Neurology

Dr. Bashar Shaker

Epilepsy

Epilepsy

Epilepsy

Seizure

Epileptic Seizure

Epilepsy

A condition in which an individual suffers from recurrent epileptic seizures which is not temporary. Epilepsy, a group of disorders characterized by recurrent seizures, is a common cause of episodic loss of consciousness.

Convulsion

The overt, major motor manifestations of a seizure (rhythmic jerking of the limbs ).

Aura

Subjective disturbance of perception that represents the start of certain seizures (actually represents a focal electrical disturbance at the start of the seizure).

Ictus or Ictal phase

Post-ictal phase



The period after the convulsion or actual seizure where the “brain is tired” and the individual is sleepy, confused, disoriented or experiences temporary neurological dysfunction .

Interictal

Between seizure


The recurrence rate after a single seizure is about 70 % within the first year , and most recurrent attacks occur within a month or two of the first. Furthur seizures are less likely if a trigger factor is definable and avoidable.

TRIGGER FACTORS

Sleep deprivation Alcohol (particularly withdrawal) Recreational drug misuse Physical and mental exhaustion Flickering lights, including TV and computer screens (primary generalised epilepsies only) Intercurrent infections and metabolic disturbances Uncommonly: loud noises, music, reading, hot baths


In some conditions, Epilepsy is the only feature underlying disease,while in others epilepsy is just one of the manifestation. The annual incidence of new cases of epilepsy after infancy is 20-70/100000. The lifetime risk of having a single seizure is about 5 %.while the prevalence of epilepsy in Europian countries is about 0.5 %. The prevalence in developing countries is up to five times higher.

Classification of epilepsy

Seizure type Physiology Anatomical site Pathological cause

Seizure type

Partial (simple or complex ) Partial with secondary generalization Absence Tonic-clonic Tonic Atonic Myoclonic

Physiology

Focal spikes /sharp waves Generalized spikes and waves

Anatomical site

Cortex : temporal frontal parietal occiital Generalized (diencephalon ) Multifocal

Pathological cause

Genetic Developmental Tumours Trauma Vascular

Infection Inflammation Metabolic Drugs(alcohol or toxins) Degenerative

Primary generalized epilepsy


The primary or idiopathic epilepsy make up 10 % of all epilepsies,including some 40 % of those with tonic clonic seizures. Onset is almost always in childhood or adolscence. No structural abnormality is present and there is often a substantial genetic predisposition. Some ,like childhood absence epilepsy are relatively uncommon,while others like juvenile myoclonic epilepsy are common(5-10 % of all patients with epilepsy)

PRIMARY GENERALISED EPILEPSIES

Box 26 -32

Partial Epilepsy


Partial seizures may arise from any disease of the cerebral cortex,congenital or acquired, and frequently, generalise. With the exception of few idiopathic partial epilepsies of benign outcome in childhood,the presence of partial seizures signifies the presence of focal cerebral pathology.

Causes of partial epilepsy

Idiopathic Benign Rolandic epilepsy of childhood Benign occipital epilepsy of childhood Focal structural lesions Genetic Tuberous sclerosis Neurofibromatosis von Hippel-Lindau disease Cerebral migration abnormalities Infantile hemiplegia Dysembryonic Cortical dysgenesis Sturge-Weber syndrome Mesial temporal sclerosis (associated with febrile convulsions Cerebrovascular disease Intracerebral haemorrhage Cerebral infarction Arteriovenous malformation Cavernous haemangioma Tumours (primary and secondary)Trauma (including neurosurgery) Infective Cerebral abscess (pyogenic) Toxoplasmosis

Secondary generalized epilepsy

Generalized epilepsy may arise from spread of partial seizures due to structural disease,or may be secondary to drugs or metabolic disorders. Epilepsy presenting in adult life is almost always secondary generalised,even if there is no clear history of a partial seizure before the onset of the major attack(an aura). The occurance of epilepsy in those over the age of 60 is frequently due to CVD.

CAUSES OF SECONDARY GENERALISED EPILEPSY

Genetic Inborn errors of metabolism ,Storage diseases Cerebral birth injury Hydrocephalus Cerebral anoxia Drugs Antibiotics: penicillin, isoniazid, metronidazole Antimalarials:chloroquine, mefloquine ,Ciclosporin Cardiac anti-arrhythmics: lidocaine; disopyramide Psychotropic agents: phenothiazines, tricyclic antidepressants, lithium Amphetamines (withdrawal( Alcohol (especially withdrawal( Toxins Heavy metals (lead, tin( , Organophosphates (sarin( Metabolic disease Hypocalcaemia , Hyponatraemia ,Hypomagnesaemia,Hypoglycaemia Renal failure ,Liver failure Infective Meningitis , Post-infectious encephalopathy Inflammatory Multiple sclerosis (uncommon( , SLE Diffuse degenerative diseases Alzheimer's disease (uncommonly( ,Creutzfeldt-Jakob disease (rarely)

Etiology and age of onset

Pathophysiology

Examples

Tonic clonic seizures


A tonic clonic seizure may be preceeded by a partial seizure (aura ) which can take many forms.However ,a history of such aura is commonly not obtained probably because the subsequent generalized seizure causes some retrograde amnesia for immediately preceding events.The patient then goes rigid and becomes unconscious, falling down heavily if standing and often sustaining injury..during this phase , respirstion is arrested and central cyanosis may occur.After a few moments the rigidity is periodically relaxed, producing clonic jerks.Soe patients don’t have clonic phase and the rigidity is replaced by a flaccid state of deep coma which can persist for many minutes.The patient then gradually regains consciousness , but is in a confused and disoriented state for half an hour or more after regaining consciousness.Full memory functions may not be recovered for some hours.

Tonic clonic seizures

During the attack urinary incontinence and tongue bitting may occur. A severe bitten bleeding tongue after an attack of loss of consciousness is pathognomonic of a generalized seizure. After generalized seizure the patient feels terrible , may have headache and often wants to sleep. Witnesses of a seizure are usually frightened by the event often believe the patient to be dying and may not give a clear account of the episode.this in itself can be a helpful diagnostic pointer since syncope seldom produce such fear in onlookers. Patients may have no tonic or clonic phase and may not become cyanosed or bite their tongues. However ,postictal confusion is useful in differentiating seizures from syncope

Absence seizure

They always start in childhood.The attacks may be mistaken for complex partial seizures but are shorter in duration ,they occur much more frequently (20 – 30 times per day ) and are not associated with post-ictal confusion.They do not cause loss of posture.

Atonic seizures

Sudden loss of postural tone with a collapse to the ground (“drop attack). If more restricted, can just involve nuchal and head muscles (head nod). Can often be intermixed with other seizure types (atypical absence, myoclonic).) Often causes injury.

Tonic &clonic fits

Tonic seizures are characterized by continuing muscle contraction that can lead to fixation of the limbs and axial musculature in flexion or extension and are a cause of drop attacks; the accompanying arrest of ventilatory movements leads to cyanosis. Consciousness is lost, and there is no clonic phase to these seizures. Clonic seizures are characterized by repetitive clonic jerking accompanied by loss of consciousness. There is no initial tonic component.

Myoclonic epilepsy

Complex partial seizures


Involve episodes of altered consciousness without the patient collapsing to the ground,especially if they arise from the temporal and less frequently the frontal lobes.Patients stop what they are doing and stare blankly,often blinking repetitively , making smacking movements of the lips,or displaying other automatisms, such as picking at their clothes.After a few minutes, consciousness returns but the patient may be muddled and feels drowsy for a period of up to an hour.Immediately before such an attack the patient may report alteration of mood,memory or perception (suh as undue familiarity- Dйjа vu – or unreality – Jamais vu ) , or complex hallucinations invlving sound , smell , taste , vision , emotion (fear , sexual arousal ) or visceral sensations (nausea , epigastric discomfort ).

Complex partial seizures

If these changes of memory or perception occur without subsequent alteration in awareness, the seizure is said to be simple partial seizure.

Complex partial seizures

If these seizures arise from the anterior parts of the temporal lobes,they may produce bizarre behaviour pattrens including limb posturing , sleep walking , or even ill –directed motor activities with incoherent screaming.These can sometimes be very difficult to distinguish from psychogenic attacks . however abruptness of onset and relative brevity may help point to frontal seizures , as may a tendency to occur out of sleep.

Partial motor seizures

Epileptic activity arisingin the precentral gyrus causes partial motor seizures in the contralteral face, arm,trunk or legs. Seizures are characterized by rhythmical jerking or sustained spasm of the affected parts. They may remain localized to one part or may spread to involve the whole side. Some attacks begin in one part of the body (e.g. mouth , thumb , great toe ) and sprea (march ) gradually to other parts of the body;this is known as Jacksonian seizure.

Partial motor seizures

Attacks vary in duration from a few seconds to several hours (epilepsia partialis continua). More prolonged episodes may be followed by paresis of the involved limb lasting for several hours after the seizure ceases (Todd palsy ).

Partial sensory seizures

Seizures arising in the sensory cortex cause unpleasent tingling or electric sensations in the contralateral face or limbs. Jacksonian march may also occur.

Versive seizures

A frontal epileptic focus may involve the frontal eye field causing forced deviation of the eyes and sometimes turning of the head to the opposite side. This type of attack often generalises to become a tonic clonic seizure.

Partial visual seizures

Occipital epileptic foci cause simple visual hallucinations such as balls of light or patterns of colour.formed visual hallucinations of faces or scenes arise ore anteriorly in the temporal lobes.

Investigations

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. Other investigations for infective, toxic and metabolic causes may be appropriate. An EEG performed immediately after a seizure may be more helpful in showing focal features than if performed after a delay. An EEG is often useful when more than one seizure has occurred, in order to establish the type of epilepsy and guide therapy.

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


The increasing sophistication of imaging techniques now allows the identification of the cause of epilepsy in an increasing number of patients, especially those with partial seizures. Investigations should be pursued more vigorously if the epilepsy is intractable to treatment.


The EEG may help to establish a diagnosis and characterize the type of epilepsy. Interictal records are abnormal in about 50 % (sharp waves or spikes ) of patients with definite epilepsy so that the EEG cannot be reliably used to exclude epilepsy.However epileptiform changes on the EEG are fairly specific for epilepsy (falsely positive in 1/1000). The sensitivity can be incresed to about 80 % prolonging recording time or including a period of natural or drug-induced sleep. Ambulatory EEG recording or video EEG monitoring may provide helpful information when attacks are frequent.

Primary generalized epilepsy

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

Management

Explain the nature and cause of seizures to patients and their relatives.Instruct relatives in the first aid management of major seizures.Epilepsy is common-affects 0.5 – 1%of the population.Good control of seizures is expected in 80 % of patients

First aid (by relatives and witnesses)

Move person away from danger (fire, water, machinery, furniture) After convulsions cease, turn into 'recovery' position (semi-prone) Ensure airway is clear Do NOT insert anything in mouth (tongue-biting occurs at seizure onset and cannot be prevented by observers) If convulsions continue for more than 5 minutes or recur without person regaining consciousness, summon urgent medical attention Person may be drowsy and confused for some 30-60 minutes and should not be left alone until fully recovered

Immediate management of seizures

Ensure airway is patent Give oxygen to offset cerebral hypoxia Give intravenous anticonvulsant (e.g. diazepam 10 mg) ONLY IF convulsions are continuous or repeated (if so, manage as for status epilepticus) Consider taking blood for anticonvulsant levels (if known epileptic) Investigate cause

Lifestyle modification

Patients should be made aware of the riskiness of any activity where loss of awareness would be dangerous, until good control of seizures has been established. This includes work or recreational activities involving exposure to heights, dangerous machinery, open fires or water. Only shallow baths or showers should be taken, and then with someone else in the house and with the bathroom door unlocked. Cycling should be discouraged until at least 6 months' freedom from seizures has been achieved. Activities requiring prolonged proximity to water (e.g. swimming, fishing or boating) should always be in the company of someone who is aware of the risk of a seizure and able to rescue the patient if necessary. In the UK and many other countries, legal restrictions regarding vehicle driving apply to patients with epilepsy, defined as more than one seizure over the age of 5 years. The patient should inform the licensing authorities about the onset of seizures. It is also wise for patients to notify their motor insurance company. Certain occupations, such as airline pilot, are not open to anyone who has ever had an epileptic seizure;

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,aheck 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

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.

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 .

Prognosis

Overall , generalized seizures are more readily controlled than partial seizures. The presence of structural lesion makes complete control of the epilepsy less likely. There is a 40 fold increased risk of sudden unexplained death in epilepsy (SUDEP) and patients may need to be made aware of this in order to help them rearrange their lifestyle and comply with treatment.

Epilepsy outcome after 20 years

50 % are seizure free, without drugs , for last 5 years. 20 % are seizure free for last 5 years but continue to take medication. 30 %continue to have seizures in spite of AEDs .

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

Non-epileptic attack disorder ('psychogenic attacks', 'pseudo-seizures')

Patients may present with attacks that superficially resemble epileptic seizures but which are caused by psychological phenomena and not associated with abnormal epileptic discharges in the brain. Such patients may present in apparent status epilepticus. People with epilepsy may have non-epileptic attacks as well, and this diagnosis should be considered if a patient fails to respond to anti-epileptic therapy, especially in the absence of a structural abnormality. Non-epileptic attacks may be quite difficult to distinguish from truly epileptic attacks. Clues pointing towards non-epileptic attacks include elaborate arching of the back in an attack, pelvic thrusting and/or wild flailing of limbs. Cyanosis and severe biting of the tongue are rare in non-epileptic attacks, but urinary incontinence can occur. The distinction between epileptic attacks originating in the frontal lobes and non-epileptic attacks may be especially difficult, and may require videotelemetry with prolonged EEG recordings. Non-epileptic attacks are three times more common in women than in men and have been associated with a history of sexual abuse in childhood. They are not necessarily associated with formal psychiatric illness. Treatment is often difficult and usually requires psychotherapy and/or counselling rather than drug therapy.

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