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Pharmacotherapeutics > Epilepsy I > Flashcards

Epilepsy I Flashcards

1
Q

Differences between seizures and epilepsy

A

Epilepsy is unprovoked, seizures can be provoked.
Epileptic seizures are spaced out for >24h apart, seizures could occur any time based on medical or extenuating conditions.
At least 2 seizures are required to be considered as epilepsy, the number of seizures for a general seizure does not matter.
Diagnosis of epilepsy syndrome vs none
Epilepsy causes:
- Genetic: fragile chromosome
- Structural: previous brain injury or structural abnormality
- Metabolic: mitochondrial disorder, GLUT1 deficiency
-Immune, infectious (HIV, TB, meningitis)
Seizure causes:
-electrolyte imbalances, toxic substances, brain injury, stroke, CNS infection

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2
Q

Pathophysiology of seizures and epilepsy

A

A. Hyperexcitability

  • imbalances between extracellular and intracellular substances (Na+, K+, Ca2+, Cl-)
  • excessive amount of excitatory neurotransmitters, few inhibitory neurotransmitters.

B. Hypersynchronization
- Hyper-excitable neuron will end up excessively exciting the entire group of neurons

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3
Q

Classification of epilepsy

A
  1. Focal onset
    - Originates from one hemisphere of the brain
  2. Generalized onset
    - Originates from both hemispheres of the brain
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4
Q

What is the ILAE 2017 Classification of Seizure Types (Expanded Version)?

A
  1. Where seizures begin in the brain
  2. Level of awareness during the seizure
    - Focal: can be aware, or impaired awareness
    - Generalized: usually unaware
  3. Other features of the seizure
    - Focal (motor onset): automatisms
    - Generalized onset (non-motor, absence): eyelid monoclonia
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5
Q

Factors that affect the clinical presentation of the symptoms

A
  1. Site of the focus
  2. Degree of “irritability” of the areas of the brain surrounding the focus
  3. Intensity of the impulse
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6
Q

Focal onset (without discognitive features) / simple partial

A
  1. Motor symptoms
    - Clonic movements (e.g. twitching and jerking)
    - Speech arrest
  2. Sensory
    - Feelings of numbness or tingling
    - Visual disturbances
    - Rising epigastric sensation
  3. Autonomic symptoms
    - Sweating, salivation or pallor
    - BP, HR
  4. Psychic (or somatosensory symptoms)
    - Flashbacks
    - Visual, auditory, olfactory, gustatory hallucinations
    - May experience fear
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7
Q

Clinical presentation of focal onset (With Dyscognitive Features)/Complex Partial)

A
  • Automatisms
  • Aura
  • Amnesia
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8
Q

Generalised onset of seizures:

  1. Tonic-clonic Grand Mal
  2. Absence Petit Mal
A
  1. GTC
    - begin with stiffening of the limbs, followed by jerking.
    - cyanosis
    - may stop breathing or cease breathing during the jerking.
    - incontinence may occur, along with the biting of the tongue.
    - patients may appear lethargic, confused or sleepy.
    - last for a few minutes to hours.
  2. Absence (petit mal)
    - comes and goes without warning
    - abrupt, lasts for a few seconds
    - no after effects
    - persistent staring
    - different from complex partial seizures in the sense that:
    » there are no auras
    » last seconds (rather than minutes
    » begin frequently and end abruptly
    » produce characteristics EEG pattern “3Hz spike waves”
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9
Q

Diagnosis of epilepsy

A
  1. Thorough history-taking is important
    - Description of onset, duration and characteristics of a seizure
    - Accurate history is best provided by the person who has observed the patients
    - Patient is useful in describing details of auras, preservation of consciousness and post-ictal state.
  2. Neurologic examination
  3. Concomitant medical conditions
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10
Q

Investigations for epilepsy

A
  1. Scalp EEG
    - Essential tool for diagnosis and classification of seizures and epileptic syndrome.
    - If diagnosis of seizures or epilepsy is considered, epileptiform discharges on EEG confirm diagnosis.
    - A normal EEG does not exclude possibility of epilepsy.
    - Limitations
    » Not all epileptic patients have an abnormal EEG.
    » EEG can be abnormal in normal persons (false positive)
  2. MRI with gadolinium
    - Ordered for: adult patient with first seizure, patients with focal neurologic difficulties, suggestion of focal onset seizure
    - Identify focal lesions:
    » Mesial temporal sclerosis
    » Focal cortical dysplasia
    » Remote injury (old stroke etc.)
    » Tremor
    » Vascular malformation
  3. Biochemical/toxicology
    » Rule out electrolyte abnormalities
    » Serum prolactin – considerable variability, not used routinely
    » Creatine kinase – raised after GTC
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11
Q

Risk after seizure recurrence

A
  • After a single, unprovoked seizure occurring, within the next 5 years, 30%. Risk is higher in the first 2 years.
  • Risk of second seizure is higher in the presence of:
    » Epileptiform abnormalities on EEG
    » Prior brain insult (e.g. stroke, brain trauma)
    » Structural abnormality in brain imaging
    » Nocturnal seizure
  • After 2 unprovoked seizures, risk of recurrence is 70%.
  • Treatment after first seizure:
    » Reduced risk of 2nd seizure
    » No effect on long-term prognosis
    » No evidence of higher risk of death, injuries or status epilepticus
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12
Q

Treatment goals for epilepsy

A
  • Absence of epileptic seizures
  • Absence of anti-epileptic drug (AED)-related side effects
  • Attainment of optimal QoL
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13
Q

Factors that influence AED choice

A
  • Seizure type, epilepsy syndrome
  • Co-medication and co-morbidity
    » Migraine: valproate; Depression/anxiety: levetiracetam with caution
    » Drug-drug interactions with HIV patients: immunosuppressants
    » Route of elimination: e.g. renal or liver impairment
    » Special population:
    »> Women with child-bearing potential: levetiracetam / lamotrigine
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14
Q

Pharmacological treatment: general principles

A
  1. Monotherapy is preferred
  2. Initiation of treatment
    - Start with low dose of 1st-line AED appropriate for the particular seizure type
    - If seizures continue but no side effects occur: gradually increase dose of AED
    » Diagnosis should be reviewed
    » Ensure that patient has received the appropriate drug for seizure type / epileptic syndrome
    » Check adherence
  3. Choice of seizure freedom after failure of first AED is low
    - Consider substitution if the first AED produces an adverse drug reaction or is not tolerated at low doses.
    - Consider combination therapy if the patient tolerates the first or second AED but with a suboptimal response.
  4. Drug resistant epilepsy:
    - Failure of adequate trials of two appropriately chosen, and used AEDs (can be monotherapy, or in combination) to achieved sustained seizure freedom.
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15
Q

Non-pharmacological methods (ketogenic diet)

A
  • Used in patients who cannot tolerate or have not responded well to AED treatment.
  • Low carbohydrates, high fat in diet
    » Induction of ketosis
    » Prevention of seizures (used mainly in young children – evidence)
    » Challenging to adhere long term
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16
Q

Non-pharmacological methods (vagus nerve stimulator)

A
  • Indicated for only intractable focal seizures
  • Electrodes attached around left branch of vagus nerve, as well as connected to programmable stimulator.
  • Stimulator delivers cyclical stimulation
  • During seizure, stimulation can be delivered by placing a magnet next to a subcutaneously-implanted stimulator.
17
Q

Non-pharmacological methods (responsive neurostimulator syndrome)

A

NeuroPace FDA

  • Comprises stimulator implanted in the skull under the scalp and leads implanted in the brain.
  • New adjunctive therapy: reduce the frequency of partial-onset seizures, in patients who have:
    » Undergone diagnostic testing that localized ≤ 2 epileptogenic foci.
    » Are refractory to ≥ 2 antiepileptic medications.
  1. Continuously monitors electrical activity in the brain, detects patient-specific patterns, and delivers brief pulses of stimulation when it detects activity that can lead to a seizure.
18
Q

Non-pharmacological methods (surgery)

A
  • May be useful in up to 90% of patients with selected forms of epilepsy to achieve improvement of symptoms or seizure-free status.
  • Usually advocated as early therapy for specific epileptic syndromes.
19
Q

What should one document in his seizure diary?

A 
o	Document seizure frequency and types 
o	How long they last 
o	Changes in AEDs 
o	AED side effects 
o	Seizure triggers 
*nowadays they have a smartphone seizure app
20
Q

What are some appropriate seizure first aid?

A

o Ease the person to the ground, turn the person gently on one side, clear the area, remove specs and loosen ties. Time the seizure. Call 911 if the seizure lasts longer than 5 minutes.
o Do not:
» Perform CPR or offer the person food or water (put anything in the person’s mouth)
» Attempt to hold the person down

21
Q

Describe psychosocial challenges in people with epilepsy

A
  1. Social stigma
    - Marriage
    - Starting a family
  2. Employment
    - PwE may require more time away from work for medical follow-up
    - Higher medical costs borne by employer
  3. Prohibited from driving, depending on country/state
  4. Caregiver burden

Pharmacotherapeutics (28 decks)

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