Use Of Cerebrospinal Fluid Research Articles

Third cranial nerve palsy with confirmed HHV-6 positivity

We present a rare case of a 38-year-old man diagnosed with third cranial nerve paralysis, where no abnormalities were detected on MRI. Human Herpes Virus-6 (HHV-6) infection affecting the central nervous system and associated with cranial nerve paralysis is an unusual occurrence. This report underscores the importance of considering HHV-6 as a differential diagnosis in patients presenting with cranial nerve palsy and suggests the use of cerebrospinal fluid (CSF) HHV-6 polymerase chain reaction (PCR) testing for confirmation.

Diagnostic Value of sLR11 and sIL-2R in the Cerebrospinal Fluid for Malignant Central Nervous System Lymphoma.

Objective We previously reported that patients with acute leukemia and malignant lymphoma (ML) demonstrated significantly increased serum soluble LR11 (sLR11) levels compared to normal controls. Accurately diagnosing ML of the central nervous system (CNS ML) using cytology is frequently difficult. Therefore, we evaluated the use of cerebrospinal fluid (CSF) sLR11 and soluble interleukin-2 receptor (sIL-2R) as diagnostic and treatment response markers for CNS ML. Methods We retrospectively evaluated the CSF results for CNS ML using clinical data at our institution, and then analyzed the usefulness of sLR11 and sIL-2R in CSF for both the diagnosis and as surrogate markers that reflect the therapeutic effect. Patients We enrolled patients with CNS ML who received intrathecal anticancer drugs between 2017 and 2023. We analyzed the sLR11 and sIL-2R levels in CSF and cytological malignant grades. We studied 22 patients, including 17 with central nervous system (CNS) clinical conditions and five who received prevention treatment. Results The CSF sLR11 levels were significantly and positively correlated with CSF sIL-2R levels. The CSF sLR11 and sIL-2R levels in patients with CNS ML were significantly higher than those in the prevention group. A receiver operating characteristic (ROC) curve analysis showed the cut-off value of sLR11 for CNS invasion to be 21.7 ng/mL. Moreover, the chemotherapy-responder group demonstrated significantly decreased CSF sLR11 and sIL-2R levels after treatment. Conclusion CSF sLR11 and sIL-2R of CSF were found to be useful biomarkers for the diagnostic and treatment response evaluation in patients with CNS ML.

The Novel Biomarkers for Predicting Prognosis and Recurrence in Primary Central Nervous System Lymphoma: Exosomal Protein and Exosomal microRNA

Abstract Purpose Primary central nervous system lymphoma (PCNSL) is a highly heterogeneous tumor. Therefore, it is crucial to identify biomarkers that can dynamically monitor disease progression for individualized treatment and to improve prognosis. Exosomes carry a large amount of genetic and proteomic information and are stable and easy to obtain. They play important roles in disease diagnosis, treatment, and prognosis. This study aimed to evaluate the use of cerebrospinal fluid (CSF) exosomes in patients with PCNSL as biomarkers of tumor evolution. Methods From October 2021 to October 2022, patients diagnosed with PCNSL via pathology were selected from Beijing Tiantan Hospital affiliated to Capital Medical University. None of the patients had received any cancer-related treatment before diagnosis. Primary intraocular lymphoma and HIV-positive patients were excluded. Clinical information and laboratory findings of patients were recorded in detail. The responses were evaluated according to the response criteria formulated by the International Primary Nervous System Lymphoma Cooperation Group in 2005. According to the time of collecting CSF samples, the patients were divided into diagnosis group (before treatment, n=12), treatment group (after 2-4 treatment cycles, n=11) and complete remission (CR) group (achieved CR after 6 treatment cycles, n=11). We analyzed and compared the exosomal protein concentrations and microRNA expression in the CSF of patients in different groups using western blotting and quantitative reverse transcription PCR. Results There are CD20-positive exosomes in the CSF of patients with PCNSL (Figure 1). In the diagnosis group, the exosomal protein concentration of patients who achieved CR after 2 cycles induction treatment (early remission) was significantly lower than that of patients who did not achieve early remission (p=0.03). Higher exosomal protein concentrations (p=0.022) and exosomal miR-3681-3p expression (p=0.036) at diagnosis were significantly associated with shorter progression-free survival (Figure 2). The expression levels of miR-21-5p (p=0.001), miR-29b-3p (p=0.043), and miR-101-3p (p=0.007) in exosomes were significantly higher in the diagnosis group than in the CR group. Higher exosomal protein concentrations (p=0.012) and exosomal miR-101-3p expression (p=0.013) after CR were significantly associated with recurrence and shorter disease-free survival (Figure 2). The predictive efficacy of exosomal protein concentration and exosomal has-miR-101-3p in PCNSL was analyzed. The area under the receiver operator characteristic curve (AUC) was 0.833 (95% confidence interval 0.524-1.000; p<0.05) and 0.917 (95% confidence interval 0.731-1.000; p=0.033), respectively. Conclusions Exosomes in CSF may have the potential to evaluate prognosis and predict recurrence in PCNSL. It provides clinicians with selectable biomarkers for dynamic evaluation of disease progression.

Reuse of Nasoseptal Flaps for Endoscopic Endonasal Skull Base Reconstruction.

Introduction Pedicled nasoseptal flap (NSF) placement is a critical component of skull base reconstruction after endoscopic endonasal approaches (EEAs). The effectiveness of NSF reuse has not been thoroughly studied. Prior reports using flaps harvested at one center and reused at another may have technical variability bias. Methods We identified patients who underwent both their initial and NSF-reused surgeries at Weill Cornell Medical College from 2004 to 2022 using a prospective database of all EEAs. Surgical pathology, intraoperative leak grade, use of cerebrospinal fluid (CSF) diversion and skull base coverage were examined. The primary outcome measure was occurrence of CSF leak. Results Fourteen patients (six women, eight men) underwent 14 first time and 14 revision operations with median age of 36.6 years (interquartile range [IQR]: 23.9-61.3) at the time of the NSF reuse. The median interval between the first NSF use and reuse was 70.6 months (IQR: 16.6-87). Eight patients were operated on for pituitary adenoma. Nonadenomas included three craniopharyngiomas and one case each of epidermoid, ependymoma, and chordoma. There were 16 high-flow, 8 low-flow intraoperative leaks, and 4 with no leak. CSF diversion was used in 24 operations. There were three postoperative leaks, one after a first operation and two after NSF reuse. All postoperative CSF leaks, whether first or second operations, occurred in cases with both high-flow intraoperative CSF leak and incomplete NSF coverage ( p = 0.006). Conclusion NSF reuse is effective at preventing postoperative CSF leak. The primary predictors of leak are high-flow intraoperative leak and inadequate defect coverage with NSF, regardless of the operation number.

Liquid biopsy of circulating tumor DNA in cerebrospinal fluid for early diagnosis of brain malignancies: A review

Brain cancer is the most aggressive intracranial disease: once diagnosed, 70% of patients will not survive. Early and accurate diagnosis is essential to improving the survival rate of diagnosed patients. Currently, imaging scans and pathological biopsies are mainly relied on to confirm the diagnosis of brain tumors. However, imaging scans do not confirm the diagnosis or tumor grade, nor do assess response and monitor treatment effect. Similarly, pathological biopsies are highly invasive and difficult to repeat. To address these limitations, the field has proposed the use of cerebrospinal fluid (CSF) as a liquid biopsy method to detect circulating tumor DNA (ctDNA). This review focuses on how liquid biopsy of CSF ctDNA can facilitate and complement the clinical care of patients with brain tumors. Relevant reviews in the past five years show that ctDNA is highly expressed and its content in CSF is higher than that in plasma. By sequencing the ctDNA of CSF, the diagnosis and prognosis information of brain tumors can be obtained, the best treatment method can be selected, the treatment response can be monitored, and the tumor evolution can be tracked. Because ctDNA detection is still in the research stage and lacks standardized technology, its effectiveness and practicality require further investigation before they can be used in clinical practice.

Artificial cerebrospinal fluid use during burr-hole surgery and reoperation rate in patients with chronic subdural hematoma: an analysis using a nationwide inpatient database

BackgroundThe optimal surgical procedure to reduce the recurrence rate of chronic subdural hematoma (CSDH) after burr-hole surgery remains to be established. This study aimed to investigate the association between artificial cerebrospinal fluid (ACF) use during burr-hole surgery and reoperation rate in patients with CSDH.MethodIn this retrospective cohort study, we used the Japanese Diagnostic Procedure Combination inpatient database. We identified patients aged 40–90 years who were hospitalized for CSDH and had undergone burr-hole surgery within 2 days of admission, between July 1, 2010 and March 31, 2019. We performed a one-to-one propensity score-matched analysis to compare the outcomes between patients with and without ACF irrigation during burr-hole surgery. The primary outcome was reoperation within 1 year of surgery. The secondary outcome was the total hospitalization costs.ResultsOf the 149,543 patients with CSDH from 1100 hospitals, ACF was used in 32,748 patients (21.9%). Propensity score matching created highly balanced 13,894 matched pairs. In the matched patients, the reoperation rate was significantly lower in the ACF users than that in the non-users group (6.3% vs. 7.0%, P = 0.015), with a risk difference of −0.8% (95% confidence interval, −1.5 to −0.2). There was no significant difference in the total hospitalization costs between the two groups (5079 vs. 5042 US dollars, P = 0.330).ConclusionsACF use during burr-hole surgery may be associated with lower reoperation rate in patients with CSDH.

260MO Liquid biopsy NGS test identifies actionable DNA mutations from CSF specimens of lung cancer patients

Lung cancer is one of the top causes of cancer death. Liquid biopsies have emerged as a non-invasive method to identify patients who may respond to therapy, enabling dynamic monitoring of minimal residual disease and drug resistance. While plasma specimens have commonly been used for liquid biopsies, we validated the use of cerebrospinal fluid (CSF) for liquid biopsy next-generation sequencing (NGS) testing.

Establishing an Autopsy-Based Cerebrospinal Fluid Biomarker Signature in Alzheimer Disease Patients.

Featured Article: Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer's Disease Neuroimaging Initiative subjects. Ann Neurol 2009;65:403-13.† At the time this work was conducted (2007 to 2008), the research use of cerebrospinal fluid (CSF) biomarker proteins linked to Alzheimer disease (AD) hallmarks—β-amyloid (Aβ) plaque load and tau pathology (Aβ1-42, t-tau, and p-tau181) —was becoming established practice amongst a number of experienced laboratories as reliable and accurate indices of brain pathology in living subjects (1–3). These studies mainly used either a widely employed ELISA methodology (4) or the newer (at the time) microbead-based biomarkers multi analyte profiling (xMAP) immunoassay format, developed by Innogenetics (now Fujirebio) (5). The data generated from more than 25 studies that used these techniques and CSF provided strong support for a more objective measurement of amyloid and tau pathology in living individuals, compared to clinical diagnosis of AD dementia (6). The clinical diagnosis of AD is only up to about 80% accurate and our 2009 study in Annals of Neurology and other studies provided the foundation for moving towards a biological basis (protein biomarker profile) for more accurate clinical diagnosis of the presence of ongoing AD brain pathology. Two populations were used in our study: (a) participants in the multicenter study, the Alzheimer's Disease Neuroimaging Initiative (ADNI; 100 patients with early AD, 196 patients with mild cognitive impairment, and 115 cognitively normal age-matched controls, all clinically diagnosed), provided CSF samples collected at 56 centers at the participants’ baseline visit, and (b) an independent population, followed at the University of Pennsylvania Alzheimer's Disease Clinical Core, of 56 autopsy-confirmed AD participants and 52 age-matched living cognitively normal controls. Besides inclusion of an ADNI-independent population for assessment of cutpoint values for each of the 3 AD biomarkers as well as for the ratios t-tau/Aβ1-42 and p-tau181/Aβ1-42, another key feature in this study was the close collaboration between an in vitro diagnostic company and a university laboratory with the aim of generating best-in-class assays for the benefit of patients, and the inclusion of autopsy diagnosis for the patients with AD, the accepted gold standard for diagnosis of this disease. This enabled (a) determination of the accuracy of prediction of AD pathology assessed by receiver operating characteristic curve (AUC) analyses, (b) determination of cutpoints for the individual proteins and their ratios, and (c) establishment of a logistic regression model that combined Aβ1-42, t-tau, and APOε4 genotype. AUC values ranged from 0.913 for CSF Aβ1-42 concentration alone up to 0.942 for the combination of Aβ1-42, t-tau, and APOε4 genotype. Importantly, the same lot of reagents was used for the analyses in both populations, thus removing lot-to-lot variability from measurement errors. At the time this work was done, it was a considerable source of variability using this “for research-use-only (RUO)” immunoassay. It was an important additional feature of this study.

Prevention of spinal cord ischemia by cerebrospinal fluid drainage during the endovascular treatment of extensive aortic pathologies

Spinal cord ischemia is a dramatic complication of extended endovascular aortic repair. Preventive measures are necessary to reduce its occurrence. The preventive use of cerebrospinal fluid (CSF) drainage is controversial. This work reports the experience of our center after introduction of a protocol of prevention of spinal cord ischemia including CSF drainage.

Терапевтическая эффективность биостимулятора на основе спинномозговой жидкости коров при агалактии у кошек

Agalactia is a condition that is a complication of the postpartum period and is characterized by a complete absence of milk from the mother. The article presents data on the spread and causes of agalactia in cats, the results of the therapeutic effectiveness of the use of various drugs in its treatment. It was found that the main causes of agalactia in 6,6 % of cats were stresses of various etiologies in 27 % of cases, hormonal disorders in 23 %, infectious diseases in 41 %, and breast underdevelopment in only 9 %. Cats with agalactia by generally accepted pattern were intramuscularly injected with oxytocin 0.3 ml, twice a day, 5 days in a row; biogenic stimulator Apilak 1/2 tablet 2 times a day, 5–7 days; and subcutaneous injections of natural biogenic stimulator — cerebrospinal fluid obtained from cows 3 ml 1 time a week. Subcutaneous injections of cerebrospinal fluid as a biostimulator, which lacks the species specificity of cows at a dose of 1 ml per 1 kg of weight once a week, allow 94 % of newborn kittens to be preserved during 30 days of follow-up after childbirth, which confirms its stimulating effect on the hypothalamus, pituitary gland and central regulation of endocrine functions in general. Application in practice for blood loss and neurological diseases actualize the use of cerebrospinal fluid in obstetrics and gynecology with theoretical justification and clinical studies.

Shunt technology for infants and a lifetime.

The use of cerebrospinal fluid (CSF) shunts remains a fundamental therapeutic modality in the management of hydrocephalus. Nowadays, neurosurgeons have an arsenal of different shunt technologies on their hands, with several companies producing many different configurations of them. The greatest difficulty of treating a child with hydrocephalus is to deal with a brain that will enormously change its size and hydrodynamic conditions and a body that will multiply its height and weight in a short time. Detailed knowledge of the hydrodynamic properties of shunts is mandatory for any neurosurgeon and much more for those taking care of pediatric patients. It is necessary to know that these properties of the valve may influence the evolution of the patient after shunting and it is recognized that a patient physiology-specific valve selection may yield better outcomes and decrease complications. This article provides a summary of the most common available CSF valves and overdrainage control devices, their technology, and possible combinations. The objective is to offer a quick overview of the armamentarium to facilitate the recognition of the implanted device and improve the selection of the most suitable valve for each patient.

BrainStorm: A brain metastases research platform to tackle the challenge of central nervous system (CNS) metastases in solid tumors (Oncodistinct 006).

TPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]

Идиопатическая гидроцефалия взрослых: современное состояние проблемы

The term "idiopathic hydrocephalus" in adults is a broader concept that includes larger spectrum of patients compared to "idiopathic normotensive hydrocephalus". It includes both young and elderly patients with various forms of the disease, patients with various levels of obstruction. Th ere is no general classification and general approach to treat patients with such a pathology. Endoscopic triventriculostomy in idiopathic aqueductal stenosis and cerebrospinal fluid shunting after a positive test of cerebrospinal fluid (tap test) evacuation in idiopathic normotensive hydrocephalus are proved to be effective. In patients with other forms of cerebrospinal fluid pathway obstruction, treatment approach is represented by the opinions of some surgeons. At the same time, most surgeons consider the use of cerebrospinal fluid shunting operations to be effective and justified, and they use endoscopic techniques as an option for examining ventricular system and for performing auxiliary manipulations. The high frequency of various complications of bypass surgery and slightly lower efficiency of endoscopic operations indicates the need to systematize patients; to improve selection criteria and to expand the indications for the use of endoscopic surgical techniques.

Commentary: The aggregation of marginal gains for spinal cord protection

Commentary: The aggregation of marginal gains for spinal cord protection

Impact of laboratory work-up of lymphoma guidelines on cytopathology practices

A multi-society expert panel recently published evidence-based guidelines and recommendations for the primary diagnosis and classification of lymphoma, which included a public comment period. The guideline concludes: "primary diagnosis and classification of lymphoma can be achieved with a variety of specimens." The guideline recommends that fine-needle aspiration biopsy (FNAB) cytomorphology not be used without ancillary testing, and that either flow cytometry or immunohistochemical immunophenotyping be performed for any type of specimen. Either excisional or core biopsy should be obtained when there is a high suspicion of lymphoma, and excision is recommended when feasible for Hodgkin lymphoma primary diagnosis. The use of cerebrospinal fluid to diagnose central nervous system lymphoma is discussed. For any patient with initial negative biopsy or fluid specimens and a high suspicion of lymphoma, additional tissue samples should be obtained. Additional molecular testing and good practice statements are summarized in the guideline. Cytopathologists should continue to advocate for judicious use of lymph node FNAB as an excellent triage tool that may require additional tissue biopsy for definitive diagnosis.

Decision analysis and personalized clinical tool for cerebrospinal fluid drains in thoracoabdominal aortic aneurysms repair.

The routine use of cerebrospinal fluid (CSF) drainage in patients undergoing operative repair of thoracoabdominal aneurysms (TAAA) has been associated with decreased rates of spinal cord ischemia. The use of CSF drains is not without consequence, howeverwith complications including subarachnoid hemorrhage, epidural hematoma, meningitis, and, in 1% of cases, death. To date, a decision analysis tool to help clinicians decide when to use and not to use a CSF drain does not exist. In this analysis, we set out to develop a decision analysis tool for CSF drain placement in patients undergoing operative repair of TAAA. A Markov state-transition cohort model that compared TAAA repair with adjunctive CSF drain insertion to TAAA repair without drain insertion for the outcome of life expectancy was developed in TreeAge 2020. The cycle length was 1 month and the time horizon was 60 months. The use of a CSF drain was associated with improved 5-year life expectancy (3.21 ± 0.10 vs. 3.09 ± 0.11 life-years gained). In the sensitivity analysis that varied the effectiveness of a CSF drain (odds ratio closer to 1 = less effective), the use of a CSF drain resulted in higher life expectancy in almost all scenarios. The routine use of a CSF drain in patients undergoing TAAA repair is safe and effective, with few exceptions. This decision analysis tool can be used by clinicians to develop a personalized approach.

Endoscopic extrasellar skull base reconstruction using bioabsorbable plates.

Many techniques have been utilized for reconstruction of the anterior skull base. Each method has advantages and disadvantages with respect to effectiveness, morbidity, strength, and cost. Rigid reconstruction may provide advantages in certain patients. We evaluated all patients who had placement of rigid absorbable reconstruction plates in the anterior skull base in a variety of extrasellar locations and describe results and complications compared with other published techniques. A retrospective review was conducted of consecutive patients at a tertiary referral institution who underwent endoscopic extrasellar skull base reconstruction, 2012-2019, using resorbable poly (D,L) lactic acid plates (Resorb-X Sellar Wall Plate; KLS Martin; Jacksonville, FL). Data reviewed included demographic information, indication for surgery, location and size of defect, pathology, peri-operative use of cerebrospinal fluid (CSF) diversion, postoperative complications, post-operative CSF leak, adjuvant therapy, and length of follow-up. Twenty-four subjects and 25 operative procedures met inclusion criteria. Mean age was 53years (range 11-77). Average BMI was 34kg/m2. Mean follow-up time was 30months (range 1-78). Indications for surgery were CSF rhinorrhea (spontaneous, post-traumatic, or iatrogenic) or reconstruction after tumor resection. Four cases were revision procedures. Twenty patients had lumbar drains placed intraoperatively. Only two nasoseptal flaps and two free mucosal grafts were used. None of the patients had a postoperative CSF leak. There was no mortality or morbidity related to the skull base reconstruction or implanted material. The Resorb-X resorbable rigid plate provides an effective, customizable, bioabsorbable option that is easily manipulated for skull base reconstruction of defects of a variety of sizes in diverse locations. Reconstruction incorporating this plate provides an effective alternative to other previously described techniques.

Global trends in the evaluation and management of cerebrospinal fluid shunt infection: a cooperative ISPN survey.

Ventriculoperitoneal shunts (VPS) is commonly performed by pediatric neurosurgeons and there is no consensus in management of VPS infection as it relates to diagnosis and treatment. We utilized an international practitioner-based survey to study the variability in VPS infection diagnostic and therapeutic measures. A survey gauging practice patterns of pediatric neurosurgeons regarding VPS and its complication management was distributed. Survey endpoints were analyzed by VPS case volume and pediatric-focused case volume regarding diagnostic measures, use of cerebrospinal fluid (CSF) profile, microbiology, and treatment. A total of 439 surveys were distributed, with a response rate of 31%. Responders ranged from Americas (44.9%), European (31.4%), Asian (18.6%), African (2.5%), to Australian continents (2.5%). Practitioners were stratified based on number and percentage pediatric VPS performed. Institutions performing highest VPS and percentage pediatric case volumes had lower rate of VPS infection. Shunt tap was the most widely used diagnostic study. Overall CSF profile did not affect decision making towards VPS internalization, except for leukocyte count ≤ 20 × 109/L. Practitioners utilized 3 negative cultures prior to VPS internalization. Discrepancies in surgical management were noted amongst centers with high versus low VPS volume and proportion of pediatric-focused case volume. Practice patterns were not noted to be organism dependent. Antibiotic-impregnated shunts were utilized in the Americas and Europe over other regions but only in one third of all initial VPS or as a preventive strategy after a VPS infection has been resolved respectively. Survey results from 6 continents in VPS management revealed patterns of lower infection in high-volume centers, 3 negative cultures prior to internalization and aggressive surgical VPS infection management in high-volume institutions.

Diagnostic Biomarkers for Alzheimer's Disease Using Non-Invasive Specimens.

Studies in the field of Alzheimer’s disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage—before critical neurons are lost. Several studies have been investigating the use of cerebrospinal fluid (CSF) and blood as clinical samples for the detection of AD with a number of established core markers, such as amyloid beta (Aβ), total tau (T-tau) and phosphorylated tau (P-tau), being at the center of clinical research interest. The use of oral samples—including saliva and buccal mucosal cells—falls under one of the least-investigated areas in AD diagnosis. Such samples have great potential to provide a completely non-invasive alternative to current CSF and blood sampling procedures. The present work is a thorough review of the results and analytical approaches, including proteomics, metabolomics, spectroscopy and microbiome analyses that have been used for the study and detection of AD using salivary samples and buccal cells. With a few exceptions, most of the studies utilizing oral samples were performed in small cohorts, which in combination with the existence of contradictory results render it difficult to come to a definitive conclusion on the value of oral markers. Proteins such as Aβ, T-tau and P-tau, as well as small metabolites, were detected in saliva and have shown some potential as future AD diagnostics. Future large-cohort studies and standardization of sample preparation and (pre-)analytical factors are necessary to determine the use of these non-invasive samples as a diagnostic tool for AD.

Clinical Phenotypes in Corticobasal Syndrome with or without Amyloidosis Biomarkers.

Corticobasal syndrome (CBS) is a neuropathologically heterogeneous entity. The use of cerebrospinal fluid and amyloid biomarkers enables detection of underlying Alzheimer's disease (AD) pathology. We thus compared clinical, eye movement, and 18FDG-PET imaging characteristics in CBS in two groups of patients divided according to their amyloid biomarkers profile. Fourteen patients presenting with CBS and amyloidosis (CBS-A+) were compared with 16 CBS patients without amyloidosis (CBS-A-). The two groups showed similar motor abnormalities (parkinsonism, dystonia) and global cognitive functions. Unlike CBS-A+ patients who displayed more posterior cortical abnormalities, CBS-A- patients demonstrated more anterior cortical and brain stem dysfunctions on the basis of neuropsychological testing, study of saccade velocities and brain hypometabolism areas on 18FDG-PET. Interestingly, Dopamine Transporter SPECT imaging showed similar levels of dopaminergic degeneration in both groups. These findings confirm common and distinct brain abnormalities between the different neurodegenerative diseases that result in CBS. We demonstrate the importance of a multidisciplinary approach to improve diagnosis in vivo in particular on oculomotor examination.