Fatigue

Fatigue – A Common & Disabling Symptom

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.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.

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.

Post Traumatic Agitation

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.

Acquired Brain Injury

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 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.

The Cytokine Storm

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.

The Immune Response

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.

Rehabilitation

Rehabilitation

Rehabilitation & recovery for ANE patients will vary greatly from person to person. Some progress steps are usually made in the initial weeks after the Acute stage of ANE but many steps are not made for months or even years down the recovery road. In our experience, the earlier and more intensive rehabilitation the better the outcomes. Rehabilitation may include the expertise of the therapies listed below. We encourage the main caregivers to take time out for themselves to better help the patient. Keeping a journal or some video’s to look back on and see progress can be a great encouragement. Never be afraid to question clinicians about any treatment or therapy. You, the carer, know your ANE patient the best.

Treatments

Treatments

At this time there is no recommended therapies for the treatment of ANE in the acute stage. Intensive care, symptomatic treatment and empirical treatments such as the use of anti virals and immunomodulatory agents are tested in the majority of cases. The following are therapies that may be used for ANE patients as decided by their treating physicians. Since no ANE patient is identical to another, hence no two patient treatments will be identical. The majority of patients will be placed in a drug induced coma. Attending Doctors and Neurologists will assess the situation carefully and treat the patient according to their needs.

Underreported

Underreported

“Acute necrotizing encephalopathy (ANE) is underreported;the prevalence and incidence of ANE remain unknown. Due to ascertainment bias, it is not possible to estimate the proportion of ANE that results from mutation of RANBP2 (and thus is classified as infection-induced acute encephalopathy 3 [IIAE3]).’

DR DEREK NEILSON

GENETICS & METABOLISM

PHOENIX CHILDRENS HOSPITAL

What ANE Families Are Saying

What ANE Families Are Saying

Do not be afraid to ask the Dr’s a million questions. They are always there to help and want the best for your child. They will listen to your concerns. Listen to your gut feelings. You know your child best and be their advocate.

Grief will come, and that is ok. Grieving a child is the hardest thing you will do as a parent. You will grieve your child’s losses and your child may grieve some of those losses as well. This will be HARD!

Any progress is good progress

Fight for everything you feel you need for your child, do not give up and work every step with your child and don’t let the school be ok with only simple things for goals, challenge your child at all times

Prevalance

Prevelance

“It’s so rare that we are not able to give an incidence number. So, in medicine we like to say how common something happens in a certain percentage of a population, say per 1000 or 100,000, but it is so rare that at this point we aren’t able to give it a number”.

DR MICHAEL ESSER

PEDIATRIC NEUROLOGIST & RESEARCHER

CUMMING SCHOOL OF MEDICINE