Last edited: 2/11/2022

SEIZURES
Seizures | Status Epilepticus Medical Editor: Dr. Ana Guerra

OUTLINE (B) INFECTIOUS CAUSES

I) DEFINITION (i) Meningitis

II) ETIOLOGY
III) PATHOPHYSIOLOGY
IV) CLINICAL FEATURES
V) DIAGNOSIS (ii) Encephalitis
VI) TREATMENT
VII) STATUS EPILEPTICUS (SE)
VIII) REVIEW QUESTIONS (iii) Brain abscess
IX) REFRENCES

I) DEFINITION (iv) Toxoplasmosis

A seizure is defined as an abnormal excessive (v) Malaria
synchronous electrical activity, that occurs within the (vi) Neurocysticercosis
central nervous system and that can lead to outward
manifestations depending on the location or the extension
of the seizure.

II) ETIOLOGY

(A) VASCULAR CAUSES

(1) Strokes
This is a common cause of focal seizures but can cause
generalized as well. (C) TRAUMATIC CAUSES
Can happen in:
(i) Epidural hematoma:
(i) Acute ischemic strokes
(ii) Hemorrhagic strokes:
(ii) Subdural hematoma:
Intracerebral hemorrhage
Subarachnoid hemorrhage

(2) Posterior reversible encephalopathy syndrome

(PRES):
This is produced by a very high pressure that leads
to a vasogenic edema inside of the posterior cerebral
territories that can be visible on MRI.
(D) AUTOIMMUNE CAUSES
(1) Systemic lupus erythematosus
(3) Anoxic brain injury
Caused by a severe hypoxia to the brain.
(2) Paraneoplastic syndromes (ovarian and lung
cancer)

(i) Anti-NMDA antibodies:

(ii) Anti-Hu antibodies

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 (E) METABOLIC CAUSES

(i) ↓vit B (i) Medications

(ii) Hypoglycemia and Hyperglycemia a. Opioids (Tramadol & Meperidine)
(iii) Electrolyte imbalance: b. TCAs
c. Isoniazid
a. Hyponatremia/hypernatremia: regulates movement
d. Salicylate toxicity
of water between brain tissue and blood (↓Na
e. Cocaine & Cefepime
especially
b. Hypocalcemia ↓Ca:
g. Metronidazole
c. Hypomagnesemia, ↓Mg stabilizes membrane and
h. Penicillins
regulates activity of Ca- channels
i. Benzodiazepine withdrawal & Bupropion
d. Hypophosphatemia ↓PO4)
j. Ethanol withdrawal
(iv) Uremia k. Lithium
(v) Liver failure

(vi) Thiamine deficiency

(vii) Hyperthyroidism

(I) ECLAMPSIA AND EVERYTHING ELSE

(1) Eclampsia:

(2) Fevers:
(F) IDIOPATHIC CAUSES Febrile seizures common in children infected with HHV-6/7

(3) Genetics
(i) Causes: Phenylketonuria
i. Antiepileptic drugs: Either not taking them or not Lysosomal storage disorders
taking enough. Peroxisomal storage disorders
ii. West syndrome, Lennox-Gasaut syndrome, Juvenile Angelman syndrome
myoclonic epilepsy.

(G) NEOPLASTIC MNEMONICS

(i) Glioblastoma
(ii) Meningioma
(iii) Metastatic brain cancer

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 III) PATHOPHYSIOLOGY IV) CLINICAL FEATURES

Neurons→↑abnormal, synchronous firing (A) ANATOMY OF SEIZURES

Clinical features are determined by the area of the brain
(i) ↑Neuron excitation: that is being affected.
i. ↑↑Glutamate →↑NMDA and ↑AMPA receptors
stimulation→ ↑Cation influx (Mg+, Ca2+, Na+)→
↑Depolarization of the neuron → ↑Neuron firing→
Seizure.

(ii) ↓Neuron inhibition:

i. GABA receptors are dysfunctional: They don’t
respond to GABA stimulate anymore
ii. GABA released→ GABA-R won't open→ ↓Anion
influx (Cl-) → ↓Hyperpolarization → ↓inhibition of
neurons→ ↑Neuron firing→ Seizure.

(i) Frontal Lobe

(a) Primary Motor Cortex

(b) Supplementary Motor Cortex

(ii) Parietal Lobe

(iii) Occipital Lobe

(iv) Temporal Lobe and Insula

(B) EVENTS DURING A SEIZURE

(1) Trigger

(2) Aura

a. Déjà vu
b. Nausea
c. Automatisms (rapid movement of the eyes,
abnormal chewing, lips smacks).
(3) Ictal Event

(i) Focal
(ii) Generalized
(4) Postictal Phase

a. Focal with impairment seizures

b. Generalized seizures
c. Focal with secondary generalization

(i) Symptoms include:

i. Confusion
ii. Lethargy
iii. Amnesia
iv. Todd’s paralysis (common in focal with impairment)

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 (C) FOCAL SEIZURES

(1) Focal Motor Symptoms (2) Focal sensory symptoms

(i) Primary and supplementary motor cortex

(i) Primary somatosensory cortex

 Paresthesia and/or pain

i. Atonic
• Loss of muscle tone (ii) Primary auditory cortex
ii. Tonic
• Sudden stiffening of muscles  Ringing sounds
iii. Clonic
• Rhythmic twitching of muscles
iv. Myoclonic
• Fast and jerky contractions  Visual hallucinations
v. Jacksonian march
• Abnormal motor movement in an extremity that (iv) Primary olfactory cortex
starts distally and spreads proximally
• Usually with clonic movements  Unusual or intense smells

1. Unilateral limb movements (v) Primary gustatory cortex

2. Turning head to one side
3. Gaze deviation to contralateral side
 Unusual tastes
• Metallic tastes

(vi) Jacksonian march

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 (3) Focal psychological symptoms (5) Focal seizures with impairment
a. Déjà vu

b. Derealization

c. Depersonalization (i) Loss of consciousness

(ii) Aura
d. Emotional expressions: i. Sensation of impending seizure/doom (Deja vu)
ii. Automatisms (temporal lobe involvement)
• Anger 1. Chewing
• Sexual 2. Lip smacking
(4) Focal autonomic symptoms 3. Rapid eye blinking
4. Unusual smells
(i) Temporal lobe involvement, especially insula 5. Nausea

(iii) Postictal amnesia/confusion

o Postictal paralysis of one side of body

o Resolves in time
(6) Focal seizure without impairment (complex partial)

a. Tachycardia, hypertension
b. Urinary incontinence
c. Sweating
d. Salivating

(7) Focal seizure with secondary generalization

Focal seizure→ Impairment of thalamus and reticular
formations → Spread to both cerebral hemispheres
though corpus callosum → Generalized tonic clonic
seizure

(i) History:
i. Auras
ii. Automatisms
iii. Postictal amnesia/confusion
iv. Todd’s paralysis

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 (D) GENERALIZED SEIZURES

(1) Generalized Motor Seizures (2) Generalized non-motor seizures

(i) Absence seizure (petit mal)

i. Sudden, brief loss of consciousness→ Described as
“staring into space”
ii. No loss of muscle tone, may show automatisms
(i) Atonic iii. Can occur up to 100x/day
 Loss of muscle tone → Sudden collapse

(ii) Tonic
 Sudden stiffening of muscles
 Extreme flexion or extension of extremities,
head or trunk

(iii) Clonic
 Rhythmic twitching/jerking of muscles

(iv) Myoclonic
 Fast, nonrhythmic and jerky contractions

(v) Tonic-Clonic (grand mal)

i. Mixture of stiffening of muscles and rhythmic jerking
ii. Common muscles affected:
1. Vocal cord muscles

2. Extraocular muscles

3. Oropharyngeal muscles

4. Mastication muscles

5. Sphincter muscles

iii. ↑Sympathetic activity

• ↑HR (tachycardia) & ↑BP (hypertension)
• Followed by postictal state: Amnesia,
confusion, lethargy.

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 V) DIAGNOSIS

(A) IF THE PATIENT HAS HISTORY OF SEIZURES

(i) Epilepsy
i. ≥ 2 unprovoked seizures
ii. Unprovoked seizure with 60% recurrence rate

o Causes are usually inadequacy of antiepileptic drug (AED)

1. If subtherapeutic AED level → ↑ AED dosage

2. If normal AED level → ↑ AED dosage to maximum dosage before supratherapeutic range or switch to another
AED
3. Also consider underlying trigger/cause for breakthrough seizure as stated below.

(B) FIRST TIME SEIZURE

(1) Vascular (7) Neoplasia

CT/MRI CT→ MRI with and without contrast
Lumbar Puncture for SAH not seen on imaging May require biopsy to find type of cancer
CT of chest, abdomen and pelvis to search for
malignancy
(2) Infectious
MRI with and without contrast
a. Vasogenic edema and leptomeningeal enhancement (8) Drugs
on MRI with meningoencephalitis Urine toxicology
b. MRI with contrast shows ring enhancing abscess Review medication list
CT
Lumbar puncture
Blood cultures
(9) Eclampsia & Everything else
CBC: Elevated white cell count can mean infection
Urine/serum Beta-HCG
Fever
(3) Trauma Genetic testing

(10) Additional Studies

(4) Autoimmune
Lumbar puncture
(i) Electroencephalogram
a. Pleocytosis i. May show seizure activity or seizures that are
b. Increased protein nonconvulsive
Autoimmune panel (ANA) ii. Remember if you see a 3Hz Spike and wave
a. Lupus pattern→ Think absence seizures.
b. Anti-NMDA, Anti-Hu antibodies
CT of chest, abdomen and pelvis and testicular (ii) Lactate
ultrasound: i. Increased glycolytic flux during seizures→ ↑lactate
a. To search for malignancy as cause of paraneoplastic ii. Order ABG to check for metabolic acidosis.
syndrome.
(iii) Creatinine kinase (CK)
i. Seizures→ Rhabdomyolysis →↑CK spills out of cells
(5) Metabolic
and in the blood.
Thiamine level
a. Thiamine deficiency (iv) Prolactin
Point of care glucose i. Seizures→ ↑Prolactin
a. Hypoglycemia ii. Helpful in distinguishing pseudoseizures from real
CMP (+ Mh2+ and PO4+) seizures.
a. Renal function
b. Liver function (v) Troponin and 12 Lead ECG
c. Electrolyte abnormalities
i. Seizures→ rhabdomyolysis→↑troponin leaks out of
Check NH3 levels
cells
TSH with reflex
ii. Obtain 12 lead ECG to rule out ischemia/infarction.
a. Hyperthyroidism

(6) Idiopathic (see epilepsy above)

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 VI) TREATMENT

(A) ANTIEPILEPTIC DRUGS (AEDS)

(i) Sodium channel blockers:
(v) AMPA blockers
1. Felbamate
2. Magnesium

(vi) NMDA blockers

1. Valproate 1. Ketamine
2. Phenytoin 2. Topiramate
3. Topiramate (vii) GABA reuptake inhibitors
4. Lamotrigine
5. Fosphenytoin 1. Tiagabine
6. Carbamazepine
(viii) GABA transaminase inhibitors
7. Lacosamide
1. Valproate
(ii) Calcium channel blockers: 2. Vigabatrin

(ix) GABA agonists

1. Ethosuximide: Used especially for absence 1. Benzodiazepines
seizures 2. Barbiturates
2. Topiramate a. Pentobarbital
3. Lamotrigine b. Phenobarbital
3. Propofol
(iii) Α2૪ subunit calcium channel blockers 4. Topiramate
1. Gabapentin
2. Pregabalin

(iv) SV2A blockers

1. Levetiracetam

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 VII) STATUS EPILEPTICUS (SE)

(1) Definition:

(2) Treatment
(i) Initial Treatment (ii) AED initiation
i. ABCs
 Most commonly utilized in SE:
1. Levetiracetam
ii. Reverse easily reversible causes
1. Hypoglycemia 2. Phenytoin

2. Alcoholic with thiamine deficiency 3. Fosphenytoin

3. Tuberculosis patient taking Isoniazid 4. Valproate

4. Pregnant + HTN + seizure (Eclampsia) 5. Lacosamide

5. Opioid overdose (iii) Intubation with IV AED infusions

i. If not already intubated ⟶ Intubate
iii. Give benzodiazepine and repeat this step as needed ii. Start IV AED infusion of commonly used AEDs
until max doses have been reached 1. Propofol infusion
 0.1mg/kg IV lorazepam 2. Midazolam infusion
3. Ketamine infusion
 0.1mg/kg IV midazolam 4. Pentobarbital Infusion
iii. Ketogenic diet and search for refractory causes that
 0.2-0.4mg/kg IV diazepam may have been overlooked

iv. Hyponatremia

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 VIII) REVIEW QUESTIONS
1) Select the correct answer:
a) A seizure is defined as an abnormal excessive
synchronous electrical activity, that occurs within the
central nervous system.
b) A seizure is defined as an abnormal excessive
synchronous electrical activity, that occurs within the
peripheral nervous system.
c) A seizure is defined as an abnormal inhibitory
electrical activity, that occurs within the central
nervous system.
d) A seizure is defined as an abnormal excessive
synchronous electrical activity, that occurs within the
central nervous system due to metabolic causes.
2) Which of the following metabolic alterations will be
more likely to find in a patient with liver failure, and
which can lead to a seizure?
a) ↓Na
b) ↓Mg
c) ↓PO4
d) ↑NH3
3) Which is the neurotransmitter responsible of
increasing the influx of Mg+, Ca2+ and Na+ into the
neuron?
a) GABA
b) Glutamate
c) Serotonin
d) Acetylcholine
4) A 22 years old male is presented for sudden
stiffening of his right leg muscles as well as rhythmic
twitching of the same extremity.
According to your knowledge of the anatomy of
seizures, what area of the brain is more likely to be
having an abnormal electrical activity?
a) Parietal lobe
b) Occipital right lobe
c) Frontal lobe
d) Frontal left lobe
IX) REFRENCES
● Bickley LS, Szilagyi PG, Hoffman RM, Soriano RP, Bates B.
Bates' Guide to Physical Examination and History Taking.
Philadelphia: Wolters Kluwer; 2021.
● Longmore JM. Mini Oxford Handbook of Clinical Medicine.
Oxford: Oxford University Press; 2015.
● Sabatine MS. Pocket Medicine: the Massachusetts General
Hospital Handbook of Internal Medicine. Philadelphia: Wolters
Kluwer; 2020.
● Williams DA. Pance Prep Pearls. Middletown, DE: Kindle Direct
Publishing Platform; 2020.
● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL,
Loscalzo J. Harrison's Principles of Internal Medicine. New York
etc.: McGraw-Hill Education; 2018.
● The Pocket Guide to Neurocritical Care: A Concise Reference
for the Evaluation and Management of Neurologic Emergencies.
Chicago, IL: Neurocritical Care Society; 2017.
● Westover MB, DeCroos EC, Awad KM, Bianchi MT. Pocket
Neurology. Philadelphia: Wolters Kluwer; 2016.
● Le T, Bhushan V, Skelley N. First Aid for the USMLE Step 2 CK.
McGraw-Hill Education; 2012
● Lee K. The NeuroICU Book. New York: McGraw-Hill Education;
2018.
● Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-
Hill Education; 2014
● Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline:
Treatment of Convulsive Status Epilepticus in Children and Adults:
Report of the Guideline Committee of the American Epilepsy
Society. Epilepsy Currents .2016; 16(1): p.48-61. doi:
10.5698/1535-7597-16.1.48
● Schachter SC. Advances in the assessment of refractory
epilepsy. Epilepsia 1993; 34 Suppl 5:S24.
● Schachter SC. Update in the treatment of epilepsy. Compr Ther
1995; 21:473.
● Fountain NB, Van Ness PC, Swain-Eng R, et al. Quality
improvement in neurology: AAN epilepsy quality measures: Report
of the Quality Measurement and Reporting Subcommittee of the
American Academy of Neurology. Neurology 2011; 76:94.
● Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of
the epilepsies: Position paper of the ILAE Commission for
Classification and Terminology. Epilepsia 2017; 58:512.
● Fisher RS, Cross JH, D'Souza C, et al. Instruction manual for
the ILAE 2017 operational classification of seizure types. Epilepsia
2017; 58:531.
● Fisher RS, Cross JH, French JA, et al. Operational classification
of seizure types by the International League Against Epilepsy:
Position Paper of the ILAE Commission for Classification and
Terminology. Epilepsia 2017; 58:522.
●

5) What type of ictal event is the one presented on the

previous case?
a) Focal seizure with impairment
b) Tonic-clonic
c) Myoclonic
d) Focal seizure

6) A 32 year old pregnant woman is presented to the ER

for abnormal movements of extremities and neck
reported by her husband. Medical history reveals
HTN during her pregnancy without any treatment.
Which of the following drugs would be the most
appropriate to treat the patient?
a) Levetiracetam
b) Naloxone
c) Magnesium
d) Valproate

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