Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial

In order to define the impact of needle type on post-lumbar puncture headache (PLPH), we performed a prospective, randomized trial comparing the incidence of PLPH in patients undergoing lumbar punctures (LPs) with traumatic vs atraumatic 22-gauge needles. Fifty-eight patients underwent 85 LPs. The incidence of PLPH was 36% in the traumatic vs 3% in the atraumatic group (p = 0.002).     

"Atraumatic" Sprotte needle reduces the incidence of post-lumbar puncture headaches.

Post-lumbar puncture headache (PLPH) is best explained by spinal fluid leakage due to delayed closure of a dural defect. In a prospective, randomized, double-blind study, taking into consideration all known methodological problems, the authors compared the incidence of PLPH using the "atraumatic" Sprotte needle vs the "traumatic" Quincke needle. Of the 230 patients included in the final analysis, 24.4% of patients in the "traumatic" group developed PLPH, whereas only 12.2% of patients in the "atraumatic" group did (p < 0.05). Therefore, use of the "atraumatic" Sprotte needle for lumbar puncture is recommended.     

Le syndrome post-ponction lombaire. Revue de la littérature et expérience des urgences céphalées

Post-lumbar puncture headache (PLPH) is a well-known syndrome resulting from spinal fluid leakage and delayed closure of a dural defect. The main symptom of PLPH is headache in upright posture relieved by lying down. Outcome is usually benign and complications are uncommon. The functional impact can however be important, leading to delayed discharge, sick leave and, if information delivery is ineffective, iterative consultations. Preventive measures have been published, but the prevalence of PLPH remains high (15 to 40% after diagnostic lumbar puncture). Needle size and type are probably the most important factors for reducing the risk of PLPH. Recovery can be rapid, within a few days. If PLPH persists after four days, an epidural blood patch should be discussed. The objective of this review is to summarize the literature on PLPH, and share the experience of our emergency headache center with an atraumatic 25-gauge needle (pencan, 0.5 × 90 mm or 0.5 × 103 mm, Braun, Germany).     

A dedicated lumbar puncture clinic: performance and short-term patient outcomes

The purpose of the study was to evaluate patient outcomes, including success rates, factors associated with unsuccessful procedures and frequency of post-lumbar puncture headaches (PLPH), at a dedicated academic outpatient lumbar puncture (LP) clinic. All patients referred to our LP clinic between June 1, 2014 and May 31, 2015 were included in this consecutive observational series. We collected information about patient characteristics, operational parameters of the procedure, and complications. We also recorded rates of participation in biomedical research involving use of cerebrospinal fluid. Univariate analysis used Student’s t test and Fisher’s exact test. Logistic regression was used to determine independent risk factors associated with unsuccessful LP and PLPH. The mean age of patients referred to our LP clinic was 46 ± 17 years. Of the 307 referrals, 281 patients (92%) started the procedure, with successful acquisition of CSF in 267 (95%). Factors contributing to unsuccessful procedures included higher body mass index [odds ratio (OR) 1.8], older age (OR 1.9), and female sex (OR 10.3). The rate of PLPH was 5.7%. Younger age (OR 0.5), female sex (OR 6.9), high mean arterial pressure (OR 2.2), and a traumatic LP (OR 10.0) were identified as risk factors for PLPH. Notably, 202 patients (72%) consented to biomedical research. A standardized approach to outpatient LP demonstrates high procedural success rate, low PLPH rate, and high participation in biomedical research. Awareness of a group of patients at higher risk for complications including procedure failure or PLPH provides guidance for decision-making regarding referral to the outpatient LP clinic.     

Low frequency of post-lumbar puncture headache in demented patients

The frequency of post-lumbar puncture headache (PLPH) was registered prospectively in 395 consecutive demented patients at a dementia diagnostic unit. The incidence of PLPH was low, occurring in only 8 patients (2.0%), the severity was mild, and the duration was less than 2 days in all cases but one. The reasons for this low frequency of PLPH in patients with dementia disorders may include disease- and/or age-related low pain sensitivity, rigid dural fibres and arteriosclerotic vessels, and large CSF space due to cerebral atrophy. Analysis of CSF is essential to identify secondary causes of dementia, preferentially chronic infections. The low frequency and severity of PLPH found in the present study shows that, with low risk of complications, lumbar puncture can be included in the routine clinical examination of demented patients.     

Incidence of post-lumbar puncture headache is independent of daily fluid intake

Summary The clinical practice of advising patients to increase their daily fluid intake after lumbar puncture in order to increase CSF production by re-hydration and thus try to prevent post-lumbar puncture headache (PLPH) has not yet been shown to be effective. In 100 patients the different effects of re-hydration on the incidence of PLPH (1.51 compared with 3.01 oral fluid per day over a period of 5 days) were tested prospectively. The incidence of PLPH was independent of the amount of fluid intake in both groups (18, 36%), as was the duration of PLPH. The physiology of CSF production and resorption suggests that PLPH is not a problem of CSF dynamics but a simple mechanical problem of how to close the dural rent and thereby stop the continuous leakage. It is no longer justifiable to advise patients to drink more than usual since there is no physiological or empirical basis for this and it does not seem to have even a placebo effect.     

EEG multifractal analysis correlates with cognitive testing scores and clinical staging in mild cognitive impairment

Alzheimer’s disease and mild cognitive impairment are increasingly prevalent global health concerns in aging industrialized societies. There are only limited non-invasive biomarkers for the cognitive and functional impairment associated with dementia. Multifractal analysis of EEG has recently been proposed as having the potential to be an improved method of quantitative EEG analysis compared to existing techniques (e.g., spectral analysis). We utilized an existing database of a study of healthy elderly patients (N = 20) who were assessed with cognitive testing (Folstein Mini Mental Status Exam; MMSE) and resting state EEG (4 leads). Each subject’s EEG was separated into two 30 s tracings for training and testing a statistical model against the MMSE scores. We compared multifractal detrended fluctuation analysis (MF-DFA) against Fourier Transform (FT) in the ability to produce an accurate classification and regression trees estimator for the testing EEG segments. The MF-DFA-based statistical model MMSE estimation strongly correlated with the actual MMSE when applied to the test EEG parameter dataset, whereas the corresponding FT-based model did not. Using a standardized cutoff value for MMSE-based clinical staging, the MF-DFA-based statistical model was both sensitive and specific for clinical staging of both mild Alzheimer’s disease and mild cognitive impairment. MF-DFA shows promise as a method of quantitative EEG analysis to accurately estimate cognition in Alzheimer’s disease.     

Atraumatic needle reduces the incidence of post-lumbar puncture syndrome

We investigated the occurrence of the post-lumbar syndrome (PPS) in relation to the puncture technique used, in a prospective randomised double-blind study comprising 100 patients. A new atraumatic 22-gauge cannula was compared with a 20-gauge cannula with a Quincke bevel. The atraumatic cannula is a needle with a tip shaped like a closed circular cone with a lateral opening, usually used with an outer cannula (introducer). The study showed that both the frequency of PPS and of acute complaints during lumbar puncture can be dramatically reduced with the atraumatic puncture technique. A marked PPS occurred after lumbar puncture with the 20-gauge cannula in 31% of patients, whereas only 5% of patients reported marked post-puncture symptoms after lumbar puncture with the atraumatic cannula.     

Cerebral blood flow characteristics in patients with post-lumbar puncture headache

The aim of this study was to verify if diagnostic lumbar puncture (DLP) in post-lumbar puncture headache (PLPH) patients is related to significant changes in cerebral blood flow which could be visualized by transcranial Doppler (TCD). Sixty-six patients were enrolled in this study. TCD was performed 24 h before DLP and repeated within 24 h after the procedure. The measurements included mean velocity (V _mean), peak systolic velocity (V _max), and Gosling’s pulsatility index (PI), in the left and right middle cerebral artery (MCA). PLPH was observed in 21 patients (32%). No significant differences were noted in V _mean, V _max and PI between the right and left MCAs—both before DLP and following this procedure. In patients who developed PLPH, bilateral pre-puncture values of V _mean and V _max were significantly higher and PI was significantly lower compared to unaffected individuals. No significant differences were observed between these groups in terms of post-puncture V _mean and V _max, but the post-puncture PI was still significantly lower in PLPH cases. In PLPH cases, the post-puncture values of V _mean and V _max were significantly lower than the respective baseline parameters. A significant inverse correlation was present between PLPH severity and bilateral pre-puncture PI. In conclusion, this study revealed that higher baseline values of V _mean and V _max and low PI in bilateral MCAs predispose patients to PLPH.     

Post-dural puncture related complications after diagnostic lumbar puncture, myelography and spinal anaesthesia

Objectives – This study was conducted to investigate complications after dural puncture. Material and methods – A 15 months' prospective observation study of routine clinical practice with dural puncture at a university hospital was conducted. Quincke spinal needles 0.90 to 1.0 mm O.D. (20–19 g) were used for diagnostic lumbar puncture, 0.70 mm O.D. (22 g) for myelography and 0.40 to 0.50 mm O.D. (27–25 g) for spinal anaesthesia. A questionnaire about post-puncture discomfort was given to the patients, to be returned after 1 week. Results – Of 679 questionnaires 537 (79.1%) were returned. Discomfort was experienced by 53.8% of the patients, most often after diagnostic lumbar puncture and myelography. The difference in incidence of headache after diagnostic lumbar puncture and myelography compared with spinal anaesthesia were 27.9% (95% CI: 18.6 to 37.2) and 18.3% (95% CI: 9.1 to 27.5). Conclusion – Small diameter and atraumatic spinal needles will reduce patients' discomfort after dural puncture.     

Safety and acceptability of the research lumbar puncture

Three hundred forty-two subjects underwent 428 research lumbar punctures for studies of cerebrospinal fluid (CSF) biomarkers. Subjects were 67 Alzheimer disease or mild cognitive impairment (AD/MCI) patients and 275 cognitively normal adults aged 21 to 88. Lumbar puncture was performed in the lateral decubitus or sitting position using the Sprotte 24 g atraumatic spinal needle. Up to 34 ml of cerebrospinal fluid were collected. Anxiety and pain experienced during lumbar puncture were rated on a visual analog scale. The frequency of any adverse event (11.7%), clinically significant adverse events (3.97%), and typical post-lumbar puncture headache (PLPHA) (0.93%) was low. Risk of post-lumbar puncture headache was unrelated to age, gender, position during lumbar puncture, ml of cerebrospinal fluid collected, or minutes of recumbent rest following lumbar puncture. The frequency of post-lumbar puncture headache was lower in AD/MCI (P = 0.03) than any other subject group. Anxiety and pain ratings were low. Younger subjects reported more anxiety than old (P = 0.001) and AD/MCI subjects (P = 0.008) and more pain than older normal subjects (P = 0.013). Pain ratings for women were higher than those for men (P = 0.006). Using the Sprotte 24 g spinal needle, research lumbar puncture can be performed with a very low rate of clinically significant adverse events and with good acceptability in cognitively impaired persons and cognitively normal adults of all ages.     

Drug development status for Alzheimer’s disease: present scenario

Recent advances in the understanding of Alzheimer’s disease pathogenesis have led to the development of numerous compounds that might ameliorate the disease process. Research in the field of Alzheimer’s disease therapy has been partly successful in terms of developing symptomatic treatments, but also had several failures in terms of developing disease-modifying therapies. These successes and failures have led to a debate about the potential deficiencies in our understanding of the pathogenesis of Alzheimer’s disease and potential pitfalls in diagnosis, choice of therapeutic targets, development of drug candidates, and design of clinical trials. Many clinical and experimental studies are ongoing, but we need to acknowledge that a single cure for Alzheimer’s disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information on pieces of the complex Alzheimer’s disease puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Several promising randomized controlled trials are ongoing, and the increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach for the treatment of Alzheimer’s disease.     

Abducens palsy after lumbar puncture.

OBJECTIVE: We report the case of a 43-year-old patient with neuralgic shoulder amyotrophy who developed abducens palsy on the left 4 days after diagnostic lumbar puncture (LP), which recovered completely within 4 months. RESULTS: Side effects after spinal tap are due to prolonged spinal fluid leakage and delayed closure of a dural defect causing intracranial hypotension. Downward 'sagging' of the brain and traction on cranial nerves may lead to abducens palsy. This case and a review of the literature illustrate the higher risk with the use of large-size traumatic needles in LP for cranial sixth nerve palsies. CONCLUSION: The presented case emphasizes the use of atraumatic small-size needles for lumbar puncture.     

Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition

BACKGROUND: Decreased cerebrospinal fluid (CSF) beta-amyloid 42 (A beta 42) concentration, but not A beta 40 concentration, is a biomarker for Alzheimer disease. This A beta 42 concentration decrease in CSF likely reflects precipitation of A beta 42 in amyloid plaques in brain parenchyma. This pathogenic plaque deposition begins years before the clinical expression of dementia in Alzheimer disease. Normal aging and the presence of the apolipoprotein E (APOE*4) allele are the most important known risk factors for Alzheimer disease. OBJECTIVE: To estimate the interactive effects of normal aging and presence of the APOE*4 allele on CSF A beta 42 concentration in adults with normal cognition across the life span. DESIGN: The CSF was collected in the morning after an overnight fast using Sprotte 24-g atraumatic spinal needles. The CSF A beta 42 and A beta 40 concentrations were measured in the 10th milliliter of CSF collected by sandwich enzyme-linked immunosorbent assay. The APOE genotype was determined by a restriction digest method.Subjects One hundred eighty-four community volunteers with normal cognition aged 21 to 88 years. RESULTS: The CSF A beta 42, but not the A beta 40, concentration decreased significantly with age. There was a sharp decrease in CSF A beta 42 concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A beta 42 concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele. CONCLUSION: These CSF A beta 42 findings are consistent with acceleration by the APOE*4 allele of pathogenic A beta 42 brain deposition starting in later middle age in persons with normal cognition.     

A new technique for acute and chronic recording of crural diaphragm EMG in cats

We have developed a percutaneous technique for placement of electromyogram electrodes in cat diaphragmatic crura. The technique is convenient and relatively atraumatic. Guided by external landmarks, small gauge hypodermic needles are used to advance electrodes through implant sites within or in contact with the crural portions of the diaphragm. Satisfactory EMG is reliably obtained from both acute and chronic preparations.     

The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer’s dementia

Since Alzheimer’s disease may affect driving performance, patients with Alzheimer’s disease are assessed on fitness to drive. On-road driving assessments are widely used, and attempts have also been made to develop strategies to assess fitness to drive in a clinical setting. Preferably, a first indication of fitness to drive is obtained quickly after diagnosis using a single test such as the Mini-Mental State Examination (MMSE). The aim of this study is to investigate whether the MMSE can be used to predict whether patients with Alzheimer’s disease will pass or fail an on-road driving assessment. Patients with Alzheimer’s disease (n?=?81) participated in a comprehensive fitness-to-drive assessment which included the MMSE as well as an on-road driving assessment [PLoS One 11(2):e0149566, 2016]. MMSE cutoffs were applied as suggested by Versijpt and colleagues [Acta Neurol Belg 117(4):811–819, 2017]. All patients with Alzheimer’s disease who scored below the lower cutoff (MMSE?≤?19) failed the on-road driving assessment. However, a third of the patients with Alzheimer’s disease who scored above the upper cutoff (MMSE?≥?25) failed the on-road driving assessment as well. We conclude that the MMSE alone has insufficient predictive value to correctly identify fitness to drive in patients with very mild-to-mild Alzheimer’s disease implicating the need for comprehensive assessments to determine fitness to drive in a clinical setting.     

Deep Brain Stimulation for Alzheimer’s Disease: Tackling Circuit Dysfunction

ObjectivesTreatments for Alzheimer’s disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer’s disease.Materials and MethodsWe review the literature on 1) circuit dysfunction in Alzheimer’s disease and 2) DBS for Alzheimer’s disease. Human and animal studies are reviewed individually.ResultsThere is accumulating evidence of neural circuit dysfunction at the structural, functional, electrophysiological, and neurotransmitter level. Recent evidence from humans and animals indicate that DBS has the potential to restore circuit dysfunction in Alzheimer’s disease, similarly to other movement and psychiatric disorders, and may even slow or reverse the underlying disease pathophysiology.ConclusionsDBS is an intriguing potential treatment for Alzheimer’s disease, targeting circuit dysfunction as a novel therapeutic target. However, further exploration of the basic disease pathology and underlying mechanisms of DBS is necessary to better understand how circuit dysfunction can be restored. Additionally, robust clinical data in the form of ongoing phase III clinical trials are needed to validate the efficacy of DBS as a viable treatment.     

Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise

The majority of putative disease-modifying treatments in development for Alzheimer’s disease are directed against the amyloid-β (Aβ) peptide. Among the anti-Aβ therapeutic approaches, the most extensively developed is immunotherapy—specifically, passive immunization through administration of exogenous monoclonal antibodies (mAbs). Although testing of mAbs has been fraught with failure and confusing results, the experience gained from these trials has provided important clues for better treatments. This review summarizes the experience to date with anti-Aβ mAbs to enter clinical trials for Alzheimer’s disease and examines the evidence for clinical efficacy and the major problems with safety—i.e., amyloid-related imaging abnormalities. As mAbs differ considerably with regard to their epitopes and the conformations of Aβ that they recognize (monomers, oligomers, protofibrils, fibrils), the consequences of targeting different species are also considered. An often-cited explanation for the failure of anti-Aβ mAb trials is that they are set too late in the disease process. New trials are indeed evaluating treatments at prodromal and preclinical stages. We should expect to see additional studies of presymptomatic Alzheimer’s disease to join the ongoing prevention trials, for which mAbs continue to serve as the mainstay.     

Matrix metalloproteinase 14 modulates diabetes and Alzheimer’s disease cross-talk: a meta-analysis

Diabetes mellitus is associated with dementia, but whether diabetes is associated with Alzheimer’s disease remains controversial. Alzheimer’s disease is characterized by amyloid beta aggregation. We hypothesized that genes, involved in amyloid beta degradation, may be altered due to diabetes and thus participate in progression of Alzheimer’s disease. Expression profiling of amyloid beta-degrading enzymes in streptozotocin-induced diabetic mice and their correlation with expression of amyloid precursor protein in hippocampus of Alzheimer’s disease patients were accessed. We found that matrix metalloproteinase 14 decreased in brain but not in other tissues of streptozotocin-induced diabetic mice, and was negatively correlated with expression of amyloid precursor protein in hippocampus of Alzheimer’s disease patients. These findings suggested matrix metalloproteinase 14 may link insulin-deficient diabetes to Alzheimer’s disease.     

Confirmatory factor analysis of the ADNI neuropsychological battery

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a large multi-center study designed to develop optimized methods for acquiring longitudinal neuroimaging, cognitive, and biomarker measures of AD progression in a large cohort of patients with Alzheimer’s disease (AD), patients with Mild Cognitive Impairment, and healthy controls. Detailed neuropsychological testing was conducted on all participants. We examined the factor structure of the ADNI Neuropsychological Battery across older adults with differing levels of clinical AD severity based on the Clinical Dementia Rating Scale (CDR). Confirmatory factor analysis (CFA) of 23 variables from 10 neuropsychological tests resulted in five factors (memory, language, visuospatial functioning, attention, and executive function/processing speed) that were invariant across levels of cognitive impairment. Thus, these five factors can be used as indicators of cognitive function in older adults who are participants in ADNI.