Cerebrospinal Fluid Pleocytosis Research Articles

Clinical characteristics and factors affecting disease severity in hospitalized tick-borne encephalitis patients in Norway from 2018 to 2022.

To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE). This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified. Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease. This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease. Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results

GRN mutations cause progranulin haploinsufficiency, which eventually leads to frontotemporal dementia (FTD-GRN). PR006 is an investigational gene therapy delivering the granulin gene (GRN) using an adeno-associated virus serotype 9 (AAV9) vector. In non-clinical studies, PR006 transduced neurons derived from induced pluripotent stem cells of patients with FTD-GRN, resulted in progranulin expression and improvement of lipofuscin, lysosomal and neuroinflammation pathologies in Grn-knockout mice, and was well tolerated except for minimal, asymptomatic dorsal root ganglionopathy in non-human primates. We initiated a first-in-human phase 1/2 open-label trial. Here we report results of a pre-specified interim analysis triggered with the last treated patient of the low-dose cohort (n = 6) reaching the 12-month follow-up timepoint. We also include preliminary data from the mid-dose cohort (n = 7). Primary endpoints were safety, immunogenicity and change in progranulin levels in cerebrospinal fluid (CSF) and blood. Secondary endpoints were Clinical Dementia Rating (CDR) plus National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) rating scale and levels of neurofilament light chain (NfL). One-time administration of PR006 into the cisterna magna was generally safe and well tolerated. All patients developed treatment-emergent anti-AAV9 antibodies in the CSF, but none developed anti-progranulin antibodies. CSF pleocytosis was the most common PR006-related adverse event. Twelve serious adverse events occurred, mostly unrelated to PR006. Deep vein thrombosis developed in three patients. There was one death (unrelated) occurring 18 months after treatment. CSF progranulin increased after PR006 treatment in all patients; blood progranulin increased in most patients but only transiently. NfL levels transiently increased after PR006 treatment, likely reflecting dorsal root ganglia toxicity. Progression rates, based on the CDR scale, were within the broad ranges reported for patients with FTD. These data provide preliminary insights into the safety and bioactivity of PR006. Longer follow-up and additional studies are needed to confirm the safety and potential efficacy of PR006. ClinicalTrials.gov identifier: NCT04408625.

HaNDL Syndrome: The Innocent Lymphocytic Pleocytosis.

HaNDL syndrome is a transient and rare condition that presents with neurological deficit and headache accompanied by lymphocytosis on cerebrospinal fluid (CSF) analysis. It is usually characterized by spontaneous recovery without neurological sequelae. This is a benign condition, which has not yet been adequately defined and includes many diseases in the differential diagnosis. We indicated 2 different cases that applied with acute neurological findings. Two patients who were admitted to our hospital with transient neurological deficits and headaches were evaluated. There was no significant pathology in cranial imaging and EEG reports. Lymphocytic pleocytosis was observed in CSF. Patients were followed up with attacks but were discharged without deficits. We diagnosed the patients with HaNDL syndrome with clinical features, imaging, and laboratory findings. HaNDL is an underdiagnosed syndrome and it should be considered especially for young patients with headaches is prominent without a risk factor for ischemia, recurrent episodes with neurological symptoms, CSF pleocytosis, and normal imaging findings.Therefore, we wanted to raise awareness for the existence of this rare disease which is a waste of time by performing unnecessary tests and therapies during the diagnosis period.

Comparison of Acute COVID-19 Encephalopathy with Seasonal Influenza A-Associated Encephalopathy

Objectives: To compare the clinical presentations and neurobiological features in children with acute Coronavirus disease 2019 (COVID-19) encephalopathy and Seasonal influenza A virus (IAV)-associated encephalopathy. Methods: We conducted a retrospective cohort study on patients diagnosed with COVID-19 encephalopathy between December 15, 2022, and January 15, 2023, and children diagnosed with IAV-associated encephalopathy between November 2017 and March 2023, who were less than 18 years old at the Children’s Hospital, Zhejiang University School of Medicine. Results: A total of 34 patients with acute COVID-19 encephalopathy and 37 patients with IAV-associated encephalopathy were included in this study. Elevation of cerebrospinal fluid (CSF) pleocytosis and CSF glucose, as well as downregulation of monocyte and TNF-α, were observed in both the COVID-19 ICU group and the moderate & severe group. The median age was younger (P < 0.001) and the median time for the occurrence of neurological symptoms was shorter (P < 0.001) in the COVID-19 group compared with the IAV group. More patients in the IAV group had altered levels of consciousness (P < 0.001) and were admitted to the ICU (P < 0.001). Consequently, more severe cases were observed in the IAV group (P = 0.007). Brain imaging showed a predominance appearance of acute necrotizing encephalopathy in the IAV group (P = 0.038). Regarding blood parameters, leukomonocyte levels were lower in the IAV group (P = 0.003) with lower expression of CD4 (P = 0.047). Random blood glucose (P = 0.001), D dimer (P = 0.004), and cytokine IL-2 (P = 0.005) were lower in the COVID-19 group, while IFN-γ (P = 0.013) was significantly higher. Conclusions: Influenza A virus-associated encephalopathy presented more severe manifestations. However, IFN-γ may act as a protective cytokine in COVID-19 encephalopathy.

Cefaleas y neuralgias craneofaciales descritas por autores españoles

Spanish physicians have made important contributions to the nosology of headaches by describing various syndromes. In 1954, Eduardo Tolosa Colomer published the first case of Tolosa-Hunt syndrome, a clinical picture characterized by orbital pain and paralysis of extraocular muscles due to the presence of granulomatous inflammation in the cavernous sinus. In 1980, José Félix Martí Massó described pseudomigraine with cerebrospinal fluid pleocytosis, which manifests with episodes of migraine-type headache, transient neurological deficits, and elevated lymphocytes in the cerebrospinal fluid, usually with a benign prognosis. Since 2002, Juan Pareja and his group have identified several entities including: nummular headache, characterized by pain localized in a small coin-shaped area of the skull; primary trochlear headache, originating in the trochlea, in the superointernal angle of the orbit; epicrania fugax, which manifests with episodes of paroxysmal pain radiating along the surface of the head, following a linear or zigzag trajectory, and idiopathic ophthalmodynia and rhinalgia, which present with pain in the eyeball or nose with no apparent cause. Juan Pareja has also described several trigeminal terminal branch neuralgias, which are characterized by pain limited to the corresponding cutaneous territory and which typically respond to anesthetic blockade of the nerve. Finally, paroxysmal pressing headache, described by the same author, is manifested by brief episodes of unilateral pressing pain without accompanying symptoms. All these descriptions have been documented in scientific publications, and most of them have had a significant impact on clinical practice.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study

BackgroundIt remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.MethodsThis large-scale cohort study included persons with MS with CSF data documented...

Enterococcal Central Nervous System Infections in Children: A 22 Years' Experience in a Tertiary Center and Review of the Literature.

Enterococcal meningitis in children is rare, and its clinical presentation, laboratory characteristics and outcomes are not well defined. We conducted a retrospective analysis of Enterococcal meningitis cases during 2002-2023 at our tertiary center. We identified 10 cases in children aged 2 weeks to 15 years (median age: 8 months). Seven children were males and 9 had comorbidities, including a ventriculoperitoneal shunt in 5 children. All children with shunt infections presented with nonspecific signs and symptoms. While 8 children presented with fever, only 3 had signs of meningeal irritation and altered consciousness. Cerebrospinal fluid pleocytosis was evident in almost all children with a median of 173 cells/mL. Nine cases were due to Enterococcus faecalis, and 1 case was due to E. faecium. All 5 children with ventriculoperitoneal shunt underwent shunt removal and replacement. All children recovered without documented sequelae. Enterococcal meningitis is rare, especially in healthy neonates. It typically occurs following neurosurgical interventions and may only present with fever and shunt malfunction, without overt meningeal signs and with mild inflammation. The prognosis is favorable.

Rare Cases of Pseudomonas aeruginosa Meningitis in Children: 10-Year Experience in a Single Center.

The primary objective was to elucidate the epidemiologic characteristics, risk determinants, and clinical outcomes associated with Pseudomonas aeruginosa-induced meningitis. All cases of meningitis caused by Pseudomonas aeruginosa that were treated at the hospital between 2012 and 2022 were retrospectively analyzed and detailed. During a 10-year period, only 10 patients satisfied the inclusion criteria. Three patients had previously undergone neurosurgical procedures and 4 patients had leukemia. Although Pseudomonas aeruginosa meningitis possesses a low incidence rate, the rate of mortality is high. Patients with leukemia or those who have undergone neurosurgery are the most susceptible to diagnosis. Cases of severe neutropenia present only mild or no cerebrospinal fluid pleocytosis. In patients with sensitive Pseudomonas aeruginosa meningitis, the timely use of anti-Pseudomonas carbapenems for intravenous treatment is highly effective. For drug-resistant Pseudomonas aeruginosa meningitis, intrathecal polymyxins administration can be an effective treatment option.

Effects of tofersen treatment in patients with SOD1-ALS in a “real-world” setting – a 12-month multicenter cohort study from the German early access program

In April 2023, the antisense oligonucleotide tofersen was approved by the U.S. Food and Drug Administration (FDA) for treatment of SOD1-amyotrophic lateral sclerosis (ALS), after a decrease of neurofilament light chain (NfL) levels had been demonstrated. Between 03/2022 and 04/2023, 24 patients with SOD1-ALS from ten German ALS reference centers were followed-up until the cut-off date for ALS functional rating scale revised (ALSFRS-R), progression rate (loss of ALSFRS-R/month), NfL, phosphorylated neurofilament heavy chain (pNfH) in cerebrospinal fluid (CSF), and adverse events. During the observation period, median ALSFRS-R decreased from 38.0 (IQR 32.0-42.0) to 35.0 (IQR 29.0-42.0), corresponding to a median progression rate of 0.11 (IQR-0.09 to 0.32) points of ALSFRS-R lost per month. Median serum NfL declined from 78.0pg/ml (IQR 37.0-147.0pg/ml; n=23) to 36.0pg/ml (IQR 22.0-65.0pg/ml; n=23; p=0.02), median pNfH in CSF from 2226pg/ml (IQR 1061-6138pg/ml; n=18) to 1151pg/ml (IQR 521-2360pg/ml; n=18; p=0.02). In the CSF, we detected a pleocytosis in 73% of patients (11of 15) and an intrathecal immunoglobulin synthesis (IgG, IgM, or IgA) in 9 out of 10 patients. Two drug-related serious adverse events were reported. Consistent with the VALOR study and its Open Label Extension (OLE), our results confirm a reduction of NfL serum levels, and moreover show a reduction of pNfH in CSF. The therapy was safe, as no persistent symptoms were observed. Pleocytosis and Ig synthesis in CSF with clinical symptoms related to myeloradiculitis in two patients, indicate the potential of an autoimmune reaction. No funding was received towards this study.

Surveillance for Acute Flaccid Myelitis - United States, 2018-2022.

Acute flaccid myelitis (AFM) is a serious neurologic condition primarily affecting children; AFM can cause acute respiratory failure and permanent paralysis. AFM is a rare but known complication of various viral infections, particularly those of enteroviruses (EVs). Increases in AFM cases during 2014, 2016, and 2018 were associated with EV-D68 infection. This report examines trends in confirmed AFM cases during 2018-2022 and patients' clinical and laboratory characteristics. The number of AFM cases was low during 2019-2022 (28-47 cases per year); the number of cases remained low in 2022 despite evidence of increased EV-D68 circulation in the United States. Compared with cases during the most recent peak year (2018), fewer cases during 2019-2021 had upper limb involvement, prodromal respiratory or febrile illness, or cerebrospinal fluid pleocytosis, and more were associated with lower limb involvement. It is unclear why EV-D68 circulation in 2022 was not associated with an increase in AFM cases or when the next increase in AFM cases will occur. Nonetheless, clinicians should continue to suspect AFM in any child with acute flaccid limb weakness, especially those with a recent respiratory or febrile illness.

Autoimmune Encephalitis. An Analysis of Three Cases

The diagnosis of diseases from the group of autoimmune encephalitis (AE) requires a detailed analysis of clinical data and correlation of results from a wide range of laboratory and instrumental research methods. This article presents three clinical cases of patients with AE. In one patient, AE was associated with a malignant neoplasm, in the second one – with the novel coronavirus infection, and in the third patient, no comorbid pathology was detected. The specific type of encephalitis was determined for each of the three patients. The diagnosis of “autoimmune limbic encephalitis” was established in two patients based on visualization of changes in the medial temporal structures in the magnetic resonance imaging of the brain, detection of pathological bioelectrical activity in the temporal lobe cortex in electroencephalography, and pleocytosis in cerebrospinal fluid. The diagnosis of “anti-NMDA receptor encephalitis” was made based on the detection of specific antibodies to the subunit of the corresponding receptor. Neurological deficit regression was observed in two patients after the application of combined immune therapy methods and in one patient without the use of immune therapy.

The incidence of VP shunt infection in a middle-income nation: a retrospective analysis of a pediatric population.

To investigate the incidence of infection after ventriculoperitoneal shunt (VPS) insertion at the Bustamante Hospital for Children (BHC), Jamaica, West Indies. Of the 178 patients managed by the Neurosurgery team at BHC, who underwent surgery between 2010 and 2016, 122 patients were subjected to the cerebrospinal fluid (CSF) diversion procedure through a VPS placement. The patients excluded from this study included those with a VPS placed at another institution or one placed prior to the study period. There is a notable transition that saw a switch from the use of the Codman uni-port to Medtronic shunts in 2014-2015, which initiated the process of reuse of shunt passers. Clinical data were retrospectively collected from operating theater logs and available manual health records. Over the 7-year study period of the 122 first-time shunt placements done, 17 patients (13.9%) had positive CSF cultures, with an additional six (4%) having CSF pleocytosis with negative cultures. The most common isolate was the Staphylococcus species, occurring in 60% of VPS infections. The median time to shunt infection was 2 months. Of the 72 Codman shunts placed, six became infected, and 21.7% (10 of 46) of the Medtronic shunts became infected. The rate of incidence of VPS infection was 13.9% for the period between 2010 and 2016, with most infections occurring after 2014. The major causative agent was Staphylococcus species at 60% within a median 2 months of surgery. Overall, this compares well with data reported in the literature.

Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection.

HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it associated with plasma and CSF HIV-1 RNA during untreated acute HIV infection (AHI). Seventy participants underwent lumbar puncture during Fiebig stages I-V AHI. WBC and HIV-1 RNA with a lower limit of quantification (LLQ) of 80 copies/ml were measured in CSF. Sixty-nine (99%) participants were men, with a median age of 26. Their blood CD4 + and CD8 + T-cell counts were 335 [interquartile range (IQR) 247-553) and 540 (IQR 357-802) cells/μl, respectively. Forty-five (64%) were in Fiebig stages III-V whereas 25 (36%) were in Feibig stages I-II. Fifty-two (74%) experienced acute retroviral syndrome. Median plasma and CSF HIV-1 RNA were 6.10 (IQR 5.15-6.78) and 3.15 (IQR 1.90-4.11) log 10 copies/ml, respectively. Sixteen (23%) CSF samples had HIV-1 RNA below LLQ. Median CSF WBC was 2.5 (IQR 1-8) cells/μl. CSF pleocytosis (WBC >5) was observed in 33% and was only present in CSF samples with detectable HIV-1 RNA. The frequencies of CSF pleocytosis during Fiebig stages III-V and among CSF samples of higher viral load (>1000 copies/ml) were 42 and 45%, respectively. Pleocytosis independently associated with CSF HIV-1 RNA in multivariate analysis [adjusted coefficient: 0.79, 95% confidence interval (CI) 0.41-1.14), P < 0.001] and a lower plasma to CSF HIV-1 RNA ratio ( P < 0.001). CSF pleocytosis was present in one-third of participants with AHI. It associated with higher CSF HIV-1 RNA and a lower plasma to CSF HIV-1 RNA ratio, suggesting a potential association with HIV-1 neuroinvasion.

Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy: An Emerging Cause of Meningoencephalomyelitis in Children and Adolescents.

Introduction: We describe 5 children with GFAP astrocytopathy with the goal of further characterizing this rare form of meningoencephalomyelitis. Methods: Retrospective chart review of patients diagnosed with GFAP astrocytopathy between 2019 and 2021. Results: Patients were 8-17 years old, and all were male. Fever, headache, and vomiting were common presenting symptoms, and weakness, tremor, and ataxia were common initial examination findings. Initial magnetic resonance imaging (MRI) showed spinal cord abnormalities in 2 patients and leptomeningeal enhancement in 1. Most patients had cerebral spinal fluid pleocytosis, and all screened negative for malignancy. Three patients progressed to coma, and all were treated with immunosuppressant therapy. By discharge, all patients had improved over their clinical nadir, although none had returned to baseline. Discussion: GFAP astrocytopathy is a recently recognized cause of meningoencephalomyelitis in children. Here, we expand our understanding of this entity with the goal of aiding those treating children with GFAP astrocytopathy.

Clinical and imaging features of lymphomatosis cerebri: analysis of 8 cases and systematic review of the literature

Lymphomatosis cerebri (LC) is a rare type of primary central nervous system lymphoma with diffuse, nonenhancing infiltrative lesions and is often misdiagnosed. Our study aimed to investigate the clinical characteristics and prognosis of LC through analyzing patients from the literature and our own center, so as to improve early diagnosis and treatment. PubMed, Web of Science and our hospital databases were reviewed, and information on demographic, clinical, pathological, cerebrospinal fluid (CSF), neuroimaging and treatment options was extracted. Univariate survival analysis was conducted by generating survival curves and comparing them using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to identify the prognostic predictors. A total of 81 patients (median age: 58 years; interquartile range, IQR: 50–66.5 years), 45 males and 36 females, were included. The most common symptoms were cognitive impairment (65.4%) and gait impairment (50.6%). Imaging studies indicated that all 81 patients had supratentorial structure involvement, and 93.8% (76/81) had bilateral hemisphere involvement. There were 53.3% (32/60) patients with CSF pleocytosis and 65% (39/60) patients with increased CSF protein levels. The median time of diagnosis was 4.8 months (IQR: 2.3–6.9 months). Compared with 4 (95% CI: 1.78–6.22) months for all 81 patients, the median OS was 20 (95% CI: 8.24–31.76) months for those who had chemotherapy plus radiotherapy. Multivariate Cox analysis revealed that chemoradiotherapy (HR: 0.12; 95% CI: 0.02–0.68) and higher CSF glucose level (HR: 0.01; 95% CI: 0.00–0.26) were inversely associated with death. The diagnosis of LC should be alerted when neuroimaging with bilateral hemispheric involvement and CSF abnormality with pleocytosis and increased protein. Once the diagnosis is confirmed, the combination of chemotherapy and radiotherapy can be considered if the patient’s physical condition permits.Journal standard instruction requires an unstructured abstract. Kindly check and confirm.We have checked and confirmed that there is no problem.

Abstract 109: Endonasal Endoscopic Approach Associated Cerebral Vasospasm and Management: A Case Report

Introduction Endoscopic endonasal approach(EEA) techniques have been increasingly utilized and have been associated with development of cerebrospinal fluid(CSF) leak, meningitis, diabetes insipidus post‐operatively. Cerebral vasospasm following EEA has rarely been described. Here, we describe the clinical course and management of a patient who underwent EEA for encephalocele repair whose course was complicated by postoperative subarachnoid hemorrhage(SAH) and cerebral vasospasm. Methods n/a Results Case Presentation: 40 year old female with past medical history significant for cerebral venous sinus stent on aspirin, CSF rhinorrhea secondary to right nasal encephalocele s/p endoscopic transnasal transethmoidal repair with nasoseptal flap reconstruction and lumbar drain placement eleven days prior presented with speech difficulties and right sided weakness. On exam, patient was noted to have mild right hemiparesis and expressive aphasia. MRI brain showed subacute infarcts in left greater than right frontal lobes, corpus collosum and right anterior perforated substance. MRA head demonstrated multifocal arterial stenosis. In light of postoperative CT head showing SAH in the basilar, perimesencephalic, prepontine cisterns, interhemispheric fissure and right frontal sulci as well as intraventricular hemorrhage in fourth ventricle, her presentation was thought to be secondary to cerebral vasospasm in the setting of postoperative SAH. She was treated with intravenous hydration, permissive hypertension with head of bed in flat position and transferred for further evaluation. On arrival, she continued have mild right hemiparesis and aphasia. Repeat CTA head/neck and CT perfusion showed severe stenosis of bilateral M1 segments and left greater than right A1 segments as well as ischemic penumbra in left ACA/MCA watershed territory. Diagnostic cerebral angiogram showed bilateral severe A1 stenosis and mild to moderate bilateral M1 and supraclinoid ICA stenosis which improved with intra‐arterial verapamil. She was started on nimodipine. Systolic blood pressure was augmented with vasopressors for goal of 150‐180mmHg. Daily TCDs were followed. She developed worsening right leg weakness following day, thus she was taken for repeat diagnostic cerebral angiogram during which time she was re‐administered intra‐arterial verapamil with improvement in vasospasm. After the second treatment, she had improvement in speech and motor strength. Systolic blood pressure goal was gradually normalized. She was noted to have incidental left internal jugular (IJ) vein thrombosis for which anticoagulation was held in the setting of recent neurosurgical procedure and SAH. Workup for vasculitis and hypercoagulability was unrevealing. Lumbar puncture demonstrated 13 WBC/cu mm with lymphocytic predominance(90%), 23 RBC/cu mm, glucose 89mg/dl, protein 30mg/dl. CSF cultures were negative. Pleocytosis in CSF was attributed to recent neurosurgical procedure. Her neurological exam improved to baseline on hospital day(HD) 9.On HD12, she was found to have left common femoral deep venous thrombus in addition to the left IJ thrombus. Anticoagulation with low dose heparin infusion was started which was transitioned to apixaban on discharge. She was discharged home on HD20. Conclusion We report a case of EEA associated with severe multifocal cerebral vasospasm secondary to postoperative SAH that was successfully treated with induced hypertension, oral nimodipine and intra‐arterial verapamil as an adjunct therapy with an excellent outcome.

The role of intrathecal free light chains kappa for the detection of autoimmune encephalitis in subacute onset neuropsychiatric syndromes

Intrathecal synthesis of free light chains kappa (FLCK) is increasingly recognized as a marker of inflammatory CNS pathologies. Here, we tested the performance of FLCK in differentiating autoimmune encephalitis (AIE) from non-inflammatory etiologies in subacute onset neuropsychiatric syndromes. Patients undergoing diagnostic work-up for suspected autoimmune encephalitis at our department between 2015 and 2020 were retrospectively assessed for definitive diagnosis, available CSF and blood samples, as well as complete clinical records. Intrathecal FLCK was measured along with established CSF markers of CNS inflammation. The study cohort consisted of 19 patients with antibody-mediated AIE (AIE+), 18 patients with suspected AIE but without detectable autoantibodies (AIE–), 10 patients with infectious (viral) encephalitis (INE), and 15 patients with degenerative encephalopathies (DGE). 25 age- and sex-matched patients with non-inflammatory neurological diseases (NIND) were used as a control group. All AIE+ patients exhibited intrathecal synthesis of FLCK compared to only 39% of AIE– patients and 81% of patients in the INE group. No intrathecal synthesis of FLCK was found in DGE and NIND patients. While intrathecal FLCK was equally specific for an inflammatory etiology as oligoclonal bands (OCB) in the cerebrospinal fluid (CSF), the sensitivity of intrathecal FLCK for any inflammatory intrathecal process was higher than that of OCB (83% vs. 38%). Intrathecal FLCK synthesis was found to discriminate AIE+ from non-inflammatory encephalopathies and AIE– when the CSF cell count was normal [receiver operating characteristic (ROC) analysis area under the curve (AUC): 0.867, p = 0.002], while it failed to differentiate between AIE+ and INE in the presence of CSF pleocytosis (AUC: 0.561, p = 0.607). In conclusion, in the absence of CSF pleocytosis, intrathecal FLCK discriminated AIE+ from competing diagnoses in our cohort of subacute onset neuropsychiatric syndromes. In addition to established markers of CSF inflammation, intrathecal FLCK might support clinical decision-making and contribute to selecting patients for (repeated) antibody testing.

Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis

PurposeThere is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital.MethodsA retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis.ResultsThe most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956).ConclusionOverall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making.

Pituitary apoplexy as a mimicker of infectious meningitis in an adolescent female patient.

Pituitary apoplexy can cause a chemical meningitis and its mimicry in presentation with infectious meningitis poses a diagnostic challenge. Here we report an 18-year-old woman who presented with acute headache, altered mental status, and cerebral spinal fluid (CSF) pleocytosis, and clinically improved with antibiotics and steroids. Despite an unremarkable head computed tomography scan, brain magnetic resonance imaging showed a pituitary macroadenoma with apoplexy. This is one of the first reports of an adolescent with pituitary apoplexy masquerading as infectious meningitis and underscores the importance of keeping this rare condition, often missed on CT scans, on the differential for CSF pleocytosis.