Autoimmune Encephalitis

• Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis (see Anti-N-Methyl-D-Aspartate Receptor Encephalitis, [[Anti-N-Methyl-D-Aspartate Receptor Encephalitis]])
  • Epidemiology
• Anti-VGKC complex Antibodies
  • Epidemiology
• Paraneoplastic Syndrome
  • xxxx

Cardiovascular

• Cerebral Venous Thrombosis (see Cerebral Venous Thrombosis, [[Cerebral Venous Thrombosis]])
• Epidural Hematoma (see xxxx, [[xxxx]])
• Hypertensive Encephalopathy (see Hypertensive Encephalopathy, [[Hypertensive Encephalopathy]])
  • Epidemiology
• Hypoxic-Ischemic Brain Injury (see Hypoxic-Ischemic Brain Injury, [[Hypoxic-Ischemic Brain Injury]])
  • Cardiac Arrest (see xxxx, [[xxxx]])
  • xxx
  • xxx
• Intracerebral Hemorrhage (see xxxx, [[xxxx]])
• Ischemic Cerebrovascular Accident (CVA) (see xxxx, [[xxxx]])
• Posterior Reversible Leukoencephalopathy Syndrome (PRES) (see Posterior Reversible Encephalopathy Syndrome, [[Posterior Reversible Encephalopathy Syndrome]])
  • Clinical
    • xxxx
• Subarachnoid Hemorrhage (SAH) (see xxxx, [[xxxx]])
• Subdural Hematoma (SDH) (see xxxx, [[xxxx]])

Structural

• Brain Tumor
  • Epidemiology: seizures are a common clinical presentation of brain tumor
• Cortical Dysplasia
• Traumatic Brain Injury (TBI) (see xxxx, [[xxxx]])
  • Epidemiology:

Infection

• Brain Abscess (see xxxx, [[xxxx]])
  • Epidemiology
• Encephalitis (see xxxx, [[xxxx]])
  • Epidemiology
• Malaria (see Malaria, [[Malaria]])
• Meningitis (see xxxx, [[xxxx]])
• xxx
• Sepsis (see Sepsis, [[Sepsis]])
  • Epidemiology:

Metabolic

• Acute Intermittent Porphyria (see Acute Intermittent Porphyria, [[Acute Intermittent Porphyria]])
• Central Pontine Myelinolysis (CPM) (see Central Pontine Myelinolysis, [[Central Pontine Myelinolysis]])
• Hypoglycemia (see Hypoglycemia, [[Hypoglycemia]])
  • Epidemiology:
• Hyponatremia (see Hyponatremia, [[Hyponatremia]])
  • Epidemiology:
• Inborn Errors of Metabolism
  • Epidemiology: in children
• Metabolic Alkalosis (see Metabolic Alkalosis, [[Metabolic Alkalosis]])
  • Epidemiology: seizures may occur with severe metabolic alkalosis
• Rapid Change in pCO2 During Mechanical Ventilation
  • Epidemiology: this may particularly occur during the initial mechanical ventilation of a patient with chronic hypercapnia (chronic hypoventilation)
  • Mechanism: rapid shift in arterial pCO2 is almost immediately transmitted throughout the total body water (including the intracellular fluid compartment, the brain, and the cerebrospinal fluid), resulting in potential neurologic injury (it is likely that the rapid change in pCO2 is responsible rather than the alkalosis itself)
  • Clinical
    • Obtundation/Coma (see Obtundation-Coma, [[Obtundation-Coma]])
    • Seizures
  • Prevention: maintain pCO2 near patient’s baseline (or gradually decrease the pCO2)
• xxx

Drug

• Amantadine (Symmetrel, Symadine) (see Amantadine, [[Amantadine]])
• Atypical Anti-Psychotics
  • Risperidone (Risperdal) (see Risperidone, [[Risperidone]])
  • xxx
• Lidocaine Toxicity (see Lidocaine, [[Lidocaine]])
• xxx
• xxx
• xxx

Toxic

• Barium Intoxication (see Barium, [[Barium]])
• Diborane Gas Inhalation (see Diborane Gas, [[Diborane Gas]])
• Ethanol Intoxication (see Ethanol, [[Ethanol]])
• Ethylene Glycol Intoxication (see Ethylene Glycol, [[Ethylene Glycol]]): may occur in severe cases
• Hydrogen Sulfide Gas Inhalation (see Hydrogen Sulfide Gas, [[Hydrogen Sulfide Gas]])
• Methamphetamine Intoxication (see Methamphetamine, [[Methamphetamine]])
• Methemoglobinemia (see Methemoglobinemia, [[Methemoglobinemia]])
• Paraquat (see Paraquat, [[Paraquat]])
• Serotonin Syndrome (see Serotonin Syndrome, [[Serotonin Syndrome]])
• xxx

Withdrawal

• Barbiturate Withdrawal (see Barbiturates, [[Barbiturates]])
• Benzodiazepine Withdrawal (see Benzodiazepines, [[Benzodiazepines]])
• Ethanol Withdrawal (see Ethanol, [[Ethanol]])
• Gabapentin Withdrawal (see Gabapentin, [[Gabapentin]])
• Opiate Withdrawal (see Opiates, [[Opiates]]): in neonates
• xxx

Other

• Epilepsy
  • Epidemiology
    • Breakthrough Seizures
    • May Be Associated with Anticonvulsant Non-Compliance
    • May Be Associated with Anticonvulsant Withdrawal
• Febrile Seizures
  • Epidemiology: in children
    • Febrile Seizures are the Most Common Etiology of Status Epilepticus in Children
• xxx

Endocrinologic Manifestations

Hyperprolactinemia (see Hyperprolactinemia, [[Hyperprolactinemia]])

• xxx

Neurologic Manifestations

Obtundation/Coma (see Obtundation-Coma, [[Obtundation-Coma]])

• Clinical
  • During Non-Convulsive Status Epilepticus
  • During Post-Ictal State

Increased Intracranial Pressure (see Increased Intracranial Pressure, [[Increased Intracranial Pressure]])

• Physiology: seizures cause cerebral vasodilation
• Clinical: potentiation of neurologic injury in traumatic brain injury (TBI), etc

Status Epilepticus

• Definition: ≥5 min of continuous clinical and/or electroencephalographic seizures OR ≥5 min of recurrent seizure activity without recovery to baseline between seizures (Neurocrit Care, 2012)[MEDLINE]
  • *Definition Recognizes that Most Clinical/Electroencephalographic Seizures Last <5 min and that Seizures Which Last Longer than 5 min Often Do Not Stop Spontaneously
  • Animal Data Suggests that Permanent Neuronal Injury and Pharmacoresistance May Occur Before the Traditional Definition of 30 min of Continuous Seizure Activity Has Passed
• Recommendations (Neurocritical Care Society Guidelines for Status Epilepticus, 2012) (Neurocrit Care, 2012) [MEDLINE]
  • Status Epilepticus Should Be Classified as Either Convulsive Status Epilepticus or Nonconvulsive Status Epilepticus (Strong Recommendation, High Quality)
  • The Etiology of Status Epilepticus Should be Diagnosed and Treated as Soon as Possible (Strong recommendation, High quality)

Convulsive Status Epilepticus

• Definition: convulsions that are associated with rhythmic jerking of the extremities
  • Generalized Tonic-Clonic Movements of Extremities
  • Mental Status Impairment
    • Coma (see Obtundation-Coma, [[Obtundation-Coma]])
    • Confusion (see Delirium, [[Delirium]])
    • Lethargy
  • Focal Neurologic Deficits in the Post-Ictal Period
    • Temporary Neurologic Deficit Lasting Hours-Days Following a Seizure
    • Todd’s Paralysis
  • Note: focal motor status epilepticus and epilepsia partialis continua are not included in this definition

Nonconvulsive Status Epilepticus

• Definition: seizure activity seen on EEG without clinical findings associated with generalized convulsive status epilepticus
• Epidemiology
  • Nonconvulsive Status Epilepticus Frequently Occurs Following Uncontrolled or Partially-Treated Generalized Convulsive Status Epilepticus
• Diagnosis: ictal activity may be generalized or focal
• Clinical Phenotypes
  • Patient with a Chronic Epileptic Syndrome
  • “Wandering, Confused” Patient Presenting to the ED: typically has a good prognosis
  • Critically Ill Patient with Severely Impaired Mental Status (“Subtle Status”) with/without Subtle Motor Movements (Such as Twitching, Tonic Eye Deviation, etc)
    • Approximately 90% of Critically Ill Patients with Seizures Recorded in the ICU Have Nonconvulsive Status Epilepticus That is Unrecognized at the Bedside without EEG
    • Nonconvulsive Status Epilepticus is Found in Approximately 8–37% of Patients with Altered Mental Status
• Clinical (Clin Neurophysiol, 2007) [MEDLINE]
  • Agitation
  • Anorexia (see Anorexia, [[Anorexia]])
  • Aphasia/Mutism (see Aphasia, [[Aphasia]])
  • Amnesia
  • Automatisms
  • Blinking
  • Catatonia (see Catatonia, [[Catatonia]])
  • Coma (see Obtundation-Coma, [[Obtundation-Coma]])
  • Crying
  • Delirium (see Delirium, [[Delirium]])
  • Delusions
  • Echolalia
  • Facial Twitching
  • Laughter
  • Lethargy
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
  • Nystagmus/Eye Deviation (see Nystagmus, [[Nystagmus]])
  • Perseveration
  • Psychosis (see Psychosis, [[Psychosis]])
  • Staring
  • Tremulousness (see Tremor, [[Tremor]])
• Prognosis
  • Mortality Rate: 18% (Neurology, 2003) [MEDLINE]

Refractory Status Epilepticus

• Definition: patients who do not respond to standard regimen for status epilepticus
  • Controversy Exists as to How Many Anticonvulsants Need to Have Failed to Consider a Patient Refractory
  • Duration of Status Epilepticus After Treatment is Not Considered a Criteria for Refractory Status Epilepticus
• Recommendations (Neurocritical Care Society Guidelines for Status Epilepticus, 2012) (Neurocrit Care, 2012) [MEDLINE]
  • Refractory Status Epilepticus Should Be Defined as Status Epilepticus Which Does Not Respond to a Standard Regimen of an Initial Benzodiazepine, Followed by an Additional Anticonvulsant (Strong Recommendation, Moderate Quality)

Renal Manifestations

Lactic Acidosis (see Lactic Acidosis, [[Lactic Acidosis]])

• Epidemiology: common after seizure activity

Other Manifestations

• xxx

Management of Status Epilepticus (Neurocritical Care Society Guidelines for Status Epilepticus, 2012) (Neurocrit Care, 2012) [MEDLINE]

General Management

• Airway Management/Mechanical Ventilation (see xxxx, [[xxxx]]): as required
• Hemodynamic Support: as required to maintain ened-organ perfusion
• Determination of Serum Glucose: required to rule out hypoglycemia as a contributing factor or etiology
• Intravenous Access: required
  • Intravenous Fluid Resuscitation
  • Anticonvulsant Administration
• Neurologic Assessment: required to evaluate for mass lesion or acute intracranial process
• Foley Catheter (see Foley Catheter, [[Foley Catheter]]): usually required
• Diagnostic Modalities: as above
• Intracranial Pressure Monitoring: as required
  • External Ventricular Drain (EVD)

Emergent Anticonvulsants for Status Epilepticus

• General Comments
  • Benzodiazepines are the First-Line Agents (see Benzodiazepines, [[Benzodiazepines]])
  • Benzodiazepines May Be Administered via Intravenous, Intramuscular, Rectal, Nasal, or Buccal Routes
    • IV: lorazepam is the preferred agent
    • IM: midazolam is the preferred agent
    • Nasal/Buccal: midazolam is the preferred agent
    • Rectal: diazepam is the preferred agent
  • Benzodiazepines Manifest Less Respiratory Depression than Placebo When Used to Treat Generalized Convulsive Status Epilepticus (NEJM, 2001) [MEDLINE]
• Lorazepam (Ativan) (see Lorazepam, [[Lorazepam]]): Class I, Level A Recommendation
  • Typical Dosing: 0.1 mg/kg IV (max: 4 mg per dose), repeated q5-10 min
• Midazolam (Versed) (see Midazolam, [[Midazolam]]): Class I, Level A Recommendation
  • Typical Dosing: 0.2 mg/kg IM (max: 10 mg per dose)
• Diazepam (Valium) (see Diazepam, [[Diazepam]]): Class IIa, Level A Recommendation
  • Typical Dosing: 0.15 mg/kg IV (max: 10 mg per dose), may repeat in 5 min
• Fosphenytoin (xxx) (see Fosphenytoin, [[Fosphenytoin]]): Class IIb, Level A Recommendation
  • Cardiac Monitoring is Required During Intravenous Infusion
  • Typical Dosing: 20 mg phenytoin equivalents/kg IV, may give additional 5 mg/kg IV
• Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]]): Class IIb, Level A Recommendation
  • Cardiac Monitoring is Required During Intravenous Infusion
  • Typical Dosing: 20 mg/kg IV, may give additional 5-10 mg/kg IV
• Phenobarbital (see Phenobarbital, [[Phenobarbital]]): Class IIb, Level A Recommendation
• Valproate Sodium (XXXXXX) (see Valproic Acid, [[Valproic Acid]]): Class IIb, Level A Recommendation
• Levatiracetam (Keppra) (see Levatiracetam, [[Levatiracetam]]): Class IIb, Level C Recommendation
  • Typical Dosing: 1000-3000 mg IV

Urgent Anticonvulsants for Status Epilepticus

• Valproate Sodium (XXXXXX) (see Valproic Acid, [[Valproic Acid]]): Class IIa, Level A Recommendation
• Fosphenytoin (xxx) (see Fosphenytoin, [[Fosphenytoin]]): Class IIa, Level B Recommendation
  • Cardiac Monitoring is Required During Intravenous Infusion
• Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]]): Class IIa, Level B Recommendation
  • Cardiac Monitoring is Required During Intravenous Infusion
• Midazolam (Versed) by Continuous Infusion (see Midazolam, [[Midazolam]]): Class IIb, Level B Recommendation
• Phenobarbital (see Phenobarbital, [[Phenobarbital]]): Class IIb, Level C Recommendation
• Levatiracetam (Keppra) (see Levatiracetam, [[Levatiracetam]]): Class IIb, Level C Recommendation

Anticonvulsants for Refractory Status Epilepticus

• Midazolam (Versed) by Continuous Infusion (see Midazolam, [[Midazolam]]): Class IIa, Level B Recommendation
  • Typical Dosing: 2-4 mg/hr infusion
• Propofol (Diprivan) by Continuous Infusion (see Propofol, [[Propofol]]): Class IIb, Level B Recommendation
  • Typical Dosing: start 10-20 μg/kg/min
• Pentobarbital by Continuous Infusion (see Pentobarbital, [[Pentobarbital]]): Class IIb, Level B Recommendation
  • Typical Dosing: initial 5–15 mg/kg IV (may give additional 5–10 mg/kg IV), infusion ≤50 mg/min
• Thiopental (Sodium Pentothal) by Continuous Infusion (see Thiopental, [[Thiopental]]): Class IIb, Level B Recommendation
  • Typical Dosing: initial 2–7 mg/kg IV, infusion ≤50 mg/min
• Valproate Sodium (XXXXXX) (see Valproic Acid, [[Valproic Acid]]): Class IIa, Level B Recommendation
• Levatiracetam (Keppra) (see Levatiracetam, [[Levatiracetam]]): Class IIb, Level C Recommendation
• Fosphenytoin (xxx) (see Fosphenytoin, [[Fosphenytoin]]): Class IIb, Level C Recommendation
  • Cardiac Monitoring is Required During Intravenous Infusion
• Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]]): Class IIb, Level C Recommendation
  • Cardiac Monitoring is Required During Intravenous Infusion
• Lacosamide (Vimpat) (see Lacosamide, [[Lacosamide]]): Class IIb, Level C Recommendation
• Topiramate (Topamax) (see Topiramate, [[Topiramate]]): Class IIb, Level C Recommendation
• Phenobarbital (see Phenobarbital, [[Phenobarbital]]): Class IIb, Level C Recommendation
• Alternative Therapies for Refractory Status Epilepticus
  • Ketamine (see Ketamine, [[Ketamine]])
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]]): for Rasmussen’s encephalitis or Hashimoto’s encephalopathy
  • General Anesthesia (see General Anesthesia, [[General Anesthesia]])
  • Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]]): for epilepsia partialis continua or Rasmussen’s encephalitis
  • Vagus Nerve Stimulation: for catastrophic epilepsy in infants
  • Ketogenic Diet: for Landau-Kleffner syndrome, mainly used in children
  • Therapeutic Hypothermia (see Therapeutic Hypothermia, [[Therapeutic Hypothermia]]): data from small case series
  • Electroconvulsive Therapy (ECT): data from small case series
  • Transcranial Magnetic Stimulation: for epilepsia partialis continua
  • Surgical Management: generally used and successful in children

Therapeutic Hypothermia (see Therapeutic Hypothermia, [[Therapeutic Hypothermia]])

• Clinical Efficacy
  • Protocol of the HYBERNATUS Trial Studying Therapeutic Hypothermia After Convulsive Status Epilepticus (Ann Intensive Care, 2016) [MEDLINE]

Electroencephalogram (EEG) Assessment and Monitoring (see Electroencephalogram, [[Electroencephalogram]])

• Recommendations (Neurointensive Care Section of the European Society of Intensive Care Medicine, ESCIM, Recommendations, 2013) (Intensive Care Med, 2013) [MEDLINE]
  • EEG is Recommended in Generalized Convulsive Status Epilepticus
  • EEG is Recommended to Rule Out Non-Convulsive Status Epilepticus in Brain Injured Patients
  • EEG is Recommended in Comatose ICU Patients without Brain Injury Who Have Unexplained and Persistently Altered Consciousness
  • EEG is Suggested to Detect Ischemia in Comatose Patients with Subarachnoid Hemorrhage
  • EEG is Suggested to Improve Prognostication of Coma After Cardiac Arrest
  • Continuous EEG is Recommended Over Intermittent EEG for the Monitoring of Refractory Status Epilepticus
• Recommendations (Neurocritical Care Society Guidelines for Status Epilepticus, 2012) (Neurocrit Care, 2012) [MEDLINE]
  • Continuous EEG is Usually Required for the Treatment of Status Epilepticus (Strong Recommendation, Very Low Quality)
  • Continuous EEG Should Be Initiated within 1 hr of Status Epilepticus Onset if Ongoing Seizures are Suspected (Strong Recommendation, Low Quality)
  • Continuous EEG Should Be at Least 48 hrs in Comatose Patients to Evaluate for Nonconvulsive Status Epilepticus (Strong Recommendation, Low Quality)