A 58-year-old woman has been brought to the Emergency Department (ED) having been found with a reduced level of consciousness. Witnesses describe possible seizures. She has been unwell for a number of weeks with complaints of dysuria and frequency and progressive lethargy.
Her current medications are atorvastatin and metoprolol. She has been intubated in the ED because of her level of consciousness, and is easy to ventilate and haemodynamically stable. Non-contrast brain CT is normal.
What are the likely causes for this patient’s presentation?
Differentials for "unconscious lady with seizures" are broad:
Differential Diagnosis of Unconsciousness
With focal signs
Without focal signs
Metabolic problem: one of the many encephalopathies (see COATPEGS):
- Carbon dioxide
- Oxygen (hypoxia)
- pH (acidosis)
- Electrolytes, eg. sodium
- Serum osmolality
Diffuse cerebral vascular issues
Brainstem problem (eg. stroke)
The patient was described as having "status epileptics" by the ambulance crew. What is the definition for this term?
Status epilepticus is variably defined as
- 5 minutes or more of continuous seizure activity, or two seizures with no intervening recovery of consciousness. (Oh's Manual; also 2012 Guidelines)
- A continuous state of seizures, or multiple seizures, without return to baseline, resulting in observable or even subjectively perceived sensory, motor, and/or cognitive dysfunction for at least 30 minutes (Question 16 from the second paper of 2014)
The patient is not paralysed, minimally sedated and still unconscious. No seizure activity is taking place.
What other clinical features will you look for?
Clinical features of a non-convulsive status:
- aphasia/ mutism
- fixed-gaze staring.
- uncontrollable blinking
- delirium, delusions, psychosis
- facial twitching (particularly, small periorbital muscles)
- nystagmus/eye deviation
Trainees may also look for evidence of malignancy, drug use, cardiovascular disease, sepsis, etc
What initial investigations will you ask for?
- Bloods (a whole variety of bloods might be appropriate here)
- Tumour markers might be appropriate (limbic encephalitis)
- Inflammatory markers
- CT brain or MRI (though the stem says CT was normal)
LP is performed; opening pressure is 20cm. The following CSF result is revealed:
75 cells / mm3* (60 lymphocytes, 15 RBCs)
0 – 5
0.17- 0.55 g/L
2.8 – 4.5
What differential diagnosis does this suggest?
Different Aetiologies of Encephalitis
Aetiologies of encephalitis
|Mimics of encephalitis
- Viral (eg. HSV)
- Bacterial (eg. tuberculosis, syphilis)
- Protozoal (eg. malaria)
- Fungal (eg, cryptococcus)
- Paraneopladtic encephalitis (immune-mediated)
Inflammatory and idiopathic
- Vertically transmitted infections, eg. neurosyphilis and CMV (Arbalaez, 2014)
- Autoimmune disseminated encephalomyelitis (ADEM)
- Anti-NMDA receptor encephalitis
- Paraneoplastic limbic encephalitis
- many others (see below)
- SAH, intracranial haemorrhage
- Cerbral venous sinus thrombosis
- Reversible vasoconstriction syndrome (Ducros, 2012)
Inflammatory and idiopathic
- Hepatic encephalopathy
- Uraemic encephalopathy
- Electrolyte disturbances (calcium, sodium)
- Wernicke's encephalopathy
The neurology team agrees for a joint admission with themselves and ID, asking for infectious aetiologies to be ruled out. What are the infectious aetiologies which are possible in this scenario?
Infectious Aetiologies of Encephalitis
- Human herpersvirus 6
- Epstein-Barr virus
- Lymphocytic choreomeningitis virus
- Herpes simplex
- Rabies virus
- Rocky Mountain spotted fever
- Q fever
- North American blastomycosis
- Syphilis (secondary or meningovascular)
- Borrelia burgdorferi infection (Lyme disease)
- Mycoplasma pneumoniae infection
- Cat-scratch fever
- Brucellosis (particularly due to Brucella melitensis)
- Typhoid fever
- Whipple's disease
Protozoa and parasites
- Plasmodium falciparum infection
- Amebiasis (due to Naegleria and Acanthamoeba)
What additional tests will you order on the CSF?
- Cryptococcal antigen
- Mycobacterial PCR
- Syphilis PCR
- HSV PCR
- VZV PCR
- India ink stain
- Fungal cultures
- Oligoclonal bands and IgG index
- HIV PCR
- NDMA receptor antibodies
What immediate management will you recommend for this patient?
For the seizures:
First line therapy
- Benzodiazepines: boluses every 2-5 minutes (lorazepam apparently superior)
- Earlier is better (late benzodiazepine therapy is less effective)
- Phenytoin: 20mg/kg loading dose
Second line therapy
- Midazolam infusion
- More phenytoin (O'hs Manual recommends up to 30mg/kg total dose)
- Sodium valproate, 30mg/kg (Oh's Manual recommends a dose range of 10-40mg/kg)
- Phenobarbital/thiopentone, and levetiracetam
For the encephalitis:
- HSV: aciclovir 10mg/kg IV q8h
- Typical bacteria: ceftriaxone and vancomycin
- Autoimmune causes: Dexamethasone
Two days later, ant-NMDA receptor antibody serology returns positive. What is the diagnostic implication of this? What additional management and ivestigations would you recommend?
- This is likely autoimmune-mediated limbic encephalitis
- Investigations looking for malignancy (especially ovarian carcinoma) are in order
- Plasmapheresis is first-line therapy, and should be commenced immediately
The patient continues to have seizures almost every day. EEG suggests ongoing epileptiform activity even while the patient has no outwardly motor manifestations of seizures. What additional management would you recommend?
- Propofol infusion, or midazolam infusion, or thiopentone infusion.
- No real way to discriminate between them all in terms of efficacy
- Continuous EEG monitoring
- Probably no benefit from adding any more traditional antiepileptic drugs once burst suppression is achieved
- Once the seizures resolve, it is recommended you wait for 12 hours before weaning the infusion of anaesthetic drugs.
Fourth line agents: for these, there is little evidence.
Fifth line therapies: