Encephalitis

Question 1

Encephalitis is a broad term that refers to inflammation of the brain ….

Answer 1

Encephalitis is a broad term that refers to inflammation of the brain parenchyma.

Question 2

Infectious causes of encephalitis - viral

Answer 2

Viral pathogens are commonly implicated in encephalitis. HSV is a common cause of sporadic encephalitis that can be targeted with treatment. Other viral pathogens can include Arboviruses (e.g. West Nile virus), varicella-zoster virus, Epstein-Barr virus, and human immunodeficiency virus (HIV).

Question 3

Infectious causes of encephalitis - bacteria/parasites

Answer 3

Other infectious microorganisms can include bacteria (e.g. Mycoplasma, Tuberculosis, Rickettsial infections), fungi (e.g. Histoplasmosis), and parasites (e.g. Echinococcus). With these types of infections, there may be concurrent inflammation of the meninges leading to meningoencephalitis.

Question 4

The non-infectious causes of encephalitis include a broad range of aetiologies with complex underlying mechanisms. Three of the most pertinent causes include:

Answer 4

Paraneoplastic encephalitis
Post-infectious encephalitis
Autoimmune encephalitis

Question 5

… encephalitis: abnormal immune response against different parts of the brain in the setting of cancer. Thought to be due to shared antigens expressed exclusively by the tumour and nervous system.

Answer 5

Paraneoplastic encephalitis: abnormal immune response against different parts of the brain in the setting of cancer. Thought to be due to shared antigens expressed exclusively by the tumour and nervous system.

Question 6

Herpes simplex virus (HSV) is one of the human herpes viruses that can cause a severe …

Answer 6

Herpes simplex virus (HSV) is one of the human herpes viruses that can cause a severe encephalitis.

Question 7

HSV encephalitis can occur in all ages and may be due to either HSV type 1 or HSV type 2. HSV1 is most commonly seen outside of the neonatal period and causes a clinical syndrome characterised by …

Answer 7

HSV encephalitis can occur in all ages and may be due to either HSV type 1 or HSV type 2. HSV1 is most commonly seen outside of the neonatal period and causes a clinical syndrome characterised by rapid onset of fever, headache, altered mental status, new-onset seizures, and/or neurological deficits (e.g. dysphasia, hemiparesis). Behavioural changes may also be seen in the condition.

Question 8

HSV can cause infection of the central nervous system (CNS) by direct invasion via the … nerve or olfactory tract following primary oropharyngeal infection. Alternatively, invasion into the CNS may occur due to reactivation of the virus that is able to lay dormant within neuronal ganglia after a primary infection that may have been subclinical.

Answer 8

HSV can cause infection of the central nervous system (CNS) by direct invasion via the trigeminal nerve or olfactory tract following primary oropharyngeal infection. Alternatively, invasion into the CNS may occur due to reactivation of the virus that is able to lay dormant within neuronal ganglia after a primary infection that may have been subclinical.

Question 9

Post-infectious encephalitis, also known as acute disseminated encephalomyelitis (ADEM), is a … condition affecting the central nervous system.

Answer 9

Post-infectious encephalitis, also known as acute disseminated encephalomyelitis (ADEM), is a demyelinating condition affecting the central nervous system. Demyelination refers to the destruction/loss of myelin that surrounds nerve axons and helps increase the rate of electrical impulses.

Question 10

Post-infectious encephalitis results in the development of encephalopathy (e.g. confusion, altered mental status, irritability) and other neurological signs (e.g. hemiparesis, cranial nerve palsy, myelopathy) around …-… days following an infection or vaccination.

Answer 10

Post-infectious encephalitis results in the development of encephalopathy (e.g. confusion, altered mental status, irritability) and other neurological signs (e.g. hemiparesis, cranial nerve palsy, myelopathy) around 4-13 days following an infection or vaccination.

Question 11

In NMDA-encephalitis (i.e. autoimmune encephalitis secondary to an autoantibody that targets the NMDA receptor) there is a classic set of symptoms that include (but not limited to) …

Answer 11

psychiatric manifestations (e.g. agitation, bizarre behaviour, hallucinations, delusions), memory deficits, sleep deficits, seizures, altered mental status and autonomic instability (e.g. hyperthermia, fluctuations in blood pressure).

Question 12

… encephalitis: inflammation localised to areas of the … system within the brain that are important in emotion, behaviour, and memory.

Answer 12

Limbic encephalitis: inflammation localised to areas of the limbic system within the brain that are important in emotion, behaviour, and memory.

Question 13

… encephalitis: inflammation affecting the …. Typical features include gaze palsies, dysphagia, dysarthria, central hypoventilation and vertigo.

Answer 13

Brainstem encephalitis: inflammation affecting the brainstem. Typical features include gaze palsies, dysphagia, dysarthria, central hypoventilation and vertigo.

Question 14

The classic presentation of acute encephalitis is …, …, altered mental status and/or … neurological deficits.

Answer 14

The classic presentation of acute encephalitis is fever, headache, altered mental status and/or focal neurological deficits.

Question 15

Possible features of encephalitis: (8)

Answer 15

Fever
Headache
Seizures
Altered mental status: confusion, agitation, irritability, reduced consciousness
Behavioural changes: psychotic features (e.g. delusions, hallucinations) and affective features (e.g. anxiety, depression)
Brainstem dysfunction: dysphagia (abnormal swallowing), dysarthria (abnormal articulation), gaze palsies
Memory problems: cognitive impairment, memory deficits
Focal neurological deficits: hemiparesis (unilateral weakness), cranial nerve neuropathies, cerebellar ataxia

Question 16

It can be difficult to differentiate between meningitis and encephalitis - what are they key differences?

Answer 16

Meningitis refers to inflammation of the meninges and typically presents with headache, photophobia, and neck stiffness (‘meningism’) - invariably present with fever

Brain function should be preserved in meningitis, however in some cases patients may have features of both meningitis and encephalitis that is known as meningoencephalitis

Question 17

What diagnostic tests and investigations are important in the work-up of encephalitis?

Answer 17

Neuroimaging, electroencephalography (EEG) and cerebrospinal fluid (CSF) analysis are important in the work-up of encephalitis.

Question 18

Basic investigations in a suspected encephalitis:

Answer 18

Bedside: observations, urinalysis, ECG, sputum cultures
Bloods: full blood count, urea & electrolytes, bone profile, liver function tests, CRP, blood cultures, coagulation
Imaging: chest x-ray, CT head

Question 19

Neuroimaging for encephalitis

Answer 19

Imaging of the brain is useful to exclude an alternative diagnosis such as cerebrovascular event (i.e. stroke) or space-occupying lesion (e.g. tumour). A CT may be completed initially because it is relatively easy to access and produces a quick result. However, MRI can provide more detail and some features on MRI may be supportive of encephalitis.

Question 20

EEG in suspected encephalitis - why may this be done?

Answer 20

Imaging of the brain is useful to exclude an alternative diagnosis such as cerebrovascular event (i.e. stroke) or space-occupying lesion (e.g. tumour). A CT may be completed initially because it is relatively easy to access and produces a quick result. However, MRI can provide more detail and some features on MRI may be supportive of encephalitis.

Question 21

Performing a lumbar puncture and taking a sample of cerebrospinal fluid is often completed as part of the work-up for encephalitis. This is particularly important for infective causes when analysis of the CSF can directly identify the causative pathogen (e.g. HSV).

A variety of tests may be performed on CSF samples:

Answer 21

CSF protein: a rise in the protein content is typical with encephalitis. May be normal.
CSF viral PCR: involves amplification of viral genetic material within the CSF. Can be used to confirm the diagnosis of HSV encephalitis or other viral pathogens that can be tested.
CSF microscopy, culture and sensitivity: provides a white cell count that may be elevated in encephalitis. HSV1 and autoimmune encephalitis typically cause an elevation in lymphocytes. Microscopy and culture are completed to exclude a bacterial pathogen.
CSF glucose: typically normal in viral encephalitis
CSF serology: antibody tests can be performed on the CSF. Particularly important for paraneoplastic and autoimmune aetiologie

Question 22

CSF protein: a rise in the protein content is typical with …. May be normal.

Answer 22

CSF protein: a rise in the protein content is typical with encephalitis. May be normal.

Question 23

CSF viral PCR: involves amplification of viral genetic material within the CSF. Can be used to confirm the diagnosis of … … or other viral pathogens that can be tested.

Answer 23

CSF viral PCR: involves amplification of viral genetic material within the CSF. Can be used to confirm the diagnosis of HSV encephalitis or other viral pathogens that can be tested.

Question 24

CSF microscopy, culture and sensitivity: provides a white cell count that may be elevated in encephalitis. HSV1 and autoimmune encephalitis typically cause an … in lymphocytes. Microscopy and culture are completed to exclude a bacterial pathogen.

Answer 24

CSF microscopy, culture and sensitivity: provides a white cell count that may be elevated in encephalitis. HSV1 and autoimmune encephalitis typically cause an elevation in lymphocytes. Microscopy and culture are completed to exclude a bacterial pathogen.

Question 25

CSF glucose: typically normal in viral …

Answer 25

CSF glucose: typically normal in viral encephalitis

Question 26

CSF serology: antibody tests can be performed on the CSF. Particularly important for … and autoimmune aetiologies.

Answer 26

CSF serology: antibody tests can be performed on the CSF. Particularly important for paraneoplastic and autoimmune aetiologies.

Question 27

Serological testing - what is this?

Answer 27

This involves performing a blood test and checking the serum for the presence of antibodies associated with paraneoplastic or autoimmune encephalitis.

Question 28

The principal treatment of HSV encephalitis is IV…

Answer 28

aciclovir

Question 29

The primary antiviral treatment available for … encephalitis is aciclovir that works by competitively inhibiting the viral DNA polymerase, which prevents replication

Answer 29

The primary antiviral treatment available for HSV encephalitis is aciclovir that works by competitively inhibiting the viral DNA polymerase, which prevents replication

Question 30

Given that HSV encephalitis is associated with significant morbidity and mortality, intravenous … should be started empirically in anyone with suspected encephalitis.

Answer 30

. Given that HSV encephalitis is associated with significant morbidity and mortality, intravenous aciclovir should be started empirically in anyone with suspected encephalitis.

Question 31

The HSV PCR result from the CSF can then be used to help exclude the diagnosis and enable aciclovir to be discontinued. Occasionally, patients with a high probability of HSV encephalitis may need to continue treatment even with a negative PCR, although the likelihood reduces to 5%. If the HSV PCR is positive, or the disease is highly suspected, a full course of treatment is given over …

Answer 31

The HSV PCR result from the CSF can then be used to help exclude the diagnosis and enable aciclovir to be discontinued. Occasionally, patients with a high probability of HSV encephalitis may need to continue treatment even with a negative PCR, although the likelihood reduces to 5%. If the HSV PCR is positive, or the disease is highly suspected, a full course of treatment is given over 14-21 days.

Question 32

Untreated, HSV encephalitis is associated with a …

Answer 32

Untreated, HSV encephalitis is associated with a high mortality.

Question 33

The mortality associated with HSV encephalitis can be as high as …% even in patients who receive appropriate treatment. Furthermore, residual neurological deficits may remain such as amnesia, impaired new learning, or behavioral abnormalities.

Answer 33

The mortality associated with HSV encephalitis can be as high as 30% even in patients who receive appropriate treatment. Furthermore, residual neurological deficits may remain such as amnesia, impaired new learning, or behavioral abnormalities.

Question 34

Interestingly, HSV encephalitis has been linked with the development of …

Answer 34

Interestingly, HSV encephalitis has been linked with the development of autoimmune encephalitis due to the formation of NMDA receptor antibodies. Therefore, patients who develop recurrent neurological symptoms after treatment for HSV encephalitis should be investigated for a possible autoimmune cause.