Encephalitis Overview

• Refers to inflammation of the brain parenchyma, usually due to infection, that causes altered mental status as well as various neurological deficits depending on the area that is affected. 
• As opposed to meningitis, patients with encephalitis tend to present with more profound alterations in mental status and neurological deficits.  Seizures can be seen with both meningitis and encephalitis, as can fever and headache.  In reality, the distinction is often blurred as many patients have both parenchymal and meningeal processes (“meningoencephalitis”).

 

Etiologies – 3 main categories:
1. Infectious – most common cause, and majority from viruses, less commonly bacterial and parasitic.
2. Postinfectious Encephalitis (aka Acute disseminated Encephalomyelitis – mainly affects children/adolescents - see below).
3. Autoimmune/Paraneoplastic  - being increasingly recognized now, but still much less common than infectious etiologies (see below).

 

I.  Viral Encephalitis
A whole host of viruses can cause encephalitis.  The most common fall into 3 groups:
1)  Herpes Viruses – HSV-1 (and HSV-2 to a much lesser extent), VZV, CMV, EBV, HHV-6.  Herpes viruses tend to be the most devastating among viral encephalitides (except for rabies).

** Of all causes of viral encephalitis, it is most important to recognize HSV-1 encephalitis (and to a less extent VZV, which is much less common) because these are often fatal, yet potentially treatable with prompt Acyclovir therapy. **

2)  Enteroviruses – coxsackievirus, echovirus, enterovirus, poliovirus

3)  Arboviruses – West Nile virus, St. Louis encephalitis, Eastern and Wester Equite Encephalitis, Colorodo Tick Fever, La Crosses.  These tend to be transmitted via mosquitoes.  West Nile virus is the most common arbovirus to cause encephalitis in the US (~100 cases were reported in California in 2009), although it causes neuroinvasive disease in less than 1% of infected immunocompetent patients.
Less common causes of viral encephalitis:

• Rabies – very rare in the US now, but causes 30,000-70,000 deaths/year worldwide.  Majority in developing countries are from dog bites, but in the US the #1 cause is bat bites (and patients are often unaware that they were bitten).   Incubation period usually is 1-3 months, but can be up to 1 year or more!  Followed by a prodrome period of nonspecific symptoms, then acute neurological syndrome (encephalitic rabies vs paralytic rabies), followed by coma and death.  Once neurological symptoms develop, the disease is almost uniformly fatal, so important to recognize this early!
• Influenza, Mumps, Measles, Rubella – rare, and can also cause Postinfectious encephalitis / ADEM (see below)
• HIV

Diagnosis:

• CT scan – more helpful to rule out other causes, but temporal lobe enhancement can help point towards herpes encephalitis (but MRI is superior to CT scan)
• MRI – as above, temporal lobe enhancement suggests HSV, but other herpes viruses can also do this (as can noninfectious limbic encephalitis).
• LP – CSF findings look like an aseptic meningitis picture:

- Pleocytosis, but usually < 250 WBC, with lymphocyte predominance
- Mildly elevated protein, usually < 150
- Normal to mildly low glucose
- If RBCs present (with nontraumatic tap) – suggests HSV-1 encephalitis (present in 84% of patients)
- Normal opening pressure

• CSF PCRs are extremely useful – available PCRs include HSV, VZV, CMV, EBV, Adenovirus, and Enterovirus.  PCR is generally very sensitive and specific.  West Nile Abs can be sent (IgM in the CSF is diagnostic for WNV encephalitis).
• Multiple serum serologies for viruses can be helpful as well.

Starting empiric Acyclovir (10 mg/kg IV q8 hrs) ASAP for empiric HSV and VZV coverage is generally a good idea while waiting for PCR confirmation, as early therapy has been shown to significantly reduce mortality and neurologic disability in HSV encephalitis.  For most of the other viral encephalitides, treatment is mostly supportive.

 

 

II.  Postinfectious Encephalitis, aka ADEM (Acute Disseminated Encephalomyelitis)

• Demyelinating disease, similar to multiple sclerosis, that can affect brain or spinal cord or both.
• Occurs after viral infections (like influenza, mumps, measles, rubella), but can also occur after vaccination, and bacterial and parasitic infections.
• Majority of cases occur in children and adolescents (average age is 5-8).
• Mortality is about 5%, with full recovery in 50-70% of patients.  However, adults have a worse prognosis.
• Treatment = steroids, IVIG, and plasmapheresis.

 

 

III.  Autoimmune/Paraneoplastic Encephalitis

• "Limbic Encephalitis”presents similar to viral encephalitis, with prominent mood and behavioral changes, short term memory loss, seizures, cognitive dysfunction, and hypothalamic dysfunction.
•  Most frequently associated with lung cancer (especially squamous cell carcinoma), also seminomas/testicular cancers, thymomas, breast cancer, and hodkins lymphoma. 
• Pathophysiology involves "onconeural" antigen: an appropriate immune response against a tumor antigen cross-reacts with similar antigens expressed by the nervous system

Classified by their associated Abs – obviously, not important for us to memorize these, but just to be aware that they exist!  Here are just a few examples:
1. NMDA Receptor Associated Limbic Encephalitis – recently recognized entity, associated with ovarian teratomas in women.  In males, tumor is often not detectable.  Presents with viral-like prodrome, followed by psychotic symptoms, insomnia, seizures, dyskinesias, and automnomic instability.  These patients often require ICU care for weeks to months.  Can affect young children as well as adults.
2. Ma2-associated Encephalitis - limbic encephalitis or brain stem encephalitis, seminomas and nonseminomatous or mixed germ cell tumors
3. Anti-Hu Abs - severe sensory irreversible neuronopathy + limbic encephalitis
... and many more.
Treatment for these paraneoplastic limbic encephalitides involves finding the tumor, resecting it if possible; also, steroids, IVIG, and plasmapheresis are associated with improved outcomes.

 

 

IV.  Overview of the California Encephalitis Project

• Started in 1998 to study encephalitis.  Samples are sent to Richmond, CA.
• From 1998-2005, 1570 patients were studied, and a confirmed or probable etiology for encephalitis was only found in 16% of cases.  Of those, the majority were viral (69%) and 20% were bacterial.  13% of cases had a possible etiology identified, 8% had noninfectious etiology, and 63% had no identifiable etiology.

Process involves sending 4 things to the Richmond lab, as well as filling out multiple forms and summarizing history, labs, exposures, physical exam, etc.
1. CSF – they test with PCR for HSV1 + 2, VZV, HHV-6, and Enterovirus.  Other studies are done as appropriate per the history.
2. Acute phase serum: they test for serologies for EBV, Mycoplasma pneumonia, Parvovirus B19, and West Nile.
3. Nasopharyngeal/throat swab – test for PCR for enterovirus and mycoplasma, and respiratory viruses (influenza, adenovirus, RSV, metapneumovirus).
4. Convaslescent phase serum (10-14 days after acute serum)

 

(Chanu Rhee MD, 2/8/11)