# data[].attributes.attachment_link.readable_text
Front Pediatr. 2023; 11: 1151770.

Abstract

Background

Febrile seizures (FS) and benign convulsions in children with mild gastroenteritis (CwG) are acute symptomatic seizures, transiently occurring in infants and young children, probably related to the immaturity of the brain. Our paper aims to review the literature data on patients with FS and CwG.

Methods

A review of series of patients with FS and CwG was performed by literature search on PubMed January 1960 to October 2022. Several parameters were considered, including epidemiology, pathophysiology, clinical features, electroencephalographic findings and other diagnostic studies, and treatment.

Results

FS and CwG share an age-dependent course, but they show significant differences in the pathophysiology, clinical features, diagnostic studies, and treatment.

Conclusion

Acute symptomatic seizures include seizures that are caused by acute structural brain pathologies, such as stroke, as well as seizures that are provoked by a reversible factor, such as hyponatraemia, although the two groups should be not equated. Furthermore, FS and CwG should be set apart as "age-dependent acute symptomatic seizures", reinforcing the concept of their self-limited course over a certain period.

Keywords: febrile seizures, benign convulsions in children with mild gastroenteritis, epilepsy, electroencephalography, PPMD

1. Introduction

Febrile Seizures (FS) and benign convulsions in children with mild gastroenteritis (CwG) are quite common in infants and young children. The American Academy of Pediatrics (AAP) defines FS as "a seizure accompanied by fever (temperature 100.4°F or 38°C by any method), without central nervous system (CNS) infection, that occurs in infants and children 6 through 60 months of age" ( 1). Benign convulsions associated with mild gastroenteritis (CwG) have been defined as afebrile seizures occurring in otherwise healthy children with mild acute gastroenteritis, who do not have central nervous system infection, dehydration, or electrolyte imbalances ( 2). However, in clinical practice, the occurrence of febrile CwG is not uncommon ( 3). Although the presence of fever seems to influence the clinical characteristics of seizures associated with mild gastroenteritis ( 4), distinguishing between febrile CwG and FS is not easy for the clinician ( 5).

FS and CwG are considered situation-related seizures, which are essentially transient and functional disorders of infants and young children, probably related to the immaturity of the brain ( 6- 10). Nevertheless, the two entities show significant differences in clinical features and management ( 6, 11- 15). Our paper aims to review the epidemiology, clinical features, diagnostic investigations and treatment options in patients with FS and CwG.

2. Literature search

A review of a series of patients with FS and CwG was performed by literature search on PubMed from January 1960 to October 2022. This review is not meant to be exhaustive. We have selected some of the more comprehensive articles on FS, febrile CwG and afebrile CwG. We do not pretend to have included all the better contributions, but most of those included have extensive references that should be consulted for more complete coverage. Our search terms included "Febrile seizures," "Benign convulsions", "Gastroenteritis", and "Acute symptomatic seizures". The main data are summarized in Table 1 .

Table 1

Lloyd et al. 2010 (16)

Zifman et al. 2011 (17)

Lee and Chung 2013 (18)

Kang et al. 2013 (19)

Hu et al. 2017 (20)

Higuchi et al. 2017 (5)

Wu et al. 2020 (4)

Cappellari et al. 2022 (3)

3. Epidemiology

Both FS and CwG are transient and functional disorders occurring in infants and young children ( 6).

3.1. FS

FS affects 2%-5% of children under five years of age ( 21), with a peak incidence around 18 months ( 22). Viral infections are the most frequent cause of febrile illnesses associated with FS (up to 82% of cases) ( 23). Some vaccinations have also been linked to FS, with the risk period following vaccination varying between vaccines ( 24). Other risk factors for FS include fever above 38°C, shorter fever duration and a positive family history of FS or epilepsy ( 25, 26). Up to 41% of children who have febrile status epilepticus (FSE) go on to experience another FS in the future, increasing their risk of other negative outcomes ( 27).

3.2. CwG

CwG occur in children aged one month to 6 years, with a peak incidence at 1-2 years of age ( 28). CwG mostly occur during the winter and early spring months, which is the period of the year associated with the largest circulation of several viruses such as rotavirus, norovirus and adenovirus ( 28- 31). Furthermore, CwG have been more frequently reported in East Asian countries, suggesting that the genetic characteristics of the host may contribute to the occurrence of seizures in children with gastroenteritis ( 28, 32).

4. Pathophysiology

The rapid development of the immature CNS in childhood may increase the susceptibility to seizures in infants and young children with FS and CwG ( 6).

4.1. FS

The height of the body temperature is considered to play a major role in the pathogenesis of FS, compared to the rapidity of its rise ( 33, 34). Increasing the temperature of the brain has been suggested to increase neuronal firing, which in turn increases the likelihood of synchronised neuronal activity that leads to seizure induction ( 35). The seizure threshold varies between patients. A lower seizure threshold to excitatory input both in vivo (kainic acid) and in vitro (electrical stimulation) had been associated with prolonged FS ( 36). Children prone to FS produce more pro-inflammatory cytokines in the CNS, such as IL-1Beta, which might induce seizures ( 37). Also, the type of infection seems to play a role in the pathogenesis of FS, with human herpes virus 6 (HHV6), viral upper respiratory tract infections and gastroenteritis frequently involved.

4.2. CwG

Among the various organisms causing gastroenteritis, rotavirus has been detected in a wide number of stool specimens of CwG patients ( 28, 38- 41). There are different hypotheses on the relationship between rotavirus infection and its effect on the CNS. One hypothesis is that rotavirus may directly invade the CNS via the bloodstream ( 42, 43). Indeed, rotavirus RNA in the cerebrospinal fluid (CSF) has been reported in patients with gastroenteritis and seizures ( 43, 44). Another hypothesis is that rotavirus may indirectly provoke seizures by various mediators produced in the gastrointestinal tract and released in the general circulation ( 45).

5. Clinical features

FS and CwG are benign conditions sharing several clinical and prognostic features ( 6).

5.1. FS

Children with FS can develop seizures within one hour of the onset of the fever (21% of cases), between 1 and 24 h of the fever (57%) or more than 24 h after the fever (22%) ( 46). However, the fever can occur at any time, not infrequently after the seizure. Children with FS have higher temperatures with illness compared with febrile controls ( 47). Seizure types include tonic-clonic seizures, which can be asymmetrical, or focal impaired awareness seizures. FS have been classified as simple FS or complex based on duration, recurrence, and presence of focal features ( 48). Febrile seizures have an average duration of 4-7 min, with only 10%-15% of them lasting longer than 10 min ( 49). Simple FS are generalized seizures, with duration <15 min, and not recurrent within 24 h. Complex FS are seizures either focal, with a duration >15 min, or repetitive within 24 h. Most FS are simple FS, while 25%-35% are complex FS ( 50).

Up to a third of children with FS have a recurrence, and 75% of these occur within one year ( 51). Risk factors for recurrent FS include age at onset <18 months, history of FS in a first-degree relative, low grade of fever associated with seizures (<39°C), short duration of fever before a seizure (<1 h) and multiple seizures during the same febrile illness ( 50). EEG findings have also been reported as an independent risk factor for FS recurrence ( 50).

5.2. CwG

In many cases of CwG, seizures follow gastrointestinal symptoms, although they can also occur before or simultaneously with the development of diarrhoea ( 41).

Although the seizures are mostly reported as generalized tonic-clonic, ictal EEG recordings have always demonstrated a focal origin ( 41, 52). Seizures are mostly brief (<5 min), and often repetitive, usually occurring in clusters ranging from one to 8 seizures within a 24 h period ( 19). Cluster seizures were observed in 13%-75% of patients with CwG ( 53).

The overall prognosis of CwG is favourable, and the incidence of seizure recurrence is low ( 54). The risk of recurrence can be predicted by age at onset <18 months and repeated seizures over 24 h ( 54).

6. Electroencephalographic findings

EEG could play a role in predicting FS recurrence ( 50) or epilepsy development ( 55) in patients with FS, while the role of EEG is of limited value in the evaluation of CwG since most EEG findings return to normal during the follow-up period ( 41).

6.1. FS

There is a longstanding debate on the usefulness of EEG in children with FS ( 56). The value of EEG in patients with simple FS has been traditionally denied ( 1), although some recent papers suggest its usefulness. If an EEG is obtained, it should be taken at least 48 h after the FS to prevent conflating postictal electrical activity with aberrant activity ( 21). First, pseudo-petit mal discharge (PPMD) pattern and abnormal EEG have been recently reported as independent risk factors for FS recurrence ( 50). Second, PPMD has been reported as a marker of favourable prognosis in terms of epilepsy development, since epilepsy has been diagnosed in patients without PPMD but not in those with PPMD ( 55). The value of EEG in patients with complex FS remains controversial ( 57), and the absence of epileptiform activity does not exclude seizures ( 58).

6.2. CwG

Interictal EEG findings have been usually reported as normal in CwG, although some patients may initially present slow background activity, focal spikes or epileptiform discharges. Ictal EEG recordings reveal a focal onset, usually with secondary generalization and rarely with persisting focality ( 9, 41, 59).

7. Other diagnostic studies

The role of diagnostic studies is quite different in FS and CwG.

7.1. FS

Blood tests are not necessary in the presence of typical history and physical examination ( 60). In patients with simple FS, a lumbar puncture should be performed in children with a history and clinical features of meningitis, while it is an option in infants between 6 and 12 months of age with incomplete or unknown immunization status, as well as in a child pretreated with antibiotics ( 1). A lumbar puncture should also be considered in children with complex FS ( 60). Neuroimaging studies, including cranial computed tomography (CT) and magnetic resonance imaging (MRI), are not routinary indicated in children with FS ( 60- 62). Imaging studies should be performed in patients with focal neurological findings, raised intracranial pressure or suspected intracranial structural pathology ( 60, 63, 64).

7.2. CwG

Diagnosis of CwG is based on clinical findings. Laboratory investigations and neuroimaging are not necessary, except in a few selected cases ( 65). Reversible abnormalities of high intense signal of the splenium of the corpus callosum on brain MRI have been reported in patients with CwG associated with rotavirus infection ( 66).

8. Treatment

FS and CwG have significant differences in management ( 6).

8.1. FS

Most FS are self-limited and stop on their own before patients arrive at the hospital. However, seizures lasting longer than 5 min are unlikely to stop, and a benzodiazepine is required to break the seizure ( 67). Therefore, intervention to stop the seizure usually is unnecessary in simple FS, since the seizure has typically resolved by the time the child is evaluated by a physician, while the treatment may be required in complex FS if the seizure is still ongoing by the time the child arrives at a medical facility ( 68). Intravenous lorazepam and diazepam have been reported to have similar rates of seizure resolution and respiratory depression. When intravenous access is unavailable, buccal midazolam or rectal diazepam are good alternatives ( 69).

Given the usually benign course of FS and the risk of adverse effects with medications, there is currently no role for prophylactic anti-seizure drugs in preventing FS. The use of antipyretics does not decrease the risk of FS ( 69).

8.2. CwG

Antiseizure drugs are not necessary if the patient has seizures of brief duration, even if they occur in clusters. Prolonged seizures may respond to conventional therapy, although some authors report that benzodiazepines were effective in stopping the seizures in only a limited number of cases (38%) ( 28, 41, 70, 71). Some authors suggest that carbamazepine is the most effective drug at the dose of 5 mg/Kg/die to treat prolonged seizures. Although there is no consensus on the drug of choice for CwG treatment, all authors agree to avoid benzodiazepines in the routinary treatment of patients with CwG ( 28).

9. Conclusion

FS and CwG are considered situation-related seizures, occurring in infants and young children ( 6- 10). In clinical practice, several terms, such as "situation-related seizure", "provoked seizure", and "reactive seizure" are frequently used, but the ILAE has proposed that these terms are synonymous with and should be replaced by the term "acute symptomatic seizure" ( 72). Acute symptomatic seizures have been defined as seizures that occur within a certain period of an inciting event ( 73). A major issue in the definition of acute symptomatic seizures is the difficulty in combining, in a single concept, both seizures that are caused by acute structural brain pathologies, such as stroke, and seizures that are provoked by a reversible factor such as hyponatraemia, which should be not equated ( 74). In our opinion, FS and CwG should not be equalled to other symptomatic seizures too, owing to their propensity to exclusively occur on the immature brain. Indeed, FS and CwG could be set apart as "age-dependent acute symptomatic seizures", reinforcing the concept of their self-limited course over a certain period. This term is not so far from other terms used to indicate specific age-dependent neurologic disorders, such as "self-limited epilepsies" ( 75) or transient benign paroxysmal movement disorders in infancy ( 76). Although the theoretical concept and definition of an acute symptomatic seizure suggests that the seizure recurrence risk should be relatively low, the risk varies according to the causes of acute symptomatic seizures ( 77). Among the age-dependent acute symptomatic seizures, the prognosis for subsequent epileptic seizures in children with simple FS is similar to that of the general population, while the risk of afebrile seizures is increased to 15%-20% among children with complex FS ( 78).

10. Open issues

There is controversy regarding whether benign seizures occurring in gastroenteritis with fever should be placed in the category of CwG ( 6). Seizures occurring in gastroenteritis with fever have been regarded as "FS", while those occurring during gastroenteritis without fever are classified as "CwG". However, febrile seizures during viral gastroenteritis may clinically resemble those of CwG rather than those of FS concerning the frequency of clustered seizures and the antiepileptic drug responses, suggesting that they may have a pathogenic mechanism distinct from FS due to other causes ( 6). Furthermore, we recently reported that children with febrile CwG showed a higher rate of complex seizures as compared with those with FS ( 3). Overall, these findings suggest that the relationship among FS, febrile CwG and afebrile CwG is quite complex. Although there are some studies investigating the difference between febrile CwG and FS, they are few single-center studies with a small number of patients ( 5). Future studies and discussions are required to resolve this issue.

Funding Statement

Open Access article charges are covered by "Ricerca Corrente' (IRCCS RC-2023 Grant no. 01) from the Italian Ministry of Health.

Author contributions

AMC and SM: contributed to the conception and writing of the manuscript. GB: contributed to review the literature data. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

47. Gordon KE, Dooley JM, Wood EP, Bethune P. Is temperature regulation different in children susceptible to febrile seizures? Can J Neurol Sci. (2009) 36(2):192-5. [[ PubMed] Google Scholar]

55. Dilber B, Kamaşak T, Arslan EA. Pseudo-petit mal discharge: a marker of favorable prognosis in febrile seizure. Arch Epilepsy. (2022) 28(1):18-22. 10.54614/ArchEpilepsy.2022.35119 [[ CrossRef] Google Scholar]

64. Millar JS. Evaluation and treatment of the child with febrile seizure. Am Fam Physician. (2006) 73:1761-4. [[ PubMed] Google Scholar]

69. Smith DK, Sadler KP, Benedum M. Febrile seizures: risks, evaluation, and prognosis. Am Fam Physician. (2019) 99(7):445-50. [[ PubMed] Google Scholar]

Articles from Frontiers in Pediatrics are provided here courtesy of Frontiers Media SA

# data[].attributes.attachment_link.title
Febrile seizures and convulsions with mild gastroenteritis: age-dependent acute symptomatic seizures

# data[].attributes.attachment_link.description
Febrile seizures (FS) and benign convulsions in children with mild gastroenteritis (CwG) are acute symptomatic seizures, transiently occurring in infants and young children, probably related to the immaturity of the brain. Our paper aims to review the ...

# data[].attributes.attachment_link.title
MOOC Enseñanza en consulta y medio hospitalario - 4.1. Snapps: Explicación teórica

# data[].attributes.attachment_link.title
MOOC Enseñanza en consulta y medio hospitalario- 4.2 SNAPPS: caso práctico

# data[].attributes.attachment_link.readable_text
Even after 180 years since Dr. William West described a peculiar form of infantile convulsions in his son, ¹ the field of pediatric neurology and epilepsy has not achieved unanimity on the definitions of infantile spasms or West syndrome. Depending on the author, the term infantile spasms has been used inconsistently in the literature to refer to either a seizure type or an epilepsy syndrome. However, the use of the term infantile spasms as an epilepsy syndrome is at odds with the widely accepted use of the term West syndrome as an epilepsy syndrome. Yet, we are without consensus about whether the criteria of West syndrome, in addition to infantile spasms, should require one or both of hypsarhythmia and developmental regression. Finally, although a careful review of the recent classification system from the International League Against Epilepsy (ILAE) has clarified much of the confusion outlined here, there is a growing misperception about the appropriateness of the term infantile spasms and whether this term should be abandoned.

The unique definitions used for infantile spasms and West syndrome will determine the populations studied within research studies and thus impact the relevance (including generalizability) of the data acquired. In addition, some clinicians may inappropriately withhold standard therapy for infantile spasms if the child fails to meet the traditional criteria for West syndrome (eg, the term hypsarhythmia does not appear in the electroencephalogram [EEG] report). Herein I review historical perspectives, relying heavily on published monographs and consensus statements, and promote practical definitions and diagnostic criteria for infantile spasms and West syndrome. My goal is to encourage best clinical practice and research methodology.

In his letter to the Lancet in 1841, in the first published description of what would later be called infantile spasms, William West was clearly describing an ictal phenomenon in his use of the word convulsions. ¹ Consistent with this original intent, Gibbs and Gibbs coined the term infantile spasms in 1952 and used this term to refer to a seizure type. ² They described the seizure as follows: "The seizures are characterized clinically by one or more of the following: sudden jerking of the head, rolling of the eyes, upward flinging of the arms, or quivering of the entire body...They could be considered miniature convulsions, but they are so short in duration that the term convulsion seems inappropriate and spasm is considered a more apt designation." ², pp. 24

In the 1970 ILAE classification of seizures, Gastaut described infantile spasms as a seizure type. ³ Lacy and Penry, in their 1976 monograph titled "Infantile Spasms," acknowledged Gastaut's use of the term infantile spasms as a "distinct seizure type." However, Lacy and Penry also used the term infantile spasms to refer to a disorder ("the disorder of infantile spasms") or a type of epilepsy ("an unusual form of epilepsy"). Unfortunately, the subsequent classification systems from the ILAE did not clarify the terminology for infantile spasms. The 1981 classification of epileptic seizures did not include infantile spasms (or any version of this term) as a seizure type. ⁴ The 1985 classification of epilepsies and epilepsy syndromes used the term West syndrome synonymously with infantile spasms, but required infantile spasm seizures in the criteria for West syndrome. ⁵ Then, the 1992 ILAE workshop on infantile spasms proposed to abandon the term "infantile spasms" in favor of the term "spasms," and recommended the latter be added to the 1981 classification of seizures. ⁶

In subsequent decades, many authors favored the use of the term infantile spasms to refer to an epilepsy syndrome. For example, Dulac, Chugani and Bernardina, in their 1994 monograph titled "Infantile Spasms and West Syndrome," acknowledged that "spasms are no more than a special type of epileptic seizure." ⁷, pp. 1 Yet, these authors preferred to use the terms infantile spasms and West syndrome as terms referring to epileptic syndromes, with the designation of West syndrome as a subtype of infantile spasms when hypsarhythmia is present. In addition, they preferred to use the term epileptic spasms as the preferred name for the seizure type.

Frost and Hrachovy, in their 2003 monograph titled "Infantile Spasms: Diagnosis, Management and Prognosis," highlighted the inconsistent use of the term infantile spasms in the medical literature. ⁸ They noted that many authors used the term infantile spasms to be synonymous with the term West syndrome. Although they acknowledged that this was at odds with the original description by Gibbs and Gibbs, Frost and Hrachovy likewise preferred to use the terms infantile spasms and West syndrome interchangeably. They also preferred to use the term spasms as the preferred name for the seizure type.

The preference of the term infantile spasms to indicate an epilepsy syndrome was strengthened by the 2004 West Delphi consensus statement on the proposal for case definitions by Lux and Osborne. ⁹ These authors preferred the use of the term epileptic spasms to refer to the seizure type - a position consistent with the 1998 Semiological Seizure Classification by Luders and colleagues. ¹⁰

The definition of infantile spasms has come full circle with the clarification provided by the 2017 ILAE classification of seizures and the accompanying instruction manual, both by Fisher and colleagues. ¹¹,¹² The term infantile spasms does not appear in the article titled "Operational classification of seizure types by International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology." ¹² In this article, the authors utilized the term epileptic spasms - a seizure type that may have a focal, generalized or unknown onset. ¹² However, it is within the companion article titled "Instruction Manual for the ILAE 2017 Operational Classification of Seizure Types" that clarification about the term infantile spasms is found. Fisher and colleagues clarify that the "term infantile spasms remains suitable for epileptic spasms occurring at infantile age" and note that regarding epileptic spasms, "Infantile spasms are the best known form, but spasms can occur at all ages." ¹¹, pp. 536 Thus, within this framework, infantile spasms are seizures and not an epileptic syndrome. In addition, infantile spasms remains a suitable term when epileptic spasms occur during infancy. It is my opinion that infancy, as it pertains to infantile spasms, refers to children who are ≤2 years of age given that many children presenting with infantile spasms in the second year of life will achieve remission with standard therapy (defined ¹³ as adrenocorticotropic hormone, high-dose prednisolone, and vigabatrin). With that said, however, there is no established age cutoff for the use standard therapies for early life epileptic spasms.

The gold standard method of diagnosing infantile spasms is to capture them on video-EEG to confirm the ictal correlate of the seizure. Although multiple variations are known, ⁸ the ictal correlate is often that of a diffuse high amplitude slow wave with subsequent electrodecrement. ¹⁴ Yet, continuous video-EEG is an expensive and time-intensive resource that is often unavailable in developing countries as well as in many regions of developed countries. Furthermore, in the appropriate clinical scenario, continuous video-EEG may be unnecessary. For example, a review of home video with typical spasms combined with a definitively epileptic outpatient EEG is certainly adequate for the diagnosis of infantile spasms. Such a means of diagnosis was advocated for by a working group of the Child Neurology Society and Pediatric Epilepsy Research Consortium. ¹⁵ Guidance for the diagnosis of infantile spasms can be found in Table 1.

William West's description of peculiar convulsions in his son James included two key features - the seizures (later termed infantile spasms) and developmental regression. Yet, following the description of hypsarhythmia by Gibbs and Gibbs in 1952, many authors considered hypsarhythmia as a more important feature than the presence of developmental delay. Although some authors required the full triad of infantile spasms, developmental delay and hypsarhythmia, others required the presence of infantile spasms and only one of these other features.

The ILAE recognized West syndrome in the 1985 and 1989 classifications of epilepsies and epileptic syndromes. ⁵,¹⁶ Although this classification system noted the typical triad of "infantile spasms, arrest of psychomotor development, and hypsarrhythmia," these authors permitted the absence of one element. ¹⁶ However, the 1992 ILAE Workshop on Infantile Spasms placed greater emphasis on the presence of hypsarhythmia by defining West syndrome as the combination of spasms and hypsarhythmia without the requirement of developmental delay (though noting the common occurrence of "mental retardation"). ⁶ The monographs on infantile spasms by Dulac, Chugani, and Bernardina ⁷ and Frost and Hrachovy ⁸, as well as the consensus statement by the 2004 West Delphi group, ⁹ all used a definition of West syndrome consistent with that used by the 1992 ILAE workshop on infantile spasms - requiring spasms plus hypsarhythmia. The 2004 West Delphi group went further to require the presence of clustering spasms (as opposed to single spasms alone). ⁹

The most recent classification system and on-line resource ( www.epilepsydiagnosis.org ) from the ILAE does not specifically address the criteria for West syndrome. ¹⁷,¹⁸ However, it is noteworthy that the most recent classification system and on-line resource from the ILAE identify the epilepsy syndrome as West syndrome (and not the syndrome of infantile spasms). It should be noted that at the time of this writing, as stated by Scheffer and colleagues, "there has never been a formal classification of syndromes by the ILAE." ¹⁸, pp. 516

Gibbs and Gibbs defined Hypsarhythmia (originally spelled with a single "r") as an interictal pattern of nearly continuous random high voltage slow waves and spikes. ² In their series of 237 children with infantile spasms, all were reported to have hysarhythmia. ¹⁹ However, not long after this report, several authors noted that many children with infantile spasms did not have hypsarhythmia. For example, Bower and Jeavons noted that only about half of the children diagnosed with infantile spasms had hypsarhythmia in their series. ²⁰ Several contemporary inclusive single center cohorts reported that about 60% of children presenting with infantile spasms had hypsarhythmia. ²¹,²² Thus, the first problem with hypsarhythmia is that many children presenting with infantile spasms do not meet criteria for this classic pattern.

An additional problem with hypsarhythmia is that the presence or absence of this term on a pretreatment EEG report does not predict the response to treatment, risk of subsequent seizures, or ultimate developmental outcome. ²²,²³ Even more concerning is the fact that some clinicians may inappropriately withhold standard therapies from children who have EEG reports that do not include the term hypsarhythmia. ²³ Thus, the overemphasis on the presence of hypsarhythmia can have serious consequences for children presenting with infantile spasms.

Finally, there is poor agreement among EEG reviewers on the determination of hypsarhythmia. Although Gibbs and Gibbs considered that hypsarhythmia "is the easiest to detect of the cerebral dysrhythmias of epilepsy," ² recent studies have confirmed that the determination of hypsarhythmia has poor inter-rater reliability. ²⁴,²⁵ Hussain and colleagues reported that the inter-rater reliability for both hypsarhythmia and modified hypsarhythmia were unacceptably low despite the high levels of confidence among reviewers. ²⁵

In summary, (1) many children with infantile spasms do not have hypsarhythmia; (2) the presence or absence of hypsarhythmia on pretreatment studies does not appear to impact the response to treatment or later outcome; and (3) the determination of hypsarhythmia has poor inter-rater reliability. These facts call into question the use of hypsarhythmia resolution as an important clinical and research outcome measure.

To address this knowledge gap, we have developed the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. This is a 0- 5 scale with 0 being normal and 5 being most epileptic. We showed that the final score of the 2015 version of the BASED score had excellent inter-rater reliability. ²⁴ We modified and improved this scoring system in the creation of the 2021 BASED score. The 2021 BASED score includes elements with high levels of inter-rater reliability and correlates well with the presence or absence of infantile spasms. ²⁶

In our study of the 2021 BASED score, we found that most (93%) children had a pretreatment score of 4 or 5. Thus, we defined a probable epileptic encephalopathy as a score of 4 and a definite epileptic encephalopathy as a score of 5. Uncommonly (7%), children with infantile spasms had a pretreatment score of 3. We established electrographic remission criteria to include a pretreatment score of 4 or 5 improving to a score of ≤3, or a pretreatment score of 3 improving to a score of ≤2. ²⁶

In contrast to study methodology that would require the exclusion of children who do not have hypsarhythmia, the 2021 BASED score would allow for nearly all children with infantile spasms to be enrolled in clinical research. Indeed, as noted, there is no evidence-based reason to exclude children who do not have classic hypsarhythmia from infantile spasms clinical trials.

Although the 2021 BASED score can be applied quickly in the clinical and research setting, and is founded on elements with high inter-rater reliability, additional work is necessary to evaluate the relationship between this scoring method and long-term outcome. The 2021 BASED score is seen in Table 2 and a case-based example of its application is seen in the Figure 1. The 2021 BASED score instructional video and scoring sheet are available at: https://doi.org/10.1016/j.eplepsyres.2021.106631

For the reasons stated above, the major problem with the past West syndrome diagnostic criteria is the requirement for hypsarhythmia. For those with infantile spasms, the available evidence does not warrant a distinction between children with and without hypsarhythmia. In addition, there is no evidence that warrants the exclusion of children with single spasms (without clustering spasms) from meeting criteria for West syndrome if other features are present. The latter position is further supported by the fact that infantile spasms are often subtle and clusters may be missed by caregivers and clinicians without the use of long-term video-EEG monitoring. Inclusive guidance for the diagnosis of West syndrome is seen in Table 3.

# data[].attributes.attachment_link.title
Definitions and Diagnostic Criteria for Infantile Spasms and West Syndrome - Historical Perspectives and Practical Considerations

# data[].attributes.attachment_link.description
The term infantile spasms has been used inconsistently within the medical literature for decades. We are also without formal consensus on the diagnost...

# data[].attributes.attachment_link.description
Recursos educativos (Froggy Jumps): Frecuentes en Pediatría () - Repasemos...

# data[].attributes.attachment_link.description
Recursos educativos (Relacionar Columnas): Frecuentes en Pediatría (formación de personal) - Relaciona las siguientes palabras de acuerdo a los estudiado

# data[].attributes.attachment_link.title
Clasificación operacional de los tipos de crisis por la Liga Internacional contra la Epilepsia

# data[].attributes.attachment_link.title
1.a. Normativa Simulación e Innovación en Salud USS v_2018

# data[].attributes.attachment_link.title
Infección baja de manejo ambulatorio MINSAL

# data[].attributes.attachment_link.title
2. Glosario Simulación e Innovación en Salud USS (v_2019)