Information & Terminology


Like many of us, as a newly diagnosed family you will most likely be struggling to come to terms with the fact you or your child has a Rare Disease. Not only a rare disease, but a disease that comes with many titles and information that will be new .

In this section we will address in simple terms what some of these titles are. We will also cover information that we feel is relevant to newly diagnosed families.

What's in a Name?
ANE – Acute Necrotizing Encephalopathy (occasionally known as Acute Necrotizing Encephalitis)

ANEC – Acute Necrotizing Encephalopathy of Childhood, ANEC is a name used less as more teenage & adult cases have been reported.

ANE1 – This is the correct name for ANE survivors with the Genetic Mutation of RanBP2.

IIAE – Infection Induced Acute Encephalopathy, another not as recognized name for ANE.

IIAE3 – As above but the 3 recognizes the survivor as having the RANBP2 mutation.

Encephalitis or Encephalopathy?
Here’s our medical clarification on the terminology definition for encephalopathy vs encephalitis:

“The endings of the word give the definition:

“-itis” means inflammation. That term usually implies the infiltration of immune cells, which are releasing inflammatory factors, causing swelling, warmth, pain, etc.

“-pathy” means disease state. Its only requirement is that the organ in question does not work properly.

We have typically used the term encephalopathy for ANE because we do not see immune cells invading the CNS and we do not believe that there is a direct invasion of the CNS by a virus, either. “Encephalitis” has more commonly been used to indicate viral or bacterial infections.

On the other hand, with ANE, there is localized swelling and evidence of inflammation, so encephalitis could be viewed as an accurate term for the process.

The terminology can be a little fuzzy, but encephalopathy has been the more traditional term for this.

Rare Disease
A rare disease is any life-threatening or chronically debilitating disorder or condition which, as the name suggests, is uncommon in the general population. Rare diseases typically exhibit a high level of symptom complexity and as a result they very frequently require special combined treatments.


• Rare diseases are often chronic, progressive, degenerative, and often life-threatening

• Rare diseases are disabling: the quality of life of patients is often compromised by the lack or loss of autonomy

• High level of pain and suffering for the patient and his/her family

• No existing effective cure

• There are between 6,000 and 8,000 rare diseases

• 75% of rare diseases affect children

• 30% of rare disease patients die before the age of 5

• 80% of rare diseases have identified genetic origins.

Other rare diseases are the result of infections (bacterial or viral), allergies and environmental causes, or are degenerative and proliferative.

Relatively common symptoms can hide underlying rare diseases, leading to misdiagnosis.

Reference: A disease or disorder is defined as rare in Europe when it affects less than 1 in 2,000 citizens (Orphan Drug Regulation 141/2000) . Rare diseases may affect 30 million European Union citizens.

Note*  The figure for occurence of ANE is 1>1,000,000.

The Immune Response
ANE is known as an immune mediated disease but is not primarily known as an autoimmune disorder. An Auto Immune disorder is described as a malfunction of the body’s immune system that causes the body to attack its own tissues, it sounds the same, but we need the element of proof.

The immune system defends the body against what it perceives to be foreign or dangerous substances. Such substances can be virus’s, infections, certain cancer cells, and even transplanted organs. These substances have molecules that the immune system can identify and that can stimulate a response by the immune system. These molecules are called antigens. Antigens may be contained within cells or on the surface of cells (such as bacteria or cancer cells) or be part of a virus.

Cells in a person’s own tissues also have antigens. But normally, the immune system reacts only to antigens from foreign or dangerous substances, not to antigens from a person’s own tissues. However, the immune system sometimes malfunctions, interpreting the body’s own tissues as foreign and producing antibodies (called auto antibodies) or immune cells that target and attack particular cells or tissues of the body. This response is called an autoimmune reaction. It results in inflammation and tissue damage.
And this is where ANE whilst having the characteristic of the immune system attacking the body (brain) is not completely labelled as an auto immune disease because no antibodies have been definitively linked to ANE.

There has been evidence that some antibodies (ephrin type B receptor 2 (EphB2), have been singled out in ANE but further research & investigation is required.

The Cytokine Storm
Although the exact pathogenesis (the manner of development of a disease.) of ANE remains obscure, the most prevalent hypothesis is the hypercytokinemia, that is, “cytokine storm”. Individuals suffering from ANE often have an exaggerated immune response to various viral infections by producing elevated proinflammatory cytokines.

How do cytokine storms start?

Pathogens (infections, virus’s etc) attack the immune system, so cytokines (which are protein-based signals) signal T-cells and macrophages (immune cells) to travel to the site of the infection.
Cytokines also activate these immune cells, and stimulate them to produce more cytokines. This positive feedback loop will attract more T-cells and macrophages to join the fight. Usually, the body is able to keep the feedback loop in check so that a cytokine storm (which is energy-consuming and harms the body) doesn’t occur.

Sometimes the body is unable to control the loop, for reasons we don’t fully understand and we end up with a CS. It’s speculated that a CS might be triggered when the immune system is attacked by a new and highly pathogenic invader. The “cytokine storm” results in systemic symptoms, such as liver dysfunction, acute renal failure, and shock. In the nervous system, it leads to brain injury through alteration of vessel wall permeability without vessel wall disruption. According to this hypothesis, ANE is an encephalopathy concomitant with systemic immune imbalance.

Blood Brain Barrier (BBB)

Water diffusion between the blood and the brain is tightly regulated by the blood-brain barrier (BBB). The BBB provides two kinds of barrier: a physical barrier (by the presence of tight junctions) and a chemical barrier (by the presence of solute carriers and drug efflux pumps).

More detailed information can be found at:

Acquired Brain Injury
An Acquired Brain Injury (ABI) is any injury sustained after birth, in the case of ANE, primarily due to infection/disease. The long term effects of an ABI vary for each person. It is important to remember that for a child, unlike an adult their brain is still developing. A child depending on age is not just relearning skills but learning them for the first time. Extra support is therefore required to assist in normal developmental progress.

The outcomes of an ABI may include:


Fatigue and sleep disorders
Movement disorders
Visual, hearing & speech problems
Chronic pain
Loss of taste & smell
Hormone changes


Memory issues
Lack of initiative, insight, awareness, motivation and poor judgement
Difficulty planning, solving problems & organising
Reduced concentration & attention skills
Irritability, anger and easily stressed
Poor social skills and slow to respond
Impulsive behaviour

Recovery from a ABI may be rapid at first with improvements occurring as swelling subsides. This improvement continues as damaged cells heal BUT healing can be very slow, taking months or even years.

The 3 very broad stages of recovery are;

*The acute stage, whilst initially in hospital.

*The rehabilitation stage, intensive therapy with emphasis on regaining previous skills and strategies for dealing with ongoing problems.

*The third stage is re entry into everyday living, also known as tertiary rehabilitation. The focus is on helping the person & family find ways to adapt and compensate for any long term problems & disabilities.

Post Traumatic Agitation
Agitation seems to be a natural healing process. Although post traumatic agitation can be a challenging problem for acute and rehabilitation staff, persons with traumatic brain injury, and their families. Specific variables for evaluation and care remain elusive. It may include inappropriate vocalizing, intolerance of medical management or equipment, and directed or diffuse aggressive behaviors. Careful consideration of environmental factors should be given before medicating a person with agitation. When medications are eventually pursued to modulate behavior, measurement of agitation with an objective tool is highly recommended in determining the success of treatment.


Fatigue - A Common & Disabling Sympton
Fatigue is a common and very disabling symptom experienced by people with a brain injury.

It may be a continual sense of mental fatigue or it can happen when a person is trying to do too much and the brain is overloaded, often resulting in mind-numbing fatigue that can last for several days.

Acquired brain injury can be likened to a highway when one of three lanes is closed down. If traffic is light, there will be no difference but once the traffic reaches a critical point, the cars barely move and it can take ages for the traffic jam to clear.

It is important to avoid fatigue as much as possible, as any other problems are worsened as well, such as:
Vision problems
Slurred speech
Difficulty finding words
Poor concentration
Cramps or weak muscles
Poor coordination or balance.

Fatigue can occur for no apparent reason or after physical activity, but is quite likely to occur from too much mental activity. Examples include planning the week’s errands, organizing schoolwork or a work schedule or simply reading.

Fatigue can be managed with good planning and rest periods, but carers and the family member must realize fatigue is a very real problem.

Symptoms of fatigue

The following symptoms may all suggest fatigue:
Withdrawal, short answers, dull tone of voice
Loss of appetite
Shortness of breath
Slower movement and speech
Irritability, anxiety, crying episodes
Increased forgetfulness
Lack of motivation and interest.


Be aware of the first signs of fatigue and immediately stop and rest – overloading a injured brain can easily result in several days of extreme tiredness. Make a note of how long it takes to do certain activities before fatigue starts e.g. if fatigue starts after 30 minutes of reading, only read for 20 minutes in future.

What a Brain Injury Warrior Wants You To Know

“Part of the problem with the word ‘disabilities’ is that it immediately suggests an inability to see or hear or walk or do other things that many of us take for granted. But what of people who can’t feel? Or talk about their feelings? Or manage their feelings in constructive ways? What of people who aren’t able to form close and strong relationships? And people who cannot find fulfilment in their lives, or those who have lost hope, who live in disappointment and bitterness and find in life no joy, no love? These, it seems to me, are the real disabilities.”

Fred Rogers, The World According to Mister Rogers

I need a lot more rest than I used to. I’m not being lazy. I get physical fatigue as well as a “brain fatigue.” It is very difficult and tiring for my brain to think, process, and organize. Fatigue makes it even harder to think.

My stamina fluctuates, even though I may look good or “all better” on the outside. Cognition is a fragile function for a brain injury survivor. Some days are better than others. Pushing too hard usually leads to setbacks, sometimes to illness.

Brain injury rehabilitation takes a very long time; it is usually measured in years. It continues long after formal rehabilitation has ended. Please resist expecting me to be who I was, even though I look better.

I am not being difficult if I resist social situations. Crowds, confusion, and loud sounds quickly overload my brain, it doesn’t filter sounds as well as it used to. Limiting my exposure is a coping strategy, not a behavioural problem.

If there is more than one person talking, I may seem uninterested in the conversation. That is because I have trouble following all the different “lines” of discussion. It is exhausting to keep trying to piece it all together. I’m not dumb or rude; my brain is getting overloaded!

If we are talking and I tell you that I need to stop, I need to stop NOW! And it is not because I’m avoiding the subject, it’s just that I need time to process our discussion and “take a break” from all the thinking. Later I will be able to rejoin the conversation and really be present for the subject and for you.

Try to notice the circumstances if a behaviour problem arises. “Behaviour problems” are often an indication of my inability to cope with a specific situation and not a mental health issue. I may be frustrated, in pain, overtired or there may be too much confusion or noise for my brain to filter.

Patience is the best gift you can give me. It allows me to work deliberately and at my own pace, allowing me to rebuild pathways in my brain. Rushing and multi-tasking inhibit cognition.

Please listen to me with patience. Try not to interrupt. Allow me to find my words and follow my thoughts. It will help me rebuild my language skills.

Please have patience with my memory. Know that not remembering does not mean that I don’t care.

Please don’t be condescending or talk to me like I am a child. I’m not stupid, my brain is injured and it doesn’t work as well as it used to. Try to think of me as if my brain were in a cast.

If I seem “rigid,” needing to do tasks the same way all the time; it is because I am retraining my brain. It’s like learning main roads before you can learn the shortcuts. Repeating tasks in the same sequence is a rehabilitation strategy.

If I seem “stuck,” my brain may be stuck in the processing of information. Coaching me, suggesting other options or asking what you can do to help may help me figure it out. Taking over and doing it for me will not be constructive and it will make me feel inadequate. (It may also be an indication that I need to take a break.)

You may not be able to help me do something if helping requires me to frequently interrupt what I am doing to give you directives. I work best on my own, one step at a time and at my own pace.

If I repeat actions, like checking to see if the doors are locked or the stove is turned off, it may seem like I have OCD — obsessive-compulsive disorder — but I may not. It may be that I am having trouble registering what I am doing in my brain. Repetitions enhance memory. (It can also be a cue that I need to stop and rest.)

If I seem sensitive, it could be emotional liability as a result of the injury or it may be a reflection of the extraordinary effort it takes to do things now. Tasks that used to feel “automatic” and take minimal effort, now take much longer, require the implementation of numerous strategies and are huge accomplishments for me.

We need cheerleaders now.


Internet Resources
Strategies to Assist Learning

Emotional Problems after Traumatic Brain Injury

Cognitive Problems after Traumatic Brain Injury