Mimickers of infantile epileptic spasms …

Roberto H Caraballo MD

Epilepsy & Seizures

Updated 05.29.2024
Released 02.10.1995
Expires For CME 05.29.2027

Mimickers of infantile epileptic spasms

Author: Roberto H Caraballo MD

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Editor: Solomon L Moshé MD

Mimickers of infantile epileptic spasms

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Introduction

Overview

Benign myoclonus of early infancy, named Fejerman syndrome, is a nonepileptic disorder that mainly affects normal infants aged 3 to 8 months. It manifests with frequent or repeated jerks of the neck or upper limb muscles and leads to abrupt flexion or rotation of the head and extension with abduction of the limbs without changes in consciousness. In some patients, a brief tonic or nonepileptic spasm with flexion of the upper limbs is observed. A small group of infants may present with head drops or loss of tone in the trunk, suggestive of nonepileptic atonia or negative myoclonus. In a significant number of patients, the movements are described as shuddering of the head, shoulders, or upper limbs. Fejerman syndrome is an entirely benign condition that usually remits by the age of 2 years. There is no need for treatment other than reassuring the parents. The problem with Fejerman syndrome is that it may be misdiagnosed as epileptic spasms. In this updated article, the author details this condition and provides clues for differentiating it from other epileptic and nonepileptic disorders of infancy.

Key points

	• Fejerman syndrome is a nonepileptic paroxysmal disease in infants with a broad motor-clinical spectrum and a benign course.
	• Infantile epileptic spasms syndrome (IESS), previously termed “West syndrome” and “epileptic spams in clusters without hypsarrhythmia” are the most important differential diagnoses.
	• The etiology of Fejerman syndrome is not well known; however, a genetic etiology should be considered.

Historical note and terminology

In 1976, Fejerman presented as benign myoclonus of early infancy 10 infants with fits somehow resembling infantile spasms but with clinical and EEG features and an evolution that allowed clear differentiation from West syndrome (11; 12; 12). These cases were later included in another report by Lombroso and Fejerman, and eight additional personal cases were added to the series by 1984 (12; 13). Fejerman and Caraballo expanded their personal series to 41 patients who were followed between 2 and 34 years up to 2002 (15). Brief series of cases were reported throughout the world (20; 10; 08; 26; 29; 27; 18). Regarding the mechanisms underlying these paroxysmal movements in infants, several brief series of patients were reported, including video-EEG recordings to support the nonepileptic nature of the condition (20; 10; 29; 21; 27; 30). Caraballo and colleagues analyzed the clinical spectrum of 102 patients, and Dalla Bernardina in an editorial on this last paper, proposed to name the entity Fejerman syndrome in honor of the significant contribution of Dr. Fejerman to the identification of the syndrome over many years (04; 09).

A case carrying a PRRT2 mutation and with benign infantile epilepsy presenting with an episode of focal status epilepticus has been published. During follow-up the patient developed benign myoclonus of early infancy or Fejerman syndrome (25).

Clinical manifestations

Presentation and course

The typical onset of Fejerman syndrome is between 4 and 12 months of age. Affected infants usually have had normal psychomotor development prior to onset. The clinical examination remains normal. Motor manifestations usually remit spontaneously before 2 years of age without leaving any neurologic or motor sequelae (04). The types of motor phenomena in this syndrome include myoclonic spasms (which by definition are nonepileptic infantile spasms) and brief tonic contractions (with a duration of 200 or 300 msec), shuddering, and atonia or negative myoclonus (04). Additional cases with atonic episodes have been studied, including a patient with nonepileptic myoclonias in clusters that started at the end of the second year of life. Late-onset Fejerman syndrome may also occur.

The attacks are likely to occur in clusters, sometimes recurring at frequent and brief intervals several times a day. The attacks occur more frequently while awake but may also happen during drowsiness and light sleep. The intensity of the paroxysmal motor movements varies. They are usually mild and inconspicuous but may, at times, become severe and imitate infantile spasms (29). They occur in awake states and may also be triggered by excitement, fear, anger, frustration, or the need to move the bowels or to void.

Some patients may have more than one type of nonepileptic motor manifestation in different episodes or during a single episode mainly when the seizures occur in a cluster. The latter event may be considered a nonepileptic phenomenon rather than an epileptic manifestation. Home video and video-EEG recording are important to recognize the semiological characteristics of the clinical spectrum of Fejerman syndrome.

Transient immaturity or imbalance of the serotonergic system might underlie various myoclonic phenomena, as has been postulated for benign neonatal sleep myoclonus. This could be genetic, accounting for occasional familial cases of both benign neonatal sleep myoclonus and Fejerman syndrome. We evaluated four infants with self-limited focal epilepsy of infancy associated with Fejerman syndrome. These nonepileptic episodes are part of the spectrum of Fejerman syndrome and mutations in the PRRT2 gene may be involved in the etiology (25). Therefore, this particular association should be taken into account, as it may be more common than currently believed and the genetic etiology should be investigated.

Three particular cases with Fejerman syndrome were evaluated (06). Two of them were boys of 10 and 11 months of age, respectively, who had cluster events characterized in the same event by asymmetric spasms, atonic episodes, and jerks in one and spasms and shuddering episodes in the other child. We previously described infants with more than one type of motor event at different moments, but not in the same episode. The third patient was an 8-month-old female who presented with shuddering when she was crying.

The exclusion criteria are the following:

	1. Abnormal neurologic examination or neuropsychological development before onset of the clinical manifestations.
	2. Events occurring only during sleep.
	3. Events occurring as a reflex reaction to a posture or stimulus.
	4. Nonparoxysmal motor disturbances or abnormal movements lasting more than 1 minute.
	5. EEG with epileptiform interictal or ictal abnormalities.

Two infants with benign focal seizures have been evaluated (25). After starting seizures and in the first year of life, the first had nonepileptic spasms in clusters. The second had nonepileptic lateralized atonic head episodes. These two nonepileptic episodes are part of the spectrum of Fejerman syndrome, and mutations in the PRRT2 gene may be involved in the etiology.

Prognosis and complications

Fejerman syndrome or nonepileptic myoclonus of early infancy has a good prognosis with spontaneous remission in the first 4 years of life, often within months from onset and usually by the age of 2 years. Importantly, these children do not tend to have other seizure types and do not develop psychomotor deficits. Definition of the different nonepileptic paroxysmal motor disorders in infants is important for differential diagnosis, treatment, and prognosis.

Clinical vignette

A 10-month-old male with normal development started having brief shuddering attacks while awake. Two weeks later, during drowsiness, he had a brief tonic episode followed by myoclonic jerks while being breastfed. The attacks were sporadic, and the episodes did not occur in clusters. The EEG recordings were normal. Video-EEG documented that these were nonepileptic events. This patient presented with more than one type of nonepileptic motor manifestation. Parents were reassured about the good prognosis. The episodes started to improve gradually over the following 2 months and finally remitted by the age of 12 months. The patient was well at the last examination at the age of 6 years.

Differential diagnosis

Confusing conditions

The main disorder to be differentiated from Fejerman syndrome is infantile epileptic spasms syndrome (IESS), previously termed “West syndrome” (34). Both IESS and Fejerman syndrome are characterized by spasms occurring during infancy. A specific diagnosis cannot be made based solely on the behavioral manifestations of the spasms. However, in Fejerman syndrome the spasms do not occur as frequently, rarely involve the legs, and may have no temporal relationship to sleep. In West syndrome, the spasms usually occur on awakening. The most decisive difference is the normal ictal and interictal (including sleep) EEG and the absence of psychomotor deficits in Fejerman syndrome (10; 27; 18; 14; 30; 04; 19). Three patients with idiopathic West syndrome had nonepileptic events compatible with Fejerman Syndrome at 3.5 and 5.5 months of life, respectively, after the epileptic spams had disappeared. Interestingly, a patient who had Fejerman syndrome associated with self-limited focal seizures and epileptic spasms without hypsarrhythmia had an excellent response to carbamazepine (24).

Fejerman syndrome should also be differentiated from nonepileptic tonic reflex seizures described by Vigevano and Lispi (33; 32). These occur between the first and third months of life. All children have normal psychomotor development with no neurologic antecedents. The attacks are characterized by a diffuse tonic contraction with extension of all four limbs, apnea, and cyanosis lasting for 3 to 10 seconds without loss of consciousness. The attacks occur only during wakefulness and while an adult holds the child in a vertical position. They are triggered by movement or tactile stimulation. Ictal and interictal EEGs are normal. Prognosis is good with spontaneous remission within 2 months after onset (33; 32). Capovilla and colleagues described a type of nonepileptic episode characterized by repeated head drops that appeared in the second semester of the first year of life with a benign course (01). The episode could correspond to a variant of Fejerman syndrome rather than a new entity.

Fever-induced myoclonus is characterized by frequent myoclonus, which resolves with resolution of the fever in otherwise healthy children (02).

Other transient movements in normal infants characterized by more complex motor phenomena have been described by Fernandez-Alvarez as well as Piscitello and colleagues (17; 31). These authors consider these particular movements to be grouped under the same umbrella term of transient infant movements together with Fejerman syndrome; however, independently of the fact that all of them are benign and transient, we consider the transient infant movements should be differentiated from Fejerman syndrome. Home video and video-EEG recordings are fundamental to differentiate the type of motor phenomena from those of Fejerman syndrome and from epileptic events. On the other hand, we are studying a group of patients similar to those evaluated by Fernandez Alvarez and Piscitello and colleagues to confirm the existence of transient infant movements and to propose a more precise term to define this entity (02).

Sandifer syndrome is the syndrome of gastroesophageal reflux associated with head-cocking, or torticollis, and abnormal dystonic posturing of the body, including opisthotonus (02). There may be associated eye and limb movements. These spells, particularly the opisthotonic posturing, may be mistaken for spasms (22; 30). Historical features can help establish the diagnosis, although not all babies with reflux will exhibit obvious signs, such as vomiting, failure to thrive, and respiratory symptoms. Spells often occur in relation to feeding. EEG is normal. Barium esophagogram, esophagoscopy, or pH probe may demonstrate the reflux.

Benign myoclonic epilepsy of infancy is another epilepsy syndrome with similar age at onset (02). However, the seizures are brief myoclonic jerks, each lasting less than 100 ms. The interictal EEG in benign myoclonic epilepsy of infancy is usually normal, but seizures are associated with bursts of polyspike-and-wave discharges. The EEG of Fejerman syndrome, both interictal and during the episodes, is always normal (10; 04).

Epileptic spasms without hypsarrhythmia in clusters, but also those that are isolated, should also be taken into account in the differential diagnosis. The EEG of Fejerman syndrome is also always normal interictally and during the spasms (10; 04). According to the different motor manifestations, the differential diagnoses of Fejerman syndrome are shown in Table 1 (07; 05; 04; 28; 03).

The importance of the differential diagnosis, particularly between Fejerman syndrome and epileptic infantile spasms, has been emphasized by Ghossein and Pohl (19).

Table 1. Differential Diagnosis of Benign Myoclonus of Early Infancy

Other nonepileptic conditions

	• Hyperekplexia
	• Sandifer syndrome
	• Tonic reflex seizures of early infancy
	• Adverse reactions or intolerance to exogenous agents (monosodium glutamate, metoclopramide, etc.)
	• Upward gaze deviation syndrome
	• Paroxysmal torticollis
	• Paroxysmal dystonia or choreoathetosis (paroxysmal torticollis, kinesigenic paroxysmal choreoathetosis, benign infantile dystonia)

Epileptic syndromes

	• Benign familial and nonfamilial infantile seizures
	• Infantile spasms without hypsarrhythmia
	• West syndrome
	• Myoclonic epilepsy in infancy
	• Symptomatic epileptic syndromes with tonic or myoclonic seizures

References

01: Capovilla G, Montagnini A, Peruzzi C, Beccaria F. Head atonic attacks: a new type of benign non-epileptic attack in infancy strongly mimicking epilepsy. Epileptic Disor 2013;15(1):44-8. PMID 23531441
02: Caraballo R, Vigevano F. Nonepileptic neurologic paroxysmal disorders and episodic symptoms in infants. Chapter 317. In: Engel Jr J, Moshé SL, editors. Epilepsy: A Comprehensive Textbook. Wolters Kluwer, 2024:3248-58.
03: Caraballo RH. Epilepsia en pediatría: manejo práctico. Editorial Panamericana: Buenos Aires, 2021.
04: Caraballo RH, Capovilla G, Vigevano F, Beccaria F, Specchio N, Fejerman N. The spectrum of benign myoclonus of early infancy: clinical and neurophysiologic features in 102 patients. Epilepsia 2009;50(5):1176-83.** PMID 19175386
05: Caraballo RH, Cersósimo RO, Espeche A, Fejerman N. Benign familial and non-familial infantile seizures: a study of 64 patients. Epileptic Disord 2003b;5(1):45-9. PMID 12773296
06: Caraballo RH, Falsaperla R, Gutierrez R, et al. Single-epileptic spasms with or without hypsarrhythmia: a study of 16 patients. J Pediatr Epilepsy 2017; 06(03):197-202. PMID 21167750
07: Caraballo RH, Fejerman N, Bernardina BD, et al. Epileptic spasms in clusters without hypsarrhythmia in infancy. Epileptic Disord 2003a;5(2):109-13.** PMID 12875954
08: Caviedes Altable BE, Moreno Belzue C, Artega Manjon-Cabeza R, Herranz Fernandez JL. Mioclonías benignas de la infancia temprana. An Esp Pediatr 1992;36(6):496-7. PMID 1497238
09: Dalla Bernardina B. Benign myoclonus of early infancy or Fejerman syndrome. Epilepsia 2009;50(5):1290-2. PMID 19496809
10: Dravet C, Giraud N, Bureau M, Roger J, Gobbi G, Dalla Bernardina B. Benign myoclonus of early infancy or benign nonepileptic infantile spasms. Neuropediatrics 1986;17:33-8. PMID 3960282
11: Fejerman N. Mioclonías benignas de la infancia temprana. Comunicación peliminar. Actas IV Jornadas Rioplatenses de Neurología Infantil. Neuropediatría Latinoamericana. Delta, Montevideo, 1976:131-4.
12: Fejerman N. Mioclonias benignas de la infancia temprana. Rev del Hospital de Niños 1977a;19(75):130-5.
13: Fejerman N. Mioclonías benignas de la infancia temprana. An Esp Ped 1984;21(8):725-31.
14: Fejerman N. Nonepileptic disorders imitating generalized idiopathic epilepsies. Epilepsia 2005;46(Suppl 9):80-3.** PMID 16302879
15: Fejerman N, Caraballo R. Appendix to “Shuddering and benign myoclonus of early infancy” (Pachatz C, Fusco L, Vigevano F). In: Guerrini R, Aicardi J, Andermann F, editors. Epilepsy and Movement Disorders. Cambridge: University Press, 2002:343-51.
16: Fejerman N, Medina CS. Convulsiones en la infancia. Ergon, Buenos Aires, 1977.
17: Fernandez-Alvarez E. Transient benign paroxysmal movement disorders in infancy. Eur J Paediatr Neurol 2018;22(2):230-7. PMID 29366536
18: Fujikawa Y, Sugai K, Iwasaki Y. Three cases of benign myoclonus of early infancy. No To Hattatsu 2003;35(3):243-8. PMID 12755056
19: Ghossein J, Pohl D. Benign spasms of infancy: a mimicker of infantile epileptic disorders. Epileptic Disord 2019;21(6):585-9.** PMID 31843733
20: Gobbi G, Dravet C, Bureau M, Giovanardi Rossi P, Roger J. Les spasmes benins du nourrisson (sindrome de Lombroso et Fejerman). BollLega It Epil 1982;39(suppl):17.
21: Kanazawa O. Shuddering attacks-report of four children. Pediatr Neurol 2000;23(5):421-4. PMID 11118798
22: Kotagal P, Costa M, Wyllie E, Wolgamuth B. Paroxysmal nonepileptic events in children and adolescents. Pediatrics 2002;110:e46.** PMID 12359819
23: Lombroso CT, Fejerman N. Benign myoclonus of early infancy. Ann Neurol 1977;1:138-43. PMID 889296
24: Loos M, Touzon LM, Reyes G, Juanes M, Caraballo R. Variable phenotypes in the same patient with PRRT2-associated disorders. J Pediatr Epilepsy 2024.
25: Maini I, Iodice A, Spagnoli C, et al. Expanding phenotype of PRRT2 gene mutations: A new case with epilepsy and benign myoclonus of early infancy. Eur J Paediatr Neurol 2016;20(3):454-6.** PMID 26876767
26: Martinez Pastor P, Diez Domingo J, Ausina Gomez A, Rigual Calvo F, Lopez Gomariz E. Mioclonias benignas de la infancia. An Esp Pediatr 1993;38(4):369-76. PMID 8480953
27: Maydell BV, Berenson F, Rothner AD, Wyllie E, Kotagal P. Benign myoclonus of early infancy: an imitator of West syndrome. J Child Neurol 2001;16(2):109-12.** PMID 11292215
28: Moshé S, Cross H, de Bellescize, J, de Vries L, Nordli D, Vigevano F. Seizures and syndromes of onset in the two first years of life. John Libbey, 2015.
29: Pachatz C, Fusco L, Vigevano F. Benign myoclonus of early infancy. Epileptic Disord 1999;1(1):57-61. PMID 10937134
30: Panayiotopoulos CP. Imitators of epileptic seizures. In: Panayiotopoulos CP, editor. A Clinical Guide to Epileptic Syndromes and Their Treatment. 2nd ed. London: Springer, 2007:79-117.
31: Piscitello LM, Volponi C, Santarone ME, Mariani R, Fusco L. Transient infant movements (TIM): frequent infant non-pathological developmental motor phenomena. Epileptic Disord 2021;23(5):713-7. PMID 34519642
32: Vigevano F. Non-epileptic paroxysmal disorders in the first year of life. In: Panayiotopoulos CP, editor. A Practical Guide to Childhood Epilepsies. Volume 1. Oxford: Medicinae, 2006:107-14.
33: Vigevano F, Lispi ML. Tonic reflex seizures of early infancy: an age-related non-epileptic paroxysmal disorder. Epileptic Disord 2001;3(3):133-6.** PMID 11679304
34: Zuberi SM, Wirrell E, Yozawitz E, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022;63(6):1349-97. PMID 35503712

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Roberto H Caraballo MD

Dr. Caraballo of Hospital Nacional de Pediatria Juan P Garrahan has no relevant financial relationships to disclose.
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Editor

Solomon L Moshé MD

Dr. Moshé of Albert Einstein College of Medicine has no relevant financial relationships to disclose.
See Profile

Former Authors

C P Panayiotopoulos MD PhD

Patient Profile

Age range of presentation: 1 to 23 months
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

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Mimickers of infantile epileptic spasms

Differential Diagnosis

infantile epileptic spasms syndrome
nonepileptic tonic reflex seizures
benign febrile myoclonus in childhood
Sandifer syndrome
benign myoclonic epilepsy of infancy
- epileptic spasms in cluster without hypsarrhythmia
- hyperekplexia
- adverse reactions or intolerance to exogenous agents (monosodium glutamate, metoclopramide, etc.)
- upward gaze deviation syndrome
- paroxysmal dystonia or choreoathetosis (paroxysmal torticollis, kinesigenic paroxysmal choreoathetosis, benign infantile dystonia)
- benign familial and nonfamilial infantile seizures
- symptomatic epileptic syndromes with tonic or myoclonic seizures

Also Relevant

Epilepsy
Myoclonic epilepsy in infancy
Panayiotopoulos syndrome
Self-limited (familial) neonatal epilepsy

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Mimickers of infantile epileptic spasms …

Mimickers of infantile epileptic spasms

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Differential diagnosis

Confusing conditions

Table 1. Differential Diagnosis of Benign Myoclonus of Early Infancy

Other nonepileptic conditions

Epileptic syndromes

Diagnostic workup

Management

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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to access the full version.

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Also in This Category

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Alcohol withdrawal seizures

Epileptic lesions due to malformation of cortical development

Epileptic spasms

Sleep and epilepsy

Neocortical temporal lobe seizures

Jacksonian seizures

Mimickers of infantile epileptic spasms

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Differential diagnosis

Confusing conditions

Table 1. Differential Diagnosis of Benign Myoclonus of Early Infancy

Other nonepileptic conditions

Epileptic syndromes

Diagnostic workup

Management

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Alcohol withdrawal seizures

Epileptic lesions due to malformation of cortical development

Epileptic spasms

Sleep and epilepsy

Neocortical temporal lobe seizures

Jacksonian seizures

This is an article preview.
Start a Free Account
to access the full version.