The Disseminated acute encephalomyelitis (EAD) consists of strong and brief bouts of swelling involving primarily the white matter of the brain, optic nerves and spinal cord.
EAD, also called postinfectious encephalomyelitis and immune-mediated encephalomyelitis, is an inflammatory demyelinating condition (it means it affects myelin, or lining of neurons that allow nerve impulses to travel through them), and appears to be immune-mediated.
The essential manifestation of encephalomyelitis is encephalopathy, or encephalic disease, of an acute type and is related to various neurological problems.
It is mainly a disease that occurs in infants and children under 10, but not exclusively.
Its cause seems to be sometimes attributed to the outbreak of an infectious disease such as a virus or, although much less common, with the vaccines.
On the other hand, it is very frequently confused with multiple sclerosis (MS); Since the symptoms are very similar. For example, they have in common the presentation of weakness, loss of balance, sensation of numbness and loss of vision.
In addition, the two are related to immune system responses to myelin and spinal cord . Although disseminated water encephalomyelitis is different from other pathologies for one Demyelination With an uneven pattern, conserving parts of the axons and affecting the Microglial cells , Which suppose the immune system of the brain.
We further explain the differences between these two diseases in more detail.
Causes of disseminated acute encephalomyelitis
This condition usually begins with a fever due to viral or bacterial infections, coughing up with a sore throat, or may even appear after receiving a vaccine.
In fact, most cases appear 2 to 21 days after such infection or even after 3 months of vaccination. Although many times it has not been identified what has been able to provoke it.
However, the longer the interval between fever or vaccine and the onset of encephalomyelitis, the less cause and effect relationship may be between them; So that it may be caused by other factors. It is important to note here that there is a minority of cases that do not have this initial fever.
The two phases of the disease (fever and encephalomyelitis) are characteristically separated by an interval of time in which the affected one recovers of the fever and appear other infectious signs that indicate that the encephalomyielitis is beginning.
The agents that have been most clearly related to the onset of disseminated water encephalomyelitis are: Epstein-Barr virus , Herpes simplex virus, cytomegalovirus, mycoplasma or the rabies vaccine. Other vaccines that have been less commonly associated with encephalomyelitis include measles, tetanus, hepatitis B , Rubella, chickenpox, smallpox or polio, among others.
What happens is that the immune system Of the body, which is responsible for protecting us against infections and keeping us healthy, works incorrectly attacking the body's own healthy tissues. Finally, this causes certain areas to become inflamed.
Curiously, this disease appears in the coldest times of the year; Although it has its logic because they are the stages where more viral diseases sprout.
It is important to note that multiple factors, such as genetic aspects, of the individual's own immune system, or exposure to harmful environmental factors are likely to be involved. For example, there is a genetic predisposition to encephalomyelitis associated with different genes involved in the regulation of the immune system, such as the HLA-DQB1 gene; For example (Alves-Leon et al., 2009).
Other factors that may contribute to putting the person at risk are genetic factors, high probability of infectious pathogens, vaccination status, degree of skin pigmentation, and diet.
Therefore, it is not the infection itself that causes damage to nerve cells; But rather it is the bad reaction of the immune system to the infection that damages the tissues.
However, the mechanisms of this disease are not fully understood today and more research is needed to find out.
What are the symptoms?
In most cases, the clinical course is progressive and rapid; And its more severe symptoms can reach in hours and even days (an average of 4 days). Less frequently, the symptoms can last from a couple of weeks to months. However, they can be resolved quickly with the right treatment.
The symptoms vary according to the stage of the disease, but as we said begin with symptoms such as:
- Fever.
- Tiredness.
- Headaches , Which can be intense and persistent in children.
- Nausea and vomiting.
- It sometimes appears after respiratory or gastrointestinal diseases related to a virus.
- Some patients have linked back pain as a history of this disease.
- Loss of reflexes at first.
- In the most severe cases, they may have seizures and even go into a coma.
Disseminated water encephalomyelitis is characterized by a recovery period of at least one day with no fever between the infectious phase and the onset of the disease itself.
Subsequently, damage to the white matter of the brain (which is named because of the white color of myelin present) causes neurological symptoms such as:
- Irritability.
Confusion or severe drowsiness.
- Loss of vision in one eye or both, which is associated with swelling of the optic nerve. See Neuritis Optica .
- Nystagmus Or involuntary and spasmodic movements of the eyes.
- Ophthalmoparesia or problems in the muscles to move the eyes.
- Hemiparesis Acute
- Ataxia Or difficulty coordinating voluntary muscular movements, presenting little balance and an unstable gait (walking). It is found between 28 and 65% of the cases of EAD.
- Clonus: strong involuntary repetitive muscle contractions in certain muscle sets.
- Altered speech, more commonly speech.
- Trouble swallowing.
- Weakness (75% of cases) and even paralysis of the muscles.
- Stiff neck.
- Feeling of tingling or numbness.
- Paralysis of the cranial nerves.
- Convulsions in up to 35% of cases.
- Alteration of consciousness, being able to reach the state of coma.
- Psychosis and hallucinations especially in adolescents and adults.
- Up to 30% of patients may also have meningitis (inflammation of the meninges, which are membranes covering the central nervous system).
- It can be accompanied in a quarter of the cases approximately, for transverse myelitis .
It is essential to mention that the symptoms may be different, since they depend on the place of the inflammation; And also vary slightly if the presentation is in children or in adults.
How is the course of the disease?
Although the course of AED may vary, most cases recover almost completely, including those with more severe symptoms. Spontaneous recovery usually starts within a few days and can continue for up to a year. However, some patients may continue to have symptoms such as weakness, numbness, or blurred vision.
As for the onset of symptoms, the typical antecedent infection appears in approximately two-thirds of children; But in adults, it appears in less than half.
It is possible that after an occurrence of disseminated water encephalomyelitis, the risk of presenting others in the future increases; Mainly within the first 2 to 8 years after the first attack. In fact, this happens to about 10% of children with this condition, and is called multiphase EAD.
If one of the facilitating causes appears to be measles, it has been associated with a high rate of morbidity and mortality.
In one of the studies, he followed 35 cases for almost 6 years, found that most recovered completely after a few weeks. 20 patients had no long-term alterations, permanent neurological problems such as motor dysfunctions occurred in 6 patients, Cognitive impairment In 4, visual loss in 4 and behavior problems in 4 others. In 3 patients epilepsy was developed, but only in his case remained.
On the other hand, another study focused on 40 patients with adult EAD, finding two deaths. This may mean that adults with this disease have a poorer prognosis than children.
What is its frequency?
This condition appears to affect approximately 1 in 125,000 to 250,000 individuals per year. 5% of cases appear to be related to vaccination.
Although it can occur at any age, it seems that children are much more likely than adults to present it. A proof of this is that it has been estimated that more than 80% of cases appear in children under 10 years, with an average age ranging from 5 to 8 years. The remaining 20% is linked to ages between 10 and 20 years, roughly estimated, which can occur in 3% of adults.
On the other hand, its frequent overlap with the diagnosis of multiple sclerosis Can cause them to be underestimated in adults.
It has also been shown that this disease is more common in children than in girls, with 1.3 children per 1 girl.
In addition, it seems to spring up in all parts of the world and in all ethnic groups.
How can you diagnose?
This disease can be easily diagnosed in children, through observation of signs and symptoms, and through neuroimaging and laboratory techniques. However, a specific biological marker for disseminated acute encephalomyelitis has not been defined. That is why a correct diagnosis and long-term follow-up of the disease is essential, as there are some cases that have been classified as EAD and over time it has been discovered that it was multiple sclerosis.
The diagnostic criteria that must be met to say that someone has acute disseminated encephalomyelitis are:
- An event of inflammatory demyelinating polyfocal alterations.
- Encephalopathy that can not be explained by the fever itself.
- During the acute stage, brain magnetic resonance presents abnormalities, but no new damage is found after 3 months or more after the EAD appears.
- These abnormalities consist of diffuse, disseminated lesions that involve the white matter of the brain; Which may also cause damage to the deep gray matter.
The diagnostic process may contain:
- Recent medical history, focusing on possible infections or whether there were vaccines and which vaccines.
- Blood tests to look for other infectious causes or other conditions that may be mistaken for EAD.
- Neurological examination.
- CT scan Or magnetic resonance imaging or the brain and spinal cord to look for lesions. These images may appear to be normal, although diffuse or disseminated lesions in the subcortical white matter of the brain are very often present.
- Lumbar puncture, with the aim of extracting the cerebrospinal fluid and checking if there is infection. In that case the patient may have meningitis or encephalitis.
- Cerebral biopsy: may be necessary to perform the differential diagnosis of EAD with other infectious disorders.
How is it different from Multiple Sclerosis (MS)?
As it is commonly difficult to distinguish acute disseminated encephalomyelitis (EAD) from multiple sclerosis (MS), we have decided to include a section explaining the differences between them in order to arrive at a more accurate diagnosis.
How did EAD and MS vary?
- Acute disseminated encephalomyelitis usually occurs only once, whereas in multiple sclerosis there are several repeated attacks of inflammation in both the brain and spinal cord. In fact, there are authors who postulate that they are part of a continuum, that is, the EAD can be a first sign of multiple sclerosis.
- If we look at subjects with these disorders through magnetic resonance, we see that those with EAD do not develop new brain lesions, but those with multiple sclerosis do. We can differentiate the lesions of both clinical conditions since the ones present in the EAD are larger and have a particular distribution: they cover symmetrically the white matter of the brain and cerebellum. In addition, it is seen that all these lesions appeared at the same time, unlike the typical temporal diffusion of multiple sclerosis. It should be noted that brain lesions may appear before symptoms occur if it is MS, something that does not occur with EAD.
- Symptoms of headache, confusion, fever, vomiting and convulsions typical of encephalomyelitis are not commonly seen in patients with multiple sclerosis.
- EAD is more common in children, while multiple sclerosis is usually diagnosed in adults.
- Multiple sclerosis is more frequent in women, as opposed to EAD; Which appears more in men.
- As we said, acute encephalomyelitis is typical of seasons such as winter and spring. In contrast, the occurrence of MS does not depend on the seasons.
How can it be treated?
As it is a rare disease, there is still no specific treatment to combat encephalomyelitis.
It is usually sought to reduce inflammation through anti-inflammatory drugs (National Institute of Neurological Disorders and Stroke, 2016). For example, substances such as Corticosteroids In high doses, intravenously. Approximately 20 to 30 mg per kg of methylprednisolone or other steroids for a period ranging from 3 to 5 days, although improvement is observed in hours.
On the other hand, it is true that this treatment is widely used and advocated by experts, however, the natural course of encephalomyelitis is a spontaneous recovery. So it is difficult to know if the improvement is really due to the treatment, or if it is not effective and the patient is recovering alone.
There is even evidence that these types of drugs may have other long-term problem effects for the disease. As facilitating their occurrence again in the future (Nishikawa et al, 1999)
Although in general, the recent trend indicates a better survival of these patients due to the Methylprednisolone specific. In addition, it seems that, if this treatment is withdrawn, relapse is more likely. However, other oral drugs are often included to prevent relapse.
Other alternative therapies that are performed when the patient does not respond to the above, include injection of intravenous immunoglobulin, which comes from the blood of healthy people; Cyclosporine, cyclophosphamide, mitoxantrone, or plasmapheresis, which involves removing all of the blood from the body to remove its plasma (or components of the immune system) and re-introducing it into the patient.
On the other hand, the symptoms due to the encephalomyelitis will be alleviated and will be intervened in the problems that each individual presents. For example, patients who also have high intracranial pressure will improve through surgical interventions.
The patient is also advised that as this disease is associated with both vaccines; These or other immunological stimuli are avoided for at least 6 months after a diagnosis of EAD.
A better understanding of the mechanism of acute disseminated encephalomyelitis will facilitate the development of more specific and effective treatments.
References
- Acute Disseminated Encephalomyelitis Information Page . (March 21, 2016). Retrieved from the National Institute of Neurological Disorders and Stroke.
- Alves-Leon, S.V., Veluttini-Pimentel M.L., Gouveia, M.E., Malfetano, F.R., Gaspareto, E.L., Alvarenga, M.P., et al. (2009). Acute disseminated encephalomyelitis: clinical features, HLA DRB1 * 1501, HLA DRB1 * 1503, HLA DQA1 * 0102, HLA DQB1 * 0602, and HLA DPA1 * 0301 allelic association study. Arq Neuropsiquiatr . 67 (3A): 643-51.
- Bennetto, L., Scolding, N. (2004). Inflammatory / post-infectious encephalomyelitis. J Neurol Neurosurg Psychiatry, 75: 222-228.
- Brenton, J. (December 30, 2015). Acute Disseminated Encephalomyelitis . Obtained from Medscape.
- Dale, R.C., de Sousa, C., Chong, W.K., Cox T.C., Harding, B., Neville, B.G. (2000). Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain, 12 3 (12): 2407-22.
- Nishikawa M., Ichiyama T., Hayashi T., Ouchi K., Furukawa S. (1999). Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol . 21 (2): 583-6.
- Symptoms and Diagnosis of ADEM . (S.f.). Retrieved on July 1, 2016, from National Multiple Sclerosis Society.
- Image source .