Abnormal Cerebrospinal Fluid Research Articles

NCMP-02. BIOPSY OUTCOMES OF PATIENTS WITH SUSPECTED LEPTOMENINGEAL CARCINOMATOSIS: A RETROSPECTIVE CASE SERIES

Abstract BACKGROUND Leptomeningeal carcinomatosis is commonly considered when patients present with meningeal enhancement on magnetic resonance imaging (MRI), even without a known primary malignancy. In practice, some clinicians advocate for early meningeal biopsy to expedite diagnosis, citing lack of specificity of other testing, such as cerebrospinal fluid (CSF) analysis. METHODS We identified a cohort of patients with meningeal enhancement that underwent biopsy for diagnostic purposes between 2010 and 2022. Presenting symptoms, physical exam, enhancement pattern on MRI, other imaging findings, CSF parameters, other laboratory results, final diagnosis, and recommended treatment were recorded when available. RESULTS Out of nearly 100 cases included, the majority were autoimmune or inflammatory in etiology. Only 13 patients were diagnosed with malignancy-related enhancement, and 10 of these cases were felt to be true carcinomatosis. Nine out of the 13 patients were diagnosed with lymphoma. Four of these lymphomas were diagnosed on systemic biopsy, with meningeal biopsies negative for malignant cells. The other malignancies included systemic adenocarcinoma, oligodendroglioma, and a rare hematologic cancer. Nearly all 13 patients had abnormal CSF parameters, notably pleocytosis, but none had malignant cells in the fluid. Most frequent presenting symptoms were encephalopathy, vision changes, and strength/sensory changes. MRI often showed cranial nerve or general cerebral and cerebellar involvement, and physical exam often showed cranial nerve, strength, and sensory deficits. All patients proceeded with chemotherapy after diagnosis. CONCLUSIONS When leptomeningeal carcinomatosis is considered based on MRI enhancement, the clinical approach should continue to revolve around indirect testing such as CSF analysis, serum studies, and other imaging techniques to consider alternative biopsy sites before pursuing direct sampling with meningeal biopsy. With this approach, many patients with suspected carcinomatosis can avoid undergoing meningeal biopsy and decrease the chance of treatment delay.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients

ABSTRACT Background Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. Methods Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People’s Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. Results Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. Conclusion mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

Clinical Features and Therapeutic Evaluation of Central Nervous System Involvement in Pediatric Anaplastic Large Cell Lymphoma

Objective：To analyze the clinical features of central nervous system involvement (CNS3) in pediatric anaplastic large cell lymphoma (ALCL) and evaluate the efficacy of CNCL-ALCL-2017 protocol for the treatment of CNS3. Methods：The clinical data of 215 pediatric ALCL patients ≤18 years old enrolled in the Chinese Children's Cancer Group (CNCL) between April 2017 and March 2023 were collected sequentially. All enrolled patients staging and CNS layering were according to the IPNHLSS staging system and treated with CNCL-ALCL-2017 protocol (modified BFM-ALCL99 protocol). The clinical features at diagnosis and treatment outcomes of CNS3 patients were analyzed. All patients were followed up until June 30, 2023. Data were collected using a unified information platform. Associations between patient characteristics were analyzed with Chi-squared or Fisher's exact tests. Eventfree survival (EFS) and overall survival (OS) curves were estimated according to the KaplanMeier method and compared by Logrank test. Furthermore, statistical analysis was performed using SPSS 22.0 software. P<0.05 was considered statistically significant. Results: Among the 215 ALCL pediatric patients, 17 (7.9%) had CNS3, including 13 males and 4 females with median age of 8.0 (range 1.0-14.0) years. In this patients, brain parenchyma and spinal cord involvement were found in 58.8% (10/17) patients on imaging, with space-occupying lesions in 7 cases and abnormal signals on MRI in 4 cases. Concurrent space-occupying lesions and abnormal signals on MRI was detected in 1 case. Cerebrospinal fluid (CSF) positivity was detected in 35.3% (6/17) patients, including 2 cases with positive ALK gene and 5 cases with positive flow cytometry, with 1 case positive for both. Cranial nerve deficits such as facial nerve palsy, visual or hearing impairment were observed in 23.5% (4/17) patients. Concurrent CSF, imaging and cranial nerve abnormalities were present in 5.9% (1/17), while two of this were present in 29.4% (5/17). Isolated CSF positivity without other abnormalities was detected in 23.5% (4/17). Pathological subtypes included common type (76.5%, 13/17), histiocyte-rich variant (5.9%, 1/17), small cell variant (5.9%, 1/17), others (11.8%, 2/17). Immunohistochemistry showed ALK + in 94.1% (16/17) and CD3 + in 76.5% (13/17). Concurrent ALK gene positivity in both peripheral blood and bone marrow was detected in 64.7% (11/17), with 58.8% (10/17) positive in both samples. The median follow-up of all patients was 35.4 months (range 0.5-74.9). All CNS3 patients had stage IV disease and were treated with regimen D (with 5 g/m 2 methotrexate). The 3-year OS was 94.3%, 98.2% and 93.3% for CNS1 (144, 67.0%), CNS2 (54, 25.1%) and CNS3 (17, 7.9%) patients, respectively; the 3-year EFS was 85.6%, 90.3% and 86.7%, respectively. No significant differences were found among the three groups. The 3-year OS and EFS for the whole cohort were 95.1% and 84.7%, respectively, also with no significant differences from the CNS3 group. Of the CNS3 patients, 1 was lost to follow-up after the first course, 1 died during treatment, and the interim CR rate was 75.0% (12/16). CSF conversion was achieved in 3/6 (50%) CSF-positive patients. 6.25% (1/16) patient had CSF ALK gene re-positivity during maintenance and persistent positivity despite additional ALK inhibitor alectinib and intrathecal therapy. In the CNS1 group, 2 cases were lost to follow-up and 4 cases died. The relapse rate was 11.4% (16/140), and the rate of central nervous system relapse was 2.1% (3/140). Additionally, the rate of CNS1 relapse was slightly higher but not statistically significantly different for CNS2. Conclusions: CNS involvement is relatively rare in pediatric ALCL. Detection rate of CNS3 can be improved by CSF flow cytometry and gene screening. The prognosis of CNS3 was significantly improved with CNCL-ALCL-2017 protocol, which may be related to the increased dose of methotrexate in the protocol. The short follow-up time and the small number of cases in this group may affect the results. Furthermore, CNS relapse rate of CNS2 was not markedly higher compared to CNS1. Keywords: Anaplastic large cell lymphoma; Pediatric; Central nervous system; Clinical features; Prognosis

Diagnostic and Prognostic Value of Circulating Cell-Free DNA in Cerebrospinal Fluid and Plasma in Newly Diagnosed Diffuse Large B Cell Lymphoma

Background:Diffuse large B cell lymphoma (DLBCL) is a clinically and molecularly heterogeneous non-Hodgkin lymphoma. The clinical risk assessment for central nervous system (CNS) recurrence is still challenging in DLBCL due to the limited conventional biomarkers and techniques available. Circulating cell-free DNA (cfDNA), which reflects comprehensive tumor genetic profiles, has emerged as a potential novel strategy in the era of precision medicine. However, the clinical value of cfDNA detected in different samples in newly diagnosed DLBCL in China remains elusive. This study aims to explore the diagnostic and prognostic value of cfDNA detection in cerebrospinal fluid (CSF) and plasma in DLBCL. Methods:Next-generation sequencing (NGS) was performed on cfDNA derived from CSF, plasma, encompassing single nucleotide variants (SNV), insertion/deletions, copy number variants (CNV), IG related fusions, and clonotypic immunoglobulin gene rearrangements，alongside systemic tumor tissues in newly diagnosed DLBCL patients. Results:We recruited 30 patients, among whom CSF cfDNA was detected in 19 patients, with 6 (31.6%) being positive for SNV only. The positive rate of CSF cfDNA increased to 36.8% when considering both SNV, IG related fusion, and clonotypic immunoglobulin gene rearrangement. Notably, cfDNA was detected in 100% of CSF samples from 3 patients with known CNS involvement, and in 4 patients without known CNS involvement based on absent evidence of abnormal CSF cytology, flow cytometry, or radiography. The positive rates of SNV, IG related fusion, and clonotypic immunoglobulin gene rearrangement in CSF were 80%, 40%, and 40%, respectively, relatively confirmed by available paired tumor tissues or bone marrow samples. CfDNA was detected in 100% of plasma samples. When accounting for both SNV, IG related fusion, and clonotypic immunoglobulin gene rearrangement, the positive rate increased to 76.7% from 73.3%, which was much higher than paired peripheral blood genomic DNA (20%). The cfDNA detected in plasma exhibited high concordance rates with matched systemic tumor tissues or bone marrow samples, with concordance rates of 100%, 76.9%, and 76.5% for SNV, IG related fusion, and clonotypic immunoglobulin gene rearrangement, respectively. Interestingly, cfDNA was detected in plasma samples of 2 patients while tumor tissues' genomic DNA was negative. In total, 24 gene alterations were identified in CSF, 172 in plasma, and 160 in tumor tissue or bone marrow. Commonly mutated genes in plasma and CSF cfDNA included PIM1 (36.7% vs. 14.2%), MYD88 (33.3% vs. 28.6%), TET2 (30% vs. 28.6%), and CD79B (26.7% vs. 28.6%). The most common types of immunoglobulin gene rearrangement were IGK in different samples, and the common IG related fusions were IGH:: BCL6, IGH:: MYC, and IGH:: BCL2. Conclusion:Our study suggests that plasma cfDNA exhibits a high concordance rate with tumor tissues and can aid in the precise diagnosis and measurable residual disease monitoring. CSF cfDNA is more sensitive than conventional methods for diagnosing CNS invasion and could serve as a more accurate biomarker for predicting the risk of CNS recurrence among patients with newly diagnosed DLBCL, helping to select patients who may require enhanced CNS prophylaxis. Moreover, synchronous detection of SNV, CNV, IG related fusion, and clonotypic immunoglobulin gene rearrangement could be helpful in improving the positive rate of cfDNA.

CSF, Blood, and MRI Biomarkers in Skogholt's Disease-A Rare Neurodegenerative Disease in a Norwegian Kindred.

Skogholt's disease is a rare neurological disorder that is only observed in a small Norwegian kindred. It typically manifests in adulthood with uncharacteristic neurological symptoms from both the peripheral and central nervous systems. The etiology of the observed cerebral white matter lesions and peripheral myelin pathology is unclear. Increased cerebrospinal fluid (CSF) concentrations of protein have been confirmed, and recently, very high concentrations of CSF total and phosphorylated tau have been detected in Skogholt patients. The symptoms and observed biomarker changes in Skogholt's disease are largely nonspecific, and further studies are necessary to elucidate the disease mechanisms. Here, we report the results of neurochemical analyses of plasma and CSF, as well as results from the morphometric segmentation of cerebral magnetic resonance imaging. We analyzed the biomarkers Aβ1--42, Aβ1-40, Aβx-38, Aβx-40, Aβx-42, total and phosphorylated tau, glial fibrillary acidic protein, neurofilament light chain, platelet-derived growth factor receptor beta, and beta-trace protein. All analyzed CSF biomarkers, except neurofilament light chain and Aβ1/x-42, were increased several-fold. In blood, none of these biomarkers were significantly different between the Skogholt and control groups. MRI volumetric segmentation revealed decreases in the ventricular, white matter, and choroid plexus volumes in the Skogholt group, with an accompanying increase in white matter lesions. The cortical thickness and subcortical gray matter volumes were increased in the Skogholt group. Pathophysiological changes resulting from choroidal dysfunction and/or abnormal CSF turnover, which may cause the increases in CSF protein and brain biomarker levels, are discussed.

A comparison between neurological clinical signs, cerebrospinal fluid analysis, cross-sectional CNS imaging, and infectious disease testing in 168 dogs with infectious or immune-mediated meningoencephalomyelitis from Brazil.

This retrospective study evaluated canine patients with presumptively diagnosed meningoencephalomyelitis (ME) based on neurological clinical signs, cerebrospinal fluid (CSF) analysis, cross-sectional imaging, and infectious disease testing with a limited neurological-focused polymerase chain reaction (PCR) panel performed on blood and CSF. The first goal was to determine the proportion of dogs where the condition was caused by an infectious agent versus a probable immune-mediated etiology (i.e., meningoencephalomyelitis of unknown origin; MUO) in our geographic region. The secondary goals of this study were to examine and define associations between abnormal CSF test results and cross-sectional neuroimaging findings, in addition to defining the age and most common neurological clinical signs in each group of ME. A total of 168 dogs matched the inclusion criteria with magnetic resonance imaging (MRI) performed in 130 dogs and computed tomography (CT) performed in 38 dogs. Presumptive MUO was observed in 152/168 (90.5%) of dogs and infectious ME was identified in 16/168 (9.5%) of dogs (p < 0.0001). Canine distemper virus (CDV) was the most common cause of infectious ME in 10/16 dogs (62.5%). Of the total cases with a positive infectious disease result, 3/16 (18.7%) had normal CSF results and 13/16 (81.3%) had abnormal CSF results (p = 0.0078). MRI and CT abnormalities in the brain were detected in 74 and 39% of dogs with inflammatory CSF, respectively. MRI and CT abnormalities in the spinal cord were detected in 90 and 57% of dogs with inflammatory CSF results, respectively. Age was not significantly different between infectious ME and presumptive MUO groups (p = 0.15). Seizures were the most common clinical sign reported for both MUO (36.8% of cases) and infectious ME (31.2% of cases). In conclusion, presumptive MUO is significantly more common than infectious ME in this population of dogs. Furthermore, although normal CSF results were uncommon in dogs with infectious ME, this finding occurred in several patients (3/16), suggesting that infectious disease testing should be considered even in the face of normal CSF results. Finally, MRI was more sensitive than CT in the detection of abnormalities when dogs with ME had inflammatory CSF results but was not 100% sensitive, suggesting CSF analysis should be performed to rule out inflammation even when no abnormalities are detected on MRI or CT.

Predictors of respiratory failure in Guillain-Barré syndrome: a 22 year cohort study from a single Italian centre.

The study aimed to identify predictors of respiratory failure leading to mechanical ventilation (MV) and tracheostomy in Guillain-Barré syndrome (GBS). Two hundred and thirty adult cases admitted to the Neurology Unit of Modena, Italy, between January 2000 and December 2021 were studied. A cut-off of MV starting within 8 weeks from onset of weakness was used. Univariable, multivariable logistic and Cox regression analyses were used to determine which pre-specified clinical and diagnostic characteristics were capable of predicting MV and tracheostomy, due to weaning failure. The model was internally validated within the full cohort. The Erasmus GBS Respiratory Insufficiency Score was retrospectively applied. One hundred and seventy-six cases (76.5%) were classified as classical sensorimotor GBS and 54 (23.4%) as variants. Thirty-two patients (13.9%) needed MV: 84.3% required respiratory support within 7 days. Independent predictors of respiratory failure and MV were older age, facial, bulbar, neck flexor weakness, dysautonomia, axonal electrophysiological subtype, cardiovascular comorbidities and higher disability score at entry. There was no association with abnormal spinal fluid parameters nor with positive serology for recent infections. Twenty-two patients (68.7%) were ventilated for more than 7 days; 4.7% died within 8 weeks. The patients who required MV were treated more often with plasma exchange. Independent predictors of tracheostomy due to weaning trial failure were facial, bulbar, neck flexor weakness, autonomic dysfunction, associated cardiovascular morbidities and axonal electrophysiological subtype on nerve conduction study. Our study indicates distinct predictors of MV and tracheostomy in GBS patients.

Preclinical Brain Network Abnormalities in Patients with Subjective Cognitive Decline.

Alzheimer's disease (AD) is the most common form of dementia worldwide. Currently there are no disease modifying treatments available. Detecting subjects with increased risk to develop dementia is essential for future clinical trials. Subjective cognitive decline (SCD) is a condition defining individuals who perceive a decrease in their own cognitive functioning in the absence of any detectable deficit on neuropsychological testing. SCD individuals show AD-related biomarkers abnormalities in cerebrospinal fluid. The aim of the present study was to assess brain functional connectivity (FC) changes in SCD individuals. 23 SCD and 33 healthy subjects (HS) underwent an extensive neuropsychological assessment and 3T-MRI scanning including a T1-w volume and resting-state fMRI (RS-fMRI) to assess brain atrophy and brain FC. No between-group differences in grey matter volumes were detected. SCD subjects compared to HS showed both increased and decreased FC in the executive and parietal networks. Associations between cognitive measures, mainly assessing working memory, and FC within brain networks were found both in SCD and HS separately. SCD individuals showed FC abnormalities in networks involving fronto-parietal areas that may account for their lower visuo-spatial working memory performances. Dysfunctions in executive-frontal networks may be responsible for the cognitive decline subjectively experienced by SCD individuals despite the normal scores observed by formal neuropsychological assessment. The present study contributes to consider SCD individuals in an early AD stage with an increased risk of developing the disease in the long term.

Single-level ossified ligamentum flavum causing a holocord syrinx: illustrative case.

Syringomyelia is a neurological disorder that is caused by abnormal cerebrospinal fluid flow or circulation. It is an incidental finding in most cases, predominantly presenting with sensory symptoms of insensitivity to pain and temperature. Spinal ossified ligamentum flavum (OLF) leading to syringomyelia is one of the rare causes. The authors report an unusual case of syringomyelia due to a thoracic OLF. A 54-year-old female presented with backache, difficulty walking, spasticity in the bilateral lower limbs, tingling sensation in the bilateral lower limbs, and paraparesis for 5 years. Her radiological investigations were suggestive of an OLF causing a syrinx. She underwent laminectomy, and her syrinx resolved on subsequent follow-up. A syrinx due to a single-level OLF is rare, and this uncommon cause should be kept in mind while formulating treatment plans.

A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India.

Autoimmune encephalitis (AIE) is a group of rare, increasingly recognized, potentially reversible, noninfectious causes of unexplained encephalitis. It affects any age-group and has a plethora of clinical presentations, the most common being the neuropsychiatric manifestation. The diagnosis of this entity at the right time and proper treatment with immunotherapy can save many lives. In this study, we describe the demographic profile, clinical spectrum, diagnosis, and treatment of 42 patients with features of AIE. This is a prospective study where 42 cases were selected from a tertiary care center in Northwestern India. Patients with suspected AIE underwent detailed clinical assessment, routine blood tests, magnetic resonance imaging (MRI) brain, electroencephalography (EEG), cerebrospinal fluid (CSF) study, and autoimmune profile in blood and CSF. Screening for malignancy was done in all patients with computer tomography (CT) thorax and abdomen and tumor markers. Among 42 patients, males, and females were almost equally affected. The mean age of onset was 31 years. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) Encephalitis was the commonest of all AIE (57%) followed by anti-leucine-rich glioma inactivated-1 (anti-LGI-1) related AIE (11.9%), anti-contactin-associated protein 2 (anti-CASPR2) related AIE (4.7%), and steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) related to antithyroid peroxidase (anti-TPO) antibody (2.3%). Neuropsychiatric manifestation is the commonest. The seizure was noted in around 72% of patients, the commonest in the anti-NMDAR group. Faciobrachial dystonic seizure (FBDS) was noted in all five anti-LG1-1 encephalitis patients. CSF abnormalities were seen in 33.3% of patients in the form of pleocytosis or raised protein, or both. MRI abnormality was seen in 52% of patients. EEG was abnormal in 10% of patients, and delta brush was noted in three anti-NMDAR patients. All patients received immunotherapy in the form of intravenous immunoglobulin (IVIg) or pulse IV methylprednisolone (IVMPS), or both. Two patients nonresponsive to IVIg and IVMPS received rituximab. Almost all patients responded to immunotherapy. Autoimmune encephalitis (AIE), a potentially treatable immune-responsive entity, is a common neurological problem and may be an answer to a large number of cases having unexplained encephalitis. Good clinical acumen and knowledge are required for early diagnosis and treatment of this potentially reversible disorder. How to cite this article: Sharma B, Paul M, Bagaria AK. A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India. J Assoc Physicians India 2023;71(9):39-44.

Ependymal cyst in the caudal cranial fossa of a young Belgian Malinois dog with abnormal cerebrospinal fluid findings

Abstract Fluid-filled cavities within the brain are well-recognized in human and veterinary medicine. Congenital or acquired brain cystic lesions could be isolated or associated with other diseases. Clinical signs related to cysts depend on their size and the mass effect they exert on surrounding neuroanatomical structures. We present a case of a 5-month-old Belgian Malinois dog with cervical pain and right head tilt. The dog had a normal haematochemical profile and negative infectious disease tests. A contrast enhancement Computed Tomography scan revealed the presence of a thin-walled cystic lesion in the caudal cranial fossa at the level of the right pontine-cerebellar junction. A cerebrospinal fluid tap was performed by lumbar puncture, revealing a monocytic pleocytosis. After initial improvement following corticosteroid and antibiotic therapy, clinical signs worsened, and the dog underwent a second clinical evaluation and magnetic resonance imaging examination. After euthanasia a complete postmortem examination was performed. Histological and immunohistochemical findings were suggestive of an ependymal cyst.

Evolving etiologies, comorbidities, survival, and costs of care in adult encephalitis.

Encephalitis is a central nervous system disorder, often caused by infectious agents or aberrant immune responses. We investigated causes, comorbidities, costs, and outcomes of encephalitis in a population-based cohort. ICD-10 codes corresponding to encephalitis were used to identify health services records for all adults from 2004 to 2019. Data were cross-validated for identified diagnoses based on laboratory confirmation using univariate and multivariate statistical analyses. We identified persons with a diagnosis of encephalitis and abnormal cerebrospinal fluid (CSF) results (n = 581) in whom viral genome was detected (n = 315) in a population of 3.2 million adults from 2004 to 2019. Viral genome-positive CSF samples included HSV-1 (n = 133), VZV (n = 116), HSV-2 (n = 34), enterovirus (n = 4), EBV (n = 5), and CMV (n = 3) with the remaining viruses included JCV (n = 12) and HHV-6 (n = 1). The mean Charlson Comorbidity Index (2.0) and mortality rate (37.6%) were significantly higher in the CSF viral genome-negative encephalitis group although the mean costs of care were significantly higher for the CSF viral genome-positive group. Cumulative incidence rates showed increased CSF VZV detection in persons with encephalitis, which predominated in persons over 65years with a higher mean Charlson index. We detected HSV-2 and VZV more frequently in CSF from encephalitis cases with greater material-social deprivation. The mean costs of care were significantly greater for HSV-1 encephalitis group. Encephalitis remains an important cause of neurological disability and death with a viral etiology in 54.2% of affected adults accompanied by substantial costs of care and mortality. Virus-associated encephalitis is evolving with increased VZV detection, especially in older persons.

Long-term observations of feline meningoencephalitis of unknown etiology: clinical, CSF, and MRI findings

A 4-year-old neutered female Turkish Angora cat presented with acute onset of obtundation, right-sided head turn, and rolling. On neurologic examination, postural reactions were found either absent or decreased in all four limbs. Cranial nerve examination, such as menace response, pupillary light, and oculocephalic reflex, showed absent or decreased results. Magnetic resonance imaging (MRI) demonstrated demarcated lesions in the thalamus and brainstem, which were marked hyperintense on T2-weighted and FLAIR images and isointense on T1-weighted images. Cerebrospinal fluid (CSF) nucleated cell count was markedly elevated (258 cells/µl) with a neutrophilic pattern. The CSF polymerase chain reaction for infectious agents was negative. Based on these results, a diagnosed of feline meningoencephalitis of unknown etiology (FMUE) was made. The cat was treated with prednisolone (3 mg/kg, twice a daily), which was gradually tapered off. The follow-up of clinical signs, MRI, and CSF analysis was performed at 33, 118, and 611 days after the initial therapy. At 33 days, abnormalities of clinical signs, MRI, and CSF almost disappeared. At 139 days, because all examinations showed normal findings, the treatment was stopped. At 611 days, the final examinations showed no remarkable findings. This is the first case describing changes in the clinical signs, MRI findings, and CSF analysis of FMUE with long-term follow-up.

Severe encephalitis: aetiology, management and outcomes over 10 years in a paediatric intensive care unit

ObjectiveTo describe the characteristics, differential diagnoses, management and outcomes of severe encephalitis in children.DesignA 10-year retrospective cohort study in children admitted to a tertiary paediatric intensive care unit (PICU) with...

Papilledema in Patients with Presumed Idiopathic Intracranial Hypertension Diagnosed Without a Lumbar Puncture: A Case Report

Purpose: The purpose of this case report is to present two cases of papilledema secondary to presumed IIH and medically managed with an oral diuretic without first obtaining cerebrospinal fluid opening pressure and composition. Method: A 31-year-old female presented for evaluation of blurry vision in both eyes and a history of transient vision loss with postural changes. A 22-year-old female presented for evaluation of blurry vision in both eyes and headaches that started during her pregnancy. She reported double vision that was relieved when she closed one eye. This is a case report of two overweight females who presented with bilateral optic disc edema and were referred for neuro-ophthalmological evaluation. Both patients were treated with oral acetazolamide without lumbar puncture to confirm elevated intracranial pressure or abnormal cerebrospinal fluid components. Result: The features associated with idiopathic intracranial pressure may include papilledema, a headache, pulsatile tinnitus, blind spot enlargement on visual field testing, and diplopia. Conclusion: Although the diagnosis of IIH has historically been contingent on cerebrospinal fluid opening pressure of 25 cm H2O measured by a lumbar puncture, the health professions community should be aware that some patients are being managed with oral acetazolamide for presumed IIH-related signs and symptoms without the evidence of elevated intracranial pressure or cerebrospinal fluid abnormalities.

Diagnostic Yield of Combined Lumbar Puncture and Brain MRI in Critically Ill Patients With Unexplained Acute Encephalopathy: A Retrospective Cohort Study.

We sought to characterize the yield of combined LP and brain MRI (bMRI) in such patients as determined by both the frequency of abnormal results and the therapeutic efficacy of these investigations, that is, how often results changed management. Retrospective cohort study of medical ICU patients admitted to a tertiary academic center between 2012 and 2018 who had documented diagnoses of "AMS" and/or synonymous terms, no clear etiology of encephalopathy, and had undergone both LP and bMRI. The primary outcome was the frequency of abnormal diagnostic testing results determined objectively for LP using cerebrospinal fluid (CSF) findings and subjectively for bMRI through team agreement on imaging findings deemed significant through retrospective chart review. We subjectively determined the frequency of therapeutic efficacy. Finally, we analyzed the effect of other clinical variables on the likelihood of discovering abnormal CSF and bMRI findings through chi-square tests and multivariate logistic regression. One hundred four patients met inclusion criteria. Fifty patients (48.1%) had an abnormal CSF profile or definitive microbiological or cytological data by LP, 44 patients (42.3%) had bMRI with significant abnormal findings, and 74 patients (71.2%) had abnormal results on at least one of these investigations. Few clinical variables were associated with the abnormal findings in either investigation. We judged 24.0% (25/104) of bMRI and 26.0% (27/104) of LPs to have therapeutic efficacy with moderate interobserver reliability. Determining when to perform combined LP and bMRI in ICU patients with unexplained acute encephalopathy must rely on clinical judgment. These investigations have a reasonable yield in this selected population.

Coronavirus Disease 2019-Related Fulminant Idiopathic Intracranial Hypertension

AbstractIdiopathic intracranial hypertension or pseudotumor cerebri syndrome (PTCS) is defined as an increase in intracranial pressure (ICP) without an identifiable and/or structural cause or abnormal cerebrospinal fluid content. The most common symptoms of PTCS include headache, vomiting, pulsatile tinnitus, blurred vision, and diplopia. In 2 to 3% of PTCS patients, severe and rapidly progressive vision loss may develop within 1 month since symptoms begin; this clinical condition is usually defined as fulminant idiopathic intracranial hypertension (FIIH). This study presented a patient admitted to the hospital with headache and blurred vision, who also had high severe acute respiratory syndrome coronavirus 2 infections total antibody level and was treated with a lumboperitoneal shunt due to medical treatment-resistant increased ICP. We also reviewed similar cases previously reported in the literature. To the best of our knowledge, no children affected with coronavirus 2019 related to FIIH and requiring surgical treatment have been yet reported in the literature.

Risk Factors and Prognosis in Anti-NMDA Receptor Encephalitis Patients with Disturbance of Consciousness.

Disturbance of consciousness is common in patients with severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, little is known about it. This study aimed to analyze the clinical manifestations and prognostic factors of anti-NMDAR encephalitis with disturbance of consciousness. In this retrospective study, the clinical features, treatment results, and long-term outcomes of anti-NMDAR encephalitis patients with disturbance of consciousness were analyzed, and multivariate logistic regression was used to analyze the factors affecting their prognosis. In the group with disturbance of consciousness, the incidences of seizures, involuntary movements, pulmonary infection, mechanical ventilation, intensive care unit (ICU) admission, neutrophil-lymphocyte ratio (NLR), abnormal cerebrospinal fluid index, plasma exchange, and immunosuppressive therapy were higher than those in the group without disturbance of consciousness (all P<0.05). During the follow-up period (median: 36 months, range: 12-78 months), the modified Rankin scale (mRS) score, the maximum mRS score during hospitalization, the mRS score at discharge, and the mRS score at 12 months after discharge were higher in the disturbance of consciousness group (all P < 0.001). However, there was no significant difference in long-term outcomes and recurrence between the two groups. Multivariate logistic regression analysis showed that mechanical ventilation, elevated IgG index, and delayed immunotherapy were independent risk factors for poor outcomes in patients with anti-NMDAR encephalitis with disturbance of consciousness at 12 months (odds ratio: 22.591, 39.868, 1.195). The receiver operating characteristics (ROC) curve analysis showed that the area under the curve (AUC) of mechanical ventilation, elevated IgG index, and delayed immunotherapy was 0.971 (95% CI=0.934-1.000, P<0.001). Mechanical ventilation, elevated IgG index, and delayed immunotherapy may be the influencing factors of poor prognosis of anti-NMDAR encephalitis patients with disturbance of consciousness. Although their condition is relatively serious, most patients with anti-NMDAR encephalitis with disturbance of consciousness will achieve favorable long-term outcomes after long-term treatment.

Vasculitis in the Central Nervous System: Treatment and Outcomes in a Large Single-Center Cohort (P9-5.014)

<h3>Objective:</h3> To describe the demographics, treatment, and outcomes of patients presenting with vasculitis involving the central nervous system (CNS) at a major referral center covering a five-state catchment area in the Intermountain West. <h3>Background:</h3> CNS vasculitis is inflammation of blood vessel walls in the brain or spine that can be life-threatening and/or result in ischemic strokes. Markers suggestive of CNS inflammation include cerebrospinal fluid (CSF) pleocytosis and/or elevated protein level, and on neuroaxis imaging, the presence of parenchymal, leptomeningeal, or vessel wall enhancement. At the time of symptom onset, the diagnostic evaluation focuses on classifying the size of the involved vessels and determining if the vasculitis is a primary angiitis of the CNS or if it is occurring secondary to another process elsewhere in the body, such as a systemic vasculitis, connective tissue disorder, infection, malignancy, or toxic/drug exposure. <h3>Design/Methods:</h3> A retrospective chart review for patients within the University of Utah Health system queried all International Classification of Diseases (ICD) 9 codes for 437.4 (Cerebral arteritis) and ICD10 codes for I67.7 (Cerebral arteritis, not elsewhere classified) with one encounter with a neurologist. Of the 144 total patients identified between January 2012 to October 2022, we further confirmed the diagnosis based on neurologists’ review of each record and categorized patients further to determine if the CNS presentation of vasculitis was primary, secondary, or indeterminate/uncertain. <h3>Results:</h3> We described the demographic characteristics of vasculitis patients with CNS involvement seen at the University of Utah, as well as presenting symptoms, relevant comorbidities, distinct imaging findings (including a focus on imaging modality), CSF abnormalities, treatments, and outcomes. <h3>Conclusions:</h3> This is a comprehensive characterization of patients with vasculitis involving the CNS in a large area of the Intermountain West. Understanding the differences in these patient characteristics, symptoms, and variability in diagnostic and treatment plans will inform better, more efficient approaches. <b>Disclosure:</b> Dr. Hoshina has nothing to disclose. Alen Delic has nothing to disclose. Mr. Wong has nothing to disclose. Dr. Lyden has nothing to disclose. Dr. Kadish has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Kadish has received research support from Alexion Pharmaceuticals. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.

Prognostic value of cerebrospinal fluid biomarkers in mild cognitive impairment due to Alzheimer disease

We performed a retrospective analysis of the patients assessed at our memory unit for whom Alzheimer disease (AD) cerebrospinal fluid biomarker results were available. We selected patients diagnosed with mild cognitive impairment due to AD (National Institute on Aging-Alzheimer’s Association clinical criteria), confirmed neuropsychological deficit, a Global Deterioration Scale score of 3, and an abnormal profile of cerebrospinal fluid biomarkers. Of the 588 cases reviewed, 110 met the inclusion criteria. During follow-up, 50 cases (45.45%) progressed to dementia due to AD. Baseline levels of total and phosphorylated tau were higher in the group of patients that progressed to dementia than in those remaining with mild cognitive impairment. After adjusting for age, sex, history of hypertension, diabetes, and educational level, a 10% increase in total tau protein values was associated with a 7.60% increase in the risk of progression to dementia (hazard ratio: 2.22; 95% confidence interval, 1.28–3.84]; P = .004). Among patients with mild cognitive impairment due to AD and abnormal cerebrospinal fluid biomarker profiles, progressively higher concentrations of total or phosphorylated tau were associated with increased risk of progression to dementia.