In terms of published material, Arun Venkatesan's dossier on encephalitis appears both recent (2017) and comprehensive. Unfortunately the free copy available online does not have information regarding  what it was written for or whether it underwent peer review A slightly less recent paper by the same author (2014) seems somehow more authoritative because it has the official stamp of the AAN all over it. Both articles are excellent and each compliments the other. These papers were blended together with random factoids and pointless trivia to produce the summary offered below.

Clinical features of encephalitis

What peculiarities must one manifest in order for one's coma to be declared an "encephalitis"? What, even, is the definition of this term? Lot's of people have tried to come up with something workable, partly for the purpose of classifying papers or organising epidemiological data. In general, all are in agreement that certain fundamental features must be present:

  • Major criteria:
    • Encephalopathy and altered level of consciousness, personality or some other CNS function: i.e., with an encephalitis, clinically one should not have a perfectly functioning brain. 
    • A protracted time course, i.e. greater then 24 hrs (to discriminate this from your bog-standard delirium)
  • Minor ciriteria: some features to distnguish encephalitis from encephalopathy, to demonstrate an inflammatory change in the CNS:
    • Seizures in a non-epileptic
    • New focal neurological signs
    • Pleocytosis of the CSF
    • Fever
    • MRI (or CT) changes suggestive of inflammation
    • EEG abnormalities suggestive of encephalitis

This group of criteria comes from the Venkatesan's 2014 paper, and Venkatesan quotes himself (Venkatesan, 2012) as the source. The latter article has an enhanced credibility because it was a consensus statement of a massive international panel of experts (the  International Encephalitis Consortium).  This group themselves admitted freely that the manifestations of encephalitis are protean, and that no workable definition could possibly encompass the entire case spectrum (for example, isolated brainstem encephalitis might not satisfy the major criteria because of preserved consciousness)

Differential diagnosis for encephalitis

This, judging by what eminent authors have written, should be divided into "aetiologies of different kinds of encephalitis" and "things which are not encephalitis but are similar enough to fool the person applying a set of standard criteria". Beyond that, clearly there is a need to expand on the infectious and autoimmune aetiological categories, as they are larger than the rest and also because they account for such a large proportion of the presentations.  As such:

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)

Autimmune

  • 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
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)

The list of viral and bacterial agents comes from an excellent (but somewhat dated) paper by Johnson (1996). Specifically, the viral agents are organised in increasing order of severity (i.e. coxsackie viruses are the least severe and rabies the most severe). The same article also contains an excellent table of different historical details, joined to the aetiology they suggest. It is so good that one could not help but reproduce it in full here:

causes of encephalitis with historical details

Additionally, the LIFTL entry on encephalitis lists this group of locally important infectious aetiologies:

Unique infectious etiologies to consider in Australia, include:

  • Hendra virus
  • Australian bat lyssavirus
  • Murray Valley encephalitis virus

Causes of encephalitis that are importnat regionally have potential for introduction into Australia include:

  • Japanese encephalitis virus
  • Enterovirus 71
  • Dengue virus
  • Nipah virus

Though these lists seem comprehensive, if one is indeed in need of a significantly larger level of detail, the article by Granerod et al (2010)  has a massive table (Table 1) which goes into extensive detail regarding the specific clinical features associated with every possible pathogen. 

Autoimmune encephalitis is a group of diverse aetiologies which are usually associated with either cancer somewhere (i.e. they are paraneoplastic) or with some co-existing autoimmune disease (eg. lupus or sarcoidosis). They are easily arrayed according to what cancer and what antibody they tend to test positive for.  The table below was concocted mainly using data from Dalmau et al (2014), and is far from complete.

Autoimmune Aetiologies for Encephalitis
Syndrome Antibody Associated cancer  or  autoimmune disease
PEM Anti-Hu SCLC
PCD Anti-Yo Gynaecological and breast cancer
Anti-CV2/CRMP5 SCLC, thymoma
Anti-Tr  Hodgkins lymphoma
Opsoclonus-myoclonus  Anti-Ri Gynaecological and breast cancer
Limbic encephalitis NMDA receptor  Ovarian teratoma
AMPA receptor  Gynaecological and breast cancer, thymoma
GABAB receptor  Neuroendocrine tumour, esp.  lung
LGI1 Thymoma
mGluR5  Hodgkin lymphoma 
PERM Glycine receptor Stiff-person syndrome
Basal gangial encephalitis Dopamine receptor Sydenham's chorea

Other encephalitis-producing autoimmune disease:

  • Systemic lupus
  • Sarcoidosis
  • Behcet's disease

Diagnostic tests

To borrow again from the 2014 paper by Venkatesan, the following routine and "conditional" investigations are recommended:

Routine studies

  • CSF:  opening pressure, cell count with differential, protein, glucose
  • Gram stain and bacterial culture
  • HSV-1/2 PCR (if test available, consider HSV CSF IgG and IgM in addition)
  • VZV PCR 
  • Enterovirus PCR
  • Cryptococcal antigen or India ink staining
  • Oligoclonal bands and IgG index
  • VDRL for syphilis

Serum

  • Routine blood cultures
  • HIV serology (consider RNA)
  • Treponemal testing (rapid plasma reagin, specific treponemal test)

Imaging

  • Neuroimaging (MRI preferred to CT, if available)
  • Chest imaging (chest x-ray or CT)

Neurophysiology

  • EEG

Other tissues/fluids

  • When clinical features of extra-CNS involvement are present, this may be appropriate (e.g., biopsy of skin lesions; bronchoalveolar lavage or endobronchial biopsy)

Conditional studies

  • Immunocompromised host:
    • CMV PCR, HHV6/7 PCR, Toxoplasma gondii; MTB, fungal infections, West Nile Virus PCR
  • Geographic factors
    • Africa—malaria, trypanosomiasias, dengue
    • Asia—Japanese encephalitis virus, dengue, malaria, Nipah virus
    • Australia—Murray Valley encephalitis, Kunjin virus, Australian bat lyssavirus
    • Europe—tick-borne encephalitis virus; if Southern Europe, consider WNV testing, Toscana virus testing
    • Central and South America—dengue, malaria, WNV, Venezuelan equine encephalitis
    • North America—geographically appropriate arboviruses (e.g., WNV, Powassan, LaCrosse, Eastern equine encephalitis virus, St. Louis encephalitis, dengue, Lyme)
  • Season and exposure
    • Summer/autumn: WNV and other arboviruses, tick-borne disease
    • Cat (particularly if with seizures, paucicellular CSF)—Bartonella
    • Tick exposure—tick-borne disease
    • Animal bite/bat exposure—rabies
    • Swimming or diving in warm freshwater or nasal/sinus irrigation—Naegleria fowleri

Management

It goes without saying that:

  • Different aetiologies of encephalitis require different management strategies
  • Many are so rare that expert opinion and case reports are all the guidance we have
  • Each individual case is going to be potentially very different
  • No intensivist would ever undertake to treat such a scenario in a professional vacuum, and consultation with multiple specialities is going to be the most important step they can take

But, for the answer to Question 21 form the second paper of 2019, the trainees needed to produce a list of specific management strategies without having been given a specific aetiology. Given that the pass rate was around 23%, one might assume they found it difficult. This very basic list of steps is offered here as a launchpad for their own thinking: 

  • Supportive management
    • A, B, C: Intubate the patientto facilitate investigations (LP and MRI are challenging if they are having seizures or in the grip of a violent psychosis)
    • Manage cerebral oedema with head positioning, hypetonic saline or mannitol
    • Protect them from seizures with sedation and benzodiazepines or antiepileptics
  • Specific management
    • HSV: aciclovir 10mg/kg IV q8h
    • CMV: ganciclovir, cidofovir, foscarnet
    • HHV6: ganciclovir 5mg/kg IV q12h
    • HIV: antiretroviral drugs
    • Rabies: rabies immune globulin
    • Bacterial aetiologies:
      • TB: isoniazid, rifampicin, pyrazinamide and streptomycin
      • Typical bacteria: ceftriaxone and vancomycin
    • Autoimmune causes
      • Methylprednisolone
      • Dexamethasone
      • Rituximab
      • Cyclophosphamide
      • Plasmapheresis

References

Venkatesan, Arun. "CLINICAL APPROACH TO ACUTE ENCEPHALITIS." (2017).

Singh, Tarun D., Jennifer E. Fugate, and Alejandro A. Rabinstein. "The spectrum of acute encephalitis: causes, management, and predictors of outcome." Neurology 84.4 (2015): 359-366.

Granerod, J., et al. "Challenge of the unknown: a systematic review of acute encephalitis in non-outbreak situations.Neurology 75.10 (2010): 924-932.

Granerod, J., et al. "Causality in acute encephalitis: defining aetiologies." Epidemiology & Infection 138.6 (2010): 783-800.

Venkatesan, Arun, and Romergryko G. Geocadin. "Diagnosis and management of acute encephalitis: A practical approach." Neurology: Clinical Practice 4.3 (2014): 206-215.

Virchow, Rud. "über interstitielle Encephalitis." Virchows Archiv 44.4 (1868): 472-476.

Venkatesan, Arun, et al. "Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium.Clinical Infectious Diseases 57.8 (2013): 1114-1128.

Johnson, Richard T. "Acute encephalitis." Clinical Infectious Diseases (1996): 219-224.

Arbelaez, Andres, et al. "Congenital Brain Infections." Topics in Magnetic Resonance Imaging 23.3 (2014): 165-172.

Ducros, Anne. "Reversible cerebral vasoconstriction syndrome." The Lancet Neurology 11.10 (2012): 906-917.

Dalmau, Josep, and Myrna R. Rosenfeld. "Autoimmune encephalitis update." Neuro-oncology 16.6 (2014): 771-778.