Cerebral Spinal Fluid Testing Research Articles

Alzheimer's Disease: Why is Early Detection Important?

Early detection of Alzheimer’s disease (AD) can bring benefits to the patient by giving them time to process and prepare for the development of the disease in the future. To detect the early stages of AD, patients can take brain imaging tests, auto-encoders, genetic tests, mental state tests, and cerebral spinal fluid tests. Through these tests, patients can determine their amyloid build-up levels, tau build-up levels, possible chromosomes related to AD, and mental health illnesses related to AD.

A case of EBV encephalomyelitis with positive anti-GFAP-IgG antibody with recurrent fever and dysuresia as the main symptoms: Case report and retrospective analysis

Due to neuronal destruction caused by Epstein-Barr virus (EBV) infection, exposure to neuronal surface antigens may lead to an imbalance in immune tolerance, which in turn triggers an autoimmune response. In addition, due to the involvement of nonspecific B-cell activation or molecular mimicry, EBV and Glial Fibrillary Acidic Protein (GFAP) receptors may have common epitopes. Viral infection triggers activation of B-cell and cross-reaction with viral antibodies, resulting in autoimmune encephalomyelitis. The clinical presentation may be complex or even atypical. A small number of patients may develop autoimmune reactions. Most patients with EBV encephalomyelitis have a good prognosis, with the disease generally having a short course, few complications, and a good prognosis. In most patients, after treatment, their neurological function basically recovers within a few weeks or months. The patient had fever and headache. His 3 tests for cerebral spinal fluid (CSF) are consistent with the features of viral encephalomyelitis. Pathogenic examination of CSF confirmed EBV, and imaging suggested brain and spinal cord involvement. After antiviral treatment, the patient's symptoms relieved. The diagnosis of EBV encephalomyelitis was considered. However, the patient's temperature continued to increase. He was transferred to a superior hospital and was given GFAP-Ab in CSF, which was strongly positive. The patient was given immunoglobulin and antiviral therapy. This supports the diagnosis of GFAP-IgG antibody positive with EBV encephalomyelitis. After treatment with antiviral drugs and immunoglobulins, the patient's symptoms improved and he was able to function. EBV encephalomyelitis is a rare clinical disease. Therefore, more attention should be paid to the early diagnosis and treatment of similar patients to avoid misdiagnosis. CSF tests, genetic tests, and imaging tests can confirm the diagnosis.

Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist.

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis.

1250 Agrypnia Excitata in a Patient with Paraneoplastic Autoimmune Encephalitis

Abstract Introduction Agrypnia Excitata (AE) is a syndrome characterized by loss of sleep with permanent motor and autonomic hyper activation. This case describes this peculiar syndrome in a patient with paraneoplastic autoimmune encephalitis. Report of Case DG is a 35 yr old male with a history of anti-Ma2 limbic encephalitis secondary to cystic teratoma of the left testis diagnosed 6 months prior to presenting in Sleep Clinic. His parents described significant sleep disturbances including short sleep and wake periods throughout the day and night with no apparent pattern, acting out dreams, motor activity during sleep including pulling at his clothes or using his hands to manipulate invisible objects. Additionally they described low-grade fevers, and severe hyperphagia. Polysomnogram showed absence of slow-wave sleep and what appeared to be an admixture of stage 1 non-rapid eye movement (NREM) with rapid-eye movement (REM) sleep. Multiple sleep-latency testing (MSLT) demonstrated a mean sleep latency of 5.2 minutes and four sleep-onset REM periods (SOREMPs). Magnetic resonance imaging of the brain revealed persistent inflammation of the mesial temporal lobes and hippocampal region. Cerebral spinal fluid testing showed persistent anti-Ma2 antibodies. Based on this clinical presentation we made a diagnosis of Agrypnia Excitata. Conclusion Agrypnia Excitata is a syndrome characterized by loss of the normal sleep-wake rhythm. Sleep consists of the disappearance of spindle-delta activities, and persistent stage 1 NREM sleep mixed with recurrent episodes of REM sleep. The second hallmark of AE is persistent motor and autonomic hyperactivity observed during wake and sleep. AE has been described in three distinct clinical syndromes: Morvan Syndrome (autoimmune encephalitis), Fatal Familial Insomnia, and Delirium tremens. The pathogenesis of AE consists of intra-limbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. In autoimmune encephalitis, antibodies that act on voltage-gated potassium channels within the limbic system have been implicated in the pathophysiology.

Pre-operative biomarkers and imaging tests as predictors of post-operative delirium in non-cardiac surgical patients: a systematic review

BackgroundPost-operative delirium (POD) is a common post-operative complication in elderly individuals and imposes a significant health and financial burden. Identifying predictive biomarkers may help understand the pathophysiology of POD. Our objective is to summarize the evidence of pre-operative biomarkers and imaging tests to predict POD in patients undergoing non-cardiac surgery.MethodsA systematic search of English language articles in MEDLINE, EMBASE, Cochrane Database, PsychINFO, PubMed and ClinicalTrials. Gov up to January 2018 was performed. Studies that used biomarkers or imaging tests to predict POD and a validated POD assessment tool were included. Animal studies, paediatric, cardiac and intracranial surgery were excluded. Risk of bias was assessed using the Quality In Prognosis Study tool.ResultsThirty-four prospective cohort studies involving 4424 patients were included. Nineteen studies described serum tests [Interleukin-6, Insulin-like Growth Factor 1, C-Reactive Protein (CRP), cholinesterases, apolipoprotein-E genotype, leptin, hypovitaminosis, hypoalbuminaemia, gamma-amino butyric acid], 10 described cerebral-spinal fluid tests (monoamine precursor, melatonin, acute phase proteins, S100B and neurofibrillary tangles), and 5 described imaging tests. Two studies had high risk of bias due to unclear outcome measurement and study participation. CRP was significantly associated with POD in 5 studies. Other biomarkers were either examined by only a single study or two or more studies with conflicting results.ConclusionCRP is the most promising biomarker associated with POD. However, we are still in the early stages in identifying biomarkers and imaging tests that may further understanding of the pathophysiology of POD.

Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid Analysis.

Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies. We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif. We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91). Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity. NCT01802385.

Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings

Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD. To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing. This case-control study included 32 participants recruited from the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, Missouri. Results of extensive neuropsychometric testing determined that all participants were cognitively normal. Participants underwent positron emission tomography and/or cerebral spinal fluid testing to determine biomarker status. Individuals with prior ophthalmic disease, media opacity, diabetes, or uncontrolled hypertension were excluded. Data were collected from July 1, 2016, through September 30, 2017, and analyzed from July 30, 2016, through December 31, 2017. Automated measurements of retinal nerve fiber layer thickness, ganglion cell layer thickness, inner and outer foveal thickness, vascular density, macular volume, and foveal avascular zone were collected using an OCTA system from both eyes of all participants. Separate model III analyses of covariance were used to analyze individual data outcome. Fifty-eight eyes from 30 participants (53% female; mean [SD] age, 74.5 [5.6] years; age range, 62-92 years) were included in the analysis. One participant was African American and 29 were white. Fourteen participants had biomarkers positive for AD and thus a diagnosis of preclinical AD (mean [SD] age, 73.5 [4.7] years); 16 without biomarkers served as a control group (mean [SD] age, 75.4 [6.6] years). The foveal avascular zone was increased in the biomarker-positive group compared with controls (mean [SD], 0.364 [0.095] vs 0.275 [0.060] mm2; P = .002). Mean (SD) inner foveal thickness was decreased in the biomarker-positive group (66.0 [9.9] vs 75.4 [10.6] μm; P = .03). This study suggests that cognitively healthy individuals with preclinical AD have retinal microvascular abnormalities in addition to architectural alterations and that these changes occur at earlier stages of AD than has previously been demonstrated. Longitudinal studies in larger cohorts are needed to determine whether this finding has value in identifying preclinical AD.

Idiopathic Central Nervous System Inflammatory Disease in the Setting of HLA-B27 Uveitis

ABSTRACTPurpose: The purpose of the article is to describe a novel case of idiopathic central nervous system inflammatory disease with bilateral human leukocyte antigen (HLA)-B27-positive anterior uveitis.Methods/Results: A 15-year-old African American boy with bilateral HLA-B27-positive anterior uveitis controlled with topical and oral steroids for 8 months acutely developed headaches, left eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory and infectious workup were negative. He received intravenous methylprednisolone without initial symptomatic improvement; repeat magnetic resonance imaging (MRI) showed reduced lesion burden. Oral steroids were continued; his symptoms resolved in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion resolution.Conclusions: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27 positivity may represent a novel association with CLIPPERS.

Extreme delta brush guides to the diagnosis of anti-NMDAR encephalitis

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a treatable but often misdiagnosed autoimmune encephalitis. Diagnosis depends on NMDAR antibody testing, which may not be readily available. Alternatively, the electroencephalogram (EEG) extreme delta brush pattern may provide a valuable immediate indicator for the diagnosis of anti-NMDAR encephalitis. A 32-year-old female (case 1) presented with fever, headache, behavioral changes, confusion, intractable seizures, central hypoventilation, dysautonomia, facial and limb dyskinesias, and comorbid ovarian teratoma. Cerebral spinal fluid (CSF) testing revealed mild lymphocytic pleocytosis while brain MRI results were normal. A 45-year-old male (case 2) presented with major behavioral changes and rare seizures. Results of routine CSF testing and brain MRI scanning were unremarkable. In both cases, EEG initially revealed the extreme delta brush (EDB) pattern of beta bursting on the peaks and/or the troughs of delta waves, which led to subsequent NMDAR antibody testing and the confirmative diagnosis. Thus, EDB may be a readily accessible sign for suspected anti-NMDAR encephalitis.

Peripheral facial palsy as an initial symptom of Lyme neuroborreliosis in an Austrian endemic area.

The objective of this study was to analyze the percentage as well as clinical and laboratory characteristics of Lyme neuroborreliosis (LNB) in patients admitted with peripheral facial palsy. Additionally, we looked for diagnostic criteria to distinguish Bell's palsy from facial palsy due to LNB. Data collection was done retrospectively from 2007 until 2012. We identified 278 consecutive patients, who were admitted to the department of Neurology due to peripheral facial palsy. Patients were routinely investigated for LNB including clinical neurological examination and cerebral spinal fluid (CSF) analysis. Demographic and clinical data were analyzed according to a standardized protocol. In 19 (male (m)=14/female (f)=5) out of 278 patients (7%), a diagnosis of LNB was established. There were 8 patients (3%) identified with varicella zoster (VZV) (m=7/f=1) and 13 patients (5%) with facial palsy due to diabetic mononeuropathy (m=5/f=8). A total of 207 patients (75%) were diagnosed as Bell's palsy (m=110/f=97). Compared with CSF of patients with facial palsy due to VZV and diabetic mononeuropathy, patients with LNB showed higher cell count, protein and lactate levels, whereas patients with facial palsy due to diabetic mononeuropathy showed higher glucose level. With respect to seasonal clustering, an accumulation of 74% of the LNB cases was detected from June to October, whereas in the rest of the year there were only 26% of the LNB cases. Patients with Bell's palsy are more evenly distributed over the year. Regarding neurological signs and symptoms, radicular symptoms were only reported in the LNB group. Despite radicular symptoms for LNB, no specific signs or symptoms were found for facial palsy due to VZV, Bell's palsy, or diabetic mononeuropathy. According to the results of our study, we recommend CSF testing in any case for patients with facial palsy in an endemic area from June to October especially if additional radicular symptoms are present. To establish recommendations for a diagnostic workup in patients with facial palsy in areas endemic for Borrelia, the seasonal clustering of LNB as well as specific clinical features should also be confirmed in a future prospective trial.

Simultaneous detection of multiple designer drugs in serum, urine, and CSF in a patient with prolonged psychosis

This case report is considered exempt from University of California-San Diego Investigational Review Board.Introduction. There is a limited published experience detailing detection and toxicity of multiple novel psychoactive substances. We report a case of a patient with prolonged psychosis who had JWH-072, cannabicyclohexanol, 3’,4’-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and methylenedioxyamphetamine (MDA) identified in multiple biological samples. Case details. An 18-year-old man presented to the emergency department (ED) with acute onset psychosis after allegedly smoking “spice.” Due to agitation and psychosis refractory to multiple medications, a lumbar puncture was performed and he was admitted. All blood, urine, and CSF (cerebral spinal fluid) testing was normal. He remained psychotic for almost 1 week. MDPPP, JWH-072 and MDA were detected in initial blood, urine, and CSF samples. Cannabicyclohexanol was detected only in his serum. Discussion and conclusion. JWH-072 is a cannabinoid-2 receptor (CB-2) agonist which has not been reported previously in the literature. Its clinical effects are unknown. Cannabicyclohexanol is a known component of “spice” products and has been associated with agitation and psychosis. MDPPP and MDA are designer phenylethylamines likely to cause agitation and sympathomimetic symptoms. Simultaneous detection of novel psychoactive substances in multiple biological fluids has not been previously reported. This case suggests that the interaction of these particular substances may be associated with prolonged psychosis.