Epilepsy, Syncope, & the Unconscious Patient

Question 1

What determines a patient’s state of arousal?

Answer 1

• the central reticular formation, located throughout the brainstem and to the thalamus

Question 2

Which three things should you always consider in an unconscious patient?

Answer 2

• hypoglycemia
• opioid overdose
• upper airway obstruction (if the patient is cyanosed)

Question 3

What are the most common causes of unconsciousness?

Answer 3

• reflex syncope (such a postural hypotension)
• concussion
• CVAs (cerebrovascular accidents)

Question 4

What are the five general levels of consciousness?

Answer 4

• consciousness: awake
• cloudy consciousness: confused
• stupor: unconscious, awakened by shakes and shouts
• semicomatose: unconscious, responds to pain
• comatose: unconscious, unresponsive

Question 5

Which three breathing patterns should be considered in the unconscious patient?

Answer 5

• Cheyne-Stokes (periodic respiration): suggests cerebral dysfunction
• ataxic respiration (shallow, irregular): suggests brainstem lesion
• Kussmaul respiration (deep, rapid hyperventilation): suggests metabolic acidosis

Question 6

What are four major causes of unconsciousness?

Answer 6

• C.O.M.A.
• CO2 narcosis (respiratory failure)
• Overdose (alcohol, carbon monoxide, opioids, etc.)
• Metabolic (diabetes, uremia, hypothyroidism)
• Apoplexy (CVAs, also: trauma, meningitis, tumor)
• (apoplexy is bleeding into internal organs)

Question 7

What are blackouts? What are the major causes? Which is the most common?

Answer 7

• blackouts are episodes of L.O.C.
• major causes: epilepsy, reflex syncope, cardiac syncope, autonomic syncope, respiratory syncope, carotid sinus syncope, and migrainous syncope
• epilepsy is the most common cause

Question 8

How do we manage the unconscious patient?

Answer 8

• maintain airway and circulation
• “coma cocktail”: TONG (Thiamine, Oxygen, Naloxone, and Glucose); may lesson metabolic injury to the brain
• Naloxone is an opiate antagonist

Question 9

What is epilepsy? How common is it? What types of epilepsy are there?

Answer 9

• epilepsy is a condition of recurrent seizures (a seizure is the symptom of paroxysmal neuronal activity) due to an enduring predisposition to generate seizures (as opposed to symptomatic seizures as an acute result of infection, etc.)
• present in 1-2% of population, 4% in children
• seizures can be focal (L.O.C. may or may not occur) or generalized (L.O.C. occurs; absence, tonic-clonic, myoclonic, clonic, tonic, atonic)

Question 10

What are the major types of generalized epileptic seizures?

Answer 10

• absence: AKA “petit mal” seizures, common in kids, frequent, brief (less than 30 seconds) loss of awareness and behavioral arrest with immediate recovery of alertness; patient may not immediately recognize what happened
• tonic-clonic: AKA “grand mal” seizures, most severe type, rigid tonic phase (less than 1 minute) followed by a convulsive clonic phase (less than 2-3 minutes); cyanosis, tongue-biting, incontinence are common; postictal phase of confusion and amnesia
• atonic: “drop attacks,” sudden loss of lower limb tone results in sudden falls to the ground (patient usually immediately gets right back up)

Question 11

Following a tonic-clonic “grand mal” seizure, what may patients experience?

Answer 11

• status epilepticus: patient experiences at least one other seizure without recovering consciousness between episodes (total even is longer than 30 minutes)
• serial seizures: patient recovers consciousness and then experiences another seizure
• postepileptic automatism: patient experiences abnormal behavior immediately following the seizure with no memory of the event

Question 12

What investigations should be performed in a patient experiencing a seizure?

Answer 12

• MRI (the best imaging for epileptic seizures)
• if contraindicated, CT scan is OK as well
• (imaging is indicated in the patient’s 1st seizure, often it is not done for a future seizure if the cause seems to be the same)

Question 13

DDx of Focal Seizures and DDx of Generalized Seizures

Answer 13

• focal: transient ischemic attack (TIA), rage attack, panic attack
• generalized: syncope, cardiac disease, PNES (psychogenic nonepileptic seizure)

Question 14

How do we treat epilepsy? How efficient is drug therapy?

Answer 14

• anti-epileptic drugs (AEDs) are usually given to prevent future seizures
• these are usually continued for at least 2 years (if the patient is seizure free for these 2 years, they can decide if they want to continue or stop therapy)
• 50% will respond to the 1st drug, 20% to a 2nd drug, 30% will fail to respond (called pharmacoresistant epilepsy; 80% of kids fall into this category)
• other therapies: surgery (if seizures are very focal), chronic vagal nerve stimulation, ketogenic diet (high fat, low protein)

Question 15

Other than an epileptic disorder, what is another major cause of generalized tonic-clonic “grand mal” seizures?

Answer 15

• alcohol withdrawal!

Question 16

What is the most common cause of status epilepticus? What are some other causes? How do we treat it?

Answer 16

• poor compliance with anti-epileptic drug (AED) regimen
• others: alcohol withdrawal, intracranial infection/neoplasm, metabolic disorders, drug overdose
• (note that status epilepticus is a medical emergency)
• 1st line therapy is with benzodiazepines (clonazepam, diazepam)

Question 17

What is syncope?

Answer 17

• a sudden, transient loss of consciousness and postural tone due to reduced cerebral perfusion
• patients recover spontaneously, rapidly, and fully (vs. the slower recovery seen in the postictal phase of epilepsy)
• if a patient does not recover: comatose

Question 18

Which two general events can cause syncope?

Answer 18

• 1) dysfunction of the reticular activating system (RAS)
• 2) dysfunction of BOTH cerebral hemispheres
• (the dysfunction is due to inadequate cerebral perfusion)

Question 19

What is a focal seizure? If focal seizures are strong enough to generate a generalized seizure, which type of seizure will be generated?

Answer 19

• focal seizures are confined to one hemisphere (usually they arise in the medial temporal lobe), and exhibit a high degree of unique stereotypy for each patient (often includes an aura, as well)
• focal seizures (when generating a generalized seizure) will ALWAYS result in tonic-clonic “grand mal” seizures (this is called secondary generalization)

Question 20

What are the major risk factors for developing epilepsy? In patients with epilepsy, what lowers the seizure threshold?

Answer 20

• trauma, stroke, viral encephalitis, alcohol, Alzheimer’s, bacterial meningitis, heroin use, family Hx
• sleep deprivation, alcohol, and stress all lower the seizure threshold in epileptic patients (others: depression, menstruation, dehydration, infection, malnutrition, etc.)

Question 21

What are the major causes of epilepsy? Which is the most common

Answer 21

• cerebrovascular disease/structural/metabolic
• genetic
• cryptogenic (unknown); this is the most common

Question 22

What are two major genetic causes of epilepsy?

Answer 22

• A.D. nocturnal frontal lobe epilepsy: seizures in childhood
• Dravet syndrome: seizures in infancy (due to mutation in SCN1A gene encoding neuronal sodium channels)

Question 23

What are the major causes of syncope? Which is the most common?

Answer 23

• peripheral vascular syncope (the most common)
• cardiac/central vascular syncope (the most deadly potentially)
• cerebrovascular syncope (uncommon)

Question 24

Examples of Peripheral Vascular Syncope

Answer 24

• (these causes of syncope usually have an immediate prodrome of “feeling faint”)
• vasovagal: sudden onset of lowered pulse rate and vascular tone; this occurs with extreme emotion, sight of blood, etc.
• orthostatic hypotension: loss of compensation to maintain BP when going from sitting/lying down to standing
• cough, sneeze, and micturition syncopes

Question 25

Cardiac (Central Vascular) Syncope

Answer 25

- these are due to myocardial dysfunction (arrhythmia, CAD, etc.) and are therefore the most potentially deadly - these usually lack a noticeable prodrome, and patients experience a sudden syncope - investigating a syncope patient is mainly to make sure it was not cardiac syncope!

Question 26

Cerebrovacular Syncope

Answer 26

- this type of syncope is relatively rare (because hemorrhage rarely gets into the RAS and it is unlikely for a CVA to affect both hemispheres) - subarachnoid hemorrhage: massive headache with potential syncope - TIA/stroke involving the vertebrobasilar system (supplies brainstem)

Question 27

What examinations and investigations should be performed for a patient with syncope?

Answer 27

- examination: postural hypotension, pulse rate/rhythm, cardiac murmurs, abdotenderness - investigations: blood sugar and ECG (all other tests are indicated only if suspicion is justifiable)

Question 28

After a patient's 1st epileptic seizure, what is the risk for experiencing a 2nd?

Answer 28

- 40% chance of having a 2nd seizure once the 1st occurs

Question 29

What are the main general adverse affects of anti-epileptic drugs? What about for specific drugs?

Answer 29

- general: *somnolence and sedation*, cognitive impairment, ataxia (these promptly resolve after discontinuation); long-term use associated with *loss of bone density*; *teratogenic* - phenytoin: hirsutism, diplopia, acne, gum hypertrophy, rash/SJS - carbamazepine: hyponatremia, rash/SJS, weight-gain, diplopia, leukopenia - valproic acid: GI, weight-gain, tremor, alopecia, pancreatitis, thrombocytopenia, hepatotoxicity (rare, but fatal) - (SJS: Stevens-Johnson syndrome; a severe cutaneous reaction to a drug) - (valproate is least sedative, while the benzodiazepines are the most)

Question 30

Which patients are at an increased risk of developing Stevens-Johnson syndrome?

Answer 30

- Asians with HLA-B1502; screen all Asians before commencing carbamazpeine - *especially with carbamazepine*

Question 31

AEDs and Contraception and Pregnancy; AEDs and Chemo/Radiotherapy

Answer 31

- enzyme-inducing AEDs (carbamazepine and phenytoin) decrease the efficacy of the contraceptive pill by increasing estrogen clearance - contraceptive pill and pregnancy greatly reduce the serum level of lamotrigine (breakthrough seizures can result if the dose is not increased) - all AEDs are also teratogenic, doubling the risk of congenital malformations (3% chance to 6% chance); valproate is the most teratogenic of the drugs (3x-5x greater risk) - however, pregnant patients suffering from epilepsy ARE given AEDs as a seizure would cause potentially severe damage to the fetus; give folate to help reduce risk of malformations - many AEDs are excreted in breast milk (lamotrigine > levetiracetam > valproate/carbamazepine) - enzyme-inducing AEDs also interfere with chemotherapy and radiotherapy as they speed up the clearance of these drugs, making them less effective

Question 32

What is GEFS+ (Generalized Epilepsy w/ Febrile Seizures Plus)?

Answer 32

- GEFS+ occurs in patients who have a history of febrile seizures as a child and who later develop epileptic seizures

Question 33

On EEG, what characterizes a generalized absence seizure?

Answer 33

- 3Hz generalized spike-and-wave activity

Question 34

Major AEDs and Their MOAs

Answer 34

- block Na+ channels: carbamazepine, phenytoin, valproic acid, lamotrigine, topiramate - block Ca2+ channels: ethosuximide, gabapentin - stimulate GABA transmission: benzodiazepines, phenobarbital (these allosterically enhance GABA receptors), valproic acid (inhibits GABA degradation), topiramate - block glutamate receptors: levetiracetam - (blocking ion channels, blocking glutaminergic input, and increasing GABAergic input all prevent action potential generation and NT release!)

Question 35

Epilepsy and Driving

Answer 35

- after suffering a seizure, patients are not allowed to drive for at least 6 months (assuming they are seizure-free during this period) - in addition, patients are not allowed to drive for 4 months after stopping drug therapy - truck/bus drivers must be seizure-free for 10 years

Question 36

What are the major co-morbitidies of epilepsy? What is the mortality rate of epileptic patients?

Answer 36

- co-morbidities: depression and anxiety (suicide is not uncommon) - mortality rate is 2-3x greater than normal population, due to: - status epilepticus (20% mortality rate) - injuries during seizures, aspiration pneumonia - sudden death (occurs in 1.7%)

Question 37

What are the first line drugs used to manage tonic-clonic seizures? Absence seizures? Partial seizures? What about status epilepticus? What about for second line drugs?

Answer 37

- tonic-clonic: *phenytoin, carbamazepine, valproic acid*, phenobarbital, topiramate, lamotrigine, levetiracetam - absence: *ethosuximide*, valproic acid, lamotrigine - partial: *carbamazepine*, phenytoin, valproic acid, phenobarbital, and all others except for ethosuximide (which is ONLY used for absence seizures) - status epilepticus: *treat acute with benzodiazepines (diazepam, lorazepam) and then give phenytoin for prophylaxis/long-term management*