Introduction

Cerebellar Agenesis is an extremely rare condition defined by the lack of development of the Cerebellum; the part of the brain responsible for coordinating balance and movement. 

Historically, this has been a difficult disease to diagnose as CT or MRI scans are required to confirm the absence of this part of the brain. This has led to recent cases of patients being diagnosed with the condition as late as the age of 71 after struggling with motor, balance and speech issues since birth.^1,2 

Current technology now allows the imaging of fetal imaging before birth, allowing diagnosis to be confirmed at a very early stage, often through the use of ultrasound or MRI. This can allow those diagnosed to receive support from birth and help parents to navigate how best to support their child, however, there are also many challenges presented when trying to detect this developmental disorder.

Cerebellar agenesis

Some patients may exhibit Subtotal Cerebellar Agenesis, where small parts of the cerebellum have developed, or Total Cerebellar Agenesis, where there is no trace of the cerebellum developing at all. Whilst this is non-fatal, it can have a profound effect on motor skills, muscle tone and speech development, though symptoms seem to vary depending on the patient. 

Many documented case studies imply a normal lifespan and high quality of life with some reporting very mild symptoms and surprisingly normal motor function.³

The cause of these issues is difficult to precisely determine and could come from a range of sources often related to other health issues. 

Spina Bifida is a condition where the spinal cord does not finish developing correctly, which is thought to then lead to issues in the development of the cerebellum. Other suggested causes include decreased blood flow and prenatal infections such as the Zika Virus that is mainly spread by infected mosquitoes. Correlations with low birth weight also suggest this could be a factor in this developmental disorder.³

Prenatal imaging using ultrasound

Ultrasound is often the first examination carried out to assess the health of a fetus by creating images of the heart, spine and head. This can be done using a transabdominal or transvaginal ultrasound, which uses a transducer that is moved across the mother’s abdomen, or inserted into the vagina respectively.⁴ 

The transducer emits waves that are reflected to different degrees when crossing through mediums of different density. Reflected waves are then detected to build up an image of the fetus. The development of the brain and head are observed by taking 2D images in the sagittal and axial planes to provide a clear view of different structures.

 At this point cerebellar agenesis may be apparent if the absence of a brain section is detected, however, this could be confused with other similar issues such as Spina Bifida and the Dandy-Walker continuum.⁵

Other issues are encountered when using ultrasound, for example, due to the location of the cerebellum and brainstem within the brain, this area is particularly difficult to image and has produced many false-positive and false-negative diagnoses. A study from 2000 identified that in 77% of cases, autopsy revealed the same results as ultrasound scans, implying that this imaging technique is only correct around 77% of the time. This demonstrates that there is still a reasonably high level of uncertainty in this imaging technique so any results should take this into consideration.⁶ 

Ultrasound is generally considered to be safe, exhibiting no side effects other than a possibility that it may insignificantly decrease birth weight which is nothing to be concerned about. Being a non-invasive, quick and easy procedure, it is commonly used as a first port of call to check fetal health though these issues with accuracy may require a secondary imaging technique to be used.⁷

Fetal MRI

If ultrasound findings prove inconclusive, fetal MRI can be carried out to further clarify a diagnosis as they are generally of a higher quality.⁸ Amniotic fluid surrounding the fetus can also affect the clarity of MRI, making this form of imaging more challenging than usual. 

While many studies claim that MRI is superior to ultrasound in terms of detecting anomalies in the posterior fossa, the only actual statistically analysed study found no significant advantage to MRI compared to ultrasound. It was found that in 69% of cases both MRI and ultrasounds performed by an expert were just as accurate compared to one another. Furthermore, MRIs taken before 25 weeks can contribute to an incorrect diagnosis due to misleading images, as well as being much more expensive and time-consuming.¹⁰

Diagnostic challenges - similar conditions

Several different conditions can be confused with cerebellar agenesis, including; cerebellar hypoplasia, Dandy-Walker malformation and vermian dysgenesis.

Cerebellar hypoplasia is hard to distinguish from cerebellar agenesis as this is when the cerebellum is smaller or not fully developed, so in some ways is a milder version of cerebellar agenesis as some of the cerebellum has developed, just not to the extent that it should have.

 This can lead to similar issues with motor skills, muscle tone, balance and speech development. These symptoms can get progressively worse over time but this varies from patient to patient and can often be treated effectively with the correct support to limit the impact of this condition on quality of life.¹¹

The Dandy-Walker malformation is another similar condition which is defined by eitherthe lack of vermis (an area within the cerebellum), enlargement of the fourth ventricle (another area of the posterior fossa), displacement of the tentorium and torcula (other nearby areas of the brain) or the general enlargement of the posterior fossa. This is the most common posterior fossa disorder with similar symptoms to the previously mentioned disorders.

 Diagnosis is only possible by ultrasound and MRI after 18 weeks of pregnancy and cases in which there is a lack of vermis or other missing areas of the brain can be easily confused with cerebellar agenesis making diagnosis more difficult.¹²

The final condition that cerebellar agenesis can often be confused with is Vermian Dysgenesis, which is when a specific structure in the center of the cerebellum is either not present or under developed. This can also be mistaken for cerebellar agenesis due to the similar areas appearing absent when the brain is imaged, particularly on smaller fetal brains where it is harder to distinguish sections of the brain.¹³

All of these conditions can be difficult to distinguish with our current technology and all options should be considered when making a diagnosis. The similarities between these disorders are a challenging part of using ultrasound and MRI in fetal imaging as they will appear similar on most scans and, other than autopsy, these are the only viable methods of obtaining a diagnosis.

Future directions and recommendations

Several studies have provided new insight into ways to improve fetal ultrasound and MRI as a diagnostic tool.

One way that has been proposed to improve diagnosis of cerebellum disorders using ultrasound is the creation of a clear set of standards for normal fetal cerebellar growth. This has been achieved using a large-scale collection of international data so that images taken can now be compared to these standards and accurately inform diagnosis.¹⁴ 

A similar approach has been taken with MRI imaging using large data sets to provide a reference frame for healthy brain development allowing developmental disorders to be more easily detected.¹⁵

Multidisciplinary assessment, which involves a comprehensive evaluation performed by a team of professionals with different areas of expertise, has also been shown to be helpful to accurately detect brain scan anomalies with several specific case studies, illustrating that care from interdisciplinary professionals provides a more accurate diagnosis.¹⁶

In addition, Artificial Intelligence has been shown capable of accurately predicting the age of a developing fetus from brain scans. It has been suggested that this technology could be adapted and utilised to suggest certain abnormalities in brain development, though this has not been put into practice yet.¹⁶

Summary

Ultrasound and MRI are both techniques currently used in fetal imaging to diagnose cerebellar agenesis, however, these do not provide the most accurate diagnoses and often produce false-positive or false-negative results. Whilst these remain our best current diagnostic tools in this situation, there is room for improvement when it comes to accurately detecting fetal posterior fossa anomalies.