Aseptic Meningitis Differential Diagnoses

Updated: Mar 01, 2021
  • Author: Nitin Butala, MBBS, MS; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Diagnostic Considerations

With few exceptions, the clinical and laboratory findings accompanying acute viral meningitis are insufficiently distinct to allow an etiologic diagnosis, and distinguishing these disorders from a number of nonviral diseases may be difficult. Nevertheless, it is important to differentiate acute viral meningitis, for which no specific treatment is available in immunocompetent individuals (except meningitis due to herpes), from meningitis caused by conditions that are treatable.

Enteroviruses are the principal causes of aseptic meningitis. The major focus of diagnosis remains confirming enteroviral infection or ruling out bacterial infection. Bacterial and aseptic meningitis cannot be distinguished by clinical characteristics alone. Until CSF findings become available, the differential diagnosis of aseptic meningitis is very broad (see Background).

The diagnosis of viral meningitis is based on the clinical presentation and cerebrospinal fluid (CSF) findings that include lymphocyte-predominant pleocytosis of fewer than 500 cells/µL, normal glucose concentration, normal or slightly elevated protein, and negative bacterial antigen tests. The CSF profile in drug-induced aseptic meningitis, which includes neutrophilic pleocytosis, does not distinguish this disorder from infectious meningitis.

Properly implemented nucleic acid tests of CSF are more sensitive than cultures in diagnosing enteroviral infections and have the potential to reduce cost and unnecessary treatment. Other findings, including low concentrations of tumor necrosis factor (TNF) and lactic acid, add further validity for diagnosing aseptic rather than bacterial meningitis.

Diagnosis of HIV encephalitis

HIV encephalitis is characterized by progressive intellectual impairment, behavior disturbances, and sensorimotor deficits. DNA analysis helps to detect HIV in the brains of these patients, and HIV-specific immunoglobulin is produced intrathecally. Congenital HIV encephalitis is more severe than the adult forms and may result in microcephaly and basal ganglia calcification.

Diagnosis of nonviral infectious etiologies

In contrast to the viral causes of aseptic meningitis, nonviral causes of meningitis usually produce a more complicated course and always must be considered because they can be managed with specific treatments.

Consider partially treated bacterial meningitis, especially when the patient has a history of previous oral antimicrobial therapy and when CSF exhibits persistently low glucose or polymorphonuclear pleocytosis. Latex agglutination tests may be useful in these patients.

Diagnosis of tuberculous meningitis

In a healthy host, tuberculous meningitis usually takes the form of an acute-to-subacute illness characterized by fever, headache, drowsiness, meningism, and confusion over a period of approximately 2-3 weeks. Less frequent presentations of CNS tuberculosis include atypical febrile seizures in children, isolated cranial nerve palsies, bilateral papilledema, and acute confusional states. Tuberculous meningitis is difficult to diagnose, and a high index of suspicion is needed for making an early diagnosis.

Diagnosis of brucellosis meningitis

Clinical symptoms of brucellosis are extremely variable. Most commonly, onset occurs 1-2 months after exposure. In the acute form, brucellosis takes the form of a flulike illness, with fever, sweats, malaise, anorexia, headache, myalgia, and back pain.

In the undulant form (< 1 year from onset of illness), symptoms include undulant fevers, arthritis, and orchiepididymitis in males. Neurological sequelae occur in as many as 5% of patients. In the chronic form (>1 year from onset), a chronic fatigue syndrome–like picture with depression and arthritis is typical.

Other complications of brucellosis include granulomatous hepatitis, spondylitis, anemia, leukopenia, thrombocytopenia, uveitis, optic neuritis, papilledema, and endocarditis. Diagnosis is confirmed by the isolation of bacteria from the Brucellaceae family from a bacterial culture or an increase over time in antibodies in the blood that are specific for Brucella species.

Diagnosis of Lyme meningitis

Lyme meningitis typically manifests several weeks after the skin lesions have appeared but may occur while erythema migrans lesions are still present. Hypoglycorrhachia is not a prominent finding. Facial nerve palsy, sometimes bilateral, may be observed.

Diagnosis of ehrlichiosis meningitis

Acute monocytic ehrlichiosis is another tick-borne infection that may present similarly to aseptic meningitis. Laboratory tests may reveal pancytopenia and elevated levels of hepatic transaminases, blood urea nitrogen (BUN), and creatinine.

Diagnosis of syphilitic meningitis

Syphilitic meningitis is becoming more common in the AIDS era. It may coexist with the primary infection or follow it by as long as 2 years. Because of the lack of a typical clinical presentation, a Venereal Disease Research Laboratory test (VDRL) of CSF always must be included in the workup of aseptic meningitis.

Diagnosis of fungal meningitis

Fungal meningitis occurs primarily in patients with AIDS and after organ transplantation, immunosuppressive chemotherapy, or long-term corticosteroid therapy. Nonetheless, disease from the most common fungal meningitis pathogen, Cryptococcus neoformans, can occur in immunocompetent patients. Performing a cryptococcal antigen assay on CSF can be helpful in these situations.

Diagnosis of recurrent benign lymphocytic meningitis

Recurrent benign lymphocytic meningitis is typically a recurring, innocuous, painful form of aseptic meningitis. It is usually caused by herpes simplex virus type 2, which can be confirmed by detection of viral DNA in the CSF using polymerase chain reaction.

Diagnosis of SAPHO syndrome

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is characterized by multifocal aseptic osteomyelitis of an uncertain etiology. Hiwatani et al report a rare case of aseptic meningitis with multiple lower cranial nerve palsy with SAPHO syndrome. [11]

Diagnosis of Vogt-Koyanagi-Harada syndrome

Typically, this syndrome affects dark-skinned individuals or those of Asian races. Symptoms consist of impaired vision, headache, tinnitus, impaired hearing, photophobia, vertigo, vomiting, and seizures. Findings include alopecia, cavities, vitiligo, iridocyclitis, uveitis, and serous retinal detachments. Occasionally, elevated protein and pleocytosis have been found in the CSF.

The disease usually occurs in the third decade of life and follows a recurrent course. Many neurological manifestations are believed to be secondary to adhesive arachnoiditis. Cranial nerve palsies and hemipareses may result. Confusion, psychosis, and seizures also have been reported.

Diagnosis of Behçet syndrome

A triad of uveitis, painful oral ulcers, and genital ulcers characterizes this disease. Other manifestations include arthritis and thrombophlebitis. CNS manifestations include meningoencephalitis, benign intracranial hypertension, papilledema, brainstem lesions, cranial nerve palsies, spinal cord lesions, and mental status changes.

Diagnosis of Mollaret meningitis

Mollaret meningitis is characterized by recurrent episodes of severe headache, meningismus, and fever. These episodes resolve spontaneously and are followed by symptom-free periods of weeks to months

Transient neurological abnormalities, including seizures, diplopia, pathologic reflexes, cranial nerve pareses, hallucinations, and coma, occur in as many as 50% of patients. Cases without fever, with increased CSF gamma globulin and transient neurological signs and symptoms, have been reported.