Adult Seizure Disorders Flashcards
What is a seizure?
Episode of abnormally synchronized and high frequency firing of neurons resulting in abnormal behavior or experience
What is epilepsy?
Chronic brain disorder of various etiologies characterized by recurrent, unprovoked seizures.
Not all seizures are epileptic seizures. Only seizures that are recurrent and are clearly unprovoked can be considered to be epileptic in etiology.
What are some provoking factors that could precipitate a seizure (remember if there’s a provoking factor then its not epilepsy)?
fever, acute head trauma, metabolic disorders such as hypo and hyperglycemia, and electrolyte disturbances such as hyponatremia.
What are epilepsy syndromes?
Grouping of similar epileptic patients according to seizure type, EEG age of onset, prognosis and clinical signs
A well known example of an epileptic syndrome is the syndrome of Juvenile myoclonic epilepsy (JME).
How common are epileptic seizures?
The prevalence of epileptic seizures is roughly 0.5% world wide, and can be as high as 5% in countries where some communities have inadequate access to primary health care facilities.
The increase in patients over age 60 is partly the result of increased rate of Strokes in that age group. Strokes may predispose to epileptic seizures.
Note the incidence peaks in children and in the elderly.
What are some common causes of adult-onset epileptic seizures?
Cerebrovascular disease
Trauma
Tumors
Infections
Cerebral degeneration
Describe the ILAE classicifcation of epileptic seizures
ILAE is the International League Against Epilepsy.
Partial seizures are focal onset seizures that emanate from a specific cortical head region, and may sometimes spread to become secondarily generalized. Generalized seizures refer to Primarily Generalized seizures with no focal onset, thought to emanate from the brainstem structures; with spread to both hemispheres at the same time.
What is often a key to distinguishing between simple partial seizures, complex partial seizuresm, and partial seizures with secondary generalization?
The level of consciousness
Describe simple partial seizures
Signs/symptoms depend on the nidus (motor, somatosensory, autonomic, psychic)
Simple partial seizures emanating from the motor cortex may demonstrate a classic “Jacksonian march”, with focal seizure starting from the hand, for instance and “marching” up to involve the arm and face on the same side.
Somatosensory partial seizures have a focus in the sensory cortex and present with tingling and numbness of an extremity or side of face.
Autonomic seizures may present with rising epigastric sensations, nausea, while psychic seizure presentations may include sensations of fear, Déjà vu, or Jamais vu phenomena.
T or F. Consciousness is intact in a simple partial seizure
T. And an EEG may appear normal
What are Auras?
Auras are brief, simple partial seizures with no overt behavioral manifestations.
Describe the presentation of complex partial seizures
Impaired consciousness
Lasts about 1 min.
Blank stare
Oral / ipsilateral hand automatisms (Include chewing and lip-smacking movements.Typical hand automatisms are hand rubbing and picking movements)
Contralateral dystonic posturing
Amnesia for ictal event and confusion
Focal abnormality on routine EEG
Where do complex partial seizures arise from?
the temporal or frontal lobes
What causes the Contralateral dystonic posturing seen in complex partial seizures?
results from spread of seizure activity from the temporal lobe to the ipsilateral basal ganglia..
What are the types of primary generalized seizures
Absence (Petit Mal)
Tonic-Clonic
Clonic
Tonic
Myoclonic
Atonic
Describe the presentation of absence seizures
There is a brief (10-20sec) loss of consciousness, associated with a staring spell, subtle myoclonic movements, eyelid flutter, but no post-ictal confusion
No baseline neurologic deficits
How does an EEG for an absence seizure present?
may show generalized 3Hz spike-wave discharges
How does a tonic-clonic seizure (aka “Grand Mal” seizures) present?
Cry, loss of consciousness
Muscular rigidity (tonic)
Patient may fall
Rhythmic jerking (clonic) and/or Tongue-biting/injury common Bladder/bowel incontinence
Post-ictal confusion / sleep
How do myoclonic seizures present?
- Brief, shock-like muscle contractions that are sually bilaterally symmetrical: Head/ Upper extremities common
- Consciousness preserved
- May progress into tonic-clonic seizures
What causes myoclonic seizures
Precipitated by awakening or falling asleep
NOTE: Juvenile myoclonic epilepsy commonly presents with myoclonic seizures.
Describe the presentation of atonic seizures
- Impaired consciousness (Brief duration (few seconds))
- Loss of muscle tone
- Head drop
- Fall (Injury common)
How are seizures diagnosed?
Eyewitness description of seizures are very helpful.
Neurological examinations are usually normal in the patients with epileptic seizures.
Metabolic panels (CBC, CMP) help to detect abnormalities like hypoglycemia or hyponatremia which may have provoked seizure..
Serum levels of antiepileptic drugs (AED) that the patient may be taking helps to detect non-compliance or inadequate dosing of AED.
wInitial EEG detects an epileptiform discharge in __-__% of patients.
29-55. While Serial EEGs reveal epileptiform discharges in 80-90% of patients.
Repeat studies, with sleep deprivation and extended recording times, helps increase chances of detecting epileptiform discharges in patients with epilepsy
This EEG indicates that the seizure focus is in the left anterior temporal head region.
Sharp waves, spikes, and sharp-and slow wave discharges are examples of epileptiform abnormalities which are sometimes seen in the EEGs of patients with epileptic seizures.
This EEG demonstrates a bilateral burst of epileptiform spike and slow wave discharges (starting at red arrow and continuing to the right). which is typical for primary generalized seizures such as in Juvenile myoclonic epilepsy. The discharge occurs simultaneously and symmetrically in both hemispheres.
Bilateral and symmetrical spike and wave activity occurring at a frequency of 3 per second (3 Hz) is classic for petit mal absence seizure, a primary generalized seizure type..
Recent-onset epilepsy in adults requires imaging sequences, including gadolinium-DPTA enhanced sequences to find primary or secondary tumors, infection or inflammation
Coronal MRI showing an atrophic and sclerotic hippocampus (arrow).
What is Video-EEG monitoring?
Simultaneous recording of EEG and seizure.
Useful in differentiating epileptic seizures from non-epileptic seizures.
Useful for characterizing seizure type.
Essential for pre-surgical localization of the seizure focus.
What causes seizures?
GABA activates GABAa receptors that mediate fast synaptic inhibition (IPSP) by permitting rapid influx of Cl ions (anions), resulting in hyperpolarization.
Glutamate activates 3 classes of ion channels (AMPA, Kainate, NMDA) that mediate fast synaptic excitation by permitting a rapid influx of NA and Ca ions (cations).
In most neuronal circuits, GABAergic inhibition exerts a powerful suppression of excitability. This inhibition is overcome during the development of a focal seizure.
What are the goals of antiepileptic drug (AED) therapy?
Two types of remission:
–Medical Remission: Seizure free without side effects on 1 or 2 AEDs
–Disease Remission: Seizure free off all AEDs
The major goal of AED therapy is to achieve medical remission.
Surgical therapy in well-selected cases may result in disease remission.
What factors influence AED selection?
- Efficacy for specific seizure types or epilepsy syndromes
- Efficacy for co-morbid conditions
- Interactions with other drugs
- Ease of introduction, follow-up
- Drug safety
- Cost
What is the drug of choice for primary generalized seizures and syndromes such as JME?
Depakote
What AEDs are indicated only for partial onset seizures with or without secondary generalization?
Some antiepileptic drugs (such as Trileptal, Lyrica and carbamazepine)
Co-morbid conditions to consider iwhen choosing an AED include:
obesity, Migraines, Depression and Bipolar disorder.
What AEDs can result in weight loss as a side effect?
Topamax and Zonegran
Topamax is FDA-approved for Migraine prophylaxis, Lamictal is effective in depression and mood disorders while Depakote is effective in Bipolar disorder.
Enzyme-inducing AEDs may interfere with the metabolism of several drugs, including Coumadin, statins and HIV medications.
How does phenobarbital work?
enhances activity of GABA receptor, depresses glutamate activity, reduces sodium, potassium conductance
How does phenytoin work?
Produces blockade of sodium channels and inhibitory action on calcium and chloride conductance
How does Carbamazepine work?
Produces blockade of neuronal sodium channel conductance
How does Valproate work?
affects GABA glutamatergic activity and reduce threshold of calcium and potassium conductance
How does Ethosuximide work?
Inhibits calcium T-channel conductance
How does Lamotrigine work?
Blockage of voltage-dependent sodium conductance
How does Oxcarbazepine work?
Sodium channel blocker
How does Topiramate work?
NA channel blocker, and enhancement of GABA mediated choride influx
How does Zomisamide work?
Blockade of sodium, potassium and calcium channels, inhibits glutamate excitation.
How does Gabapentin work?
Modulation of N-type Ca channels
What AEDs are effective in partial and tonic-clonic seizures?
Valproate, Phenytoin, Carbamazepine and phenobarbital
What AEDs are effective for absence seizures (petit mal)?
Ethosuximide and Valproate
What drugs are used for partial seizures?
Gabapentin, and Oxcarbazepine
What AEDs are broad spectrum for partial and generalized seizures?
Lamotrigine, Topiramate, Levetiracetam and Zonisamide
What are the AEs of Carbamazepine?
Aplastic anemia, hepatotoxicity, Stevens Johnson syndrome (SJS), Lupus –like syndrome.
What are the AEs of Ethosuximide?
Bone marrow depression, hepatotoxicity
What are the AEs of Lamotrigine?
SJS or toxic epidermal necrolysis
What are the AEs of Phenytoin?
Aplastic anemia, hepatic failure, SJS, lupus
What are the AEs of Oxcarbazepine?
Hyponatremia, rash
What are the AEs of Topiramate and Zonisamide?
renal calculi, hypohidrosis
What are the AEs of Phenobarbital?
Hepatotoxicity, connective tissue disorder, SJS
What are the AEs of Valproate?
Hepatotoxicity, hyperammonemia, leukopenia, thrombocytopenia, pancreatitis
What AEDs are CYP450 inducers?
Carbamazepine
Phenobarbital
Phenytoin
Oxcarbazepine (minimal)
Topiramate (minimal)
What might be the effect of using CYP450 inducing AEDs?
lead to failure of oral contraceptives
cause osteopenia, osteoporosis, fractures
increase metabolism of androgens and estrogens
Note: The older AEDs cause malformations in 4-8% of children (twice the normal rate) with risk increasing with higher AED dose and polytherapy.
The older AEDs are category D drugs, while the newer AEDs are category C
How common is medical remission from seizures in newly diagnosed pts?
Seizure free for 2 or more years
- 47% with 1st AED used in monotherapy
- 14% with 2nd AED used in monotherapy
- 4% with 2 AEDs used
Thus, Most patients who respond to AEDs do so with the first AED used in monotherapy.
What is intractable epilepsy?
Patients with intractable epilepsy have disabling seizures recurring despite optimized therapy.
- Disabling seizures –seizures causing impaired quality of life, limited educational or occupational opportunities, physical injuries, or social compromise.
- Optimized treatment –AED treatment is optimum if patient is on at least 2 AEDs, at maximally tolerated dose and with good compliance.
How common is intractable epilepsy?
Seizures are effectively controlled with AEDs in 70-80% of patients.
20-30% are not seizure-controlled using currently available AEDs and are therefore intractable.
What are some therapy options for refractory epilepsy?
- Polytherapy with antiepileptic drugs
- Vagus nerve stimulator
- Epilepsy surgery
How does vagus nerve stimulation work?
An electrical pulse generator is implanted subQ in the chest, and a lead is attached to the left vagus nerve (MOA unknown, but about 40-50% have 50+% seizure reduction, but rarely seizure free)
What are some surgery options for epilepsy?
- Temporal lobectomy
- Lesionectomy
- Corticectomy
- Corpus callosotomy
- Multiple subpial transections
- Hemispherectomy
What is generalized convulsive status epilepticus?
A continuous, generalized, convulsive seizure lasting more than 5 minutes or two or more sequential seizures occurring without full recovery of consciousness.
Non-convulsive status epilepticus is an EEG diagnosis.
How is GCSE managed?
- ABCs, IV access
- Labs, brief history and exam
- 50mls of 50% glucose, thiamine
- Ativan 0.1-0.15mg/kg IV
- Order bedside EEG monitoring
- Start Dilantin 20 mg/kg bolus by slow IV. May give additional doses to total of 30 mg/kg.
What is ‘refractory’ GCSE ?
GCSE is refractory if patient fails to respond to lorazepam.
How is refractory GCSE tx?
If convulsive seizures persist, consider intubation.
Start continuous EEG monitoring
Midazolam 0.2mg /Kg bolus, then 0.05 -0.5 mg/kg/hr
Propofol 1-2mg/kg bolus, then 2-10 mg/kg/hr
Pentobarbital 8 mg /Kg
