electrical flow travels from hemisphere [37-39]. tDCS also holds the same principles
one electrode to the other, ie, from the anode (positive of IHI, intracortical inhibition and facilitation, priming,
electrode) to the cathode (negative electrode). This and associative plasticity described for rTMS.
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
 A. Leo et al. / PM R 9 (2017) 1020-1029
Given the effects of NINM on neuronal excitability
and plasticity, rTMS and tDCS have been used to
modulate neural circuitry plasticity in the brain (and the
spine) in an attempt to foster neurorecovery processes
with a potential effect on spasticity [40-43]. To this
purpose, NINM has been used in patients with multiple
sclerosis, stroke, spinal cord injury, and cerebral palsy
[40-43]. This review will summarize the use of rTMS and
tDCS in managing spasticity during neurorehabilitation
and will discuss their potential for reducing spasticity.
Assessment of the Literature
A literature search was performed in the PubMed,
Medline, Cochrane, Scopus, and Web of Science data-
bases using the search terms “spasticity AND repetitive
transcranial magnetic stimulation AND/OR transcranial
direct current stimulation”. The search criteria included
the studies in humans and the articles published in
English, without restrictions on the publication date.
This primary search yielded 128 citations.
Two independent reviewers screened the abstracts,
identified relevant articles, namely, those related to
stroke, cerebrovascular accidents, multiple sclerosis,
spinal cord injury, traumatic brain injury, amyotrophic
lateral sclerosis, and disorders of consciousness (96
articles). Subsequently, complete articles with full text
were gathered. The reference lists of these publications
(and pertinent reviews) were also scrutinized for other
studies that might have been omitted during the pri-
mary search. Of these 96 articles, 30 were randomized
controlled trials focusing on the effects of rTMS/tDCS on
upper/lower limb spasticity. Review articles, case
reports, and those not focusing primarily on spasticity
were excluded. Table 2 shows the main characteristics
of the randomized controlled trials included in our
review.
Repetitive Transcranial Magnetic Stimulation in
the Rehabilitation Setting
Most of the studies used low-frequency rTMS over the
healthy hemisphere in stroke patients [44-56] or the less
affected side in the patients with multiple sclerosis
[57]. Some studies used stand-alone high-frequency
rTMS or intermittent theta-burst stimulation (a type of
high-frequency rTMS in which patterned magnetic
stimuli, ie, grouped in repeated small trains of stimuli,
are used) [41,49,55-64], combined high-frequency with
low-frequency rTMS, or used combined approaches
[46-49,58,65]. Among the combined approaches, NINM
was intended as a primer; that is, rTMS constituted a
pretreatment or pre-protocol stimulation that enhances
the effect of subsequent treatments. This means that an
earlier stimulation or bout of activity predisposes the
synapses for a second stimulation protocol to produce
an enhanced potentiation or depression of synaptic
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
1023
activity, with a significant effect on the cortical excit-
ability and, therefore, spasticity. rTMS was delivered by
using a standard figure-of-eight coil over the cortical
representation of the target muscles (hand, leg) in the
primary motor area, whereas sham rTMS was adminis-
tered by placing the coil perpendicular to the scalp or
over the vertex or by using a dedicated sham coil.
Unfortunately, not all of the studies used a sham-
controlled study design (Table 2).
About 250 patients with stroke were overall enrolled
in the rTMS studies included in the present review, and
at least 90% were re-evaluated postintervention. Most of
the enrolled patients experienced a unilateral cortical
or subcortical stroke in the chronic phase (from few
months to almost 20 years), yielding a moderate-to-
severe spastic hemiparesis (Brunnstrom scale 3-5),
whereas one study also included patients with a sub-
acute stage [52]. The after-effects of rTMS were eval-
uated mostly in the terms of Modified Ashworth Scale
(MAS) change in upper (most of the studies) and lower
limb, which was thus considered as the primary
outcome (on which we selected the double-blind ran-
domized controlled trials pertinent to the aims of our
narrative review). However, a few other outcome
measures were also used in the selected articles to es-
timate clinical (eg, kinematic motion analysis, handgrip,
Wolf Motor Function Test, finger tapping, movement
accuracy, and reaction time) and neurophysiological
after-effects (eg, H-reflex and motor evoked potential
amplitude). The MAS score was assessed at the end of
the training and, in some studies, at the follow-up,
ranging from 1 week to 1 month. In these papers, low-
frequency rTMS, applied over the healthy hemisphere,
either alone or as a primer for PT or other interventions
[44-55], was reported to reduce chronic poststroke
spasticity in the upper limb for up to 1 month, except
for one study [50]. We found only one paper regarding
lower limb chronic poststroke spasticity that reported a
beneficial effect of low-frequency rTMS [54]. Another
investigation on subacute poststroke patients also re-
ported an advantageous effect on upper limb spasticity
[52]. On the other hand, high-frequency rTMS was found
to exert limited beneficial effects on chronic poststroke
spasticity [59-64]. There were no substantial differ-
ences concerning stroke location (ie, cortical or
subcortical), even though one study indicated that rTMS
exerted more favorable effects on subcortical rather
than cortical stroke [66]. An investigation using high-
frequency rTMS applied on the healthy hemisphere
showed a well-defined negative effect on spasticity and
motor functions [64].
There is a limited number of studies concerning the
treatment of spasticity with rTMS in patients with mul-
tiple sclerosis. About 80 patients with a relapsing-
remitting multiple sclerosis (Expanded Disability Status
Scale 3-6), aged 25-65 years, and with a long duration of
the disease, were overall included in randomized
1024 Spasticity Management

Table 2
Summary of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) studies on spasticity
MAS Follow-up
Frequency/ MAS Decrease (Other Outcome
Pathology, Paradigm, First Author Polarity Setting n. Patients, DD After Protocol Improvements)
CP HF Gupta [65] 5 HzþPT 15 minþ1 h PT 20 d 20, 8 y > Combined NA (i)
10 HzþPT > Combined NA
Valle [59] 5 Hz # 1500 p, 5 d, 90% RMT, UL 17, 6
12 y Significant NA
1 Hz # NS NA
tDCS Aree-uea [37] Anodal # 20 min, 5 d, UL 46, adolescent Significant 2d
MS HF Centonze [57] 5 Hz # 900 p, 1 d, 100% RMT LL 19, NA NS NA
5 Hz # 900 p, 15 d, 100% RMT LL Significant 1 wk (ii)
Mori [40] iTBSþPT # 15 d, 80% AMT LL 20, 1
23 y Significant 2 wk
Nielsen [41] 5 Hz 80-stimuli burst for 38, NA Significant NA (ii)
25 Hz 5 min (twice), Significant NA
90% RMT LL, 7 d
LF Centonze [57] 1 Hz # 900 p, 15 d, 90% RMT LL 19, NA Significant 2 wk (ii)
(< HF)
1 Hz # 900 p, 1 d, 90% RMT LL 19, NA NS NA
tDCS Iodice [69] Anodal # 20 min, 5 d, LL 20, 6
9 y NS NA (i)
SCI HF Benito [62] 20 Hz # 1600 p, 15 d, 90% RMT LL 17, 3
17 mo Significant 2 wk (iii, vi)
Kumru [60] 20 Hz # 1800 p, 5 d, 90% RMT UL 17, 3
17 mo Significant 1 wk (iii)
Kumru [61] 20 Hz # 1800 p, 15 d, 90% RMT UL 17, 3
17 mo Significant 2 wk (iii)
Stroke Double Sung [49] 1 Hz /iTBS 600 p (1 Hz) 90% RMT þ 600p 54, chronic Significant NA (iv, v)
rTMS (in 3-pulse bursts at 50 Hz)
80% AMT, 20 d
Yamada [79] 1 Hz and 2000 p (1 and 10 Hz)þ 8, chronic Significant NA (iv, v)
10 Hz þOT 4 h OT, 15 d
HF Kim [63] iTBS # 600 p (in 3-pulse bursts 15, chronic Significant NA (i, ii, iii)
at 50 Hz) 90% AMT, 1 d
Sung [49] iTBS # 600 p in 3-pulse bursts 54, chronic NS NA
at 50 Hz
80% AMT, 20 d
Terreaux [55] 10 Hz # 1000 p (20 5-s bursts) 100% RMT 5, chronic NS NA
Wupuer [64] 10 Hz # 1000 p,1 d,110% RMT UL* 12, chronic MAS increase NA
LF Etoh [50] 1 Hz # 90% RMT UL, 2 wk 18, chronic NS NA (iv)
Sung [49] 1 Hz # 600 p, 90% RMT, 20 d 54, chronic NS NA
Barros-Galvão [51] 1 HzþPT # 1500 p, 90% RMT UL, 3 d/wk 20, chronic Significant 1 mo
Izumi [44] 0.1 Hz # 400 p/d, 4 wk 9, chronic Significant 1 wk (iii, iv)
Kakuda [46] 1 HzþOT 1200 p, 100% RMT UL, 10 d 39, chronic Significant 1 mo (iv,v)
Kakuda [48] 1 HzþOTþL-Dopa 1200 p, 2/d, 14, chronic Significant 1 mo (iv,v)
90% RMT UL, 15 d
Kakuda [47] 1 HzþOTþBoNTA 1200 p, 2/d, 14, chronic Significant 1 mo (iv,v)
90% RMT UL, 15 d
Mally and Dinya [45] 1 Hz 100 p, 2/d, 30% MSO UL, 7 d 64, chronic Significant 2 mo (iii)
Naghdi [53] 1 Hz 1200 p, 5 d 7, chronic Significant 1 wk
Rastgoo [54] 1 Hz 1000 p, 90% AMT LL, 5 d 20, chronic Significant 1 wk (iv)
Terreaux [55] 1 Hz # 1000 p, 90% RMT UL 5, chronic Significant NA (ii,iv,vi)
Kondo [56] 0.5 HzþOT # 1200 pþ4 h OT, UL, 15 d 10, chronic Significant NA (ii, iii)
Theilig [52] 1 Hz # 900 p, 100% RMT UL, 10 d 24, subacute Significant NA (i, ii)
and chronic
tDCS Bradnarn [67] Cathodal # 20 min UL, 1 d 12, 2
34 mo Significant NA (iii)
Del Felice [68] Double # 20 min UL, 5 d 10, 2 y Cathodal> 2 mo
Double
Cathodal # 10, 2y Significant NA
Ochi [39] AnodalþRAAT 20 min UL, 5 d 18, >6 mo Significant NA (ii, iii)
Cathodalþ RAAT 18, >6 mo NS NA
Wu [42] Cathodal # 5 d/wk, 20 min UL, 4 wk 90, >2 mo Significant 1 mo
High-frequency rTMS and anodal-tDCS were delivered on the affected hemisphere (except one*), whereas low-frequency rTMS and cathodal tDCS
were applied on the healthy hemisphere. Double stimulation includes both the polarities and frequencies. Pound sign (#) indicates the studies with
a sham-treatment group.
AMT ¼ active motor threshold; CP ¼ cerebral palsy; d ¼ days; DD ¼ disease duration; MAS ¼ Modified Ashworth Scale; HF ¼ high-frequency;
LF ¼ low-frequency; BoNT ¼ botulinum neurotoxin; iTBS ¼ intermittent theta-burst; LL ¼ lower limbs; MS ¼ multiple sclerosis; NA ¼ not
available; NS ¼ not significant; p ¼ pulses; PT ¼ physiotherapy; RMT ¼ resting motor threshold; OT ¼ occupational therapy; PT ¼ physiotherapy;
SCI ¼ spinal cord injury; UL ¼ upper limbs; i ¼ range of movement; ii ¼ Hmax/Mmax ratio, F-wave; iii ¼ motor and gait scales; iv ¼ Fugl-Meyer
assessment; v ¼ Wolf Motor Function Test; vi ¼ Timed Up and Go; RAAT ¼ robotic-assisted arm training.

Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
 A. Leo et al. / PM R 9 (2017) 1020-1029
controlled trials in the selected studies. MAS score was
the primary outcome, and it was assessed from lower
limbs, immediately after and up to 2 weeks after the
end of the conditioning protocol. Standard high-
frequency protocols yielded a greater MAS score
reduction as compared to standard lower-frequency
protocols, even when combined with other approaches
[41,57,58].
Even though there are few rTMS studies on incom-
plete spinal cord injury [60-62], there is converging
evidence on the positive effect of high-frequency rTMS
on spasticity. Indeed, 50 patients in American Spinal
Injury Association Class C-D in a subacute or chronic
stage have been overall enrolled in high-frequency rTMS
trials (1800 pulses, 5 sessions per week, stimulation
intensity at 90% resting motor threshold) and showed
improvements in MAS up to 2 weeks after the end of the
rTMS protocol.
Concerning cerebral palsy, there are 2 studies that
enrolled 17 patients [59] and 20 patients [65], respec-
tively, aged 6-12 years, who underwent standard high-
and low-frequency rTMS, paired with conventional
physiotherapy. As compared to stand-alone 1-Hz rTMS
and sham rTMS, the association between 5-Hz rTMS and
physiotherapy was found to be the only treatment
efficacious in reducing spasticity significantly [59,65].
Finally, there were no studies available on the effects
of rTMS for spasticity in other neurological conditions
such as amyotrophic lateral sclerosis, traumatic brain
injury, or disorders of consciousness. There were no
complications or major adverse effects reported during
or after rTMS application, except for transient facial
twitching [60-61].
tDCS in the Rehabilitation Setting
Double-blinded, sham-controlled tDCS studies aimed
at reducing spasticity used cathodal-tDCS over the
unaffected primary motor area and anodal-tDCS over
the affected primary motor area in the patients with
stroke in the chronic phase [39,42,67,68]. Only one
study used sham-controlled anodal-tDCS over the most
affected hemisphere in patients with cerebral palsy [37]
or multiple sclerosis [69]. tDCS was usually administered
with the setting of 1 mA, 20 minutes daily, 5 days per
week for 1-4 weeks, consecutively. MAS score was
the main outcome measure that was assessed from
the upper or lower limb. As secondary outcomes,
some studies considered a range of movements, the
ratio between the H and M response, and multiple
sclerosis
specific scales.
Only one cathodal-tDCS study (sham-controlled),
carried out in 90 subacute or chronic stroke patients,
reported a decrease in mild-to-severe upper limb spas-
ticity up to 1 month [42]. Other two tDCS studies, one
cathodal (sham-controlled) and one anodal (cathodal-
controlled), reported a significant MAS score decrease in
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
1025
upper limb subacute or chronic stroke patients but
lacked a follow-up period [39,67]. Only one study
applied the double-tDCS (ie, cathodal-tDCS on the un-
affected hemisphere and anodal-tDCS over the affected
one) to reduce spasticity in 10 chronic stroke patients,
with a consistent reduction of MAS up to 2 months as
compared to cathodal-tDCS alone [68]. Overall, tDCS
effects were greater in the proximal than in the distal
muscles [36].
Anodal-tDCS was reported as ineffective in reducing
lower limb spasticity in 20 relapsing-remitting multiple
sclerosis patients, with a disease duration of about a
decade [69], whereas anodal-tDCS yielded a MAS score
reduction in upper limb up to 2 days following 5 days of
anodal stimulation in cerebral palsy [37].
Overall, there were no complications or major adverse
effects during or after tDCS application, except for a
transient tingling sensation beneath the electrodes [39].
Discussion
Based on the accumulated data from the literature
survey, we can highlight 2 main points on the use of
NINM for spasticity management: (1) NINM is useful in
reducing spasticity, but its effects critically depend on
the applied hemisphere and the underlying pathology
[45]; and (2) NINM is more effective in reducing spas-
ticity when coupled with another form of medical and/
or physical therapy rather than used as a stand-alone
therapy [39,46-48,56,58,65,70-72].
rTMS inhibitory protocols (low-frequency) on the
unaffected hemisphere exert after-effects that are
higher in magnitude and longer in duration than facili-
tatory rTMS protocols (high-frequency) on the affected
hemisphere. This difference seems to depend on the
underlying pathophysiology. In other words, inhibitory
protocols could shape the IHI and intracortical inhibitory
and facilitatory networks more specifically and finely
than facilitatory protocols, resulting in a better
re-modulation of corticospinal excitability imbalance
between the affected and unaffected hemispheres [73].
This issue however, needs to be confirmed, given that
only some studies have used high-frequency rTMS
because of the increased risk of seizure [32]. In addi-
tion, the comparison between anodal- and cathodal-
tDCS, both acting on IHI, yielded similar results [74].
The difference with rTMS findings may depend on the
fact that tDCS has gross effects on brain excitability,
and therefore it can less selectively shape IHI or finely
modulate intracortical inhibitory and facilitatory net-
works (which in turn influence IHI) [75].
rTMS seems to have more consistent effects in terms
of magnitude and duration than tDCS, in either stroke or
cerebral palsy, multiple sclerosis, and spinal cord injury;
even though no studies have directly compared the
effects of rTMS and tDCS on post-stroke spasticity
(considering that tDCS studies are rather few as
1026
compared with rTMS studies). This difference in the
terms of magnitude and duration of the after-effects
may depend on the underlying neurophysiological
mechanism of action. Indeed, rTMS shows better focus
in targeting specific structures and can also have far
effects by altering brain rhythms that subtend neuro-
recovery processes. tDCS has less focal effects on
brain excitability [76].
Only a few reports support the conclusion that rTMS
and tDCS are effective as a single intervention, whereas
there is evidence suggesting that rTMS and tDCS
contribute only by improving the outcomes of medical
and/or physical therapy [39,46-48,56,58,65]. The
superiority of the combined approach may be justified
by the principles of priming or of associative plasticity
[29-31].
Despite these arguments, convincing evidence on the
efficacy of NINM in post-stroke spasticity is still missing.
This is likely due to the bias affecting the randomized
controlled trials in the studies that we reviewed, which
may include the small sample size and not always ho-
mogeneous sampling (with a few exceptions), besides
the different stimulation settings. In particular, patient
age ranged from middle age to the elderly, which may
obviously influence the chances of recovery, given that
this significantly depends on age as well as disease
duration [77]. In terms of disease duration, patients
with chronic poststroke spasticity were mainly included,
even though a few studies enrolled subjects in the
subacute phase (Table 2). There were no substantial
differences concerning stroke location (ie, cortical or
subcortical) and etiology (ischemic or hemorrhagic),
even though it has been argued that rTMS has more
favorable effects on subcortical rather than cortical
strokes [66].
Finally, the discrepancies in stimulation setting
(including the number, frequency, density, and the
duration of rTMS sessions, combinations with other
treatments, the presence and types of sham stimulation)
between the NINM studies may further challenge the
consistency of rTMS effects on poststroke spasticity.
Beyond the choice of the target hemisphere and the
underlying pathology, which remain crucial issues [45]
and significantly modify the pattern of IHI, intra-
cortical inhibition and facilitation [78] along with the
duration of NINM sessions, critically influence the
longevity of the after-effects in a proportional manner
[42,45,49,57,60,61]. Moreover, the combination of
different NINM paradigms also plays an important role
[49,79] in keeping with the principles of priming or of
associative plasticity. In addition, the robustness of rTMS
is partially invalidated by the discontinuous use of sham-
rTMS controls. Notably, most of the studies used MAS
score as the primary outcome to quantify spasticity.
Even though MAS is widely used by clinicians to assess
spasticity routinely, it has been reported as no longer
suitable for systematic evaluation [80-83]. Therefore,
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Spasticity Management
the use of a more objective scale would be beneficial in
the assessment of NINM after-effects on spasticity [84].
Unfortunately, the available data on the subjects
with multiple sclerosis, spinal cord injury, and cerebral
palsy (all mainly limited to high-frequency rTMS and
anodal-tDCS paradigms) are very limited to draw some
conclusion on NINM-based spasticity management. All of
the randomized controlled trials reviewed here indicate
that NINM may be of some help in reducing spasticity. It
is not clear, however, whether poststroke spasticity
conveys NINM after-effects more than other models or,
rather, whether the other conditions are less suscepti-
ble than a stroke to NINM. However, we may hypothe-
size that poststroke spasticity may overall comply with
NINM better than multiple sclerosis, cerebral palsy, and
spinal cord injury, as both rTMS and tDCS have more
prominent local than far (subcortical or spinal) effects.
Therefore, the underlying pathological processes
involved in stroke may be more susceptible to NINM in
comparison to the multifocal models (as multiple scle-
rosis and cerebral palsy) or lesions distant from cerebral
cortex (as spinal cord injury).
The clinical applicability of the findings of this review
needs to be confirmed in well-designed randomized
controlled trials with a larger sample size and long-term
follow-up. We also suggest that the assessment of brain
plasticity in patients with spasticity should be the focus
of future research in this area. In fact, plasticity and
recovery processes play a key role in function restora-
tion and adaptation, as well as spasticity generation and
maintenance. Indeed, a better understanding of plas-
ticity processes in spasticity may allow therapists to
provide treatments tailored to patient’s needs, to adapt
successfully to the treatment resources, and to optimize
the recovery process.
Acknowledgments
We thank Jennifer Gabriel and Giovanna Orlando for
English language revision.
References
1. Trompetto C, Marinelli L, Mori L, et al. Pathophysiology of spas-
ticity: Implications for neurorehabilitation. Biomed Res Int 2014;
2014:354906.
2. Mullick AA, Musampa NK, Feldman AG, Levin MF. Stretch reflex
spatial threshold measure discriminates between spasticity and
rigidity. Clin Neurophysiol 2013;124:740-751.
3. Lance JW. Symposium synopsis. In: Feldman RG, Young RR,
Koella WP, eds. Spasticity: Disordered Control. Chicago: Yearbook
Medical; 1980; 485-494.
4. Tardieu G, Tardieu C, Colbeau Justin P, Bret MD. Effects of muscle
length on an increased stretch reflex in children with cerebral
palsy. J Neurol Neurosurg Psychiatry 1982;258:348-352.
5. Rymer WZ, Houk JC, Crago PE. Mechanisms of the clasp-knife
reflex studied in an animal model. Exp Brain Res 1979;37:93-113.
 A. Leo et al. / PM R 9 (2017) 1020-1029
6. Kamper DG, Schmit BD, Rymer WZ. Effect of muscle biomechanics
on the quantification of spasticity. Ann Biomed Eng 2001;29:
1122-1134.
7. Mukherjee A, Chakravarty A. Spasticity mechanisms for the clini-
cian. Front Neurol 2010;1:149.
8. Kheder A, Nair KP. Spasticity: Pathophysiology, evaluation and
management. Pract Neurol 2012;12:289-298.
9. Lim JS, Kang DW. Stroke connectome and its implications for
cognitive and behavioral sequelae of stroke. J Stroke 2015;17:
256-267.
10. Thibaut A, Chatelle C, Ziegler E, Bruno MA, Laureys S, Gosseries O.
Spasticity after stroke: Physiology, assessment and treatment.
Brain Inj 2013;27:1093-1105.
11. Reinkensmeyer DJ, Guigon E, Maier MA. A computational model of
use-dependent motor recovery following a stroke: Optimizing
corticospinal activations via reinforcement learning can explain
residual capacity and other strength recovery dynamics. Neural
Netw 2012;30:60-69.
12. Berg HE, Larsson L, Tesch PA. Lower limb skeletal muscle function
after 6 weeks of bed rest. J Appl Physiol 1997;82:182-188.
13. Ferretti G, Berg HE, Minetti AE, Moia C, Rampichini S, Narici MV.
Maximal instantaneous muscular power after prolonged bed rest in
humans. J Appl Physiol 2001;90:431-435.
14. Tizard JP. Cerebral palsies: Treatment and prevention. The
Croonian Lecture 1978. J R Coll Physicians Lond 1980;14:72-80.
15. Hefter H, Jost WH, Reissig A, Zakine B, Bakheit AM, Wissel J.
Classification of posture in post-stroke upper limb spasticity: A
potential decision tool for botulinum toxin A treatment? Int J
Rehabil Res 2012;35:227-233.
16. Marciniak C. Post-stroke hypertonicity: Upper limb assessment and
treatment. Top Stroke Rehabil 2011;18:179-194.
17. Phillips MM, Miljkovic N, Ramos-Lamboy M, et al. Clinical experi-
ence with continuous intrathecal baclofen trials prior to pump
implantation. PM R 2015;7:1052-1058.
18. Steins S, O’Young B, Young M. Person-centered rehabilitation:
Interdisciplinary intervention to enhance patient enablement. In:
O’Young B, Young M, Steins S, eds. Physical Medicine and Reha-
bilitation Secrets. Philadelphia: Hanley & Belfus; 2002; 4-9.
19. Katz PS, Calin-Jageman RJ. Neuromodulation. In: Squire LR, ed.
Encyclopedia of Neuroscience. London: Elsevier; 2009; 497-503.
20. Mozzachiodi R, Byrne JH. More than synaptic plasticity: Role of
non-synaptic plasticity in learning and memory. Trends Neurosci
2010;33:17.
21. Debanne D, Poo MM. Spike-timing dependent plasticity beyond
synapse—pre- and post-synaptic plasticity of intrinsic neuronal
excitability. Front Synaptic Neurosci 2010;2:21.
22. Conforto AB, Nascimento-Farias da Guarda S. Transcranial mag-
netic stimulation. In: Ovbiagele B, ed. Ischemic Stroke Thera-
peutics. New York: Springer; 2016; 235-248.
23. Daskalakis ZJ, Christensen BK, Fitzgerald PB, Chen R. Transcranial
magnetic stimulation. J Neurol Neurosurg Psychiatr 2002;14:
406-415.
24. Xu Y, Hou Q, Russell SD. Neuroplasticity in post-stroke gait re-
covery and non-invasive brain stimulation. Neural Regen Res 2015;
10:2072-2080.
25. Kobayashi M, Pascual-Leone A. Transcranial magnetic stimulation
in neurology. Lancet Neurol 2003;2:145-156.
26. Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. Structural basis
of long-term potentiation in single dendritic spines. Nature 2004;
429:761-766.
27. Cooke SF, Bliss TV. Plasticity in the human central nervous system.
Brain 2006;129:1659-1673.
28. Gentner R, Wankerl K, Reinsberger C, Zeller D, Classen J.
Depression of human corticospinal excitability induced by mag-
netic theta-burst stimulation: Evidence of rapid polarity reversing
meta-plasticity. Cereb Cortex 2008;18:2046-2053.
29. Hara Y. Brain plasticity and rehabilitation in stroke patients.
J Nippon Med Sch 2015;82:4-13.
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
1027
30. Marconi B, Filippi GM, Koch G, et al. Long-term effects on cortical
excitability and motor recovery induced by repeated muscle vi-
bration in chronic stroke patients. Neurorehabil Neural Repair
2011;25:48-60.
31. Verhoog MB, Goriounova NA, Obermayer J, et al. Mechanisms
underlying the rules for associative plasticity at adult human
neocortical synapses. J Neurosci 2013;33:17197-17208.
32. Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical
considerations, and application guidelines for the use of trans-
cranial magnetic stimulation in clinical practice and research. Clin
Neurophysiol 2009;120:2008-2039.
33. Nitsche MA, Paulus W. Sustained excitability elevations induced by
transcranial DC motor cortex stimulation in humans. Neurology
2001;57:1899-1901.
34. Priori A. Brain polarization in humans: A reappraisal of an old tool
for prolonged non-invasive modulation of brain excitability. Clin
Neurophysiol 2003;114:589-595.
35. Lefaucheur JP. Principles of therapeutic use of transcranial and
epidural cortical stimulation. Clin Neurophysiol 2008;119:2179-2184.
36. Nitsche MA, Fricke K, Henschke U, et al. Pharmacological modu-
lation of cortical excitability shifts induced by transcranial direct
current stimulation in humans. J Physiol 2003;553:293-301.
37. Aree-uea B, Auvichayapat N, Janyacharoen T, et al. Reduction of
spasticity in cerebral palsy by anodal transcranial direct current
stimulation. J Med Assoc Thai 2014;97:954-962.
38. Vandermeeren Y, Lefebvre S, Desfontaines P, Laloux P. Could dual-
hemisphere transcranial direct current stimulation (tDCS) reduce
spasticity after stroke? Acta Neurol Belg 2013;113:87-89.
39. Ochi M, Saeki S, Oda T, Matsushima Y, Hachisuka K. Effects of
anodal and cathodal transcranial direct current stimulation com-
bined with robotic therapy on severely affected arms in chronic
stroke patients. J Rehabil Med 2013;45:137-140.
40. Mori F, Codeca C, Kusayanagi H, et al. Effects of intermittent theta
burst stimulation on spasticity in patients with multiple sclerosis.
Eur J Neurol 2010;17:295-300.
41. Nielsen JF, Sinkjaer T, Jakobsen J. Treatment of spasticity with
repetitive magnetic stimulation; a double-blind placebo-
controlled study. Mult Scler 1996;2:227-232.
42. Wu D, Qian L, Zorowitz RD, Zhang L, Qu Y, Yuan Y. Effects on
decreasing upper-limb post-stroke muscle tone using transcranial
direct current stimulation: A randomized sham-controlled study.
Arch Phys Med Rehabil 2013;94:1-8.
43. Gunduz A, Kumru H, Pascual-Leone A. Outcomes in spasticity after
repetitive transcranial magnetic and transcranial direct current
stimulations. Neural Regen Res 2014;9:712-718.
44. Izumi S, Kondo T, Shindo K. Transcranial magnetic stimulation
synchronized with maximal movement effort of the hemiplegic
hand after stroke: A double-blinded controlled pilot study.
J Rehabil Med 2008;40:49-54.
45. Mally J, Dinya E. Recovery of motor disability and spasticity in
post-stroke after repetitive transcranial magnetic stimulation
(rTMS). Brain Res Bull 2008;76:388-395.
46. Kakuda W, Abo M, Kobayashi K, et al. Anti-spastic effect of low-
frequency rTMS applied with occupational therapy in post-stroke
patients with upper limb hemiparesis. Brain Inj 2011;25:496-502.
47. Kakuda W, Abo M, Momosaki R, et al. Combined therapeutic
application of botulinum toxin type A low-frequency rTMS, and
intensive occupational therapy for post-stroke spastic upper limb
hemiparesis. Eur J Phys Rehabil Med 2012;48:47-55.
48. Kakuda W, Abo M, Kobayashi K, et al. Combination treatment of
low-frequency rTMS and occupational therapy with levodopa
administration: An intensive neurorehabilitative approach for
upper limb hemiparesis after stroke. Int J Neurosci 2011;121:
373-378.
49. Sung WH, Wang CP, Chou CL, Chen YC, Chang YC, Tsai PY. Efficacy
of coupling inhibitory and facilitatory repetitive transcranial
magnetic stimulation to enhance motor recovery in hemiplegic
stroke patients. Stroke 2013;44:1375-1382.
1028 Spasticity Management
50. Etoh S, Noma T, Ikeda K, et al. Effects of repetitive transcranial
magnetic stimulation on repetitive facilitation exercises of the
hemiplegic hand in chronic stroke patients. J Rehabil Med 2013;45:
843-847.
51. Barros Galvão SC, Borba Costa dos Santos R, Borba dos Santos P,
Cabral ME, Monte-Silva K. Efficacy of coupling repetitive trans-
cranial magnetic stimulation and physical therapy to reduce
upper-limb spasticity in patients with stroke: A randomized
controlled trial. Phys Med Rehabil 2014;95:222-229.
52. Theilig S, Podubecka J, Bosl K, Wiederer R, Nowak DA. Functional
neuromuscular stimulation to improve severe hand dysfunction
after stroke: Does inhibitory rTMS enhance therapeutic efficiency?
Exp Neurol 2011;230:149-155.
53. Naghdi S, Ansari NN, Rastgoo M, Forogh B, Jalaie S, Olyaei GJ. A
pilot study on the effects of low frequency repetitive transcranial
magnetic stimulation on lower extremity spasticity and motor
neuron excitability in patients after stroke. Bodyw Mov Ther 2015;
19:616-623.
54. Rastgoo M, Naghdi S, Nakhostin Ansari N, et al. Effects of repeti-
tive transcranial magnetic stimulation on lower extremity spas-
ticity and motor function in stroke patients. Disabil Rehabil 2016;
38:1918-1926.
55. Terreaux L, Gross R, Leboeuf F, et al. Benefits of repetitive
transcranial magnetic stimulation (rTMS) for spastic subjects:
Clinical, functional, and biomechanical parameters for lower limb
and walking in five hemiparetic patients. Sci World J 2014;2014:
389350.
56. Kondo T, Kakuda W, Yamada N, Shimizu M, Abo M. Effects of re-
petitive transcranial magnetic stimulation and intensive occupa-
tional therapy on motor neuron excitability in poststroke
hemiparetic patients: A neurophysiological investigation using
F-wave parameters. Int J Neurosci 2015;125:25-31.
57. Centonze D, Koch G, Versace V, et al. Repetitive transcranial
magnetic stimulation of the motor cortex ameliorates spasticity in
multiple sclerosis. Neurology 2007;68:1045-1050.
58. Mori F, Ljoka C, Magni E, et al. Transcranial magnetic stimulation
primes the effects of exercise therapy in multiple sclerosis.
J Neurol 2011;258:1281-1287.
59. Valle AC, Dionisio K, Pitskel NB, et al. Low and high frequency
repetitive transcranial magnetic stimulation for the treatment of
spasticity. Dev Med Child Neurol 2007;49:534-538.
60. Kumru H, Murillo N, Samso JV, et al. Reduction of spasticity with
repetitive transcranial magnetic stimulation in patients with spinal
cord injury. Neurorehabil Neural Repair 2010;24:435-441.
61. Kumru H, Benito J, Murillo N, et al. Effects of high-frequency re-
petitive transcranial magnetic stimulation on motor and gait
improvement in incomplete spinal cord injury patients. Neuro-
rehabil Neural Repair 2013;27:421-429.
62. Benito J, Kumru H, Murillo N, Costa U, Medina J, Tormos JM, et al.
Motor and gait improvement in patients with incomplete spinal
cord injury induced by high-frequency repetitive transcranial
magnetic stimulation. Top Spinal Cord Inj Rehabil 2012;18:
106-112.
63. Kim DH, Shin JC, Jung S, Jung TM, Kim DY. Effects of intermittent
theta burst stimulation on spasticity after stroke. Neuroreport
2015;26:561-566.
64. Wupuer S, Yamamoto T, Katayama Y, et al. F-wave suppression
induced by supra-threshold high-frequency repetitive transcranial
magnetic stimulation in post-stroke patients with increased spas-
ticity. Neuromodulation 2013;16:206-211.
65. Gupta M, Lal Rajak B, Bhatia D, Mukherjee A. Effect of r-TMS over
standard therapy in decreasing muscle tone of spastic cerebral
palsy patients. J Med Eng Technol 2016;40:210-216.
66. Ameli M, Grefkes C, Kemper F, et al. Differential effects of high-
frequency repetitive transcranial magnetic stimulation over ipsi-
lesional primary motor cortex in cortical and subcortical middle
cerebral artery stroke. Ann Neurol 2009;66:298-309.
Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
67. Bradnam LV, Stinear CM, Barber PA, Byblow WD. Contra-lesional
hemisphere control of the proximal paretic upper limb following
stroke. Cereb Cortex 2012;22:2662-2671.
68. Del Felice A, Daloli V, Masiero S, Manganotti P. Contra-lesional
cathodal versus dual transcranial direct current stimulation for
decreasing upper limb spasticity in chronic stroke individuals: A
clinical and neurophysiological study. J Stroke Cerebrovasc Dis
2016;25:2932-2941.
69. Iodice R, Dubbioso R, Ruggiero L, Santoro L, Manganelli F. Anodal
transcranial direct current stimulation of motor cortex does not
ameliorate spasticity in multiple sclerosis. Restor Neurol Neurosci
2015;33:487-492.
70. Klomjai W, Lackmy-Vallée A, Roche N, Pradat-Diehl P, Marchand-
Pauvert V, Katz R. Repetitive transcranial magnetic stimulation
and transcranial direct current stimulation in motor rehabilitation
after stroke: An update. Ann Phys Rehabil Med 2015;58:220-224.
71. Hao Z, Wang D, Zeng Y, Liu M. Repetitive transcranial magnetic
stimulation for improving function after stroke. Cochrane Data-
base Syst Rev 2013;5:CD008862.
72. Elsner B, Kugler J, Pohl M, Mehrholz J. Transcranial direct current
stimulation for improving spasticity after stroke: A systematic
review with meta-analysis. J Rehabil Med 2016;48:565-570.
73. Pal PK, Hanajima R, Gunraj CA, et al. Effect of low-frequency
repetitive transcranial magnetic stimulation on interhemispheric
inhibition. J Neurophysiol 2005;94:1668-1675.
74. Tazoe T, Endoh T, Kitamura T, Ogata T. Polarity specific effects of
transcranial direct current stimulation on interhemispheric inhi-
bition. PLoS One 2014;9:e114244.
75. Sandrini M, Cohen LG. Noninvasive brain stimulation in neuro-
rehabilitation. Handb Clin Neurol 2013;116:499-524.
76. Priori A, Hallett M, Rothwell JC. Repetitive transcranial magnetic
stimulation or transcranial direct current stimulation? Brain Stimul
2009;2:241-245.
77. Lehmann JF, DeLateur BJ, Fowler RS, et al. Stroke rehabilitation:
Outcome and prediction. Arch Phys Med Rehabil 1975;56:383-389.
78. Buetefisch CM. Role of the contra-lesional hemisphere in post-
stroke recovery of upper extremity motor function. Front Neurol
2015;6:214.
79. Yamada N, Kakuda W, Kondo T, Shimizu M, Mitani S, Abo M.
Bi-hemispheric repetitive transcranial magnetic stimulation com-
bined with intensive occupational therapy for upper limb hemi-
paresis after stroke: A preliminary study. Int J Rehabil Res 2013;36:
323-329.
80. Sunnerhagen KS. Stop using the Ashworth Scale for the assessment
of spasticity. J Neurol Neurosur Psych 2010;81:2.
81. Mehrholz J, Major Y, Meissner D, Sandi-Gahun S, Koch R, Pohl M.
The influence of contractures and variation in measurement
stretching velocity on the reliability of the Modified Ashworth Scale
in patients with severe brain injury. Clin Rehabil 2005;19:63-72.
82. Mehrholz J, Wagner K, Meissner D, et al. Reliability of the Modified
Tardieu Scale and the Modified Ashworth Scale in adult patients
with severe brain injury: A comparison study. Clin Rehabil 2005;19:
751-759.
83. Yam WK, Leung MS. Interrater reliability of Modified Ashworth
Scale and Modified Tardieu Scale in children with spastic cerebral
palsy. J Child Neurol 2006;21:1031-1035.
84. Kim J, Park H-S, Damiano DL. Accuracy and reliability of haptic
spasticity assessment using HESS (Haptic Elbow Spasticity Simu-
lator). Conf Proc IEEE Eng Med Biol Soc 2011;2011:8527-8530.
This journal-based CME activity is designated for 1.0 AMA PRA
Category 1 Credit and can be completed online at www.me.
aapmr.org. This activity is FREE to AAPM&R members and avail-
able to nonmembers for a nominal fee. For assistance with claim-
ing CME for this activity, please contact (847) 737-6000.
 A. Leo et al. / PM R 9 (2017) 1020-1029 1029

Disclosure

A.L. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy P.B. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose Disclosure: nothing to disclose

A.N. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose
F.M. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose
P.T. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose
I.S. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose
A.B. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose
M.R. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
Disclosure: nothing to disclose
A.Q. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy; Department of
Biomedical, Dental Sciences, and Morphological and Functional Images, Uni-
versity of Messina, Italy
Disclosure: nothing to disclose
R.S.C. IRCCS Centro Neurolesi “Bonino-Pulejo” S.S. 113, Contrada Casazza,
98124, Messina, Italy. Address correspondence to: R.S.C.; e-mail: salbro77@
tiscali.it
Disclosure: nothing to disclose
A.L. and A.N. contributed equally to the manuscript.
Peer reviewers and all others who control content have no financial relationships
to disclose.
Submitted for publication September 6, 2016; accepted March 31, 2017.

CME Question
Transcranial direct current stimulation has the most evidence to support its use in reducing spasticity in which anatomic
location?
a. Lower limb.
b. Upper limb.
c. Both upper and lower limbs.
d. Truncal.
Answer online at me.aapmr.org

Downloaded for Anonymous User (n/a) at Universidad El Bosque from ClinicalKey.com by Elsevier on September 06, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.