Key facts:
Authors: Katharine Elliott and Judith Timms
Top Tip: If you think of it, treat it. Missing it can lead to death or permanent brain damage
Key Differential Diagnoses
- Bacterial/viral meningitis
- Neuroinflammatory disease (eg SLE)
- All acute cerebral diseases (epilepsy, CVA, coma, confusion and abnormal behaviour)
Key Investigations
- FBC, ESR, CRP
- U+E, LFT, Bone, Glucose
- ECG, CXR
- CT ± LP (if no raised ICP; send for HSV PCR)
Note: both CT and LP can be NORMAL
Key Treatments
- IV (NOT ORAL) ACICLOVIR 10 mg/kg tds, for 14-21 days
- (Reduce dose in renal failure)
Key Management Decision
- IV (NOT ORAL) ACICLOVIR (may give even if CT and LP are normal, initially)
Background
If you think of it, treat it; it can take two weeks to prove it. Symptoms can be few and vague. Signs absent
Introduction
- The condition may be a primary infection or as the result of activation of the virus lying dormant (from a previous infection); spreading centripetally from cranial nerve ganglia to frontal and temporal lobes. It may develop in apparently well children without skin lesions. The outcome of this disease depends on early diagnosis and treatment
- It is difficult to diagnose initially. So, if you think of it, treat it
- It is often due to Herpes Simplex 1, which can cause meningitis, encephalitis or meningo-encephalitis. The latter two conditions are frequently severe, causing an acute necrotising encephalitis
- INTRAVENOUS aciclovir should be administered empirically and attempts to establish the diagnosis made by examination of the CSF. The standard dogma that HSV is the commonest cause has been challenged. In a large Finnish study, it was found that VZV was underestimated, and HSV perhaps overestimated in frequency
- Nevertheless HSV detection in viral encephalitis is still critical because there is effective treatment for it: Infections of the central nervous system of suspected viral origin: a collaborative study from Finland: [Ref]
Definition
- Brain inflammation
Distinction between encephalitis and meningitis
- The distinction between meningitis and encephalitis is not as clear cut as it seems. Meningitis is a mainly meningeal condition (as the name would suggest) that can also affect the deeper cerebral tissue; causing some encephalitic inflammation. This may show itself as a reduced conscious level, fitting or 'cerebral irritation' (in which the patient looks a bit 'jumpy', with hyper-reflexia)
- Whereas encephalitis is an inflammation predominantly affecting the deeper cerebral tissue; but can also cause inflammation of the more superficial meninges, causing the syndrome of 'meningism' (headache, neck pain, photophobia)
- You can have both - ie meningo-encephalitis. For example, the same organism (eg HSV) can cause either condition, or both
Epidemiology
- Incidence: 2-5/million/year
- Peaks 31-40 yrs
[Ref]
Causes
- Herpes simplex 1 (90% due to HSV1 in immunocompetent patients; 10% HSV2; mainly in immunocompromised [Ref]
- Other herpes viruses: varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus 6 (HHV6)
- Adenoviruses
- Influenza A
- Enteroviruses, poliovirus
- Measles, mumps and rubella viruses
- Rabies
- Arboviruses - eg Japanese B encephalitis, West Nile encephalitis virus
- Bunyaviruses - eg La Crosse strain of California virus
- Reoviruses - eg Colorado tick fever virus
- Arenaviruses - eg lymphocytic choriomeningitis virus
Types
- Encephalitis
- Meningo-encephalitis
Risk factors
- Other illness
- Immunsosuppression
- HIV
- Sunlight, menstruation
Symptoms
- The symptoms may be vague, noticed by friends and family only
- The history is vital
- Never accept that the 'history is not available' for a confused patient; track down a relative or neighbour on the phone. Comments from relatives that a patient 'does not seem right', should not be ignored, even if the Glasgow Coma Score is 15; remember this is a very crude tool that was devised for assessing patients with head injuries
- It can present in virtually any 'neurological way', sometimes abruptly, following a viral prodrome:
- Headache/meningism, fever
- Abnormal behaviour (from mild personality change (eg strange affect, maybe reported by family) to acute psychiatric disorder)
- Acute confusion
- Myelitis
- Focal neurological symptoms or signs (can be dysphasic, aphasic or mute)
- Generalised or focal seizures
- Decreased level of consciousness
Note: NICE recommends in a child <5y, it should be considered the diagnosis of exclusion, with these last three presentations
Key questions
- "When did the symptoms start?"
- "Have you been abnormally sleepy, confused recently?"
- "Have you had a viral illness recently, especially 'cold sores'?"
Signs
- There may be no signs
- Meningism, fever
- Myelitis
- Focal neurology/speech disorder
- Seizures
- Reduced conscious level
Investigation
All patients with a febrile illness and altered behaviour or consciousness should be investigated for CNS infection (CT/LP), unless there is very clear evidence of another diagnosis
Blood
- FBC, ESR, CRP
- U+E, LFT, Bone, Glucose
- ABG, if unwell
Other
- ECG
- CXR (?aspirated if fitted)
- CT; if impaired consciousness, signs of raised ICP or focal signs then a CT of the head should be done before LP (and no LP done, if brain is 'tight')
Note: in HSV encephalitis there may be low attenuation lesions in one or both temporal lobes. There may be diffuse brain oedema (MRI more sensitive to these changes) - LP:
- mild-moderately increased cell count (5-500), mostly lymphocytes .. or NORMAL (5%)
- mildly raised protein (0.6-6.0 g/L)
- normal glucose (vs bacterial meningitis)
- no organisms on Gram stain
- HSV PCR; may detect viral antigens; can take 72h to become positive
Note: false -ve HSV PCR usually encountered if CSF collected too early (can take 8-24h to become abnormal after onset of symptoms), too late (after 10-14 days), after aciclovir therapy, or if there was a long delay in processing the sample that was stored inappropriately after collection
Note: all these changes are unreliable, so do not let initial CT/LP affect treatment, if you have a high index of suspicion
Key investigations
- CT
- LP
Specialist investigation
- MRI; more sensitive than CT at detecting early encephalitic changes
This MRI show symmetrical bilateral putaminal vasogenic oedema with mild restriction on diffusion and no bleed
Possible sequelae
EEG; in HSV, there may be generalised slowing and bursts of high-voltage slow wave complexes, particularly over the temporal lobes
Note: these changes are unreliable, so do not let MRI/EEG affect treatment, if you have a high index of suspicion- Brain biopsy; occasionally needed
Differential diagnosis
- Bacterial/viral meningitis
- Neuroinflammatory disease (eg SLE)
- All causes of epilepsy
- All causes of stroke
- All causes of comaAll causes of acute confusion
- All causes of acute abnormal behaviour
- Brain abscess
- Subarachnoid haemorrhage
- Migraine
- TB
Treatment
Encephalitis is rare. But patients with CNS problems who MIGHT have viral encephalitis, are not. So, if in doubt, treat, until an alternative diagnosis comes out
Treatment (first line)
Drugs
- IV (NOT ORAL) ACICLOVIR 10 mg/kg tds for 14-21d (reduce dose in renal failure); many clinicians stop Rx too soon - resulting in a relapse
- ± IV CEFTRIAXONE 2 g od; ie, you should have a low threshold for covering bacterial meningitis too (especially if has been given prior AB, by GP)
Procedures
- IV (+fluids, if dry)
- OYXGEN, if hypoxic
Key management decision
- IV (NOT ORAL) ACICLOVIR (may give even if CT and LP are normal, initially)
Stop/reduce
- Immunosuppression (after DW prescriber)
Treatment (second line)
Drugs
- If not responding within 24h, DW Microbiology/Virology
- If suspect raised ICP, consider
- IV/O DEXAMETHASONE 10 mg stat, then 4 mg qds
- ± IV MANNITOL
- ± decompressive surgery (eg shunt), if hydrocephalus develops. These are all specialist decisions
Note: another cause of raised ICP is haemorrhage into necrotic tissue
Procedures
- If unwell, urinary catheter, CVP line, arterial line
Prescribing issues
Only use INTRAVENOUS ACICLOVIR; and for a long course (14-21d); reduce dose in renal failure
Admit?
- Always
Bed plan
- Medical admission ward
- Neurology
- ± ITU
Referrals
Medical
- Neurology
- Microbiology (± infectious disease, and/or virology, if you have a service)
- ± ITU
The Rest
Maxim
- "If you miss viral encephalitis, the consequences will be disasterous .. for everyone (see complications"
Complications
- Permanent brain damage, causing:
- Weakness (eg hemiparesis)
- Behavioral and emotional (personality change)
- Cognitive (memory, speech)
- Sensory (vision, hearing)
- Some patients who experience memory problems and personality changes afterward describe their condition as being an 'invisible disease'. They appear to be normal to others, but they are plagued with forgetfulness and lapses in attention; this has a considerable affect on their Quality of Life (QoL)
Note: the degree and type of brain damage can vary from mild-to-severe and from focal (in one part of the brain) to multifocal (several parts of the brain) to diffuse (throughout the brain)
Epilepsy
Follow-up
- Neurology 2 weeks
Prognosis
- Poor if Rx delayed
- 20% mortality (70% untreated HSV)
2° Prevention + Health promotion
- Patients with HSV elsewhere (eg oral) should be prewarned to seek medical help urgently, if they become generally unwell, confused or drowsy
Don't forget
- Presentation very variable; from mild affect change to coma
- If in doubt, cover bacterial meningitis as well
- HSV PCR can take two weeks to come back
- IV (NOT ORAL) ACICLOVIR 10 mg/kg tds, for 14-21 days (LONG COURSE)
Red flags
- Focal neurology
- Seizures
