Document Type : Original Article
Authors
1 Departments of Pediatrics, Faculty of Medicine, Al-Azhar University
2 Departments of Diagnostic Radiology, Faculty of Medicine, Al-Azhar University
3 Departments of Rheumatology, Physical Medicine and Rehabilitation, Faculty of Medicine, Al-Azhar University
Abstract
Keywords
CORRELATION BETWEEN BRAIN MAGNETIC RESONANCE CHANGES AND RESPONSE TO FUNCTIONALLY BASED REHABILITATION PROGRAM IN CHILDREN WITH SPASTIC CEREBRAL PALSY
By
Abd El-Hamed Fikry Abd El-Aziz1, El-Sayed Mohammed Al-Nagar1, Abd El-Naby Biomy Mohammed2 and Hassan Mohammed Awwad3
Departments of 1Pediatrics, 2Diagnostic Radiology and 3Rheumatology, Physical Medicine and Rehabilitation, Faculty of Medicine, Al-Azhar University
Corresponding author: Abd El-Hamed Fikry Abd El-Aziz,
Mobile: (+20) 01128421706, E-mail: Abd-Elhamedfk@Yahoo.com
ABSTRACT
Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood with prevalence rates of 2–3 per 1000 live births in developed countries. CP is the leading cause of physical disability in children. Thus, neuroimaging is currently recommended as a standard evaluation in children with cerebral palsy.
Objective: To investigate the relationship and inter-relation between functional profiles including; gross motor function and manual ability, with brain magnetic resonance imaging characteristics in children with CP before and at end of functionally based exercise program.
Patients and Methods: This study was carried out on twenty five spastic CP children of both genders at age ranged from 3 months old to 12 years old, attending the out-patient pediatric clinic of Bab Al Sha’reya University Hospital, during the period from May 2019 to December 2019.
Results: Diplegia was the most common represented type, followed by quadriplegia and hemiplegia. The common causes were hypoxic ischemic encephalopathy (52%), Post-kernicterus CP (32%), and Post traumatic CP (16%). History of mother drug intake, hypoxia, pre-mature birth, cyanosis and severe RDS, delivery with caesarian section, neonatal convulsion, jaundice and post-kernicterus complication, and head trauma were significantly associated with increased risk of CP.
Conclusion: History of mother drug intake, hypoxia, pre-mature birth, cyanosis and severe RDS, delivery with cesarian section, neonatal convulsion, jaundice and post-kernicterus complication, and head trauma were significantly associated with increased risk of CP. MRI scan was useful in revealing underlying brain abnormalities and speculating on the etiology of cerebral palsy.
Keywords: Brain Magnetic Resonance, Based Rehabilitation Program in Children, Spastic Cerebral Palsy.
INTRODUCTION
As a chronic condition, individuals with CP usually require lifetime medical, psychological, educational and social support. People with CP present with alterations in sensation, perception, cognition, communication and behavior that hinder activities of daily life, participation and quality of life (QOL) (García-Galant et al., 2020).
The cause of CP is very diverse. The neuroanatomical findings on imaging also correlating with the clinical phenotype are also varied, and degrees of involvement range from mild to severe, all resulting in different clinical presentations. All of these factors contribute to children having different functional levels. Two children with similar CP phenotypes due to similar causes may then ultimately have different courses due to the additional role of personal and environmental factors and the interplay of other existing medical comorbidities (Schwabe, 2020).
A number of functional scales have been validated by multiple studies for CP. They include Gross Motor Function Classification System (GMFCS), Manual Ability Classification System, Communication Function Classification System (CFCS) and Eating and Drinking Ability Classification System (EDAC). They are mainly used for predicting current and future management needs of children with CP, and their use agrees with current thinking in management of CP (Ogoke, 2018). The functional classification remains the best classification of CP because it is a useful guide to providing care for patients appropriate for their functional level and helps clinicians set and discuss with parents/caregivers realistic rehabilitation goals (Bax et al., 2012).
The most widely-used test battery that measures the functional motor level in order to determine the motor development level of children with CP is the Gross Motor Function Measurement (GMFM). With GMFM, we can define the motor function level of the child; obtain aid in specifying the targets of the treatment, follow-up the post treatment development and present objective information regarding the child to relevant colleagues, other inter-discipliner professionals and families (Franki et al., 2020).
Neuroimaging, especially magnetic resonance imaging (MRI), contributes significantly to the understanding of the etiology and pathology of CP, the timing of insults, and patients evaluations. Thus, categorizing patients with CP based on neuroradiologic findings were applied (Pakula et al., 2013).
Making a correlation between MRI brain finding and response to functionally based exercise program for spastic CP children would be a predictor of response to such a program in the future especially when comparing it with conventional physiotherapy (Franki et al., 2020).
This present study aimed to investigate the relationship and inter-relation between functional profiles including gross motor function and manual ability, with brain magnetic resonance imaging characteristics in children with CP before and at the end of functionally based exercise program.
PATIENTS AND METHODS
This study was carried out for spastic CP children attending the out-patient pediatric clinic of Bab Al Sha’reya University hospital, during the period from May 2019 to December 2019.
Inclusion criteria:
Twenty five spastic CP children of both genders at age range from 3 months old to 12 years old.
Exclusion Criteria:
1. Age of the patients more than 12 years and less than 3 months.
2. Any other type than spastic CP.
All children were subjected to:
1. Complete history taking including, prenatal, natal, and post-natal history, developmental history, vaccination, family history, relevant medical, surgical, trauma, and drugs used.
2. Clinical pediatric examination was performed stressing on neurological examination as related to our study.
3. All patients were examined by brain MRI and were classified functionally by GMFM and MAS.
4. Children were subjected to functionally based exercise program composed of circuit training of series exercises including aerobic and resistance exercises in every exercise session, of two weekly or at least three monthly schedules lasting for 6 to 8 months.
5. Using MRI scanning, investigate the relationship and inter-relation between functional profiles including; gross motor function and manual ability, with brain magnetic resonance imaging characteristics in children with CP before and at end of functionally based exercise program.
Modified Ashworth Scale (MAS) instructions:
General Information according to Rw and Smith (1987): Place the patient in a supine position. If testing a muscle that primarily flexes a joint, place the joint in a maximally flexed position and move to a position of maximal extension over one second (count "one thousand one”). If testing a muscle that primarily extends a joint, place the joint in a maximally extended position and move to a position of maximal flexion over one second (count "one thousand one”).
Scoring:
• 0 No increase in muscle tone.
• 1 Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension.
• 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM.
• 2 More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved.
• 3 Considerable increase in muscle tone, passive movement difficult.
• 4 Affected part(s) rigid in flexion or extension.
Gross Motor Function Measure (GMFM):
The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy. The scoring key is meant to be a general guideline. However, most of the items have specific descriptors for each score. It is imperative that the guidelines contained in the manual be used for scoring each item.
Scoring key:
• 0 = does not initiate.
• 1 = initiates.
• 2 = partially completes.
• 3 = completes.
• 9 (or leave blank) = not tested (NT) [used for the GMAE-2 scoring*].
It is important to differentiate a true score of “0” (child does not initiate) from an item which is Not Tested (NT) if you are interested in using the GMFM-66 Ability Estimator (GMAE) Software.
Statistical analysis:
Data collected throughout history, basic clinical examination, laboratory investigations and outcome measures coded, entered and analyzed using Microsoft Excel software. Data were then imported into Statistical Package for the Social Sciences (SPSS version 22.0) software for analysis. According to the type of data qualitative represent as number and percentage, quantitative continues group represent by mean ± SD. Wilcoxon Test Was Used, And Parried Test Was Used to compare before and after Treatment. Differences between parametric quantitative independent groups by t test. P value was set at <0.05 for significant results.
RESULTS
64% of studied group were males with mean age of 3.8 years old. Commonest type of CP presented among studied group was diplegia among 48% of them and commonest cause was 52% hypoxic ischemic encephalopathy (Table 1).
Table (1): Basic characteristics of the studied population
Studied group (n=25) Variables |
N |
% |
Gender Male Female |
16 9 |
64 36 |
Type of spastic CP Hemiplegia Diplegia Quadriplegia |
4 12 9 |
16 48 36 |
Cause of CP Post-kernicterus Hypoxic ischemic encephalopathy Post-traumatic |
8 13 4 |
32 52 16 |
|
Mean ± SD |
|
Age (years) |
3.8 ± 2.5 1 - 9 |
There was a statistical significant difference in both reading of Aschor scale before and after GMFM regarding upper and lower limbs results, while change in trunk reading after GMFM not reach significant level (Table 2).
Table (2): Difference in Aschor scale before and after GMFM among the studied population (Mean ± SD)
P-value |
After Rehabilitation |
Before Rehabilitation |
Difference Aschor scales |
<0.001 |
2.04 ± 0.61 1 – 3 2 |
3.2 ± 0. 91 2 – 4 4 |
UL Range Median |
0.01 |
2.52 ± 1.4 0 – 4 3 |
3.68 ± 0.72 2 – 4 4 |
LL Range median |
0.08 |
2.56 ± 1.41 0 – 4 3 |
3.52 ± 1.12 1 – 4 4 |
Trunk Range median |
There was a statistical significant difference in percentages of two results of GMFM regarding total score and lying and rolling item (Table 3).
Table (3): GMFM among the studied population (Mean ± SD)
P-value |
After Rehabilitation |
Before Rehabilitation |
Difference GMFM |
0.01 |
72 ± 14.96 58 – 86 72 |
5.9 ± 4.2 2 – 9.8 5.9 |
Lying & rolling (%) Range Median |
<0.001 |
63.7 ± 44.8 0 – 100 100 |
18.2 ± 25.1 0 – 60 1.7 |
Sitting Range Median |
0.001 |
49.2 ± 48.5 0 – 100 86 |
13.8 ± 25.3 0 – 69 0 |
Crawling & kneeling Range Median |
0.001 |
48 ± 47.6 0 -100 80 |
10.1 ± 13.9 0 – 30.8 0 |
Standing Range Median |
0.001 |
38.6 ± 40.3 0 – 100 52.8 |
3.38 ± 5.1 0 - 12.5 0 |
Walking, running & jumping Range Median |
<0.001 |
60.7 ± 41.9 2 – 100 77.5 |
15.6 ± 19.5 0 – 48 4 |
Total (%) Range Median |
.
68% of studied patients presented with abnormal MRI changes, commonly peripheral brain atrophy among 29.4% of them (Table 4).
Table (4): MRI changes among the studied population
% |
N |
Studied group N =25 Variables |
32 68 |
8 17 |
MRI before GMFM Normal for age Abnormal CNS insult |
23.5 29.4 23.5 23.5 |
(n=17) 4 5 4 4 |
Type of MRI change: Post hypoxic insult Peripheral brain atrophy Post cerebellar arachnoid cyst Impressive of lissencefhaly type 1 |
100 |
25 |
MRI after GMFM No change |
DISCUSSION
Twenty five spastic CP children of both genders at age range from (3 month old to 12 years old), were attending the out-patient pediatric clinic of Bab Al Sha’reya University Hospital. All children were subjected to complete history followed by clinical examination with special attention for neurological assessment. Finally, all children were examined by brain MRI and classified according to GMFM classification. Children were subjected to functionally based exercise program composed of circuit training of series exercises including aerobic and resistance exercises in every exercise session, of two weekly or at least three monthly schedules lasting for 6 to 8 months.
An epidemiological data in the current study of patients with CP determines the demographical, risk factors as well as clinical features of patients with CP. The current study showed that 64% and 36% of studied group were males and female, respectively, with no significant difference in age between different groups, with 1.7:1 male to female ratio. Similar results were reported (Pinto et al., 2016; Choi et al., 2018 and Hawe et al., 2020). In accordance, high prevalence rates in boys compared to girls were reported. Philip et al. (2020) documented that gender distribution was 52.1 % male and 48 % female. Also, Kundu et al. (2020) found that males were more affected than females (67.7% boys and 30.3% girls) with male to female ratio 2.09: 1, which might be conducted to the male sex hormones and difference in brain development between two genders. In contrary, Soleymani et al. (2010) reported that female prevalence was higher than male (52.7% and 47.3%, respectively).
Regarding types of cerebral palsy in the current study, diplegia was (48%), the most common represented type, followed by quadriplegia and hemiplegia ((36% and 16%, respectively). Previously reported distributions of motor subtypes within large CP populations have been highly variable, with hemiplegia, diplegia, quadriplegia, and other CP subtypes reported by Goel and Ojha (2015), Pinto et al. (2016) and Philip et al. (2020). Kundu et al. (2020) reported that most cases were 53.3% quadriplegic type, 20.7% hemiplegic, 10% diplegic. On the other hand, Springer et al. (2019) found that the distribution of CP types were 37.2% Hemiplegia, 19.9% diplegia, 30.4% tri/quadriplegia, 1.72% ataxic, 10.8% dyskinetic. Ara et al. (2018) documented that diplegia, quadriplegia and hemiplegia were 8.6%, 71.4% and 11.4%, respectively. However, Hou et al. (2014) noticed that spastic diplegia was the main type in preterm infants while hemiplegia and ataxia were mainly seen in term infants (Hou et al., 2014).
The major known etiological risk factors for CP were bleeding and threatened miscarriages in prenatal period, birth asphyxia, premature baby and low birth weight in the perinatal period, convulsions, and hyperbilirubinemia in the postnatal period (Ogoke, 2018). Whatever, presence of any of these conditions, it does not mean this will result in CP, rather it means higher prevalence of CP (Rana et al., 2017).
However, the common causes were observed in the current study were (52%) hypoxic ischemic encephalopathy, followed by (32%) Post-kernicterus CP and (16%) Post traumatic CP. However, relatively little data are available on the etiology of CP especially in low- and middle-income countries (LMIC). The limited data available suggest that CP in these countries is less often caused by complications associated with preterm birth than in western industrialized countries, and more often by asphyxia and hyperbilirubinemia at term, and by postnatal infections, such as meningitis (Hadders-Algra, 2014).
Prenatal, natal and post-natal risk factors for CP in the current study were been. As demonstrated in the results, history of mother drug intake, hypoxia, pre-mature birth, cyanosis and sever RDS, delivery with caesarian section, neonatal convulsion, jaundice and post-kernicterus complication, and head trauma were significantly associated with increased risk of CP. Comparable results were reported by Soleymani et al. (2010), who reported that neonatal convulsion and postnatal epilepsy, preterm delivery and maternal drug intake during pregnancy were significantly associated with CP.
The current study showed a statistical significant difference in percentages of results of GMFM between beginning and at end of program, regarding total score and lying and rolling item (high significant and significant, respectively).
The majority of research into the effectiveness of rehabilitation and the mechanisms that underlie responses to therapy has been conducted with school-aged children with CP, but major brain growth and development occurs in the first 2 years of life. This period could represent a critical window during which rehabilitation might be most effective (Reid et al., 2015). Such critical periods of development might primarily reflect time windows during which abnormal neural organization can be prevented, rather than periods during which the brain is simply more able to repair existing damage. One pilot study (n = 5) of lower limb rehabilitation has indicated that intense rehabilitation is feasible and effective in children with CP aged <2 years, and a follow-up clinical trial is in progress (Eyre, 2013).
In previous studies significant associations between gross motor function and manual ability were demonstrated (Hidecker et al., 2012, Himmelmann et al., 2013 and Compagnone et al., 2014). In the current study, results showed a statistical significant difference in both reading of MAS before and after GMFM program regarding upper and lower limbs results, while change in trunk reading after GMFM not reach significant level. Different responses were reported previously. Theis et al. (2015) and Kalkman et al. (2018) reported acute response to stretching, It was hypothesized that would be explained by the increase in fascicle strain. In contrary, Hösl et al. (2018) reported low response. However, the effectiveness of stretching-based interventions for improving function is poor. This may be due to the behavior of a spastic muscle during stretch, which is poorly understood (Kalkman et al., 2020).
That response might be explained by different theories. The neurological lesion in CP causes adaptations in the muscle, including muscle atrophy, fibrosis, muscle shortening and overstretched sarcomeres. Additionally, there is a lack of muscle growth (Willerslev-Olsen et al., 2018). This dynamic shortening of the muscles is typically treated with stretching exercises, botulinum toxin injections, casting or ankle-foot-orthoses (Kalkman et al., 2020). In children with CP this is additionally complicated by the fact that growth factor seems to be further altered from typical (Von Walden et al., 2018 and Pingel et al., 2019). Thus, stretching exercises, there is limited evidence to support functional improvements (Katalinic et al., 2011, Harvey et al., 2017 and Kalkman et al., 2020).
Brain imaging methodologies particularly Magnetic Resonance Imaging (MRI) have been employed to understand the micro and microstructural changes in the brain structure and function in CP patients (Ouyang et al., 2019). The brain lesions on MRI are classified as brain mal-developments, periventricular white matter lesions (PWML), grey matter lesions or post-natal lesions (Philip et al., 2020).
In the current study, abnormal MRI scans were reported in 68% of studied subjects, which classified into (52.9%) grey matter lesions; peripheral brain atrophy and post hypoxic insult (29.4% and 23.5%, respectively), in addition to (47.1%) brain mal-developments; impressive of lissencefhaly type 1, and post cerebellar arachnoid cyst (23.5%, each).
MRI imaging abnormalities were reported in different studies. Philip et al. (2020) reported that in 796 cases 97.6 % showing abnormalities on MRI. Also, Springer et al. (2019) and Kundu et al. (2020) reported that total 94.4% and 84.7%, respectively, had documented abnormal MRI.
Normal MRI findings were reported in different studies (van Genderen et al., 2012 and Qin et al., 2018). In the current study, normal MRI scans were detected among 32% of studied subjects. However, lower rate were reported by (15%) Reid et al. (2014), (12%) Arnfield et al. (2013), (10.4%) Yim et al. (2017) and (5.6%) Springer et al. (2019).
There are specific situations where one would expect a normal MRI; causal mechanisms that are sub-structural are one of them. Another one would be genetic or metabolic conditions. Although genetic causes of CP were previously thought to be uncommon, this notion is being challenged by multiple studies suggesting that there might be a stronger genetic link than was previously postulated (Springer et al., 2019). Also, Leonard et al. (2011) and Benini et al. (2013) suggested that the limitations of contemporary imaging may be part of the explanation. Franki et al. (2020) concluded that the quality of the certain type of MRI may have been higher scan quality compared to less recent types.
Among neuroimaging studies, brain magnetic resonance imaging (MRI) is regarded as the most suitable tool to visualize brain lesion and to obtain insight into the functional outcomes of patient with CP (Himmelmann et al., 2013). Several researches reported significant improvement of motor function after interventions (Kakuda et al., 2012 and Ueda et al., 2020). Mailleux et al. (2020) reported that global classification scales (i.e. GMFM, MAS) were related with MRI.
MRI changes in the current study after GMFM were not detected. Absence of MRI changes and its correlation with measures of clinical improvement suggested possible mechanisms underlying these changes (Wu et al., 2020).
Studies examining structure-function relationships in children with CP were limited (Wang et al., 2014, Arrigoni et al., 2016 and Meyns et al., 2016). However, structure function relationships cannot be thoroughly investigated using such conventional MRI measures (Mailleux et al., 2020). The use of more sensitive measures of function, such as robotics, might aid in detecting more subtle changes in function and as such allow for a better discrimination between the children. Diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging and fast spin echo imaging have improved greatly the possibility of a comprehensive radiologic changes (Pakula et al., 2013). Therefore, It was difficult to identify a clear relationship between brain structural changes on MRI with different motor type of CP (Philip et al., 2020).
Wu et al. (2020) hypothesized that after comprehensive treatments patients would develop regional and network topological alterations involving typical motor regions, as well as sensory/atypical regions; and these alterations in neural activities would correlate to clinical motor function scores.
CONCLUSION
History of mother drug intake, hypoxia, pre-mature birth, cyanosis and sever RDS, delivery with caesarian section, neonatal convulsion, jaundice and post-kernicterus complication, and head trauma were significantly associated with increased risk of CP. MRI scan was useful in revealing underlying brain abnormalities and speculating on the etiology of cerebral palsy.
There were associations between neuroimaging findings and neurological subtype and CP severity (i.e. GMFM Level). These observed associations may improve our understanding of the pathogenesis and etiology of CP and provide clinicians and families with information to aid in management of CP.
REFERENCES
العلاقة بین تغیرات الرنین المغناطیسی فی الدماغ والاستجابة لبرنامج إعادة التأهیل القائم وظیفیا لدى الأطفال المصابین بالشلل الدماغی التشنجی
عبدالحمید فکری عبدالعزیز عطیه1، السید محمد النجار1، عبدالنبى بیومى محمد2، حسن محمدعواد3
أقسام 1طب الأطفال و2الأشعة التشخیصیة و3الروماتیزم والطب الفیزیائى وإعادة التأهیل
کلیة الطب، جامعة الأزهر
خلفیة البحث: الشلل الدماغی هو السبب الأکثر شیوعًا للإعاقة الجسدیة فی مرحلة الطفولة مع معدلات انتشار تتراوح بین 2-3 فی 1000 ولادة فی البلدان المتقدمة. الشلل الدماغی هو السبب الرئیسی للإعاقة الجسدیة لدى الأطفال. وبالتالی یُنصح بالتصویر العصبی حالیًا کتقییم قیاسی فی الأطفال المصابین بالشلل الدماغی.
الهدف من البحث: بحث العلاقة والترابط بین الملامح الوظیفیة بما فی ذلک الوظیفة الحرکیة الإجمالیة والقدرة الیدویة مع خصائص التصویر بالرنین المغناطیسی للدماغ لدى الأطفال المصابین بالشلل الدماغی قبل برنامج التمرینات الوظیفیة وعند نهایته.
المرضی وطرق البحث: أجریت هذه الدراسة لخمسة وعشرین طفلاً یعانون من الشلل الدماغی من کلا الجنسین تتراوح أعمارهم من 3 أشهر إلى 12 سنة، فی عیادة الأطفال الخارجیة فی مستشفى باب الشعریة الجامعی خلال الفترة من مایو 2019 حتى دیسمبر 2019.
وقد تم لجمیع المرضى فحص التاریخ الطبی الکامل, فحص سریری کامل, تصویر بالرنین المغناطیسی للدماغ, تم التصنبف حسب GMFM و MAS, برنامج تمارین وظیفیة لمدة 6-8 أشهر, التحقیق فی العلاقة والعلاقة المتبادلة بین الملامح الوظیفیة مع خصائص التصویر بالرنین المغناطیسی فی الدماغ لدى الأطفال المصابین بالشلل الدماغی قبل برنامج التمرینات الوظیفیة وعند نهایته.
نتائج البحث: کان الشلل النصفی هو النوع الأکثر تمثیلاً ، یلیه الشلل الرباعی و کانت اکثر الأسباب الشائعة هی اعتلال الدماغ الإقفاری بنقص التأکسج (52٪). و ارتبط تاریخ تناول الأم للأدویة، ونقص الأکسجة، والولادة قبل النضوج، والزراق والضائقة التنفسیة الحادة، والولادة القیصریة، والتشنج الولیدی، والیرقان ومضاعفات ما بعد الصدمة، وصدمة الرأس، تزید بشکل کبیر خطر الإصابة بالشلل الدماغی. کشف فحص الجهاز العصبی المرکزی أن 84٪ من الأشخاص أغلقوا الیافوخ الأمامی منذ الولادة مما تسبب فی صغر الرأس. هذا بالإضافة إلى أنه، تم الکشف عن (48٪) تشنجات غیر منضبطة و(32٪) فرط ضغط الدم وفرط المنعکسات. وتم تسجیل أشعة رنین مغناطیسی غیر طبیعیة فی 68٪ من الأشخاص الذین تم دراستهم ، والتی انقسمت لآفات المادة الرمادیة (52.9٪) و سوء نمو الدماغ (47.1٪).
الإستنتاج: یرتبط تاریخ تناول الأم للأدویة، ونقص الأکسجة، والولادة قبل النضوج، واللون الأزرق والضائقة التنفسیة الحادة، والولادة القیصریة، والتشنج الولیدی، والیرقان ومضاعفات ما بعد الصدمة، وصدمة الرأس، بشکل کبیر مع خطر الإصابة بالشلل الدماغی. التصویر بالرنین المغناطیسی مفید فی الکشف عن تشوهات الدماغ الأساسیة فی مسببات الشلل الدماغی. وهناک ارتباطات بین نتائج التصویر العصبی والنوع الفرعی العصبی وشدة الشلل الدماغی (أی مستوى GMFM)، وتحسن هذه الارتباطات التی تم ملاحظتها فهم مسببات المرض ومسببات الإصابة بالشلل الدماغی وتزوید الأطباء والعائلات بالمعلومات للمساعدة فی إدارة الشلل الدماغی.
REFERENCES