New epilepsy classification helps with orientation in diagnosis and therapy decisions

XXIII WCN 2017, Kyoto, Japan, 16-21 September 2017

There are different types of epilepsy: In years of work, the International League Against Epilepsy (ILAE) has devised a new classification system for this complex and varied disease. It is being presented at the World Congress for Neurology in Kyoto. 

Kyoto, September 2017 - At the XXIII World Congress for Neurology (WCN) in Kyoto, Japan, the International League Against Epilepsy (ILAE) presented the results of a Herculean task which took many years to complete: a new classification system for epileptic seizures and for epilepsy. Combined efforts from hundreds of professionals around the world, with added input from people with epilepsy, their caregivers and lay associations, have contributed to this framework. Prof Emilio Perucca, President of the ILAE states: “The international discussions of our community were very challenging but urgently needed. Over the past 20 years, a completely new understanding of this elusive disease has emerged. This classification is a good instrument for actual practice. It will make diagnosis and therapy decisions easier and thus finally improves the quality of care.” Moreover, new and easy-to-understand terminology should help in future to describe the disease and its symptoms in a precise manner, using a common language across the world. 

Level 1: Determine the seizure type

“The classification has three levels and takes a clinical diagnosis approach. It helps us to determine the type of epilepsy the patient is suffering from,” explained Prof Jaqueline French from the NYU School of Medicine, New York, a member of the ILAE Task Force. At level one, after establishing the epileptic nature of a seizure, we need to determine the seizure type based on the site of origin of the seizures in the brain. “Focal seizures” are those that originate within networks limited to one hemisphere – these seizures may spread to the contralateral hemisphere and evolve into bilateral tonic-clonic seizures. “Generalized seizures” originate at some point within, and rapidly engaging, bilaterally distributed networks, which can include cortical and subcortical structures but not necessarily the entire cerebral cortex. A third category covers seizures for which the location of onset is unknown. 

Level 2: Determine epilepsy type

Then the epilepsy type is determined. In the case of “generalized epilepsy”, patients typically show generalized spike-wave activity on the EEG. They can have a wide range of seizure types, including absence seizures, myoclonic seizures, tonic seizures, atonic seizures, and the well-known tonic-clonic seizures which involve loss of consciousness, diffuse muscle stiffening and rhythmic jerking of both arms and legs. “Focal epilepsies” are characterised by focal seizures which arise from one hemisphere of the brain. Prof Perucca: “We introduced a new group, namely “combined generalized and focal epilepsies.” This group covers patients that have both generalized and focal seizures. Prof French added: “There is also an ‘unknown’ group, when the epilepsy type cannot be determined because there is insufficient information available.” 

Level 3: Determine the epileptic syndrome

At the third level, the epileptic syndrome is determined whenever possible. A syndrome is a complex of clinical, EEG and imaging features that together define a distinctive, recognizable clinical entity. The syndromes frequently have age-dependent characteristics and may or may not be associated with distinctive comorbidities, such as intellectual disability and psychiatric disorders. 

The importance of ascertaining the etiology

Each of the three levels is linked, wherever possible, to specification of the underlying cause (etiology). There are six main etiological subgroups: 

  • “Structural” refers to an anatomical abnormality which is detectable on structural neuroimaging and is plausibly the cause of the patient’s seizures. 
  • “Genetic” means that genetic changes are responsible for the patient’s seizures. Importantly, genetic does not mean ‘inherited’, because in many cases the epilepsies arise from de novo mutations. At times, such as in idiopathic generalized epilepsies, there is strong evidence for a genetic basis (e.g. studies in twins), but the specific genetic defect is largely unknown.  
  • “Metabolic” designates epilepsies brought about by a known or assumed metabolic disorder, for example porphyria, or aminoacidopathies.
  • “Infectious” refers to epilepsies caused by an infection of the brain, such as neurocysticercosis.
  • “Immune” means that a disorder of the immune system is responsible for the epilepsy. “Diagnosis of autoimmune encephalitides is rapidly increasing because there are more and more antibody tests available,” Prof Perucca added.
  • “Unknown” refers to epilepsies in which the cause has not been ascertained. 

It should be noted that some epilepsies may have more than one etiology, as for epilepsies associated with tuberous sclerosis in which the cause is both “structural” and “genetic”.

Keeping an eye on comorbidities

Neurologists are increasingly aware of the need to also consider epilepsy comorbidities. These include learning difficulties, psychological problems, mood and behavioural disorders, sleep or gastrointestinal problems. In certain cases, motor deficits such as cerebral palsy or deterioration in gait may be seen as well as sideways curvature of the spine. “It is therefore vital to consider possible comorbidities at each level of classification. This enables an early diagnosis and identification of the disease as well as appropriate treatment,” Prof French noted. 

New terminology and definitions

The term “epileptic encephalopathy” is incorporated in the ILAE categorization. This term is used where the epileptic activity itself contributes to severe cognitive and behavioural impairments above and beyond what might be expected from the underlying 

pathology alone (e.g., cortical malformation). In some cases, however, a separate developmental dysfunction (unrelated to the epileptic activity) may contribute to the patient’s cognitive and behavioural impairments. In such cases, the ILAE suggests using the term “developmental and epileptic encephalopathy” instead of “epileptic encephalopathy” alone. Developmental encephalopathies involve fixed alterations in brain function. Epileptic encephalopathies are more dynamic as they are caused by the epileptic activity itself, and can be improved if this activity is eliminated.

There have been several other terminology changes, aimed at introducing a more transparent language. For example, the old term ‘simple partial seizure’ is replaced by the term ‘focal aware seizure’, whereas the old term ‘complex partial seizure’ has been changed to ‘focal seizure with impaired awareness’. The term “benign” is replaced by the term “self-limited” (referring to the likely spontaneous resolution of a syndrome) and/or “pharmacoresponsive” (referring to responsiveness to medications), as appropriate. 

“We know too little about the genesis, course and mechanisms of epilepsy to create a complete scientific system of classification for the disease. However, we hope that this current system will prove being useful for clinical practice in the years ahead. As our knowledge of the disease grows, we will continuously refine the system,” Prof Perucca said in conclusion. 

Sources: Fisher, Robert S et al: Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia: 1-9, 2017; Scheffer, Ingrid E et al: ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia: 1-10, 2017

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