A prospective double-blind clinical trial, comparing the sharp Quincke needle (22G) with an "atraumatic" needle (22G) in the induction of post-lumbar puncture headache

Posture-dependent, post-lumbar puncture headache is most likely caused by continuous leakage of cerebrospinal fluid through the dura mater perforation with a consecutive downward sagging of the intracranial content and an irritation of pain-sensitive structures of meninges and blood vessels. A psychogenic co-factor may also play a role. It is generally acknowledged that the incidence and intensity of the headache correlate significantly with the diameter of the needles used. A second factor, the shape of the needle point plays a crucial role as is shown in our prospective, double-blind, clinical trial with 75 patients: employment of the "atraumatic" Sprotte needle with a rounded off point significantly reduced the incidence of post-puncture headache from 36% to 4%. Beside the discussion of pathogenic factors, remarks on a rational therapy are made.     

Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease

BACKGROUND: The isoprostane 8,12-iso-iPF(2alpha)-VI, a specific marker of in vivo lipid peroxidation, is increased in Alzheimer disease (AD). The pathological changes associated with AD have a long silent phase before the appearance of clinical symptoms. Several studies have shown that AD is preceded by a prodromal phase characterized by mild cognitive impairment (MCI). OBJECTIVE: To investigate levels of this biomarker in subjects with MCI. DESIGN AND MAIN OUTCOME MEASURES: Using gas chromatography-mass spectrometry analysis, we measured 8,12-iso-iPF(2alpha)-VI levels in urine, plasma, and cerebrospinal fluid of patients with AD, subjects with MCI, and cognitively normal elderly subjects. SETTING AND PATIENTS: Subjects attending the Memory Disorders Clinic. RESULTS: We found significantly higher 8,12-iso-iPF(2alpha)-VI levels in cerebrospinal fluid, plasma, and urine of subjects with MCI compared with cognitively normal elderly subjects. CONCLUSIONS: These results imply that individuals with MCI have increased brain oxidative damage before the onset of symptomatic dementia. Measurement of this isoprostane may identify a subgroup of patients with MCI with increased lipid peroxidation who are at increased risk to progress to symptomatic AD.     

"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.     

Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer’s Disease Dementia in Individuals With Mild Cognitive Impairment

Background

Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects.

Ambulante Durchführung einer diagnostischen Lumbalpunktion in der Gedächtnissprechstunde

Lumbar puncture (LP) is growing in relevance for the diagnosis of cognitive impairment in the elderly. Due to the expected risk of post-lumbar puncture syndrome or other complications LPs have rarely been performed in the outpatient setting. Using a questionnaire, the post-lumbar puncture symptoms of 100 patients (54-84 years old; mean: 68.87 years; SD: 7.9) have been prospectively gathered after consecutively performed LPs in the Memory Clinic of the Department of Psychiatry, University of Bonn. Some of these patients were included in the early diagnosis program of the German Dementia Competence Network. Of the patients 9% developed a post-lumbar puncture syndrome of mild or middle intensity. The influence of gender, age, cognitive status, as well as a supplementary diagnosis of depression and needle size (G20 or G22 atraumatic Sprotte needle) on the incidence of the post-LP syndrome was evaluated by means of logistic regression. Only the patients' age was identified as a significant risk factor as with increasing age a diminishing risk of developing a post-lumbar puncture syndrome was found (OR=0.83; CI=0.71-0.97 per year). None of the other factors evaluated proved to be of significant influence. The post-LP symptoms did not necessitate supplementary consultations in any of the cases.     

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).     

Reducing post-lumbar puncture headaches with small bore atraumatic needles

Lumbar puncture for testing of Alzheimer’s disease pathophysiology for diagnostic confirmation is likely to become more common in the coming years. Minimizing adverse effects from this testing will be essential for clinical practice. Small bore, atraumatic needles reduce the occurrence of post-lumbar puncture headache (PLPH). Our goal was to extend this recommendation specifically to a well-characterized aging population. We assessed PLPH in the Alzheimer’s Disease Neuroimaging Initiative cohort and found that PLPH occurrence was reduced only when using a 24 gauge atraumatic needle. We recommend that lumbar punctures for clinical and research purposes in Alzheimer’s disease be conducted with 24 gauge atraumatic needles.     

Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment

OBJECTIVE: To use proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides able to differentiate between patients with stable mild cognitive impairment (MCI) and those who will progress to Alzheimer disease (AD). DESIGN: Baseline cerebrospinal fluid samples from patients with MCI and healthy controls were profiled using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. SETTING: Memory disorder clinic. PARTICIPANTS: Patients with MCI (n = 113), of whom 56 were cognitively stable and 57 progressed to AD with dementia during a 4- to 6-year follow-up, as well as 28 healthy controls who were followed up for 3 years. Main Outcome Measure During follow-up, 57 patients progressed to AD and 56 patients had stable MCI. Cerebrospinal fluid from these 2 groups of patients was compared using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: We identified a panel of 17 potential biomarkers that could distinguish between patients with stable MCI and patients with MCI who progressed to AD. We have positively identified and characterized 5 of the potential biomarkers. CONCLUSIONS: Proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of MCI progression to AD. The 5 identified biomarkers are relevant to the pathogenesis of AD and could help gain an understanding of the molecular pathways in which they may function.     

Cerebrospinal fluid diagnostics in first-episode schizophrenia

We evaluated the clinical use and the safety of cerebrospinal fluid diagnostics in 155 patients with the suspected diagnosis of first-episode schizophrenia. Five patients (3.2%) revealed pathological findings that lead to diagnostic re-evaluation and changes in clinical management. No serious adverse events occurred, but we documented 16 (10.3%) cases of mild to moderate headache or local pain at the puncture site. Our results underline the value of lumbar puncture in the clinical workup of first-episode patients with suspected schizophrenia.     

Simultaneous papilledema and optic disc drusen in a child

Idiopathic intracranial hypertension is a headache syndrome characterized by elevated intracranial pressure with normal cerebrospinal fluid content, normal cranial imaging, and elevated appearance of the optic disc. We report on a 6.5-year-old boy with complaints of headache and right esotropia causing diplopia. A lumbar puncture indicated an opening cerebrospinal fluid pressure of 28 cm H(2)O. The headache, diplopia, and esodeviation resolved after the lumbar puncture. However, at 2-week follow-up, the elevated appearance of the optic disc continued despite normal cerebrospinal fluid pressure. A second ophthalmologic consultation revealed optic disc drusen, as also demonstrated by ocular ultrasonography. To date, two such cases have been reported in the literature. To our knowledge, this patient is the youngest with coexisting optic disc drusen and idiopathic intracranial hypertension.     

Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years

This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau(181) (P-tau(181)) and amyloid-beta(1-42) (Abeta(1-42)). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau(181) levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p<0.01), while baseline Abeta(1-42) levels were lower (p<0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.     

Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment

CONTEXT: Cerebrospinal fluid tau protein and beta-amyloid 42 (Abeta42) protein are altered even in very mild Alzheimer disease (AD). So far, few data exist for subjects with mild cognitive impairment (MCI). OBJECTIVE: To investigate the potential of cerebrospinal fluid tau and Abeta42 for predicting progression from MCI to AD in a longitudinal study of 28 patients with MCI who received follow-up for 18 months. DESIGN: An 18-month prospective study. SETTING: Clinical follow-up study of community-residing subjects with MCI. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau and Abeta42 concentrations were measured using enzyme-linked immunosorbent assay at baseline. The potential of both biomarkers was evaluated to predict the progression to dementia, the end point of this study, using multiple logistic regression analysis. RESULTS: Of 28 subjects with MCI, 12 progressed to dementia (2 to frontotemporal dementia; 10 to AD). Six subjects had progressive MCI, and 10 subjects showed stable MCI. Cerebrospinal fluid tau levels were significantly elevated in patients who progressed to probable AD (P =.002) and subjects with progressive MCI (P =.003) compared with subjects who had stable MCI. Cerebrospinal fluid Abeta42 levels were significantly lower in patients who progressed to probable AD (P =.007) and those with progressive MCI (P =.04) than in subjects with stable MCI. Logistic regression analysis identified elevated tau protein level as a predictor of cognitive deterioration (P =.02), whereas a delayed verbal recall score at baseline was significantly associated with the development of probable AD (P =.03). CONCLUSION: Our results indicate that altered tau and Abeta42 concentrations may be detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.     

Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease

BACKGROUND: To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease. OBJECTIVE: To determine whether plasma levels of amyloid beta protein (Abeta40 and Abeta42) are useful for identifying cognitively normal elderly white subjects at increased risk for mild cognitive impairment (MCI) and AD. DESIGN: Using well-established sandwich enzyme-linked immunosorbent assays, plasma Abeta40 and Abeta42 levels were analyzed at baseline in a prospective, elderly white cohort followed up for 2 to 12 (median, 3.7) years to detect incident cases of MCI or AD. SETTING: Cognitively normal, community-based white volunteers recruited from primary care settings into the Mayo Rochester Alzheimer Disease Patient Registry. Patients We followed up 563 cognitively normal white volunteers (median age, 78 years; 62% female) who had at least 1 follow-up visit after measurement of baseline plasma Abeta levels. MAIN OUTCOME MEASURES: The primary outcome was time to development of MCI or AD. The secondary outcome was the annualized rate of cognitive change in patients for whom we had 2 Mattis Dementia Rating Scale evaluations 3 to 7 years apart. RESULTS: During follow-up, 53 subjects developed MCI or AD. Subjects with plasma Abeta42/Abeta40 ratios in the lower quartiles showed significantly greater risk of MCI or AD (P = .04, adjusted for age and apolipoprotein E genotype). Comparison of subjects with plasma Abeta42/Abeta40 ratios in the lowest vs the highest quartile gave a relative risk of 3.1 (95% confidence interval, 1.1-8.3). After adjusting for age and apolipoprotein E genotype, regression analysis using annualized changes in the Dementia Rating Scale scores as an outcome variable showed that participants with lower Abeta42/Abeta40 ratios had greater cognitive decline (P = .02). CONCLUSION: The plasma Abeta42/Abeta40 ratio may be a useful premorbid biomarker for identifying cognitively normal elderly white subjects who are at increased risk for developing MCI or AD.     

Syndrome of cerebrospinal fluid hypovolemia following lumbar puncture cerebrospinal fluid leak in a patient with idiopathic intracranial hypertension

An 11-year-old girl presented with headache of 3 months' duration. There was bilateral disc edema. The cerebrospinal fluid pressure was 50 cm of water with normal cerebrospinal fluid cytology and biochemistry. She developed severe headache (different and disabling), dizziness, vomiting, and backache on sitting up 6 hours after lumbar puncture, and lying supine relieved all of her symptoms. Intravenous fluids, analgesics, and complete bed rest did not relieve her symptoms over the next 72 hours. She was completely relieved of her symptoms on receiving two tablets of Caffergot containing 200 mg of caffeine and 2 mg of ergotamine 72 hours after lumbar puncture. The symptoms recurred 48 hours later, and a repeat dose of Caffergot was required. Magnetic resonance imaging (MRI) done 96 hours after lumbar puncture revealed the entire dura overlying the brain, including the posterior fossa, showing intense enhancement on contrast injection with leak at the lumbar puncture site. Oral caffeine (coffee, three times a day) was advised over 1 week. The patient remained asymptomatic, and a repeat MRI scan after 10 days showed complete clearing of the cerebrospinal fluid leak with no dural enhancement. The syndrome of cerebrospinal fluid hypovolemia following lumbar puncture is reported in a girl with idiopathic intracranial hypertension.     

Longitudinal changes of CSF biomarkers in Alzheimer's disease

Longitudinal changes of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) have been studied, but there are few consistent conclusions and even less is known about their variation during the different stages of the disease. We hypothesized that changes in CSF biomarker values would correlate with the progression of the cognitive decline in AD. One hundred and thirty-one memory clinic patients [56 AD, 57 mild cognitive impairment (MCI), 10 other neurological disorders, eight unimpaired subjects] underwent a clinical follow-up with repeated Mini-Mental Status Examination (MMSE) tests and two lumbar punctures with a median interval of 3 years. Levels of CSF amyloid-β (Aβ)(42), tau, and p-tau-181 were measured using commercially available ELISA. Twenty-one of the MCI subjects progressed to AD, whereas 26 subjects remained stable and 56 subjects had AD already at the baseline. The subjects displaying the most rapid MMSE decline rate had the lowest baseline Aβ(42), highest tau, and highest p-tau-181 CSF concentrations. An annual decrease of 2.20 pg/ml/year in the CSF p-tau-181 concentration was seen in AD-AD patients (p = 0.001). The difference was significant compared to stable MCI-MCI (increase of 1.24 pg/ml/year, p = 0.001) and cognitively healthy (increase of 0.84 pg/ml/year, p = 0.013) subjects (p for group difference 0.004). The decrease rate of p-tau-181 correlated with the MMSE decrease rate in AD subjects (r = 0.579, p < 0.001). The CSF Aβ(42) level decreased in the AD-AD group (decrease 11.9 pg/ml/year, p < 0.001). Concentrations of hyperphosphorylated tau decline in the late stages of the AD process. The decrease of p-tau-181 appears to correlate with cognitive functioning and probably reflects neuronal loss. More longitudinal studies of CSF biomarker dynamics are needed, especially in patients during the preclinical stage of the disease.     

Characteristic profiles of instrumental activities of daily living in Chinese older persons with mild cognitive impairment

Increasing evidence suggests that performance of the instrumental activities of daily living (IADL) can be impaired at the mild cognitive impairment (MCI) stage. Our study aimed at investigating the profiles of functional impairment in Chinese subjects with MCI. Subjects with MCI were categorized into single-domain amnestic MCI (a-MCI) (n=54) and multiple-domain amnestic MCI (md-MCI) (n=93) groups. Their functional scores of Disability Assessment of Dementia (DAD) were compared with those of cognitively normal elderly controls (NC) (n=78) and those with mild Alzheimer's disease (AD) (n=85).Subjects with md-MCI had intermediate performance in IADL between the NC and those with mild AD. Subjects with a-MCI had functional scores similar to those of normal controls. Age, education, and global cognitive test scores were not associated with functional scores in MCI subjects. Our results demonstrated that Chinese older persons with md-MCI had impairment in IADL, as compared to NC and subjects with a-MCI. This finding suggests that assessment of IADL should be incorporated in the clinical evaluation of MCI.     

Cerebrospinal fluid sulfatide is decreased in subjects with incipient dementia

We recently noted a profound decline in brain sulfatides (ST) in subjects who died with incipient dementia due to Alzheimer's disease. Herein, we measured ST levels in cerebrospinal fluid in cognitively normal elderly and in subjects with mild cognitive impairment due to incipient demenia of the Alzheimer type. There was a significant decrease in cerebrospinal fluid ST and in the ST to phosphatidylinositol ratio in MCI subjects. The ST to phosphatidylinositol ratio accurately differentiated very mildly impaired subjects from controls on an individual basis. The cerebrospinal fluid ST to phosphatidylinositol ratio may be a very useful biomarker for the earliest clinical stage of Alzheimer's disease.     

Evaluation of CSF biomarkers as predictors of Alzheimer's disease: a clinical follow-up study of 4.7 years

In this study, we determined the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers to predict development of Alzheimer's disease (AD) within five years in patients with mild cognitive impairment (MCI). To do so, the levels of tau, phosphorylated tau, Aβ42, Aβ40, Aβ38, sAβPPα, and sAβPPβ were analyzed in 327 CSF samples obtained at baseline from patients with AD (n = 94), MCI (n = 166), depressive disorder (n = 29), and cognitively healthy controls (n = 38). In the cohort with MCI at baseline, 33% subsequently developed AD and 16% developed other types of dementia; however, 51% were still cognitively stable after a followup of 4.7 years (range 3.0-7.2). Optimal cutoffs for each biomarker or combinations of biomarkers were defined in the AD, control, and depressive disorder groups. Several combinations resulted in sensitivity and specificity levels > 85% for differentiation of AD from controls and depressive disorder. Using the previously established cutoffs, a combination of Aβ42 and tau could predict future development of AD in MCI patients with a sensitivity of 88%, specificity 82%, positive predictive value 71%, and negative predictive value 94%. MCI patients with both low Aβ42 and high tau levels had a substantially increased risk of developing AD (OR 20; 95% CI 6-58), even after adjustment for confounding factors. Ultimately, CSF biomarkers can stratify MCI patients into those with very low or high risk for future development of AD. However, the specificities and positive predictive values are still too low to be able to diagnose AD before the patients fulfill the clinical criteria.     

Incidence and Effect of Traumatic Lumbar Puncture in the Neonate

The incidence of non-traumatic, traumatic and unsuccessful lumbar punctures in 181 neonates was similar whether a needle with a stylet, a butterfly needle without stylet, or a standard venipuncture needle without stylet was used. Comparison of 20 lumbar puncture pairs in 17 patients showed that traumatic lumbar puncture does not result in a cerebrospinal fluid pleocytosis between two and 13 days after initial traumatic lumbar puncture.     

Prediction of Alzheimer's disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment

Evidence supports an important role for beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Here, we investigate baseline levels of the 40- and 42-amino-acid-long Abeta peptides (Abeta40 and Abeta42) in cerebrospinal fluid (CSF) from a cohort of patients with mild cognitive impairment (MCI, n = 137) in relation to the final diagnosis after 4-6 years of follow-up time. CSF Abeta42 concentration at baseline and the Abeta42/Abeta40 ratio were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients and MCI patients who developed other forms of dementia (p < 0.001). The baseline levels of Abeta40 were similar in all MCI groups but correlated with change in Mini Mental State Examination scores in converters to AD. The Abeta42/Abeta40 ratio was superior to Abeta42 concentration with regard to identifying incipient AD in MCI (p < 0.05). In conclusion, the data provide further support for the view that amyloid precursor protein metabolism is disturbed in early sporadic AD and points to the usefulness of the Abeta42/Abeta40 ratio as a predictive biomarker for AD.