Definitions
Febrile Seizure
Seizure accompanied by fever without central nervous system infection, metabolic or electrolyte disturbances, or a history of afebrile seizure or any acute neurological insult/head trauma in children aged 6 months to 6 years. Few guidelines include younger children up to 3 months [National Institutes of Health (NIH)] and even 1 month [International League against Epilepsy (ILAE)] after ruling out causes of provoked seizures. Fever can occur anytime during or after a seizure and the majority of febrile seizures (FSs) occur within 24 hours of fever onset.
Simple Febrile Seizures
Fever with isolated, generalized tonic clonic seizures, which last <15 minutes, and do not recur within 24 hours.
Complex Febrile Seizures
Fever with seizures with any one of the following features: focal and/or prolonged for >15 minutes and/or recur within 24 hours and/or have incomplete recovery within 1 hour.
Febrile Status Epilepticus
Febrile seizure lasting for 30 minutes or more and/or series of seizures without full recovery in between that.
Afebrile Febrile Seizure
Seizures in an acute infectious illness (particularly gastroenteritis) without documented fever and features consistent with simple FS.
Febrile Seizure Plus
Febrile seizures that continue past the usual age where they are expected to resolve (6 years) and/or accompanied by afebrile generalized or focal seizures.
Genetic Epilepsy with Febrile Seizure Plus
Febrile seizures plus with a family history of FSs, FSs plus, or afebrile generalized or focal seizures.
Pathophysiology of Febrile Seizures
Several hypotheses have been proposed to explain causation of FSs. It is believed that in genetically predisposed children, increase in brain temperature leads to
perturbation of temperature sensitive ion channels that in turn causes increased neuronal firing. Moreover, interleukin-1β acts as both a pyrogen and seizure provocator, acting at glutamate pathway. Interleukin-1β is also an NMDA agonist. Last, but not the least, hyperthermia-induced brain alkalosis is also believed to result in neuronal excitability.
Diagnosis of Febrile Seizure
TABLE 1: Diagnosis of febrile seizure (FS). | ||
History | Clinical examination | Red flag signs |
þ Nature and duration of the convulsions and postictal phase þ Recent fever/ear discharge/dysuria þ Recent antibiotic therapy/ antipyretics/rescue anticonvulsants Immunization history þ Past history of previous episodesof FS, a diagnosis of epilepsy, andother neurologic conditions and diseases þ Family history of FS, epilepsy, orneurologic diseases þ History of neonatal intensive care unit stay or developmental delay,if any | þ Vitals þ Obvious focus of infection þ Anthropometry þ Features of raised intracranial pressure þ Features of meningitis like bulging fontanelle, neck retraction, or meningeal signs þ Neurocutane ousmarkers þ Dysmorphism þ Focal neurological signs þ Meningeal signs | þ Focal neurological signs þ Persistent altered sensoriumafter 1 hour of seizure þ Features of raised intracranial pressure such as headache, vomiting, papilledema, brisk deep tendon reflexes, Cushing’s triad of bradycardia, irregular respiration, and hypertension þ Features of meningoencephalitis/non- blanching rash in an unwellchild þ Features of sepsis/shock/ respiratory distress |
Diagnosis of febrile seizure is depicted in Table 1.
Evaluation of a Child with First Episode of Febrile Seizure
Flowchart 1: Algorithm for evaluation and management of febrile seizure.
(CBC: complete blood count; CFS: complex febrile seizure; CRP: C-reactive protein; EEG: electroencephalography; GTCS: generalized tonic-clonic seizure; Hib: Haemophilus influenzae type B; PCV: pneumococcal conjugate vaccine)
Evaluation of a Child with First Episode Febrile Seizure
TABLE 2: Evaluation of a child with first episode febrile seizure. | ||
|
Simple febrile seizure (SFS) | Complex febrile seizure (CFS)/ febrile status epilepticus (FSE) |
Basic history, examination,and red flags (Table 1) | Yes | Yes |
Lumbar puncture | If features of meningitis; children <12 months of age who have not received the Hib or pneumococcalvaccines, children pretreated with antibiotics or children with severe protein energy malnutrition | Consider in children who remainobtunded after 1 hour of seizure |
Neuroimaging | Neuroimaging is routinely not recommended. Consider neuroimaging prior to lumbar puncture in children with focalneurological deficits or clinicalsymptoms and signs of raised intracranial pressure | MRI brain should be preferably considered within 72 hours for features of viral encephalitis, acute disseminated encephalomyelitis, intracranial space-occupying lesions, cortical malformations, andfor hippocampal abnormalities Also do if preexistent developmental delay |
Electroencephalogr aphy(EEG) | No | Yes, prognostic significance ofthe abnormalities to predict future epilepsy is unclear. Perform preferably after 48 hours and within 1 week of febrile seizure |
Complete blood countwith CRP | Not routinely, but may be considered to find cause of fever | Yes |
Serum electrolytes | No | Yes |
Serum calcium | If <1 year | Yes |
Serum magnesium | No | Yes |
Blood sugar | No | Yes |
Serum iron | If clinical pallor | |
Urine analysis | If <18 months or if clinical features suggestive of urinary tract infection(dysuria, frequency, and urgency), if >18 months of age | |
Genetic testing for Dravet syndrome (SCN1A, SCN1B, GABRG2, and SCN2A) | Recurrent febrile status epilepticus, onset of prolonged hemiconvulsive seizures below 1 year age, vaccine- associated encephalopathy, or GEFS+ | |
(CRP: C-reactive protein; GEFS+: genetic epilepsy with febrile seizure plus; Hib: Haemophilus influenza type B)
Acute Management during Seizure
· The drug of choice for rescue management at home is intranasal midazolam (0.2 mg/kg; maximum: 5 mg). Other effective drugs are intramuscular/buccal midazolam, buccal lorazepam, and per rectal diazepam. Maximum two doses, 5 minutes apart.
· Management of febrile status epilepticus at hospital is similar to management of convulsive status epilepticus.
· Stabilize with ABCDE approach (airway, breathing, circulation, disability, and exposure/ examination).
· If diagnosed with Dravet syndrome, FS+, GEFS+, sodium channel blockers (phenytoin) may be avoided.
· In young children, in case of clinical suspicion of meningitis and febrile status start thirdgeneration cephalosporin till lumbar puncture results.
Points to Ponder before Institution of Prophylactic Therapy
· Children with FSs are prone to recurrence.
· Slightly increased risk of epilepsy in this population is the result of genetic predisposition.
· No difference in learning has been identified in children with simple FSs, except in those children who had neurologic abnormalities before their first seizure.
· There is a negligible risk of a child dying during a simple FS due to injury, aspiration, or cardiac arrhythmia.
· Successful treatment of simple FSs can neither prevent later development of epilepsy nor simple FSs cause any structural damage to the brain.
· Possible adverse effects of prophylactic therapy include rare fatal hepatotoxicity (especially in children younger than 2 years who are also at greatest risk of FSs), thrombocytopenia, weight loss and gain, gastrointestinal disturbances, and pancreatitis with valproic acid and hyperactivity, irritability, lethargy, sleep disturbances, and hypersensitivity reactions with phenobarbital; lethargy, drowsiness, and ataxia for intermittent diazepam as well as the risk of masking an evolving central nervous system infection.
· Antipyretics and tepid sponging, if properly done, may improve the comfort of the child, they do not prevent fever or FSs, e.g., paracetamol 15 mg/kg/dose SOS up to 6 hourly.
Prophylactic Regimens
· Neither continuous nor intermittent anticonvulsant therapy is recommended for children with one or more simple FSs as there is preponderance of harm over benefit with therapy.
· Intermittent prophylaxis with oral benzodiazepine may be considered among children with frequent recurrent simple FSs with parental anxiety and residence far from medical facilities or complex FS who have not been started on continuous prophylaxis.
· Continuous prophylaxis with anticonvulsants may be considered among children with febrile status epilepticus, FSs in children with neurodevelopmental delay like cerebral palsy, global developmental delay or autism spectrum disorder, frequent complex FSs, and children with FS+/GEFS+ with afebrile seizures.
Prophylactic Drugs
The drug of choice for intermittent prophylaxis is clobazam (0.5–1 mg/kg/day in two divided doses for 3 days without tapering; maximum dose 20 mg/day).
Drug of choice for continuous prophylaxis is sodium valproate (20–40 mg/kg/day), others are phenobarbital (3–5 mg/kg/day); primidone (15–20 mg/kg/day). Carbamazepine and phenytoin are ineffective.
Duration
The anticonvulsants should be considered for 2 years seizure freedom period or guided individually based on primary syndrome (GEFS+/Dravet syndrome).
TABLE 3: Future prognosis. | |
Future risk of epilepsy | Recurrence of febrile seizures |
Children with simple febrile seizures have 1% risk ofdeveloping epilepsy by the age of 7 years (same as the general population) and 2.4% by 25 years of age Children who have had multiple simple febrile seizures are younger than 12 months at the time oftheir first febrile seizure and have a family history ofepilepsy are at higher risk Risk of epilepsy after complex febrile seizuresdepends on number of complex features: þ With 1 complex feature: 6–8% þ With 2 complex features: 17–22% þ With 3 and more features: 49% Risk factors for developing subsequent epilepsyinclude: family history of epilepsy, any neuro- developmental problem, prolonged or focal febrile seizures, and febrile status epilepticus | 32% children have recurrent seizures17% have one recurrence 9% have two recurrences 6% have three or more recurrences Recurrence rate within 1 year and 2-year of firstfebrile seizure is 75% and 90%, respectively Risk factors for recurrent febrile seizures þ Early onset <18 months of age þ Family history of febrile seizures or epilepsy ina first-degree relative þ Low grade fever associated with seizure onset(<39oC) þ Short duration of fever before the seizure(<1 hour) þ Complex febrile seizure þ Attendance at a day care nursery— presumedincreased viral exposure |
Family History of Febrile Seizure
· One-third of children with FS have a positive family history.
· Prevalence risk increase to one in five if one sibling affected and one in three if both parents and sibling have been affected.
· Concordance rate of FS are higher in monozygotic (35–69%) than dizygotic twins (14–20%).
Further Reading
· Clinical Practice Guidelines. Subcommittee on Febrile Seizures American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011;127(2):389-94.
· Kaushik JS, Sondhi V, Yoganathan S, Dubey R, Sharma S, Vinayan KP, Association of Child Neurology (AOCN) Consensus Statement on the Diagnosis and Management of Febrile Seizures. Indian Pediatr. 2022;59:300-6.
· Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281-6.
· Whelan H, Harmelink M, Chou E, Sallowm D, Khan N, Patil R, et al. Complex febrile seizures— a systematic review. Dis Mon. 2017;63(1):5-23.
References
- Clinical Practice Guidelines. Subcommittee on Febrile Seizures American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011;127(2):389-94.
- Kaushik JS, Sondhi V, Yoganathan S, Dubey R, Sharma S, Vinayan KP, Association of Child Neurology (AOCN) Consensus Statement on the Diagnosis and Management of Febrile Seizures. Indian Pediatr. 2022;59:300-6.
- Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281-6.
- Whelan H, Harmelink M, Chou E, Sallowm D, Khan N, Patil R, et al. Complex febrile seizures— a systematic review. Dis Mon. 2017;63(1):5-23.