Status

Epilepticus
Ebele Uzo-Peters
 Definitions

Time Frame Procedure

Basic 5 minutes or more of continuous seizure
or recurrent seizure activity without
return to baseline.
Official Condition characterized by an epileptic
seizure that is so frequently repeated or so
prolonged as to create a fixed and lasting
condition.
NB: The OLD definition of 30 minutes or
more is no longer used
 Classification
Generalized • Tonic-Clonic SE Focal • Somatomotor SE (Epilepsia
Convulsive SE (Simple partialis continua)
Partial) SE
• Tonic SE
• Sensory  Somatosenso-
SE ry
• Clonic SE
 Special sensory
• Myoclonic SE

Generalized • Absence SE • Aphasic SE

Nonconvulsive • Autonomic SE
SE

Complex • Absence SE
Partial SE
 Epidemiology

Time Frame Procedure

Prevalence Around 50 million people worldwide (4
– 10/1000)
Incidence 5 million people diagnosed each year
High-income 49/100,000
1
Low & middle income – 139/100,000
- Close to 80% of people with epilepsy

Prevalence 3.7 - 37/1000 (8/1000)

SE (Childhood) – 3.03% (UCTH, 2019)
 Epidemiology

Age Distribution Bimodal – high incidence in the first

decade of life, and after 60 years

Mortality Increased rate among PWE - 30%

- SUDEP, SE, injuries, suicide

SE – 10% of epilepsy related deaths

 Etiologies
Acute Processes Chronic Processes
Metabolic disturbances: electrolyte abnormality, renal Epilepsy: breakthrough
failure seizures
Sepsis Chronic ETOH abuse
CNS infection: meningitis, encephalitis, abscess CNS tumors
Remote CNS pathology (e.g.
Stroke: ischemic, ICH, SAH
stroke, abscess)
TBI
Drugs (medication NON-ADHERENCE, intoxication,
or withdrawal from benzodiazepines, barbiturates,
ETOH, and other sedatives)
Cardiac arrest, hypoxia
Hypertensive encephalopathy, PRES
Autoimmune encephalitis, paraneoplastic
 Frequency and Mortality vs Etiology

Etiology Frequency (%) Mortality (%)

AED Noncompliance 10-20 0-10
Cerebrovascular Disease 10-40 20-60
Anoxia 5-10 60-100
Metabolic Disorders 5-15 10-35
CNS Infections 0-10 0-30
Alcohol Abuse/withdrawal 5-15 0-10
Drug OD/toxicity 0-10 10-25
Head Trauma 0-10 0-25
Brain Tumors 0-10 0-20
Idiopathic 5-15 5-20
 Pathophysiology

• SE has a distinct natural history

• The more prolonged the status, the more intractable to
treatment it becomes
• The more prolonged the status, the poorer the prognosis
 Pathophysiology

• Why seizures start and stop is unknown.

• It is believed to be caused by an imbalance between excitatory
and inhibitory neurotransmission, leading to the initiation of
abnormal neural impulses.
• The seizure threshold in the immature brain appears to be lower
than in the mature brain, but the mechanisms that underlie this
susceptibility remain unclear.
• Some authorities believe that some microscopic scarring occur in
the brain resulting from various causes
 Pathophysiology

• In about 70 – 80% of cases of CSE there is a focal onset

that eventually becomes generalized.
• CSE starts with localized epileptic activity followed by
isolated generalized burst of seizure activity with a
normal EEG in between.
- If the patient does not regain consciousness between
these episodes, then s/he meets the criteria for CSE.
10
 Pathophysiology

• The systemic effects of CSE are initially dominated by the

body’s attempt to maintain homeostasis
- BP and CVP increase
- Blood glucose increases and the patient becomes
tachycardic .
• CSE may also result in electrolyte imbalance and
hyperthermia.
 Pathophysiology

• Initially, cerebral blood flow, blood glucose and oxygen utilization

increase to maintain cerebral homeostasis.
• After 30 minutes homeostatic failure begins and the patient may
need systemic support
• Cerebral blood flow, brain glucose and parenchymal oxygenation all
decrease and potentially play a part in the cell damage associated
with CSE.

12
 Pathophysiology

• If the patient does not regain consciousness between these episodes,

then the CSE continues.
• The isolated ictal discharges merge and become a continuous
discharge after 30 minutes
• Discharges then fragment and are interspaced with flat periods.
• Ultimately, periodic epileptiform discharges, which may reflect
underlying metabolic failure, will occur.
13
 CNS Consequences

Prolonged status Damage to the cortex, cerebellum,

thalamus, amygdaloid body,
hippocampus
Childhood status May lead to hippocampal sclerosis and
complex partial seizures later in life
Mechanisms Reduced GABA inhibition, enhanced
glutaminergic excitation, calcium
mediated cell damage
 EEG Patterns

• Discrete seizures with interictal slowing

• Waxing and waning of ictal discharges
• Continuous ictal discharges
• Continuous ictal discharges punctuated by flat periods
• Periodic epileptiform discharges on a flat background
Management
 Management

• Initial assessment Administer oxygen if needed.

• Airway Observe seizures briefly to ascertain that patient is

really in status.
• Breathing
Initiate ECG monitoring
• Circulation Urgent bedside glucose check
• Call for help Baseline blood work (CBC, chemistry panel,
• Hospitalist antiepileptic drug levels), ABGs (for pO2 and pH),
toxicology screen.
• Neuro team
Quickly assess patient for signs of cardio-
• PICU/RRT respiratory compromise, hyperpyrexia, focal
neurologic signs, head trauma, CNS infection.
 History
• Ask for more history
• How long has the patient been seizing?
• New-onset vs. known seizure disorder
• Baseline seizure frequency, is this typical or not?
• Events leading up to this episode
• Medications/triggers
• Relevant history
 Initial Treatment
Recommended Dosing

Lorazepam 4 mg IV over 2 min, may repeat in 5-10 minutes (8 mg max)

Alternatives Dosing

Diazepam 5-10 mg IV (0.15 mg/kg max) or 20 mg PR

Midazolam 10 mg IM / IV / IN / buccal / IO
Urgent Control
Dosing
Options
Phenytoin 20 mg mg/kg IV at maximum rate of 50 mg/min
Fosphenytoin 20 mg PE/kg IV at a maximum rate of 150 mg/min
20 mg/kg IV at a rate of 50-100 mg/min (may give additional
Phenobarbital
5-10 mg/kg)
Levetiracetam 1-3 g IV over 5 minutes or 2-5 mg/kg/min
 Further Treatment if SE is Terminated

• Further workup for etiology

• Start long-acting AED to prevent seizure
recurrence
 Fosphenytoin and levetiracetam are
good options as they are available in IV
formulations
 Study found similar efficacy for IV
VPA vs IV phenytoin*
• If not back to baseline, connect to cEEG if
available
*Agarwal P, et al. Seizure 2007
 Further Treatment if SE Continues

Recommended Dosing
Fosphenytoin 20 mg/kg IV at up to 150 mg/min

Other options Dosing

20 mg/kg IV at up to 50 mg/min (or 1-3 mg/kg/min in
Phenytoin
pediatrics, whichever is slower)
20 mg/kg IV at 50-100 mg/min, can give additional 5-
Phenobarbital
10 mg/kg after 10 minutes if needed
Levetiracetam 1-3 g IV over 5 minutes or infused at 2-5 mg/kg/min

If seizures continue, intubate and initiate

advanced treatment of refractory SE
 Treatment of Refractory SE
Recommend Dosing Major Side Effect
Midazolam • Load 0.2 mg/kg IV at 2 mg/min • Prolonged sedation in
continuous IV • Repeat 0.2-0.4 mg/kg boluses every 5 patients with hepatic and
infusion min until seizures stop renal impairment
• Maintenance 0.05 – 2 mg/kg/hr • Tachyphylaxis (within
24-28 hours)

Propofol continuous • Load 1-2 mg/kg IV over 3-5 min • Hypotension

IV infusion • Repeat boluses every 3-5 min until • Propofol infusion
seizures stop syndrome
• Maintenance 30-200 mcg/kg/min

Pentobarbital • Load 5 mg/kg IV • Severe hypotension

continuous IV • Maintenance 1-3 mg/kg/hr • Gastric stasis
infusion • May be used more frequently in • Prolonged effective half
children than propofol life
• Metabolic acidosis
 Status Epilepticus in Children
• First-line emergent treatment similar to adults
• Refractory treatment
 Use continuous IV infusions after failure of three first- or
second-line agents
 Favor midazolam and pentobarbital
» Higher risk of propofol infusion syndrome
• Administer IV pyridoxine early
 Due to rare genetic disorder of pyridoxine metabolism
 Clinical Pearls for Status Epilepticus
• Early recognition and optimized treatment of SE can
improve outcomes.
• Benzodiazepines (lorazepam IV or midazolam IM)
are the first-line agents in the treatment of SE and are
often under-dosed.
• Continuous EEG monitoring is required for optimal
treatment of ongoing status epilepticus.
 Clinical Pearls for Status Epilepticus

• Monitoring appropriate drug levels and response to

treatment is necessary when treating SE.
• Fosphenytoin is the prodrug of phenytoin; it can be
administered more rapidly than phenytoin, is
compatible in more solutions, is not formulated with
propylene glycol, and can be administered IM.
SE Management Concepts
• ABCs
• Control seizures ASAP
• Do NOT undertreat
• Determine underlying cause of seizures
and address if necessary
• Once convulsions have ceased, consider
nonconvulsive seizures if patient
comatose
• No evidence-based recs for NCSE but
most would treat similar to convulsive SE
• Do not approach above measure
sequentially but simultaneously
• World Health Organisation; Epilepsy; February 9, 2023; https://www.who.int/news-room/fact-sheets/detail/epilepsy
• Epilepsy & Behaviour; Volume 92; P226-234; Prevalence and burden of epilepsy in Nigeria: A systematic review and
meta-analysis of community-based door-to-door surveys January 25, 2019;
https://www.epilepsybehavior.com/article/S1525-5050(18)30942-9/fulltext
• East African Medical Journal; Vol. 97 N0.9 (2020); Prevalence and outcome of childhood status epilepticus in a
tertiary hospital in the Coastal City of Calabar, Nigeria; https://www.ajol.info/index.php/eamj/article/view/202793
• Frontiers; Epidemiology; Volume 3 – 2023; Mortality, and life expectancy in Epilepsy and Status epilepticus—
current trends and future aspects; 23 February 2023;
https://www.frontiersin.org/articles/10.3389/fepid.2023.1081757/full
• AAP Subcommittee on Febrile Seizures. Clinical Practice Guideline—Neurodiagnostic Evaluation of the Child With a
Simple Febrile Seizure. Pediatrics 2011, 127(2): 389-394
• Singh RK, Gaillard WD. Status Epilepticus in Children. Current Neurology and Neuroscience Reports 2009, 9:137–
144
• Wilfong A. Overview of the classification, etiology, and clinical features of pediatric seizures and epilepsy. Up To
Date, 2011.
• Shorvon S, Baulac M, Cross H, Trinka E, Walker M. Taskforce on Status Epilepticus of the ILAE Commission for
Europe Affairs. The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first
London Colloquium on Status Epilepticus. Epilepsia. 2008;49(7):1277-1285.
• Maganti R, Gerber P, Drees C, Chung S. Non-convulsive status epilepticus. Epilepsy Behav. 2008;12(4):572-586.
• Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: usefulness of clinical features in selecting
patients for urgent EEG. J Neurol Neurosurg Psychiatry. 2003;74(2):189-191
Thank
You