Our Epilepsy Team

First let's do a little introduction

Epilepsy is one of the most common neurological conditions in the world. More than 65 million people in the world are affected, from it around the world and statistics show that on average one in 20 people will suffer from some type of these crises at some point in their life (although this does not necessarily mean a diagnosis of epilepsy). While epilepsy is most commonly diagnosed in children and people over the age of 65, it can occur to anyone and at any age, with no gender or ethnicity preferences, making it highly unpredictable. It is characterized by disorders in the activity of the brain, which cause seizures, periods of unusual behaviors or feelings, sensations and sometimes loss of awareness.

Symptoms of seizures can vary, some people stare at one point for a few seconds others have repeated and involuntary twitching of the limbs. All this affects the safety, relationships, work and many other aspects of the life of people with epilepsy, who too often find themselves in a state of isolation due to the lack of perception of these problems by public opinion.

What is behind

According to the International League Against Epilepsy (ILAE), there are more than 30 types of epileptic syndromes, including some more severe and debilitating forms often seen in very young children in the first months of life such as Ohtahara syndrome, Dravet syndrome and West syndrome. The causes of these diseases are varied and complex. They can result from brain damage caused by injuries such as trauma suffered due to an accident or a problematic birth, brain tumors, viral and bacterial infections such as meningitis or from genetic factors.

Therefore, receiving a diagnosis can be extremely challenging and not always achievable, as of today six out of ten patients do not have a diagnosis of their condition. A quick and accurate genetic analysis can help confirm or refine a clinical diagnosis of epilepsy. There are also many important comorbidities associated with epilepsy such as autism, intellectual disability and developmental delays. At the base there may be structural changes in the brain due to genetic conditions, such as tuberous sclerosis or neurofibromatosis. It is thought that 30% of epilepsies are due to genetic factors and this is associated with many different clinical phenotypes and genotypes, the genetic landscape is made even more difficult by complex models of inheritance and interaction with the environment.

The detail

After the discovery of the first gene associated with epilepsy in 1995, there have been numerous advances to understand the genetics of epilepsy in fact in 2019 more than 140 genes or loci were associated on the OMIM databases. The genetic mechanisms that contribute to epilepsies are also being studied continuously, for example a repeated expansion of nucleotides has been identified as the cause of a myoclonic familial epilepsy and in some cases somatic mosaicism has also been found to cause focal epileptogenic lesions.

The very large non-coding portion of the genome is also interesting, of which we are only at the beginning of understanding; in fact, in recent years there has been an increase in studies on de novo variants in regulatory regions (e.g. promoters) even very far from the gene of interest and this, also thanks to the lowering of sequencing prices for WGS, makes it an exciting research frontier.

The way to Precision Medicine

Current drug therapies offer a range of about 30 antiepileptic drugs (AEDs) that aim to prevent the occurrence of epileptic seizures, but do not cure epilepsy. With the prescription of the correct antiepileptic drugs, almost 70% of patients are able to control their seizures, however these are not without side effects and adverse reactions to this type of drugs vary greatly from individual to individual. Thanks to new insights into pharmacogenetics, a detailed understanding of the patient's genome offers the promise of more targeted treatment based on his/her genotype.

Other treatments in use are the ketogenic diet, brain surgery, deep brain stimulation, and neuromodulation therapies such as vagus nerve stimulation, in which a device sends electrical impulses to the brain that help reduce the severity of seizures.

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