Articles on Medical Diseases and Conditions

Tag: Cryptococcus

  • Human Immunodeficiency Virus Meningitis

    As noted in Chapter 17, the HIV-1 (AIDS) virus may produce a mild aseptic meningitis lasting 2-3 weeks as the first clinical manifestation of infection. The exact incidence is unknown, but it is probably greater than the 2%-5% estimated in one report. The majority of patients do not manifest this stage but develop more advanced disease at some time in the future. Later in the disease, more than 30%-70% of patients develop symptoms of CNS infection. Some of these cases are due to superimposed infection by other organisms (Toxoplasma, Cryptococcus) rather than HIV alone. HIV infection of the brain is most often manifested by dementia, but more than 15% develop progressive focal leukoencephalopathy. There is relatively little information about CSF findings in this disorder. In one report, 27% had elevated protein levels and 14% had elevated WBC count, with all cell counts being less than 25/mm3 and with 80%-100% of the cells being mononuclear. The brain abnormalities are best shown by CT or MRI.

  • Viral and Aseptic Meningitis

    Viral meningitis is one component of a syndrome known as aseptic meningitis. The aseptic meningitis syndrome is now usually defined as meningitis with normal CSF glucose levels, normal or elevated protein levels, and elevated cell count with a majority of the cells being lymphocytes. A less common definition is nonbacterial meningitis; a definition no longer used is meningitis with a negative bacterial culture. The CSF findings of aseptic meningitis may be caused by a wide variety of agents, including different viruses, mycobacteria, Listeria, syphilis, Leptospira, Toxoplasma, fungi, meningeal carcinomatosis, and meningeal reaction to nearby inflammatory or destructive processes or to some medications in a few patients. However, viral meningitis is the most common and typical of the conditions that produce this syndrome. The commonest virus group associated with meningitis is enterovirus, which includes ECHO (enteric cytopathic human orphan) virus and coxsackievirus and comprises 50%-80% of viral meningitis patients; the second most common (10%-20%) is mumps. Other viruses include herpes simplex, arbovirus group, herpes zoster-varicella, and lymphocytic choriomeningitis. Although not usually listed, human immunodeficiency virus 1 (HIV-1) (or acquired immunodeficiency syndrome [AIDS]) may be, or may become, one of the most frequent etiologies. There are several reasons for describing the aseptic meningitis syndrome and specifically mentioning viral meningitis. First, it is useful to know what etiologies to expect with this pattern of CSF results. Second, this pattern is not specific for viral etiology. Third, a significant number of patients infected by many of these etiologies do not present with textbook aseptic meningitis findings. This is most true for lymphocytes versus neutrophils as the dominating cell in early enterovirus, mumps, and arbovirus infections. Reports estimate that 20%-75% of patients with viral meningitis have neutrophil predominance in the first CSF specimen obtained. For example, one investigator found that about 50% of enteroviral meningitis patients had more than 10% neutrophils on the first CSF specimen, and about 25% had neutrophils predominating; about 66% had normal protein levels; and about 10% had decreased glucose. Most reports indicate that repeat lumbar puncture in 8-12 hours frequently shows change from neutrophil to lymphocyte predominance, with conversion of the remainder taking place in 24-48 hours. In enterovirus, mumps, herpes simplex, and lymphocytic choriomeningitis, initial CSF glucose is sometimes mildly decreased rather than the expected normal value.

    Differential diagnosis of aseptic meningitis syndrome etiologies generally involves differentiating virus etiology from mycobacterial and cryptococcal infection. CSF culture can be done for all the usual virus possibilities, but viral specimens usually must be sent to a reference laboratory, and the results are not available for several days or even longer. It has been recommended that CSF specimens either be processed in less than 24 hours or be frozen at – 70°C to preserve infectivity. Many viruses lose infectivity when frozen at the usual temperature of – 20°C. Serologic tests are also available but require acute and convalescent serum specimens and thus take even longer than culture. As noted there, herpes simplex type 1 has a predilection for involvement of the temporal lobe of the brain. Cryptococcus and mycobacterial tests have been discussed earlier in this chapter. CSF lactate (lactic acid) has been advocated to separate viral from nonviral etiology but, as discussed earlier, is not always helpful and thus is still somewhat controversial.

  • Cryptococcal Meningitis

    Cryptococcus neoformans is the most common fungus producing CNS infection and is an important, although not numerically frequent, etiology of meningitis. The organism is discussed in detail in Chapter 16. About 70% of cryptococcal meningitis cases are male, and the majority are of middle age. About one-half are associated with malignancy or other severe diseases or with immunodeficiency (either from underlying disease or from therapy). Meningitis due to Cryptococcus is said to produce an elevated cell count in about 95% of cases (range, 90%-97%). The count is usually less than 300/mm3 and in the majority of cases is less than 150/mm3. In one series, the CSF cell count was less than 100/mm3 in about 60% of patients. More than one half of the cells are lymphocytes. Protein levels are elevated in about 90% of cases. The CSF glucose level is decreased in 50%-75% of cases.

    The LA slide test for cryptococcal antigen in CSF is the best rapid diagnostic test. It is reported to detect about 85%-90% of cases (literature range, 71%-100%). There is a slightly increased detection rate if both CSF and serum are tested. Serum testing alone detects about 50% of cases (range, 18%-71%). The LA test is discussed in detail in Chapter 16. The older procedure for detection of Cryptococcus in CSF was a wet mount using india ink or nigrosin. C. neoformans has a thick gelatinous capsule that gives the appearance of a clear zone or halo around the organism against the dark background of india ink particles. However, only about 50% (range, 40%-79%) of cases can be detected by india ink preparations, and some of these may require repeated examinations. In addition, experience is needed to avoid false positive and negative results. India ink has been replaced by the LA test.

    Although LA tests for cryptococcal antigen are reasonably sensitive, culture of CSF is still considered essential. In some cases, culture may reveal organisms when the CSF cell count, protein levels, and glucose levels are all normal. Culture detects about 80% of patients on initial lumbar puncture (range, 72%-90%). Fungi require different culture media for optimum growth than the standard bacterial media, so the laboratory should be notified if fungi are suspected. In some patients, cryptococcal antigen latex studies on CSF have been positive when cultures were negative, and in a few cases, cultures were positive when the LA test result was negative.