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1.  The role of cranial CT in the investigation of meningitis 
JRSM Short Reports  2011;2(3):20.
To assess the usage of cranial computed tomography (CT) in patients admitted with meningitis.
Retrospective study.
Heart of England NHS foundation trust, a teaching hospital in the West Midlands.
Two groups of adult patients admitted with meningitis between April 2001 and September 2004 and from September 2006 until September 2009.
Main outcome measures
The numbers of patients having cranial CT and lumbar puncture and whether any complications had arisen following lumbar puncture. The appropriateness of the CT request according to local criteria.
A total of 111 patients were admitted in the initial time period and 47 patients in the second time period. In the first group, 67 patients underwent CT (61%), compared with 36 patients (80%) in the second group. There were eight abnormal scans (12%) in the initial group including three patients with radiological features of cerebral oedema. Of these patients, one underwent lumbar puncture and had no neurological sequelae. In the second group, there were five abnormal scans (14%) with one presenting a contraindication for lumbar puncture due to mild ventricular dilatation. A lumbar puncture was performed in this patient without complication. All patients with abnormal scans had clinical features to suggest raised intracranial pressure. CT scan requests were considered inappropriate in 26% of patients in the initial study period and 56% of patients in the second study period.
More patients with meningitis are undergoing CT and the number of inappropriate requests are increasing. There are few abnormal CT scans presenting a contraindication for lumbar puncture and the majority of these patients usually have clinical signs to suggest raised intracranial pressure.
PMCID: PMC3086327  PMID: 21541088
2.  Testing for Meningitis in Children with Bronchiolitis 
The Permanente Journal  2014;18(4):16-19.
The authors present a retrospective, case-control study of hospitalized infants younger than age one year diagnosed with viral bronchiolitis who underwent lumbar puncture as part of an evaluation for meningitis. The presence of apnea, cyanosis, meningeal signs, positive urine culture results, and young age were factors found to be preliminarily associated with the performance of a lumbar puncture in the setting of bronchiolitis. Young age was the only significant clinical factor found after multivariable regression; no other demographic, clinical, laboratory, or radiologic variables were found to be significant.
Viral bronchiolitis accounts for almost 20% of all-cause hospitalizations of infants (ie, children younger than age 1 year). The annual incidence of fever in viral bronchiolitis has been documented at 23% to 31%. However the incidence of concurrent serious bacterial infections is low (1%–7%), with meningitis occurring in less than 1% to 2% of cases, but lumbar puncture is performed in up to 9% of viral bronchiolitis cases. To our knowledge, no study has examined clinical factors that influence a physician’s decision to perform a lumbar puncture in the setting of viral bronchiolitis.
We present a retrospective, case-control study of hospitalized infants younger than one year diagnosed with viral bronchiolitis who underwent lumbar puncture as part of an evaluation for meningitis. The objective of the study was to determine clinical factors that influence a physician’s decision to perform a lumbar puncture in the setting of viral bronchiolitis. Although the presence of apnea, cyanosis, meningeal signs, positive urine culture results, and young age were factors found to be preliminarily associated with the performance of a lumbar puncture in the setting of bronchiolitis, young age was the only significant clinical factor found after multivariable regression; no other demographic, clinical, laboratory, or radiologic variables were found to be significant.
PMCID: PMC4206166
3.  The role of lumbar puncture in children with suspected central nervous system infection 
BMC Pediatrics  2002;2:8.
The use of the lumbar puncture in the diagnosis of central nervous system infection in acutely ill children is controversial. Recommendations have been published but it is unclear whether they are being followed.
The medical case notes of 415 acute medical admissions in a children's hospital were examined to identify children with suspected central nervous system infection and suspected meningococcal septicaemia. We determined whether lumbar punctures were indicated or contraindicated, whether they had been performed, and whether the results contributed to the patients' management.
Fifty-two children with suspected central nervous system infections, and 43 with suspected meningococcal septicaemia were identified. No lumbar punctures were performed in patients with contraindications, but only 25 (53%) of 47 children with suspected central nervous system infection and no contraindications received a lumbar puncture. Lumbar puncture findings contributed to the management in 18 (72%) of these patients, by identifying a causative organism or excluding bacterial meningitis.
The recommendations for undertaking lumbar punctures in children with suspected central nervous system infection are not being followed because many children that should receive lumbar punctures are not getting them. When they are performed, lumbar puncture findings make a useful contribution to the patients' management.
PMCID: PMC126268  PMID: 12350236
4.  Prospective surveillance of neonatal meningitis. 
Archives of Disease in Childhood  1993;69(1 Spec No):14-18.
Neonatal meningitis is a serious problem with a high mortality and frequent neurological sequelae. The incidence of neonatal meningitis was calculated and the aetiology, clinical and laboratory features, and the treatment of cases recorded prospectively over a 7 year 8 month period was documented. It was further investigated whether secondary meningitis had occurred after lumbar puncture. The estimated incidence of bacterial, viral, and fungal meningitis was 0.25, 0.11, and 0.02 per 1000 live births respectively. There were eight cases of early onset meningitis (seven definite, one probable) and group B streptococci accounted for six (75%) of these. Blood cultures were negative in only one of seven cases of definite early bacterial meningitis. Of the 15 late onset cases, Gram negative organisms accounted for six of the seven bacterial cases. The overall mortality was 26%. Of the 11 survivors of bacterial meningitis, three (27%) had significant neurological sequelae at follow up (between three months to three years later). As in the first 48 hours after birth an initial blood culture is unlikely to be negative if bacterial meningitis is present, lumbar puncture can be deferred if the procedure might exacerbate respiratory distress. Although approximately 1880 infants had a lumbar puncture during the review period, only one case of meningitis was found where it was possible that lumbar puncture in a bacteraemic infant may have caused meningeal infection. The incidence of this potential complication must therefore be low.
PMCID: PMC1029390  PMID: 8346945
5.  Computed tomography before lumbar puncture in acute meningitis: a review of the risks and benefits. 
OBJECTIVE: To determine the indications, if any, for routine computed tomography (CT) of the brain before lumbar puncture in the management of acute meningitis. DATA SOURCES: Original research papers, reviews and editorials published in English from 1965 to 1991 were retrieved from MEDLINE. The bibliographies of these articles and of numerous standard texts were examined for pertinent references. A survey of local neurologists was conducted, and legal opinion was sought from the Canadian Medical Protective Association. DATA EXTRACTION: There were no studies directly assessing the risks of lumbar puncture in meningitis; however, all sources were culled for other pertinent information. RESULTS: No cases could be found of patients with acute meningitis deteriorating as a result of lumbar puncture. The neurologic consensus refuted the need for CT in typical acute meningitis. All sources stressed speedy lumbar puncture and the early institution of appropriate antibiotic therapy to minimize the severity of the illness and the risk of death. CONCLUSIONS: (a) There is no evidence to recommend CT of the brain before lumbar puncture in acute meningitis unless the patient shows atypical features, (b) for patients with papilledema the risks associated with lumbar puncture are 10 to 20 times lower than the risks associated with acute bacterial meningitis alone, (c) CT may be necessary if there is no prompt response to therapy for meningitis or if complications are suspected, (d) the inability to visualize the optic fundi because of cataracts or senile miosis is not an indication for CT and (e) there are no Canadian legal precedents suggesting liability if physicians fail to perform CT in cases of meningitis.
PMCID: PMC1490723  PMID: 8448711
6.  Effect of the introduction of a lumbar‐puncture sticker and teaching manikin on junior staff documentation and performance of paediatric lumbar punctures 
Quality & Safety in Health Care  2006;15(5):325-328.
Performing a lumbar puncture in an unwell child can cause anxiety in both the parent and the junior doctor. There is increasing evidence of post‐lumbar‐puncture complications in this age group.
To improve the documentation, consent for and technical performance of paediatric lumbar punctures to 100% of the required standard within 3 months.
The paediatric emergency department of a the Royal North Shore Hospital (University of Sydney, Sydney, Australia).
Paediatric emergency staff, including residents, registrars and consultants.
Medical records of 40 consecutive children who had undergone a lumbar puncture in the 6 months before the introduction of the lumbar‐puncture proforma were reviewed. After introduction of the proforma, the records of 25 consecutive patients were reviewed to assess changes in the outcome measures. Before introduction of the proforma, junior medical staff were instructed in the procedure using specialised lumbar puncture manikins (Baby Stap; Laerdel, USA).
Before introduction of the proforma, the median number of documented indicators was 4, out of a maximum of 12. There was almost no documentation of parental consent, patient complications and analgesia. Introduction of the proforma resulted in a highly marked increase to a median of 12 documented indicators per patient (p<0.01, 95% confidence interval 6 to 8).
The introduction of a lumbar‐puncture proforma and formal teaching sessions using a paediatric manikin led to a marked improvement in the documentation of paediatric lumbar‐punctures. Lumbar‐punctures can be performed only by accredited medical officers who have achieved competency on the lumbar‐puncture teaching manikin.
PMCID: PMC2565814  PMID: 17074867
7.  Lumbar puncture and subarachnoid haemorrhage. 
Postgraduate Medical Journal  1986;62(733):1021-1024.
Medical notes of 123 patients with subarachnoid haemorrhage were examined. No patient deteriorated at the time of lumbar puncture. All but 2 patients with associated intracerebral haematomas had markedly impaired consciousness or focal signs. Two of 30 patients with meningitis were initially diagnosed as subarachnoid haemorrhage, and one died without lumbar puncture. If consciousness is not markedly impaired and focal signs are absent, lumbar puncture is safe in patients with subarachnoid haemorrhage.
PMCID: PMC2418952  PMID: 3628146
8.  Clinical and prognostic features among children with acute encephalitis syndrome in Nepal; a retrospective study 
BMC Infectious Diseases  2011;11:294.
Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases.
Children with AES (n = 225) were identified through admission records from two hospitals in Kathmandu between 2006 and 2008. Patients without available lumbar puncture results (n = 40) or with bacterial or plasmodium infection (n = 40) were analysed separately. The remaining AES patients with suspected viral aetiology were classified, based on positive IgM antibody in serum or cerebral spinal fluid, as JE (n = 42) or AES of unknown viral aetiology (n = 103); this latter group was sub-classified into Non-JE (n = 44) or JE status unknown (n = 59). Bad outcome was defined as death or neurological sequelae at discharge.
AES patients of suspected viral aetiology more frequently had a bad outcome than those with bacterial or plasmodium infection (31% versus 13%; P = 0.039). JE patients more frequently had a bad outcome than those with AES of unknown viral aetiology (48% versus 24%; P = 0.01). Bad outcome was independently associated in both JE and suspected viral aetiology groups with a longer duration of fever pre-admission (P = 0.007; P = 0.002 respectively) and greater impairment of consciousness (P = 0.02; P < 0.001). A higher proportion of JE patients presented with a focal neurological deficit compared to patients of unknown viral aetiology (13/40 versus 11/103; P = 0.005). JE patients weighed less (P = 0.03) and exhibited a higher respiratory rate (P = 0.003) compared to Non-JE patients.
Nepali children with AES of suspected viral aetiology or with JE frequently suffered a bad outcome. Despite no specific treatment, patients who experienced a shorter duration of fever before hospital admission more frequently recovered completely. Prompt referral may allow AES patients to receive potentially life-saving supportive management. Previous studies have indicated supportive management, such as fluid provision, is associated with better outcome in JE. The lower weight and higher respiratory rate among JE patients may reflect multiple clinical complications, including dehydration. The findings suggest a more systematic investigation of the influence of supportive management on outcome in AES is warranted.
PMCID: PMC3219745  PMID: 22035278
9.  Randomised controlled trial of atraumatic versus standard needles for diagnostic lumbar puncture 
BMJ : British Medical Journal  2000;321(7267):986-990.
To compare the ease of use of atraumatic needles with standard needles for diagnostic lumbar puncture and the incidence of headache after their use.
Double blind, randomised controlled trial.
Investigation ward of a neurology unit in a university hospital.
116 patients requiring elective diagnostic lumbar puncture.
Standardised protocol for lumbar puncture with 20 gauge atraumatic or standard needles.
Outcome measures
The primary end point was intention to treat analysis of incidence of moderate to severe headache, assessed at one week by telephone interview. Secondary end points were incidence of headache at one week analysed by needle type, ease of use by operator according to a visual analogue scale, incidence of backache, and failure rate of puncture.
Valid outcome data were available for 97 of 101 patients randomised. Baseline characteristics were matched except for higher body mass index in the standard needle group. By an intention to treat analysis the absolute risk of moderate to severe headache with atraumatic needles was reduced by 26% (95% confidence interval 6% to 45%) compared with standard needles, but there was a non-significantly greater absolute risk of multiple attempts at lumbar puncture (14%, −4% to 32%). Higher body mass index was associated with an increased failure rate with atraumatic needles, but the reduced incidence of headache was maintained. The need for medical interventions was reduced by 20% (1% to 40%).
Atraumatic needles significantly reduced the incidence of moderate to severe headache and the need for medical interventions after diagnostic lumbar punctures, but they were associated with a higher failure rate than standard needles.
PMCID: PMC27505  PMID: 11039963
10.  Necessity of Lumbar Puncture in Patients Presenting with New Onset Complex Febrile Seizures 
Introduction: This study aims to characterize the population of patients presenting to a pediatric emergency department (ED) for a first complex febrile seizure, and subsequently assess the rate of acute bacterial meningitis (ABM) occurrence in this population. Furthermore, this study seeks to identify whether a specific subset of patients may be at lesser risk for ABM or other serious neurological disease.
Methods: This retrospective cohort study reviewed the charts of patients between the ages of 6 months to 5 years of age admitted to an ED between 2005 and 2010 for a first complex febrile seizure (CFS). The health information department generated a patient list based on admission and discharge diagnoses, which was screened for patient eligibility. Exclusion criteria included history of a complex febrile seizure, history of an afebrile seizure, trauma, or severe underlying neurological disorder. Data extracted included age, gender, relevant medical history, descriptions of seizure, treatment received, and follow-up data. Patients presenting with two short febrile seizures within 24 hours were then analyzed separately to assess health outcomes in this population.
Results: There were 193 patients were eligible. Lumbar puncture was performed on 136 subjects; it was significantly more likely to be performed on patients that presented with seizure focality, status epilepticus, or a need for intubation. Fourteen patients were found to have pleocytosis following white blood cell count correction, and 1 was diagnosed with ABM (0.5% [95% confidence interval: 0.0–1.5, n=193]). Forty-three patients had 2 brief febrile seizures within 24 hours. Of the 43, 17 received lumbar puncture while in the ED. None of these patients were found to have ABM or other serious neurological disease.
Conclusion: ABM is rare in patients presenting with a first complex febrile seizure. Patients presenting only with 2 short febrile seizures within 24 hours may be less likely to have ABM, and may not require lumbar puncture without other clinical symptoms of neurological disease.
PMCID: PMC3656699  PMID: 23687537
11.  Cryptococcosis of the central nervous system 
(1) A survey of cryptococcal infections of the nervous system in Queensland, Australia, revealed the nine year prevalence rate for the Australian aboriginal to be some 17 times greater than that of the white population. Uncommon in the first decade of life, the disease was developed by 79% of 29 patients between 20 and 59 years, males being affected twice as commonly as females. (2) Cryptococcosis appears to be more common in Australia than in the United Kingdom, and in Queensland the nine year incidence of neurological cryptococcosis was 4·7 per 100,000 in the tropical north compared with 1·8 per 100,000 in the southern parts of the State. Because of this, and since 20 of the 29 patients were regarded as having outdoor occupations, it is suggested that a high environmental exposure to the fungus may be associated with an animal reservoir and with dry, dusty conditions. It is also possible that geographical and occupational factors rather than racial predisposition account for the high incidence of the disease in the Australian aborigine. However, individual resistance and susceptibility are probably also important factors, since the clinical disease appears to be positively correlated with certain other diseases, or with steroid therapy, which would impair the immune responses of the body. (3) Headache is the outstanding symptom of neurological cryptococcosis and fever or evidence of meningeal reaction, though often present, may be absent. An awareness of the possibility of neurological cryptococcosis in the differential diagnosis of various intracranial disorders should lead to identification of the encapsulated C. neoformans in the cerebrospinal fluid. Although in eight of 26 patients the lumbar cerebrospinal fluid was sterile on repeated examination, in five cases C. neoformans was found on direct examination of cerebrospinal fluid obtained by ventricular puncture. The remaining three died before further investigations could be performed. (4) Before the introduction of amphotericin B, neurological cryptococcosis was almost invariably fatal. At the present time, the infection can be eradicated in some 80% of patients. Intravenous administration of amphotericin B is generally adequate, but the intrathecal route should be used for cases in relapse or in critically ill patients. In addition to the toxic effects of the drug, the possibility of later deterioration in the patient's condition due to meningeal reaction—for example, occult hydrocephalus—merits consideration and appropriate neurosurgical treatment.
PMCID: PMC493494  PMID: 5535907
12.  Frequency of Meningitis in Children Presenting with Febrile Seizures at Ali-Asghar Children’s Hospital 
Febrile seizures (FS) are the most common type of childhood seizures, affecting 2–5% of children. As the seizure may be the sole presentation of bacterial meningitis in febrile infants, it is mandatory to exclude underlying meningitis in children presenting with fever and seizure. To determine the frequency of meningitis in children with FS and related risk factors, the present study was conducted at Ali-Asghar Children’s Hospital.
Materials & Methods
The records of children aged from 1-month–6 years of age with fever and seizure admitted to the hospital from October 2000–2010 were studied. The charts of patients who had undergone a lumbar puncture were studied and cases of meningitis were selected. The related data was collected and analyzed with SPSS version 16.
A total of 681 patients with FS were known from which 422 (62%) lumbar punctures (LP) were done. Meningitis (bacterial or aseptic) was identified in 19 cases (4.5%, 95% CI 2.9–6.9 by Wilson- Score internal) and bacterial meningitis in 7 (1.65%, 95% CI 0.8–3.3). None of the patients with bacterial meningitis had meningeal irritation signs. Complex FS, first attack of FS, and impaired consciousness were more common in patients with meningitis when compared to non- meningitis patients.
Meningitis is more common in patients less than 18 months presenting with FS; however, complex features of seizures, first attack of FS, or impaired consciousness seem significant risk factors for meningitis in these children and an LP should be considered in this situation.
PMCID: PMC4308616  PMID: 25663842
Bacterial meningitis; Febrile seizure; Meningitis
13.  Epidemiology and clinical management of meningococcal disease in west Gloucestershire: retrospective, population based study. 
BMJ : British Medical Journal  1997;315(7111):774-779.
OBJECTIVE: To study changes in the epidemiology and management of meningococcal disease in one health district during a period of high local incidence of disease. DESIGN: Prospective case ascertainment and data collection over 14 years, with retrospective analysis of cases. SETTING: West Gloucestershire (population 320,000). SUBJECTS: Residents developing meningococcal disease between 1 January 1982 and 31 December 1995. RESULTS: 252 cases of invasive meningococcal disease were identified, of which 102 (40%) were officially notified and 191 (76%) were confirmed by culture from a deep site. The observed disease incidence of 5.6/100,000/year was about 2.7 times the national incidence (as measured by either statutory notifications or reference laboratory reports). The period 1983-90 was characterised by a prolonged localised outbreak due to serogroup B serotype 15 sulphonamide resistant (B15R) strains. General practitioners gave benzylpenicillin before hospital admission to 18% of patients who presented with meningococcal disease in the first half of the study period and to 40% who presented in the second half. The overall case fatality rate was 6.7% (17/252). Four deaths were directly or indirectly related to lumbar puncture. Of 120 patients whose lumbar puncture yielded meningococci, nine (8%) showed no abnormality on initial examination. CONCLUSIONS: Neither laboratory records nor formal notifications alone can give an accurate estimate of the incidence of meningococcal disease. Because of the dangers of lumbar puncture, the frequency of misleading negative initial findings, and the advent of new diagnostic techniques, the need for samples of cerebrospinal fluid should be critically questioned in each case of suspected meningococcal disease.
PMCID: PMC2127533  PMID: 9345169
14.  Cerebral herniation during bacterial meningitis in children. 
BMJ : British Medical Journal  1993;306(6883):953-955.
OBJECTIVE--To see whether the incidence of cerebral herniation is increased immediately after lumbar puncture in children with bacterial meningitis and whether any children with herniation have normal results on cranial computed tomography. DESIGN--Retrospective review of case notes; computed tomograms were read again. SETTING--Large paediatric teaching hospital. SUBJECTS--445 children over 30 days old admitted to hospital with bacterial meningitis. MAIN OUTCOME MEASURES--Timing of herniation in relation to lumbar puncture; findings on computed tomography in children with herniation. RESULTS--Cerebral herniation was detected in 19 (4.3%) of the 445 children (21 episodes; herniation occurred twice in two children). Herniation occurred in 14 (45%) of the 31 children who died. Nineteen episodes of herniation occurred in the 17 children who had a lumbar puncture; 12 of the episodes occurred in the first 12 hours after the lumbar puncture and seven over six other 12 hour periods (odds ratio 32.6 (95% confidence interval 8.5 to 117.3); p < 0.001). The results of cranial computed tomography were normal in five (36%) of the 14 episodes of herniation in which scanning was performed at about the time of herniation. CONCLUSIONS--The temporal relation between lumbar puncture and herniation strongly suggests that a lumbar puncture may cause herniation in some patients, and normal results on computed tomography do not mean that it is safe to do a lumbar puncture in a child with bacterial meningitis.
PMCID: PMC1677428  PMID: 8490469
15.  Cerebro Spinal Fluid Analysis in Childhood Bacterial Meningitis 
Oman Medical Journal  2008;23(1):32-33.
The aim of this study was to analyze the lumbar puncture of all suspected cerebrospinal fluid (CSF) for suspected meningitis.
This study was undertaken in the department of Child Health, the Royal Hospital. The details of CSF of all files of the children who had undergone lumbar puncture for suspected meningitis from January 1, 2004 to December 31, 2004; were enrolled for the study.
A total of 395 lumbar punctures were done to exclude bacterial meningitis. Out of the 142 CSF studies in neonates, 17 (12%) had the cytology suggestive of bacterial meningitis and 15 (88%) of them being culture positive. The commonest pathogen was Group B Streptococcus (70%).The bacterial antigens were positive only in 41% of the confirmed cases of bacterial meningitis, all being that of Group B Streptococcus and gram stain positivity in 45 percent of cases. In the 1- 3 months group all the 17 lumbar punctures were normal. Of the 179 lumbar punctures done in 3-18 months group, only 11(6%) were abnormal, 72% being culture positive. Streptococcus pneumonia was the commonest organism (88%). Bacterial antigens were positive only in 2 of the 8 culture positive cases where gram stain was positive in 4 out of 8 cases. Irritability, lethargy and sick looking appearance were present in all the positive cases. None of the 28 children from 18 months to 5 years had abnormal CSF or positive CSF culture.
Based on the fact that only 7% of the 395 CSF studies were abnormal, we conclude that better clinical judgment and diagnostic criteria are warranted, before laying out guidelines for lumbar puncture to confirm or exclude the diagnosis of bacterial meningitis. Besides fever and convulsions as indicators for CSF studies clinical parameters such as irritability, lethargy and sick looking appearance are better indicators.
PMCID: PMC3338990  PMID: 22567207
16.  Lumbar Puncture in HIV-Infected Patients with Syphilis and No Neurologic Symptoms 
The decision to perform lumbar puncture in patients with asymptomatic human immunodeficiency virus (HIV) infection and syphilis is controversial. The Centers for Disease Control and Prevention recommend certain criteria that warrant lumbar puncture. Here, we assess the performance of these criteria for detecting asymptomatic neurosyphilis (ANS).
Eligible subjects consisted of all patients with concurrent HIV infection and syphilis in a prospective clinical cohort who had no neurologic symptoms at the time of lumbar puncture. We retrospectively applied different stratification criteria to calculate the performance of lumbar puncture in detecting ANS: (1) lumbar puncture in patients with late latent syphilis or syphilis of an unknown duration, regardless of the CD4 cell count or rapid plasma reagin titer; (2) lumbar puncture if the CD4 cell count was ≤350 cells/mL and/or the rapid plasma reagin titer was ≥1:32, regardless of the syphilis stage; and (3) lumbar puncture in the context of serologic nonresponse to syphilis therapy.
Two hundred two of 231 patients with syphilis did not have neurologic symptoms. Immediate lumbar puncture was performed for 46 patients, and 10 cases (22%) of ANS were detected. With use of the first criterion, 2 (14%) of 10 cases of ANS in patients with early-stage syphilis would have been missed (sensitivity, 80% [95% confidence interval {CI}, 44%–97%]; specificity, 76% [95% CI, 60%–89%]). Criterion 2 would not have missed any cases of ANS (sensitivity, 100% [95% CI, 70%–100%]; specificity, 87% [95% CI, 72%–96%]) but would have required that a lumbar puncture be performed for 88% of patients. Performance of lumbar puncture performed in 13 cases based on serologic nonresponse to syphilis therapy yielded 4 cases (31%) of ANS.
In patients with concurrent HIV infection and syphilis, the use of criteria based on rapid plasma reagin titer and CD4 cell count, instead of stage-based criteria, improved the ability to identify ANS.
PMCID: PMC2716000  PMID: 19187028
17.  Diagnostic lumbar puncture. Comparative study between 22–gauge pencil point and sharp bevel needle 
The Journal of Headache and Pain  2005;6(5):400-404.
Post–lumbar puncture headache is a frequent clinical problem. Needle design is expected to reduce post–puncture headache. In this study, we compared two different lumbar puncture needle designs in diagnostic lumbar puncture and analysed post–dural puncture headache (PDPH) and social and economical harm associated with the diagnostic lumbar puncture procedure. This prospective, controlled study consisted of 80 consecutive adult patients requiring elective diagnostic lumbar puncture due to various neurological symptoms. Lumbar puncture was completed either with Spinocan® 22 G sharp bevel needle or Whitacre® 22G pencil point needle. Patients were asked about previous headache symptoms and pain provoked by puncture. One week after the lumbar puncture all patients were interviewed by telephone and occurrence and type of headache, headache intensity, medication and frequency of impairment in activities of daily living were asked. Need for epidural blood patch was also recorded. Thirty–three of 78 (42%) patients experienced headache after diagnostic lumbar puncture and in 26 (33%) the headache could be classified as PDPH. There were no statistically significant differences between needle types in the frequency of common headache, PDPH, puncture pain intensity, need for epidural blood patch or sick leave. Also, there were no other complications except local back pain or headache. In this study, the needle design did not affect the frequency of PDPH. Also, PDPH was common, occurring in 33% cases and caused a considerable amount of disturbance in daily activities. Seeking help for this condition was insufficient and only part of these PDPH patients were treated with epidural blood patch.
PMCID: PMC3452066  PMID: 16362713
Post–lumbar puncture headache; Diagnostic lumbar puncture; Puncture needle
18.  Role of computed tomography before lumbar puncture: a survey of clinical practice 
Postgraduate Medical Journal  2006;82(965):162-165.
It is becoming increasingly common to request computed tomography (CT) to rule out space occupying lesions before lumbar puncture (LP), even in patients with no clinical signs. Imaging trends within a busy district general hospital in Oxfordshire, UK were analysed with results used to clarify when imaging should be considered mandatory.
A retrospective six month sample was obtained comprising all adults considered for LP. Observed frequencies of abnormal examination findings compared with abnormal investigations were used to determine sensitivity, specificity, positive predictive, and negative predictive values to assess the validity of using a normal clinical examination as a basis for excluding CT.
64 patients were considered for LP. In total, 58 patients underwent LP, with a single patient receiving two. After an abnormal CT scan, six patients did not undergo a planned LP. In all six of these cases subarachnoid haemorrhage was detected, and in all cases this was considered a probable diagnosis. In no case was an LP precluded by an unsuspected space occupying lesion. Neurological examination showed a sensitivity of 0.72 (0.52 to 0.93), specificity 0.78 (0.64 to 0.91), positive predictive value 0.61 (0.41 to 0.83), and negative predictive value 0.85 (0.73 to 0.97).
The high sensitivity and negative predictive values support normal neurological examination as an effective predictor of normal CT scan. This permits the recommendation in cases where subarachnoid haemorrhage is not suspected, a CT scan can be avoided provided there are no abnormal findings on physical or fundoscopic examination.
PMCID: PMC2563700  PMID: 16517796
computed tomography; lumbar puncture; meningitis; subarachnoid haemorrhage
19.  Febrile Seizure: Measuring Adherence to AAP Guidelines Among Community ED Physicians 
Pediatric emergency care  2006;22(7):465-469.
In 1996, the American Academy of Pediatrics published practice parameters for the acute management of febrile seizure. These guidelines emphasize the typically benign nature of the condition and discourage aggressive neurodiagnostic evaluation. The extent to which these suggestions have been adopted by general emergency medicine practitioners is unknown. We sought to describe recent patterns of the emergency department (ED) evaluation of febrile seizures with respect to these parameters.
A retrospective review of records of children between 6 month and 6 years of age diagnosed with “febrile seizure” (International Classification of Diseases, Ninth Revision, Clinical Modification 780.31) at 42 community hospital general EDs nationwide was performed. Electronic records of an ED physician billing service from October 2002 to September 2003 were used to identify relevant records. Data had been entered into a proprietary template documentation system, and all charts were reviewed by a professional coder blinded to outcomes of interest. Rates of resource utilization (including lumbar puncture, radiography, hospital admission) were noted.
A total of 1029 charts met inclusion criteria. The overall rate of lumbar puncture was 5.2%, and variations were strongly associated with age (8.4% <18 months old vs 3.3% >18 months old). This low rate and age discrimination were consistent with the guidelines of the American Academy of Pediatrics. Although not recommended in the routine evaluation of febrile seizure, computed tomography was part of the evaluation in 11%. The overall rate of admissions or transfers was 12%.
Six years after publication of practice parameters, the use of lumbar puncture in the evaluation of febrile seizure is uncommon and most patients are discharged home. However, the relatively frequent use of head computed tomography is inconsistent with these practice guidelines and merits further investigation.
PMCID: PMC2925644  PMID: 16871103
febrile seizure; practice variation; clinical guidelines
20.  Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis 
PLoS Medicine  2012;9(9):e1001316.
David Boulware and colleagues assess the cost effectiveness of different treatment strategies in low- and middle-income countries for cryptococcal meningitis, one of the most common opportunistic infections of people with HIV.
Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.
Methods and Findings:
We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.
Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease.
Please see later in the article for the Editors' Summary.
Editors' Summary
Cryptococcal meningitis, a fungal infection of the membranes around the brain and spinal cord, affects about a million people every year (most of them living in sub-Saharan Africa and Southeast Asia) and kills about 640,000 people annually. People become infected with Cryptococcus neoformans, the fungus that causes cryptococcal meningitis and which is found in soil and dirt, by breathing it in. In healthy individuals, infection rarely causes disease. But in people living with AIDS, whose immune system has been damaged by HIV infection, and in people whose immune system is compromised for other reasons, the fungus can invade and damage many organs, including the brain. Cryptococcal meningitis, the symptoms of which include fever, stiff neck, headache, and vomiting, is diagnosed by looking for the fungus in fluid taken from the spinal cord in a procedure called a lumbar puncture. Cryptococcal meningitis is treated with antifungal drugs such as amphotericin, fluconazole, and flucytosine (induction therapy); recurrence of the infection is prevented by taking fluconazole daily for life or until the immune system recovers.
Why Was This Study Done?
The World Health Organization (WHO) recommends a 14-day regimen of intravenous (injected) amphotericin and oral flucytosine or fluconazole for induction therapy of cryptococcal meningitis. Unfortunately, this regimen is impractical in many resource-limited settings because of the cost of the drugs and hospital care and the need for intensive monitoring—amphotericin is extremely toxic. Consequently, high-dose fluconazole monotherapy is the usual treatment for cryptococcal meningitis in resource-limited countries, although this regimen is much less effective. Another regimen that has improved survival in trials is flucytosine with fluconazole for two weeks. However, flucytosine is very expensive and is not licensed in most sub-Saharan African countries. Stakeholders in developing countries badly need guidance, therefore, on which induction treatment for cryptococcal meningitis they should recommend to optimize outcomes in their particular countries. In this cost-effectiveness analysis (a study that compares the costs and health effects of different interventions), the researchers use costs in Uganda to estimate the survival, cost, and cost per benefit associated with various induction treatments for cryptococcal meningitis in HIV-infected patients.
What Did the Researchers Do and Find?
The researchers calculated the overall cost of six induction treatments using 2012 healthcare costs in Uganda for medications, supplies, and hospital care, and average laboratory costs for monitoring treatment from three African countries. They used data from published trials of cryptococcal meningitis treatment in resource-limited areas to estimate ten-week and one-year survival, life expectancy, and quality-adjusted life years (QALYs, the number of years of life added by an intervention, adjusted for the quality of life) for each intervention. Finally, they calculated the cost-effectiveness ratio (cost per QALY gained) and the incremental cost effectiveness ratio (ICER, the additional cost of a treatment strategy compared to fluconazole monotherapy divided by the incremental improvement in QALYs) for each intervention. The estimated costs per person for each induction treatment strategy ranged from US$154 for 14 days of fluconazole monotherapy to US$467 for 14 days of amphotericin plus flucytosine. Estimated average one-year survival was lowest for fluconazole (40%) and highest for short-course (seven days) amphotericin plus 14 days of fluconazole (66%), similar to other amphotericin-based treatments. Cost-effectiveness ratios ranged from US$20 per QALY for short-course amphotericin plus fluconazole to US$44 per QALY for 14 days of amphotericin plus flucytosine. Short-course amphotericin plus fluconazole had the lowest ICER (US$15.11 per additional QALY over fluconazole monotherapy).
What Do These Findings Mean?
These findings suggest that, among the treatments investigated, a seven-day course of amphotericin with high-dose fluconazole for at least two weeks is the most cost-effective induction treatment for cryptococcal meningitis in Uganda. Although this result should be generalizable to other African countries, it needs to be treated with caution because very few trials have actually looked at the clinical effectiveness of this particular regimen. While short short-course amphotericin appears to be substantially more effective than fluconazole monotherapy, large-scale trials comparing short-course amphotericin regimens with more traditional 14-day regimens in resource-limited countries must be undertaken before short-course amphotericin-based treatments are adopted. Notably, however, if these trials confirm that survival with short-course amphotericin with fluconazole is about 30% better than with fluconazole alone, the researchers calculate that moving to short-course amphotericin could save about 150,000 lives every year in sub-Saharan Africa at a cost of US$220 per life saved.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Andrew Farlow provides a clearinghouse for updated guidelines for cryptococcal diagnosis and treatment.
The US Centers for Disease Control and Prevention provides information on Cryptococcus neoformans and a training manual called the Cryptococcal Screening Program Training Manual for Healthcare Providers
NAM/aidsmap provides information about all aspects of infection with Cryptococcus neoformans, including a personal story about cryptococcal meningitis
AIDS InfoNet has a fact sheet on cryptococcal meningitis (in several languages)
The not-for-profit organization Project Inform, which provides information, inspiration, and advocacy for people with HIV/AIDS and hepatitis C (in English and Spanish), has a fact sheet on cryptococcal meningitis
The MedlinePlus encyclopedia has a page on cryptococcal meningitis (in English and Spanish)
PMCID: PMC3463510  PMID: 23055838
21.  An unusual case of chronic meningitis 
BMC Family Practice  2004;5:21.
Chronic meningitis is defined as symptoms and signs of meningeal inflammation and persisting cerebrospinal fluid abnormalities such as elevated protein level and pleocytosis for at least one month.
Case presentation
A 62-year-old woman, of unremarkable past medical history, was admitted to hospital for investigation of a four-week history of vomiting, malaise an associated hyponatraemia. She had a low-grade pyrexia with normal inflammatory markers. A CT brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of the right frontal cortex but with no evidence of meningeal enhancement. Due to increasing confusion and patient clinical deterioration a lumbar puncture was performed at 17 days post admission. This revealed gram-negative coccobacilli in the CSF, which was identified as Neisseria meningitidis group B. The patient made a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for meningococcal meningitis.
1) Chronic bacterial meningitis may present highly atypically, particularly in the older adult. 2) There may be an absent or reduced febrile response, without a rise in inflammatory markers, despite a very unwell patient. 3) Early lumbar puncture is to be encouraged as it is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate antibiotic therapy can still lead to a good outcome.
PMCID: PMC524513  PMID: 15469610
22.  A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children 
BMC Clinical Pathology  2014;14(1):43.
Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons.
The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals.
Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011.
We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters.
Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.
PMCID: PMC4255930  PMID: 25477764
Acute bacterial meningitis; Homocysteine; Neurotoxicity
23.  Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. 
BMJ : British Medical Journal  1989;298(6674):636-642.
OBJECTIVE--To determine the efficacy of oral nimodipine in reducing cerebral infarction and poor outcomes (death and severe disability) after subarachnoid haemorrhage. DESIGN--Double blind, placebo controlled, randomised trial with three months of follow up and intention to treat analysis. To have an 80% chance with a significance level of 0.05 of detecting a 50% reduction in an incidence of cerebral infarction of 15% a minimum of 540 patients was required. SETTING--Four regional neurosurgical units in the United Kingdom. PATIENTS--In all 554 patients were recruited between June 1985 and September 1987 out of a population of 1115 patients admitted with subarachnoid haemorrhage proved by the results of lumbar puncture or computed tomography, or both. The main exclusion criterion was admission to the neurosurgical units more than 96 hours after subarachnoid haemorrhage. There were four breaks of code and no exclusions after entry. One patient was withdrawn and in 130 treatment was discontinued early. All patients were followed up for three months and were included in the analysis, except the patient who had been withdrawn. INTERVENTIONS--Placebo or nimodipine 60 mg was given orally every four hours for 21 days to 276 and 278 patients, respectively. Treatment was started within 96 hours after subarachnoid haemorrhage. END POINTS--Incidence of cerebral infarction and ischaemic neurological deficits and outcome three months after entry. MEASUREMENTS--Demographic and clinical data, including age, sex, history of hypertension and subarachnoid haemorrhage, severity of haemorrhage according to an adaptation of the Glasgow coma scale, number and site of aneurysms on angiography, and initial findings on computed tomography were measured at entry. Deterioration, defined as development of a focal sign or fall of more than one point on the Glasgow coma scale for more than six hours, was investigated by using clinical criteria and by computed tomography, by lumbar puncture, or at necropsy when appropriate. All episodes of deterioration and all patients with a three month outcome other than a good recovery were assessed by a review committee. MAIN RESULTS--Demographic and clinical data at entry were similar in the two groups. In patients given nimodipine the incidence of cerebral infarction was 22% (61/278) compared with 33% (92/276) in those given placebo, a significant reduction of 34% (95% confidence interval 13 to 50%). Poor outcomes were also significantly reduced by 40% (95% confidence interval 20 to 55%) with nimodipine (20% (55/278) in patients given nimodipine v 33% (91/278) in those given placebo). CONCLUSIONS--Oral nimodipine 60 mg four hourly is well tolerated and reduces cerebral infarction snd improves outcome after subarachnoid haemorrhage.
PMCID: PMC1835889  PMID: 2496789
24.  Iatrogenic Intraspinal Epidermoid Cyst 
Korean Journal of Spine  2014;11(3):195-197.
Epidermoid cyst is generally regarded as congenital disease, and commonly related to other congenital spinal anomalies. However, it also develops iatrogenically. We report one rare case of epidermoid cyst that we experineced among intradural extramedullary tumors. A 21-year-old female patient was admitted to the hospital due to low back pain with radiating pain into a right lower extremity that initiated about a month ago. She complained sensory lose and motor weakness (grade 4+) on her right extremity as well as urinary dysfunction and sphincter dysfunction. She had a lumbar puncture three times due to Pneumococcal meningitis when she was 13 years old. The well-circumscribed intradural extramedullary mass of 1.8×1.6×4 cm size was found on the L4-5 in a magnetic resonance image. Gross total tumor removal was garried out after the total laminectomy L5 and partial laminectomy L4. The tumor mass was gray-colored and so fragile that it was easy to be removed. The histological diagnosis confirmed epidermoid cyst without malignancy. After the operation, the patient progressively showed remarkable neurological recovery. In this case, the cause of epidermoid cyst is considered iatrogenic concerning history of several times of lumbar puncture as meningitis.
PMCID: PMC4206976  PMID: 25346768
Epidermoid cyst; Lumbar puncture; Iatrogenic
25.  A case of enteroviral meningoencephalitis presenting as rapidly progressive dementia 
A 70-year-old immunocompetent male presented to a memory disorders clinic with a 7-month illness that had begun with somatic complaints including transient right temporal head pain, left buttock pain, and right conjunctival injection. About 3 months after the first signs of illness, the patient had begun to develop insidious cognitive and behavioral decline, which progressed most rapidly in the 2 months before presentation. An assessment completed during hospitalization for intermittent fevers and confusion had not revealed an infectious etiology, although mild pleocytosis in the cerebrospinal fluid had been noted. Upon presentation to the memory disorders clinic, the patient was disoriented, distractible, laughed at inappropriate moments, and followed only one-step commands. He had hypophonic speech and had mildly increased axial tone. He scored 5 out of 30 on the Mini Mental State Examination and was admitted for expedited evaluation.
Physical examination, brain MRI, electroencephalogram, lumbar puncture, autoimmune and paraneoplastic testing, cerebral angiogram, cerebrospinal fluid analysis, enterovirus group-specific reverse transcriptase polymerase chain reaction assay, and RNA sequencing in brain biopsy samples.
Enteroviral meningoencephalitis.
Intravenous steroids with oral taper and intravenous immunoglobulin.
PMCID: PMC2637149  PMID: 18477991
dementia; echovirus; encephalitis; enterovirus; meningitis

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