State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease.

Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.

Where there is no brain imaging: Safety and diagnostic value of lumbar puncture in patients with neurological disorders in a rural hospital of Central Africa.

Analysis of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) is an essential step for the diagnostic approach of neurological disorders, in particular neuro-infections. In low-resource settings, it is even often the only available diagnostic method. Despite its key contribution, little is known on the risks and benefits of LP in the large tropical areas where hospital-based neuroimaging is not available. The objectives of this study were to assess the safety and diagnostic yield of LP in a rural hospital of central Africa and to identify predictors of CSF pleocytosis (white blood cell count >5/µL) as surrogate marker of neuro-infections. From 2012 to 2015, 351 patients admitted for neurological disorders in the rural hospital of Mosango, Kwilu province, Democratic Republic of Congo, were evaluated using a systematic clinical and laboratory workup and a standard operating procedure for LP. An LP was successfully performed in 307 patients (87.5%). Serious post-LP adverse events (headache, backache or transient confusion) were observed in 23 (7.5%) of them but were self-limiting, and no death or long-term sequelae were attributable to LP. CSF pleocytosis was present in 54 participants (17.6%), almost always associated with neuro-infections. Presenting features strongly and independently associated with CSF pleocytosis were fever, altered consciousness, HIV infection and positive screening serology for human African trypanosomiasis. In conclusion, the established procedure for LP was safe in this hospital setting with no neuroimaging and CSF analysis brought a substantial diagnostic contribution. A set of presenting features may help accurately selecting the patients for whom LP would be most beneficial.

Cost of managing meningitis and encephalitis among adult patients in the United States of America.

OBJECTIVE: To determine the associated costs related to the diagnosis and treatment of meningitis and encephalitis (ME) in adult patients in the USA. METHODS: A retrospective observational study design was used to assess the use and costs of diagnostic tests and antimicrobial treatment and the total hospitalization costs for adult patients with suspected ME, who received a lumbar puncture procedure during an emergency department visit or during the first two service days of an inpatient stay. Related costs were calculated by timing of lumbar puncture performed and infectious etiology. RESULTS: A total 26429 adult patients with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost was $15 572±27168, with antimicrobial medication cost of $1144±4052 and laboratory test cost of $210±244. The total visit cost increased with delayed lumbar puncture procedure, intensive care unit stay, and if the etiology was fungi, arbovirus, or bacteria. CONCLUSIONS: Higher diagnostic and treatment costs are associated with a delayed lumbar puncture procedure, the etiological agent, and the requirement for an intensive care unit stay.

Examining Invasive Bedside Procedure Performance at an Academic Medical Center.

OBJECTIVES: Explore the performance patterns of invasive bedside procedures at an academic medical center, evaluate whether patient characteristics predict referral, and examine procedure outcomes. METHODS: This was a prospective, observational, and retrospective chart review of adults admitted to a general medicine service who had a paracentesis, thoracentesis, or lumbar puncture between February 22, 2013 and February 21, 2014. RESULTS: Of a total of 399 procedures, 335 (84%) were referred to a service other than the primary team for completion. Patient characteristics did not predict referral status. Complication rates were low overall and did not differ, either by referral status or location of procedure. Model-based results showed a 41% increase in the average length of time until procedure completion for those referred to the hospital procedure service or radiology (7.9 vs 5.8 hours; P < 0.05) or done in radiology instead of at the bedside (9.0 vs 5.8 hours; P < 0.001). The average procedure cost increased 38% ($1489.70 vs $1023.30; P < 0.001) for referred procedures and 56% ($1625.77 vs $1150.98; P < 0.001) for radiology-performed procedures. CONCLUSIONS: Although referral often is the easier option, our study shows its shortcomings, specifically pertaining to cost and time until completion. Procedure performance remains an important skill for residents and hospitalists to learn and use as a part of patient care.

Cost-effectiveness analysis of CTA and LP for evaluation of suspected SAH after negative non-contrast CT.

OBJECTIVES: Diagnostic workup of patients presenting with thunderclap headache and negative initial head CT remains a challenge, with most commonly employed strategies being lumbar puncture (LP) and CT angiography (CTA). The objective of this study was to determine the cost-effectiveness of these options. PATIENTS AND METHODS: A decision model was designed using clinical probabilities, costs, and utilities from published values in the literature. Base case analysis and Monte Carlo simulation were performed using the model to determine the cost-effectiveness of both options. RESULTS: CTA was associated with an expected cost of $747 and an expected utility of 0.798603029. In comparison, LP was associated with a cost of $504 and an expected utility of 0.799259526, making it the optimal strategy from both the cost and the utility perspectives. LP was also the more cost-effective strategy in all iterations in the Monte Carlo simulation. A sensitivity analysis showed that with the 2014 US Medicare reimbursement values, LP would remain the more cost-effective strategy unless its cost exceeded 4 times its current value. CONCLUSION: LP should remain the preferred strategy for evaluation of SAH in patients presenting with thunderclap headache and negative non-contrast head CT. CTA is not an effective replacement, from either a utility or cost perspective.

Cost-effectiveness Analysis of Follow-up Strategies for Thunderclap Headache Patients With Negative Noncontrast CT.

OBJECTIVES: Accurate diagnosis of acute subarachnoid hemorrhage (SAH) is critical in thunderclap headache patients due to high morbidity and mortality associated with missed aneurysmal bleeds. The objective of this study was to determine the utility of computed tomography angiography (CTA) in managing patients with acute, severe headaches and negative noncontrast CT and assess the cost-effectiveness of three different screening strategies-no follow up, CTA, and lumbar puncture (LP). METHODS: A modeling-based economic evaluation was performed with a time horizon of 1 year for thunderclap headache patients in the emergency department with negative noncontrast CT for SAH. Sensitivity analyses were performed to determine the effect of sensitivity of CT and the prevalence of SAH on cost-effectiveness. RESULTS: Lumbar puncture follow-up has the lowest cost and the highest utility in the mathematical model. The Monte Carlo simulation shows noncontrast CT with LP follow-up to be the most cost-effective strategy in 85.3% of all cases even at a $1 million/quality-adjusted life-years willingness-to-pay. Sensitivity analyses demonstrate that LP follow-up should be performed, except for when CT sensitivity exceeds 99.2% and the SAH prevalence is below 3.2%, where no follow-up may be considered. CONCLUSIONS: Although CTA is frequently used for evaluation of thunderclap headache patients, its utility is not clearly defined. LP follow-up is shown to be the most cost-effective strategy for evaluation of thunderclap headache patients in most clinical settings.

Availability, accessibility, and affordability of neurodiagnostic tests in 37 countries.

OBJECTIVE: To determine the availability, accessibility, and affordability of EEG, EMG, CSF analysis, head CT, and brain MRI for neurologic disorders across countries. METHODS: An online, 60-question survey was distributed to neurology practitioners in 2014 to assess the presence, wait time, and cost of each test in private and public health sectors. Data were stratified by World Bank country income group. Affordability was calculated with reference to the World Health Organization's definition of catastrophic health expenditure as health-related out-of-pocket expenditure of >40% of disposable household income, and assessment of providers' perceptions of affordability to the patient. RESULTS: Availability of EEG and EMG is correlated with higher World Bank income group (correlation coefficient 0.38, test for trend p = 0.046; 0.376, p = 0.043); CSF, CT, and MRI did not show statistically significant associations with income groups. Patients in public systems wait longer for neurodiagnostic tests, especially MRI, EEG, and urgent CT (p < 0.0001). The mean cost per test, across all tests, was lower in the public vs private sector (US $55.25 vs $214.62, p < 0.001). Each drop in World Bank income group is associated with a 29% decrease in the estimated share of the population who can afford a given test (95% confidence interval -33.4, 25.2; p < 0.001). In most low-income countries surveyed, only the top 10% or 20% of the population was able to afford tests below catastrophic levels. In surveyed lower-middle-income countries, >40% of the population, on average, could not afford neurodiagnostic tests. CONCLUSIONS: Neurodiagnostic tests are least affordable in the lowest income settings. Closing this "diagnostic gap" for countries with the lowest incomes is essential.

Defending a traditional practice in the modern era: The use of lumbar puncture in the investigation of subarachnoid haemorrhage.

INTRODUCTION: Acute severe headache is a common medical presentation, and a common area of diagnostic uncertainty. Subarachnoid haemorrhage (SAH) is the cause in a minority of patients and has a high rate of morbidity and mortality. Therefore, its conclusive diagnosis with computed tomography (CT) or lumbar puncture (LP) is paramount. With advancement in imaging technology, emerging evidence now suggests that LP is no longer required for a subset of patients as CT has 100% sensitivity in detecting SAH, when performed under specific conditions. OBJECTIVES: To assess the proportion of patients with conclusive CSF xanthochromia results following a negative CT scan in suspected SAH to determine the diagnostic efficacy of LP. METHODS: CSF bilirubin and oxyhaemoglobin spectrophotometric absorbance data from all centres in a regional health board were identified for consecutive patients over a 6-month period. Results were stratified as conclusive (positive or negative), or inconclusive according to national guidelines. RESULTS: 239 of 255 (93.7%) results were conclusive: 89.0% were negative (227 of 255). 4.7% of results were positive (12 of 255), revealing 4 cerebral aneurysms requiring treatment. 16 out of 255 (6.3%) samples were inconclusive, yielding 1 aneurysm requiring treatment. In the same period, there were 27 CT-positive cases of SAH. CONCLUSIONS: LP has a high diagnostic yield, eliminating the need for neurosurgical opinion or investigation in almost 90% of cases. The test is both cost and time efficient and subjects only a small number of patients to the radiation and contrast risks of angiography.

[Is it always useful to perform lumbar puncture for the diagnosis of multiple sclerosis? No]. / Est-il toujours utile de faire une ponction lombaire lors d'une suspicion de sclérose en plaques? Non.

In the absence of a specific test for the diagnosis of multiple sclerosis (MS), cerebrospinal fluid analysis (CSF) remains discussed. There are robust evidences which demonstrated that an early diagnosis of MS must be done, due to the availability of disease-modifying drugs that could influence the natural history of the disease. However, several arguments can be put forward to assert that CSF analysis is not useful for the diagnosis of MS and thus should not be realized in a systematic way. First, MRI remains the most sensitive and specific marker to validate dissemination in space and in time and CSF analysis is not recommended by the 2010 McDonald criteria. The second argument is related to the low sensitivity and specificity of abnormalities detected in CSF analysis to confirm the diagnosis of MS. Moreover, there is currently no evidence that the presence of oligoclonal bands could represent a surrogate marker on an individual prognostic way. Furthermore, lumbar puncture could be traumatic, may entail some infrequent risks and represents unnecessary expense. Thus, there are strong reasons to not recommend systematic CSF examination to diagnose MS.

Cost-effectiveness of diagnostic strategies for evaluation of suspected subarachnoid hemorrhage in the emergency department.

OBJECTIVES: Diagnosing subarachnoid hemorrhage (SAH) in emergency department (ED) patients is challenging. Potential diagnostic strategies include computed tomography (CT) only, CT followed by lumbar puncture (CT/LP), CT followed by magnetic resonance imaging and angiography (CT/MRA), and CT followed by CT angiography (CT/CTA). The objective was to determine the relative cost-effectiveness of diagnostic strategies for SAH. METHODS: The authors created a decision model to evaluate the cost-effectiveness of SAH diagnostic strategies in ED patients with suspected SAH. Clinical probabilities were obtained from published data; sensitivity analyses were conducted across plausible ranges. RESULTS: In the base-case scenario, CT-only had a cost of $10,339 and effectiveness of 20.25 quality-adjusted life-years (QALYs), and CT/LP had a cost of $15,120 and effectiveness of 20.366 QALYs. Among the alternative strategies, CT/CTA had a cost of $12,840 and effectiveness of 20.24 QALYs, and CT/MRA had a cost of $16,207 and effectiveness of 20.27 QALYs. In sensitivity analyses, probability of severe disability from SAH, sensitivity of noncontrast CT, and specificity of LP and MRA were key drivers of the model, and CT-only and CT/LP were preferable. CONCLUSIONS: In the base-case scenario, CT-only was preferable to the CT/CTA and CT/MRA strategies. When considering sensitivity analyses and the current medicolegal environment, there are no overwhelming differences between the cost-effectiveness of CT/LP and the alternative strategies to suggest that clinicians should abandon the standard CT/LP approach.

Pharmacoeconomical consequences of postoperative CSF leaks after intracranial surgery--a prospective analysis.

Cerebrospinal fluid (CSF) leaks are well-known and frequent complications of intracranial procedures with their clinical aspects covered by numerous studies. Little, however, is known about the pharmacoeconomical aspects of this specific complication. 545 patients with a variety of intracranial procedures (elective and trauma) were recruited for a multicenter, prospective, observational study over a 13-month period. A specific pharmacoeconomic analysis was performed in 168 of these patients from the institution of the first author covering all clinical and pharmaco-economical aspects of this specific complication. Of all patients, 5.36% developed a postoperative CSF leak. Treatment of the leak required numerous diagnostic and therapeutic procedures such as reoperations (n = 6), lumbar punctures (n = 11) or lumbar drainages (n = 4). Costs for these procedures and prolonged hospital stays nearly doubled the costs per case (€14079/case without a fistula vs. €25499/case with a fistula). Reimbursement for the hospital covered these extra costs, but net earnings per case were diminished by €565 in cases with a CSF leak. The authors conclude that the presence of a CSF leak after an intracranial operation - although not influencing outcome in general - results in additional diagnostic and therapeutic procedures for the patient, an enormous increase in costs for the community, and a financial loss for the hospital. Strategies to lower this complication rate should therefore urgently be developed both from a clinical and a pharmacoeconomical point of view.

Cost comparison between the atraumatic and cutting lumbar puncture needles.

OBJECTIVE: The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache. METHODS: A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model. RESULTS: Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year. CONCLUSION: The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.

Headache rate and cost of care following lumbar puncture at a single tertiary care hospital.

BACKGROUND: American Academy of Neurology guidelines recommend the use of noncutting needles because of lower rates of headache following lumbar puncture in randomized trials. We sought to determine the rate of headache using cutting needles and the potential cost savings of switching to noncutting needles. METHODS: We retrospectively reviewed the charts of all patients who had a lumbar puncture in the outpatient neurology clinic at a single institution between January 2004 and December 2005. Outcome data included occurrence of headache, back pain, or epidural hematomas within 2 weeks of the procedure. Costs associated with the use of the current system were compared with the projected costs of switching to a noncutting needle system. RESULTS: A total of 274 patients underwent lumbar puncture (62% women, mean age 53 ± 17 years, average weight 178 ± 43 pounds). Of these, 38 (14%) had a post-lumbar puncture headache. Eight patients (3%) reported back pain. No patients had an epidural hematoma. Twelve patients were admitted for a total of 18 hospital days, mainly for headache. Predictors of headache were younger age and no prior aspirin use. The rate of headache associated with the noncutting needle according to published literature is 4%. The estimated cost savings would have been approximately $20,000 per year (or approximately $73 per person). CONCLUSIONS: In this single-institution study, use of a noncutting needle would have potentially been associated with less adverse events and less cost. Further studies are warranted, including the possibility of premedication with aspirin.

Herpes simplex virus testing and hospital length of stay in neonates and young infants.

OBJECTIVE: To examine whether ordering testing of cerebrospinal fluid (CSF) for herpes simplex virus (HSV) by polymerase chain reaction (PCR) in neonates and young infants is associated with increased hospital length of stay (LOS) or increased hospital charges. STUDY DESIGN: This retrospective cohort study enrolled infants age

Postdural puncture headache: a randomized comparison of five spinal needles in obstetric patients.

This prospective, blinded, randomized study compares the incidence of postdural puncture headache (PDPH) and the epidural blood patch (EBP) rate for five spinal needles when used in obstetric patients. One thousand two women undergoing elective cesarean delivery under spinal anesthesia were recruited. We used two cutting needles: 26-gauge Atraucan and 25-gauge Quincke, and three pencil-point needles: 24-gauge Gertie Marx (GM), 24-gauge Sprotte, and 25-gauge Whitacre. The needle for each weekday was chosen randomly. Cutting needles were inserted parallel to the dural fibers. The incidences of PDPH were, respectively, 5%, 8.7%, 4%, 2.8%, and 3.1% for Atraucan, Quincke, GM, Sprotte, and Whitacre needles (P = 0.04, chi(2) analysis), and the corresponding EBP rates in those with PDPH were 55%, 66%, 12.5%, 0%, and 0% (P = 0.000). The Quincke needle had a more frequent PDPH rate than the Sprotte or the Whitacre needle (P = 0.02) and a more frequent EBP rate than the GM, Sprotte, or the Whitacre needle (P = 0.01). The Atraucan needle had a more frequent EBP rate than the Sprotte or Whitacre needle (P = 0.05). Neither the PDPH rate nor the EBP rates differed among the pencil-point needles. The cost of EBP must be taken into consideration when choosing a spinal needle. We conclude that pencil-point spinal needles should be used for subarachnoid anesthesia in obstetric patients.