EPILEPSY

Epilepsy

Definitions


A seizure is an abnormal, unregulated electrical discharge that occurs within the brain's cortical gray matter and transiently interrupts normal brain function. A seizure typically causes altered awareness, abnormal sensations, focal involuntary movements, or convulsions (widespread violent involuntary contraction of voluntary muscles).


About 2% of adults have a seizure at some time during their life. Two thirds of these people never have another one.


a chronic brain disorder characterized by recurrent (≥ 2), unprovoked seizures (ie, not related to reversible stressors). A single seizure is not considered an epileptic seizure. Epilepsy is often idiopathic, but various brain disorders, such as malformations, strokes, and tumors, can cause symptomatic epilepsy.


epilepsy due to a known cause (eg, brain tumor, stroke). The seizures it causes are called symptomatic epileptic seizures. Such seizures are most common among neonates and the elderly.


are provoked by a temporary disorder or stressor (eg, metabolic disorders, CNS infections, cardiovascular disorders, drug toxicity or withdrawal, psychogenic disorders). In children, fever can provoke a seizure



symptoms that simulate seizures in patients with psychiatric disorders but that do not involve an abnormal electrical discharge in the brain.

Etiology

Seizures can result from either primary central nervous system dysfunction or an underlying metabolic derangement or systemic disease. This distinction is critical, since therapy must be directed at the underlying disorder as well as at seizure control. The age of the patient may help in establishing the cause of seizures .

AGE OF ONSET ;PROBABLE CAUSE

Neonatal Congenital maldevelopment, birthinjury, anoxia, metabolic disordershypocalcemia, hypoglycemia,vitamin B6 deficiency, biotinidase deficiency, phenylketonuria, and others)Infancy (1–6 months) As above; infantile spasms; West syndromeEarly childhood (6 months–3 years) Infantile spasms, febrile convulsions,birth injury and anoxia, infections,trauma, metabolic disorders, cortical dysgenesis, accidental drug poisoningChildhood (3–10 years ) Perinatal anoxia, injury at birth or later,infections, thrombosis of cerebral arteries or veins, metabolic disorders,cortical malformations, Lennox-Gastaut syndrome, “idiopathic,”probably inherited, epilepsy (Rolandic epilepsy)


Adolescence (10–18 years ) Idiopathic epilepsy, includinggenetically transmitted types, juvenilemyoclonic epilepsy, trauma, drugsEarly adulthood 18-25 years ) Idiopathic epilepsy, trauma, neoplasm,withdrawal from alcohol or othersedative drugsMiddle age (35–60 years ) Trauma, neoplasm, vascular disease,alcohol or other drug withdrawalLate life (over 60 years ) Vascular disease (usuallypostinfarction), tumor, abscess,degenerative disease, trauma

Etiology and age of onset

Classification

Classification


Infantile spasms Absence seizures Tonic-clonic seizures Tonic seizures Atonic seizures Myoclonic seizures (eg, in juvenile myoclonic epilepsy)

Classification

Classification


Simple (no impairment of consciousness) Complex (reduced but not complete loss of consciousness)

Classification

Partial seizures may evolve into a generalized seizure (called secondary generalization), which causes loss of consciousness. Secondary generalization occurs when a partial seizure spreads and activates the entire cerebrum bilaterally. Activation may occur so rapidly that the initial partial seizure is not clinically apparent or is very brief.

Symptoms and Signs

Seizures may be preceded by an aura. Auras are simple partial seizures that begin focally. Auras may consist of motor activity or sensory, autonomic, or psychic sensations (eg, paresthesias, a rising epigastric sensation, abnormal smells, a sensation of fear, a dйjа vu or jamais vu sensation). In jamais vu, a familiar place or experience feels very unfamiliar—the opposite of dйjа vu.


Most seizures end spontaneously in 1 to 2 min. Generalized seizures are often followed by a postictal state, characterized by deep sleep, headache, confusion, and muscle soreness; this state lasts from minutes to hours. Sometimes the postictal state includes Todd paralysis (a transient neurologic deficit, usually weakness, of the limb contralateral to the seizure focus).


Most patients appear neurologically normal between seizures, although high doses of the drugs used to treat seizure disorders, particularly anticonvulsants, can reduce alertness. Any progressive mental deterioration is usually related to the neurologic disorder that caused the seizures rather than to the seizures themselves. Rarely, seizures are unremitting, as in status epilepticus.

Partial seizures

Oral automatisms (involuntary chewing or lip smacking) Limb automatisms (eg, automatic purposeless movements of the hands) Utterance of unintelligible sounds without understanding what they say Resistance to assistance Tonic or dystonic posturing of the extremity contralateral to the seizure focus Head and eye deviation, usually in a direction contralateral to the seizure focus



Motor symptoms subside after 1 to 2 min, but confusion and disorientation may continue for another 1 or 2 min. Postictal amnesia is common.

Consciousness is usually lost, and motor function is abnormal from the onset.

may be primary or secondarily generalized. Primarily generalized seizures typically begin with an outcry; they continue with loss of consciousness and falling, followed by tonic contraction, then clonic (rapidly alternating contraction and relaxation) motion of muscles of the extremities, trunk, and head. Urinary and fecal incontinence, tongue biting, and frothing at the mouth sometimes occur. Seizures usually last 1 to 2 min. There is no aura. Secondarily generalized tonic-clonic seizures begin with a simple partial or complex partial seizure.


consist of 10- to 30-sec loss of consciousness with eyelid fluttering. Patients do not fall or convulse; they abruptly stop activity, then just as abruptly resume it, with no postictal symptoms or knowledge that a seizure has occurred. Absence seizures are genetic and occur predominantly in children.


Without treatment, such seizures are likely to occur many times a day. Seizures often occur when patients are sitting quietly, can be precipitated by hyperventilation, and rarely occur during exercise. Neurologic and cognitive examination results are usually normal.


occur most often in children, usually as part of Lennox-Gastaut syndrome. Atonic seizures are characterized by brief, complete loss of muscle tone and consciousness. Children fall or pitch to the ground, risking trauma, particularly head injury.


occur most often during sleep, usually in children. The cause is usually the Lennox-Gastaut syndrome. Tonic (sustained) contraction of axial muscles may begin abruptly or gradually, then spread to the proximal muscles of the limbs. Tonic seizures usually last 10 to 15 sec. In longer tonic seizures, a few, rapid clonic jerks may occur as the tonic phase ends.



brief, lightning-like jerks of a limb, several limbs, or the trunk. They may be repetitive, leading to a tonic-clonic seizure. The jerks may be bilateral or unilateral. Unlike other seizures with bilateral motor movements, consciousness is not lost unless the myoclonic seizure progresses into a generalized tonic-clonic seizure.

History

History should include information about the first and any subsequent seizures (eg, duration, frequency, sequential evolution, longest and shortest interval between seizures, aura, postictal state, precipitating factors).

All patients should be asked about risk factors for seizures:

Prior head trauma or CNS infection Known neurologic disorders Drug use or withdrawal, particularly of recreational drugs Alcohol withdrawal Nonadherence to anticonvulsants Family history of seizures or neurologic disorders


Patients should also be asked about rare triggers (eg, repetitive sounds, flashing lights, video games, touching certain parts of the body) and about sleep deprivation, which can lower the seizure threshold.

Physical examination

In patients who have lost consciousness, a bitten tongue, incontinence (eg, urine or feces in clothing), or prolonged confusion after loss of consciousness suggest seizure.


pseudoseizures can usually be distinguished from true seizures by clinical characteristics:


Pseudoseizures often last longer (several minutes or more). Postictal confusion tends to be absent. Typical tonic phase activity, followed by clonic phase, usually does not occur. The progression of muscular activity does not correspond to true seizure patterns (eg, jerks moving from one side to the other and back [nonphysiologic progression]), exaggerated pelvic thrusting). Intensity may wax and wane. Vital signs, including temperature, usually remain normal. Patients often actively resist passive eye opening.


Physical examination rarely indicates the cause when seizures are idiopathic but may provide clues when seizures are symptomatic

Neurocutaneous disorders (eg, neurofibromatosis, tuberous sclerosis

Structural abnormality (eg, tumor, stroke) Postictal paralysis
Focal neurologic defects (eg, asymmetry of reflexes or muscle strength)
Generalized neuromuscular irritability (eg, tremulousness, hyperreflexia)Drug toxicity (eg, sympathomimetics)Withdrawal syndromes (eg, of alcohol or sedatives)Certain metabolic disorders (eg, hypocalcemia, hypomagnesemia)
Generalized neuromuscular irritability (eg, tremulousness, hyperreflexia)
Increased intracranial pressure ( specificity is 80–90%*) Loss of spontaneous venous pulsations (noted during funduscopy)
Increased intracranial pressure
Papilledema
Meningitis Subarachnoid hemorrhage Meningoencephalitis
Fever and stiff neck
Possible Cause
Finding


Clinical Clues to the Causes of Symptomatic Seizures


EEG


However, normal EEG cannot exclude the diagnosis of epileptic seizures, which must be made clinically. EEG is less likely to detect abnormalities if seizures are infrequent. The initial EEG may detect an epileptiform abnormality in only 30 to 55% of patients with a known epileptic seizure disorder. Serial EEG may detect epileptiform abnormalities in up to 80 to 90% of such patients.

Primary generalized epilepsy

After a first seizure, cerebral imaging with CT or MRI is advisable, particularly in patients over 20 years of age, although the yield of structural lesions is low unless there are focal features to the seizure or there are focal signs.

Indications for imaging

Epilepsy starts after the age of 20 years Seizures have focal features clinically EEG shows a focal seizure source Control of seizures is difficult or deteriorates



Investigations


Epileptic nature of attacks? Ambulatory EEG Videotelemetry Type of epilepsy? Standard EEG Sleep EEG EEG with special electrodes (foramen ovale, subdural( Structural lesion? CT MRI Metabolic disorder? Urea and electrolytes Liver function tests Blood glucose Serum calcium, magnesium Inflammatory or infective disorder? Full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) Chest X-ray Serology for syphilis, HIV, collagen disease CSF examination

Prognosis

Treatment


Elimination of the cause if possibleAvoidance of or precautions during situations when loss of consciousness could be life threateningDrugs to control seizuresSurgery if ≥ 2 drugs in therapeutic doses do not control seizures


During a generalized tonic-clonic seizure, injury should be prevented by loosening clothing around the neck and placing a pillow under the head. Attempting to protect the tongue is futile and likely to damage the patient's teeth or the rescuer's fingers. Patients should be rolled onto their left side to prevent aspiration. These measures should be taught to the patient's family members and coworkers.


Because partial seizures can become generalized, patients are at risk of losing consciousness and thus should be advised to take certain precautions. Until seizures are controlled, patients should refrain from activities in which loss of consciousness could be life threatening (eg, driving, swimming, climbing, operating power tools, bathing in a bathtub).



Anticonvulsant therapy


Drug treatment should certainly be considered after more than one seizure has occurred and the patient agrees that seizure control is worthwhile; A wide range of anti-epilepsy drugs is available. The mode of action of these drugs is either to increase inhibitory neurotransmission in the brain or to alter neuronal sodium channels in a way to prevent abnormally rapid transmission of impulses. In 80 % ofpatients whose epilepsy is controlled,only a single drug is necessary. The combination of more than 2 drugs is seldom required. Dose regimens should be kept as simple as possible to promote compliance.

Anticonvulsant therapy

With few exceptions, There is no hard evidence indicating that one drug is superior to another. The first choice should be one of the first line drug with the more recently introduced drugs as second choice. Phenytoin and carbamazepine are not ideal for a young woman wishing to use oral contraceptives (inducer drugs). Carbamazepine, lamotrigene and sodium valproate are preferable to phenytoin because of the side effect profile of the latter and its complicated pharmacokinetics.

clonazepam

Sodium valproate
myoclonic
Sodium valproate
ethosuximide
absence
Lamotrigine topiramate
Sodium valproate
Primary GTCS
Lamotrigine Sodium valproate Levetiracetam topiramate
carbamazepine
Partial and/or secondary GTCS
Third line
Second line
First-line drug
Epilepsy type

Guidelines for choice of AEDs

Guidelines for anticonvulsant therapy


Start with one first-line drug. Start at a low dose , increase,dose until effective control of seizures is achieved or side effects develop (drug level may be helpful). Optimise compliance (use minimum number of doses per day ). If first drug fails,start second first-line drug while gradually withdrawing first. If second drug fails,start second-line drug in combination of preferred first-line drug at maximum tolerated dose (beware of interaction )

Guidelines for anticonvulsant therapy

If this combination fails replace second-line drug with alternative second-line drug. If this combination fails, check compliance and reconsider diagnosis (is there an occult structural or metabolic lesion or are seizures truly epileptic ?). If this combination fails consider alternative non-pharmacological treatment (surgery or VNS). Do not use more than 2 drugs in combination at any one time.

Monitoring therapy

With some drugs such as phenytoin and carbamazepine , occasional measurement of the blood level can be a guide whether the patient is on an appropriate dose and is complying with the medication ,but blood levels need to be interpreted carefully. The dose of AED in an individual patient should primarily be governed by the efficacy of seizure control and the development of side effects rather than blood levels alone. With sodium valproate, there is a poor relationship between blod level and anticonvulsant efficacy and so levels are only useful to assess compliance. Repeated measurement of blood levels is not generally useful and monitoring is of most value in dealing with suspected toxicity,the pharmacokinetic effect of pregnancy or in suspected non-compliance.

Withdrawing AEDs

After complete control of seizures for 2 – 4 years,withdrawal of medication may be considered.Childhood – onset epilepsy particularly classical absence seizures carries the best prognosis.Juvenile myoclonic epilepsy have a marked liability to recur after drug withdrawal.Seizures that begin in adult life particularly those with partial features are likely to recur especially if there is a structural lesion.

Withdrawing AEDs

Overall ,the overall recurrence rate is about 40 % . The EEG is generally a poor predictor of recurrence but if the record is still very abnormal,drug withdrawal is unwise. Withdrawal should be undertaken slowly , reducing the drug dose gradually over 6-12 months.

VNS THERAPY  Vagus Nerve Stimulation

VNS Therapy consists of electrical signals that are applied to the vagus nerve in the neck for transmission to the brain. The vagus nerve has proven to be a good way to communicate with the brain because: There are few if any pain fibers in the vagus nerve. Over 80% of the electrical signals applied to the vagus nerve in the neck are sent upwards to the brain. The surgical procedure to attach the lead to the vagus nerve does not involve the brain. It is not brain surgery.

THE KETOGENIC DIET

Very high in fat and low in carbohydrates and protein. 4 grams of fat for each gram of protein and carbohydrate consumed. Caloric intake is usually 75% of the recommended calorie intake A minimum of 1 gram of protein per kilogram of body weight per day is provided. Restricting fluid to 65 mL per kilogram of body weight per day

Pregnancy

With the exception of gabapentine, all AEDs is associated with fetal abnormalities such as cleft lip ,spina bifida and cardiac defects. The risk is greatest when treatment is given in the 1st trimester ,rising from a background risk of 2-4% to about 4-8% with one drug and to 15 % with two drugs or more. Folic acid (5 mg daily ) taken 2 months before conception may reduce the risk of some fetal abnormalities

Pregnancy

Seizures often become more frequent during pregnancy , especially during the 3rd trimester when plasma anticonvulsant level tend to fall. Monitoring of blood levels of anticonvulsants can be helpful with adjustment of drug doses. Occasionally in a well controlled patient , AEDs can be withdrawn before conception ,but if major seizures have occurred in the preceding year , this is unwise , since uncontrolled maternal seizures represent a significant risk to the fetus .

Contraception

Many AEDs, including carbamazepine,phenytoin,barbiturate , induce hepatic enzymes,accelerate metabolism of estrogen and cause breakthrough bleeding and contraceptive failure. Lamotrigine and oxcarbazepine have little interaction. Sodium valproate has no interaction with oral contraceptives. The safest policy is to use an alternative contraceptive method, but it is sometimes possible to overcome the problem by giving higher dose of estrogen.

Status epilepticus

Defined a seizure or a series of seizures lasting 30 minutes without the patient regaining awareness between attacks . Most commonly, this refers to recurrent tonic clonic seizures (major status) and is a life-threatening medical emergency. Partial motor status is obvious clinically, but complex partial status and absence status may be difficult to diagnose because the patient may merely present in a dazed, confused state. Status is never the presenting feature of idiopathic epilepsy but may be precipitated by abrupt withdrawal of anticonvulsant drugs, the presence of a major structural lesion or acute metabolic disturbance, and tends to be more common with frontal epileptic foci. It should be remembered that psychogenic or non-epileptic attacks commonly masquerade as 'status epilepticus', so electrophysiological confirmation of the seizures should be obtained as early as possible

Management of status epilepticus

Initial :Ensure airway is patent , give oxygen to prevent cerebral hypoxia and secure intravenous access. Draw blood for glucose , urea and electrolytes (including Ca and Mg), and liver function and store a sample for future analysis (e.g. drug misuse ).Give diazepam 10 mg i.v. or rectally or lorazepam 4 mg i.v. –repeat once only after 15 minutes.Transfer to intensive care area ,monitor neurological condition,blood pressure ,respiration and blood gases.intubating and ventilating patient if appropriate.

Management of status epilepticus

If seizure continue after 30 minutes Intravenous infusion (with cardiac monitoring) with one of: Phenytoin: i.v. infusion of 15 mg/kg at 50 mg/min Fosphenytoin: i.v. infusion of 15 mg/kg at 100 mg/min Phenobarbital: i.v. infusion of 10 mg/kg at 100 mg/min If seizures still continue after 30-60 mins Start treatment for refractory status with intubation and ventilation, and general anaesthesia using propofol or thiopental

Management of status epilepticus

Once status controlled Commence longer-term anticonvulsant medication with one of: Sodium valproate 10 mg/kg i.v. over 3-5 mins, then 800-2000 mg/day Phenytoin: give loading dose (if not already used as above) of 15 mg/kg, infuse at < 50 mg/min, then 300 mg/day Carbamazepine 400 mg by nasogastric tube, then 400-1200 mg/day Investigate cause

Differential Diagnosis of Seizures

Syncope Vasovagal syncope Cardiac arrhythmia Valvular heart disease Cardiac failure Orthostatic hypotension Psychological disorders Psychogenic seizure Hyperventilation Panic attack Metabolic disturbances Alcoholic blackouts Delirium tremens Hypoglycemia Hypoxia Psychoactive drugs (e.g., hallucinogens) Migraine Confusional migraine


Basilar migraine Transient ischemic attack (TIA) Basilar artery TIA Sleep disorders Narcolepsy/cataplexy Benign sleep myoclonus Movement disorders Tics Nonepileptic myoclonus Paroxysmal choreoathetosis Special considerations in children Breath-holding spells Migraine with recurrent abdominal pain and cyclic vomiting Benign paroxysmal vertigo Apnea Night terrors Sleepwalking

Never more than 15 s

30–60 s Duration of tonic or clonic movements
Seconds
Minutes
Duration of unconsciousness
Gradual over seconds
Often immediate
Transition to unconsciousness
Usually erect
Variable
Posture at onset
Tiredness, nausea, diaphoresis, tunneling of vision
None or aura (e.g., odd odor)
Premonitorysy mptoms
Emotional stress, Valsalva, orthostatic hypotension, cardiac etiologies
Usually none
Immediate precipitating factors
Syncope
Seizure
Features

Features That Distinguish Generalized Tonic-Clonic Seizure from Syncope

Rarely
Sometimes
Headache
Sometimes
Sometimes
Incontinence
Rarely
Sometimes
Biting of tongue
Sometimes
Often
Aching of muscles after event
5 min
Many minutes to hours
Disorientation and sleepiness after event
Pallor
Cyanosis, frothing at mouth
Facial appearance during event
Syncope
Seizure
Features

Features That Distinguish Generalized Tonic-Clonic Seizure from Syncope