Cerebrospinal Fluid Laboratory Research Articles

Fulminant Idiopathic Intracranial Hypertension

Fulminant idiopathic intracranial hypertension is extremely rare but invariably is associatedwith permanent blindness unless there is prompt intervention. Hypothetically, a rapid increase in pressure in the perineural space around the optic nerve can lead to ischemic opticneuropathyandblindness.1An 18-year-oldoverweightwoman with rapidly progressive visual loss over 4 days (leading to no light perception), nonreactive pupils, binocular abduction deficit suggestiveof sixthnervepalsies,bilateraloptic-discedema(Frisenstage 5),2 and cerebrospinal fluid opening pressure at 600 mm H2O receivedadiagnosisof fulminant idiopathic intracranialhypertension.1 The results of cerebrospinal fluid laboratory studies,magnetic resonance imaging of the brain, and vascular imagingwere normal. Our Figure, AandB, showsmagnetic resonance imagingscansof thepatient’s orbits at the time of presentation. Anemergent,controlled lumbardrainwasput inplace,andtreatment with intravenous methylprednisolone sodium succinate and furosemide was started on the first day. Five days later, her visual acuitywas20/400 inbotheyes, herpapilledema improved, andher abduction deficits resolved. Our Figure, C and D, shows follow-up magnetic resonance imaging scans on day 5. A ventriculoperitoneal shunt was performed for relatively long-term control of cerebrospinal fluidpressure.Onday9, herpapilledema improved toFri-

Neoplastic Meningitis: How MRI and CSF Cytology Are Influenced by CSF Cell Count and Tumor Type

Background. Although CSF cytology and MRI are standard methods to diagnose neoplastic meningitis (NM), this complication of neoplastic disease remains difficult to detect. We therefore reevaluated the sensitivity of gadolinium (GD)-enhanced MRI and cerebrospinal-fluid (CSF)-cytology and the relevance of tumor type and CSF cell count. Methods. We retrospectively identified 111 cases of NM diagnosed in our CSF laboratory since 1990 with complete documentation of both MRI and CSF cytology. 37 had haematological and 74 solid neoplasms. CSF cell counts were increased in 74 and normal in 37 patients. Results. In hematological neoplasms, MRI was positive in 49% and CSF cytology in 97%. In solid tumors, the sensitivity of MRI was 80% and of cytology 78%. With normal CSF cell counts, MRI was positive in 59% (50% hematological, 72% solid malignancies) and CSF cytology in 76% (92% in hematological, 68% in solid neoplasms). In cases of elevated cell counts, the sensitivity of MRI was 72% (50% for hematological, 83% for solid malignancies) and of CSF cytology 91% (100% for haematological and 85% for solid neoplasms). 91% of cytologically positive cases were diagnosed at first and another 7% at second lumbar puncture. Routine protein analyses had a low sensitivity in detecting NM. Conclusions. The high overall sensitivity of MRI was only confirmed for NM from solid tumors and for elevated CSF cell counts. With normal cell counts and haematological neoplasms, CSF-cytology was superior to MRI. None of the analysed routine CSF proteins had an acceptable sensitivity and specificity in detecting leptomeningeal disease.

Two cases of medically-refractory spontaneous orthostatic headaches with normal cerebrospinal fluid pressures responding to epidural blood patching: Intracranial hypotension versus hypovolemia and the need for clinical awareness

The diagnosis of spontaneous intracranial hypotension or cerebrospinal fluid (CSF) hypovolemia syndrome requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features. A 31-year-old male, presented with subacute onset moderate occipital and sub-occipital headaches precipitated by upright posture and relieved on recumbency and neck pain for 2 years. There was no trauma, cranial/spinal surgery. Clinical examination was normal and CSF opening pressure and laboratory study were normal. Magnetic resonance imaging (MRI) brain showed thin subdural hygroma. Another patient, 41-year-old male presented with 1 month of subacute onset severe bifrontal throbbing orthostatic headaches (OHs). CSF opening pressure was normal. Contrast MRI brain showed the presence of bilateral subdural hygromas, diffuse meningeal enhancement, venous distension, sagging of the brain, and tonsillar herniation. We report two cases of “spontaneous OHs” with normal CSF pressures who were successfully treated with epidural blood patching after poor response to conservative management.

Normal reference values for testing of cerebrospinal fluid in term and preterm infants

Srinivasan et al have provided a valuable service to clinicians and infants worldwide by performing and analyzing in an exacting way the cerebrospinal fluid (CSF) findings of preterm and term infants who did not have central nervous system infections. Their findings provide most reliable, clinically relevant cutpoints for normal findings that we ever have had or likely will have in the future. Contrary to tenets from previously published data, CSF white blood cell counts in preterm and term infants are similar and are low (upper bound cutpoints of 14 cells/mm3), even in the first week of life. This study is superior to others in the past, most notably because of careful exclusion criteria and prospective approach that aided correct patient categorization and minimized missing data. An important caveat is that infants with CSF red blood cell counts of >500 cells/mm3, presumably from hemorrhage, birth trauma, or traumatic lumbar puncture, were excluded. Inclusion of such infants in prior studies speculatively could be a major reason why we held as “normal” higher limits of white blood cell counts and protein concentrations. It is noteworthy that 30% of infants evaluated for inclusion in the study were excluded because of high red blood cell counts. Findings are not generalizable to this group.The additional finding that short-term antibiotic therapy prior to lumbar puncture did not affect cutpoints in a clinically meaningful way will be most useful in settings in the neonatal intensive care unit, when cardiorespiratory instability precludes CSF examination prior to therapy and when CSF is only successfully obtained 1-2 days after treatment of neonates admitted from emergency departments.Article page 729▶ Srinivasan et al have provided a valuable service to clinicians and infants worldwide by performing and analyzing in an exacting way the cerebrospinal fluid (CSF) findings of preterm and term infants who did not have central nervous system infections. Their findings provide most reliable, clinically relevant cutpoints for normal findings that we ever have had or likely will have in the future. Contrary to tenets from previously published data, CSF white blood cell counts in preterm and term infants are similar and are low (upper bound cutpoints of 14 cells/mm3), even in the first week of life. This study is superior to others in the past, most notably because of careful exclusion criteria and prospective approach that aided correct patient categorization and minimized missing data. An important caveat is that infants with CSF red blood cell counts of >500 cells/mm3, presumably from hemorrhage, birth trauma, or traumatic lumbar puncture, were excluded. Inclusion of such infants in prior studies speculatively could be a major reason why we held as “normal” higher limits of white blood cell counts and protein concentrations. It is noteworthy that 30% of infants evaluated for inclusion in the study were excluded because of high red blood cell counts. Findings are not generalizable to this group. The additional finding that short-term antibiotic therapy prior to lumbar puncture did not affect cutpoints in a clinically meaningful way will be most useful in settings in the neonatal intensive care unit, when cardiorespiratory instability precludes CSF examination prior to therapy and when CSF is only successfully obtained 1-2 days after treatment of neonates admitted from emergency departments. Article page 729▶ Cerebrospinal Fluid Reference Ranges in Term and Preterm Infants in the Neonatal Intensive Care UnitThe Journal of PediatricsVol. 161Issue 4PreviewTo determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit. Full-Text PDF

Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data

An affordable, highly immunogenic Neisseria meningitidis serogroup A meningococcal conjugate vaccine (PsA-TT) was licensed for use in sub-Saharan Africa in 2009. In 2010, Burkina Faso became the first country to implement a national prevention campaign, vaccinating 11·4 million people aged 1-29 years. We analysed national surveillance data around PsA-TT introduction to investigate the early effect of the vaccine on meningitis incidence and epidemics. We examined national population-based meningitis surveillance data from Burkina Faso using two sources, one with cases and deaths aggregated at the district level from 1997 to 2011, and the other enhanced with results of cerebrospinal fluid examination and laboratory testing from 2007 to 2011. We compared mortality rates and incidence of suspected meningitis, probable meningococcal meningitis by age, and serogroup-specific meningococcal disease before and during the first year after PsA-TT implementation. We assessed the risk of meningitis disease and death between years. During the 14 year period before PsA-TT introduction, Burkina Faso had 148 603 cases of suspected meningitis with 17 965 deaths, and 174 district-level epidemics. After vaccine introduction, there was a 71% decline in risk of meningitis (hazard ratio 0·29, 95% CI 0·28-0·30, p<0·0001) and a 64% decline in risk of fatal meningitis (0·36, 0·33-0·40, p<0·0001). We identified a statistically significant decline in risk of probable meningococcal meningitis across the age group targeted for vaccination (62%, cumulative incidence ratio [CIR] 0·38, 95% CI 0·31-0·45, p<0·0001), and among children aged less than 1 year (54%, 0·46, 0·24-0·86, p=0·02) and people aged 30 years and older (55%, 0·45, 0·22-0·91, p=0·003) who were ineligible for vaccination. No cases of serogroup A meningococcal meningitis occurred among vaccinated individuals, and epidemics were eliminated. The incidence of laboratory-confirmed serogroup A N meningitidis dropped significantly to 0·01 per 100 000 individuals per year, representing a 99·8% reduction in the risk of meningococcal A meningitis (CIR 0·002, 95% CI 0·0004-0·02, p<0·0001). Early evidence suggests the conjugate vaccine has substantially reduced the rate of meningitis in people in the target age group, and in the general population because of high coverage and herd immunity. These data suggest that fully implementing the PsA-TT vaccine could end epidemic meningitis of serogroup A in sub-Saharan Africa. None.

Cerebrospinal Fluid Reference Ranges in Term and Preterm Infants in the Neonatal Intensive Care Unit

To determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit. Data were collected prospectively as part of a multisite study of infants aged <6 months undergoing lumbar puncture for evaluation of suspected sepsis. Infants with a red blood cell count >500 cells/μL or a known cause of CSF pleocytosis were excluded from the analysis. A total of 318 infants met the inclusion criteria. Of these, 148 infants (47%) were preterm, and 229 (72%) received antibiotics before undergoing lumbar puncture. The upper reference limit of the CSF white blood cell (WBC) count was 12 cells/μL in preterm infants and 14 cells/μL in term infants. CSF protein levels were significantly higher in preterm infants (upper reference limit, 209 mg/dL vs 159 mg/dL in term infants; P < .001), and declined with advancing postnatal age in both groups (preterm, P = .008; term, P < .001). CSF glucose levels did not differ in term and preterm infants. Antibiotic exposure did not significantly affect CSF WBC, protein, or glucose values. CSF WBC counts are not significantly different in preterm and term infants. CSF protein levels are higher and decline more slowly with postnatal age in preterm infants compared with term infants. This study provides CSF reference ranges for hospitalized preterm and term infants, particularly in the first month of life.

Three Cases of Ophthalomplegic Migraine

Purpose: To report three cases of ophthalmoplegic migraine which is a rare condition characterized by the association of headaches with an oculomotor nerve palsy. Case summary: A 44-year-old male and two eight-year-old females were presented with diplopia developed after headaches. All of the three patients showed abnormal eye movement and they had past episodes of transient diplopia with headaches. Visual evoked potential (VEP), cerebrospinal fluid (CSF) examination, laboratory findings, and other neurologic tests were all normal, also there was no tumor or cerebrovascular disease on brain MRA & MRI. The symptoms of all patients improved gradually within several weeks from first the visit, with complete recovery seen in all three. Conclusions: Any patient who has a headache with paresis of the extraocular muscle should be considered for ophthalmoplegic migraine. To diagnose ophthalmoplegic migraine, family history, past medical history, associated symptoms and signs, neurologic examinations and neuroimaging tests are needed.

Relative Quantity of Cerebrospinal Fluid Herpes Simplex Virus DNA in Adult Cases of Encephalitis and Meningitis: Table 1

Herpes simplex virus (HSV) remains an important cause of meningitis and encephalitis in adults, and polymerase chain reaction (PCR)-based tests are the "gold standard" for diagnosis. The objective of this study was to assess differences in semiquantitative PCR values, based on the crossing threshold (Ct) value for cases of HSV meningitis and encephalitis. A retrospective chart review was performed for 29 patients with a documented diagnosis of HSV meningitis or encephalitis during the course of 5 years from a large urban academic hospital. Demographic information, cerebrospinal fluid (CSF) laboratory findings, and PCR data were obtained for each patient. There was no statistically significant difference in the Ct values in patients with meningitis or encephalitis. In addition, no differences were found in CSF chemistry and hematology parameters. There is a broad range in relative concentrations of HSV DNA in the CSF in cases of meningitis and encephalitis.

Neoplastic meningitis—Is MRI as sensitive as CSF cytology?

9566 Background: Although CSF cytology and MRI are standard methods for the diagnosis of neoplastic meningitis (NM), this complication of neoplastic disease still remains to be difficult to detect in some cases. We therefore re-evaluated the sensitivity of gadolinium(GD)-enhanced MRI and cerebrospinal-fluid (CSF)-cytology for the diagnosis of LM differentially for solid and haematological malignancies and for normal or elevated cell counts. Methods: We identified retrospectively 101 cases of NM diagnosed in our CSF laboratory since 1990 with complete data of both MRI and CSF-cytology. 34 had haematological, 67 solid neoplasms. CSF-cell counts were increased in 63 and normal in 35 patients. Results: For haematological neoplasms, MRI was positive in 53%. CSF cytology was positive in 97%. In solid tumours, we found MRI-sensitivity of 0.81 and cytological sensitivity of 0.76. With normal CSF-cell-counts, MRI was positive in 63%, (0.57 haematological, 0.75 solid malignancies), CSF-cytology in 78%, (0.9 in haematological, 0,64 in solid neoplasms). In cases of increased cell-counts, MRI-sensitivity was 0.75 (0.52 for haematological, 0.87 for solid malignancies), and sensitivity of CSF-cytology was 0.89 (1.0 for haematological and 0.82 for solid neoplasms). 23 patients were treated with intrathecal MTX or Ara-C, 16 patients with liposomal Ara-C. 62 patients were not treated intrathecally. Conclusions: We confirmed here the high overall sensitivity of MRI for the diagnosis of neoplastic meningitis. The best sensitivity, however, was seen in solid tumours and elevated cell counts. In haematological malignancies, a markedly lower sensitivity of MRI was seen. Of note, we consider the very high sensitivity of cytology in haematological malignancies to be artificial due to methodological reasons of this retrospective study. We conclude that MRI is a very sensitive method to detect NM especially in solid tumours and elevated cell counts. With normal cell counts and haematological neoplasms, CSF-cytology remains to be superior to radiological methods. [Table: see text]

Increased intrathecal synthesis of fibronectin in bacterial and carcinomatous meningitis

Immunoreactive fibronectin (Fn) was quantified in paired cerebrospinal fluid (CSF) and serum samples from patients with bacterial meningitis (n = 46), tick-borne encephalitis (TBE) (n = 6), HIV infection (n = 6), Guillain-Barré syndrome (n = 5), carcinomatous meningitis (n = 11), multiple sclerosis (n = 15), disk disease (n = 11), and controls (n = 28). A highly significant elevation of CSF Fn was found in bacterial meningitis, TBE, and carcinomatous meningitis. There were no significant differences in serum Fn between any of the groups. An Fn index to estimate the rate of intrathecal Fn synthesis reached the highest value in bacterial meningitis. Our findings suggest that CSF Fn may be an indicator of adequate host reaction and tissue repair. For diagnostic purposes, the determination of CSF Fn probably does not add much to routine CSF laboratory tests.

Phase 2 Safety Trial Targeting Amyloid β Production With a γ-Secretase Inhibitor in Alzheimer Disease

To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease. Multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial. Community-based clinical research centers. Patients Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100 mg [n=22] or 140 mg [n=14]), with 43 completing the treatment phase. Intervention The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks. Primary outcome measures were adverse events, plasma and cerebrospinal fluid Abeta levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assessment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale. Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups. There were 3 adverse event-related discontinuations, including 1 transient bowel obstruction. The plasma Abeta(40) concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (P<.001). No significant reduction was seen in cerebrospinal fluid Abeta levels. No group differences were seen in cognitive or functional measures. LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma Abeta concentrations were consistent with inhibition of gamma-secretase. Trial Registration clinicaltrials.gov Identifier: NCT00244322.

β‐Glucuronidase activity in cerebrospinal fluid pleocytosis due to urinary tract infection

This study examines the beta-glucuronidase activity in the cerebrospinal fluid (CSF) of patients with urinary tract infection (UTI) and sterile CSF pleocytosis and the feasibility of using these measurements for diagnostic purposes. beta-Glucuronidase activity was measured in the CSF from 22 in each group neonates and infants with UTI and sterile CSF pleocytosis, bacterial meningitis, aseptic meningitis of apparently viral etiology and controls without CSF pleocytosis. The median (range) beta-glucuronidase activity in UTI with sterile CSF pleocytosis was 44.1 (33.2-57.1), whereas in the controls without CSF pleocytosis it was 19.1 (7.0-22.7), in aseptic meningitis of apparently viral etiology it was 26.5 (21.0-30.0) and in bacterial meningitis it was 168 (70.0-1152). The difference between the enzyme activity in the CSF of the patients with UTI and those in the other groups of neonates and infants is significant (p < 0.0001), with no overlapping between UTI and the other groups of children studied. Both the sensitivity and specificity of the activity was 100%. Conversely, there was a broad overlapping of the classic CSF laboratory parameters among the groups of subjects studied. beta-Glucuronidase activity in cell-free CSF discerns, with much greater accuracy than the classic CSF laboratory parameters, sterile CSF pleocytosis due to UTI from that of bacterial and viral meningitis and from control subjects without CSF pleocytosis.

Cerebrospinal Fluid Biomarkers in Primary Headache Disorders

The object of this review is to examine the published literature for cerebrospinal fluid laboratory measures of primary headache disorders to identify biomarkers and provide recommendations for future biomarker discovery. Biomarkers may distinguish deviation from a normal state, provide insight into mechanisms of pathophysiology, quantify the degree of change, discriminate what may be clinically overlapping disorders, and allow monitoring and/or selection of specific treatment. High-throughput, discovery technologies fuel the ability to reveal more biomarkers than past hypothesis-driven studies. DESIGN OR METHODS: Publications were identified in PubMed, ISI web of knowledge (both Web of Science and BIOSYS), and SciFinder, using the key words for cerebrospinal fluid (CSF) and migraine, headache, or biomarkers. Additional references were sought from the papers identified in these searches. Data were assessed relating to all primary headache types for clinical and scientific methods and results. Fifty-five out of 82 biomarkers were found from 55 publications, though none have been validated for clinical utility. Data for site (ventricular, cervical, lumbar) and timing of CSF collection, headache state, and diagnostic description were patchy, and controls were often poorly defined. Most routinely performed CSF measurements were within normal limits. Most levels of pain-related molecules were reduced, and concentrations of most neurotransmitters, neuropeptides, proteins, and small molecules were increased. Though few studies assessed the specificity of biomarkers for primary headaches, it is clear that there are differences in CSF biomarkers between migraine, cluster headache, tension-type headache, and trigeminal neuralgia. The high proportion (67%) of biomarkers identified from laboratory measures tested thus far predicts that many more biomarkers will be identified for primary headaches when more candidates are evaluated. In order to discover and evaluate more biomarkers, especially those that may have clinical application for headache management, 3 recommendations are encouraged: prospective design of care-independent studies; evaluation of more clinical variables; and evaluation of substantially more candidates by using discovery-based research methods. Outlines of approaches to pursue these aims are proposed.

Enterovirus meningitis in Greece from 2003–2005: diagnosis, CSF laboratory findings, and clinical manifestations

Enteroviruses (EVs) are the most commonly identified cause of aseptic meningitis. Rapid detection and characterization of EV meningitis is essential in making decisions for patient management and treatment. A total of 52 cases of acute aseptic meningitis that occurred from March 2003 to April 2005 were investigated for EVs using viral culture and/or molecular methods directly in the cerebrospinal fluid (CSF). EVs were detected in 21 out of 52 (40.4%) patients using reverse transcription-PCR (RT-PCR) and/or tissue culture. EVs were isolated from six out of 37 (16.2%) cultured specimens, while 20 out of 52 (38.4%) specimens yielded positive results when 5'non-coding region (5'NCR) RT-PCR assay was used. One specimen that was culture-positive was RT-PCR-negative. Using the VP1-2A RT-PCR and sequence analysis, 14 of the 21 positive EVs were identified as: four strains of Coxsackie virus B5, five echovirus 11, two echovirus 9, one echovirus 5, one echovirus 14, and one Coxsackie virus A9. Fever, headache, vomiting, and stiff neck were the most pronounced symptoms. Pleocytosis with the predominance of lymphocytes and mild elevated protein levels characterized the CSF specimens. Coxsackie virus B5 and echovirus 11 were the predominant serotypes during the study period. Although there was seasonal enteroviral activity (April-November), cases also occurred in the cold months. The 5'NCR and VP1-2A RT-PCR with sequence analysis were found to be superior to conventional methods for direct diagnosis and the typing of EVs.

Diagnostic Utility of Borrelia burgdorferi Cerebrospinal Fluid Polymerase Chain Reaction in Children with Lyme Meningitis

Cerebrospinal fluid (CSF) laboratory tests are frequently collected to help differentiate Lyme meningitis from other causes of aseptic meningitis. Previous studies using Lyme CSF polymerase chain reaction (PCR) have yielded varied results (sensitivity between 10 and 90%). No studies have specifically examined the diagnostic utility of Lyme CSF-PCR in North American children with Lyme meningitis. Retrospective chart review of children presenting to a children's hospital in a Lyme-endemic region between October 1999 and September 2004. Patients were included if they had both Lyme serology and Lyme CSF-PCR performed during the same hospital encounter and had documented meningitis. Patients were considered to have Lyme meningitis if they had meningitis and met CDC criteria for Lyme disease. The Lyme CSF-PCR assay amplified a Borrelia burgdorferi DNA flagellin gene sequence. Of 108 patients with meningitis who qualified for the study, 20 patients met criteria for Lyme meningitis and 88 were classified as aseptic meningitis. Positive Lyme CSF-PCR was found in 1 patient (1 of 20, 5%) with Lyme meningitis and one patient classified as aseptic meningitis (1 of 88, 1%). Lyme CSF-PCR had a sensitivity of 5% and a specificity of 99%. The only Lyme meningitis patient with positive Lyme CSF-PCR had the highest CSF white blood cell count and CSF protein values compared with the other Lyme meningitis patients. This is the first study to evaluate Lyme CSF-PCR exclusively in North American children. This commercially available laboratory test is not generally helpful for identifying Lyme meningitis because of its low sensitivity.

Special populations: the management of seizures in HIV-positive patients.

An increasing percentage of patients with new-onset seizures are HIV positive. The evaluation and management is distinctly different from managing the non-HIV-infected patient. Clinicians must be familiar with comorbid infectious etiologies and the relative value of electroencephalogram, imaging, and serum and cerebrospinal fluid laboratory tests. Traditional antiepileptic drug (AED) therapies are contraindicated and may lead to increased HIV viral replication through either directed cellular mechanisms or interference with antiretroviral therapies. Newer AEDs have pharmacokinetic properties that make them reasonable choices, although none have been specifically studied for efficacy or safety in HIV. Lastly, optimal choice of an AED should reflect commonly encountered neurologic and psychiatric comorbidities.

Presence of Cytomegalovirus in Cerebrospinal Fluid of Patients with Guillain‐Barré Syndrome

Because poliomyelitis has been almost completely eradicated, Guillain-Barre syndrome (GBS) now accounts for most cases of acute flaccid paralysis. Understanding of the role of cytomegalovirus (CMV) in the pathogenesis of GBS is still very limited. We identified 42 CMV-seropositive patients with GBS between 1998 and 2001. Cerebrospinal fluid (CSF) and serum samples obtained from these patients were tested by CMV-specific polymerase chain reaction, and the glycoprotein B (gB) segment of the detected CMV genome was analyzed. Virological findings were compared with clinical characteristics and CSF laboratory values. CMV DNA was detected in 13 (31%) of 42 CSF samples from patients with GBS but was not detected in 42 CSF samples from age-matched control subjects with acute encephalopathy. CSF samples obtained early after the onset of GBS were significantly more likely to be positive for CMV DNA (P=.048). gB1 was the most prevalent genotype detected in patients with GBS (88%), followed by gB3 (8%) and gB2 (4%). CMV DNA was detected frequently in CSF samples from CMV-seropositive patients with GBS, especially early during the course of the disease. The clinical significance of this finding has yet to be elucidated, but early administration of antiviral therapy might prove to be beneficial for selected patients with GBS.

Clinical comparisons of La Crosse encephalitis and enteroviral central nervous system infections in a pediatric population: 2001 surveillance in East Tennessee

Background La Crosse encephalitis (LAC) is a mosquito-borne illness that primarily affects children. In 1997, an initial cluster of cases was identified by the regional pediatric referral center in East Tennessee. Since that time, public health officials, pediatric infectious disease physicians, infection control nurses, laboratory personnel, entomologists, and Centers for Disease Control and Prevention consultants have collaborated to provide ongoing surveillance activities. Studies comparing LAC cases with non-LAC (no etiologic diagnosis) central nervous system infections have yielded no statistical significance in signs and symptoms or laboratory values. Objective To determine any differences in signs, symptoms, and/or diagnostic laboratory values between LAC cases and enteroviral central nervous system (EV-CNS) infections. Methods In 2001, descriptive public health surveillance for LAC was performed concurrent with an outbreak investigation of EV-CNS infections at a pediatric referral center in East Tennessee. All patients being evaluated for suspected meningitis and/or encephalitis were interviewed for signs and symptoms of illness. Patients with positive test results for LAC and negative results for EV or positive results for EV and negative results for LAC were included in the study. Results Compared with patients with EV-CNS infection, patients with LAC were significantly more likely to have aphasia ( P = .001), loss of consciousness ( P = .0003), seizure ( P = .0003), and admission to the pediatric intensive care unit ( P = .02). Presence of fever, headache, vomiting, stiff neck (subjective), photophobia, behavioral changes, confusion, need for mechanical ventilation, age, and sex showed no statistical significance ( P > .05). Statistical differences were not demonstrated in cerebrospinal fluid laboratory values ( P > .05). Conclusion Patients with LAC demonstrated more severe symptoms on presentation to the hospital than did patients with EV-CNS infection. A possible advantage of identifying specific viral etiologic factors of pediatric CNS disease by clinical characteristics may be the ability to take advantage of emerging antiviral therapies.

A diagnostic decision rule for management of children with meningeal signs.

In a previous study we devised a diagnostic decision rule to improve management of children with meningeal signs, suspected of having bacterial meningitis. The decision rule aimed to guide decisions on (1) whether a lumbar puncture is necessary in children with meningeal signs, and (2) which children need hospitalisation and empirical antibiotic treatment for bacterial meningitis. In this study we assessed the validity of this rule in an external population of four (paediatric) hospitals in The Netherlands. The decision rule included two scoring algorithms using symptoms, signs and quickly available blood and cerebrospinal fluid (CSF) laboratory tests. To evaluate the discriminative value of both algorithms, the absolute numbers of correctly diagnosed patients and the area under the receiver operator characteristic curve were estimated, and compared with the results from the original population (n = 360). In a 18 month period, we included 226 children, median age 2.2 years, who visited the emergency department with meningeal signs. Bacterial meningitis was present in 25 (11%). Using the scoring algorithms patients could be categorised in groups of increasing risk of bacterial meningitis. The discriminative values of the clinical and CSF algorithm in this new population were similar to those in the original population. In the total population of 586 children with meningeal signs, the rule selected 205 children (35%) who did not need a lumbar puncture and 366 children who did not need empirical treatment (62%). In conclusion, this diagnostic rule performed well in a new population of children with meningeal signs. This diagnostic decision rule is a valuable tool for the clinician when deciding to treat these children for bacterial meningitis and thus improving their management.

Tuberculous meningitis at a large inner-city medical center.

Tuberculosis in the United States has become primarily an inner-city disease. We examined the epidemiology of culture-confirmed tuberculous meningitis among patients cared for at an urban public hospital in Atlanta. During an 11.5-year period (January 1984-June 1995) cerebrospinal fluid cultures for Mycobacterium tuberculosis were positive in 34 patients, accounting for 1.5% of all culture-confirmed tuberculosis cases. All patients were born in the United States, 31 (91%) were black, 16 (47%) of 34 were human immunodeficiency virus (HIV) seropositive, 9 (26.5%) were HIV seronegative, and 9 (26.5%) had an unknown HIV serostatus. No significant differences were seen in clinical presentation, cerebrospinal fluid, or other laboratory data between HIV seropositive and HIV seronegative/ unknown groups, except for a lower serum white blood cell count among HIV seropositive patients. Mortality was striking; 14 (41.2%) died because of tuberculous meningitis despite appropriate therapy initiated a mean of 3 days after admission. Six survivors had permanent neurologic sequelae. Univariate analysis of outcome was not statistically associated with any measured demographic, laboratory value, stage at presentation, treatment regimen, or HIV serostatus. Multivariate analysis of outcome using 13 independent variables also demonstrated no significant association between these variables and outcome, although a trend was seen for increased mortality for white people (P = 0.09) and increasing age (P = 0.09). Tuberculous meningitis among inner-city residents remains a devastating disease associated with high morbidity and mortality that has changed little during the past 4 decades. HIV infection does not change markedly the clinical presentation or the response to therapy.