Absence Seizure


Article Author:
Ana Albuja


Article Editor:
Patrick Murphy


Editors In Chief:
Chaddie Doerr


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
8/2/2019 9:11:41 PM

Introduction

Absence seizures are brief seizures characterized by a behavioral arrest that correlates with generalized 3-Hertz spike-and-wave discharges on electroencephalogram (EEG)[1]. Absence seizures occur in multiple idiopathic/genetic generalized epilepsies including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), and juvenile myoclonic epilepsy (JME)[2]. Atypical absence seizures have been reported in up to 60% of patients with Lennox-Gastaut syndrome. 

Historically, absence epilepsy was known as “pyknolepsy.” This term originates from the Greek term pyknos, which means “very frequent” or “grouped”[3][4]. The term “petit mal” seizure was once used to describe an absence seizure in the past, but it is no longer encouraged. 

The International League Against Epilepsy Classification of 2017 defines absence seizures as “generalized non-motor seizures”[5]. However, this term is not entirely precise, because, as discussed below, motor manifestations of absence epilepsy are frequently seen [2].

Etiology

A genetic component exists for all generalized epilepsies and, specifically, for absence epilepsy. In 1951, Lennox reported that 66% of monozygotic twins showed concordance for the EEG pattern of 3-Hertz spike-and-wave. Doose at al., described 252 patients with absence epilepsy with a 3-Hertz spike-and-wave pattern. He proposed that there was multifactorial inheritance. The voltage-gated T-type calcium channel gene, the GABA-A receptor subunits GABRG2 and GABRG3, and the CACNA1A gene are thought to be involved in the etiology of this epilepsy syndrome [3][6][4]. However, the mode of inheritance and the majority of genes implicated in CAE are still unknown [4].

Triggers for seizrues (in any kind of epilepsy) include:

  • Lack of compliance with treatment
  • Lack of sleep
  • Use of alcohol
  • Use of medications that lower seizure threshold like isoniazid, antipsychotics
  • Withdrawal from benzodiazepines, alcohol and other CNS drugs

Epidemiology

The incidence of absence seizures is between 0.7 and 4.6 per 100,000 in the general population and around 6 to 8 per 100,000 in the pediatric population younger than 15 years[3].

CAE is a common pediatric epilepsy syndrome. Among all cases of epilepsy in school-aged children, 10% to 17% are due to CAE [1]. The age of onset for CAE is typically between 4 and 10 years, with a peak between ages 5 and 7. Girls have CAE more frequently than boys[4].

Pathophysiology

Although some of the pathways involved in the development of absence seizures have been described, their pathophysiological mechanisms are yet to be fully understood. The cortico-thalamic-cortical circuit is considered to play a major role in the pathophysiology of absence seizures [7]

Some of the neurons involved in the cortico-thalamic-cortical system include:  

  • Cortical glutamatergic neurons are originating on cortical layer VI and projecting to the nucleus reticularis of the thalamus. 
  • Thalamic relay neurons that have excitatory projections to cortical pyramidal neurons.
  • Neurons from the thalamic nucleus reticularis containing inhibitory GABA-ergic projections that connect with other neurons from the same nucleus, and with thalamic relay neurons. These neurons do not connect directly with the cortex[4].

Neurons from the thalamic nucleus reticularis can fire in an oscillatory pattern (for example, rhythmic bursts involved in the generation of sleep spindles) or continuously in single spikes (tonic firing during wakefulness). Shifts between these two firing patterns in the thalamic nucleus reticularis are modulated by spikes present in thalamocortical networks and neurons from the thalamic nucleus reticularis. These are mediated through low-threshold transient calcium channels known as T-type channels. After depolarization, T-type channels briefly allow calcium inflow before becoming inactivated. Reactivation requires a relatively long hyperpolarization facilitated by GABA-B receptors. Therefore, abnormal oscillatory rhythms can originate from T-type channel abnormalities, or from the increased GABA-B activity[4]

As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and for GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (e.g., vigabatrin) exacerbate absence seizure activity. In contrast, GABA-A agonists (e.g., benzodiazepines), that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis, can suppress absence seizures[4].

History and Physical

The age of onset of CAE is usually between 4 and 10 years, with a peak between the ages of 5 and 7 [4][2]. The onset of absence epilepsy before age 4 should raise concern for an underlying glucose transporter type 1 (Glut1) deficiency[4]

Regarding its clinical presentation, family members and teachers usually describe brief spells in which the patient has a loss of awareness, is unresponsive and has a behavioral arrest. They describe the patient during these spells as having “a blank stare”[2]. Episodes frequently occur, often 10 to more than 30 times throughout the day. Most children stop their activity completely, but some can continue the activity more slowly or in an unusual manner[1]. Some children have 3-Hertz regular eyelid fluttering[1][2]. Oral automatisms can also occur, especially with prolonged seizures or during hyperventilation. Children frequently have mild clonic or tonic movements in the first few seconds of the spell.  Pallor is frequently reported[1].  Urinary incontinence is rare. Spells usually last between 4 and 30 seconds. Hyperventilation, a state of arousal, sleep deprivation, and medication use can affect the duration of the seizure [1]. These seizures are not preceded by an aura and do not have a postictal state [7].

For JAE, the age of onset is classically between 10 and 19 years with a peak at 15 years [4]. Seizures are less frequent than in CAE but tend to last longer [3][4]

On physical examination, hyperventilation can trigger absence seizures. To test this, the examiner asks the child to blow repetitively for more than 2 minutes. It can be helpful to use a pinwheel or a paper because this encourages the child to cooperate more during testing. If hyperventilation is done successfully, the patient will develop seizures that can be seen on EEG. 

Absence status consists of generalized, non-convulsive seizures characterized by impairment of awareness, and intermittently has other manifestations such as automatisms or subtle myoclonic, tonic, atonic, or autonomic phenomena. Patients usually have a previous diagnosis of generalized epilepsy. Absence status presents as a non-convulsive seizure lasting between a half hour and several days. It usually ends spontaneously and suddenly but should be treated with anti-seizure medications at the time of diagnosis[8].

Evaluation

EEG is the main diagnostic tool for the evaluation of absence epilepsy. In the case of childhood absence seizures, EEG shows bilaterally synchronous and symmetrical 3-Hertz spike-and-wave discharges that start and end abruptly. These discharges can sometimes have maximum frontal amplitude or begin with unilateral focal spikes[2]. In 50% of seizures in CAE, the initial discharge seen has a typical spike-and-wave morphology. The remaining 50% can show a single spike, polyspikes, or an atypical, irregular, generalized spike-and-wave[1]. The background is normal[4]

Atypical absence seizures show a more insidious onset and offset, slower spike-and-wave paroxysms (less than 3 Hertz), and an abnormal interictal background[4].  

Neuropsychological testing has shown that patients with CAE have cognitive impairment, especially involving attention, executive function, verbal and visuospatial memory. The difficulty with language and reading is also commonly reported. Depression, anxiety, and attention-deficit/hyperactivity disorder also have been reported more frequently in patients with CAE[1]

Since CAE is generalized epilepsy, imaging studies are not performed routinely.

In JAE, EEG demonstrates paroxysms of generalized 3- to 4-Hertz spike-and-wave or polyspike-and-wave discharges [4]

In the case of absence status, EEG shows continuous or nearly-continuous generalized spike-and-wave or polyspike-and-wave discharges at 2–4 Hertz.

Treatment / Management

The first-line treatment for absence epilepsy is ethosuximide. A randomized controlled trial performed in 2010 that included 446 children with CAE showed that ethosuximide and valproic acid were superior to lamotrigine [9]. However, this study had a low seizure-free rate with 53% of patients in the ethosuximide group, 58% on the valproic acid group, and 29% of patients taking lamotrigine. The group that received valproic acid had significantly lower scores on attentional measures as compared to the ethosuximide and lamotrigine groups. For this reason, ethosuximide is the preferred agent for the treatment of absence epilepsy. 

The most frequent side effects of ethosuximide are abdominal pain and nausea. For this reason, ethosuximide should be taken with meals. Other medications that can be used for management of CAE include valproate, lamotrigine, and topiramate. Second-line medications that can be used as adjunct therapy include valproic acid, zonisamide, and levetiracetam.

It is important to note that some sodium channel blockers like phenytoin, carbamazepine, gabapentin, pregabalin, and vigabatrin can worsen absence seizures [4]

Women of childbearing age not using contraception should not be treated with valproic acid; the preferred agent is ethosuximide.

Some experts suggest that a ketogenic or a medium chain triglyceride diet may be beneficial, but good evidence to support their use is lacking.

Differential Diagnosis

The differential diagnosis for staring spells includes absence epilepsy, focal seizures with alteration of awareness, and non-epileptic paroxysmal events. 

Focal epilepsy with alteration of awareness (complex partial epilepsy) can also present with behavioral arrest and automatisms. However, these seizures are usually less frequent than absence seizures. Patients can have generalized seizures with focal epilepsy. Semiology of automatisms can vary depending on the area of the cerebral cortex where the seizures originate. 

A study that evaluated non-epileptic staring spells using video-EEG monitoring found that these episodes were often characterized by arrest of all activity, vague facial expression, and vision fixed on one point without blinking. When the duration of the events was quantified, staring episodes lasted anywhere between 3 and 74 seconds. In most children, it was difficult to determine the onset and end of the event. Most parents were not able to regain the child’s attention if they waved their hand in front of the child. Other more energetic measures like hand clapping or other loud sounds were successful at stopping the events in all children. A significant percentage of children (41%) were inactive at the onset of the stare, and 18% of children were watching television when the event began[10].

A retrospective chart review performed in a tertiary care epilepsy center showed that among 276 patients in the epilepsy monitoring unit to have their starring spells monitored, only 11% were deemed to have seizures [11]. Therefore, most staring spells are non-epileptic in nature. When patients present with staring spells, practitioners should be careful and not tell parents or other providers that these episodes are “absence seizures” before EEG evaluation is completed. The above-mentioned study developed a tool to determine the pretest probability of seizures in children presenting with staring spells. This tool accounts for patient variables such as results of previous EEG, previous use of antiseizure medications or treatments for psychiatric conditions, and duration of the spells [11]

Prognosis

Typical childhood absence epilepsy occurs in childhood and resolves by adolescence. Seizure freedom is reported in 57% to 74% of the patients. Patients who have generalized tonic-clonic seizures usually do not respond to initial ethosuximide monotherapy and do not achieve long term remission.

The risk for accidental injuries during absence seizures compared with controls is well reported[10]. As mentioned before, these patient have problems in the areas of attention, executive function, verbal and visuospatial memory. Difficulty with language and reading is also commonly reported. Depression, anxiety and ADHD have also been reported more frequently in patients with CAE[1].

Consultations

A general pediatric neurologist or a pediatric epileptologist should be consulted when a patient has staring spells that are suspected to be seizures. Typically, an outpatient evaluation is a reasonable first step.

Deterrence and Patient Education

As explained above, most staring spells are non-epileptic in nature. When patients present with staring spells, practitioners should explain to caregivers that the differential diagnosis includes seizures, but they should avoid giving a specific diagnosis of “absence seizures” before EEG evaluation is completed. 

It can be very useful to request caregivers to take videos of staring spells, as this can help characterize them. Event calendars/logs can assist in understanding the frequency, pattern, and possible triggers. 

Caregivers of children with CAE should know that generalized tonic-clonic seizures are rare. For this reason, rescue medications such as rectal diazepam and intranasal midazolam are not routinely prescribed. Nevertheless, caregivers should be taught what to do if the child has a generalized tonic-clonic seizure. 

Caregivers often assume that, since absence seizures are very brief, they are harmless. On occasions they question the need to treat with medications, arguing that risks could outweigh benefits. In these situations, we recommend explaining that the child is experiencing frequent episodes of altered consciousness that can increase the risk of accidents. Seizures also can interfere with learning and have a negative impact on school performance.  

Activities like swimming, diving or rock climbing should only be permitted under supervision.

Driving is not permitted if seizures are not controlled with medications.

Pearls and Other Issues

  • Absence epilepsy is a primary generalized epilepsy.
  • It is classified as typical or atypical absence depending on seizure characteristics and EEG pattern. 
  • Absence seizures are characterized by behavioral arrest and EEG showing 3-Hertz spike-and-wave discharges. Episodes usually occur multiple times per day. 
  • Absence seizures are seen in several generalized epilepsies including childhood absence epilepsy, juvenile absence epilepsy, and juvenile myoclonic epilepsy. 
  • Episodes of behavioral arrest should be called “staring spells” until EEG evaluation is performed. A patient can only be diagnosed with absence epilepsy if they have characteristic seizure semiology and EEG findings. 
  • Staring spells can be epileptic or non-epileptic, with the majority being non-epileptic. When episodes are epileptic in nature, they may be due to absence seizures or to focal seizures with impaired awareness (complex partial seizures) 
  • The first-line treatment for absence seizures is ethosuximide. Other therapies include valproate, lamotrigine, and topiramate. Second-line medications that can be used as adjunct therapy include zonisamide and levetiracetam.
  • Carbamazepine, phenytoin, gabapentin, vigabatrin, and other medications with similar mechanisms of action can worsen absence epilepsy. 
  • Approximately 60% of patients with childhood absence epilepsy eventually achieve seizure freedom.
  • Lack of response to ethosuximide and the presence of generalized tonic-clonic seizures have been associated with lack of seizure remission and life-long epilepsy. 

Enhancing Healthcare Team Outcomes

Absence seizures should be managed by a neurologist. However, the long-term care and monitoring are done by an interprofessional team that includes the neurologist (child neurologist in the case of the pediatric population), primary care provider, nurse, and pharmacist.

The pharmacist should educate the patient on the importance of medication compliance. In addition, the pharmacist should ask about any adverse reaction at the time of dispensing of the medication. The caregiver should be asked if the symptoms are controlled if not, the pharmacist should communicate with the interprofessional team about the need for change in dosage.

The primary care practitioner together with the neurologist should follow up on the liver function tests, amylase and complete blood count. In addition, birth control should be managed in women who are taking valproic acid. Finally, drug levels should be monitored periodically as these drugs have a narrow therapeutic index.

A few patients with intractable absence epilepsy may be candidates for the ketogenic diet. If this is the case a registered dietician with expertise in this type of diet should be consulted and evaluate the patient periodically. 

Finally, mental health providers may be involved in the patients care as many of these patients develop anxiety, depression, and stress.

Most of the patients need life long follow up and it is essential that the interprofessional team communicate with each other any time when there is a change in drug dose, change in drug type, or development of adverse drug reactions.


  • Image 6364 Not availableImage 6364 Not available
    Contributed by Ana C. Albuja, MD
Attributed To: Contributed by Ana C. Albuja, MD

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Absence Seizure - Questions

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Which of the following drugs is most commonly used to treat absence seizures?



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Which of the following drugs is used in the treatment of absence seizures?



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A 13-year-old female is diagnosed with absence seizures. A drug is selected which is used only to treat absence seizures. This drug is thought to act by reducing the current in the T-type calcium channels found on primary afferent neurons. Which of the following is most likely the medication of choice?



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A 7-year-old boy is brought to a clinician for behavioral assessment. The child was born full-term to a healthy mother who attended all prenatal checkups. He reached his developmental milestone on time. However, the parents state that his teacher has recently started noting some behavioral problems. The teacher reports that he is inattentive, frequently stares, and sometimes seems absent-minded during different class activities. While checking the child's class workbook, the physician notices gaps in writing. What is the most likely diagnosis?



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A 6-year girl has multiple staring spells with eye fluttering that occur daily. The episodes last for less than 20 seconds after which she resumes what she was doing. She is having problems with school performance this year. Which of the following tests is indicated?



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A 9-year-old boy has a 1-month history of "spacing out" at school and home sometimes associated with lip-smacking and eye fluttering. Select the feature that would make absence seizures more likely than focal seizures with alteration of awareness (complex partial seizures).



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Absence seizures are mostly seen in which group?



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Which of the following is false regarding absence seizures?



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Which of the following techniques is commonly used to trigger absence seizures for diagnostic purposes?



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A 7-year-old has was diagnosed with childhood absence epilepsy. Which of the following medications is the first line treatment for this disorder?



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A 6-year-old child is brought to the clinician by his parents after his class teacher complained of recent onset of behavioral problems, The parents state that their son has no significant history of any illness and reached all his developmental milestones normally. The parents add that the teacher has complained that their son starts to stare in space for a couple of minutes during different class activities. During the episode, he remains inattentive to his name being called, but after the episode, he returns to a completely normal state. Further evaluation with an electroencephalogram (EEG) shows generalized 3 Hertz spike and wave discharge, which is sometimes accompanied by behavioral pauses in the patient. What is the most likely diagnosis?



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Which of the following is false concerning the older term, "petit mal" seizures?



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An 8-year-old male presents with poor academic performance in school. The teacher has reported that the patient has many spells of unresponsiveness in the class. These spells last 10 seconds and happen 4-10 times a day. The clinician notes that hyperventilation results in the initiation of the same episodes. An EEG reveals 3 Hz spike and wave discharges, and he prescribes the patients the first-line pharmacological agent. What recommendation should be given to this patient to avoid the most common side-effect of the given drug?



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A 9-year-old male is seen in the clinic with a history of staring spells and brief periods of unresponsiveness. His episodes last a few seconds and his academic performance is lagging. The physical exam is normal. An EEG is ordered (see image). What features on the EEG will confirm that he has absence seizures?

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A 17-year-old female was brought in by her adopted parents because they noticed that she was having frequent spells of unresponsiveness. At the same time, she was having episodes of staring off into space. These episodes were occurring 20 times a day, and each spell was lasting 4-15 seconds. The parents do not know much about her past medical history as she was adopted, but she has done poorly in school. After workup, it is decided to start her on pharmacological treatment. However, the parents do admit that she is sexually active and not compliant with birth control pills. Considering the patient's status, which of the following is the preferred agent for her?



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A 12-year-old boy has staring spells with eye fluttering 3 to 4 times a week. He had a generalized tonic-clonic seizure 6 months ago and had another 2 weeks ago. His EEG shows 3 Hz generalized spike and wave discharges. What is the medication of choice for this patient?



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A 6-year-old girl was recently diagnosed with childhood absence epilepsy. She was prescribed an anti-seizure medication by her primary care provider a few days ago. She now presents to the emergency department with a 50 minute period of impairment of awareness with subtle jerking and some falls. Mother says that she was talking to her and suddenly started "acting funny" and not responding. What medication was most likely prescribed?



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A 10-year-old boy was reported by the teacher of having multiple staring spells with eye fluttering 3 to 4 times a week. The child is otherwise healthy after the episodes. The child is brought to the clinic for evaluation. During one of the spells, his EEG was obtained, which is shown in the image. The clinician decides to start on the preferred pharmacological agent for his pathology. What advice should be given regarding his treatment?

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Absence Seizure - References

References

Matricardi S,Verrotti A,Chiarelli F,Cerminara C,Curatolo P, Current advances in childhood absence epilepsy. Pediatric neurology. 2014 Mar;     [PubMed]
Unterberger I,Trinka E,Kaplan PW,Walser G,Luef G,Bauer G, Generalized nonmotor (absence) seizures-What do absence, generalized, and nonmotor mean? Epilepsia. 2018 Mar;     [PubMed]
Guilhoto LM, Absence epilepsy: Continuum of clinical presentation and epigenetics? Seizure. 2017 Jan;     [PubMed]
Pearl PL, Epilepsy Syndromes in Childhood. Continuum (Minneapolis, Minn.). 2018 Feb;     [PubMed]
Fisher RS,Cross JH,French JA,Higurashi N,Hirsch E,Jansen FE,Lagae L,Moshé SL,Peltola J,Roulet Perez E,Scheffer IE,Zuberi SM, Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;     [PubMed]
Kang JQ,Macdonald RL, Molecular Pathogenic Basis for GABRG2 Mutations Associated With a Spectrum of Epilepsy Syndromes, From Generalized Absence Epilepsy to Dravet Syndrome. JAMA neurology. 2016 Aug 1;     [PubMed]
Onat FY,van Luijtelaar G,Nehlig A,Snead OC 3rd, The involvement of limbic structures in typical and atypical absence epilepsy. Epilepsy research. 2013 Feb;     [PubMed]
Glauser TA,Cnaan A,Shinnar S,Hirtz DG,Dlugos D,Masur D,Clark PO,Capparelli EV,Adamson PC, Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. The New England journal of medicine. 2010 Mar 4;     [PubMed]
Genton P,Ferlazzo E,Thomas P, Absence status epilepsy: delineation of a distinct idiopathic generalized epilepsy syndrome. Epilepsia. 2008 Apr;     [PubMed]
Carmant L,Kramer U,Holmes GL,Mikati MA,Riviello JJ,Helmers SL, Differential diagnosis of staring spells in children: a video-EEG study. Pediatric neurology. 1996 Apr;     [PubMed]
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The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Nurse-Child Health PN. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

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Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Nurse-Child Health PN. When it is time for the Nurse-Child Health PN board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Nurse-Child Health PN.