Viva 5

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

Stroke

Haemorrhage

Abscess

Trauma

Tumour

Without focal  signs

Drugs

Metabolic problem: one of the many encephalopathies (see COATPEGS):

  • Carbon dioxide
  • Oxygen (hypoxia)
  • Ammonia
  • Temperature
  • pH (acidosis)
  • Electrolytes, eg. sodium
  • Glucose
  • Serum osmolality

Diffuse cerebral vascular issues

Brainstem problem (eg. stroke)

Encephalitis

Seizures

Vasculitis

With meningism

Vascular causes:

  • Subarachnoid haemorrhage

Infectious causes:

  • Meningitis
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:

Negative symptoms:

  • anorexia,
  • aphasia/ mutism
  • amnesia
  • catatonia
  • confusion,
  • coma
  • lethargy
  • fixed-gaze staring.

Positive symptoms:

  • agitation/aggression
  • automatisms
  • uncontrollable blinking
  • delirium, delusions, psychosis
  • echolalia
  • 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
LP is performed; opening pressure is 20cm. The following CSF result is revealed:

Parameter

Value

Normal Range

Cell count

75 cells / mm3* (60  lymphocytes, 15 RBCs)

0 – 5

Protein

0.89 g/L*

0.17- 0.55 g/L

Glucose

4.0 mmol/L

2.8 – 4.5

Gram stain

Negative
What differential diagnosis does this suggest?
Different Aetiologies of Encephalitis

Aetiologies of encephalitis

 Mimics of encephalitis

Infectious

  • Viral (eg. HSV)
  • Bacterial (eg. tuberculosis, syphilis)
  • Protozoal (eg. malaria)
  • Fungal (eg, cryptococcus)

Neoplastic /paraneoplastic

  • Paraneopladtic encephalitis (immune-mediated)

Inflammatory and idiopathic

  • Prion disease

Congenital

  • Vertically transmitted infections, eg. neurosyphilis and CMV (Arbalaez, 2014)

Autoimmune

  • Autoimmune disseminated encephalomyelitis (ADEM)
  • Anti-NMDA receptor encephalitis
  • Paraneoplastic limbic encephalitis
  • many others (see below)

Vascular

  • Stroke
  • SAH, intracranial haemorrhage
  • Cerbral venous sinus thrombosis
  • PRES
  • Reversible vasoconstriction syndrome (Ducros, 2012)

Infectious

  • Septic encephalopathy

Neoplastic /paraneoplastic

  • CNS lymphoma

Drug-induced

  • Toxins, alcohol, etc

Inflammatory and idiopathic

  • Status epiilepticus

Traumatic

  • Post-TBI encephalopathy

Metabolic

  • Hepatic encephalopathy
  • Uraemic encephalopathy
  • Hypoglycaemia
  • 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

Viral

  • Coxsackie 
  • Echovirus
  • Human herpersvirus 6
  • HIV
  • Adenoviruses
  • Epstein-Barr virus
  • Cytomegalovirus
  • Mumps
  • Lymphocytic choreomeningitis virus
  • Arboviruses
  • Herpes simplex
  • Rabies virus

Intracellular bacteria

  • Rickettsia
  • Rocky Mountain spotted fever
  • Typhus
  • Q fever

Fungi

  • Cryptococcosis
  • Coccidioidomycosis
  • Histoplasmosis
  • North American blastomycosis
  • Candidiasis

Typical bacteria

  • Syphilis (secondary or meningovascular)
  • Leptospirosis
  • Borrelia burgdorferi infection (Lyme disease)
  • Mycoplasma pneumoniae infection
  • Cat-scratch fever
  • Listeriosis
  • Brucellosis (particularly due to Brucella melitensis)
  • Tuberculosis
  • Typhoid fever
  • Whipple's disease

Protozoa and parasites

  • Toxoplasmosis
  • Cysticercosis
  • Echinococcosis
  • Trichinosis
  • Trypanosomiasis
  • 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:

 

Disclaimer: the viva stem above may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station. 

[Submit a comment or correction]