Epilepsy Flashcards
EPILEPSY
group of disorders characterized by a clear tendency of recurrence of unprovoked seizures occurring at least 24 hours apart. It is stereotyped for individual patients.
Seizure
transient disturbance of cerebral function caused by an abnormal neuronal discharge, characterized by excessive, paroxysmal, oversynchronized discharges of cerebral neurons.
Fit
Involuntary paroxysmal muscular contractions associated with loss of consciousness.
Convulsions
Involuntary contractions of muscles occur with or without loss of consciousness.
Aura
the portion of the seizure that precedes loss of consciousness and the memory preserve. It is a simple partial seizure and it is stereotyped for individual patients. The aura is sometimes the sole manifestation of the epileptic discharge.
Todd’s paralysis
focal neurological deficit such as hemiparesis that resolves over 30 minutes to 36 hours, develops in the post-ictal state. It is a manifestation of an underlying focal brain lesion.
Status epilepticus
continuous seizures last beyond 5 minutes or repetitive seizures with full consciousness are not restored between successive episodes. More than half of patients who present with status epilepticus have no seizure history.
Epilepsy syndromes
An epilepsy syndrome was defined as a complex of signs and symptoms that define a
unique disorder in which epilepsy is a predominant feature, with distinctive EEG patterns,
or associated neurologic abnormalities.
The syndromes are often age-specific
The initiation phase is characterized by two concurrent events
(1) High-frequency bursts of action potentials
(2) hypersynchronization.
The pathophysiological classification of seizures:
A) A focal seizure originates from a paroxysmal discharge in a focal area of the cerebral
cortex (often the temporal lobe); the seizure may subsequently spread to the rest of the
brain (secondary generalization) via diencephalic activating pathways.
B) In genetic (primary) generalized epilepsies the abnormal electrical discharges originate
from the diencephalic activating system and spread simultaneously to all areas of the
cortex.
Etiologies of seizures can be classified into
idiopathic (in 2/3 of the patients)
symptomatic
cryptogenic
Symptomatic seizures divided into two types
provocative: nonstructural disorders
epileptogenic: structural brain disorders
Cryptogenic
seizures occurring without a known cause, but presumably not idiopathic because of associated neurologic or developmental abnormalities.
Epileptogenesis
transformation of a normal neuronal network into one that is chronically hyperexcitable. There is often a delay of months to years between an initial insult such as trauma, stroke, or infection and the first seizure.
Primary Neurologic Disorders
VITAMIN WITH NO M 🍎 1 . Idiopathic epilepsy for which no specific cause can be established. Idiopathic epilepsy usually begins between the ages of 5 and 25 years, with more than 75% of patients having their first seizure before age 18 years. Less frequently, idiopathic epilepsy begins in later life.
2. Stroke.
3. Head trauma.
4. Mass lesions.
5. Meningitis or encephalitis caused by bacterial, tuberculous, viral, fungal, or parasitic infections.
Systemic Disorders that cause seizures are
Hypo/er AWPA
A. Metabolic disorders: especially when it develops rapidly
1. Hypoglycemia
2. Hyponatremia
3. Hyperosmolar states, including hyperosmolar nonketotic hyperglycemia and hypernatremia.
4. Hypocalcemia can produce seizures with or without tetany.
5. Uremia
6. Hepatic encephalopathy.
7. Porphyria.
8. Drug overdose and Drug withdrawal
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9. Alcohol withdrawal, which usually resolves spontaneously. Alcohol withdrawal seizures occur within 48 hours after cessation or reduction of ethanol intake in 90% of cases and are characterized by brief bursts of one to six attacks that resolve within 12 hours. 10. Autoimmune epilepsies are commonly associated with intractable epilepsy with associated cognitive, behavioral, or movement disorders. Examples of immune etiologies include Rasmussen encephalitis, anti‐N‐methyl‐D‐aspartate (NMDA) receptor encephalitis, or voltage‐gated potassium channel complex encephalitis. These are typically associated with inflammatory changes in cerebrospinal (CSF) fluid or on neuroimaging. Specific autoantibodies can usually be found on examinations of serum or CSF. Autoimmune epilepsies can respond to immunosuppressant therapies including steroids, plasma exchange, and intravenous immunoglobulin. B. Hyperthermia Hyperthermia can result from infection, exposure (heat stroke), hypothalamic lesions, or drugs such as anticholinergics or neuroleptics (neuroleptic malignant syndrome); and inhalational anesthetics or neuromuscular blocking agents (malignant hyperthermia).
C. Hyperperfusion syndromes 1. Hypertensive encephalopathy. 2. Eclampsia.
Withdrawal of ABBA cause seizures
Alcohol
Benzodiazepines
Barbiturate
Anticonvulsant
Examples of immune etiologies of seizures
Rasmussen encephalitis, anti‐N‐methyl‐D‐aspartate (NMDA) receptor encephalitis, or voltage‐gated potassium channel complex encephalitis
Neuroleptic malignant syndrome
Confusion
ANS manifestation
Lead pipe regidity
Patho physiology of malignant hyperthermia
Uncontrolled release of calcium so excessive muscle contractions that produce heat
CLASSIFICATION OF THE TYPES OF SEIZURES
A. Generalized seizures: beginning in bilaterally distributed networks synchronously in both hemispheres from onset
1. Tonic-clonic (grand mal)
2. Absence (petit mal)
3. Myoclonic
4. Other types (tonic, clonic and atonic seizures)
Tonic and atonic are usually seen as part of epilepsy syndrome and are unlikely to be isolated. B. Partial /Focal seizures: involving brain networks confined to one hemisphere
1. Simple partial
2. Complex partial (focal with impaired awareness)( psychomotor)
3. Partial seizures with secondary generalization (Focal to bilateral
Tonic-clonic seizure)
C. Unknown onset
1. Motor
2. Non-motor
3. Unclassified (Due to inadequate information or inability to place in
other categories)
Tonic phase:
initial manifestations are loss of consciousness with tonic contractions of limb muscles for 10–30 seconds, producing an extension of the extremities and arching of the body in apparent opisthotonos. Tonic contraction of the muscles of respiration may produce an expiration-induced vocalization (cry or moan) and cyanosis, and contraction of masticatory muscles may cause tongue biting.
Clonic phase:
clonic (alternating muscle contraction and relaxation) phase of symmetric limb jerking that persists for an additional 30–60 seconds or longer. Ventilatory efforts return immediately after cessation of the tonic phase, and cyanosis clears. The mouth may froth with saliva. With time, the jerking becomes less frequent, until finally all movements cease and the muscles are flaccid. Sphincteric relaxation or detrusor muscle contraction may produce urinary incontinence
Recovery
patient regains consciousness, there is postictal confusion and often headache and vomiting. Full orientation commonly takes 10–30 minutes. Transient unilateral weakness (hemiparesis) in the postictal period (Todd’s paralysis) should be sought because such a finding suggests a focal brain lesion as the cause and calls for further investigation.
Absence (petit mal) seizures
Absence (petit mal)
3 Hz spike on EEG seizures always begin in childhood and rarely persist into adolescence. The spells are characterized by a brief loss of consciousness (for 5–10 seconds) without loss of postural tone. Subtle motor manifestations, such as eye blinking or a slight head-turning, are common. Full orientation immediately follows the cessation of the seizure. There may be as many as several hundred spells daily, leading to impaired school performance and social interactions, so that children may be mistakenly thought to be mentally retarded before the diagnosis of petit mal epilepsy is made. The spells are characteristically inducible by hyperventilation.
Myoclonic seizures
Myoclonic seizures are characterized by sudden, brief, shocklike contractions that may be localized to a few muscles or one or more extremities or that may have a more generalized distribution. Myoclonic jerks occur singly or in clusters of irregularly repeating jerks, typically within one to two hours after awakening.
Simple focal seizures
motor, sensory, psychic, or autonomic phenomena, depending on the anatomical localization of the cortical region affected. Motor symptoms
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include clonic movements of a single muscle group in a limb that may occur and may spread to involve neighboring regions of the motor cortex (jacksonian march). Autonomic symptoms may consist of pallor, flushing, sweating, pupillary dilatation. Psychic symptoms include forced thinking or affective disturbances (eg, fear, depression, and inappropriate sense of pleasure), hallucinations, or illusions. During simple partial seizures, consciousness is preserved unless secondary generalization occurs.
Complex partial seizures,
called psychomotor seizures are partial seizures in which consciousness is impaired. The seizure discharge usually arises from the temporal lobe or medial frontal lobe but can originate elsewhere. The symptoms take many forms but are usually stereotyped for the individual patient. Episodes may begin with an aura. Epigastric sensations are most common, but affective (fear), sensory such olfactory hallucination also may occurs , de ja vu and Jamais vu phenomenon then tha consciousness start to impaired
the patient may feel unfamiliar things/events as familiar
déjà vu phenomenon)
familiar things/events may be felt as unfamiliar
jamais vu phenomenon),
The motor manifestations of complex partial seizures are characterized by
coordinated involuntary motor activity, termed automatism, which takes the form of orobuccolingual, facial, or neck movements. Sitting up or standing and bilateral limb movements are less common. Secondary generalization may occur.
Febrile convulsions
during the first day of a febrile illness, during the rising phase of the temperature curve, and in the absence of central nervous system infection (meningitis or encephalitis).
Febrile seizures usually occur between age
3 months and 5 years of age and have a peak incidence between 18 and 24 months.
typical scenario of febrile seizure is
generalized, tonic-clonic seizure during a febrile illness in the setting of a common childhood infection.
A simple febrile seizure
Complex febrile seizures
simple febrile seizure is a single (not recur within 24 hours), isolated febrile episode, brief (duration <15 min), no neurologic deficit postictally, and symmetric in appearance. Complex febrile seizures are characterized by repeated seizure activity, duration >15 minutes, or have focal features. Simple febrile seizures are not associated with an increase in the risk of developing epilepsy, while complex febrile seizures have a risk.
The term reflex epilepsy is reserved for this small subgroup. Classified these seizures by their evocative stimuli into five types:
(1) Visual: Visually induced seizures are by far the commonest type of reflex epilepsy. The seizures are generalized and are most often triggered by the photic stimulation of television. (2) Auditory: sudden unexpected noise (startle), specific sounds, musical themes, and voices. (3) Somatosensory: either a brisk unexpected tap or sudden movement after sitting or lying still, or a prolonged tactile or thermal stimulus to a certain part of the body (4) Writing or reading. (5) Eating. The evoked seizure may be focal or generalized and may take the form of myoclonic jerks or an absence
INVESTIGATION
EEG
Csf
MRI and ct
Epileptic drug levels
idiopathic seizure go on to develop recurrent seizures and may be higher in patients with
age over 60 years, postictal Todd’s paralysis, epileptogenic factor, status epilepticus, electroencephalographic abnormalities, the seizure was during sleep, history of febrile seizures or a family history of epilepsy.
There are three key principles of management:
- Establish the diagnosis of epilepsy or epileptic syndrome before starting drug therapy.
- Choose the right drug for the seizure type. Absence seizures and myoclonic seizures
may be aggravated by some antiepileptics. - Evaluate one drug at a time. In most cases, seizures can be controlled with a single
drug. Therefore, beginning therapy with multiple drugs may expose patients to
increased drug toxicity without added therapeutic benefit.
Start low and go slow
applies to the initiation of treatment with most antiepileptic drugs. Increase the dose every 2 weeks. If the maximally tolerated dose (side-
effects develop) of a first-line antiepileptic drug is achieved and sustained for at least 6 to 8 weeks and seizures are still not controlled (seizures continue or side-effects develop), a second antiepileptic drug should be started. The first antiepileptic drug should remain in the same dose until the second antiepileptic drug builds up to a therapeutic level.
At that point, the first antiepileptic drug can be gradually tapered. If seizures recur during the period of tapering of the first drug, the patient should continue with combination therapy of both drugs.
If this combination fails, replace the second antiepileptic drug with an alternative antiepileptic drug. Use a minimum number of drugs in combination at any one time.
Therapy should be maintained for at least
Therapy should be maintained for at least 2 to 5 years after the diagnosis of epilepsy. When a patient is seizure-free for more than 2 years, the need for therapy should be re-
evaluated.
When antiepileptics are to be withdrawn,
one drug is eliminated at a time by tapering the dose slowly over 6 weeks. In case of seizure recurrence, prior medication should be reinstituted at the previously effective levels.
Starting antiepileptic drug treatment following a single seizure is recommended if recurrent seizures are likely
one epileptogenic factor EEG abnormal Nocturnal seizure age over 60 two other risk factor to develop recurrent seizures (history of febrile seizures,
and a family history of seizures) one risk factor and patient preference
Partial seizures with or without secondary generalisation
Carbamazepine
Oxcarbazipine
Grandmas epilepsy
Valproic acid
Petite mal
Ethosuximide
Myoclonic drugs
Leveiracetam
Second gen for petit mal and my clinic are ………. While for grandmas is ……… and for partials are
Valproic
Levetiracetem
Lamotrigen
Patient-specific factors include
- seizure type
- age
- gender 4. comorbidities 5. comedications
Drug-specific factors include
- the drug’s effectiveness and/or efficacy
- adverse effects
- drug interaction
- mechanism of action
pharmacoresistant epilepsy
“Failure of adequate trials of 2 tolerated, appropriately chosen and used antiepileptic drug schedules (alone and in combination and at the highest doses the patient can tolerate) to achieve sustained seizure freedom.”
Reasons for pseudoresistance
wrong diagnosis, wrong drug, wrong dose, or poor compliance.
evaluation for possible surgical therapy should be considered if ……
no treatable cause can be found, seizures are not due to progressive neurodegenerative disease, and medical treatment has been unsuccessful for at least 2 years,
most frequent surgical candidates.
complex partial seizures arising from a single temporal lobe
Status epilepticus is a medical emergency because it
lead to permanent brain damage from hyperpyrexia, circulatory collapse, or excitotoxic neuronal damage if untreated. Mortality risk about (20%).
Early management (at arrival) of status epilepticus
a. First entails attention to A, B, and C. For detection and treatment of the life-threatening condition. The patient is positioned to prevent aspiration of stomach contents. b. The laboratory studies should be ordered without delay: draw venous blood for serum glucose, calcium, and electrolytes, hepatic and renal function blood studies, complete blood count, ESR, and toxicology. c. Dextrose, 50 mL of 50% solution, and thiamine 100mg should be given intravenously.
use of i.v. antiepileptic drugs are generally preferred
Since ileus is a frequent complication of status epilepticus
staged approach to treatment of status epilepticus
Early (stage I): 20 minutes: Give lorazepam or diazepam i.v. Established (stage II): 20 - 60 minutes: If seizures continue, consider i.v. phenytoin or fosphenytoin or valproic acid or phenobarbital. Can use 2 drugs successively. Refractory (stage III): Refractory status epilepticus is continuous seizure activity not controlled by first-line and second-line antiepileptic drugs.
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If, despite these measures, status persists > 60 minutes, use midazolam or thiopental or propofol anesthesia with assisted ventilation. Typically, the patient is weaned off the third-line agent after 24 to 48 hours. If seizures recur, the patient is placed back into the third-line agent for 3 to 7 days with intermittent weaning off the medication to assess for seizure control. Patients who have prolonged status epilepticus have a significant risk for acute organ failure, polyneuropathy, sepsis, deep venous thrombosis/ pulmonary embolism, and other common intensive care unit complications. Of those with status epilepticus, 12% to 43% progress to refractory status epilepticus and 10% to 15% progress to super-refractory status epilepticus.
Super-refractory (stage IV) is defined as status epilepticus not controlled by third-line agents. Another definition posits that super-refractory status epilepticus exists if status epilepticus continues for 24 hours or longer after anesthesia is administered. Super- refractory status epilepticus was more common in children and the elderly. If seizure control fails or seizures recur after tapering the doses, use the same drugs for longer period or use one or more of the following alternative therapies: Methylprednisolone, Intravenous Immunoglobulin Therapy (IVIg), Plasma exchange, Ketogenic diet 4:1 (fat: carbohydrate and protein grams) and Neurosurgical resection of epileptogenic focus Up to 50% of patients with super-refractory status epilepticus die
Non-convulsive status epilepticus
any patient who had a generalized convulsive status epilepticus but consciousness does not improve within 20 minutes or normalized completely within 60 minutes after convulsions stop. benzodiazepines used commonly
Side Effects of Antiepileptic Drugs
carbamazepine and valproic acid has been associated with the highest incidence of hematological and hepatic toxicity
affect cognitive function
Cyp450 stimulant such barbiturate , phynitoin , carbanezipine while the inhibitors are valproate
The less drug interaction seen in levetiricem
Steven Johnson due to ethosuxicemide
Pseudoseizures can usually be distinguished both clinically and by the EEG findings.
- In patients with pseudoseizures resembling tonic-clonic attacks, there may be
warning and preparation before the attack - there is usually no tonic phase
- The clonic phase consists of wild beating movements during which the patient
rarely comes to harm or is incontinent. - In some instances, there are abnormal movements of all extremities without loss of
consciousness; in others, there is shouting during the apparent loss of
consciousness or goal-directed behavior. - There is no postictal confusion or abnormal clinical signs following the attack.
- The EEG recorded during the episode does not show organized seizure activity,
and postictal slowing does not occur.
Localising features of focal seizures
Temporal lobe : automatism with impaired awareness such lip smacking , chewing , swallowing or manual mevements such , fiddling , fumbling and deja vu , jamais vu emotional disturbance such anger panic terror , hallucination of sounds smell taste , delusional behiavors
Frontal
One can with motor features such Jacksonian march that mean spread of focal motor with retained awareness , dysphagea and foods paralysis
Parietal lobe presentation is that sensory numbness pain or motor
Occipital lobe visual phenomena such as spots lines flashes
DDX for seizures
Suncope : vasovagal , cardiac arrhythmia or valve dis or heart failure or orthostatic hypotension
Psychological disorders : psychogenic seizure , hyperventilation , panic attack
Metabolic dis ; alcohol, hypoglycaemia , hypoxia
Migraine
TIA of basilar artery
Sleep disorders ; narcolepsy , benign myoclonus
Movement disorders : non epileptic myoclonus
TICchorio athetoid
Na+ CHANNEL BLOCKERS
Carbamazepine Fosphenytoin Lamotrigine Lamotrigine Lamotrigine Lamotrigine
Ca²+ CHANNEL BLOCKERS
Ethosuximide +
Gabapentin
SV2A RECEPTOR BLOCKER
Levetiracetam
GABAA AGONISTS
Benzodiazepines Topiramate Phenobarbital
GABA REUPTAKE INHIBITOR
Tiagabine
GABA TRANSAMINASE INHIBITORS
Valproate Vigabatrin
Side effects of Ethosuximide are 1 (……….)
While for lamotrigen is 2 (………)
Phenytoin are 3 (…………) and topiremate 4 (………) and the valproites are 5 (………..)
1- EFGHIJ—Ethosuximide ✓
causes Fatigue, GI distress, (ab s enc e) seizures
Headache, Itchin g (a nd urticaria), SJS
2- SJS (must be titrated slowly ) hemophagocytic
of
lymphohistiocytosis (black
box warning)
3- PPHENY TOIN: cytochrome P-450 induction,
Pseudolymphoma, Hirsutism, Enlarged gums, Nystagmus,
Yellow-brown skin, Teratogenicity (fetal hydantoin
s y nd r ome), Osteopenia, Inhibited folate absorption,
Neuropathy. Rare: SJS, DRESS syndrome, drug-induced
lupus. Toxicity leads to
diplopia, ataxia, sedation.
4- Sedation, slow cognition,
kidney stones, skinny (weight
prophylaxis
lo s s), sight threatened
(glaucom a), speech (word-
inding)
5-
VALPPROaTTE Vomiting Alopecia Liver damage hepatotoxic Pancreatitis P-450 inhibition, Rash,
Obesity (weight gain),
Tremor, Teratogenesis
(neural tube defects).
Epigastric pain (GI distress
