Cerebrospinal Fluid Protein Levels Research Articles

Assessing the Preanalytical Variability of Plasma and Cerebrospinal Fluid Processing and Its Effects on Inflammation-Related Protein Biomarkers

Proteomics studies are important for the discovery of new biomarkers as clinical tools for diagnosis and disease monitoring. However, preanalytical variations caused by differences in sample handling protocol pose challenges for assessing biomarker reliability and comparability between studies. The purpose of this study was to examine the effects of delayed centrifuging on measured protein levels in plasma and cerebrospinal fluid (CSF). Blood from healthy individuals and patients with multiple sclerosis along with CSF from patients with suspected neurological disorders were left at room temperature for different periods (blood: 1, 24, 48, 72 h; CSF: 1 and 6 h) prior to centrifuging. Ninety-one inflammation-related proteins were analyzed using a proximity extension assay, a high-sensitivity multiplex immunoassay. Additional metabolic and neurology-related markers were also investigated in CSF. In summary, many proteins, particularly in plasma, had increased levels with longer delays in processing likely due in part to intracellular leakage. Levels of caspase 8, interleukin 8, interleukin 18, sirtuin 2, and sulfotransferase 1A1 increased 2-fold to 10-fold in plasma after 24 h at room temperature. Similarly, levels of cathepsin H, ectonucleoside triphosphate diphosphohydrolase 5, and WW domain containing E3 ubiquitin protein ligase 2 differentiated in CSF with <6 h delay in processing. However, the rate of change for many proteins was relatively consistent; therefore, we were able to characterize biomarkers for detecting sample handling variability. Our findings highlight the importance of timely and consistent sample collection and the need for increased awareness of protein susceptibility to sample handling bias. In addition, suggested biomarkers may be used in certain situations to detect and correct for preanalytical variation in future studies.

Cerebrospinal fluid culture-positive bacterial meningitis increases the risk for neurologic damage among neonates

Objective This study aimed to compare the clinical features and outcomes of neonatal bacterial meningitis (NBM) between patients with positive and negative cerebrospinal fluid (CSF) cultures and determine the risk factors for CSF culture-positive NBM. Methods We retrospectively reviewed the medical records of all patients with NBM. Perinatal clinical data, laboratory results, and cranial radiographs were obtained. Results Among the 186 neonates who met the inclusion criteria. The risk factors for positive CSF culture results were analysed using multiple logistic regression. The multivariable logistic regression analysis showed that the possible risk factors of NBM with positive CSF culture in this study were: Length of fever [OR = 1.126; 95% CI (0.999–1.268)], Neurologic symptoms [OR = 3.043; 95% CI (1.164–7.959)], Cerebrospinal fluid protein [OR = 1.001; 95% CI (1.000–1.001)]. Cases of NBM with a longer duration of fever, more neurologic symptoms, and higher levels of CSF protein were more likely to demonstrate positive results on CSF culture. Conclusion Cases of NBM with CSF culture-positive results were more likely to have severe clinical manifestations and develop more serious neurologic damage. Patients with NBM who have longer durations of fever, more neurologic symptoms, and higher levels of CSF protein were more likely to have CSF culture-positive results, who should be followed up more closely. Key Message Bacterial meningitis is clinically defined as a serious inflammation of meningitis, usually caused by a variety of bacterial infections that may leave sequelae and long-term complications and high mortality rates. Early diagnosis is often difficult, particularly when the patient has been treated with antimicrobials.

Normal cerebrospinal fluid protein and associated clinical characteristics in children with tuberculous meningitis

Background Although abnormal cerebrospinal fluid (CSF) protein can be used to predict the outcome of tuberculous meningitis (TBM) and diagnose TBM, normal CSF protein remains a concern in patients with TBM. This retrospective study aimed to assess the clinical characteristics associated with normal CSF protein, to resolve the dilemma of CSF protein in the management of childhood TBM. Methods Between January 2006 and December 2019, consecutive child patients (≤15 years old, a diagnosis of TBM, and tested for CSF protein) were included for analysis. CSF protein was tested on a chemistry analyzer using the pyrogallol red-molybdate method. Abnormal CSF protein was defined as >450 mg/L. Patient characteristics were collected from the electronic medical records. Then, characteristics associated with normal CSF protein were estimated in the study, using univariate and multivariate logistic regression analysis. Results A total of 125 children who met the criteria were enrolled during the study period. Twenty-nine patients had a normal CSF protein and 96 had an abnormal CSF protein. Multivariate analysis (Hosmer–Lemeshow goodness-of-fit test: χ2=2.486, df = 8, p = .962) revealed that vomiting (age- and sex-adjusted OR = 0.253, 95% CI: 0.091, 0.701; p = .008) and serum glucose (>5.08 mmol/L; age- and sex-adjusted OR = 0.119, 95% CI: 0.032, 0.443; p = .002) were associated with the normal CSF protein in childhood TBM. Conclusion In suspected childhood TBM, patients without vomiting or having low serum glucose are easy to present with normal CSF protein. Hence, when interpreting the level of CSF protein in children with such characteristics, a careful clinical assessment is required. KEY MESSAGES In suspected childhood tuberculous meningitis, patients without vomiting or having low serum glucose are easy to present with normal CSF protein. Hence, when interpreting the level of CSF protein in children with such characteristics, a careful clinical assessment is required.

Dissociation of axo-glial junction in anti-neurofascin 155 chronic inflammatory demyelinating polyneuropathy.

A subset of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by the presence of anti-neurofascin 155 (anti-NF155) autoantibodies. In this paper, we investigated an anti-NF155 CIDP patient via clinical, electrophysiological, and neuropathological tests. The patient was a 15-year-old Chinese boy affected by distal limb weakness and tremor for a 6-month period. The patient was positive for serum anti-NF155 antibodies, high cerebrospinal fluid protein levels and symmetric hypertrophy of lumbosacral roots in MRI. Elongation of distal and F-wave latencies and decrease of compound muscle action potentials in motor nerves were recorded. Sensory nerve action potentials were absent. He accepted sural nerve biopsy. Sural nerve biopsy demonstrated the typical pathological change of loss of transverse bands with mild detachment of terminal myelin loop from axon at the paranode. Some thin myelinated fibers and axonal degeneration were recorded. Besides, we found some myelin balloon formations with compressed axons. We suggest that antibodies against F155 might be responsible for axo-glial junction disruptions leading to the dissociation of myelin and axon. Both conduction block and axonal impairment contributed to the neuropathy in anti-NF155 CIDP.

Clinical correlation of cerebrospinal fluid total tau levels and depression as measured by PHQ9 total in a memory clinic

AbstractBackgroundTau protein levels in cerebrospinal fluid is indicative of Alzheimer's dementia. We correlated PHQ‐9 screen severity of depression to CSF tau levels in a memory clinic sample.MethodWe analyzed data from patients attending a memory clinic in the south shore of Boston from 2010 to 2019 who had a lumbar puncture to obtain CSF tau levels. We correlated depression screening data from PHQ9 scores. Univariate analyses used Spearman correlation. A multivariate regression model was created including covariates of age, sex, and race.ResultsDepression as measured by PHQ9 total was not correlated to total tau levels in CSF.ConclusionIn a memory clinic sample, CSF tau levels did not correlate to PHQ9 scores.

Novel genetic effects on amyloid and tau protein levels in cerebrospinal fluid

AbstractBackgroundAssuming measurable biological properties to be more strongly related to the underlying Alzheimer’s disease (AD) pathogenesis than the diagnostic classification, we studied the genetics of AD‐relevant protein levels in cerebrospinal fluid (CSF). Initiated by the European Alzheimer’s disease DNA biobank (EADB), we established the largest collaborative effort on CSF amyloid beta and tau, and aimed to improve the current understanding on the genetic etiology of AD, including the identification of novel genetic risk factors.MethodA collection of 10 European dementia cohorts was explored to study the genetic effects on CSF amyloid beta (n = 6529 individuals), tau (n = 6455 individuals) and phosphorylated tau (n = 5865). Most of the genetic data was generated with Illumina Global Screening Array, and imputed with TOPMed reference genome. The protein level data was log transformed and normalized. Per variant linear regressions were performed within cohorts using PLINK v2.0, followed by meta‐analysis. We corrected for population structure (principal components), gender, age and biomarker assay type (if applicable within a cohort).ResultsBesides APOE (p = 3.16 × 10−251), no other loci reached genome‐wide significance for amyloid beta protein levels. For tau protein levels, we discovered 5 loci, including the known AD loci APOE (p = 1.61 × 10−61) and HLA‐DRB1 (p = 4.67 × 10−8). We additionally confirm the GMNC locus (p = 1.23 × 10−12) that previously was associated with CSF tau by an independent consortium. Two novel loci are seen on chromosome 9 (p = 5.76 × 10−8) and chromosome 16 (p = 3.67 × 10−8). These tau findings are strengthened by the identification of these same 5 loci for phosphorylated tau which has been measured by a different protein level assay. Both novel loci have shown associations with brain ventricular volume in previous large‐scale studies performed by other consortia, such as CHARGE and ADNI.ConclusionThe novel loci identified for CSF tau protein levels suggest an overlap in genetic etiology for tau and brain ventricular volume, thereby strengthening the theory that neurodegeneration and tau pathology are highly correlated in dementia patients.

Proteogenomic analysis of cerebrospinal fluid reveals causal role of proteins from the autophagy‐lysosome pathway in Parkinson’s disease

AbstractBackgroundIntegrating genetic variants associated with protein levels (protein quantitative trait loci; pQTLs) with variants from genome‐wide association studies (GWAS) using Mendelian randomization approaches has uncovered a causal role of previously unsuspected proteins in several diseases. We have successfully applied a combination of targeted proteomic and genomic approaches to the cerebrospinal fluid (CSF) of Alzheimer Disease (AD) patients to identify multiple novel genetic associations. However, there are currently no proteogenomic studies in Parkinson’s Disease (PD).MethodsWe used the SOMAscan 1.3k Assay (∼1,305 SOMAmers) in ∼1015 samples from the ADRC‐WUSTL. SOMAscan data from the Parkinson's Progression Markers Initiative cohort and Sasayama D, et al 2017 were used as replication cohorts. After stringent QC steps were applied to SOMA data, each SOMAmer was log10 transformed and standardized to zero. We used linear additive genetic regression models adjusted for age, sex, genotyping array and the first two principal components using Plink 1.9. We used the R package MendelianRandomization to integrate our CSF pQTL variants with PD‐related SNPs from the 2019 METAPD GWAS.ResultsWe found significant cis‐pQTLs for Cathepsin B (p = 3.6 × 10−27), Alpha‐L‐iduronidase (p = 3.4 × 10−41) and Galactin‐3 (p = 2.7 × 10−41). MR found significant causal associations of PD risk with pQTLs for IDUA (b = 1.2, p = 5.0 × 10−6), CSTB (b = ‐1.4, p = 2.7 × 10−4) and Galactin‐3 (b = ‐1, p = 4.0 × 10−2). Most importantly, we found an association with progranulin (PGRN) trans‐pQTLs (p = 2.5 × 10−9). This association was replicated in the PPMI cohort (p = 1.9 × 10−9), and MR confirmed the significant causal link of PGRN (b = 4.6, p = 1.0 × 10−4) with PD. The PGRN pQTL in CSF is located in the LRRK2 gene locus. This SNP is also associated with the CSF levels of proteins from two additional PD‐associated genes CTSB (p = 1.6 × 10−3) and glycoprotein nmb (GPNMB, p = 1.5 × 10−4).ConclusionOur proteogenomic approach identified LRRK2 as a genetic modifier of three additional PD‐associated proteins in CSF. MR analyses confirmed the causal link of proteins from the autophagy‐lysosome pathway with PD. Our data provide new biological insights into how LRRK2 modifies PD risk and novel markers for screening of LRRK2 kinase activity.

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

BackgroundNeurological manifestations are common in patients with COVID-19, but little is known about pathophysiological mechanisms. In this single-center study, we describe neurological manifestations of 58 patients, regarding cerebrospinal fluid (CSF) analysis and neuroimaging findings.Methods58 COVID-19 patients with neurologic manifestations and SARS-CoV-2 RT-PCR screening on CSF analysis were included. Clinical, laboratory, and brain MRI data were retrospectively collected and analyzed.ResultsPatients were mostly men (66%) with a median age of 62 years. Encephalopathy was frequent (81%), followed by a pyramidal dysfunction (16%), seizures (10%), and headaches (5%). Protein and albumin levels in CSF were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient suggesting impaired blood‐brain barrier integrity. CSF-specific IgG oligoclonal band was found in five (11%) cases, suggesting an intrathecal synthesis of IgG, and 26 (55%) patients presented identical oligoclonal bands in serum and CSF. Four (7%) patients harbored a positive SARS-CoV-2 RT-PCR in CSF. Regarding brain MRI, 20 (38%) patients presented leptomeningeal enhancement.ConclusionsBrain MRI abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV 2 detection in CSF remained scanty.

Genetic spectrum of Charcot-Marie-Tooth disease associated with myelin protein zero gene variants in Japan.

We aimed to reveal the genetic features associated with MPZ variants in Japan. From April 2007 to August 2017, 64 patients with 23 reported MPZ variants and 21 patients with 17 novel MPZ variants were investigated retrospectively. Variation in MPZ variants and the pathogenicity of novel variants was examined according to the American College of Medical Genetics standards and guidelines. Age of onset, cranial nerve involvement, serum creatine kinase (CK), and cerebrospinal fluid (CSF) protein were also analyzed. We identified 64 CMT patients with reported MPZ variants. The common variants observed in Japan were different from those observed in other countries. We identified 11 novel pathogenic variants from 13 patients. Six novel MPZ variants in eight patients were classified as likely benign or uncertain significance. Cranial nerve involvement was confirmed in 20 patients. Of 30 patients in whom serum CK levels were evaluated, eight had elevated levels. Most of the patients had age of onset >20 years. In another subset of 30 patients, 18 had elevated CSF protein levels; four of these patients had spinal diseases and two had enlarged nerve root or cauda equina. Our results suggest genetic diversity across patients with MPZ variants.

Predictive Factors of Resistance to High-Dose Steroids Therapy in Acute Attacks of Neuromyelitis Optica Spectrum Disorder.

High-dose steroids, the first-line therapy for acute attacks in neuromyelitis optica spectrum disorder (NMOSD), were ineffective in a proportion of NMOSD attacks. This study aimed to explore possible predictors of high-dose steroid resistance. Demographics and disease characteristics of acute attacks were compared between those who responded to high-dose intravenous methylprednisolone (IVMP) and those resistant to IVMP. In total, 197 attacks in 160 patients were identified in our NMOSD registry. Compared with responders, attacks resistant to high-dose steroids tended to have a higher proportion of previous history of immunosuppressive use (25.5 vs. 15.5%, p = 0.080). Significantly higher levels of proteins in the cerebrospinal fluid (CSF) were found in non-responders than in responders [485.5 (388–656) vs. 387 (291.5–532) mg/L, p = 0.006]. More active lesions were found in the brain stem of non-responders (8 attacks in 55, 14.5%), especially in the pons (7.3%) and medulla (14.5%), as opposed to responders (7 patients in 142, 4.9%). Multivariable logistic regression showed that resistance to high-dose steroid treatment was associated with previous immunosuppressant use [odds ratio (OR), 2.31; 95% confidence interval (CI) 1.002–5.34, p = 0.049], CSF protein level above 450 mg/L (OR 3.42, 95% CI 1.72–6.82, p < 0.001), and active lesions in the brainstem (OR 3.80, 95% CI 1.17–12.32, p = 0.026). In conclusion, NMOSD patients with previous use of immunosuppressants, higher levels of CSF protein, and active lesions in the brainstem are more likely to respond poorly to high-dose IVMP alone during an acute attack.

Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy in Children: A Retrospective Single-Center Study.

BackgroundAlthough influenza primarily affects the respiratory system, it can cause severe neurological complications, especially in younger children, but knowledge about the early indicators of acute necrotizing encephalopathy (ANE) is limited. The main purpose of this article is to summarize the clinical characteristics, diagnosis, and treatment of neurological complications of influenza in children, and to identify factors associated with ANE.Material/MethodsThis was a retrospective study of children with confirmed influenza with neurological complications treated between 01/2014 and 12/2019 at Guangzhou Women and Children’s Medical Center. A receiver operating characteristics curve analysis was performed to determine the prognostic value of selected variables.ResultsSixty-three children with IAE (n=33) and ANE (n=30) were included. Compared with the IAE group, the ANE group showed higher proportions of fever and acute disturbance of consciousness, higher alanine aminotransferase, higher aspartate aminotransferase, higher creatinine kinase, higher procalcitonin, higher cerebrospinal fluid (CSF) protein, and lower CSF white blood cells (all P<0.05). The areas under the curve (AUCs) for procalcitonin and CSF proteins, used to differentiate IAE and ANE, were 0.790 and 0.736, respectively. The sensitivity and specificity of PCT >4.25 ng/ml to predict ANE were 73.3% and 100.0%, respectively. The sensitivity and specificity of CSF protein >0.48 g/L to predict ANE were 76.7% and 69.7%, respectively. Thirteen (43.3%) children with ANE and none with IAE died (P<0.0001).ConclusionsHigh levels of CSF protein and serum procalcitonin might be used as early indicators for ANE. All children admitted with neurological findings, especially during the influenza season, should be evaluated for influenza-related neurological complications.

CSF sphingomyelin: a new biomarker of demyelination in the diagnosis and management of CIDP and GBS

ObjectiveTo validate sphingomyelin (SM) dosage in the cerebrospinal fluid (CSF) of patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) as a reliably assessable biomarker.MethodsWe prospectively enrolled...

Aspergillosis infection over 20\u2009years: a case report of probable vascular invasion in central nervous system

BackgroundAspergillosis infection of central nervous system (CNS) is rare and fatal. Diagnosis of invasive aspergillosis remains difficult. Aspergillosis of CNS can be an acute, subacute, or chronic onset, and the longest course of the disease was currently reported to be 4 years. Here, we report a case with recurrent headache over 20 years.Case presentationA 54-year-old man was admitted to our neurological disease ward due to intermittent throbbing headache lasting for more than 20 years that had grown notably worse over the past week. The headache was localized to the side of his head blown by a cold wind. He also experienced nausea and vomiting when the headache became severe. The headache usually lasted for 3–4 h after he was blown by the cold wind, though he had no fever. The neurological examination was normal. Magnetic resonance imaging (MRI) of the brain was negative for parenchymal and meningeal lesions. However, the case had increased intracranial pressure (ICP), and elevated protein level in the cerebrospinal fluid (CSF). Aspergillus fumigatus was found in CSF by nanopore targeted sequencing (NTS) and in blood by enzyme-linked immunosorbent assay (ELISA). Aspergillus fumigatus-specific antibody IgG was 104.62 AU/mL, aspergillus galactomannan (GM) antigen was 3.27 μg/L, D-dimer was 3.25 mg/L and fibrinogen degradation product was 11.50 mg/L, which were markedly higher than the normal levels. The patient was prescribed by voriconazole. After the treatment of 14 days, the ICP, CSF protein level, Aspergillus fumigatus-specific antibody IgG, GM antigen, D-dimer and fibrinogen degradation product returned normal. Aspergillus was disappeared by NTS test of CSF. His headache has never occurred again after blowing by a cold wind.ConclusionsThis report reveals that aspergillosis infection of CNS can last for more than 20 years and the major symptom is only intermittent throbbing headache in an immunocompetent patient. Vascular invasion is probably the mechanism of headache in our case with CNS aspergillosis infection. Performing high-throughput gene sequencing technology in CSF is important when the pathogen is not determined for the patients with suspected CNS infection.

Cerebrospinal fluid monocyte chemoattractant protein 1 correlates with progression of Parkinson\u2019s disease

Parkinson’s disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging a correct early diagnosis. Prognostic information is needed to predict disease progression and provide appropriate counseling. Neuroinflammation plays a role in the pathology of both disorders, as shown in genetic and postmortem tissue studies. Monocyte chemoattractant protein 1 (MCP-1) and neuroleukin (NLK) are two inflammatory proteins with potential to serve as biomarkers of the neuroinflammatory process. Here, we aimed to study the biomarker potential of both MCP-1 and NLK protein levels in cerebrospinal fluid (CSF) from a longitudinal cohort study (Radboudumc, Nijmegen, The Netherlands), consisting of PD patients (n = 46), MSA patients (n = 17) and control subjects (n = 52) using ELISA. We also correlated MCP-1 and NLK levels in CSF to several parameters of disease. We showed that MCP-1 levels in CSF positively correlate with PD progression (ρ = 0.363; p = 0.017) but could not differentiate between PD, MSA, and controls. NLK levels in CSF neither differentiated between PD, MSA, and controls, nor correlated with disease progression. Our results indicate that MCP-1 levels in CSF cannot distinguish between PD, MSA, and controls but correlate with disease progression in PD patients, suggesting that neuroinflammation is associated with clinical progression in PD. The correlation with disease progression was only moderate, so MCP-1 levels in CSF should be included in a larger battery of prognostic biomarkers that also tackle different pathophysiological processes.

Diagnostic algorithm for children presenting with epilepsia partialis continua.

To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. Fifty-four children fulfilled EPC criteria. Median age at onset was 7years (range 0.6-15), with median follow-up of 4.3years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion-positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P=.02). Preceding developmental concerns (odds ratio [OR] 22, P<.001), no seizures prior to EPC (OR 22, P<.001), bilateral slowing on electroencephalogram (EEG) (OR 26, P<.001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6months (range 3-15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole-exome sequencing on blood-derived DNA should be performed. Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis.

BACE1 and Other Alzheimer's-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer's Disease Patients from Cognitively-Impaired Neurosyphilis Patients.

Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer's disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1-40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

SHUNT MALFUNCTION IN TUBERCULOUS MENINGITIS- WHETHER GRADE AND CSF PICTURE AFFECT OUTCOME

BACKGROUND Tuberculosis remains a major global problem and a public health issue of considerable magnitude. The World Health Organisation (WHO) estimates that one third of the world’s population is infected with mycobacterium tuberculosis, with the highest prevalence of tuberculosis in Asia. Shunt surgery for hydrocephalus associated with tuberculous meningitis has proven to be highly efficacious. Few studies have addressed the issue of outcome of shunt surgery and impact of CSF (Cerebrospinal fluid) picture in post tuberculous meningitis hydrocephalus shunt surgery. MATERIAL AND METHODS The study was a prospective study conducted in Department of Neurosurgery, PGIMER, Dr. RML Hospital, New Delhi. The duration of follow up was of 6 months. 70 patients were enrolled in the study. All patients who underwent ventriculo-peritoneal shunt surgery for hydrocephalus with tuberculous meningitis in Neurosurgery department at PGIMER &amp; Dr.RML hospital were included in the study. All the patients who had hydrocephalus following tuberculous meningitis were evaluated using Modified Vellore grading of TBM and hydrocephalus. All the patients who underwent ventriculo-peritoneal shunt surgery had have their CSF analysis (cytology, protein, sugar, Gram stain, ZN stain, India ink and aerobic culture) done. Outcome of the surgery were evaluated based on Glasgow outcome score (GOS), radiological parameters and complications. Statistical analysis was performed by the SPSS program for Windows, version 17.0. RESULTS The age of patients enrolled into the study varied from 2 months to 87 years with 44.3% of patients in 1-5 years age group. Patients were divided into 4 grades according to Modified Vellore Grading. Grades at the time of admission were compared with the final Glasgow outcome scale. At the time of admission 6 patients were in Grade I, 13 patients in Grade II, 45 patients in Grade III and 6 patients in Grade IV. GOS was 5 in Grade I, 4.69 +/- in Grade II, 4.50 +/- IN Grade III and 2.17+/- in Grade IV. Outcome was compared according to Cerebrospinal fluid (CSF) cell count, sugar and protein levels but none was found to be significant. Number of shunt revisions were compared to CSF cell count and sugar level but none was found to be significant. Mean FH/ID ratio before surgery was 60.89% which was reduced to 43.70% after 6 months follow up. CONCLUSION Ventriculo-peritoneal shunt surgery is a safe and effective treatment modality to treat tuberculous meningitis with hydrocephalus in all grades of patients except in Grade IV. CSF protein, sugar levels and cell count neither affect the outcome nor increase the risk of shunt malfunction

The prognostic value of demyelinating electrophysiologic findings and cerebrospinal fluid protein levels in acute inflammatory demyelinating polyneuropathy

Guillain-Barre syndrome is an acute immune-mediated polyneuropathy characterized by rapidly evolving symptoms and disability. Cerebrospinal fluid analysis and electrophysiological studies are crucial in the diagnosis of this syndrome. To evaluate the prognostic value of the type and number of demyelinating findings and cerebrospinal fluid protein levels in patients with acute inflammatory demyelinating polyneuropathy. We retrospectively analyzed electrophysiological data and cerebrospinal fluid of 67 consecutive patients with acute inflammatory demyelinating polyneuropathy from Istanbul, Turkey (2011-2019) studied ≤ 24 hours post-onset. The patients who met a higher number of demyelinating criteria had increased disability scores in the first day and first month, and higher cerebrospinal fluid protein levels were correlated with worse prognosis both on the first day and the first month. However, the disability scores did not correlate with any single specific criterion, and no significant correlation was found between the number of satisfied criteria and cerebrospinal fluid protein levels. The number of demyelinating criteria that are met and high cerebrospinal fluid protein levels at the disease onset may be valuable prognostic markers. More systematic studies conducted with serial nerve conduction studies are required to highlight the roles of the suggested criteria in clinical practice.

Adult‐onset neuronal intranuclear inclusion disease showing markedly high phosphorylated tau protein levels in cerebrospinal fluid

Geriatrics & Gerontology InternationalVolume 20, Issue 8 p. 793-795 LETTER TO THE EDITOR Adult-onset neuronal intranuclear inclusion disease showing markedly high phosphorylated tau protein levels in cerebrospinal fluid Shuntaro Serisawa, Shuntaro Serisawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorKentaro Hirao, Corresponding Author Kentaro Hirao kentaroh@tokyo-med.ac.jp Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan Correspondence Kentaro Hirao MD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Email: kentaroh@tokyo-med.ac.jpSearch for more papers by this authorTomohiko Sato, Tomohiko Sato Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYusuke Ogawa, Yusuke Ogawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHidekazu Kanetaka, Hidekazu Kanetaka Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorMutsuo Enomoto, Mutsuo Enomoto Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorSoichiro Shimizu, Soichiro Shimizu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHirofumi Sakurai, Hirofumi Sakurai Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYasuhiro Sakashita, Yasuhiro Sakashita Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorShigeo Murayama, Shigeo Murayama Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorHaruo Hanyu, Haruo Hanyu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this author Shuntaro Serisawa, Shuntaro Serisawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorKentaro Hirao, Corresponding Author Kentaro Hirao kentaroh@tokyo-med.ac.jp Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan Correspondence Kentaro Hirao MD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Email: kentaroh@tokyo-med.ac.jpSearch for more papers by this authorTomohiko Sato, Tomohiko Sato Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYusuke Ogawa, Yusuke Ogawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHidekazu Kanetaka, Hidekazu Kanetaka Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorMutsuo Enomoto, Mutsuo Enomoto Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorSoichiro Shimizu, Soichiro Shimizu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHirofumi Sakurai, Hirofumi Sakurai Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYasuhiro Sakashita, Yasuhiro Sakashita Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorShigeo Murayama, Shigeo Murayama Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorHaruo Hanyu, Haruo Hanyu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this author First published: 02 August 2020 https://doi.org/10.1111/ggi.13964Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue8August 2020Pages 793-795 RelatedInformation

Defining and predicting transdiagnostic categories of neurodegenerative disease.

The prevalence of concomitant proteinopathies and heterogeneous clinical symptoms in neurodegenerative diseases hinders the identification of individuals who might be candidates for a particular intervention. Here, by applying an unsupervised clustering algorithm to post-mortem histopathological data from 895 patients with degeneration in the central nervous system, we show that six non-overlapping disease clusters can simultaneously account for tau neurofibrillary tangles, α-synuclein inclusions, neuritic plaques, inclusions of the transcriptional repressor TDP-43, angiopathy, neuron loss and gliosis. We also show that membership to the six transdiagnostic disease clusters, which explains more variance in cognitive phenotypes than can be explained by individual diagnoses, can be accurately predicted from scores of the Mini-Mental Status Exam, protein levels in cerebrospinal fluid, and genotype at the APOE and MAPT loci, via cross-validated multiple logistic regression. This combination of unsupervised and supervised data-driven tools provides a framework that could be used to identify latent disease subtypes in other areas of medicine.