Differentials
West Nile virus infection
SIGNS / SYMPTOMS
No differentiating signs or symptoms, but lower case fatality rate.
West Nile virus neuroinvasive disease is rarely seen in children, unlike with eastern equine encephalitis virus infection.
INVESTIGATIONS
One of following: fourfold increase in the antivirus antibody titre between acute and convalescent serum; isolation of virus from tissue, blood, or cerebrospinal fluid (CSF); detectable IgM antibody to virus in single serum or CSF sample.
La Crosse virus infection
SIGNS / SYMPTOMS
No differentiating signs or symptoms, but fatalities are rare.
INVESTIGATIONS
One of following: fourfold increase in the antivirus antibody titre between acute and convalescent serum; isolation of virus from tissue, blood, or cerebrospinal fluid (CSF); detectable IgM antibody to virus in single serum or CSF sample.
St Louis encephalitis
SIGNS / SYMPTOMS
No differentiating signs or symptoms, but symptoms are generally milder and lower case fatality rate.
INVESTIGATIONS
One of following: fourfold increase in the antivirus antibody titre between acute and convalescent serum; isolation of virus from tissue, blood, or cerebrospinal fluid (CSF); detectable IgM antibody to virus in single serum or CSF sample.
Liver enzyme elevations may be seen.
Powassan encephalitis
SIGNS / SYMPTOMS
No differentiating signs or symptoms, but lower case fatality rate.
INVESTIGATIONS
One of following: fourfold increase in the antivirus antibody titre between acute and convalescent serum; isolation of virus from tissue, blood, or cerebrospinal fluid (CSF); detectable IgM antibody to virus in single serum or CSF sample.
Western equine encephalitis (WEEV) infection
SIGNS / SYMPTOMS
No differentiating signs or symptoms, but lower case fatality rate.
WEEV infections occur mainly on the west coast of the US.
INVESTIGATIONS
One of following: fourfold increase in the antivirus antibody titre between acute and convalescent serum; isolation of virus from tissue, blood, or cerebrospinal fluid (CSF); detectable IgM antibody to virus in single serum or CSF sample.
Herpes simplex virus (HSV) encephalitis
SIGNS / SYMPTOMS
An oral or genital ulcer may be present, or the patient may have a recent history of such an ulcer.
While fever and headache are common, myalgias, arthralgias, and vomiting are less common.
INVESTIGATIONS
Positive HSV polymerase chain reaction (PCR) of cerebrospinal fluid is diagnostic.
MRI often reveals hyperintensity of the temporal lobes on T2-weighted images.
Listeria monocytogenes (rhombo) encephalitis
SIGNS / SYMPTOMS
Systemic and central nervous system symptoms are very similar to eastern equine encephalitis virus infection, but may be accompanied by respiratory failure as well.
Meningoencephalitis is mostly seen in infants, pregnant women, or immunosuppressed individuals.
INVESTIGATIONS
Cerebrospinal fluid and/or blood cultures may grow Listeria.
MRI may show lesions in the brainstem.
Rabies encephalitis
SIGNS / SYMPTOMS
Classically, excessive salivation, dysphagia, and hydrophobia may accompany headache, fever, and altered mental status.
There may be a history or physical evidence of an animal bite.
Universally fatal.
INVESTIGATIONS
Multiple tissue samples are necessary for diagnosis (saliva, skin, serum, cerebrospinal fluid).
Polymerase chain reaction (PCR) of skin biopsy or saliva is positive for rabies virus RNA.
Positive serology for rabies virus.
Paraneoplastic and autoimmune encephalitis
SIGNS / SYMPTOMS
Symptoms similar to eastern equine encephalitis virus infection.
Psychiatric symptoms, abnormal movements, seizures, autonomic instability, and hypoventilation are important hallmarks.
Underlying malignancy may be identified.
INVESTIGATIONS
Detection of paraneoplastic or autoimmune antibodies in cerebrospinal fluid.
Toxoplasma encephalitis
SIGNS / SYMPTOMS
Tends to be more subacute.
Seen typically in immunocompromised individuals (especially HIV).
INVESTIGATIONS
Cerebrospinal fluid is positive for Toxoplasma gondii DNA on polymerase chain reaction (PCR).
MRI or CT often reveals central nervous system space-occupying lesions.
Toxoplasma serum IgG is detectable (with titre).
Cryptococcal meningitis
SIGNS / SYMPTOMS
Seen typically in immunocompromised individuals (especially HIV).
Advanced disease may present with lethargy and coma.
Increased intracranial pressure is a common finding, giving rise to seizures, coma, and death.
INVESTIGATIONS
Detection of cerebrospinal fluid (CSF) or serum cryptococcal antigen.
CSF Gram stain may reveal yeast forms.
CSF culture shows growth of Cryptococcus species.
Increased opening pressure on lumbar puncture.
Bacterial meningitis
SIGNS / SYMPTOMS
May be no differentiating signs or symptoms; however, a non-blanching petechial or purpuric rash can be present with bacterial meningitis.
Post-infectious encephalomyelitis (acute disseminated encephalomyelitis)
SIGNS / SYMPTOMS
May be triggered by a viral or bacterial infection, but is autoimmune in nature.
Symptoms similar to eastern equine encephalitis virus infection.
Mostly seen in children.
INVESTIGATIONS
Diagnosis is based on clinical and radiological features, and may be a diagnosis of exclusion.
MRI findings include deep and subcortical white matter lesions, as well as grey matter lesions in the basal ganglia and thalami.
Central nervous system tuberculosis
SIGNS / SYMPTOMS
Tends to be more subacute; associated with weeks of weight loss, low grade temperatures, night sweats.
There may be evidence of concurrent pulmonary tuberculosis.
INVESTIGATIONS
Extremely low glucose in cerebrospinal fluid (CSF; <10 mg/dL).
Elevated protein in CSF (>200 mg/dL).
Mycobacterium tuberculosis may be isolated from cerebrospinal fluid (CSF), but turnaround time is very slow and sensitivity is low.
Mycobacterium tuberculosis DNA may be detected by polymerase chain reaction (PCR) of CSF, but sensitivity is low.
Amoebic meningoencephalitis
SIGNS / SYMPTOMS
Patient may have a history of exposure to freshwater or soil.
INVESTIGATIONS
Diagnosis is usually made postmortem.
Polymerase chain reaction (PCR) of brain tissue or cerebrospinal fluid for Balamuthia mandrillaris, Acanthamoeba species, or Naegleria fowleri.
Zika virus infection
SIGNS / SYMPTOMS
Zika is now found in the Americas and overlaps geographically with eastern equine encephalitis virus distribution.
Zika is a disease characterised by fever, rash, myalgias, arthralgias, headache, retro-orbital pain, conjunctivitis, and vomiting.
The disease is transmitted by Aedes mosquitoes and it has been reported in Mexico, South America, North America, Africa, and South East Asia.
INVESTIGATIONS
Diagnosis is confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Serology tests are available but they strongly cross-react with other flaviviruses, such as dengue and West Nile virus.
Leptospirosis
SIGNS / SYMPTOMS
Neurological involvement is less common with leptospirosis.
In severe cases, jaundice, renal failure, and bleeding can occur.
There is usually a history of exposure to contaminated water or soil, or contact with infected animals or their depositions.
INVESTIGATIONS
Diagnosis depends on detection of Leptospira antibodies by serology, Leptospira DNA by real-time polymerase chain reaction (PCR), or, less commonly, isolation of Leptospira on cultures of blood or urine.
Rocky Mountain spotted fever
SIGNS / SYMPTOMS
The rash tends to evolve into a purpuric appearance. It classically affects palms and soles.
Common complications include: encephalitis, adult respiratory distress syndrome, cardiac arrhythmias, coagulopathy, gastrointestinal bleeding, and skin necrosis.
INVESTIGATIONS
Diagnosis is made by detection of Rickettsia rickettsii antibodies by serology.
Polymerase chain reaction (PCR) can be used to detect R rickettsii DNA, but sensitivity is low early in the course of the disease.
Epstein-Barr virus (EBV) infection
SIGNS / SYMPTOMS
Encephalitis is very rare.
Maculopapular and pruritic rash may follow administration of ampicillin or amoxicillin.
Complications such as airway obstruction from massive adenopathy and spleen rupture may occur.
Course tends to be more prolonged (weeks) for EBV compared with eastern equine encephalitis virus infection (days).
INVESTIGATIONS
Diagnosis is made by detection of heterophile antibodies or EBV-specific antibodies and by DNA detection.
Acute retroviral syndrome following HIV infection
SIGNS / SYMPTOMS
A history of recent sexual contact is usually obtained.
During the acute retroviral syndrome, pharyngitis can be prominent.
Rash may affect the palms and soles.
INVESTIGATIONS
Best diagnosis method for acute retroviral syndrome is quantitative serum HIV RNA level (viral load) and HIV antigen/antibody immunoassay and/or HIV nucleic acid test.
Venezuelan equine encephalitis virus (VEEV) infection
SIGNS / SYMPTOMS
No differentiating signs or symptoms, although neurological sequelae may be less severe.
INVESTIGATIONS
Enzyme-linked immunosorbent assay (ELISA) with plaque reduction neutralisation test: positive for VEEV antibodies (IgG or IgM).
Tuberculous meningitis
SIGNS / SYMPTOMS
No differentiating signs or symptoms.
Birth in tuberculosis-prevalent countries.
INVESTIGATIONS
Detection of acid-fast bacilli in cerebrospinal fluid using polymerase chain reaction (PCR).
CT/MRI: can show cerebral tuberculomas or basilar arachnoiditis.[55]
Viral meningitis
SIGNS / SYMPTOMS
A non-blanching petechial or purpuric rash is typical of viral meningitis.
INVESTIGATIONS
Cerebrospinal fluid polymerase chain reaction (PCR) positive for specific viruses.
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