febrile seizures

Febrile seizures (FS) are commonest cause of seizures in pre-school children, associated with any fever of non-CNS origin, excluding intracranial pathology, e.g. CNS infections. However, all seizures with fever are not febrile seizures.

Cardinal features of a typical FS include:

• Age group-6 months to 5 years,

• Presence of fever gt;38°C, and

• No evidence of pre-existing or post-ictal neurological deficit except transient drowsiness or Todd's palsy for 24 hours in some cases.

Some guidelines include diagnosis of FS even in younger infants (lt; 6 months) after excluding other causes of provoked seizures.

Incidence: One or more attack of FS are experienced by ~4-5% of all children lt;5 years of age, more common in boys.

Family history is present in ~30% cases and genetic predisposition is known involving many genes, includ­ing FEB_1-10 genes. Many epileptic syndromes with established genetic basis, e.g. Dravet syndrome, are known to present with FS in early stages.

Pathogenesis: Exact pathogenesis of FS is not unclear, but probably relates to developmental immaturity of brain with lower threshold for neuroexcitation in response to fever due to hyperthermia induced brain alkalosis and perturbation of temperature sensitive ion channels. Interleukin-1 #946;, a pyrogen, also acts as seizure provocator through glutamate pathway.

TABLE 18.19: D/D Simple vs complex febrile seizures

or per febrile episode

Clinically, FS usually develop within 24 hours of onset of any non-specific febrile illness in susceptible age group, usually during rising phase of fever.

Depending on clinical presentation and prospective outcome, FS are divided into two distinct categories- simple and complex FS (Table 18.19).

• Simple febrile seizures (SFS) are almost always benign with following characteristics—(a) generalized, (b) short-lasting lt;15 minutes, and (c) do not recur during same episode or within 24 hours. Most episodes occur during first 24 hours of onset of febrile illness. EEG beyond 2-3 weeks in these cases is essentially normal and risk of secondary epilepsy is almost nil.

• Complex febrile seizures (CFS) account for ~15-20% of all FS, which may be—(a) focal, (b) prolonged gt;15 minutes, and/or (c) recur within 24 hours. CFS are more common in older children and many of them begin as SFS during initial episodes. CFS are more likely to have underlying brain pathology, abnormal EEG and risk of recurrence or secondary epilepsy.

Febrile seizure plus refer to FS, which—(a) continue past the usual age when they are expected to resolve (6 years) and/or (b) accompanied by afebrile generalized (tonic­colic, myoclonic, absence) or focal seizures.

Febrile status (Status febrilis) denotes persistence of FS for gt;30 minutes, either single or recurrent without regaining consciousness.

Diagnosis of FS is mainly clinical and detailed investi­gations are unnecessary in most cases, especially on subsequent attacks. However, since it is difficult to exclude intracranial pathology during first attack, follow­ing investigations are recommended in selected cases:

• CSF examination must be considered during first attack in all cases lt;12 months of age and in older children only if they appear ill or pre-treated with antibiotics. Repeat lumbar puncture is not necessary during subsequent attacks, unless strong evidence of intracranial infections is present.

• EEG: Although of doubtful value in neurologically normal cases (abnormal EEG does not predict risk of epilepsy), EEG is advisable in cases with CFS or focal findings on neuroimaging within one week of seizure.

• Neuroimaging with CT/MRI is not routinely indi­cated, unless abnormal neurological signs are present. Emergency CT without contrast is indicated in cases with status epilepticus, history of trauma, signs of raised ICP and underlying CSF shunt. MRI must be considered only after stabilization in children with febrile status epilepticus or prolonged/focal CFS to rule out underlying pathologies.

• Other investigations, e.g. blood sugar and serum calcium estimation may be considered in infants, as also the sepsis screening. Genetic testing for Dravel syndrome is indicated in cases with recurrent febrile status epilepticus

Management of FS involves: (a) management of acute attack, and (b) prevention of recurrence during subsequent febrile episodes.

a. Management of acute attack: FS usually develop at home. Parents must be reassured about the benign nature of these episodes and trained to manage them at home as follows:

• Control the acute seizure with intranasal Midazolam (0.2 mg/kg), to be given within 3-5 minutes of the onset and repeated after 5 minutes in case of per­sistent seizure. Midazolam is preferred over per rectal diazepam.

• Place the child in recovery (Lateral) position to prevent aspiration.

• Control the fever with hydrotherapy (cold-sponging) and antipyretics (paracetamol). Antipyretics decrease the discomfort but do not reduce the risk of recurrence of FS.

• Visit the nearest health facility if—(a) it is first attack,

(b) seizures are not controlled with two doses of abor­tive medication, i.e. midazolam, or (c) child remains in postictal phase for long.

Treatment of FS in hospital must follow standard guidelines for management of status epilepticus (Ch 18.6.2), along with diagnosis and treatment of the cause of fever.

Prophylactic antibiotics, e.g. a third generation cephalosporin may be started in young infants with clinical suspicion of meningitis till CSF results.

b. Prevention of recurrence: Early recognition and treat­ment of febrile illness with antipyretic therapy is the key to prevent recurrence in FS, which is common in ~30-40% cases.

Common practices for FS prophylaxis are:

• Intermittent anticonvulsant prophylaxis with PO Clobazam (0.5-1 mg/kg/day q12hr) during first 3 days of a febrile episode (gt;38°C), which may be used in cases with: (a) high-risk of recurrence (see below outcome), or (b) high parental anxiety, or

(c) residence far away from medical facility, or (d) CFS not on continuous prophylaxis. However, most FS develop during first few hours of febrile illness, which may not be recognized. Intermittent prophylaxis is not recommended for the first episode of SFS.

• Continuous anticonvulsant prophylaxis is indicated only in cases with—(a) febrile status epilepticus, (b) neurodevelopmental delay, and (c) frequent CFS, and

(d) febrile seizure plus/GEFS with afebrile seizures. Sodium valproate (PO 20-40 mg/kg/d q8hr) is the drug of choice for this purpose, as phenobarbitone affects cognitive function and phenytoin or carbamazepine are less effective. Once started, prophylaxis should continue for minimum 2 years.

• Antipyretic medications, e.g. Paracetamol 15 mg/kg/ dose every 6 hours may be advised in all cases during the febrile episode, to make the child comfortable. However, this practice of round-the-clock antipyretics do not prevent occurrence/recurrence of FS.

Outcome: SFS are almost always benign, remitting spon­taneously after 5 years of age with ~1% risk of developing epilepsy and no late-effect on intellectual or motor functions. However, risk of recurrence in SFS is ~75% within a year after the first episode, higher in those with (a) early age of onset lt; 18 months, (b) family history of FS/ epilepsy, and (c) shorter duration of fever before seizure lt; 1 hr and d) seizures with low-grade fever (lt;39°C).

Children with (a) CFS, (b) family history of epilepsy, or (c) associated neurological abnormalities/ developmental retardation, carry higher risk of recurrence as well as development of epilepsy, i.e.

Generalized epilepsy with febrile seizure plus (GEFS⁺) is an autosomal dominant syndrome with highly variable phenotype. Most cases present in early childhood with multiple febrile seizures, later followed by multiple types of afebrile generalized seizures with variable phenotypes. Remission is common by mid-childhood. A family history of FS is present.

Dravet syndrome is the most severe type of febrile seizure-associated epilepsies, usually due to de novo mutation (2q24-31). These cases present in early infancy with prolonged and focal clonic febrile seizures, often in clusters, recurring every 1 or 2 months. Later, seizures start to occur without fever and become more variable in phenotype, e.g. myoclonus, atypical absences, and partial seizures. Developmental delay is common. Milder variants are referred as Dravet syndrome spectrum.

18.6.4