Application of Low-Intensity Modified Constraint-Induced Movement Therapy to Improve the Affecter Upper Limb Functionality in Infantile Hemiplegia with Moderate Manual Ability. Case Series

Objective: To assess the functionality of the affected upper limb in children diagnosed with hemiplegia aged between 4 and 8 years after applying low-intensity modified constraint-induced movement therapy(mCIMT). Methods: Prospective case series study. A mCIMT protocol was applied for five weeks, with two hours of containment per day. The study variables were: quality of movement of the upper limb, spontaneous use, participation of the affected upper limb in activities of daily living, dynamic joint position, grasp-release action, grasp strength, supination and extension elbow movements. Four measurements were performed, using the QUEST scale, the SHUEE Evaluation, a hand dynamometer and a goniometer. Results: The sample was composed of 8 children with moderate manual ability. Statistically significant differences were detected in all the studied variables (p&lt;0.05). The greatest increase occurred in spontaneous use from assessment 1-4 (p = 0.01), reaching 88.87% active participation in bimanual tasks. The quality of movement of the upper limb obtained a significant value due to the increase in dissociated movements and grasp (p = 0.01). Conclusion: A low dose (50 hours) of mCIMT increased the functionality of children diagnosed with congenital hemiplegia between 4 and 8 years of age with moderate manual ability.


Introduction
Infantile hemiplegia is a subtype of infantile cerebral palsy, characterized by the affectation of one of the hemibodies as a consequence of brain injury. Its prevalence is 1 case per 1,300 lived births [1]. There is more affectation of the upper limb than the lower limb due to the alteration of the corticospinal tract. The affected hand has a deficit in proprioception and tactile perception, which hinders fine motor skills, generally those of the fingers and the strength exerted by them [2]. Sensory abnormalities, weak grasp and loss of manual ability (fine movements) may appear, specifically in the fingers, with slower movements, poorer coordination and longer phases associated with mirror movements. This leads to a decrease in the use of the affected hand and often interferes with the manual ability of the healthy upper limb [3] .
From early childhood, children with hemiplegia, even the least affected, use their healthy hand as the dominant hand in all tasks. Therefore, they learn "not to use" their affected upper limb, which is known as developmental disregard [4] . This "non-use" of the affected upper limb produces an increase in muscle tone in the affected segment, poor motor control, decreased active and passive range of motion, generalized weakness and delayed musculoskeletal maturation. The non-use affectation is caused by neural dysfunction as a result of brain injury. This neuronal alteration [5] can be improved through the activation of certain brain areas that remained inactive after the brain lesion and also through experience and learning (trial-error).
Thus, in order to improve the affected upper limb "non-use", Constraint-Induced Movement Therapy (CIMT) is used [6,7] , which consists in constraining the healthy upper limb with a whole or partial containment (glove), thus promoting the use of the affected upper limb in activities of daily living. The programmed tasks integrate the repetition of the motor action with a variety of exercises.
There are a variety of protocols used for CIMT, with the most widely used in pediatrics being those based on modified Constraint-Induced Movement Therapy (mCIMT), which constrain the healthy upper limb for less than 3 hours [8][9][10] . McConnell et al. [11] found that a less intensive treatment (63 hours of treatment over 21 days) produced similar benefits compared to a more intensive approach (126 hours of treatment over 21 days). Functional gains may be feasible for some children with a less intense program adjusted to 20 hours of therapy in more than two consecutive weeks.
According to Schweighofer et al. [12] , the existence of a "functional threshold" would be necessary for the maintenance of functionality after therapy, below which the use of the upper limb decreases while the benefits to the individual remain above such threshold. It would be useful to determine the specific doses of therapy in each patient.
For this reason, we consider assessing the functionality of the affected upper limb in children diagnosed with congenital hemiplegia with moderate manual ability between 4 and 8 years of age after applying low-intensity modified constraint-induced movement therapy (50 hours).

Materials and Methods
This is a case series, prospective and longitudinal study with non-probability sampling (clinical.gov NCT02178371). The study was approved (060-13) by the ethics committee of the CEU-San Pablo University of Madrid in accordance with the Declaration of Helsinki of the World Medical Association. Before initiating the study, an informed consent form was given to the children's families to participate, which guaranteed the right to withdraw from the study at any time, if required by the participants.
The inclusion criteria were: medical diagnosis of left/right congenital infantile hemiplegia, age between 4 and 8 years, lack of activity of the affected upper limb, exceeds 10º extension in the metacarpophalangeal and interphalangeal joint, completes the 20º extension of the wrist of the affected upper limb, adequate cognitive development to understand the verbal orders given for the execution of tasks and cooperation in their execution. In the same way, the exclusion criteria were: visual problems that prevented the individual from carrying out the intervention, suffering from significant balance disturbances that put the child at risk of falling as a consequence of having the healthy upper limb contained, presenting uncontrolled epilepsy, having received botulinum toxin within 6 months prior to the intervention.
All the children were selected according to the inclusion criteria by their rehabilitation doctor of the "Virgen de la Salud" Hospital in Toledo for the execution of the therapy.
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Intervention Method
The study was carried out in a period of 5 weeks of treatment, containing the healthy upper limb for 2 hours per day (not continuously) from Monday to Friday. The intervention was carried out by the family at home. Previously, an informative meeting was held with the parents, in which all the details of the study were explained to them and a program of unimanual activities was given to them to be executed with the affected upper limb every treatment week. The parents of the children were instructed to correctly carry out the intervention avoiding possible errors during the treatment protocol. The weekly exercises, the containment technique and its correct use were also taught to them.
The containment applied was partial, such as a glove or a bandage [13] . In this way, manipulation with the healthy hand was prevented and the wrist and elbow joints were also free to allow the child to react effectively to an external disturbance ( Figure 1).

Figure 1.
Child with left hemiplegia wearing a bandage as a partial containment in the right hand (dominant hand). In this task, the child is working the grasp-release action.

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Each week, the therapist and the parents of the participants had a meeting to follow-up the tasks and solve problems. The parents were asked to fill out a table with the performed tasks, completing these with photographs and videos of the tasks carried out daily and the execution time.

Data Collection
Four assessments were performed to measure the study variables and to compare the results before, during and after the intervention (Figure 2).

Quality of movement and bimanual dexterity of both upper extremities
The Quality of upper extremity test (QUEST) [14][15][16] was used, validated for children with neuromotor dysfunction with spasticity from 18 months to 8 years of age. It provides a numerical value that is obtained from the mean of the percentages in 36 items distributed in four categories: dissociated movements, grasp, weight bearing and protective extension of both extremities. It takes a value from 0 to 100, and can be expressed in percentages (%).

Active extension of the wrist and active supination of the forearm in the affected upper limb
Both variables were measured with an arm goniometer [17] , making three measurements for each variable and selecting the best result. The measurements were made with the child sitting.
Wrist extension was measured with elbow flexion, with the child leaning on a table to decrease muscle tension and associated reactions. Supination was measured with the forearm close to the body, avoiding trunk compensations to gain greater joint width.

Grasp strength in the affected hand
This was measured using a hand dynamometer [18] with a scale between 0 and 150 that expressed grasp strength in PSI (pound per square inch, 1psi = 0.0703kg / cm 2 ). The test was performed with the child sitting in a chair and with their affected forearm resting on a table to give stability to the upper limb ( Figure 3). The children were asked to press the dynamometer as hard as possible to record the measurement.

Spontaneous use, dynamic positioning of the affected upper limb, grasping and releasing action (wrist position in neutral flexion-extension), and level of functionality and integration of the affected upper limb in various activities of daily living
The Shriners Hospital for Children Upper Extremity Evaluation (SHUEE) [16,19] was used to obtain the values in the four measurements. This evaluation consists in videotaping the children while they execute a series of tasks to observe the functionality and the joint alignment of the affected upper limb, and it has been validated for use in children with hemiplegia aged between 3 and 18 years. The results are expressed in percentages, with 100% being the best result.
The level of functionality and participation of the patient's upper limbs was determined through the SHUEE assessment as dependent, assisted or independent. Activities of daily living, such as dressing upper limbs, dressing lower limbs, buttoning, putting on socks, putting on shoes, putting on splints and personal hygiene were assessed.

Statistical analysis
The statistical program SPSS version 20.0 for Windows was used. The results are shown as median and quartiles Q1-Q3 with a 95% confidence interval. The results were compared by variable with the non-parametric Friedman test. Subsequently, a Wilcoxon pair test was performed on those variables that presented statistical significance. Those with a p-value <0.05 were considered as significant values. The qualitative variable of "functionality" was turned into a quantitative variable, graduating it in 5 levels, from 0 = worst functionality to 4 = maximum functionality (Table 1).

Results
The sample consisted of 8 children, 50% males and 50% females, diagnosed with congenital hemiplegia. Of the entire sample, 62.5% had affectation of the left upper limb. The average age was 6 years, with a standard deviation of 1.77 years. After assessing the motor ability of the children, they were classified at level I in the Gross Motor Function Classification System (GMFCS) [20] and at level II in the manual ability classification system (MACS)[21]

Quality of movement of the upper limb
The total score in the quality of movement in the upper limbs obtained an increase of 94.07%.
All the variables that compose it, i.e., dissociated movements, grasp, weight bearing and protective extension, showed statistical significance (p = 0.00) in the Friedman test (Table 2).
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 17 July 2020 doi:10.20944/preprints202007.0368.v1  (Table 3). No statistically significant differences were found for weight bearing between the second and third measurements (p = 0.14), second and fourth measurements (0.10) or third and fourth measurements (p = 0.11), nor for protective extension between the baseline and second measurements or second and third measurements (p = 0.07).

Grasp strength
The Friedman test showed significance in all assessments (p = 0.00) ( Table 4). The largest increase observed occurred from the third to the fourth measurement, with 1 PSI. All comparisons between measurements were statistically significant (p <0.05), except between the baseline and second measurements (p = 1) ( Table 5).

Active elbow extension and forearm supination
Both variables increased their value in each of the assessments carried out, obtaining an increase of 21ᵒ for elbow extension between the baseline and fourth measurements (p = 0.011), and an increase of 11.50ᵒ for the supination of the forearm (p = 0.011) between the baseline and fourth measurements (Tables 6-7).

Spontaneous use, dynamic joint position of the affected upper limb, grasp and release action (wrist position in neutral flexion-extension), and level of functionality and integration of the affected upper limb in different activities of daily living.
Spontaneous use increased in all evaluations, reaching 88.87% in the fourth measurement, as well as dynamic joint position and grasp-release action with different wrist positions, with 88.20% and 91.67%, respectively. These three variables showed statistical significance in the Friedman test (Table 8). The pairwise comparison (Table 9) showed that, in spontaneous use, the values of the second and third measurements were not significant when compared with the values of the fourth measurement. In dynamic positioning, only the difference between the second (p = 0.06) and third (p = 0.09) measurements was not significant. Grasp-release action was only significant between the baseline and fourth measurements (p = 0.03) and between the second and fourth measurements (p = 0.04). An increase was observed in all the variables of functionality and integration of the affected upper limb in various activities of daily living. All increases were statistically significant (p <0.05), except for "buttoning buttons", where p = 0.163 (Table 10). In the pairwise comparison of the measurements for the action of dressing the upper limbs and putting on the orthoses, no statistical significance was detected (p >0.05). In the action of dressing the lower limbs, statistically significant differences were obtained in all assessments, except between the baseline and second measurements and between the second and third measurements (p = 0.16). In Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 17 July 2020 doi:10.20944/preprints202007.0368.v1 the action of putting on shoes, significant differences were found between the baseline and third measurements (p = 0.32), basal and fourth measurements (p = 0.06) and second and fourth measurements (p = 0.10). In the action of putting on socks, the differences between the baseline and second measurements (p = 1) and between the third and fourth measurements (p = 0.08) were not significant. Regarding personal hygiene, only the changes between the baseline and fourth measurements and between the second and fourth measurements were significant (p = 0.02) ( Table 11).

Discussion
The deterioration of hand functionality causes a weakness present in the execution of activities of daily living in children with hemiplegia. There is an alteration compared to the healthy upper limb that manifests in the general slowness of movement, discontinuous movements, variability in the trajectory of the hand with compensations of the trunk and the presence of inadequate coordination in the grasp strength of the affected hand [22] . The improvement in grasp strength and stability occurs from the third to the fourth measurement due to an increase in hand strength. The increase was observed only in the last measurement, which could be due to the need for longer treatment time (5 weeks of intervention). These children with impaired fine motor adjustment, lack of finger dissociation, and deficient proprioception in their affected hand, had greater experience In 2011, a different study [25] , conducted exclusively with a girl with hemiplegia, used mCIMT for one hour per day for two weeks. No significant results were obtained at the end of the treatment, which was thereby prolonged for one more week of intervention. This last assessment showed an increase in the overall percentage of total quality of movement (also measured by the Quest scale), appreciable in activities that involve the affected upper limb. Thus, the protocol chosen for the intervention and the initial functionality of the patient are two important factors to take into account in increasing the results obtained in the measurements.

Limitations and future lines of research
As this is an uncontrolled trial [26] due to the absence of a control group, it cannot be guaranteed that the observed response (changes produced throughout the intervention with respect to the baseline situation) is exclusively due to the mCIMT protocol used, since other uncontrolled factors may also have an influence on it. Therefore, the effectiveness of the mCIMT in increasing the Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 17 July 2020 doi:10.20944/preprints202007.0368.v1 functionality of the affected upper limb seen in the present study cannot be generalized to the population of children with hemiplegia, and thus the fundamental utility of this study is descriptive.
It is important to highlight the statistically significant results obtained in the different studied variables throughout the 5 weeks of the intervention. This suggests that, although there was no control group, it could be inferred that the changes obtained in the improvement of the functionality were due to the efficacy of the treatment, since it was a short period of time, where important differences were observed in the affected upper limb, which is unlikely to occur due to the maturation effect (learning and natural development of the child over time).
This study leads us to open different lines of research, such as including a control group to assess the effectiveness of the treatment in the functionality of the affected upper limb, to verify whether the gains obtained after the intervention are maintained over time (6 months or one year after therapy), and to study the influence of age on the obtained results due to neuronal plasticity and active participation of the subject.