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Electrical failure in the system: epilepsy


We all have moments when we don’t feel zen, when we lack inner tranquillity. Periods of time when our inner balance breaks down and we have a bad time. Sometimes, neurons also go through brief moments of imbalance. And sometimes that imbalance is electrical and you have an epileptic seizure.

Epilepsy and epileptic seizures are sudden, short-lived events in which abnormal and excessive activity occurs in the brain. The characteristic symptom is seizures, with or without loss of consciousness.

Although epilepsy is associated with movement in the collective memory, this does not necessarily always have to be the case. An epileptic seizure may manifest itself as an involuntary change in sensation or behaviour, for example.

The symptoms depend on the region of the brain affected. In the most severe, so-called de grand mal seizures, the patient loses consciousness, becomes rigid and has strong muscle spasms. In contrast, there are some very mild ones, called petit mal, which are barely perceptible and manifest themselves with rapid blinking or a few seconds of disconnection from the person’s surroundings.

On the other hand, just as it is not every time you sneeze that it is Covid, it is not every time you have a seizure that it is epilepsy. To be considered epilepsy, seizures must be recurrent over time, due to a chronic process that is the cause.

High fever, low blood sugar, or if you are a regular drug user and your body is subtly telling you that it needs its dose (withdrawal syndrome), are also causes of seizures.

The usual way to corroborate a diagnosis of epilepsy is by electroencephalogram (EGG), where increased nerve activity can be visualised. In some cases, it even indicates in which regions of the brain the abnormal electrical activity has originated.

This is not always valid, because sometimes seizures originate in such deep areas of the brain that the machine is unable to detect them. CT and/or MRI scans can also be performed.

Epilepsy is a complex disease with different possible causes that we could classify into two main, non-exclusive ones:

  1. Brain lesions. These in turn can have different causes, from brain trauma to diseases such as meningitis.
  2. Genetic origin, genetic epilepsy. There is a genetic predisposition to suffer from the disease, and family history is important and relevant. It is considered that a person with relatives who have epilepsy has a five times greater risk of suffering from it than someone with no family history. Genes are of particular importance in these cases, as modulators of the disease and key points for treatment.

Often the cause of epilepsy is unknown, so it is called idiopathic epilepsy when a genetic cause is suspected (but not confirmed), based on family history, clinical picture and rigid EEG pattern. When the cause is thought to be organic (but not genetic) but there is no idea what is going on, they are called cryptogenic epilepsies.

In the most used classification of epilepsies, they are grouped into three blocks, similar to the classification of seizure types:

  1. Generalised seizures. They are symmetrical on both sides and do not have a local origin.
  2. Partial or focal seizures. They start in a localised area. The feast of electricity occurs only in one area of the brain.
  3. Special epileptic syndromes.
fallo electrico epilepsia

When you inherit seizures

Some researchers estimate that up to 49% of cases are linked to DNA mutations. It is estimated that there are more than 800 genes involved in this disease.

Some genetic disorders are linked to an increased likelihood of epileptic seizures, such as Angelman syndrome. In these cases, we could say that epilepsy is hereditary.

In 1-2% of epilepsy cases, a single gene is responsible. Although rare, more than 200 genes have been described that can cause epilepsy on their own. As biology likes logic, all these genes are directly or indirectly related to ion channels, which are indispensable in the regulation of neuronal electrical activity by regulating the transport of ions between the cell and the outside world.

One example is pyridoxine-dependent epilepsy. This epilepsy is always caused by mutations in the ALDH7A1 gene, which encodes an enzyme with multiple functions. The resulting disease is refractory, epileptic seizures for which conventional antiepileptic drugs do not work. However, the administration of the active form of pyridoxine throughout the patient’s life allows seizures to be controlled, which is the reason for the name it has been given.

Among the complex diseases with a genetic component in which epilepsy is present, seizures are classified as idiopathic epilepsies.

Some countries such as the United States and Canada have already started programmes in which genetic tests are carried out on children under 60 months of age who are suffering from seizures without having suffered trauma or tumours. In this way, they check for hereditary epileptic seizures.

Calming the neurons

The usual treatment is the use of anticonvulsant drugs. In severe or refractory cases (a refractory case is one in which the disease decides it doesn’t care about treatment and good luck stopping it) surgery of the affected area may be necessary.

When epilepsy is due to a well-defined lesion or tumour, and is then a secondary symptom to the true pathology, surgical removal of the cause of the seizures cures the epilepsy, or at least reduces its intensity and frequency.

However, more than 90% of cases are treated with anti-epileptic drugs. It is a therapy that must be prolonged over time and can have very strong adverse side effects.

With epilepsy there is a very strong genetic component even if they are not the primary culprit. Due to the enormous variety of responses, both disease and patient, it is a pathology where pharmacogenetics is of relevance. Depending on the medical and genetic characteristics of the patient, experts can best decide which drug and dose to administer in each specific case.

In fact, treatments are intended to be monotherapy, with a single drug. Two or more drugs are used when the patient does not improve with treatments with one drug, to prevent side effects.

Sometimes pharmacological treatment is combined with psychological treatment. Withdrawal of the drugs is slow, over two to three months. Anything that touches the central nervous system must be treated with cotton wool.

Sometimes childhood epilepsies are cured naturally during adolescence.

The economic cost to society is significant. In the United States, 3.4 million people currently suffer from epilepsy, and 5.1 million have a recorded history of epileptic seizures. Worldwide, an estimated 50 million people are affected.

In addition, some drugs react negatively with people affected by epileptic seizures. Diazepam, which has become so fashionable in recent years, can cause an increase in seizures in these patients.

“De grand mal”

After an epileptic seizure, the person usually suffers a moment of confusion that progresses to pre-seizure normality. Occasionally mild hypoxia occurs because muscle movement interrupts breathing. It manifests with cyanosis (an unhealthy blue tint) of the lips and ears.

Seizures do not require hospitalisation unless status epilepticus is present.

Status epilepticus is a seizure that lasts long enough to cause neurological damage and constitutes a clinical emergency. It can range from a single seizure lasting five minutes or more, or more than one seizure of shorter duration, but leaving no time between seizures for the patient to recover.

It is estimated that 1-5% of people with epilepsy will suffer a status epilepticus at some point in their lives. Mortality from status epilepticus is 20-25%.

Although the risk of long-term damage depends on several factors, time is the most decisive. After 20 minutes, the risks of neurological damage are high.

Death and injury often occur due to oxygen deprivation. Blood pressure and body temperature may also be altered. In addition, at the neuronal level, repeated electric shocks cause an increase in intracellular calcium, and subsequently a chain of reactions leading to cell death.

An additional risk is the possibility of accidents due to involuntary movements during an epileptic seizure. In some countries jobs involving heavy machinery or driving are forbidden for people with a history of uncontrolled epilepsy.

It is a disease that also occurs in animals, with cases in cats and dogs being well known. All mammals can suffer from epilepsy. Within dogs, it is considered the most common brain disease. Interestingly, each breed of dog has a different predisposition to suffer from this disorder.

If you are concerned that in addition to your neurons, your genes may be overactive and abnormally active, you can look at this with the tellmeGen Advanced DNA Kit.

Carlos Manuel Cuesta

Graduate in Biology. PhD in Biotechnology

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