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Adrenoleukodystrophy

Cerebral ALD

Cerebral ALD (cALD) is the most rapid and most dangerous form of the disease. Inflammation in the cerebral white matter destroys myelin quickly.

It is also the only form of ALD in which time decides the outcome. Found early, progression can be halted. Found late, there is no way back.

What it is

If adrenomyeloneuropathy is a slow degeneration of spinal cord axons over years, cerebral ALD is an inflammatory reaction that switches on at some point.

Microglia, astrocytes and macrophages activate together, myelin is destroyed, and once it starts it sustains itself. Progression is measured in months, not years.

→ The mechanism is set out in more detail on About ALD.

Who develops it

Mainly boys in childhood. It is rare before age 3 and most common between 4 and 10 years.

It is not confined to children. Adult men can develop cerebral disease, and men with AMN can convert to it. Adults therefore need continued surveillance.

It essentially does not occur in females. Girls and women are not subject to routine cerebral surveillance. → Women with ALD

Symptoms

Early symptoms rarely look neurological. That is why diagnosis is delayed.

First signs

  • A sudden fall in school performance
  • Loss of attention; difficulty following instructions
  • Deteriorating handwriting, or difficulty reading
  • Behavioural change — withdrawal, or the opposite

At this stage children are not uncommonly diagnosed with ADHD or a learning disorder.

As it progresses

  • Visual field loss, difficulty seeing
  • Difficulty hearing, or understanding speech
  • Unsteady gait
  • Difficulty swallowing
  • Seizures

Later

  • Loss of vision and hearing
  • Loss of movement
  • An unresponsive state

Untreated, cerebral ALD leads to severe disability or death within a few years of symptom onset.

If there is ALD in the family and a child’s learning or behaviour changes abruptly, saying so at the consultation changes the diagnostic pathway substantially.

It has to be found before symptoms

This is the most important part of this page.

By the time symptoms appear, the lesion is already extensive. Symptoms cannot be the trigger for action. The disease has to be found on brain MRI while the child is still well.

The surveillance schedule in the 2022 international consensus recommendations:

AgeBrain MRI
2 yearsBaseline scan
2–12 yearsEvery 6 months
From 12 yearsAnnually
Adult menContinue while transplantation remains an option

The baseline is set at age 2 because myelination is incomplete before then and scans are difficult to interpret.

If symptoms suggestive of cerebral disease appear, imaging is performed immediately, regardless of the schedule.

Surveillance algorithm after a diagnosis of ALD

Judging whether a lesion is active

When a lesion is seen, the next question is whether it is active now. Gadolinium enhancement is used for that judgement. Enhancement indicates ongoing inflammation and is a central factor in deciding when to treat.

The extent of the lesion and neurological function are assessed alongside it. Each is scored on an established scale, but those scores do not by themselves determine whether treatment goes ahead. Rate of progression, age and donor availability are weighed together.

Lesions sometimes stop on their own

Cerebral lesions have been reported to arrest spontaneously. Arrested lesions can also reactivate.

A single scan therefore supports neither reassurance nor despair; what matters is the trajectory. Where a lesion appears arrested and non-enhancing, imaging is repeated after three months to confirm stability, and the interval then returns to the usual schedule.

Treatment

Early haematopoietic stem cell transplantation is the only established treatment. It can halt progression but cannot reverse damage already done.

Leriglitazone has reached the point of a positive regulatory opinion in Europe, and gene therapy is a conditional option.

→ Set out in full on the Treatment page.

What else to check

Cerebral disease does not exclude the other problems.

Adrenal insufficiency is frequently present and may precede neurological signs. Testing begins within the first six months of life. → Adrenal Insufficiency

Transplantation does not affect myeloneuropathy. Even after cerebral disease is halted, AMN symptoms may appear in adulthood. → Adrenomyeloneuropathy

Head injury

Severe head trauma has been reported as a possible trigger for cerebral disease. The causal relationship is not established.

Even so, international recommendations advise counselling male patients about the possibility so that they can make their own decisions about how they live. Having had a head injury does not mean cerebral disease will follow, and there is nothing to reproach yourself for in what has already happened.


Based on the 2022 international consensus recommendations (Neurology) and published research. Sources are indicated in the text.

Last reviewed: 7 August 2026

This page provides general medical information and does not replace care for an individual patient.