Nonepileptic paroxysmal events (NPEs) are common in infancy and may be misinterpreted as epileptic seizures. With a knowledge of common NPEs, they can usually be diagnosed based on a detailed history and examination. So far, no studies have explored the semiological presentations of NPEs in infancy without video electroencephalographic (VEEG) recordings. We aimed to describe the phenomenology of NPEs in infancy to provide useful information to clinicians, enabling easier diagnoses without VEEG studies.
We reviewed the medical records of 63 patients aged from 1 to 12 months diagnosed with NPEs at Daegu Catholic University Medical Center from September 2006 to June 2017. We classified the phenomenological features into five types: abnormal body movement, eye changes, breathing abnormalities, behavioral symptoms, and autonomic symptoms.
Of the 63 patients, 37 were male and 26 were female. The mean age at onset was 6 months, and the mean duration of symptoms was 22.5 days. Abnormal body movements were the most common feature (88.9%), followed by eye changes (31.7%), autonomic symptoms (11.1%), breathing abnormalities (6.3%), and behavioral abnormalities (3.2%). The most common type of abnormal body movements was shivering-like movement (32.1%). Initially, 30 patients (47.6%) were diagnosed with unclassified NPEs, nine (14.3%) with sleep myoclonus, six (9.5%) with benign paroxysmal tonic upward gaze, and five (7.9%) with benign myoclonus of infancy. During follow-up, two patients (3.2%) were diagnosed with epilepsy.
Knowledge of the phenomenological characteristics of NPEs in infancy can be useful for making a correct diagnosis.
Nonepileptic paroxysmal events (NPEs) are characterized by seizure-like behaviors without concomitant ictal electroencephalography (EEG), and common in infancy [
According to Visser et al. [
We aimed to describe the phenomenology of NPEs in infants to provide clinicians with useful information for more accurate and easier diagnosis, without VEEG recording.
After Institutional Review Board approval (CR-17-086-L), we retrospectively reviewed the medical records of 63 children aged from 1 to 12 months, diagnosed with NPEs, or pseudoseizure, between September 2006 and June 2017 at Daegu Catholic University Medical Center. Written informed consent by the patients was waived due to a retrospective nature of our study. We analyzed sex, age, age at onset, duration of symptoms before seeking medical attention, frequency, form of main symptom, situation of occurrence, responsiveness to stimulation during the event, preceding event, gestational age, developmental history, family history, associated medical conditions, electrocardiogram (ECG), EEG, brain imaging, initial and final diagnosis. As for the frequency of events at the initial visit, we included even a single episode, because NPEs can happen as a single episode. Based on semiological features, the main symptoms were categorized into five types as follows: abnormal body movement, eye changes, breathing abnormalities, behavioral, and autonomic symptoms. Abnormal body movements included any type of facial or bodily movements. Eye changes included eye deviation, blinking, nystagmus, fixed pupils, and opening wide. Breathing abnormalities included apnea and irregular coarse respiration. Behavioral symptoms included staring and arrest of activity. Autonomic features included retching, drooling, facial color changes, and tachycardia. Although the phenomologic character was categorized by main symptoms, many patients had multiple simultaneous features. Therefore, we also analyzed all semiological descriptions. The situation of occurrence was categorized as follows: playing, sleeping, feeding, sleepy, awakening, specific position or crying. Responsiveness was defined as changes in the event upon stimulation. Additional work ups including blood tests, ECG, EEG, and brain imaging were performed when there was a clinical suspicion for seizures based on history. The initial diagnosis was made by the physician at the first encounter based on clinical information, and the final diagnosis was made at a later date, after a period of follow-up. Highly suspecting epileptic seizures were termed as epilepsy in the initial diagnosis lists.
• Apparent life-threatening events (ALTE) or brief resolved unexplained events: an episode that is frightening to the observer and characterized by some combination of apnea, color change, marked change in muscle tone, choking or gagging [
• Benign paroxysmal vertigo (BPVC): migraine equivalent, consisting of episodes of vertigo lasting from a few seconds to minutes, that is often accompanied by postural imbalance and nystagmus [
• Startle response: also known as the startle reflex and the alarm reaction. The alarm reaction is a completely natural, involuntary reaction to a stimulus such as a flash of light, sudden threatening movement or loud noise [
• Benign paroxysmal tonic upward gaze (PTU): protracted attacks (hours to days) of continuous or episodic upward gaze deviation, during which horizontal eye movements are preserved [
• Sleep myoclonus: repetitive, usually bilateral rhythmic jerks involving the upper and lower limbs during nonrapid eye movement sleep, sometimes mimicking clonic seizures [
• Benign myoclonus of infancy (BMI): myoclonic jerks of the extremities during wakefulness and sometimes also during sleep [
• Shuddering attacks: rapid tremor of the head, shoulder, and trunk, lasting a few seconds, often associated with eating, and recurring many times a day [
• Benign paroxysmal torticollis of infancy (BPT): painless retrocollis, and later, torticollis, often triggered by changes in posture [
• Unclassified NPEs: unclassified infantile behavior (age related behavior, pseudoseizure) [
This descriptive study used mean, maximum and minimum for the two continuous variables and frequency to describe discontinuous variables.
Of the 63 patients, 37 (58.7%) were male and 26 (41.3%) were female, mean age at onset was 5.6±2.9 months (range, 1 to 11), and mean duration of symptoms was 22.5±28.3 days (range, 1 to 90). Each one (1.6%) had one of the following preceding events before symptom onset: vaccination, febrile seizure, and bronchiolitis. Family history of febrile seizure, epilepsy, and migraine was each present in one patient (1.6%). Ten patients (16%) had associated medical conditions, including developmental delay, constipation, bilateral sensorineural hearing losses with hypotonia, the chromosomal abnormality 47, XY,+der(22)t(11;22)(q23.3;q11.2), laryngomalacia, febrile seizure, hemophilia, or periventricular leukomalacia.
In 27 infants (42.9%), events occurred daily. Twenty-three (37%) showed responsiveness to external stimuli. Events most commonly occurred when playing (58.7%). Twenty-four patients (38.1%) underwent EEG and four (6.3%) showed abnormal results. Neuroimaging was performed in five patients (7.9%), and none had abnormal findings (
According to main symptom categories, abnormal body movement was the most common and present in 50 patients (79.4%). Patient numbers in the other categories were as follows: seven had eye changes (11.1%), four had breathing abnormalities (6.4%), one had behavioral symptoms (1.6%), and one had autonomic symptoms (1.6%). Among 63 patients, 15 (23.8%) had a mixture of symptoms from different categories. Overall, 56 patients (88.9%) had abnormal body movements, 20 patients (31.7%) had eye changes, and four patients (6.3%) had breathing abnormalities. Seven patients (11.1%) had autonomic symptoms, with facial color change being the most common. Staring was the only behavioral symptom observed, occurring in two patients (3.2%). Two patients (3.2%) had vocalization symptoms such as making ‘mmmm’ sounds and shouting, which were accompanied by other symptoms.
For the phenomena of abnormal body movements, shivering-like movement was the most common (18/56 patients, 32.1%). For ocular symptoms, eyeball deviation was the most common (10/20 patients, 50.0%), and six patients (6/20 patients, 30.0%) had isolated eye changes (
For the initial diagnoses, 30 patients (47.6%) were diagnosed with unclassified NPEs, nine (14.3%) with sleep myoclonus, six (9.5%) with PTU, five (7.9%) with BMI, three (4.8%) with ALTE, two (3.2%) with shuddering attack, two (3.2%) with BPVC, one (1.6%) with BPT, one (1.6%) with startle response, and four (6.3%) with epilepsy. After the study and follow-up observations, the initial diagnosis was changed in some patients (
The frequency of NPEs in children admitted to epilepsy centers for monitoring ranges between 3.5% and 43% [
Our study provides a detailed description of the phenomenology of NPEs in infants, and useful clinical tips for their differential diagnosis based on clinical information without VEEG study. Because phenomenological features of NPEs in infancy are varied and complex, they are usually classified arbitrarily according to main clinical features even with VEEG study data [
Therefore, we categorized NPEs in infancy into five types; movement, eye, breathing, behavioral, and autonomic. For comparison with previous studies and discussion purposes, we classified breathing as an autonomic symptom, and eye changes and vocalization as motor symptoms.
Motor phenomena, with paroxysmal features that interrupt normal motor background activity, are frequently observed in infants [
Myoclonus is another clinical motor feature that occurs in infants and toddlers with NPEs [
Eye changes were a major category in our study and 32.1% had ocular symptoms. Among them, eye deviation was the most common. However, there are no published studies describing this phenomenon in detail. Chen et al. [
There were two patients (3.2%) with vocalization in our study. According to Chen et al. [
Behavioral features have been previously described in 10.4% to 25.5% of children with NPEs, but mainly in the school-aged group and teenagers. Nonepileptic staring spells and arrest of activity are frequent symptoms during NPEs in infants and toddlers as well [
Kim et al. [
Arrest of activity is also a prominent feature of hypomotor seizures in infants and toddlers.
Characteristics of hypomotor seizures in this age group are as follows: (1) progression to other focal motor features, generalized seizures, or infantile spasms, and (2) subtle concomitant features, such as chewing or lip smacking, unforced eye movements, head turning, subtle irregular eye blinking, and stereotypical limb movements.
When compared to epileptic seizures, duration of nonepileptic staring was usually brief (<30 seconds), and children were mostly responsive without crying.
Fogarasi et al. [
Chen et al. [
Visser et al. [
There were several limitations in making a final diagnosis. Because we could only assume some of the conditions mimicking epileptic seizure based on clinical history reported by parents, it was difficult to make a correct diagnosis even after obtaining EEG data. In addition, as we did not follow patients after the initial encounter and presumptive diagnosis, we could not be sure how long NPEs had actually lasted, or whether they had progressed to epilepsy or other neurological problems. Shuper and Mimouni [
With advancements in technology such as YouTube and smartphones, it has become easier to observe paroxysmal events of concern, and instruct or educate parents. Moreover, mutations in several genes have recently been associated with some NPEs, such as calcium voltage-gated channel subunit alpha1 A (CACNA1A) in BPT and PTU, glycine receptor subunit alpha-1 (GLRA1) in hyperekplexia, and sodium voltage-gated channel alpha subunit 9 (SCN9A) in paroxysmal extreme pain disorder [
Therefore, we propose that knowledge of NPEs and the differentials between epileptic and nonepileptic events in infancy is useful for guiding clinicians in making the next decision, while avoiding exacting tests, in an outpatient setting.
No potential conflict of interest relevant to this article was reported.
Conceptualization: KHL. Data curation: HRN and YHK. Formal analysis: HRN, YHK, and KHL. Methodology: HRN, YHK, and KHL. Project administration: KHL. Visualization: HRN, YHK, and KHL. Writing–original draft: HRN. Writing–review & editing: KHL.
This study was presented as an oral presentation at the 67th Annual Autumn Meeting of the Korean Pediatric Society, 2017.
Clinical characteristics of 63 patients
Characteristic | Value |
---|---|
Frequency of events | |
One or two | 13 (20.6) |
Daily | 27 (42.9) |
Occasionally | 22 (34.9) |
Situation of events | |
Playing | 43 (68.2) |
Sleeping | 11 (17.4) |
Feeding | 7 (11.1) |
When feeling sleepy | 6 (9.5) |
Awakening | 1 (1.6) |
Specific position/crying | 3 (4.8) |
Electroencephalography | 24 (38.1) |
Abnormal | 4 (16.6) |
Epileptic discharge | 1 |
Slow wave | 3 |
Brain imaging | 5 (7.9) |
Electrocardiogram | 2 (3.2) |
Values are presented as number (%).
Clinical phenomenology of abnormal body movements
Variable | Value |
---|---|
Abnormal body movements | 56/63 (88.9) |
Shivering-like movement | 18/56 (32.1) |
Stiffening | 10/56 (17.9) |
Head shaking side to side | 6/56 (10.7) |
Myoclonic, startle | 6/56 (10.7) |
Clonic | 3/56 (5.4) |
Opisthotonic posturing | 2/56 (3.6) |
Shrinking | 2/56 (3.6) |
Head nodding forward | 2/56 (3.6) |
Irregular movement of the extremities | 2/56 (3.6) |
Chin movement | 2/56 (3.6) |
Atonic, limping | 2/56 (3.6) |
Ataxic | 2/56 (3.6) |
Torticollis | 2/56 (3.6) |
Shoulder shrugging | 2/56 (3.6) |
Facial grimacing | 2/56 (3.6) |
Tortipelvis | 1/56 (1.8) |
Akinetic, frozen, still | 1/56 (1.8) |
Values are presented as number (%).
Clinical phenomenology of other categories
Variable | Value |
---|---|
Eye changes | 20/63 (31.7) |
Deviation | 10/20 (50.0) |
Opening wide | 4/20 (20.0) |
Blinking | 2/20 (10.0) |
Fixed | 2/20 (10.0) |
Nystagmus | 1/20 (5.0) |
Mixed | 1/20 (5.0) |
Autonomic nervous system | 7/63 (11.1) |
Facial color change (flushing, pallor) | 4/7 (57.1) |
Digestive symptoms (retching, drooling) | 2/7 (28.6) |
Cardiovascular (tachycardia) | 1/7 (14.3) |
Breathing abnormalities | 4/63 (6.3) |
Apnea | 3/4 (75.0) |
Irregular and coarse breathing | 1/4 (25.0) |
Vocalization | 2/63 (3.2) |
Behavioral staring | 2/63 (3.2) |
Values are presented as number (%).
Initial and final diagnosis of 63 patients with nonepileptic paroxysmal events
Variable | Initial | Final |
---|---|---|
Unclassified NPEs | 30 (47.6) | 35 (55.6) |
Sleep myoclonus | 9 (14.3) | 9 (14.3) |
PTU | 6 (9.5) | 5 (7.9) |
BMI | 5 (7.9) | 6 (9.5) |
ALTE | 3 (4.8) | 2 (3.2) |
Shuddering attack | 2 (3.2) | 2 (3.2) |
BPVC | 2 (3.2) | 1 (1.6) |
BPT | 1 (1.6) | 1 (1.6) |
Startle response | 1 (1.6) | 0 (0.0) |
Epilepsy | 4 (6.3) | 2 (3.2) |
Values are presented as number (%).
NPE, nonepileptic paroxysmal event; PTU, benign paroxysmal tonic upward gaze; BMI, benign myoclonus of infancy; ALTE, apparent life-threatening events; BPVC, benign paroxysmal vertigo; BPT, benign paroxysmal torticollis of infancy.
Characteristics of two patients finally diagnosed with epilepsy
Characteristic | Patient 1 | Patient 2 |
---|---|---|
Age of onset | 6 months | 5 months |
Phenomenology | Apneic episode with limping, blank stare followed by pallor with dilated pupils and body shaking movements | Sudden upward gaze |
Frequency | Once | Daily |
Duration | 1 day | 60 days |
During sleep | Yes | No |
Responsiveness | Unknown | Unknown |
Gestational age | Full term | Full term |
Developmental delay | No | No |
Past medical history | Febrile seizure | No |
EEG | Yes, IS in the left temporal | Not done |
Brain MRI | Yes | Not done |
Initial diagnosis | ALTE | PTU |
Course | Three focal seizures with impaired awareness developed at 3 and 10 months after initial events | After 1 month, head nodding with flexor spasm developed |
Final diagnosis | Epilepsy | Epilepsy (West syndrome) |
EEG, electroencephalography; IS, intermittent slow; MRI, magnetic resonance imaging; ALTE, apparent life-threatening events; PTU, paroxysmal tonic upward gaze.