This article discusses:
- Clinical presentation of meningitis and encephalitis (and subtypes)
- Diagnostic workup: CSF analysis, imaging, electroencephalogram
- Treatment options
A 26-year-old man with a history of intravenous drug use and hepatitis C presented with headache and neck pain. Magnetic resonance imaging (MRI) of the brain and cervical spine are shown in Figure 1. T1 post-contrast imaging (right) shows diffuse leptomeningeal enhancement at the cervico-medullary junction and throughout the cord. At the time of presentation the patient was started on empiric broad spectrum bacterial meningitis coverage with ampicillin, vancomycin, and ceftriaxone without significant improvement. Leptomeningeal biopsy revealed fungal meningitis with visualized candida albicans species. Patient improved with fluconazole treatment.
The differential diagnosis of meningitis and encephalitis includes bacterial, viral, fungal, and autoimmune etiologies. Initial diagnostic testing should be directed at excluding life-threatening, common, and treatable etiologies; further work up should be focused on the temporal pattern of the illness, clinical clues, and epidemiological risk factors. Often, the first step is to distinguish between the clinical entities of meningitis, encephalitis, and encephalopathy.
Meningitis refers to the inflammation of the leptomeninges. The classic clinical presentation of meningitis includes the triad of headache, fever, and neck stiffness, though this occurs in less than half the cases, however almost all patient have at least 2 of the 4 symptoms of headache, fever, neck stiffness, and altered mental status.
Viral meningitis has the highest prevalence; the average annual rate in the US isgreater than 36,000 cases per year. The most common cause of viral meningitis are the non-polio enteroviruses, accounting for over half of reported cases.1 Other causes of viral meningitis include the herpesviruses with Herpes simplex virus (HSV)-2 as the most common cause of aseptic meningitis in the immunocompetent.
Chronic or recurrent meningitis remains a challenge and often takes several weeks to months to correctly diagnose. HSV-2 remains the most common organism for chronic meningitis. In those with eosinophils present in the cerebrospinal fluid (CSF), one must rule out parasitic infections, syphilis, and tuberculosis as potential causes. Fungal infections such as Cryptococcus neoformans and histoplasmosis can also lead to chronic meningitis and should be evaluated in the correct geographical context.
Encephalitis is defined by major and minor criteria (Table 1). Although a patient can have concurrent involvement of the spinal cord (encephalomyelitis) or meninges (meningoencephalitis), evidence of brain inflammation is the key distinguishing feature. Encephalopathy, by contrast, is a symptom that may result from underlying encephalitis or a host of toxic, metabolic, or vascular causes (Table 2).
The main differential for encephalitis includes infectious (viruses being the most common), and autoimmune etiologies. There are more than 100 pathogens known to cause infectious encephalitis. Autoimmune etiologies associated with neural autoantibodies are becoming increasingly recognized making the diagnosis challenging.
Infectious encephalitis. HSV infection is the most common and treatable cause of viral encephalitis. HSV encephalitis (HSVE) generally has temporal lobe involvement visualized on MRI defined by abnormal T2 signal abnormalities and contrast enhancement, typically with asymmetric involvement. This is in contrast to autoimmune limbic encephalitis, which tends to be symmetric involvement and without contrast enhancement.
Evaluation includes an initial HSV polymerase chain reaction on the CSF as well as immediate treatment with empiric intravenous acyclovir. If clinical suspicion remains high in the setting of a negative initial polymerase chain reaction, therapy should be continued until a repeat polymerase chain reaction is obtained. In younger patients, especially under the age of 30 years, anti N-methyl-d-aspartate (NMDA) receptor encephalitis can have a similar clinical presentation and should be evaluated for if the HSV polymerase chain reaction is negative. MRI findings in these patients are normal in about 50% of cases and can provide a useful tool with differentiating these syndromes.
If patients with recent HSVE present with relapsing symptoms a few weeks after a course of acyclovir for 14 to 21 days, repeat diagnostic work up should include evaluation for NMDA receptor antibodies. Studies suggest that HSVE can trigger anti-NMDA receptor encephalitis.2-5
Arbovirus encephalitis (Table 3) also have to be considered in the appropriate seasonal and geographical context. In the US, West Nile virus is the most common and ubiquitous arbovirus. Most infections present with a prodromal flu-like illness and, although rare, can progress to CNS involvement later in the course.
Autoimmune encephalitis. Autoimmune etiologies are increasingly recognized as a common cause of encephalitis and have been associated with neuronal autoantibodies (Table 4). Often presenting with an infectious prodrome, they can generally be distinguished from infectious etiologies through MRI, CSF analysis, and neuronal autoantibody testing.
Dr Khan is a Neuro-Infectious Diseases Neuroimmunology Fellow and Dr Piquet is Assistant Professor, Department of Neurology, University of Colorado School of Medicine, Aurora, CO.
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