Managing Epilepsy in Low Resource Settings

Abstract

Epilepsy is a chronic disorder of the brain with a tendency to have recurrent seizures and is associated with time-locked abnormal electrical discharges that arise spontaneously from the brain.

It is the commonest chronic neurological condition affecting 1% of the world’s population. It affects 40 million people worldwide with more than 80% living in resource poor countries. Its annual incidence is 100 per 100,000 in the developing world.

Epilepsy is surrounded by ignorance and prejudice and sufferers face major challenges in accessing treatment as well as discrimination. Epilepsy patients, their families, friends, teachers, and employers suffer its consequences.

Untreated, epilepsy can have major short- and long-term consequences including status epilepticus, sudden death, risk of serious accidents, and cognitive and developmental impairment. Fortunately, even with significant resource limitations over 80% of patients worldwide can be treated effectively with inexpensive and easily available anti-epilepsy medication, and in most patients it can remit permanently after 2–3 years of effective treatment.

Appendix: Epilepsy in Resource Poor Settings

Non-Epileptic Seizure Phenomena

The following are common occurrences that may be mistaken for seizures by parents and important to recognize and educate in the refugee setting.

Phenomena	Features
Febrile seizures	Caused by immaturity of the brain to cope with a sudden rise in body temperature. Most common type of non-epileptic seizure, affects 4% of children, mainly in second year of life, but can occur between age 6 months and 6 years. Usually short (<5 min) and self-limiting. Should be treated (e.g., rectal diazepam) if >5 min. Important to consider the presence of brain infection (e.g., meningitis, encephalitis, malaria)
Breath Holding Attacks	Blue breath-holding attacks: toddlers having a temper tantrum/crying—hold their breath—faint or have a brief motor generalized/focal seizure. Distraction may help to prevent these. White/Pallid breath-holding attacks: Painful stimulus causes a sudden low heart rate (vagocardiac reflex) with short loss of consciousness and seizure.
Jitteriness	Exaggerated startling in awake newborn babies. Movement can be stopped by holding the jittering limb. Hypoglycemia, hypothermia, and infection should be excluded.
Benign sleep myoclonus	Jerky limb movements in healthy infants <4 months of age during sleep, not involving the face. Harmless and resolves over time.
Behavioral stereotypies	Infants in the second half of the first year of life, when restrained shows complex repetitive stereotyped movements of the head, trunk, and limbs
Syncope/fainting	School children and teenagers—triggered by postural change, standing for a long time, heat, dehydration, skipping meals. May have a brief seizure (reflex-anoxic seizure) without postictal confusion
Benign paroxysmal vertigo	Young children <4 years, episodes of sudden falling or swaying but remains conscious. Resolves within 6–12 months, often a forerunner of migraine
Daydreaming	Common in primary school children—often mistaken for absence seizures, child is staring but is distractable and responds to name or tactile stimulus
Dissociative state	Adolescents/adults, caused by panic or anxiety, triggered by emotionally charged situations when individual feels anxious, agitated, or overwhelmed.
Tic or habit spasm	Irregular contractions of muscle groups—face or limbs. Can be voluntarily controlled for a short period of time. Often runs in families.
Cardiac dysrhythmia	Some heart rhythm abnormalities (e.g., long QT syndrome) can result in sudden onset of extremely low or fast heart rates, leading to loss of consciousness and anoxic seizure. A 12 lead ECG with rhythm strip should be performed if this is suspected.

Different Types of Epilepsy

Tonic clonic or major or grandmal seizures consist of a sudden loss of consciousness with collapse or fall and initial stiffness (tensing) of the whole body followed by generalized convulsive movements. The attack involves the facial muscles, the trunk, and limb muscles. Urinary and fecal incontinence and tongue biting may occur. Most attacks are self-limiting and cease in a matter of minutes. Occasionally attacks go on for longer periods.

The EEG between attacks (interictal record) usually shows epileptic abnormalities in 50–80% of patients but in other 20% it may be normal.

The prognosis for major motor seizures is variable. In most children attacks cease with natural remission after 2 or 3 years.

Carbamazepine, Phenobarbitone, Phenytoin, and Valproate are useful drugs in epilepsy with generalized or focal tonic clonic seizures. Newer anti-epilepsy drugs (AEDs) are available in resource rich nations and those include Levetiracetam, Lamotrigine, and Topiramate being most commonly used.

Focal motor seizures are episodes of twitching and jerking involving one side of the body which can spread to become generalized. This epilepsy suggests structural pathology in both children and adults. However, in a significant proportion of children there may be no lesion. In fact, the commonest focal motor epilepsy occurring in older children is “benign centro-temporal/rolandic epilepsy” of childhood which is genetically determined and shows no structural brain lesion.

It is benign as the prognosis is very good for cessation of seizures after 2–3 years. The EEG shows sharp and spike wave focus in one and the other central and temporal regions. Carbamazepine is very effective and less desirable alternatives are Phenobarbitone and Phenytoin.

Myoclonic and drop attacks are sudden shock like jerks which are bilateral and symmetrical associated with sudden head flexion or extension. They can be violent as to make the child drop/collapse to the floor and the child may immediately get up. They are associated with generalized discharges of slow spike and wave on EEG.

Other types of drop attacks involve temporary loss of postural tone (atonic attacks) and cuse the child to collapse to the floor.

Such attacks may occur in genetic generalized epilepsy though more often they are seen in epilepsy due to an underlying cause or brain damage.

Absence/Petit Mal seizures are episodes of impaired consciousness without significant motor accompaniments. The child stops, ceases whatever activity he is engaged in (“motor arrest”) and looks vacant for 5–20 s and then resumes normal activity as though nothing had happened.

The EEG shows burst of generalized and regular 3 per second spike and wave discharges and these can be precipitated by hyperventilation.

It is very age-related commencing usually between 5–10 years of age. Attacks usually remit after 2 or 3 years in the younger child or by early teenage years. In a small proportion of such children, estimated to be less than 10%, grand mal seizures can occur, particularly in the early hours of the morning.

This epilepsy is always genetic and there can be a helpful family history.

Ethosuximide is the drug of choice in typical absence epilepsy. Sodium Valproate is an excellent alternative.

It is important to remember that Carbamazepine and Phenytoin are specifically contraindicated in absence epilepsy and will make it worse.

Atypical absences are those which do not fit the description of the classic absence seizure—e.g., the seizures last for longer than 30 s or there may be associated complex motor symptoms like twitching of the eyelids (myoclonus) or automatisms.

The EEG does not show the regular 3 per second spike and waves of classic childhood absence; instead it may show generalized bursts of irregular polyspikes and wave or slow spike and wave pattern. Often these children have associated developmental delay. The prognosis is less favorable. Sodium Valproate is very useful. An alternative would be Phenobarbitone. Carbamazepine and Phenytoin are specifically contraindicated.

As mentioned earlier daydreaming can often be mistaken for absence epilepsy.

Temporal lobe epileptic attacks are focal and dyscognitive with altered or impaired consciousness associated with the patient experiencing strange, odd sensations while displaying complex semi-purposeful movements. The sensations patient experiences may be visual, auditory (sounds and voices may appear), sensations of vertigo may be experienced or gustatory/olfactory (peculiar tastes and sensations of smell) or emotional sensations, for example loss of reality, fear, laughter or excessive familiarity and so on. The child may talk nonsense during the episode and may display chewing or swallowing movements. Very often patients have an aura before the attack commences. The child may also display complicated movement during the attack such as aimless wandering. If fear is a significant accompaniment the child may look terrified and wide eyed. Such attacks commonly last a few minutes with significant postictal tiredness. It is quite conceivable that in developing countries or areas of the world that retain beliefs in possession and witchcraft, temporal lobe epilepsy may be mistaken for such supernatural phenomena with consequent mismanagement or failure to present.

The EEG often shows epileptic focus with spike and sharp waves in one or the other temporal region. Such attacks may progress to major motor seizures.

Behavioral disorders and specific learning disorders are often seen in children with temporal lobe epilepsy than among children with genetic generalized epilepsy. Drugs which are very helpful include Levetiracetam, Carbamazepine, and Phenytoin.

Epileptic spasms are seen in infancy when they are called “epileptic infantile spasms,” commencing usually between 3–8 months of life. The majority show flexor spasms or Salaam attacks occurring in clusters of several seizures. The child may also show extension of the head and neck and limbs. Individual spasms last 1–3 s and occur in clusters lasting 10–20 min. In most instances epileptic spasms indicate an underlying serious brain disorder and no cause is found only in a small minority. Such children may have had normal development until the spasms commence although the majority have preexisting developmental delay before the onset of the infantile spasms.

Epileptic spasms can be caused by multiple causes, including perinatally acquired brain injury, post meningitic and posttraumatic brain injury, and genetic conditions like tuberous sclerosis.

The EEG in epileptic infantile spasms shows the pattern known as “hypsarrhythmia” which is a chaotic high voltage irregular EEG with superimposed multifocal spikes and spike wave bursts followed by periods of suppression.

Treatment is with either Vigabatrin or corticosteroids though the latter has a minor superiority.

Once again smartphone videos can be invaluable in the resource poor setting to help diagnose this condition in the absence of EEG, and steroids should be widely available (?)

Symptomatic epilepsies commonly associated with underlying structural brain injury or genetic or chromosomal conditions. Hence, it is commonly associated with cerebral palsy or severe learning disability and concurrent abnormal neurological findings.

The cause may be prenatal, perinatal, or acquired. Genetic conditions associated with brain malformations may be associated with epilepsy, for example, tuberous sclerosis, arteriovenous malformations, and hydrocephalus.

Epilepsy is an uncommon mode of presentation of brain tumors as most tumors of children are infratentorial affecting the brain stem and the cerebellum.

Many of the cerebral degenerative disorders associated with epilepsy are symptomatic. Most often tonic clonic, myoclonic, and complex absences may be the clinical seizure types seen in symptomatic epilepsy with the exception of true absence. Myoclonic seizures, drop attacks and infantile spasms are particularly associated with symptomatic epilepsy.

Anticonvulsants which are helpful include Levetiracetam, Lamotrigine, and Sodium Valproate.

The prognosis is generally poor for seizure control with AEDs.

Side Effects of AEDS

All anti-epileptic drugs (AEDs) can have side effects on chronic usage though only a small proportion of patients suffer them. All AEDs should be started at low dose and the dose increased every 4–7 days to avoid excessive tiredness and sleepiness.

Phenobarbitone can cause sedation at higher doses.

Phenytoin can produce cosmetic side effects including coarsening of facial features and gum hypertrophy and cerebellar ataxia with high blood levels.

Carbamazepine can cause double vision and tiredness 30–40 min after administration. For this reason, this medication is also available in slow release form. Carbamazepine can cause a skin rash in 3–4% of children and it may have to be stopped.

Valproate does not cause sedation. In children with undiagnosed mitochondrial metabolic disease, it can cause severe liver dysfunction and may be fatal. For this reason, this AED is best avoided in children under 3 years of age as a regular AED in refugee and disaster zone settings.

Common Anticonvulsants Dose and Side Effects

AED	Common	Rare
Ethosuximide	Nausea, Rash	Bone marrow depression
Carbamazepine	Rash, fatigue, dizziness	Bone marrow depression
Phenobarbitone	None with low doses	Sedation
Phenytoin	Ataxia, gum hyperplasia, hirsutism, rash	Facial coarsening
Levetiracetam	None	Behavior disturbance
Lamotrigine	Rash	Stevens Johnson’s syndrome
Benzodiazepines	Drowsiness, salivation

Treatment of Convulsive Status Epilepticus (CSE)

A convulsing child should be seen immediately and after a brief assessment, attempt to stop the convulsion as soon as possible. A child in CSE is in danger of death or other serious harm if the attacks are not stopped promptly. Healthcare professionals should be knowledgeable and skilled to stop CSE and there are basic life support principles (A,B,C) that can be employed regardless of the setting.

Make sure the Airway is clear, the child is breathing, and check the pulse (circulation)

First Aid

The individual should be placed in the safe semi-recumbent recovery position to ensure patency of the upper airway. The tongue remains on the side of the mouth with an opportunity for the saliva and secretions to flow out.

Insert an oral airway (Guedel) or a tracheal tube that can be passed as far as the back of the throat.

Anti-epilepsy Drug Treatment in Status Epilepticus

First line is Diazepam or Paraldehyde rectally.

Diazepam can be given rectally 0.5 mg/kg and it acts almost immediately to stop the seizure. This is very safe and is an excellent anti-epilepsy drug.

An alternative will be rectal Paraldehyde if available. This is given at a dose of 0.3 ml/kg mixed with an equal volume of Arachis or Olive oil. It is an excellent AED, which will almost always stop the seizures without respiratory depression.

In advanced countries, buccal Midazolam is used as first line and administered at a dose of 0.3 mg/kg, into the cheek pouch. It is dispensed in ready prefilled syringes for buccal administration. The doses are as follows:

• Infants <12 months 2.5 mg

• Children between 2– and 5 years, 5 mg

• Children between 5 and 8 years, 7.5 mg

• Children between >9 years, 10 mg

Parents of children with established epilepsy and prone to recurrent seizures in advanced countries are instructed in the use of these drugs and are provided with a supply to be kept at home.

What to Do If Rectal Medication Fails to Stop the Seizure

One of either Diazepam, Midazolam or Lorazepam if available can be given intravenously, but has to be injected slowly over 2–3 min. They will cause respiratory depression if given rapidly and there should be facilities for resuscitation.

Venous access and access to intravenous drugs are likely to be nonexistent in refugee camps and disaster zones; so it is likely that rectal diazepam will be the mainstay of initial stabilization and this is an excellent choice.

Second line AED for CSE is intravenous Phenytoin 18 mg/kg given over 10–15 min. Phenytoin ideally needs to be given with heart rate monitoring or by feeling the child’s pulse continuously.

Third line AED if the first two drugs fail to stop the seizures, diverge depending on the resource setting the patient is in. In low resource settings intravenous Phenobarbitone 20 mg/kg injected over 10–15 min is very effective and helpful. An alternative would be intravenous Sodium Valproate 20 mg/kg given over 5–10 min.

In advanced countries, if second line Phenytoin fails after 30 min of the patient presenting to the Accident Emergency Department, rapid induction of anesthesia with Thiopentone and artificial ventilation is employed and the patient is transferred to an intensive care unit.

Management of Convulsive Status Epilepticus