Epilepsy may be defined as abnormal transient disturbances of the cerebral function, paroxysmal in nature due to abnormalities in the electrical activity of brain cells. An attack of epilepsy is characterized by tonic and clonic convulsions with loss of consciousness coming on suddenly preceded by an aura, the attack ceasing spontaneously. This is typical form of epileptic attack though a number of variations are there depending on the site of origin in the brain and its spread.
Epilepsy may be primary where no cause responsible for it can be demonstrated. Patients suffering from primary or idiopathic form generally have hereditary predisposition while in secondary form of epilepsy a number of causes both local and general are responsible for causing it. In fact epilepsy in such cases is a symptom complex.
Pathophysiology
In epilepsy there are abnormal changes in the electrical potentials of the brain and a large number of neurons are activated repeatedly. The abnormal physio chemical state of the neurons is inhibited by certain changes at the cell levels and failure of this activity leads to repeated uncontrolled neural discharge. Initially it is confined to one area in the brain but in some it may spread throughout the brain. Post epileptic symptoms characterized by loss of consciousness, transient motor or sensory disturbances result due to exhaustion of neurons which have been discharging impulses actively.
Classification
Epilepsy is classified according to type of seizures:
Primary epilepsy
1. Generalized seizures:
(a) Grand mal epilepsy (tonic clonic seizures)
(b) Petit mal (absence seizure)
(c) Myoclonic seizures
(d) Tonic seizures
(e) Atonic seizures
(f) Infantile spasm.
2. Partial seizures
(a) Simple partial seizures
(b) Complex partial seizures (temporal lobe or psychomotor seizures)
(c) Secondary generalization of partial
Secondary epilepsy
Here a cause either local or generalized responsible for causing epilepsy is operative. Causes of secondary form of epilepsy are varied and include.
1, Local causes
(a) Increased intracranial pressure (space- occupying lesion, cerebral hemorrhage).
(b) Inflammatory conditions (meningitis, encephalitis)
(c) Trauma (head injury)
(d) Congenital abnormalities (cerebral diplegia)
(e) Degenerative (diffuse sclerosis, Alzheimer’s disease)
(f) Vascular (cerebral atherosclerosis, hypertensive encephalopathy).
(g) Parasitic (neurocysticercosis)
2. General causes. Poisons, cerebral hypoxia, disturbances of metabolism (hypoglycaemia), uremia, alkalosis, hypopituitarism.
Clinical features
Grand mal epilepsy. It comes suddenly without warning in some patients while in others it is preceded by prodromal symptoms which are present for hours or even for a day and consist of irritability, depression abnormal feelings, giddiness and abdominal cramps. Often the patient is able to recognize these symptoms and know that a fit is coming.
Characteristics of hysterical fits
1. Gradual onset
2. Fits only in presence of people
3. Consciousness not completely lost seizures.
4. No aura
5. Fits are bizarre and do not fit any pattern
6. Person does not hurt himself/herself
7. No incontinence of urine
8. No biting of tongue or injury
9. Generally a young female
10. EEG is normal
These symptoms are followed by aura which may be reflected in abnormal sensations like flashing of light, hallucinations of hearing words or sounds, sensation of tingling or numbness, pain in the epigastrium and unnatural sensations in some part of the body. Aura is warning of the attack and is produced by activation of epileptic discharge in the brain. In some before patient looses consciousness there is turning of the head from side to side and flexion of the upper limb. The onset of fit is characterized by sudden loss of consciousness, patient falling to ground, tonic contraction of the muscles and an epileptic cry produced by forcible expiration though the partly closed vocal cords.
While falling the patient may injure himself. Tonic convulsions of the two sides of body occur with head and eyes rotated to one side. Tonic phase is followed by clonic phase which lasts for variable period of time. There are alternate to and fro movements of the limbs, frothing of the mouth and increased salivation. During this phase patient may bite his/ her tongue and pass urine and stools.
Factors precipitating an epileptic fit
1. Physical fatigue
2. Mental stress
3. Hypoglycaemia
4. Flashes of bright light
5. Violent exercise
6, Alcohol
7. Infection
Clonic phase is followed by phase of unconsciousness lasting for a few minutes to half an hour. After recovery patient is confused, irritable and may go to sleep. When patient wakes he complains of severe headache. In post epileptic phase, an automatism may develop. Often there is amnesia. Sometimes patient may perform harmful or dangerous acts without being aware of them.
EEG shows a low voltage fast activity during the tonic phase while during clonic phase there are bursts of sharp waves associated with rhythmic muscular contractions. In attack free period EEG may show spike waves and occasionally sharp and low wave discharge.
Petit mal (Absence seizures)
This type of epilepsy is generally seen in children. Transient loss of consciousness without any convulsions is the main symptom. These attacks usually last for a few seconds to few minutes when all motor activity including speech stops. During the attack the child looks dazed and eyes have a staring look. Recovery takes place soon. In severe forms of attack, the patient looses consciousness and falls to the ground. There may be slight motor activity like fluttering of eyelids, chewing movements and rigidity.
EEG is abnormal and shows classic, “three per second”. Spike and wave discharges. Absence seizure may occur, many times during the day but in one third of these children the attacks disappear once they reach adolescence while one third may develop tonic-clonic form of seizures in addition to them.
Myoclonic seizures
These are sudden brisk brief single or repetitive muscular contractions involving a single limb or whole body. These are often violent and uncontrollable. They may occur alone or coexist with other forms of epilepsy. BEG shows polyspike and wave discharges or sharp and slow waves.
Atonic seizures
These usually occur in children and are characterized by sudden loss of consciousness and postural tone. There are no tonic muscular contractions and the child falls to the ground without any cause. These atonic seizures may be accompanied by other forms of seizures. BEG is abnormal and shows polypikes and slow wave.
Tonic seizures
This is a form of grand mal epilepsy where person adopts a sudden rigid posture of the limbs or body. There is deviation of the head and eyes. 1onic seizures are of short dration and are not followed by clonic seizures.
Infantile spasms (Hyposarrhythmia). These fits occur in infants below one year of age. There are brief synchronous jerky movements of the neck, body and limbs. These spasms often occur in children with a preexisting neurological disorder. Prognosis in these cases is not good because of neurological disorder. EEG is grossly abnormal and is characterized by a very disorganized background.
Partial or focal seizures
These seizures start with the discharge from an epileptiform focus in one area of the cortex. The seizure has a focal onset usually from either thumb, index finger or part of face. When a muscular contraction starts it involves the whole limb followed by generalized clonic movements and loss of consciousness.
Jacksonian epilepsy is the term applied to the partial seizures when contractions start from one part, involves that side and soon spreads, to the same side of the body. This has been called Jacksonian march (right thumb to right hand to right arm to right side of face) and may not be followed by loss of consciousness or involvement of opposite side. EEG consists of regularly occurring spike discharges in the area of cortex involved, Partial seizures may have behavioral disturbances (Sensory, autonomic and psychic symptoms). The seizure discharges occur in other areas of cortex like temporal, and frontal lobes.
Complex partial seizures (Temporal lobe or psychomotorepilepsy)
This is the form of epilepsy where the aura is either auditory, visual, olfactory or gustatory. There may be feeling of an unusual smell, an emotional feeling or hallucinations. These may
constitute the only form of seizure. There is temporary cessation of activity followed by lip smacking, chewing movements or the patient may walk about aimlessly or do some complicated movements. When the seizure ends there is amnesia. Recovery may take place ranging from minutes to hours. Most of these seizures originate from temporal lobe but may also arise from other parts of limbic system or orbital frontal regions. EEG may be normal or show spike discharge or focal slow activity during the seizure.
Reflex epilepsy
This is the form of epilepsy which is precipitated by some form of external stimuli like sudden loud noise (acoustico motor epilepsy) music (musciogenic epilepsy) or visual (photogenic epilepsy) or by certain stimuli of the skin.
Diagnosis. Epilepsy is diagnosed by clinical. History about the type of fit, its onset and accompanying symptoms like biting of tongue, passing of urine in clothes injury to the patient, loss of consciousness and post epileptic features. Primary epilepsy has to be differentiated from numerous organic causes responsible for causing secondary form of epilepsy.
Main differential diagnosis of primary seizures is from hysteria where generally convulsions are bizarre type, occur in the presence of people to draw attention and patient never injures himself or herself. The seizure does not follow any specific pattern and patient usually is a young female. Electroencephalogram may be helpful in diagnosing epilepsy when it is abnormal but a normal EEG does not exclude the diagnosis. CSF is normal in cases of epilepsy. CT scan is important in excluding any organic pathology in the brain.
Management of epilepsy
Patients of epilepsy must be warned about working at hazardous occupations like working at heights, near fire or machinery.
General hygiene must be maintained. Any factor which may precipitate an attack must be avoided.
Prescription of anti epileptic drugs
Antiepileptic drugs should be started only when one is convinced about the diagnosis. They are not curative but help in controlling seizures and give symptomatic relief. Most patients will be controlled by a single drug but if response is not adequate, another drug may be added. Aim should be to have seizure free period and once treatment has begun it has to be continued for sometime after seizure free period. Sudden withdrawal of the drugs is also not advisable. When another drug is to be substituted the first drug should be slowly withdrawn and the new drug introduced.
Drugs for tonic clonic seizures
Commonly used drugs are phenytoin, phenobarbitone, carbamezapine and valporate.
Phenytoin
It is an effective drug and useful in abolition of tonic clonic seizure. It is not a CNS depressant but some sedation occurs at therapeutic doses. It limits spread of seizure activity but has little effect on intellectual impairment. Dosage 100 rug two or three times a day. Maximum dose 600 mg per day. Side effects include gum hypertrophy rashes, hirsuitism, cerebellar and vestibular disturbances, ataxia,añd diplopia.
Phenobarbitone
It is also effective like phenytoin in abolishing generalized tonic clonic seizures. It causes sedation and a dulling of intellect. Drug is started with a dose of 60 rug per day in adults and 4 mg/kg in children. Main draw back of the drug is sedation which is dose dependent. In patients where control is achieved without producing excessive sedation it is an ideal anticonvulsant. Side effects include mental confusion Rashes impaired performance, dizziness and ataxia.
Sodium vaiproate
It is a broad-spectrum anticonvulsant and has little sedative effect or other central effects. Drug action is by potentiating the inhibitory transmitter GABA. It is the drug of choice in myoclonic epilepsy and primary generalized epilepsy. Starting dose is 600 rug once or in two divided doses daily and subsequent increase by 200 mg daily at three days interval till seizures are controlled. Side effects include anorexia, vomiting, drowsiness and tremors. Weight gain, rashes, fulminant hepatitis, thrombocytopenia and edema are other side effects.
Carbamazepine
It has both antiepileptic and psychotropic activity. It is used either as monotherapy or in combination with other antiepileptic drugs. It is indicated in the treatment of partial and generalized tonic clonic seizures.
Dosage initially 200 mg once or twice a day to be raised slowly to 400 rug two to three times daily. Side effects include loss of appetite, dryness of mouth, headache, dizziness, ataxia, disorders of visual accommodation. It may produce liver impairment so blood counts and liver functions should be monitored before and at 2 weeks intervals after starting the therapy.
Partial and complex partial seizures
Drugs which are effective for tonic clonic seizures are also effective in partial seizures and these are phenytoin and carbamazepine. Complex partial seizures may be difficult to control and require more than one drug.
In addition to a primary drug, methsuximide is employed.
Trimethadione is the drug of choice for petit mal epilepsy while ethosuximide and valproic acid are used for simple and atypical absence attacks.
Trimethadione (Tridione)
This drug is effective in the treatment of petit mal epilepsy or absence attacks. Initial dose is 0.3 gm three times a day. Maximum dose is 2.1 gm a day. Side effects include visual glare, sedation and dyspepsia. Blood changes include leucopenia, neutropenia, bone marrow depression and aplastic anaemia.
Ethosuximide
Its action is mainly on thalamocortical system which raises seizure threshold. It is used for patients with uncomplicated absence seizures or in other cases where petit mal co-exists with other forms of epilepsy. Dose 500 mg daily, slowly increasing thedose to 1.5 g/day. Side effects include gastrointestinal intolerance, mood changes, headache, drowsiness, rashes and blood dyscrasias.
Clonazepam
It is effective in treatment of typical and atypical absence infantile spasms, myoclonic jerks, temporal lobe epilepsy and tonic clonic seizures. It reduces excitability of neurones and also suppresses the spread of epileptiform discharges. Dose in adults initially 1.5 mg/day increased by 0.5 mg/day. Maximum dose 20 mg per day. Side effects include drowsiness, fatigue, ataxia, muscular incoordination, vertigo, nausea and vomiting.
In addition to the above drugs there are other drugs which are effective in those patients who are refractory to main drug therapy.
Clobazam
Its antiepileptic activity is related to its binding to one or more specific GABA receptors. It is most beneficial to patients with partial seizures and refractory epilepsy. Dosage single bed time dose starting 10-20 rug increasing upto 60mg. Side effects include sedation,dizziness, depression and aggression.
Gabapentin
It is of use in adult patients who have not obtained adequate control of partial seizures with the drugs already employed. So its main use is as an adjuvctive therapy in the treatment of partial seizures with secondary generalization. Dose 900-1800 mg per day in three divided doses to a maximum of 2400 mg perday. Side effects include fatigue, headache, nausea, dizziness, diplopia and ataxia.
Lamotrigine
It is effective in all types of epileptic seizures and is mainly used as an adjuvctive therapy in patient of simple partial seizures, complex partial seizures and secondary generalized tonic colonic seizures. Initial dose is 50 mg daily for two weeks followed by 100 mg/day given in two divided doses for two weeks. Thereafter dose should be increased by 100 mg every one to two weeks till the optimal response is obtained. Side effects include skin rashes, diplopia, dizziness, drowsiness, G.I. disturbances, irritability, agitation and confusion.
Use of anti epileptic drugs
While using antiepileptic drug, select the drug which is most effective in that type of seizure. Start with a small dose and depending on the patients response dose should be increased at 1-2 weeks interval till seizure control is achieved. Dose of the drug should be minimised to the lelvel when major side effects do not occur.
Since half-life of phenytoin and phenobarbitone is such that the total daily requirement can be given in a single dose at bed time. Sometimes even when maximal dose of an anti epileptic drug has been achieved and still seizure have not been controlled it is advisable to add another anti epileptic drug like phenobarbitone with phenytoin in grand Mal epilepsy.
Withdrawal of anti-epileptic drugs. When patient is free of seizures for two years or more it is desirable to gradually withdraw the antiepileptic drugs though there is always danger of recurrence of seizures. Following are the main indications for withdrawal of anti epileptic drugs:
1. Patient’s seizures are controlled and last seizure occurred two years or more back.
2. No neurological deficit.
3. It is a primary epilepsy and there is no structural abnormality in brain.
4. Number of seizures before start of therapy were not many.
Status epilepticus
It is the condition when recurrent seizures follow each other repeatedly at very short intervals and there is no regaining of consciousness in between. Status epilepticus is a serious medical emergency and carries high degree of morbidity and mortality. The longer its duration more difficult to control it. Status epilepticus must be controlled urgently. Steps to be taken are:
1. Maintain patency of respiratory airways and prevent aspiration of secretions.
2. Intravenous fluids to maintain nutrition. Monitor hydration and electrolytes.
3. Take measures to prevent injury to any part.
4. Oxygen inhalation.
5. Treatment must be instituted immediately. Injection Diazepam 10 mg intravenously immediately followed by intravenous infusion of 100 mg in one liter fluid during the next 24 hours. Other drugs employed are Injection Dilantin 0.5-1 g intravenously stat. This achieves optimal effect. Further control is maintained by Dilantin 200 rug alternating with phenobarbitone 60 mg given parenterally every 6 hourly.
6. A broad-spectrum antibiotic (Injection Ampicillin 500 mg I/V 6 hourly) to prevent infection. Failure to control status epilepticus is due to inadequate dosage of anti epileptic drugs as well as delay in starting treatment.
Surgical management of epilepsy
In some cases of epilepsy not responding to medical treatment, surgical removal of the epileptogenic focus has been carried out. This has been done in temporal lobe epilepsy after identifying the area. Procedures include cortical excision and hemispherectomy (amputation of anterior temporal lobe). Results are satisfactory only in small percentage of cases.
