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Chamberlain

What are the Basic Seizure the clinical manifestation of an abnormal and excessive excitation and synchronization
Mechanisms which of a population of cortical neurons
Underlying Seizures Epilepsy a tendency toward RECURRENT seizures unprovoked by any systemic or acute neurologic in
and Epilepsy sults
Eleptogenesis sequence of events that converts a normal neuronal network into a hyperexcitable network
What is the Epilepsy = 2+ unprovoked seizures
Epidemiology of Affects 5‐10% of general population
Epilepsy? - ~1 in 12 persons
2+ million in US have epilepsy
50% of cases of epilepsy start before 18 125,000 new cases of epilepsy in US each year
What is the
Recurrence Risk of
Epilepsy?
What are Tumor
Epileptogenic Factors? Vascular (ischemica or hemorrhagic)
Arteriovenous malformation
Trauma (depressed fracture, penetrating wound)
Infection (Abscess, encephalitis)
Congenital and Hereditary diseases
What are the causes The normal brain is capable of having a seizure under the appropriate circumstances, and there are differences b
of Seizures and etween individuals in the susceptibility or threshold for seizures.
Epilepsy? There are a variety of conditions that have an extremely high likelihood of resulting in a chronic seizure disorder.
Seizures are episodic.
What are Episodic Metabolic, Electrolyte, Biochemical, Inborn Errors of Metabolism
Epilepsy Factors? Anoxia
Hypoglycemia
Drugs
Drug Withdrawal
Alcohol withdrawal
What are the causes Unknown (genetic or biochemical disposition
of Idiopathic Epilepsy?
What are the Age-
Related Causes of Neonates (<1 Perinatal hypoxia or ischemia
Seizures? month) Intracranial hemorrhage and trauma
Acute CNS infection
Metabolic disturbances
Drug withdrawal
Developmental disorders
Genetic
Infants and Children Febrile seizures
(>1 and <12yr) Genetic
CNS infection
Developmental disorder
Trauma
Idiopathic
Adolescents (12- Trauma
18yr) Genetic
Infection
Brain tumor
Illicit drugs
Idiopathic
Young Adult (18- Trauma
35yr) Alcohol withdrawal
Illicit drugs
Brain tumor
Idiopathic
Older adult (>35 yr) Cerebrovascular disease
Brain tumor
Alcohol withdrawal
Metabolic disorders
Degenerative CNS diseases (AD)
Idiopathic
Febrile Seizures usually in the rising phase of the temperature (T) curve (first day of T spike) in an
infection [otitis media, respiratory infection, gastroenteritis, etc.]
Usually occur between 3 mos. & 5 yrs, with a peak incidence between 18 and 24 mos
What are the drug- Tricyclic Antidepressants – 29%
induced seizures by Cocaine/Stimulants- 29%
class Diphenhydramine/Antihistamines- 7%
Theophylline-5%
Isoniazid – 5%
Misc. (Including Bupropion and Tramadol)- 25%
Drugs and Seizures? Insulin and oral hypoglycemics
Disopyramide, other antiarrhythmics
Prednisone
D5W or hypertonic salines
CNS excitatory agents
- Pharmacologic kindling
Theophylline
- Inhibits adenosine‐2 receptors, decreasing cerebral blood flow
NSAIDs
- Uncouples oxidative phosphorylatin, causing a decrease in ATP
- leads to tissue glycolysis with an increased demand for peripheral glucose
shifting away from the brain
Flumazenil and Flumanezil: Specific benzodiazepine antagonis
Seizures? - reverses sedative effects of benzodiazepines (overdose, etc.) within minutes

Initial literature on it in 1992 (n=1700) showed mild to moderate adverse events

10-15% risk of seizures when used for benzodiazepine reversal


Why do seizures Neurons need to overreact, recruit normal neurons to propagate the action potential, and have failure of either i
occur? nhibitory mechanisms or over‐stimulation of excitatory mechanisms to produce a seizure

Too much glutamate or aspartate = increased seizure potential


- Glutamate, aspartate, acetylcholine, norepinephrine = major excitatory enhancers

Not enough GABA = increased seizure potential


- GABA & dopamine = excitatory inhibitors
What does Normal Also depends on adequate supply of:
Neuronal Activity Glucose
depend on? Oxygen Without adequate glucose or oxygen, CO2 builds up
Na+ and K+
Cl‐
Calcium The more prolonged a seizure, the more likely the
Amino acids brain is to suffer damage
Systemic pH
Patients in metabolic acidosis tend to have more
profound cases
How do we diagnose Patient History Frequency & duration of episodes
Seizures? Precipitating factors (sleep, menses)
Time (of occurrence & length) Aura (y/n?)
Eyewitness of ictal activity Postictal state
FHx- family history
PMHx & developmental hx – patient medical history
SHx – surgical history
Medication Hx / adherence- medication history
Physical/ Neuro Exam
Labs Urinary analysis (UA) Complete blood count (CBC)
Fasting blood glucose (FBG)
Chem10 and Arterial blood gas (ABG)
Cerebral spinal fluid (CSF) evaluation
Electroencephalogram (EEG)
CT scan / MRI Activation Techniques
- Identifies abnormalities in brain structure - Hyperventilation
(e.g.) tumors, infarcts, etc. –Indications: - Photic stimulation (e.g., bright lights / sun)
- Any adult with first seizure - Sleep deprivation
- $$$$$
What is the EEG? The electroencephalogram (EEG) is a spatial recording of the electrical activity of the cerebral cortex, through
electrodes placed on the scalp.

- The EEG measures the electrical potentials of cortical neuronal dendrites near the brain’s surface

In clinical medicine, the EEG is an important diagnostic test in the evaluation of patients with seizure disorders,
sleep disorders, altered levels of consciousness (e.g. coma) and can help localize and diagnose certain infections
and focal processes within the CNS

Relatively inexpensive, and non-invasive

What is the Graphical depiction of cortical electrical activity, usually recorded from the scalp
Physiologic Basis of Advantage of high temporal resolution, but poor spatial resolution of cortical disorders
the EEG? EEG is the most important neurophysiological study for the diagnosis, prognosis, and the treatment of epilepsy

Why do we use the Clinical Applications


EEG? - Seizures/Epilepsy
- Sleep
- Altered consciousness
- Focal and diffused disturbances in cerebral functioning
90% of patients with absence seizures have an abnormal EEG
10% of “normal” population have an “abnormal” EEG

How do we
understand NORMAL
vs. Epileptiform EEG?
What are the Hyperventilation
conditions that mimic Migraine
seizures? Panic Attack
Psychogenic Seizures
Syncope
Transient Global Amnesia
Transient ischemic attack

What are the different Partial Seizures


types of seizures? - Simple
- Complex
Generalized Seizures
- Tonic Clonic (Grand Mal)
Absence Seizures
- Petit mal
Myoclonic
Catamenial
Status Epilepticus

What is the difference Partial (Focal) Seizures- Jacksonian Complex Partial Seizures- Temporal Lobe Epilepsy or
between a Simple Psychomotor Seizures
Partial Seizure vs. - Involves one side of the brain at onset - Produces confusion and inappropriate or
Complex Seizure (can spread) dazed behavior
- Focal, with motor, sensory, or speech - Motor activity appears as non-reflex
disturbances actions
- Confined to a single limb or muscle group - Wide variety of clinical manifestations
- Seizure symptoms don’t change during - Consciousness is impaired or lost
seizure - EEG shows activity of bilateral anterior
- No alteration of consciousness- preserved temporal lobe focal abnormalities
Occur within discrete regions of the brain
Partial seizures can occur within discrete regions of the brain
Partial seizures can subsequently spread throughout the cortex partial seizures with secondary generalization

What are generalized Grand Mal Seizure


seizures? (Tonic-Clonic - Motor symptoms are bilateral
Seizures) - Loss of consciousness
- May be preceded by an aura- less likely to be a partial seizure that is secondarily generalized if this
occurs
- Begins with a short tonic contraction of muscles followed by a period of rigidity (clonic or ‘ictal’ state)
- May be followed by unconsciousness, and frequently the patient goes into a deep sleep (post-ictal)
What are Absence Generally occur in young children or adolescents
Seizures? (Petit Mal) Remits in adulthood
Exhibit:
- Sudden onset without “aura” or precipitating signs
- Brief interruption of ongoing activities
- Blank stare
- Possibly a brief, upward rotation of the eyes
- No post-ictal symptoms
What are Myoclonic Juvenile Myoclonic Epilepsy (JME)
Seizures? - Bilateral, myoclonic jerks are brief, shock-like muscular contractions of the face, trunk and extremities
- May be isolated events or rapidly repetitive
- Most frequent in the morning after awakening- can be provoked by sleep deprivation
- Unknown cause
What is Lennox- Occurs in children
Gastaut Syndrome? Defined by a triad
1. Multiple seizure types
2. Distinct EEG pattern of slow spike-and- wave discharges
3. Impaired cognitive function (most cases)
Associated with CNS disease or dysfunction from a variety of causes (developmental abnormalities, perinatal
hypoxia, ischemia, trauma, infection)
Generally poor prognosis with severe, poorly controllable epilepsy
What is a A “psychogenic nonepileptic event”
pseudoseizure? A neurological disorder in which a patient ‘fakes’ a seizure without any underlying seizure activity occurring via an
EEG
Psychiatric diagnosis that is untreated
How does epilepsy Enzyme inducing AEDs may cause treatment failures in females taking oral contraceptics (OCPs)
affect women? Treatment with a moderate or high hormonal dose OCP is necessary PLUS supplemental form of Birth control
25-30% of women have a change in seizure frequency (increases or decreases) in pregnancy
What is catamenial Seizures that occur just before or during menses, or at the time of ovulation
epilepsy? Conventional AEDs should be first line- may need hormonal therapy +/- AEDs
High risk pregnancies both seizure AND treatment
May require increased/adequate folate intake- many times can be treated with high-dose hormonal therapy 1-
4mg/d (min. 0.4 mg/d)
What are the different GOAL: Lower/Limit/Eliminate Seizures without any (or at least minimizing) adverse effects of treatment, allowing
methods of the patient to pursue a normal lifestyle
treatment? Surgery Most commonly a temporal lobectomy (temporal lobe and the hippocampus)
- Hippocampus plays a primary role in the transmission of signaling that
goes wrong
80-90% success rates for being seizure free (doesn’t work for 10-20% of patients)
MUST:
- Have definite epilepsy
- Fail ‘adequate’ drug therapoes
- Have a localization of the seizure focused in the brain
With a temporal lobectomy can possibly cause side effects if other parts of the
brain are impacted Speech, Emotion, Sensory
Vagal Nerve Delivery of electrical impulses to the vagus nerve
Stimulation Used for treatment-resistant depression
25-50% of patients will have a 50% reduction in seizure activity
Ketogenic Diet High fat, low carb, controlled protein diet
- Butter, cream, oil-based
- MCT- medium chan faits
- Ketosis- burn fat instead of carbs for energy
Grams of Fat: Grams of CBO + Grams of protein
- 4:1 Ratio 90% fat, 10% CBO and Pro
Monitor ketogenic state by KETONES
Most children will ketones tested 2x daily
Considerations for meds?
- Must be at the lowest CBO form possible
Usually means tabs that can be crushed
All meds need to be checked for CBO and Sugar content
Possible to decrease AEDs when the diet starts
Dietary Supplements
Multivitamin
Calcium and Vitamin D
Carnitine, Magnesium, Zinc, Potassium, Omega-3s
Side Effects of the Diet
Constipation (40%)
Kidney stones / nephrolithiasis (5+%)
Acidosis (20+%)
Nausea / vomiting (15+%)
Side effects and treatment failure are the most common reasons to stop the
ketogenic diet
Medical Marijuana 545 distinct compounds of cannabis
- Delta9‐THC and cannabidiol, cannabidivarin are thought to have most direct targets
in CNS relevant to antiseizure effects
- Despite preclinical & anecdotal reports on efficacy in treatment of epilepsy,
evidence based medicine is lacking
Cochrane review concluded: “no reliable Conclusions can be drawn at present
regarding the efficacy of cannabinoids as a treatment for epilepsy” due to the lack of
data from RDBPCT Randomized Double Blinded Placebo Controlled Trial
Currently on the approved medical conditions in CT for medical marijuana
Cannabidiol Oral
Solution * on drug
chart
What is Status Status epilepticus exists when seizures recur or persist within a short period of time
Epilepticus? - Baseline consciousness not regained b/t seizures
- Lasts at least 30 minutes
- Can lead to systemic hypoxia, acidemia, hyperpyrexia, cardiovascular collapse, and renal shutdown
The most common, generalized tonic‐clonic status epilepticus is life‐threatening and must be treated immediately
with concomitant cardiovascular, respiratory and metabolic management
How do we administer
Anti Epileptic Drugs
for Status Epilepticus?

Administer Benzo first (Lorazepam/Diazepam)


Lorazepam is first choice
Use weight based dosing 0.1mg/kg IV at 2mg/min
If it fails to LORAZEPAM-->Phenytoin (2nd drug administered
20mg/kg--> 50mg/min
Only in normal saline
Contains Propylene Glycol (must be at a certain rate)
Very basic solution-burns on the way in
Can burn out the vei
Use fosphenytoin (can be in normal saline or dextrose in water)
Can be given at 150mg/min--> very $$$
Most ambulances don't stock b/c it goes out of date quickly
Phenytoin is better b/c it has multiple uses
Can't push faster than 50mg/min b/c--> can cause pro- (causes heart to beat too fast) side effects
If the patient is seizing still
Additional 5-10mg/kg OR
add Phenobarbital
@ Hospital--> Medical induced Coma--> by using Anesthesia with Midazolam or Propofol-- there is still an
active seizure going on
Administer anti-epileptics that patient is on even at the hospital
What drugs are used Benzodiazepines [BZDs]
to treat status - Lorazepam, diazepam
epilepticus Diazepam IV 5‐10 mg @ 1‐2 mg/min
- Repeat dose (5‐10 mg) every 20‐30 min
- Also available as a rectal gel
Lorazepam IV 2‐6 mg @ 1‐2 mg/min [0.1 mg/kg] = 1st line choice
- Repeat dose (2‐6 mg) every 20‐30 min
Have muscle relaxant activity
Increase frequency of GABA channel opening

Can also use IV phenytoin or IV fosphenytoin if BZDs fail


- May need to proceed to anesthesia (midazolam, propofol) if seizures persist longer than 60 – 90
minute
How do we initially As soon as the patient presents with Status Epilepticus the first thing you are going to do is administer Thiamine
manage Status and Glucose
Epilepticus? – Severe hypoglycemia can precipitate seizures
– Thiamine would be given to alcoholic patients suffering from seizures and must be given prior to glucose
– If the seizures persists, we start anticonvulsant therapy
What are the options How do we control abnormal neuronal activity by using drug therapy?
for pharmacologic - This is accomplished by elevating the seizure threshold of neurons to electrical or chemical stimul
therapy for seizures - AEDs limit the propagation of the seizure discharge from its origin
and epilepsy? - AEDs stabilize Neuronal Membranes (raising the threshold) and depress synaptic transmission of nerve
conduction (limits propagation)
What is the statistical Statistically, if you take six different drugs, you have an 80% chance of at least one drug-drug interaction
significance of taking
drugs causing
interactions
What are the As many as 40% of patients fail b/c of noncompliance with therapy; but 50% will be seizure‐free with 1 drug
principles of Anti- Exclude “fixable” causes
Epileptic Drugs? - E.g., alcohol, electrolyte abnormalities, hypoglycemia, AED‐induced seizures
Start low, go slow, and sometimes say NO
When can we stop The patient must be seizure free for 2-5 years on AEDs
taking AEDs? Must have a single type of partial seizure or single type of general tonic-clonic seizures
Normal neurologic exam/normal IQ
EEG normalized with treatment