The Role of Repetitive Transcranial Magnetic Stimulation in Spastic Hemiplegic Cerebral Palsy in a Sample of Egyptian Children

 INTRODUCTION

As a noninvasive neurostimulation technology, repetitive TMS sends magnetic pulses deep into the brain tissue using electromagnetic induction concept. Motor cortex stimulation results in corticospinal and intracortical modulation.¹

rTMS was used to treat motor-related neurological diseases such as stroke, and MS.² One such disease very common in infancy is cerebral palsy.³

CP is a collection of neurological disorders that begin in infancy or early childhood. It affects body mobility and muscle coordination permanently. Hemiplegia is a major form among spastic cerebral palsy accounting for 21 – 40% of CP cases.⁴ Spasticity causes musculoskeletal issues such as contractures, pain, and subluxation. Removal of spasticity improves motor functions and life quality.⁵

Among various interventions used to manage spasticity in CP such as using antispastic drugs, botulinum injections and surgical procedures, physical therapy (PT) is a major rehabilitation therapy which improves motor activity and decreases muscle stiffness.⁶

Additionally, rTMS has a good effect in cerebral palsy⁷ including improved motor activity ⁸ and reduced muscle tone.⁶

Following evidences from the reported literatures, we hypothesized that using rTMS combined with physical therapy in spastic hemiplegic CP children may improve motor functions and decrease muscle tightness. This will improve patients' quality of life.

We aim to assess the effect of high frequency rTMS on improvingspasticity and motor performance in spastic hemiplegic CP in a sample of Egyptian children.

PATIENTS AND METHODS

The study was approved by the Ethics Committee of the Al-Azhar Faculty of Medicine and was registered in ClinicalTrials.gov (identifier: NCT05134259). We obtained written informed consent from parents/guardians before enrollment in this study.

Sixty-five children diagnosed with spastic hemiplegic CP by consultant pediatric neurologists and met our inclusion criteria were selected from the Neuro-Pediatric Unit of Al-Azhar University hospitals in the period from beginning of Jan, 2022 to the end of June, 2022.

Inclusion criteria:

In this study, we included patients aged 4 to 18 years, with mild to moderate muscle spasticity (Grade 1, 1+,2 on modified Ashworth scale), and ability to walk with limitation or holding on (level II, III, IV according to Gross Motor Function Classification System).

Exclusion criteria:

The exclusion criteria followed were: Any metallic implant, severe abnormalities (e.g. cognitive or sensory deficits), seizures, other central or peripheral nervous system dysfunction, botulinum toxin use in the previous 4 months, clinically suspected active inflammatory or pathologic changes in lower limb joints during the previous 6 months, fixed deformities in lower limbs,  clinically suspected active medical problems (e.g. pneumonia, meningitis, or encephalitis, and finally, metabolic disorders, such as inborn error of metabolism, electrolyte, and endocrine disorders.

The recruited children were randomly assigned into control group (N: 25) and study group (N: 40). Both groups were matched in age, sex, degree of disability and cognitive functions, with the same exclusion criteria, undergoing the same physical therapy and medical treatment but with change of dose according to the body weight.

Study group; forty patients received 8 sessions of high frequency rTMS
(2 sessions per week for 4 weeks) followed by 30 minutes of physical therapy (PT).

Control group; twenty-five patients received only physical therapy (PT) of 30 minutes (2 sessions per week for 4 weeks).

Stimulation device

With Magstim Rapid² having angulated figure of eight-shaped coil as well as two channels of Neuro-EMG–MS digital system, TMS device used in this study delivers repetitive trains of magnetic pulses.

rTMS procedure

All magnetically sensitive objects were left outside the TMS room. Patients were asked to sit comfortably on a chair to be relaxed as much as it is possible.

Before starting rTMS treatment, motor threshold (MT) of study group participants was measured. Settings of the magnetic stimulator were adjusted to single pulse working mode. Vertex was determined as a point of intersection of a line connecting the nasion and inion with another line connecting the right tragus to the left one. Motor cortex hot spot for the first dorsal interosseous muscle lies approximately 7 cm lateral to the vertex in a line perpendicular to parasagittal plan.

The center of the coil was placed on the scalp in a tangential line to the area of FDI and the handle is placed at 45 degrees with the sagittal plane. Initial intensity was set and single pulse was started over the area and the muscle contraction was inspected. The intensity of stimulation was gradually decreased or increased until reaching the lowest intensity that produce muscle contraction in at least 5 of the 10 consecutive trials. This intensity is called motor threshold (MT). This was repeated before each TMS session in the study group. Stimulation intensity for the rTMS procedure was set at 90% of the MT.

The study group received 1500 pulses (50 pulses per train with total 30 trains) per session with an intensity of 90% of the MT at a frequency of 10 Hz. The coil was placed on the contralateral primary motor cortex (M1). Each train had duration of 30 sec with inter- train delay of 25 seconds. rTMS frequency of 10 Hz was kept constant based on previous studies with 5 Hz and 10 Hz. ^9&10

Outcome measures

Prior to start of the study, scaling of spasticity and motor performance using Modified Ashworth Scale(MAS)and Gross Motor Function Classification System (GMFCS) were employed to all participants. After completion of 8 sessions, again post recording of both GMFCS and MAS were performed. The PT sessions were delivered by trained experts who were kept blinded to the study's research protocol.

STATISTICAL ANALYSIS

SPSS (Statistical Package for the Social Science) program version 25.0 (IBM Inc., Chicago, USA), Microsoft Office Excel 2016 software were used to calculate the statistical significance. Improvement was measured by Mean change.

We used Kolmogorov–Smirnov test to validate normal distribution of data. Descriptive statistics were done for all studied parameters in the two studied groups. Percentages represented qualitative data. Mean ± SD (Standard deviation) represented quantitative parametric data. Difference between qualitative variables in both groups was calculated using Chi square test (χ2). Difference between parametric quantitative variables in both groups was calculated using Independent T test. Difference between two paired groups with qualitative variables was calculated using Wilcoxon signed ranks test. The obtained findings were evaluated at 5% significance level.

RESULTS

The current study showed that there was no significant difference between both groups regarding age, height, Weight, and gender. (table 1)

Pre intervention, there was no significant difference between both groups as regards spasticity assessed by MAS and gross motor activity assessed by GMFCS while post intervention, there was statistically significant difference between both groups. (Tables 2 & 3)

In control group, there was statistically significant difference between Pre and Post intervention as regards MAS and GMFCS. (Table 4)

In study group, there was statistically significant difference between Pre and Post rTMS regarding MAS and GMFCS. (Table 5)

The improvement in spasticity of participants in study group was 1.4% as compared to 0.68% in control group while the improvement in gross motor activity of participants in study group was 1.73% as compared to 0.76% in control group. (Table 6)

No adverse effects or seizures were recorded during the period of the study, so rTMS is considered safe and effective treatment option.

NS: non significant

Table 1: Participant’s characteristics in the control and study group.

NS: non significant                 S: significant

Table 2: Modified Ashworth Scale (MAS) in Control group  and Study group Pre and Post intervention.

NS: non significant                 S: significant

Table 3: Gross Motor Function Classification System (GMFCS) in Control group  and Study group Pre and Post intervention.

HS: highly significant

Table 4: Comparison between Pre and Post rTMS Regarding MAS, GMFCS, in the Control Group.

HS: highly significant

Table 5: Comparison between Pre and Post intervention regarding MAS, GMFCS, in the study Group.

Table 6: The improvement in spasticity and motor function of participants in study group VS control group.