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National Guideline Alliance (UK). Cerebral palsy in under 25s: assessment and management. London: National Institute for Health and Care Excellence (NICE); 2017 Jan. (NICE Guideline, No. 62.)
Review question: Does MRI in addition to routine clinical assessment (including neonatal ultrasound) help determine the aetiology in children and young people with suspected or confirmed cerebral palsy and, if so, in which subgroups is it most important?
8.1. Introduction
Cerebral palsy is a descriptive term incorporating many different non-progressive aetiologies. The pathogenesis is dependent upon structural or functional abnormalities of the developing brain occurring in the antenatal, perinatal or postnatal phases. The particular underlying structural pathology observed is dependent on the stage of fetal or neonatal brain development at the time of abnormal formation or insult.
Some genetic and progressive disorders may mimic cerebral palsy in their early stages and might be identified by magnetic resonance imaging (MRI). The addition of MRI to aetiological assessment might potentially identify such individuals.
As stated elsewhere, children with cerebral palsy generally present from either a ‘high risk’ population or if there is developmental diversion from population norm. As such, a child who is suspected of having or who is confirmed to have cerebral palsy will be usually a few months old. When there is a clear antenatal, perinatal or postnatal history of possible risk, clinical and developmental examination is important in revealing the type and extent of the motor disorder. However, the Committee was aware that the type of motor disorder and the geographical pattern of motor disorder – i.e. which limbs are affected – did not always correlate with presumed aetiology.
Imaging of the brain may show an explanation for impairment. Neonatal ultrasound of the brain is readily available in most neonatal units and with appropriate training is easy to do and painless for the baby. However, neonatal ultrasound does not provide as much detail of brain structure and needs the operator to be skilled in interpretation. Babies who do not have any difficulties in the neonatal period, or who were not born preterm, are unlikely to have had neonatal ultrasound scans.
The Committee considered that help in determining aetiology was important for parents particularly to identify whether there were any avoidable risk factors for future pregnancies and if genetic factors may be present. As diagnostic techniques evolve, children with cerebral palsy, particularly those who have normal MRI scan, may benefit from other investigations, including newer genetic techniques.
However, in practice, children older than 3 months of age usually need sedation or general anaesthetic for an MRI and the Committee were aware of the small risk associated with this. In determining the value of MRI scanning of all children it was also important to consider the cost implications, including anaesthetic and day admission balanced against any extra information on possible aetiology that an MRI would bring.
The Committee felt that a comparison of accuracy in determining aetiology of cerebral palsy using a variety of clinical, developmental and imaging assessments was felt to be necessary.
8.2. Description of clinical evidence
No relevant clinical studies that provided diagnostic accuracy for MRI as an index test for the identification of aetiological findings in cerebral palsy were found, in comparison to a reference test of:
- Clinical assessment alone.
- Clinical assessment with cranial ultrasound.
- Clinical assessment with cranial ultrasound and other blood urine or cerebro-spinal fluid (CSF) investigations.
- When comparing neuroimaging techniques, 1 study (De Vries 1993) was included that conducted cranial ultrasounds on infants with periventricular leukomalacia (PVL) who were later confirmed with cerebral palsy using MRI. It is important to note the following limitations with this study:
- Participants included were neonates in a neonatal intensive care unit (NICU), identified with PVL on cranial ultrasound, who later developed cerebral palsy.
- No statistical analysis, including diagnostic accuracy, p-values or correlation co-efficients were reported.
For full details see the review protocol in Appendix D. See also the study selection flow chart in Appendix F, study evidence tables in Appendix J and the exclusion list in Appendix K.
8.3. Clinical evidence profile
The results from the 1 study included (De Vries 1993) is presented in Table 29.
Table 29
Results from included studies.
8.4. Economic evidence
No economic evaluations of MRI scans in children and young people with cerebral palsy were identified in the literature search conducted for this guideline. Full details of the search and economic article selection flow chart can be found in Appendix E and Appendix F, respectively.
Table 30 below presents the cost of MRI scans, taken from NHS Reference Costs 2015. It is important to note that the national average unit costs presented in Table 30 are likely to be underestimated for scans done in children and young people with cerebral palsy. This is because many patients would need a general anaesthetic, and the procedure may take longer than average to do. The Committee noted that although a general anaesthetic is more costly than oral sedation, it is the preferred method in young children with cerebral palsy as it can provide better images at a lower risk. Moreover, an MRI done under oral sedation may need repeating if the images are unclear; hence, the additional cost of oral sedation compared to general anaesthetic would be negligible compared to the expected cost of an additional scan.
Table 30
Cost of MRI scans.
The clinical evidence base to identify if MRI scans can provide additional information to a clinical assessment in children and young people with cerebral palsy was limited. If a model was built on the study by De Vries 1993 that was included in the clinical evidence review, MRI would never be considered cost effective compared to ultrasound. Ultrasound was treated as the reference standard in the study; hence, MRI would be dominated by ultrasound as it is more expensive. According to NHS Reference Costs 2015 the cost for an ultrasound scan is £55 (RD40Z, diagnostic imaging, ultrasound scan less than 20 minutes). Because of the lack of evidence on the effectiveness of MRI scans, economic considerations were restricted to a description of the costs.
MRI scans in addition to a clinical assessment would not be considered cost effective if there was not an effective treatment for the condition being diagnosed, or if the patient’s management was not changed by the results of the scan. In other words, if MRI scans did not add any additional information to a clinical assessment and did not change the patient’s management strategy, MRI scans should not be recommended.
Overall, cost data for MRI scans have little use without associated benefits; hence, while the costs of MRI scans could be significant, without knowing the benefits of MRI scans, the Committee cannot determine if they will be cost effective. Recommendations on the population identified to need MRI scans, and the frequency of scans could have significant resource implications. Therefore a research recommendation to consider the effect of MRI scans, in addition to a clinical assessment, preferably at different frequencies, would benefit from health economic input to assess the cost effectiveness of providing an additional intervention to the clinical assessment.
8.5. Evidence statements
One study with low-quality evidence was included that showed that PVL grade I, II and III was identified using cranial ultrasound up until 40 weeks postmenstrual age. Further detail was identified using MRI between 11 and 30 months, including ventricular enlargement, periventricular hypersensitivity, delay in myelination and thinning of corpus callosum.
8.6. Evidence to recommendations
8.6.1. Relative value placed on the outcomes considered
Outcomes considered in this evidence review relate to the identification of the proportion of participants with each neuroimaging pattern against aetiologies, including periventricular leukomalacia (PVL) and diffuse encephalopathy. No studies reporting this outcome were identified for this evidence review. However, 1 study was included that provided a description of findings from cranial ultrasound and MRI in children with PVL who were later diagnosed with cerebral palsy.
8.6.2. Consideration of clinical benefits and harms
The Committee noted that evidence presented was limited and did not provide a thorough answer to the review question.
Therefore, all recommendations developed as part of this planned evidence review were based on the Committee’s clinical experience and guidance from co-opted expert opinion and were agreed by consensus. The Committee discussed at length the difficulties and limitations of assessing aetiology of cerebral palsy using only radiological imaging.
Based on expert opinion and their clinical expertise, it was agreed that MRI alone does not accurately determine the aetiology of cerebral palsy and that healthcare professionals need to take account of family, antenatal, perinatal and postnatal histories; the child or young person’s ongoing medical history; the results of clinical examination and early cranial ultrasound examination if that has occurred. They agreed that children who are suspected or known to have cerebral palsy where there is no clear aetiology of cerebral palsy based on antenatal, perinatal or postnatal history, neurological examination or other investigations, are recommended to be offered an MRI scan. It was the Committee’s view that, despite the limited evidence to support a strong recommendation, if clear aetiology could not be established from the above criteria, then doing the MRI would be the next option for these children, in line with international consensus. Equally in the presence of family history, they considered that an MRI could help with decision-making regarding the possibility of an inherited genetic cause.
The Committee discussed that limited evidence showed ultrasound (US) scans done during the neonatal period found the same areas of damage in the brain as an MRI scan done at follow-up (around 2 years of age). As such it was noted that US are routinely used in high-risk infants on the NICU, especially in preterm babies.
In determining aetiology, the Committee discussed if findings from an MRI scan could inform or alter the management of a person with cerebral palsy. It was noted that it could alter management in some individuals. For example, the MRI findings in a child and young person with hemiplegic cerebral palsy may alter clinical management, for example, the need to monitor the size of an enlarging porencephalic cyst, as it may indicate evolving hydrocephalus or the need for further investigations such as visual assessment for hemianopia.
It was noted that having a radiological diagnosis of explanation of impairment only acts as a guide and does not always provide clarity of the full extent of a child’s functional difficulties.
Following presentation of the evidence and, after expert opinion, the Committee concluded that MRI is useful in clarifying aetiology of cerebral palsy in the absence of a clear clinical history but not necessarily the timing of the cerebral injury. The Committee agreed that it was important that the MRI should be reported on by a specialist neuroradiologist. It is important for the clinician who orders the test to provide as much information with regard to history and findings to help them in their report. Even with specialist reporting there is a significant proportion of children and young people with cerebral palsy who have a ‘normal’ MRI (10%). At present, the international consensus is that further investigation in this population does not inform aetiology further.
The Committee agreed various aspects should be taken into account in terms of the timing of an MRI scan. Brain structure continues to change rapidly during early childhood. It is important to note that any abnormality may not be apparent until 2 years of age as maturation of the myelination process and development of the deep grey structures may be less obvious until around this time. However, there may be clinical circumstances that need urgent clinical decision-making, in which case an MRI must be conducted.
In the presence of an abnormal clinical or developmental trajectory, an urgent MRI might find aetiology suggestive of red flags for conditions other than cerebral palsy such as progressive disorders. As such, the Committee noted that there were certain cases that would need a repeat MRI scan and recommended that this should only be done when there is a change in the expected clinical and developmental profile or if there are any red flags for a progressive disorder.
The Committee considered that the reasons to do an MRI should be discussed with the child or young person with cerebral palsy if age appropriate and their parents and/or carers in each individual circumstance.
The Committee noted that most units in England and Wales do MRI under general anaesthetic, especially in younger children, and it was recognised that often the quality of scanning is better than if done under sedation alone.
The Committee were aware that there are older children and young people with cerebral palsy who did not have access to MRIs as young children. If aetiology is uncertain, it may be appropriate to offer an MRI scan as part of information-giving to the person or relatives on the possibility of the aetiology being a genetic disorder – for example, cortical migration disorder.
8.6.3. Consideration of economic benefits and harms
Currently, MRI scans are widely done, although their additional value above a detailed clinical assessment in clear cases was considered to be overestimated by the Committee. The expert opinion and Committee advised that a paediatric neuroradiologist would be well equipped to assess the aetiology of cerebral palsy from an MRI when provided with a clear clinical history and examination.
If a clinical and developmental history and examination in the presence of clear risk factors can sufficiently determine the patient’s aetiology of cerebral palsy, the Committee agreed an MRI should not routinely be used to confirm diagnosis. Consequently this will reduce the number of cost-ineffective MRIs that are done, freeing up resources to generate benefits elsewhere in the NHS.
Ideally, MRI would be used at the time of presentation in a child with suspected cerebral palsy where there is no clear aetiology based on obstetric perinatal or postnatal history, neurological examination or other investigations, or if there is any unexpected change in clinical or developmental profile. It is important to rule out disorders other than cerebral palsy, as patients incorrectly diagnosed with cerebral palsy but with a progressive motor disorder may not get access to available therapies, which may adversely impact on their health-related quality of life.
The Committee agreed that because of the developmental and maturational processes of the brain, the aetiology of cerebral palsy may not be fully apparent until 2 years of age; for this reason an MRI should not be done in neonates or infants if the purpose of the MRI is to determine the aetiology of cerebral palsy, unless there were other clinical reasons to do so. As a result there are potential cost savings to the NHS if only 1 MRI is done to determine the aetiology of cerebral palsy.
The use of ultrasound scans to determine the aetiology of cerebral palsy was also raised by the Committee. The Committee advised that an ultrasound scan can illustrate abnormalities earlier than MRI and every high-risk neonate should undergo an ultrasound scan on the neonatal unit. As a result, the findings from an ultrasound could be discussed with the family at an early stage, helping discussion about diagnosis and evading the need for an MRI at presentation, or delaying the MRI until the brain has structurally developed.
8.6.4. Quality of evidence
One cohort study was included in this evidence review. The quality the evidence for this review was rated as low, based on the cohort study methodology checklist (NICE Manual 2012). The reasons for this was because the study included participants from an indirect population initially (neonates from NICU as opposed to infants diagnosed with cerebral palsy) and lack of outcome reporting of any statistical analysis including diagnostic accuracy outcomes or correlation coefficients.
8.6.5. Other considerations
The recommendations related to this evidence review were based on the evidence and the Committee’s clinical experience.
8.6.6. Key conclusions
The Committee concluded that MRI should be used to confirm aetiology when this is not clear from antenatal, perinatal or postnatal history, neurological examination or other investigations.
8.7. Recommendations
- 24.
Offer MRI to investigate aetiology in a child or young person with suspected or known cerebral palsy if this is not clear from:
- antenatal, perinatal and postnatal history
- their developmental progress
- the findings on clinical examination
- results of cranial ultrasound examination.
- 25.
Recognise that MRI will not accurately establish the timing of a hypoxicischaemic brain injury in a child with cerebral palsy.
- 26.
When deciding the best age to perform an MRI scan for a child with cerebral palsy, take account of the following:
- Subtle neuro-anatomical changes that could explain the aetiology of cerebral palsy may not be apparent until 2 years of age.
- The presence of any red flags for a progressive neurological disorder (see section 7.7).
- That general anaesthesia or sedation is usually needed for young children having MRI.
- The views of the child or young person and their parents or carers.
- 27.
Explain to parents of carers and the child or young person with cerebral palsy that it is not always possible to identify a cause for cerebral palsy.
- 28.
Consider repeating the MRI scan if:
- there is a change in the expected clinical and developmental profile or
- any red flags for a progressive neurological disorder appear (see section 7.7).
- 29.
Discuss with the child or young person and their parents or carers the reasons for performing MRI in each individual circumstance.
8.8. Research recommendations
None identified for this topic.
- MRI and identification of causes of cerebral palsy - Cerebral palsy in under 25s...MRI and identification of causes of cerebral palsy - Cerebral palsy in under 25s: assessment and management
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