Choice of anticonvulsant drug in a 4-year old child with convulsions

The seizure is one of the most common neurological symptoms occurring in children. Paroxysmal cerebral dysrythmia leads to seizure and manifests as a brief episode of loss or disturbance of consciousness, with or without characteristic body movements (convulsions), sensory, autonomic or behavioral phenomenon. Anticonvulsant drug therapy is directed primarily toward reducing excitability through blockage of voltage-gated Na⁺ or Ca²⁺ channels, or increasing inhibition through enhancement of gamma-aminobutyric acid currents. Thus, these drugs block seizures without influencing the underlying tendency to generate seizures. The disease, however, fades out after years of successful control. Recently, a large number of anticonvulsant drugs have been added to the clinicians’ armamentarium. These “newer drugs” are as efficacious as the older medications, but have important advantages including the absence of adverse drug interactions and hypersensitivity reactions.

In any child presenting with seizure, detailed history is essential to confirm whether it was a seizure and rule out other conditions that mimic seizures, classify seizure, and detect any underlying etiological/provoking factor. A thorough physical examination can help in appropriate management of these patients. Table-1 lists the important points in history and physical examination of these patients.

Table-1. History and physical examination in a child with convulsions.

History

• Reliability of the person giving history

• Whether a known case of seizure disorder. If yes, then

-         Whether on treatment (drug, dose and compliance).

-         Type of seizures in the past

-         Frequency of seizures

• Time of the day: seizures in early morning hours and during early phase of sleep are common in childhood
                               epilepsy.

• Mode of onset
   

• History of fall
   

• Details of aura, if any: Most common is epigastric discomfort and a feeling of fear

• Details of involuntary movement: Part involved (generalized/ focal), progression and type of movement
                                                             (tonic/ clonic /tonic-clonic/ myoclonic).

Often, parents/witness can enact or re-create the event. The physical portrayal by the patent/witness is surprisingly similar to actual convulsion and is more accurate than verbal description. 

Description of seizures along with family history may give clue to the possibility of genetic epileptic syndrome, e.g., autosomal dominant nocturnal frontal lobe epilepsy, partial seizures with auditory symptoms, etc.

• Any tongue bite/ frothing/ loss of sphincter control
   

• Any inciting event: trauma/ fever/ missed dose of anti-convulsant in a known case.

• Duration of convulsion
   

• Associated automatism/ behavioral abnormalities
   

• Associated symptoms: fever, ear discharge, headache, vertigo, etc.

In retrospect, irritability, mood swings, headache and subtle personality changes may precede a seizure by several days. Some parents can accurately predict timing of next seizure on the basis of change in disposition.

However, prolonged personality change or intellectual deterioration may suggest degenerative disease of CNS.

Associated constitutional symptoms like vomiting, failure to thrive, etc.  suggest primary metabolic disorder or a structural lesion.

• Details of post-ictal phase
   

• Past history of similar episode: Two unprovoked seizures more than 24 hours apart suggest seizure
                                                       disorder and carry high risk of recurrences, if untreated.
   

• History suggestive of prior neurological disease.
   

• Perinatal and Developmental history is important for clues to etiology of seizures.
   

• Family history of seizure disorder/ other neurological disease 

Physical Examination

• Adequacy of airway, ventilation and circulation   

• Vital signs

• Any evidence of head trauma: May be cause/ effect of seizure

• Any evidence of ingestion of toxin
   

• Any neurodeficit: Even subtle signs like hyperreflexia, subtle hemiparesis, equivocal Babinski’s sign should be looked for. If present, whether it resolves or persists beyond 24-48 hours. If it persists, it may suggest a contra-lateral hemispheric structural lesion such as a slow-growing temporal lobe glioma, as the cause of seizure disorder. Unilateral growth arrest of a thumbnail, hand or extremity in a child with a focal seizure suggests a chronic condition such as a porencephalic cyst, arteriovenous malformation or cortical atrophy of the opposite hemisphere.
   

• Any sign of meningeal irritation: Specially look for these in case of seizures with fever.
   

• Any evidence of raised intracranial tension
   

• Any evidence of underlying degenerative/ metabolic/ congenital disorder
   

• Any sign of neurocutaneous syndrome: Café-au-lait spots, ash-leaf macule, sebaceous adenoma, Shagreen
                                                                      patch, neurofibroma, etc.
   

• Ophthalmologic exam: Especially to look for any evidence of papilledema, chorioretinitis, retinal hemorrhages,
                                         coloboma and macular changes. 

If any child has convulsions while in clinic/hospital, the acute management includes care of the airway and ventilation and control of seizure using benzodiazepines [diazepam (intravenous/ rectal) or midazolam (intravenous/ nasal/ buccal) or lorazepam (intravenous) or)]. I mostly use intravenous diazepam/ midazolam or rectal diazepam.

This article describes how I choose anticonvulsant in a 4-year-old child with convulsions in various possible clinical scenarios.

Scenario-1: Febrile seizure

For acute control of seizures, I use intravenous or rectal diazepam in dose of 0.3 or 0.5-mg/ kg respectively. In case of prolonged seizures, it can be repeated after 10 minutes. Antipyretic (Paracetamol oral or rectal) and external cooling measures are essential to bring down the temperature. I am using oral diazepam (0.3 mg/kg/dose 8 hourly for 2 days) in all cases for prophylaxis against recurrence of seizures during the febrile illness. I do not use long-term anticonvulsants in most of these patients. In case febrile seizures are very frequent, preventive therapy in the form of daily valproate is chosen. In patients with underlying neurological defect, I treat the child as one with seizure disorder (vide infra).

Scenario-2: First unprovoked seizure

I usually do not use long-term anticonvulsants in this setting. Evidence continues to accumulate to endorse this approach (1). However, drug therapy may be considered in a child with or an identifiable neurological condition or symptoms consistent with one ("symptomatic") or one with abnormal EEG/ imaging lesion (2, 3).

Scenario-3: Second unprovoked seizure (i.e., seizure disorder)

(a) Generalised tonic-clonic/ simple partial with or without generalization

Unlike in older children, I still prefer carbamazepine in young children because of fear of hepatotoxicity of valproate in young patients. I occasionally prescribe phenytoin when cost is the concern; phenobarbitone is hardly ever prescribed. Lamotrigine is fast becoming a first-line therapy for these cases (4), but my personal experience is limited with this drug. 

(b) Other types of seizures

Other types of seizures are rare and my personal experience in choosing anticonvulsant in these is limited. Table-2 lists choice of anticonvulsants in these types of seizures mainly based on the recently published European expert opinion (4).

Combination of two or more anti-convulsant drugs is attempted only if trials with two or three drugs as monotherapy fail to control seizures adequately.

Table-10. Choice of anticonvulsant in various less-common types of seizures (4, 5)

* Valproate is now considered drug of choice, even in younger children (4). However, personally I would prefer other first-line drugs in young children because of fear of hepatotoxicity of valproate.

Scenario 3: Convulsive Status Epilepticus (CSE)

I continue to use IV diazepam (0.3 mg/kg/dose slowly @ 2mg/min) as a first line drug for attempting acute control of seizures. If intravenous access is not immediately available, I usually use rectal diazepam (0.5 mg/kg/dose) and have used IM midazolam in one case. IV diazepam is repeated after 10 minutes, as seizures continue. If needed, I try intravenous lorazepam (0.1 mg/ kg slowly @ 2 mg/min) after 10 minutes.  If seizures still persist, then loading dose of intravenous phenytoin (20 mg/kg) given slowly @25-50 mg/min  (dissolved in normal saline) is given (Fosphenytoin is an alternative). Intravenous phenobarbitone (20 mg/ kg) is used next. If needed, I would use diazepam drip as a next step and ultimately endotracheal intubation and skeletal muscle relaxants would have to be used in case of refractory status epilepticus.

(A recent Cochrane review (6) has suggested that intravenous lorazepam may be as effective and safer than intravenous diazepam for treatment of acute tonic-clonic convulsions. If intravenous access is not available, buccal midazolam may be treatment of choice. Intranasal midazolam is also effective).

Scenario-4: Post-traumatic convulsions

I use intravenous phenytoin (15 mg/kg) slowly @25-50 mg/min  (dissolved in normal saline) as a loading dose in any case with “significant” head injury. The need for further anticonvulsants and duration of the therapy is individualized. However, the duration of anticonvulsant therapy does not usually exceed 6-12 months even in serious cases.

Conclusion

The seizure is one of the most common neurological symptoms occurring in children. However, with a number of types of seizures and a wide variety of underlying etiologies, there is no single drug for every case of seizure.  The drug has to be carefully chosen in each clinical situation and this article has described the approach followed by me in my clinical practice as well as the emerging new evidence in the field. Among the “newer anticonvulsants” introduced in last 2 decades, most have provided new add-on alternatives in refractory seizures, with lesser adverse effects. However, Vigabatrin has clearly surpassed older drugs for infantile spasms to become the drug of choice with over 90% efficacy. Fosphenytoin and midazolam have provided good alternatives when intravenous access is not immediately available. Lamotrigine is fast proving itself as a first line drug in a variety of seizures-types. Nevertheless, in most common clinical situations, the older drugs continue to prove that “Old is Gold”!

- Puneet Kumar, Kumar Child Clinic, Dwarka, New Delhi

References :

1.Leone MA, Solari A, Beghi F, et al. Treatment of the first tonic-clonic seizure does not affect long-term remission of
   epilepsy. Neurology, 2006: 67(12): 2227-9.

2.Berg AT. Risk of recurrence after a first unprovoked seizure. Epilepsia, 2008: 49 Suppl 1:13-8.

3.Wiebe S, Tellez-Zenteno JF, Shapiro M. An evidence-based approach to the first seizure. Epilepsia, 2008: 49 Suppl
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4.Wheless JW, Clarke DF, Arzimanoglou A, et al. Treatment of pediatric epilepsy: European expert opinion, 2007.
   Epileptic Disord, 2007: 9(4): 353-412.

5.Tripathi KD. Antiepileptic drugs. In: Essentials of Medical Pharmacology, 6^th Edition, 2008: 401-13

6.Appleton R, Macleod S, Martland T. Drug management for acute tonic-clonic convulsions including convulsive status
   epilepticus in children. Cochrane Database Syst Rev, 2008:  16;(3): CD001905.