Articles on Medical Diseases and Conditions

Month: August 2009

  • Brain Abscess

    Brain abscess is most commonly due to direct extension of infection from infected middle ear, mastoid sinus, or paranasal sinuses; traumatic injuries, or infected prostheses. There can also be more distant spread from the lungs or from infected emboli. There is increased incidence in immunosuppressed patients. The most frequent organisms cultured are various streptococci, Bacteroides, gram-negative organisms, and Staphylococcus aureus. Mixed infections are present in 30%-60% of cases. Apparently the CSF findings in brain abscess are not significantly influenced by the causative organism or the location of the lesion. About 10% of patients are said to have normal CSF test results. The remainder usually have a picture compatible with aseptic meningitis. The spinal fluid is most often clear, and about 70% of patients are said to have increased pressure. Protein levels are normal in nearly 25% of patients, in about 55% the values are between 45 and 100 mg/100 ml (0.45-1.0 g/L), and in the remaining 20% the values are more than 100 mg/100 ml. The CSF glucose level is normal. Cell counts are variable; about 30% are between 5 and 25, about 25% are between 25 and 100, and about 25% are between 100 and 500/cu mm. Lymphocytes generally predominate, but a significant percentage (5%-25%) of polymorphonuclear neutrophils are said to be nearly always present. In occasional cases, an abscess breaks through to the subarachnoid space and results in purulent meningitis. CT or MRI is very helpful in demonstrating intracerebral abscesses. Radionuclide brain scans are useful if CT is not available.

  • 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.

  • Central Nervous System Infection by Other Fungi

    Candida is said to be the most common fungal infection of the CNS. About one half of the patients with Candida CNS infection have a lymphocytic pleocytosis and about one half show a predominance of neutrophilis. Some reports have indicated a surprisingly high rate of CNS involvement in the systemic mycoses (blastomycosis, 3%-10%; histoplasmosis, up to 50%; coccidioidomycosis, up to 50%). These fungi most often produce a lymphocytic pleocytosis, but neutrophils may predominate. Cerebrospinal fluid glucose levels are typically reduced but may be normal.

  • 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.

  • Mycobacterial Meningitis

    Mycobacterial meningitis is most common in children between the ages of 6 months and 5 years and in the elderly. Chest x-ray film is reported to show hilar adenopathy in 50%-90% of children, but normal chest findings are more common in adults (in one series, about 50% of adults had normal chest x-ray findings). Purified protein derivative skin test result is negative in 5%-50% of patients. Mild to moderate anemia is frequent. The erythrocyte sedimentation rate is elevated in 80% of patients. CSF findings typically show moderate WBC elevation (usually <500/mm3 and almost always <1,000), with the majority being lymphocytes. However, there frequently are a significant number of neutrophils and sometimes, in the early stages, a majority of neutrophils. Protein level is usually mildly or moderately elevated (in one series, 76% had elevated protein levels on admission). Glucose level is decreased in 50%-85% of patients on admission. To have cell count, protein level, and glucose level all three normal on admission is extremely rare, although this happened in 3 of 21 patients in one report. Diagnosis is based on acid-fast smear, culture, exclusion of other etiologies, evidence of tuberculosis elsewhere, and clinical suspicion. Acid-fast smears on CSF are positive in about 20%-40% of cases (range, 3%-91%), and CSF culture is positive in only 37%-90% of cases. When findings are atypical, a nucleic acid probe with polymerase chain reaction (PCR) amplification on CSF can be helpful if it is available.

  • Cerebrospinal Fluid Findings in Selected Brain Diseases: CNS Syphilis

    Syphilis is discussed in Chapter 15. CNS syphilis can be diagnosed clinically but is much more accurately diagnosed through tests on CSF. In two studies, cell counts were normal (<5 cells) in 19%-62%, between 5 and 10 cells in 24%-69%, and more than 10 cells in 12%-14%. The majority of the cells were mononuclear in 60%-80% of the cases and polymorphonuclear in 20%-40% of the cases. CSF protein was normal in 14%-61% of patients, between 45 and 100 mg/dl in 34%-61%, and more than 100 mg/dl in 5%-25%. The Veneral Disease Research Laboratory (VDRL) test on CSF specimens was reactive in about 55% of the patients (literature range, 10%-70%). A serum VDRL test was reactive in 49%-86% of the patients. It was noted that before penicillin was discovered, CSF studies recorded much higher incidence and degree of abnormalities.

    CNS syphilis usually requires serologic tests for diagnosis. The standard serologic tests for syphilis such as the VDRL usually, but not always, give positive results on peripheral blood specimens when they are positive on CSF. A lack of relationship is most often found in the tertiary stage, when the peripheral blood VDRL test result may revert to normal. Conversely, the CSF response is very often negative when the peripheral blood VDRL result is positive. CNS syphilis usually is a tertiary form with symptoms appearing only after years of infection, and in many patients with syphilis the CNS is not clinically involved at all. Despite lack of clinical CNS symptoms, actual CNS involvement apparently is fairly common (in at least 30%-40% of syphilis cases), beginning in the primary and secondary stage; although specific syphilitic syndromes, if they develop, are not seen until the tertiary stage years later. There is some evidence that concurrent infection by the HIV-1 virus may increase the risk of active CNS syphilis. The best criteria of CNS disease activity are elevated CSF cell count and protein levels (however, CSF WBCs are reported to be elevated in 38%-81% of cases and CSF protein elevated in 39%-86%). A reactive CSF VDRL result indicates disease that has been present for a certain length of time, without necessarily being currently active. The CSF VDRL usually is normal in patients with biologic false positive (BFP) serologic test for syphilis (STS) reactions. After adequate treatment CSF pleocytosis usually disappears within 3 months (range, 1.5-6 months). CSF protein elevation, however, may persist as long as several years.

    The three most important forms of CNS clues are general paresis, tabes dorsalis, and vascular neurosyphilis. In general paresis, the CSF serology almost always is normal in untreated patients. In tabes dorsalis, the CSF serology is said to be abnormal in most early untreated patients, but may be normal in up to 50% of late or “burnt-out” cases. In vascular neurosyphilis, approximately 50% of results are abnormal.

    The FTA-ABS is nearly always reactive in peripheral blood when CSF shows some laboratory abnormality suggestive of neurosyphilis. The FTA-ABS has been shown to be more frequently reactive than the VDRL when testing the CSF of patients with syphilis. Several studies reported 100% of patients with the diagnosis of CNS syphilis had a reactive CSF FTA-ABS response. However, a substantial number of patients who were asymptomatic and had normal CSF cell counts and protein also had a reactive CSF FTA-ABS response. Therefore, the U.S. Centers for Disease Control (CDC) and an important segment of other investigators currently believe that a reactive CSF FTA-ABS response does not necessarily represent active CNS syphilis and that the clinical importance of a reactive FTA-ABS test on spinal fluid is uncertain when the cell count, protein, and spinal fluid VDRL results are normal. There is also the problem of spinal fluid contamination by blood, which could produce false positive results if the contaminating blood contained serum antibodies.

    Based on current CDC recommendations, the FTA-ABS test is usually not done on CSF, since there is no problem of BFP reactions in the spinal fluid VDRL (unless the CSF is contaminated with blood), and the peripheral blood FTA-ABS test is reactive in almost all cases of CNS syphilis. Unfortunately, there is currently no gold standard to determine which patients actually have CNS syphilis and therefore how accurate the various CNS laboratory tests really are.

    Up to 75% of patients with active CNS syphilis may demonstrate oligoclonal bands on CSF electrophoresis (similar to those seen in multiple sclerosis).