Diffuse midline glioma

What is a diffuse intrinsic pontine glioma (DIPG) / diffuse midline glioma tumour?

Diffuse intrinsic pontine glioma or DIPG is an aggressive, high-grade (or malignant) brain tumour, most often occurring in children. 

This tumour has been given different names over the years, as brain tumours classifications have changed. 

Still commonly referred to as DIPG, it was previously known as a grade 4 brain stem glioma and most recently renamed "diffuse midline glioma".

A diffuse brain tumour does not have a clear boundary, instead infiltrating healthy brain tissue, spreading between and around surrounding brain cells.

Other parts of the name describe where the tumour is found: “intrinsic” means within an area of the brain called the pons – hence “pontine” – in the middle of the brain stem – hence along the “midline”. 

The newer name, “diffuse midline glioma”, has been chosen partly to reflect the fact that these tumours can also be found in the thalamus and cerebellum areas of the brain, both of which are very close to the pons / spinal cord.

“Glioma” indicates that the tumour has developed from glial cells that ordinarily support and nourish the neurons (nerve cells) of the brain. These tumours have usually developed from star shaped glial cells called astrocytes, so are a form of astrocytoma brain tumour.

Is DIPG / diffuse midline glioma brain cancer?

This tumour in all instances is classified as a high-grade (fast growing), grade 4 brain tumour which means that it is also brain cancer.

Can DIPG / diffuse midline glioma tumours spread to other parts of the body?

As a malignant and aggressive cancer, it is possible for this tumour type to extend into other regions of the brain and/or the spinal cord. Tumours that originate in the brain very rarely spread to other parts of the body. As a malignant and aggressive cancer, it is possible for this tumour type to extend into other regions of the brain and/or the spinal cord. Tumours that originate in the brain very rarely spread to other parts of the body. 

Who can be diagnosed with a DIPG / diffuse midline glioma tumour?

Diffuse midline gliomas can occur in both adults and children, but tend to occur primarily in children between five to nine years of age. DIPG accounts for 10-20% of all brain tumours in young children.

What is the survival rate for DIPG / diffuse midline glioma

Unfortunately, the prognosis for this tumour type is poor.

DIPG is an aggressive, high-grade (fast-growing) form of brain cancer and is the leading cause of brain tumour deaths in children.

Median overall survival (OS) is between 8 to 12 months, though some children are able to survive longer, with survival rates approximately 30% at 1 year, 10% at 2 years and less than 1% at 5 years from diagnosis.

What are the symptoms of DIPG / diffuse midline glioma?

There are a range of symptoms that can signal that this type tumour might be present. However, it is important to note that these issues can be symptomatic of other conditions. 

It is crucial that any child displaying one or more of these symptoms is seen by a neurologist and given an MRI (brain scan) as soon as possible in order to establish a clear diagnosis.

Most cases of DIPG will be diagnosed via the combination of symptoms and an MRI, but in some cases a biopsy will help with the initial brain tumour diagnosis before determining treatment.

Three classic signs of DIPG / brain stem glioma / diffuse midline glioma

Over 50% children with a DIPG or diffuse midline glioma present with three groups of symptoms, though these can vary based on the size and specific location of the tumour within the brain stem.

1. Cranial nerve deficits 

  • Abducens palsy or sixth nerve palsy: one eye turned inwards
  • Double vision: which may be causing headaches and eye strain
  • Facial asymmetry: muscles on the face not working evenly, so one side appears dropped

2. Signs of pressure on the cerebellar area at the back and base of the brain

  • Ataxia: loss of control of certain body movements
  • Dysmetria: lack of co-ordination, sometimes an inability to judge distance
  • Dysarthria: not speaking clearly or easily

3. Signs of damage to long tract nerves originating in the brain and spinal cord 

  • Decreased strength
  • Hyperreflexia: overactive reflexes
  • Upward Babinski: when the sole of the foot is tickled, the big toe reflexes upward instead of downward – normal in infancy but not when this occurs in childhood or adult life.

Diffuse midline glioma can also cause the production of too much cerebral spinal fluid (CFS) or can interfere with the flow of it around the brain, causing increased pressure on the brain known as hydrocephalus.

Signs and symptoms of hydrocephalus may include: 

  • Blurred or double vision
  • Nausea and/or vomiting
  • Strong desire to sleep
  • Irritability
  • Headaches
  • Seizures

When a diffuse midline glioma develops in the spine, patients may have progressive weakness, numbness, and problems with bowel and bladder control.

Frequently Asked Questions

What causes a DIPG / diffuse midline glioma brain tumour?

A number of genetic, epigenetic and molecular profiles of these tumours have been identified, and mutation of a gene called H3K27M has been associated with an increased risk of developing a diffuse midline glioma. 

However, the fact that these tumours consist of a number of different types of damaged cells in varying proportions between patients makes it very difficult to identify any one cause.

There are two rare genetic conditions that can be inherited and are associated with a higher risk of developing these types of tumours: Li-Fraumeni syndrome and neurofibromatosis type 1. 

Some researchers are also investigating the notion that the formation of DIPG tumours may be linked to brain development in childhood; that particular cells present in the highest concentrations while the brain is developing at this time may influence the onset of the disease. 

What treatments are used for DIPG / diffuse midline glioma brain tumours?

The most common treatment for this tumour type is radiotherapy, which has the best evidence for prolonging survival compared to surgery or chemotherapy.

A biopsy may be undertaken for cellular and genetic analysis of the tumour and to help determine the therapeutic approach. 

However, the position and nature of DIPG brain tumours makes extensive neurosurgery too risky and means that they can never be completely removed by surgery alone.

What drugs can be used for DIPG / diffuse midline glioma brain tumours?

There are a number of clinical trials underway to identify drugs that may help children with this type of brain tumour, but there are currently no chemotherapy drugs that have been universally proven to show benefit, so each treatment regime is approached on an individual basis.

Treatment for people with this tumour type is heavily dependent upon access to clinical trials. The clinical team treating the patient will be best placed to advise which trials may be suitable for consideration.

How can we find a cure for diffuse midline glioma / DIPG brain tumours in the UK?

Research we are funding across all of our dedicated Research Centres will help lead towards finding a cure for a wide range of brain tumours.

The research team at the Research Centre located at The Institute of Cancer Research is identifying, testing and validating new therapeutic targets for PDHGG, including diffuse intrinsic pontine glioma (DIPG), as well as developing new drug delivery methods. The truly translational Centre is generating the laboratory data needed to support the launch of new clinical trials.

The team of research and clinical experts in our Research Centre at Imperial College, London, are working collaboratively with other research institutions to investigate the effectiveness of arginine-depleting drugs in the treatment of high-grade glioma brain tumours. They are also studying the way in which the ketogenic diet works in brain cancer, including its potential effects on patients diagnosed DIPG / brain stem glioma / diffuse midline glioma brain tumours.

Pioneering research at our Brain Tumour Research Centre at Queen Mary University of London is focused on using GBM stem cells to help develop unique, patient-specific treatments. Their findings are expected to translate into other types of adult and paediatric brain tumours, including DIPG / brain stem glioma / diffuse midline glioma brain tumours.

We also fund BRAIN UK at Southampton University, the country’s only national tissue bank registry providing crucial access to brain tumour samples for researchers from all clinical neuroscience centres in the UK, effectively covering about 90% of the UK population, and an essential component in the fight to find a cure for DIPG brain tumours.