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Block 8 week 5 > Clinical Epilepsy - Bloch > Flashcards

Clinical Epilepsy - Bloch Flashcards

1
Q

What is a seizure?

A

The clinical manifestation of an abnormal, excessive excitation and synchronization of a population of cortical neurons.

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2
Q

What is epilepsy?

A

Recurrent seizures (two or more) which are not provoked by systemic or acute neurologic insults.

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3
Q

Clinical seizures are characterized by what?

A

Subjective symptoms or objective signs.

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4
Q

Subclinical or electrographic seizures are what?

A

Only apparent on EEG.

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5
Q

What are the two major classifications of seizure?

A
  1. partial

2. generalized

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6
Q

List the types of partial seizure.

A
  1. Simple partial
  2. complex partial
  3. secondarily generalized
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7
Q

List the types of generalized seizure.

A
  1. absence
  2. myoclonic
  3. atonic
  4. tonic
  5. tonic-clonic
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8
Q

Partial seizures have onset….?

A

In part of the brain, they are focal.

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9
Q

What is the difference between simple partial and complex partial seizures?

A
  1. simple partial - consciousness is preserved, person is alert and can respond and can remember what happened during seizure
  2. complex partial - consciousness is altered or lost, ability to respond and remember is altered or lost
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10
Q

Partial onset seizures may progress to what?

A

Secondarily generalized seizures. These ultimately involve motor activity on both sides of the body.

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11
Q

Simple partial seizures can be further classified how?

A
  1. with somatosensory or special sensory symptoms
  2. with motor signs
  3. with autonomic symptoms or signs
  4. with psychic or experiential symptoms
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12
Q

What are some characteristics of complex partial seizures?

A 
  Impaired consciousness
  Clinical manifestations vary with site of origin and degree of spread
Presence and nature of aura
Automatisms
Other motor activity
  Duration typically < 2 minutes
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13
Q

What are automatisms?

A

Automatic movements occurring with complex partial seizure. These commonly involve the mouth, upper extremities or vocalizations.

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14
Q

Describe some characteristics of secondarily generalized seizures.

A

 Begins focally, with or without focal neurological symptoms
 Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases
 Typical duration 1-3 minutes
 Postictal confusion, somnolence, with or without transient focal deficit

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15
Q

What is Todd’s paralysis?

A

This is focal weakness on the side contralateral to seizure onset that can occur when partial seizures secondarily generalize.

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16
Q

The EEG findings in partial seizures are what?

A

Variable. They may be normal or show localized or lateralized abnormal rhythmic activity.

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17
Q

On EEG there may be a flat line at the end of the seizure. What causes this?

A

The line is flat because the neurons are no longer firing due to the depletion of neurotransmitter.

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18
Q

Generalized seizures affect what?

A

Both hemispheres from the beginning of the seizure.They produce loss of consciousness either briefly or for a longer period of time.

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19
Q

What are the main characteristics of Absence seizures?

A

 Brief staring spells (“petit mal”) with impairment of awareness
3-20 seconds
Sudden onset and sudden resolution
Often provoked by hyperventilation
Onset typically between 4 and 14 years of age (normal development and intelligence)
Often resolve by 18 years of age
 Normal development and intelligence
 EEG: Generalized 3 Hz spike-wave discharges

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20
Q

What is a key feature that allows distinguishing between absence seizure and partial complex seizures?

A

After an absence seizure there is no postictal period. The person is immediately alert and attentive after the seizure.

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21
Q

What is the EEG signature of absence epilepsy?

A

Presence of a 3 Hz spike-wave discharge - 3 spike waves every second.

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22
Q

What are the characteristics of atypical absence seizures?

A

 Brief staring spells with variably reduced responsiveness
5-30 seconds
Gradual (seconds) onset and resolution
Generally not provoked by hyperventilation
Onset typically after 6 years of age
 Often in children with global cognitive impairment
 EEG: Generalized slow spike-wave complexes (<2.5 Hz)
 Patients often also have Atonic (loss of muscle tone) and Tonic (brief shaking movements) seizures

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23
Q

Describe epileptic myoclonus.

A
  1. Brief (less than 1 second), shock-like jerk of a muscle or group of muscles
  2. Differentiate from benign, nonepileptic myoclonus (e.g., while falling asleep)
  3. EEG: Generalized 4-6 Hz polyspike-wave discharges
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24
Q

Myoclonus without seizure can occur - how can you tell if the muscle movement is a seizure or not?

A
  1. If not seizure related then EEG will be normal.
  2. Epileptic myoclonus usually causes bilateral, synchronous jerks most often affecting the neck, shoulders, upper arms, body, and upper legs.
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25
Q

Describe tonic seizures.

A
  1. Symmetric, tonic muscle contraction of
    extremities with tonic flexion of waist and neck
  2. Duration - 2-20 seconds.
  3. EEG – Sudden attenuation with generalized, low-voltage fast activity (most common) or generalized polyspike-wave.
  4. most common in people with other neurologic abnormalities in addition to epilepsy
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26
Q

Describe atonic seizures.

A
  1. Sudden loss of postural tone
    When severe often results in falls
    When milder produces head nods or jaw drops.
  2. Consciousness usually impaired
  3. Duration - usually seconds, rarely more than 1 minute
  4. EEG – sudden diffuse attenuation or generalized polyspike-wave
  5. most common in people with other neurologic abnormalities in addition to epilepsy
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27
Q

Describe generalized tonic-clonic seizures.

A
  1. Associated with loss of consciousness and post-ictal confusion/lethargy
  2. Duration 30-120 seconds
  3. Tonic phase:
    Stiffening and fall
    Often associated with ictal cry
  4. Clonic Phase:
    Rhythmic extremity jerking
  5. EEG – generalized polyspikes
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28
Q

What are some causes of seizures in infancy and childhood?

A
  1. prenatal or birth injury
  2. inborn error of metabolism
  3. congenital malformation
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29
Q

What are some causes of seizures in childhood and adolescence?

A
  1. idopathic/genetic syndrome
  2. CNS infection
  3. trauma
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30
Q

What are some causes of seizures in adolescents and young adults?

A
  1. head trauma

2. drug intoxication and withdrawal

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31
Q

What are some causes of seizures in older adults?

A
  1. stroke
  2. brain tumors
  3. acute metabolic disturbances
  4. neurodegenerative disorders
32
Q

What are some seizure precipitants?

A

 Metabolic and Electrolyte Imbalance
 Stimulant/other proconvulsant intoxication
 Sedative or ethanol withdrawal
 Sleep deprivation – depletes neurotransmitters
 Antiepileptic medication reduction or inadequate
AED treatment
 Hormonal variations – estrogen is eptileptigenic, progesterone is antiepileptigenic
 Stress
 Fever or systemic infection
 Concussion and/or closed head injury

33
Q

What are some metabolic and electrolyte imbalances that may be seizure precipitants?

A 
Low blood glucose
(or high glucose, esp. w/ hyperosmolar state)
Low sodium
Low calcium
Low magnesium
34
Q

What are some stimulants that may be seizure precipitants?

A 
Stimulants/Other Pro-convulsant Intoxication
  IV drug use
  Cocaine
  Ephedrine
  Other herbal remedies
  Medication reduction
35
Q

What are some medications that may lower the seizure threshold?

A 
1. Antidepressants: 
Bupropion
Tricyclics
2. Neuroleptics:
Phenothiazines
Clozapine
3. Theophylline
4. Isoniazid
5. Penicillins
6. Cyclosporin
7. Meperidine
36
Q

List the broad spectrum AED’s.

A 
Valproate
Felbamate
Lamotrigine
Topiramate
Zonisamide
Levetiracetam
Rufinamide
Vigabatrin
37
Q

What 4 broad spectrum (used to treat generalized and partial onset seizures) AED’s are used most frequently due to side effect profile and ease of use?

A
  1. valproic acid
  2. lamotrigine
  3. topiramate
  4. levetiracetam
38
Q

What is the MOA of valproic acid, lamotrigine and topiramate?

A

They are sodium channel blockers.

39
Q

What is the MOA of levetiracetam?

A

It is a GABA agonist.

40
Q

What are the narrow spectrum agents used to treat partial onset seizures?

A 
Phenytoin – used in ED cuz can give IV (phosphenytoin)
Carbamazepine – sodium channel blocker
Oxcarbazepine
Gabapentin
Pregabalin
Tiagabine
Lacosamide – sodium channel blocker
41
Q

What drug is used to exclusively to treat absence seizures?

A

Ethosuximide - a pure T channel calcium blocker. Valproic acid is also a T channel blocker.

42
Q

Narrow spectrum AED’s are not used to treat generalized seizures because?

A

They can potentially exacerbate some seizure types such as absence seizures. Exceptions are phenytoin and carbamazepine which are sometimes used for primary generalized tonic clonic seizures.

43
Q

Is mono therapy or polytherapy better for treating partial seizures?

A

Monotherapy.

44
Q

Describe mono therapy for partial oner seizures.

A
  1. Best evidence and FDA indication:
    Carbamazepine, Oxcarbazepine, Phenytoin, Topiramate
  2. Similar efficacy, likely better tolerated:
    Lamotrigine, Gabapentin, Levetiracetam
  3. Also shown to be effective:
    Valproate, Phenobarbital, Felbamate, Lacosamide
  4. Limited data but commonly used:
    Zonisamide, Pregabalin
45
Q

Levetiracetam should not be given to who?

A

Patients with bipolar disorder because it can cause irritability.

46
Q

Describe mono therapy for generalized tonic-clonic seizures.

A
  1. Best evidence and FDA Indication:
    Valproate, Topiramate
  2. Also shown to be effective:
    Zonisamide,Levetiracetam
    Phenytoin, Carbamazepine (may exacerbate absence and myoclonic sz )
    Lamotrigine (may exacerbate myoclonic sz of symptomatic generalized epilepsies)
47
Q

What is considered to be the gold standard in treating generalized seizures?

A

Valproic acid.

48
Q

What is one significant side effect of valproic acid?

A

It causes weight gain due to increased hunger.

49
Q

What is one significant side effect of topiramate?

A

It causes weight loss but it also causes decreased cognition.

50
Q

Valproic acid is contraindicated in what?

A

Pregnant women because it is a teratogen.

51
Q

Describe mono therapy for Absence seizures.

A
  1. Best evidence:
    Ethosuximide (limited spectrum, absence only)
    Valproate –contraindicated for pregnant women, is a teratogen
  2. Also shown to be effective:
    Lamotrigine
  3. May be considered as second-line:
    Zonisamide, Levetiracetam, Topiramate, Felbamate, Clonazepam
52
Q

Describe mono therapy for myoclonic seizure.

A
  1. Best evidence:
    Valproate
    Levetiracetam (FDA indication as adjunctive tx)
    Clonazepam (FDA indication)
  2. Possibly effective:
    Zonisamide, Topiramate
53
Q

What is Lennox-Gastaut Syndrome?

A

A seizure syndrome usually in children where they get 10-12 seizures a day of differing types. Because of the differing types of seizure, mono therapy is not effective.

54
Q

Describe thetherapy for Lennox-Gastaut syndrome.

A
  1. Best evidence/FDA indication*:
    Topiramate, Felbamate, Clonazepam, Lamotrigine, Rufinamide, Valproate
    * FDA approval is for adjunctive treatment for all except clonazepam
  2. Some evidence of efficacy:
    Zonisamide, Levetiracetam
55
Q

Which AEDs induce the metabolism of other drugs?

A
  1. carbamazepine
  2. phenytoin
  3. phenobarbital
  4. primidone
56
Q

Which AEDs inhibit metabolism of other drugs?

A
  1. valproate

2. felbamate

57
Q

Which AEDs are highly protein bound?

A

valproate, phenytoin, tiagabine
carbamazepine, oxcarbazepine
topiramate is moderately protein bound

These drugs may be affected (displaced from protein binding sites) by other drugs such as antibiotics, chemotherapeutic agents and antidepressants.

58
Q

Which AEDs decrease the efficacy of oral contraceptives?

A 
Phenytoin
Carbamazepine
Phenobarbital
Topiramate*
Oxcarbazepine*
Felbamate*

*at high doses

59
Q

What is the interaction between limotrigine and hormonal contraception?

A

Oral contraceptive pills can decrease lamotrigine levels by 50%
Lamotrigine levels will increase significantly during the placebo week, possibly leading to toxicity
Lamotrigine can decrease progesterone levels. Patients using Depo-provera may need shorter intervals between injections

60
Q

What are some common dose related adverse side effects of specific AEDs?

A

Dizziness , Fatigue , Ataxia, Diplopia - all AEDs

Irritability - levetiracetam

Word-finding difficulty - topiramate

Weight loss/anorexia -
topiramate, zonisamide, felbamate

Weight gain -valproate (also associated with polycystic ovarian syndrome )
carbamazepine, gabapentin, pregabalin

61
Q

What are some typically idiosyncratic adverse side effects of AEDs?

A

renal stones - topiramate, zonisamide
Anhydrosis, heat stroke - topiramate
Acute closed angle glaucoma - topiramate
Hyponatremia -carbamazepine, oxcarbazepine
Aplastic anemia - felbimate, zonisamide, valproate, carbamazepine
Hepatic Failure - valproate, felbamate, lamotrigine, phenobarbital
Peripheral vision loss - vigabatrin
Rash - phenytoin, lamotrigine, zonisamide, carbamazepine

62
Q

Rash is a very common side effect with AEDs. Describe some characteristics of this association.

A

15.9% patients experienced a rash attributed to an AED
Average rate of AED-related rash for a given AED 2.8%, 2.1% causing AED discontinuation.
Predictors of rash with AEDs
occurrence of another AED-rash
More common in Asian populations

63
Q

Rash is an important side effect of AED use because it might progress to what?

A
  1. Stevens Johnson syndrome

2. Toxic epidermal necrolysis

64
Q

What are the symptoms of toxic epidermal necrolysis?

A
  1. severe life threatening allergic reaction
  2. blisters and erosions of the skin, particularly palms/soles and mucous membranes
  3. fever and malaise
65
Q

Risk of toxic epidermal necrolysis with AEDs is associated with what?

A

rapid titration of lamotrigine especially in combination with valproate increases risk - because of drug drug interaction affecting metabolism

66
Q

Osteoperosis is a concern with use of which drugs?

A

Mostly worsened by the enzyme inducers: phenytoin, phenobarbital, primidone. Carbamazepine data equivocal.
Equivocal data with valproate, unavailable for other non- inducers.
Patients should take calcium 1000-1500/day; Vit D 400-4000/day

67
Q

Which two AEDs may lessen migraines?

A
  1. topiramate

2. valproate

68
Q

What is the association between depression and AED use?

A

Can be exacerbated by levetiracetam (and less so zonisamide)

Can be helped by lamotrigine and possibly gabapentin, pregabalin (and vagus nerve stimulator)

69
Q

Is depression is a major problem in epilepsy?

A

Yes. Suicide rate is 5X higher than that of general population.

70
Q

Has there been some talk of suicide risk with use of AED’s?

A

Yes, and clinicians should screen for depression/suicidality.

71
Q

What are some criterion that may be associated with discontinuing AEDs successfully?

A

 Seizure freedom for greater than 2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes
 Favorable factors:

Control achieved easily on one drug at low dose,
No previous unsuccessful attempts at withdrawal,
Normal neurologic exam and EEG, Primary generalized seizures except JME
“Benign” syndrome, cause of seizures not structural abnormality

72
Q

What are some non-drug therapies for reducing seizures?

A
  1. Adequate sleep
  2. Avoidance of alcohol, stimulants, etc.
  3. Avoidance of known precipitants – wellbutrin and tramedol can cause seizure
  4. Stress reduction — specific techniques
  5. diet - such as ketogenic diet, low glycemic index diet or mediterranean diet
73
Q

What are some criterion for patient selection for surgical therapy for seizures?

A
  1. Epilepsy syndrome not responsive to medical management
    Unacceptable seizure control despite maximum tolerated doses of 2-3 appropriate drugs as monotherapy
  2. Epilepsy syndrome amenable to surgical treatment – focal seizures
74
Q

Intermittent, programmed electrical stimulation of the left Vagus nerve has proven effective for seizure treatment. Describe some characteristics of this therapy.

A

 Adverse effects local, related to stimulus
(hoarseness, throat discomfort, dyspnea)
 Mechanism unknown
 Clinical trials show that 35% of patients have a 50% reduction in seizure frequency and 20% experience a 75% reduction after 18 months of therapy.
 May improve mood and allow AED reduction
 FDA approved for refractory partial onset seizures and refractory depression

75
Q

What is the definition of status epileptics?

A

More than 10 minutes of continuous seizure activity
or
Two or more sequential seizures without full recovery between seizures

76
Q

Status epileptics is a medical emergency. What are some adverse consequences of it?

A

Adverse consequences can include hypoxia, hypotension, acidosis, hyperthermia, rhabdomyolysis and neuronal injury.

Block 8 week 5 (4 decks)

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