Epileptic encephalopathy

Epileptic encephalopathy, definition:

Epileptic encephalopathy is the name given to a group of epilepsy syndromes related to cognitive and behavioral disturbances, which begin in the first years of life. These disorders are differentiated according to the type of epileptic seizures, age of onset, prognosis, response to treatments, etc. They all share difficult-to-control seizures that can impair cognitive and motor functions. Seizures in these patients can be of different types: absence seizures (with disconnection from the environment and little symptomatic expression), tonic seizures (causing stiffness of the muscles of the body, back, arms and legs), but they can also be focal motor, myoclonic or atonic (which can lead to the patient falling).

Until 2001, the ILAE (International League Against Epilepsy) did not include epileptic encephalopathy in its classification as a distinct category within the diagnosis of epilepsies. In 2010, epileptic encephalopathy was defined as “the condition in which the epileptic activity itself contributes to significant cognitive and behavioral disturbances, which are beyond those that the underlying disease alone would cause, and which may worsen over time”. These alterations would be potentially preventable with the correct treatment of epilepsy (pharmacological, surgical or otherwise).

Within the epileptic encephalopathies we find:

• Early myoclonic encephalopathy.
• Rasmussen’s encephalitis.
• Malignant epilepsy with migratory partial seizures in childhood.
• Epilepsy with continuous spiral waves of slow sleep.
• Myoclonic status in non-progressive encephalopathies.
• Dravet syndrome.
• Doose syndrome.
• Ohtahara syndrome.
• Landay-Kleffner syndrome.
• West syndrome.
• Lennox-Gastaut syndrome.
• Unverrich-Lundborg disease
• Angelman Syndrome
• Prader-Willy syndrome
• Rett syndrome
• Fragile X syndrome
• Others…

In these patients it is essential to correctly diagnose the electro-clinical syndrome by means of a complete clinical interview, a physical examination, an exhaustive review of the clinical history and the response to treatments, as well as prolonged video-EEG monitoring (at least 24 hours). High-field neuroimaging (high-resolution magnetic resonance imaging) and brain PET-CT will provide extra information in many cases. In patients in whom a correct diagnosis has not been reached after all the above, an extensive genetic study (specific gene study, epilepsy gene panel, array-CGH or triexome) is necessary, as these tests achieve a definitive diagnosis in about 40-50% of cases. Some genes related to epileptic encephalopathies are SCN1A, SCN2A, SCN8A, ARX, CDKL5, STXBP1, UBE3A, DEPDC5.

The correct diagnosis, with electroclinical data, neuroimaging, and in some cases genetic testing, will provide prognostic information, and will also help in many cases in the choice of the correct antiepileptic treatment (pharmacological and/or surgical), as well as enabling in some cases participation in clinical trials with new investigational therapies.

TREATMENTS:

Depending on the type of epileptic encephalopathy, treatment may vary, however in all cases, early diagnosis and appropriate treatment improves the prognosis of these patients .

1. Correct antiepileptic drugs, selected according to the electroclinical syndrome and underlying cause.
2. Intravenous immunoglobulin: May be useful in the control of inflammatory phenomena associated with epilepsy and that block inhibitory mechanisms and neuronal excitation.
3. Ketogenic diet: can be useful in a wide range of epilepsies. This diet should be controlled by a specialized nutritionist.
4. Experimental treatments: Through clinical trials, for example with fenfluramine or TAK-935 treatments.
5. Resective or minimally invasive surgery by radiofrequency thermoablation or gamma-knife radiosurgery.

Our Epilepsy Program Team has specialists in epileptic encephalopathy. If you would like to receive information , please contact us.