Proposed classification: Syndromes in Children

Members of the Nosology and Definitions Task Force of the ILAE have developed four position papers on syndrome definitions at various ages. The ILAE guideline process requires obtaining feedback and comments from its members on the proposed paper. These comments from our international community will be reviewed by the working group before finalizing the paper.

Please see the Draft: ILAE Classification and Definition of Epilepsy Syndromes with Onset in Childhood

The manuscript will be open for comments until 15 July 2021. Please use this survey to enter your comments and they will be published below.

Thank you for your help in this important effort of the ILAE.

See all four Proposed papers for Nosology and Definitions

Comments

12 June 2021

Comprehensive and clinically relevant. The introduction of the term self limiting in the nomenclature would combat a lot of stigma against these conditions.

Arun Swaminathan MD


9 June 2021

I feel that the 4 syndromes classified under self limited epilepsy can be named in a uniform manner. COVE and POLE seems to stand apart. Why can't they be renamed as 1. Selflimited epilepsy with visual paroxysm and Selflimited epilepsy with photosensitivity respectively?

Pradeep Pankajakshan Nair


7 June 2021

I was not able to find Hypothalamic Hamartoma Syndrome mentioned in any of the papers. While it might be argued that it could be included in the Neonate and Infant definition as it is a structural DEE, it may be better described in the Onset in Childhood as that is when comorbidities become advanced enough and gelastic seizures may have progressed (and may be better recognized), therefore it is most often diagnosed.

Lisa Dunn Soeby


5 June 2021

The term “childhood epilepsy with centrotemporal spikes” in the present EpilepsyDiagnosis.org implies that this syndrome is limited within childhood. I believe that renaming it to “self-limited epilepsy with centrotemporal spikes” with exclusion of “childhood” should blur its concept as childhood-limited epilepsy.

Katsuhiro Kobayashi


3 June 2021

Thank you for this important work. I have comments about the terms, Epilepsy with Eyelid Myoclonia (E-EM) and Epilepsy with Myoclonic Absence (E-MA).

The clinical difference between a clonic vs myoclonic seizure is fairly well established. As stated under the seizure description of E-EM, the eyelid motor symptom consists of "of brief, repetitive and often rhythmic, 3-6 Hz myoclonic jerks of the eyelids..." It is more typical that the "myoclonus" occurs more than once consecutively, usually multiple times. Epilepsy with Eyelid "Clonus" (E-EC) seems more appropriate. Similarly, E-MA is described as "rhythmic 3 Hz jerks of the upper limbs, superimposed on tonic abduction of the arms during the seizure (giving a ratcheting appearance)." The rhythmic jerks typically last "10-60 seconds" and actually describe clonus. The term, Epilepsy with "Clonic" Absence (E-CA), seems more appropriate. The use of the term Clonus (and not Myoclonus) for both seizure subtypes will prevent confusion and may improve identification of these subtypes.

Jun T. Park


2 June 2021

In SeLEAS, EEG characteristics are only poorly described. If SeLEAS is a clinico-electrial syndrome, the EEG characteristics should be better described in a more detailed fashion as follows because the detailed interictal EEG study of Panayiotopoulos syndrome showed characteristic age-dependent change in localization of epileptiform abnormality (Ohtsu et al. Epilepsia 2003;44:435-442.)

Multifocal, high voltage spike- or sharp-and-slow-waves are typically seen, often over the posterior regions between 2 and 5 years of age and later the predominance moves to either centrotemporal region or frontopolar region with age progress. Generalized discharges may also be seen at the peak of EEG worsening.

Myoclonic-atonic epilepsy

Development before the onset:
MAE itself has long been considered primary generalized or idiopathic generalized epilepsy, similar to absence epilepsy or juvenile myoclonic epilepsy, because patients exhibit normal development and are neurologically normal without imaging abnormality in addition to genetic predisposition. Although Doose described that 16% of 117 patients with MAE demonstrated signs of developmental retardation before the onset of epilepsy or had high-risk factors in their history, the original case series of Doose potentially included heterogeneous epilepsy syndromes because he himself admitted that he refused to subclassify the syndrome by clinicoelectrical details. According to his original concept of this syndrome, the presence of even mild developmental delay should be also placed on the “Alerts” like childhood absence epilepsy.

Seizures:
Myoclonic-flexor seizures or massive myoclonic seizures causing drop attacks should be included in addition to myoclonic-atonic seizures as a main seizure type (Oguni H, et al. Epilepsia 1992;33(5):805-813; Adv Neurol 2005;95:157-174; Epilepsia 1997;38(7):813-818).

EEG:
Interictal discharges comprised of generalized 3-6 Hz spike-and-slow-wave or polyspike-and-slow wave often occurring in bursts lasting 2-6 seconds are seen (Figure 6A). This expression of 3-6Hz SWC is not relevant for SWC frequency of MAE. Although Doose described typical EEG finding as 2-3Hz SWC, he potentially included patients with myoclonic epilepsy in infancy (presenting with 3Hz SWC) in his series. As MAE is categorized in DEE, the SWC frequency at least includes 2Hz SWC or lesser frequency (Oguni H, et al. Adv Neurol 2005;95:157-174). The 3-6Hz spike-and-wave or polyspike-wave is the same SWC frequency as that of JME, but it is doubtful whether MAE and JME have SWC of the same frequency.

Fig6BC is not typical ictal polygraph of atonic drop attacks because only brief atonia was recorded at bilateral Deltoid muscles.

Hirokazu Oguni


31 May 2021

I would like to make comments to the SeLECTS category.

It is more or less evidenced that the core syndromes (RE and Panayitopoulos sy) may transform to what is in the proposition named as „Developmental and/or Encephalopathy with spike-wave acrivation in sleep (D/S-SWAS) (incorporating previous LKS).

This would make a spectrum of the perisylvian network epilepsies with cognitive (especially causing language , or more widespread cognitive impairements, which is congruent with functions of this network, as a human communication network).The frequency of this devastating transformation is underestimated according my experiences, and the early recognition of it is highly important, threfore to dividing it fom the earlier and also present „benign” forms, hide certan dangers.

The naming the EEG abnormality as „spike-wave”and identiying this with the bilateral syncronous spike-wave pattern is misleading. In the encephalopathic forms the EEG discharges are not spike waves , but they could be identified as focal unihemspheric discharges with phase reversal,changing to bilateral appearence via callosal sencondary syncronisation mechanism. So they can be derived from CTS. The presence of augmented CTS in the encephalopathic forms is a strong argument in favour of the spectral togetherness of the core and encephalitic forms.The genetic results also supported same underlying gene mutation factors for at least in the non developmental (not underlied by brain pathology) group of patients.

Peter Halász


21 May 2021

Thank you for the substantial good work done. I will restrict my comments to the aspects I feel very strongly about.

I find many changes you have made rather confusing, particularly in context of teaching and allowing one's brain (my own brain and that of people learning or training) to compartmentalise things properly.

Therefore, I will make the following points:

1. Self limiting (SeL) is a good concept and better than benign but should be applied to ALL subsets not only to SeLECTS or SeLEAS, otherwise, there will be definite confusion to all if SeL is not used before all subsets.

2. I think it is not best/optimum or helpful to take out the words occipital & Panayiotopoulos from SeLEAS. This is an occipital epilepsy syndrome and Panayiotopoulos discovered and described it. The occipital spikes seen in this syndrome are a major helping part of diagnosing it and there is nothing confusing about saying it is early onset with more Autonomic features and the Gastaut variant late onset with CLEAR visual features, I think some breach of etiquette may be seen with taking the name of Panayiotopoulos out of his own syndrome.... something to think about seriously.

3. We now know that all epilepsies have genetic basis. I find using the word Genetic Generalised epilepsies and presuming people will know we mean previous IGE is ambitious and it also means that these are the ONLY Genetic generalised epilepsies... I always use the term "Genetically influenced" for both the Focal and Generalised Epilepsies previously known as IGE and IFE to separate them from the more serious or less benign generalised and indeed sometime focal genetic epilepsies such as Dravet, CLN2 and so forth...I think it should be considered to use the term genetically influenced for IGE and IFE families (by the way, genetically influenced as a term, I was inspired to use by your group too from earlier days so I give you credit for it and ask that you retrieve it back!). It is very useful to separate the self limiting (focal-IFE) or the usually with no serious co-morbidities (Generalised-IGE) from the more serious and/or not self limiting epilepsies.

4. I wonder f you would re-consider the rather complex title and its consequently crowded abbreviation:
"D/EE-SWAS". I am a believer that abbreviations and titles are made to simplify things and make them easy to remember.

Including "hyphen" and "forward slash" to titles is best avoided. It lends itself to all sorts of spelling errors and consequent incomplete searches of repeated titles on the net or in documents. One needn't crowd or cramp in ALL components of a syndrome in the title. I believe title are meant to be brief not detailed (details come under the heading or title, not in it) It becomes more like a deconstructed title or an unnecessarily deconstructed gateaux/pie.... with full acknowledgement of your conscious attempts to "spell out" things and make them easier and clearer

Thank you again for the continuing good work but serious reconsiderations are desired.

Amre Shahwan


13 May 2021

Comments on the prominent motor symptoms related to 3 Hz spike-waves (absences), like the perioral, or those involving head movement should also be inserted to help new beginners. Moreover, the relation of absence epilepsy with photosensitivity needs further clarification.

In POLE, the number of seizures is mostly low, and therefore ictal recording is not easy to be in hand. This could not be a reasonable diagnostic criterion, it is not required in typical cases satisfying all other criteria, which are well-presented. 

Betül Baykan


11 May 2021

Regarding the differential diagnosis of Self-Limited Epilepsy with Autonomic Seizures (SeLEAS), I'd like to add not only other medical disorders associated with intermittent vomiting, but also surgical conditions. Sometimes it mimics like an intestinal obstruction clinically.

Kyaw Linn


10 May 20201

I agree with the rationale behind the changes but there needs to be some improving internal consistency in the way that titles are constructed. This is harder to see in this paper compared to the other three.

Within the self-limited group, it is confusing to switch some to a title of self-limited but not all in that group. I can understand losing the terms idiopathic, but in one instance you have switched that to childhood whereas another you have given up the term childhood and replaced with self-limited. This is confusing to me. I would prefer an approach where we can see an improved internal consistency across the titles. These types of issues make the teaching and diagnostic coding around epilepsies really tricky to implement and also make it tricky for patients when understanding or describing their epilepsy type.

Given the pragmatic difficulties of ever increasing title lengths and the difficulties around how much of epilepsy syndromes characteristics to capture in the title, the retention of eponymous or acronym titles as legitimate alternative titles to me does seem sensible and where possible I would favour retaining these even if their more complicated non-eponymous title needs improving. The retention of some eponymous titles as practical alternative handles would help professional and patient communication in my view..

Given this, I would prefer an approach such as either

  • Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS)
  • Self-Limited Epilepsy with Autonomic Seizures (SeLEAS, Panayiotopoulos syndrome)
  • Self-Limited Occipital Visual Epilepsy
  • Self-Limited Photosensitive Occipital Lobe Epilepsy;

or

  • Childhood Epilepsy with Centrotemporal Spikes (CECTS)
  • Childhood Epilepsy with Autonomic Seizures (Panayiotopoulos syndrome)
  • Childhood Occipital Visual Epilepsy (COVE)
  • Photosensitive Occipital Lobe Epilepsy; (POLE)

Both of these approaches have an internal consistency in keeping with your rationale. On balance I favour the second list as it retains your rationale, avoids unnecessarily changing CECTS and I can see it working more easily in practice.

Colin Dunkley


7 May 2021

1. Regarding table 2 on Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS)

In the alert column its written usual seizure frequency more than daily..Doesn't it imply that SeLECTS has normally daily seizure frequency which we know isn't true and if a SeLECTS has a seizure frequency of daily episodes it should be considered as a major alert.

2. Regarding Developmental and/or Epileptic Encephalopathy with spike-wave activation in sleep (D/EESWAS)

I particularly liked its new nomenclature but in the description its written "The EEG pattern previously required for this syndrome was known as continuous spike-wave in sleep (CSWS) and the clinical correlate previously known as electrical status epilepticus in sleep (ESES). Isn't it the other way round? The EEG correlate was called ESES(obviously as term electrical is used) and the clinical correlate was called Epileptic encephalopathy with CSWS.

Regarding EEG in this syndrome its written "SWAS is usually diffuse but may occur more focally (typically
frontally) or multifocally"

I would like to point out that we have analysed EEG of more than 35 children of ESES and followed them for more than 3 years with serial EEG and neurocognitive assessment and their EEG were analysed in special source localisation and mapping software and we found that these apparently "diffuse" looking pseudo generalised spikes are infact in 100 % cases due to “almost”synchronous bilateral activation of spikes (with a lead-in of 20-40 ms from one hemisphere with shifting asymmetry ) with a tangential/oblique dipole .The rules of mapping localised all these spikes around Rolandic region(anterior and posterior walls).Morover the frontal predominance which you have mentioned is also seen due to the wrong interpretation of the spikes originating from posterior margins of the rolandic sulcus which has frontal negativity and tempero-occipital positivity with a positive phase reversal.

We have sent this study and accepted for poster presentation in AOEC 2021.I hope you consider this finding before concluding that the EEG pattern in this syndrome as "diffuse with frontal predominance".

One more thing which I wanted to add is that significance of the so called "developmental epileptic encephalopathy " in this syndrome should be infact more stressed. This in fact comprises the entity which we previously called symptomatic ESES(structural causes) and its more and more recognised than before.

3. Regarding Self-Limited Epilepsy with Autonomic Seizures (SeLEAS), "generalized discharges may also be seen"

It's seen that most of these "generalised" discharges are infact the bilateral occipito-frontal spikes which is seen in this syndrome and I hope you add this as an EEG finding in this syndrome. Also sometimes bilateral occipito-frontal spikes seen in this syndrome sometimes mimic ESES pattern if we are not aware of the clinical history.Therfore I feel that this valuable EEG finding be added in description.

Neetha

 


5 May 2021

This series of four position papers represent a monumental contribution to the establishment of well defined epilepsy syndromes.

Corrective Feedback:
The Onset in Childhood paper has a typo on Page 60 (Figure 1) in that Occipital Spikes currently shows 4 to 7 years, but should be 4 to 17 as in the narrative. 

Regards, John McGinley