epilepsy

Epilepsy is defined as a brain disorder involving recurrent seizures and is the most common chronic neurological disorder in the adolescents. There are about 40 million people are affected worldwide.

With increasing surgical advances, the present day Neurosurgeons do not seem to pay much attention to this common presenting symptom in Neurology, and leave it to the physicians. Surgeons should be aware of the basics and something about the recent trends in epilepsy. With the rebirth of 'Surgery for Epilepsy', it is all the more important.

SURGICAL NEUROPHYSIOLOGY:

Normal cells have both inhibitory and excitory influences causing excitory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Once a critical membrane depolarisation occurs an action potential is propagated. This leads to firing of individual neurons in a repetitive fashion.

Focal discharge:

Neurons in epileptogenic foci exhibit a different pattern with a parodoxical depolarisation shift (PDS) which is more prolonged than the EPSP. Such 'group 1' neurons are found at the centre of an epileptic focus and fire spontaneously, acting as a pace maker. The surrounding 'group 2' neurons are influenced and recruited, resulting in a focal seizure and corresponding EEG discharge.

The pathological changes capable of giving rise to fits are diverse.

There is selective loss of inhibitory interneurons within epileptic foci.

Decreased GABA content may be found in the epileptic foci.

There may be loss of dendritic spines and terminal branches.

A scar in the brain is NOT a focus. A dead neuron does not cause abnormal discharge.

It is the partially damaged surrounding neurons that are hyper excitable, and hyper metabolic during the ictus and hypo metabolic during the interictal phase.

These give rise to hyper excitability and paradoxical discharge either due to cortical deafferentation and resultant receptor super-sensitivity.

Increased numbers of fibrous or reactive glial cells might impair extra-cellular K+ and excitary neurotransmitters contributing to membrane instability, and may be an additional cause for focal discharge.

The spread:

Normal consciousness is maintained by the interaction of cortical structures with brainstem reticular formation. The nonspecific thalamo-cortical pathways synchronize the cortical activity when a discharge arises primarily at a reticular or thalamic level or secondarily to a focal cortical discharge.

The bilateral cortical role is of primary importance in generalized discharges. This synchrony is disrupted in corpus callosum section.

A focus in one hemisphere may, after a latent period, lead to the development of spike discharges from the contra lateral homologous cortex (Mirror focus). Eventually the mirror focus may become independent.

Commisurotomy prevents the development of mirror focus.

CLASSIFICATION OF SEIZURES :

InTERNATIONAL LEAGUE AGAINST EPILEPSY CLASSIFICATION (1989)

1) Partial (focal, local) seizures

a) Simple partial seizures (consciousness not impaired )

1) with motor signs

2) with somatosensory or special sensory symptoms

3) with autonomic symptoms

4) compound forms

b) Complex partial seizures (with impairment of consciousness)

1) Simple partial followed by impairment of consciousness

2) Impairment of consciousness at onset

c) Partial seizures with secondary generalization

2) Generalized seizures (convulsive or nonconvulsive )

a) Tonic-Clonic (grand mal)

b) Petit mal (absence)

c) Atonic (drop attack)

d) Tonic

e) Clonic

f) Myoclonic

3) Unclassified epileptic seizures (with incomplete data)

1) Partial (Focal) Seizures:

A partial, or focal, seizure is the more common type of epilepsy and is caused by a disorder of a neuron population in a specific site on one side of the brain. They are further categorized as simple partial, complex partial, and secondarily generalized seizures.

A person with a SIMPLE partial seizure (sometimes known as Jacksonian epilepsy) does not lose consciousness but may experience confusion, jerking movements, tingling, or odd mental and emotional events, such as deja vu, mild hallucinations, or extreme responses to smell and taste. After the seizure, the patient usually has temporary weakness in certain muscles.

Slightly over half the seizures in adults are COMPLEX partial types, and about 80% of these seizures originate in the temporal lobe of the brain, which is located close to the ear. Disturbances there can result in loss of judgment, involuntary or uncontrolled behavior, or even loss of consciousness. About 20% of these patients have seizures that start in the frontal lobes of the brain.

Prior to the actual seizure, people sometimes experience a warning sign, known as an aura, which can be an odd odour or a visual or auditory hallucination.

People with a complex partial seizure may lose consciousness briefly and appear to others as motionless with a vacant stare. Emotions can be exaggerated, and some sufferers appear to be drunk.

After a few seconds, some may begin to perform repetitive movements, such as chewing or smacking of lips.

Episodes usually last no more than two minutes, and people can have them infrequently or as often as every day. A throbbing headache may follow this seizure.

Aura alone is a partial seizure !!

In some cases, simple or complex partial seizures evolve into generalized seizures, which are known as secondarily generalized seizures .The progress may be so rapid that the partial stage is not even noticed.

2) Generalized Seizures:

Generalized seizures are caused by disturbances of nerve cells in more diffuse areas of the brain than with partial seizures and therefore have a more serious affect on the patient.

The first stage of a GRAND MAL seizure is called the tonic phase , in which the muscles suddenly contract, causing the patient to fall and lie rigidly for about 10 to 30 seconds. Some people experience a premonition or aura before a grand mal or tonic-clonic seizure; most, however, lose consciousness without warning.

If the throat or larynx is affected, there may be a high-pitched musical sound called strider when the patient inhales.

Spasms occur for about 30 seconds to a minute as the seizure enters the clonic phase, when the muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control.

The seizure usually lasts a total of two to three minutes, after which the patient remains unconscious for a while and then awakens to confusion and extreme fatigue. A severe, throbbing headache, similar to migraine, may also follow the tonic-clonic phases.

PETIT MAL or absence seizures are brief (3 to 30 seconds) and may consist of only a short cessation of physical movement and loss of attention. They may even pass unnoticed by others. Small children may simply be observed staring or walking distractedly. Petit mal may be confused with simple or complex partial seizures; in petit mal, however, a person loses consciousness and may experience attacks as often as 50 to 100 times a day

About 25% of patients with petit mal develop grand mal seizures.

A person who has an ATONIC or akinetic, seizure loses muscle tone. Sometimes it may affect only one part of the body, so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person suddenly falls. A brief atonic episode is known as a drop attack.

In TONIC seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic or jerking phase.

CLONIC seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not the tonic rigidity.

MYOCLONIC seizures are a series of brief, jerky, contractions of specific muscles groups ,such as the face or trunk.

3) Unclassified seizures:

They include all seizures that cannot be classified because of inadequate or incomplete data.

EPILEPSY SYNDROMES:

Epilepsy is also classified by syndrome or grouped according to a set of common characteristic, such as age, type of seizure or seizures, or whether a cause is known or not (idiopathic).

A few syndromes and inherited epilepsies are listed below:

They by no means represent all epilepsies:

West syndrome (also called infantile spasms), a disorder that involves spasms and developmental delay in children within the first year, usually infants between four and eight months.

Benign familial neonatal convulsions, a rare inherited form of generalized seizures that occur in infancy.

Juvenile myoclonic epilepsy (impulsive petit mal), characterized by generalized seizures, usually tonic-clonic signalled by myoclonia (jerky movements) or absences. This accounts for 7% of epilepsies usually occurring in individuals ages 8 to 20.

Lennox-Gastaut syndrome, a severe form of epilepsy in young children that causes multiple seizures and some developmental retardation. It usually involves absence, tonic, and partial seizures.

Myoclonic-astatic epilepsy (MAE), a combination of myoclonic seizures and atstasia (which involves loss of muscular coordination).

Progressive myoclonic epilepsy , an inherited disorder occurring between the ages six and 15.It usually involves tonic-clonic seizures and marked sensitivity to light flashes. Although previously the disease was considered to be progressive throughout life, current therapies have significantly improved its outlook.

Autosomal dominant nocturnal frontal lobe epilepsy, a rare inherited epilepsy that usually occurs during childhood, on average at 11 years (although onset varies widely within families). Seizures can be dystonic (twisting contractions), tonic (muscle contractions), or involve thrashing around. They are brief, frequent, and occur in clusters during the night. The seizures often subside with age.

Landa-Kleffner syndrome, an epileptic condition that results in the inability to communicate either with speech or by writing (aphasia).

CAUSES OF SEIZURES:

Some of the more common causes of seizures include:

1) Idiopathic (no identifiable cause)-

usually begin between ages 5 to 20, can occur at any age,

no other neurological abnormalities present,

often a family history of epilepsy or seizures.

2) Congenital defects and perinatal (near the time of birth) injuries-

seizures usually begin in infancy or early childhood.

3) Metabolic abnormalities-

may affect any age,

diabetes mellitus complications, electrolyte imbalances, kidney failure, uremia

Nutritional deficiencies,

Phenylketonuria (PKU)--can rarely cause seizures in infants,

Intoxication / withdrawal from alcohol or drugs,

4) Degenerative disorders (senile dementia Alzheimer type, or similar organic brain syndromes)-

mostly affect older people.

5) Disorders affecting the blood vessels (stroke, TIA, and so on)-

most common cause of seizures after age 60.

6) Tumors and brain lesions –

may affect any age, more common after age 30,

partial (focal) seizures most common initially, may progress to generalized tonic-clonic seizures.

7) Infections –

may affect all ages,

may be a reversible cause of seizures,

brain infections (meningitis, encephalitis), brain abscess,

acute severe infections of any part of the body, due to high fever,

chronic infections (such as neurosyphilis),

complications of AIDS or other immune disorders.

8) Post-traumatic seizures-

(a) Early (within the 1st week):

The risk of early seizures after brain injury is 2.5% to 7%.

About 35% of acute SDHs and ICHs, and 10% of EDHs,10% of Depressed fractures,10% of patients with PTA lasting for more than a day are at risk. 60% of them go on for late seizures.

1/3 of all early seizures occur within 1st hour,1/3 within 24hrs and 1/3 between the 2nd and 7th days.

More than half of all seizures are focal.

Studies suggest that anticonvulsants are administered only after the 1st seizure and that prophylactic therapy has no role.

(b) Late (after a week):

The risk is reported to be 5% in a series of unselected patients. 50% of all SDHs and ICHs, 20% of EDHs and 60% of all with neurological deficit or those with Depressed fractures with dural tear or those with PTA lasting for more than a day or the patients with early seizures run the risk.

They are more likely to have persistent epilepsy.

9) Post operative seizures-

The risk varies with the condition for which craniotomy was done.

The incidence after tumor surgery is obviously more difficult to assess, with various surgical techniques and the natural history of the tumor. Fronto parietal lesions are more prone.

It is suggested that the incidence is 20% following craniotomy for gliomas.

9% following burr hole/stereotactic biopsy.

22% following craniotomy for meningiomas

6% following craniotomy for suprasellar lesions.

24% following shunt procedures (more with revisions).

95% following craniotomy for supratentorial abscesses

20% of the patients undergoing aneurismal surgery will have seizures, preoperative hematoma and other conditions and surgical techniques do have a role.

All things being equal, the incidence is 38% following MCA aneurismal surgery.

21% following A.COM.A aneurismal surgery.

7.5% following internal carotid aneurismal surgery.

37% of all who experience postoperative seizures do so within the 1st week and 40% of this group continue to experience seizures later. Only 5% of those developing seizures later than one week postoperatively have a single seizure.

MANAGEMENT:

Investigations:

Despite numerous technologic advances in the evaluation of neurological disorders, diagnosis of the first seizure is still based predominantly on the patient's medical history.

Many paroxysmal events may be confused with epileptic seizures, including syncope, movement disorders, and psychogenic seizures.

Probably the most common entity that is confused with epileptic seizures is syncope.

Diagnostic studies must be tailored to individual patients.

1) Basic laboratory evaluation focuses on detecting systemic disturbances potentially associated with seizures and includes a complete blood count and measurements of electrolytes, calcium, magnesium, phosphorus, blood urea nitrogen, creatinine and glucose.

2) Consideration also should be given to obtaining a toxicology screen and evaluating hepatic function with synthetic and enzyme studies.

3) Lumbar puncture is essential in patients in whom meningitis or encephalitis is suspected, as well as in immuno-compromised patients, since occult meningitis is a common finding in this group.

4) All patients who experience an unprovoked seizure undergo a brain imaging study in an effort to detect underlying cerebral lesions e.g., tumor, abscess, vascular malformation, stroke, and traumatic injury.

MRI is the procedure of choice. In patients presenting with a seizure in whom the history/examination suggests new focal deficits, persistent altered mental status, fever, recent trauma, persistent headache, cancer, treatment with anti-coagulation or immunocompromised state, emergency neuroimaging is recommended.

5) Electroencephalography (EEG) is often helpful in the evaluation of patients presenting with a seizure.

The utility of EEG includes

- Detection of epileptiform activity, strengthening the diagnosis;

- Identification of focal electro cerebral abnormalities suggesting

a focal structural brain lesion;

- Documentation of specific epileptiform patterns associated with particular epilepsy syndromes.

for example, generalized spike and-wave discharges associated with a generalized epilepsy, or focal discharges associated with a localization-related epilepsy).

- While planning surgical treatment for a refractory epilepsy.

- EEG can predict the risk of recurrent seizures.

- EEG findings should be reviewed with other parameters.

People with epilepsy may have normal EEG and normal EEG alone does not rule out epilepsy.

Medical management:

Modern treatment of seizures started in 1850 with the introduction of bromides, on the basis of the theory that epilepsy was caused by an excessive sex drive. In 1910, phenobarbital, which then was used to induce sleep, was found to have antiseizure activity and became the drug of choice for many years. Since then many drugs are in use.

Some physicians prefer not to prescribe ongoing antiepileptic therapy or patients with a single seizure and the decision to treat initial seizures with medication remains controversial.

Several factors should be considered when making a decision, including he likelihood of recurrent seizures, the risk of the treatment itself, he ability of the treatment to decrease the risk of recurrent seizures and the consequence of further seizures to the patient.

Since these factors vary from patient to patient, treatment decisions need to be individualized.

The goal of treating patients with epilepsy is to control seizures completely without causing unacceptable side effects. In the past several years, a number of new antiepileptic drugs have become available, and more will soon be released. To achieve optimal treatment results, several strategies should be used.

The most important step is to select an antiepileptic drug that is appropriate for the patient's particular type of epilepsy. Specific epilepsy syndrome diagnosis is based on the history of the patient’s seizure types, neurological status and EEG findings.

From the appropriate medications, choose the agent best suited for he patient based on patient and medication characteristics.

Initiate and titrate the medication at appropriate dosages.

Increase the medication, regardless of serum levels, until complete seizure control is achieved or until persistent and unacceptable side effects occur.

If satisfactory seizure control is not achieved, change to another agent appropriate for the epilepsy syndrome being treated; the goal should be antiepileptic drug monotherapy in each patient, when possible. Plasma drug level monitoring is useful when compliance or toxicity is suspected.

Antiepileptics:

Antiepileptics	indications	DOSAGE	SIDE EFFECTS
The Barbiturates, Phenytoin, Valproic acid, and Ethosuximide have been in use for long and are considered as the first line drugs.
Phenobarbital	may be effective, especially in children, in the treatment of both generalized and simple partial seizures, including status epilepticus.	Maintenance doses average 3 to 5 mg/kg/day.	sedation and ataxia and hyperactivity is occasionally evident. Risk for idiosyncratic hepato- toxicity and for rash is probably not dose related.
Phenytoin	effective in the treatment of both generalized and partial seizures may be administered intravenously as treatment for status epilepticus.	Maintenance doses average 4 to 7 mg/kg/day. Intravenous infusion of a loading dose (18 mg/kg) should be performed slowly and cautiously due to risk of hypotension.Oral absorption is slow.	sedation and ataxia. Long-term use may be complicated by gingival hyperplasia, hirsutism, or lymphadenopathy. Potential idiosyncratic side effects include rash, hepatotoxicity, or a lupus-like syndrome.
Valproic acid	useful in treating a variety of generalized (tonic-clonic, absence) and partial seizure disorders as well as some myoclonic epilepsies. It is particularly useful in treatment of mixed seizure disorders.	Maintenance doses range from 30 to 60 mg/kg/day PO.	sedation, GI upset, thrombo cytopenia, and hyperammonemia. Fulminant hepatotoxicity is the most feared idiosyncratic complication of therapy; children under 2 years of age and children receiving multiple anticonvulsants appear to be at greatest risk.
Ethosuximide	primarily in the treatment of absence (petit mal) epilepsy and occasionally as an adjunctive agent in other generalized seizure disorders	Maintenance doses average 20 to 30 mg/kg/day.	sedation, headache, and stomach upset. Idiosyncratic reactions may include rash or blood dyscrasias.
carbamazepine,	effective against both partial and secondarily generalized seizures	Maintenance doses average 10 to 20 mg/kg/day PO.	stomach upset, sedation, and ataxia. Potential idiosyncratic reactions include leukopenia ,aplastic anemia, rash and Stevens-Johnson syndrome.
NEWER DRUGS (recommended as adjunctive therapy)
Gabapentin(Neurontin)	Adjunctive therapy for partial seizures with or without secondary generalization	Begin with 300 mg daily; increase to 900 to 1,800 mg daily given every 6-8hrs	Somnolence, fatigue, ataxia, dizziness, gastro intestinal upset, dyspnoea.
Lamotrigine(Lamictal)	Adjunctive therapy for partial seizures with or without secondary generalization	Begin with 50 mg daily; increase to 300 to 500 mg daily given every 12 hours; for concomitant use with valproic acid : begin with 25 mg every other day; increase to 150 mg daily given every 12 hours	Rash, including life-threatening rashes, dizziness, ataxia, blurred vision, nausea.
Felbamate(Felbatol)	Adjunctive therapy or monotherapy in adults when seizures are so severe as to warrant use despite risk of aplastic anemia or hepatic failure; in children with Lennox-Gastaut syndrome when seizures are not controlled	Adults: begin with 1,200 mg daily given every 6 to 8 hours children: 15 to 45 mg per kg per day given every 6 to 8 hours;	Anorexia, vomiting, insomnia, somnolence, aplastic anemia, hepatotoxicity,
Topiramate(Topamax)	Adjunctive therapy for partial onset of seizures	Begin with 50 mg daily; increase to 50 to 400 mg daily given every 12 hours	Dizziness, somnolence, ataxia, confusion, fatigue, paresthesias, speech difficulties, side effects: diplopia, impaired concentration and nausea
Fosphenytoin(Cerebyx)	Status epilepticus; parenteral maintenance of phenytoin levels;parenteral treatment and/or prevention of seizures	For status epilepticus: 22.5 to 30 mg per kg IV for nonemergent therapy: 15 to 30 mg per kg IV or IM, followed by 6 to 12 mg per kg IV orIM	Pruritus, nystagmus, dizziness, somnolence, ataxia, nausea, tinnitus, hypotension.

Only phenytoin and phenobarbital can be administered parenterally; all others must be taken orally, which precludes their use in acute seizure control.

The complex pharmacokinetic and pharmaceutical properties of antiepileptic drugs make administration difficult at times. Many of these drugs are potent enzyme inducers or inhibitors, and significant drug interactions occur when they are co administered with hormones or other medications.

AEDs & oral contraceptives:

Carbamazepine, phenytoin, phenobarbital, primidone, and ethosuximide will reduce estradiol levels by 40% through their effect on the P450 system, and they may also reduce free progestin levels. The dosage of the hormonal components need to be increased..

Valproic acid and gabapentin do not induce the P450 system, and do not affect oral contraceptive levels.

Pregnancy and AEDs:

Most women with epilepsy today can conceive and bear normal, healthy children, but their pregnancies present an increased risk for complications. Epileptics who are on anticonvulsant therapy during pregnancy have a 5% risk of fetal malformations, which is double the risk seen in the general population. Clinicians are uncertain how much of the adverse outcome is secondary to AED, maternal seizures, or simply to the genetics of having epilepsy. The most common birth defects in this group are cleft lip / cleft palate and congenital heart defects. In addition, 1% of epileptic women treated with valproic acid during pregnancy will have a baby with neural tube defects, and 5%-10% of fetuses exposed to hydantoin will have fetal hydantoin syndrome, which includes microcephaly growth deficiency developmental delays and mental retardation, dysmorphic craniofacial features, and hypoplasia of nails and distal phalanges. Despite this, it is well recognized that the benefits of anticonvulsant therapy in pregnancy outweigh the risks as long as the therapy is truly necessary, and women with epilepsy who are considering pregnancy be reevaluated by a neurologist to confirm their true need for anticonvulsant therapy. As the pregnancy progresses, a woman may need more of the drug to remain in the therapeutic range. Later in pregnancy, when seizures can also be induced by other causes, such as hypertension, hyponatremia, and hypoalbuminemia, higher doses may be needed.

Although it hasn't been proven to reduce the risk of neural tube defects in exposed babies, many would agree that women on valproic acid or carbamazepine should take 4 mg of folic acid a day rather than 0.4 mg before conception and during the first trimester.

Breastfeeding and AEDs:

Carbamazepine, valproic acid, and phenytoin are compatible with breastfeeding; a very small amount of these drugs is excreted into breast milk and has no apparent effect on the baby.Phenobarbital, however, is excreted in large amounts into breast milk and is not compatible with breast-feeding, because it may cause sedation and CNS depression in the baby.

STATUS EPILEPTICUS:

Definition:

According to the International Classification of Seizures, it is ''a condition characterized by an Epileptic seizure that is so frequent or so prolonged as to create a fixed and lasting condition".

It is an emergency.

Diagnostic evaluation:

Immediately arrange for complete blood count, a serum chemistry profile, and drug screen.

Assess for possible drug intoxication or drug withdrawal.

Keep in mind that anticonvulsant drug withdrawal is a common cause of status epilepticus.

Obtain an arterial blood gas if there is evidence of respiratory compromise.

Management:

It is important to establish that there is no respiratory compromise and no evidence of cardiovascular collapse. Preparation for possible intubation should be made. Correction for metabolic disturbance, if present, is clearly indicated. Low serum Na+, glucose, Ca++, or Mg++ can result in recurrent seizure activity. Drug or alcohol withdrawal, or certain drug intoxication, can be precipitating factors.

It is important to recognize that withdrawal from phenobarbital generally requires resumption of phenobarbital with a loading dose, which will necessitate intubation with respiratory support.

An intravenous line is mandatory.

One of the drug regimes, suggested, is given below.

Initial, i.e., short-term, control of generalized seizure activity can often be obtained with either intravenous lorazepam, at a dose of 0.1 mg/kg, or diazepam at 0.2 mg/kg. Either agent is infused over two minutes.

It is important to recognize that these agents can promote respiratory depression at relatively small doses in certain individuals. Lorazepam's effect is longer lasting (hrs) and diazepam (hrs). If either of these agents is used, it is with the understanding that longer term, i.e., maintenance, therapy must also be initiated unless there is recognized metabolic derangement that can be rapidly corrected.

The phenytoin loading dose in status epilepticus is 15 to 20 mg /kg at maximum intravenous infusion rate of 50mg /min over 10 minutes. Fosphenytoin, if available is ideal alternative for phenytoin and has no risk of cardiac events.

If the patient continues to have seizure activity despite adequate intravenous loading with phenytoin, then phenobarbital loading is indicated. Phenobarbital is given at an intravenous dose of approximately 20 mg/kg at an infusion rate of no more than 1.5 mg/kg/min.

If this is unsuccessful, then intravenous pentothal is given at a loading dose of 3 to 4 mg/kg over two minutes followed by a continuous infusion at a rate of 0.2 mg/kg/min. The dose is then adjusted upward, every 3 to 5 minutes by 0.1 mg/kg/min, until the EEG, if available bed side, becomes isoelectric.

SURGERY for intractable Epilepsy: (A detailed account is beyond the scope of this article.)

Surgery can be considered in certain patients with surgically remediable syndromes. Candidates typically have seizures that impair consciousness, that cause falling with injury, that have adverse psychosocial or social effects, and that persist after trials of three appropriate medications. A multidisciplinary evaluation should take place at a surgery centre with experience and documented success.

Favorable results from surgery can be expected in a large proportion of patients.

CONCLUSION:

Patients with epilepsy now have available to them more therapeutic options than ever before. In order for patients to benefit from these advances, physicians must make an accurate diagnosis of epilepsy syndrome, selecting and using medications properly, and promptly referring patients who do not completely respond to treatment to a comprehensive epilepsy centre.