Routine CSF Analysis Research Articles

The prominence of Oligoclonal Bands for clinical conversion in Radiologically isolated syndrome: 10-year follow-up study in Isfahan, Iran

BackgroundSince data is limited on radiologically isolated syndrome (RIS) subjects in certain regions like the Middle East, we aimed to further explore the replicability and generalizability of previously suggested predictors among a cohort of Iranian RIS subjects and report the long-term clinically definite MS (CDMS) conversion rate in this cohort. MethodsWe conducted a prospective 10-year cohort on our RIS participants, during which we collected the MRI, paraclinical, and demographic data of the subjects, and identified those who converted to CDMS. ResultsOut of 35 participants, 10 (28.5 %) developed CDMS during an average of 5.58 ± 3.08 years (range: 4 months to 10.33 years). OCB positivity was the only definitive predictor for conversion to CDMS in this cohort (P-value = 0.006), but other previously reported risk factors such as spinal cord lesions or age lacked statistical significance (P-values > 0.05). We also reported the median survival time as 114 months, the proportion surviving after 14 months as 96.9 % ± 3.1 %, and the overall conversion rate as 0.05 cases per year. ConclusionOur results highlight OCB as an important predictive factor of clinical conversion in RIS. The prominence of OCB suggests a need for routine CSF analysis in RIS subjects and could guide clinicians in deciding which RIS subjects benefit from DMTs.

Investigating Procalcitonin and C-Reactive Protein as Diagnostic Biomarkers in Pediatric Suspected Meningitis: A Forward-Looking Observational Analysis

Our study is a prospective observational study done on all suspected cases of meningitis admitted to Tertiary Care Hospital, India to study suspected meningitis cases and assess the predictive value of CRP and PCT in diagnosing meningitis. Indian studies are scarce in this regard. We included all clinically suspected cases of paediatric meningitis in our study.Basic investigations, including blood culture and sensitivity, CRP, and PCT, were sentsoon after admission, and CSF analysis and cultures were done once the child became hemodynamically stable. Based on CSF analysis and culture with a clinical profile, meningitis was diagnosed and classified as bacterial and viral meningitis. In this study,we also compared PCT and CRP in their capacity to predict meningitis and to distinguish between bacterial or viral meningitis. A majority of studies have shown that PCT levels can be used in the early diagnosis of bacterial meningitis. In our study, we found that there is no role for PCT in predicting meningitis. CRP has a positive correlation in predicting meningitis but it is elevated in infectious as well as inflammatory conditions. A simple routine complete CSF analysis is an effective, reliable and feasible way to diagnose meningitis in children. This study reiterates the fact that it is indeed the gold standard diagnostic test as no other single parameter can differentiate or diagnose meningitis.

Magnitude of neonatal meningitis and associated factors among newborns with neonatal sepsis admitted to the University of Gondar Comprehensive Specialized Hospital, North Gondar, Ethiopia.

Neonatal meningitis continues to be a devastating infection with high mortality and morbidity worldwide. The prevalence of neonatal meningitis varies across countries. However, there is a paucity of studies on neonatal meningitis in most low-resource settings. Therefore, this study aimed to determine the magnitude, clinical presentations, and associated risk factors of meningitis among newborns with neonatal sepsis. An institution-based, cross-sectional study was conducted among newborns with neonatal sepsis from May 1, 2021, to Oct 30, 2021. Neonates with neonatal sepsis admitted to the University of Gondar Comprehensive Specialized Hospital (UOGCSH) during the study period were included in the study. Single population proportion formula was used to calculate the sample size and a systematic random sampling technique was used to select the study participants. Two trained pediatric residents collected the data by using a pretested, structured questionnaire. The data was entered into Epi-info version 7.0 and exported to SPSS version 24.0 for analysis. Binary logistic regression was used to identify the associated factors. P-value<0.05 was considered statistically significant. A total of 171 participants were enrolled in this study. The mean postnatal age was 10.74±8.0 days. The male to female ratio was l.3:1. The prevalence of neonatal meningitis among suspected sepsis was 19.3%; 95% CI [13.5%-25.1%]. The prevalence of meningitis was 22.8% in Early-Onset Neonatal Sepsis and 16.8% in Late-onset Neonatal Sepsis. Neurologic symptoms (seizure & altered mentation) were seen in 25% of the patients with meningitis. Two risk factors, Prolonged labor (adjusted odds ratio [AOR]: 4.98; 95% CI: 1.99-12.48) and Prolonged Rupture of Membrane (AOR: 5:38; 95% CI: 1.92-14.42) were significantly associated with neonatal meningitis. The prevalence of neonatal meningitis was higher in early-onset neonatal sepsis than in late-onset neonatal sepsis. Obstetric factors were associated with neonatal meningitis. We recommend that routine CSF analysis should be practiced in all neonates with neonatal sepsis regardless of their postnatal age and clinical features. Early detection and treatment of obstetric factors may have the potential to reduce neonatal meningitis.

Cerebrospinal fluid pressure dynamics reveal signs of effective spinal canal narrowing in ambiguous spine conditions.

Spinal canal narrowing with consecutive spinal cord compression is considered a key mechanism in degenerative cervical myelopathy (DCM). DCM is a common spine condition associated with progressive neurological disability, and timely decompressive surgery is recommended. However, the clinical and radiological diagnostic workup is often ambiguous, challenging confident proactive treatment recommendations. Cerebrospinal fluid pressure dynamics (CSFP) are altered by spinal canal narrowing. Therefore, we aim to explore the potential value of bedside CSFP assessments for qualitative and quantitative assessment of spinal canal narrowing in DCM. In this prospective case series, seven patients with DCM underwent bedside lumbar puncture with measurement of CSFP dynamics and routine CSF analysis (NCT02170155). The patients were enrolled when standard diagnostic algorithms did not permit a clear treatment decision. Measurements include baseline CSFP, cardiac-driven CSFP peak-to-trough amplitude (CSFPp), and the Queckenstedt's test (firm pressure on jugular veins) in neutral and reclined head position. From the Queckenstedt's test, proxies for craniospinal elastance (i.e., relative pulse pressure coefficient; RPPC-Q) were calculated analogously to infusion testing. CSFP metrics were deemed suspicious of canal narrowing when numbers were lower than the minimum value from a previously tested elderly spine-healthy cohort (N = 14). Mean age was 56 ± 13 years (range, 38–75; 2F); symptom severity was mostly mild to moderate (mean mJOA, 13.5 ± 2.6; range, 9–17). All the patients showed some extent of cervical stenosis in the MRI of unclear significance (5/7 following decompressive cervical spine surgery with an adjacent level or residual stenosis). Baseline CSFP was normal except for one patient (range, 4.7–17.4 mmHg). Normal values were found for CSFPp (0.4–1.3 mmHg) and the Queckenstedt's test in normal head positioning (9.-25.3 mmHg). During reclination, the Queckenstedt's test significantly decreased in one, and CSFPp in another case (>50% compared to normal position). RPPC-Q (0.07–0.19) aligned with lower values from spine-healthy (0.10–0.44). Routine CSF examinations showed mild total protein elevation (mean, 522 ± 108 mg/ml) without further evidence for the disturbed blood brain barrier. Intrathecal CSFP measurements allow discerning disturbed from normal CSFP dynamics in this population. Prospective longitudinal studies should further evaluate the diagnostic utility of CSFP assessments in DCM.

LGI1 antibody-associated encephalitis without evidence of inflammation in CSF and brain MRI.

This study aimed to explore the frequency and distinct characteristics of adult patients with LGI1 antibody-associated encephalitis in the absence of inflammatory abnormalities in both routine CSF analysis and brain MRI. We conducted a retrospective study of adult patients with antibodies targeting LGI1 and then screened patients with no evidence of inflammation in brain MRI and normal results in routine CSF analysis, including white blood cell count, protein concentration, IgG, and oligoclonal bands. Among 80 patients with LGI1 antibody-associated encephalitis in our center, 31 (38.8%) fulfilled the screening criteria. For these patients, the onset age was 57.0 ± 14.7years, and 19 (61.3%) were female. Viral prodrome occurred in 5 patients (16.1%). Faciobrachial dystonic seizures (FBDS) were the most predominant symptom (38.7%), followed by seizure onset (22.6%) and memory deficits (19.4%). The sensitivity of antibody detection in serum was higher than CSF (96.8% vs. 48.4%, p < 0.001). Most patients (30/31, 96.8%) benefited from the first-line immunotherapy, and 23 patients (74.2%) achieved complete recovery, yet 3 patients (9.7%) had clinical relapses in 2-year follow-up after discharge. The patients had a higher prevalence of females (61.9% vs. 26.7%, p = 0.003) and were more frequently associated with FBDS during the disease course (38.7% vs. 10.2%, p = 0.004). However, there was no difference in treatment outcomes and recurrence ratio between the two groups (p = 0.144 and p = 0.515). Moreover, we divided all 80 patients into four groups according to antibody titer levels in serum and CSF at the time of diagnosis, respectively. WBC and protein concentrations in CSF showed no difference among the four groups. The absence of evidence of inflammation in routine CSF analysis and brain MRI did not rule out anti-LGI1 associated encephalitis. FBDS and the subacute onset of cognitive dysfunction should push forward with autoantibody testing for patients even without inflammatory abnormalities. The routine inflammatory indicators in CSF seemed to be unrelated to antibody titer levels.

Clinical and Radiological Profile of 122 Cases of Idiopathic Intracranial Hypertension in a Tertiary Care Centre of India: An Observational Study.

Idiopathic intracranial hypertension (IIH) is well-described entity in literature. However, large studies on clinical and radiological profile are still very few from the Indian subcontinent. To analyze the clinical and radiological profile of IIH and correlation of various clinical and radiological parameters with papilledema and CSF opening pressure. Hospital-based observational, descriptive study. This study analyzed 122 patients admitted in the department of Neurology (from January 2014 to December 2018) for detailed history, clinical examination, and neuroimaging. CSF manometry and routine CSF analysis were done. All participants met the modified Dandy criteria. Patients with secondary causes of raised ICP and primary ocular pathology were excluded. Descriptive statistics and Chi-square test. Among 122 cases 86 (70.49%) were females. The mean age was 33 years. 62 (50.82%) cases were obese. Headache was the most common symptom (114/122; 93.44%). Bilateral papilledema was noted in 114 (93.44%) cases. Higher grades of papilledema had a correlation with higher CSF opening pressure. Empty sella was the most common radiological finding (100/122; 81.97%). All radiological findings except empty sella had a correlation with higher CSF opening pressure. IIH typically affects obese females of childbearing age group. However, it is not uncommon in the nonobese and male sex. Obesity may not be a dominant risk factor for the development of IIH in the Indian subcontinent. Cases with normal BMI and male sex with clinical features of raised intracranial pressure and normal neuroimaging should also be evaluated for IIH. Cases with refractory headache and empty sella on MRI should be evaluated for IIH.

Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease: A Case Series.

Background and ObjectivesDespite detection of autoantibodies, anti-IgLON5 disease was historically considered a tau-associated neurodegenerative disease, with limited treatment options and detrimental consequences for the patients. Observations in increasing case numbers hint toward underlying inflammatory mechanisms that, early detection provided, open a valuable window of opportunity for therapeutic intervention. We aimed to further substantiate this view by studying the CSF of patients with anti-IgLON5.MethodsWe identified 11 patients with anti-IgLON5 from our database and compared clinical, MRI, and CSF findings with a cohort of 20 patients with progressive supranuclear palsy (PSP) (as a noninflammatory tauopathy) and 22 patients with functional neurologic disorder.ResultsPatients with anti-IgLON5 show inflammatory changes in routine CSF analysis, an increase in B-lymphocyte frequency, and the presence of plasma cells in comparison to the PSP-control group and functional neurologic disease controls. Patients with intrathecal plasma cells showed a clinical response to rituximab.DiscussionOur findings indicate the importance of inflammatory mechanisms, in particular in early and acute anti-IgLON5 cases, which may support the use of immune-suppressive treatments in these cases. The main limitation of the study is the small number of cases due to the rarity of the disease.

The utility of Coccidioides antigen and antibody detection in cerebrospinal fluid in the diagnosis of canine central nervous system coccidioidomycosis.

To evaluate the utility of enzyme immunoassays (EIAs) for the detection of Coccidioides antigen and antibody in CSF in the diagnosis of CNS coccidioidomycosis in dogs. 51 dogs evaluated for CNS disease in a single specialty center in Tucson in 2016. Excess CSF after routine analysis was banked after collection from dogs presented to the neurology service. Samples were tested by EIA for presence of Coccidioides antigen and antibody. Clinical data were collected from medical records retrospectively. 22 dogs were diagnosed with CNS coccidioidomycosis (CCM) or another neurologic disease (non-CCM). These groups of dogs overlapped in the presenting complaints, MRI results, and routine CSF analysis results. Four dogs, all with CCM, had positive antigen EIA results. With clinical diagnosis used as the reference standard, CSF antigen testing had low sensitivity (20%) but high specificity (100%) for diagnosis of CCM. Ten dogs with CCM and 4 dogs with other diagnoses had antibody detected in CSF by EIA. Sensitivity of CSF antibody testing was 46%, specificity was 86%, and positive and negative predictive values for the study population were 71% and 68%, respectively. Diagnosis of CNS coccidioidomycosis in dogs in an endemic region was hampered by overlap of clinical signs with other neurologic disorders and the low sensitivity of confirmatory diagnostics. The evaluated Coccidioides-specific EIAs performed on CSF can aid in the diagnosis. A prospective study is warranted to corroborate and refine these preliminary findings.

Cerebrospinal fluid Gene XPERT (CBNAAT) in children with tuberculous meningitis

SummaryObjectivesTo observe the role of CSF Gene XPERT (CBNAAT) in diagnosis of tuberculous meningitis (TBM) and determine its sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).MethodsA prospective study was done from October 2017 to March 2020. CSF samples of 55 children diagnosed as tuberculous meningitis as per defined clinical and imaging criteria, were subjected to routine CSF analysis, MGIT culture and CBNAAT. Children on prior anti-tuberculous therapy for more than one month were excluded from study.ResultsOf 55 children, meningeal signs were present in 54.5% children. Neurological deficits were present in 47.3%. Common CT brain findings were communicating hydrocephalus followed by infarct and basal exudates. CSF Gene XPERT (CBNAAT) were positive in 9 (16.4%), of which 6 was also culture positive and 3; negative. Two children were rifampicin resistant. Fifteen (27.3%) children had positive CSF culture. Gene XPERT showed sensitivity, specificity, PPV, NPV and diagnostic accuracy of 40%, 92.5%, 66.7%, 80.4% and 78.2% respectively as compared to culture.ConclusionAlthough sensitivity of CSF CBNAAT is low i.e. 40% but positive result not only confirm bacteriological diagnosis of tuberculous meningitis but also reveal about rifampicin sensitivity and resistance for plan of therapy.

Elevated cerebrospinal fluid homocysteine is associated with blood-brain barrier disruption in amyotrophic lateral sclerosis patients.

Homocysteine (Hcy) has been shown to be relevant in the pathogenesis of amyotrophic lateral sclerosis (ALS). Although the CSF Hcy changes were explored in patients with ALS previously, the outcomes were inconsistent, and the permeability of the blood-brain barrier (BBB) may involve in the process. The aim of this study was to investigate the relationship between concentration of Hcy and BBB integrity indicated by CSF/serum albumin ratio (Qalb). CSF and plasma/serum levels of Hcy, folate, and vitamin B12 and other biochemical biomarkers such as albumin, β2-microglobulin, high sensitive-C reactive protein (hs-CRP), microalbumin, immunoglobulin G (IgG), IgM, IgA, and complement 3 and 4 were analyzed in all 31 ALS patients and 34 controls. Routine CSF analysis including cells/leukocytes count, total protein, glucose, and chlorides were also performed. CSF Hcy levels (0.50 ± 0.46 vs 0.25 ± 0.27μmol/L) and Qalb (8.09 ± 3.03 vs 6.39 ± 2.21) were significantly higher in the ALS group than that in controls (P < 0.05). The generalized linear mixed model analysis showed that the CSF Hcy was positively correlated with Qalb in ALS patients (P < 0.05). BBB permeability is increased in ALS patients. CSF Hcy level is associated with BBB integrity. Qalb is a significantly independent predisposing factor for CSF Hcy.

Papilledema in a child with Acute Lymphoblastic Leukaemia during remission-A Case Report

Background: Ocular manifestations of pediatric ALL may be the presenting sign of the disease or may signify leukemic recurrence. Objective: To report papilledema in a diagnosed case of Acute Lymphoblastic Leukaemia during remission. Methods: A case report from a tertiary center in North Karnataka of a 7-year-old male, who is a known case of ALL-L1 and being treated on ICICLE protocol; presents with sudden onset headache and vomiting 7 months after documented remission. Routine blood examination, CSF analysis and MRI brain were performed. Ocular Examination: The anterior segment was normal with visual acuity of 6/6 in both eyes. IDO examination & fundus photography revealed papilledema. Results: The child was diagnosed with secondary viral meningitis based on CSF analysis and the MRI brain showed mild hydrocephalus. Papilledema and general condition of the patient improved on starting steroids and antiviral drugs along with Chemotherapy. Conclusion: Papilledema is a common ocular finding in ALL with CNS involvement, which responded to an established line of management.

Routine CSF analysis may not be indicated in febrile infants with a positive urinalysis

Routine CSF analysis may not be indicated in febrile infants with a positive urinalysis

Rapid in-house method of CSF analysis utilising sedimentation direct from the spinal needle.

To establish the utility of a novel in-house method of CSF analysis using sedimentation cytology direct from the spinal needle for the detection of laboratory-defined pleocytosis. In dogs and cats undergoing routine CSF analysis for investigation of neurological signs, an additional preparation was made at the patient's side by inverting the spinal needle on a slide and sedimenting for at least 1 hour. Nucleated cellularity and differential counts were assessed and compared with "gold-standard" analysis. Variability of cell counts between observers and within slides using the new method was evaluated to optimise the procedure. Using a ×50 objective, at least 10 fields and an average of more than five cells per field were considered appropriate guidelines to achieve correct classification of samples (normal or pleocytosis). The new method had high sensitivity (89%) and specificity (100%) for the detection of laboratory-defined pleocytosis. Agreement on the type of pleocytosis was good. Clinically useful information can be obtained from CSF samples in a patient-side setting without additional equipment. This technique may be of benefit if little fluid is available or if logistical constraints limit the availability of rapid specialist results.

Role of CSF-CRP as a Diagnostic Marker in Neonatal Meningitis

Background: Cerebrospinal fluid C-reactive protein (CSF-CRP) in adults and children has been shown to be useful for the diagnosis of bacterial meningitis; however, it has not been evaluated in neonates. Objective: To study the role of CSF-CRP as a diagnostic marker in neonatal meningitis and determine optimal cut-offs for diagnosis. Study Design: Prospective observational study from June 2017 to December 2017. Methodology: Routine CSF analysis along with CSF-CRP was performed in neonates who qualified for lumbar puncture. Results: At a cut-off value of 3.8 mg/L, CSF-CRP had a sensitivity of 0.96 and a specificity of 0.44, with positive and negative predictive values of 0.63 and 0.91, respectively. Conclusion: CSF-CRP has higher diagnostic efficiency than other CSF markers. At a value of 3.8 mg/L, it has a high sensitivity and a negative predictive value to rule out meningitis.

Low Diagnostic Yield of Routine Cerebrospinal Fluid Analysis in Juvenile Stroke.

Background: The diagnostic value of cerebrospinal fluid (CSF) analysis in juvenile stroke, i.e., stroke in young adult patients, is not well studied. We sought to determine the therapeutic impact of routine CSF-analysis in young adults with acute ischemic stroke or transient ischemic attack (TIA).Methods: We abstracted data from patients with acute cerebral ischemia aged 18–45 years who were consecutively admitted to our stroke center between 01/2008 and 12/2015. We routinely performed CSF-analysis in patients with hitherto unknown stroke etiology after complete diagnostic work up. We assessed the frequency and underlying causes of abnormal CSF-findings and their impact on secondary stroke prevention therapy.Results: Among 379 patients (median [IQR:IQR3-IQR1] age 39 [10:43-33] years, 48% female) with acute ischemic stroke (n = 306) or TIA (n = 73), CSF analysis was performed in 201 patients (53%). Of these, 25 patients (12.4 %) had CSF pleocytosis (leucocyte cell count ≥ 5 Mpt/L), that was rated as non-specific (e.g., traumatic lumbar puncture, reactive pleocytosis) in 22 patients. Only 3 patients (1.5% of all patients who underwent CSF-analysis) with CSF-pleocytosis had specific CSF-findings that were related to stroke etiology and affected secondary stroke prevention therapy. Imaging findings had already suggested cerebral vasculitis in two of these patients.Conclusions: The diagnostic yield of routine CSF-analysis in juvenile stroke was remarkably low in our study. Our data suggest that CSF-analysis should only be performed if further findings raise the suspicion of cerebral vasculitis.

P96. Intrathecal immunglobulin synthesis: Sensitivity of kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands

Objective Intrathecal immunoglobulin synthesis can be present in inflammatory diseases of the central nervous system. The gold standard with highest sensitivity for intrathecal immunglobulin G synthesis is the measurement of oligoclonal bands (OCB). There is rising evidence that the determination of a kappa free light chains (KFLC) index has a similar sensitivity in the diagnostics of diseases associated with detection of OCB in CSF. While detection of OCB is time consuming and the qualitative result relies on experienced evaluators, KFLC measurement is a quantitative method that can be rapidly performed in a highly automated setting. In the present prospective study, we aimed to determine a nonselective optimal cut-off value for determination of the KFLC index in routine clinical CSF analysis. Methods 300 consecutive routine serum and CSF samples were measured on the Siemens BN Prospec using the Siemens N Latex FLC kappa Kit on the BN Prospec. We evaluated the diagnostic performance of KFLC for the prediction of OCB in CSF by quantile regression and ROC analysis. The assessed reference limits were prospectively validated in 100 consecutive samples as well as retrospectively in 50 OCB positive paired patient samples. Results Using quantile regression for establishing the 95% percentile of KFLC quotient in relation to Albumin quotient in OCB negative patients ( n = 266) revealed a sensitivity of 88% and a specificity of 95%. The optimal cut-off value for KFLC index for OCB detection using ROC analysis was 4.93 with a sensitivity of 94% and a specificity of 91%. After extrapolation for highest sensitivity to prevent false negative results the cut-off value for KFLC index was 3.56. Validation of this value prospectively in a second cohort of 100 patient samples revealed 88% sensitivity and 93% specificity. Testing this value retrospectively in 50 OCB positive patients revealed 94% sensitivity. Discussion The KFLC index cut-off value 3.56 has a high diagnostic accuracy for detecting intrathecal immunglobulin G synthesis in comparison with OCB. We conclude that KFLC index determination is suitable for a complementary diagnostic step before applying OCB detection as control and as qualitative evaluation of intrathecal immunglobulin G synthesis. By using automated KFLC tests laboratory work flow is optimized. Multi center studies and comparison of different methods are required to confirm the results of this monocentric study.

A case of Steroid Responsive Encephalopathy associated with Autoimmune Thyroiditis: A Diagnostic Dilemma

We present a case of 42 year-old female, who presented with generalized tonic-clonic seizures with altered sensorium, not responding to antiepileptic medications. She was a diagnosed case of hypothyroidism since last three years and was on replacement therapy. Her systemic examination including the neurological examination did not point to any specific diagnosis. Her routine investigations, brain imaging and CSF analysis were also within normal limits. Thyroid function test revealed raised thyroid stimulating hormone and anti-TPO antibody with normalT4 and T3 levels. Here we considered diagnosis of “Encephalopathy Associated with Autoimmune Thyroid Disease”. She was given intravenous methylprednisolone pulse to which she responded dramatically and seizures were controlled. She was discharged on oral anti-epileptics and steroids in a stable condition.

Abstract TP214: Low Diagnostic Yield of Routine Cerebrospinal Fluid Analysis in Patients with Juvenile Stroke

Background: The diagnostic value of cerebrospinal fluid (CSF) analysis in identification of stroke etiology in patients with juvenile stroke remains not well studied. We sought to determine the frequency and underlying causes of pathological CSF-findings in juvenile stroke patients who underwent CSF-analysis as part of their diagnostic work-up. Methods: We retrospectively abstracted data from consecutive (01/2008 to 12/2015) patients aged 18 to 45 years with acute ischemic stroke or transient ischemic attack. Routine work-up included MRI with dissection-sensitive sequences, Holter-ECG, transthoracic and transesophageal echocardiography, duplex ultrasound of extra- and intracranial arteries and screening for coagulopathies, vasculitis and Fabry disease. CSF-analysis was routinely performed in patients with hitherto cryptogenic stroke. We assessed frequency and causes of pathological CSF-findings including microbiological and virological abnormalities, and their impact on the choice of specific therapy for secondary stroke prevention. Results: Among 379 juvenile patients with acute ischemic stroke or transient ischemic attack, CSF analysis was performed in 201 patients (53%). Of these, 26 patients (13%) had CSF pleocytosis (leucocyte cell count ≥5 Mpt/l). CSF-pleocytosis was rated false positive (e.g. traumatic lumbar puncture, reactive pleocytosis due to acute stroke) after exclusion of specific conditions in 23 of these patients. Only 2 patients with CSF-pleocytosis (1% of patients who underwent CSF analysis) had specific CSF-findings (Lyme disease and neurosyphilis with consecutive cerebral vasculitis) as a cause of stroke and subsequent impact on secondary stroke prevention therapy. One patient had serological evidence of chronic infection with Mycoplasma pneumoniae that was rated as a contributing factor to stroke pathophysiology. Conclusions: The diagnostic yield of routine CSF-analysis in juvenile stroke patients was remarkably low in our study. Our data suggest that CSF-analysis should only be performed if further findings raise the suspicion of cerebral vasculitis.

Do we need to measure specific antibodies in patients with limbic encephalitis?

Limbic encephalitis (LE) is an inflammatory brain disorder that predominantly involves the gray matter of the medial temporal lobes, resulting in mood and behavioral changes, seizures, and difficulty in forming new memories, often with retrograde memory loss.1 In most patients, the presence of an inflammatory process in the medial temporal lobes and hippocampi is visible on MRI fluid-attenuated inversion recovery (FLAIR) sequences and supported by demonstration of pleocytosis in the CSF.2–4 Nevertheless, several infections, systemic inflammatory diseases, and autoimmune mechanisms may lead to this syndrome (table). The recent descriptions of neuronal autoantibodies associated with LE have led to a dependency on antibody testing. However, many patients with autoimmune LE can be diagnosed on clinical grounds.1 This includes careful assessment of the syndrome and ancillary tests that are available in most institutions, such as routine CSF analysis with viral studies, brain MRI, and EEG, which usually shows unilateral or bilateral temporal lobe epileptic discharges or slow activity (for a review on the clinical diagnosis of LE, see reference 1). There are few infectious agents that predominantly affect the medial temporal lobes, and most of the other potential causes of LE shown in the table can be excluded after a thorough clinical history and examination. Some symptoms may even suggest the immunologic subtype of LE (e.g., faciobrachial dystonic seizures and leucine-rich glioma-inactivated 1 [LGI1] antibodies).5

First reported cases of anti-NMDA receptor encephalitis in Vietnamese adolescents and adults

IntroductionAnti-NMDA receptor encephalitis is increasingly recognised as an important differential diagnosis in patients with encephalitis of unknown aetiology. We report the first case series of patients diagnosed in Vietnam. MethodsSamples of CSF from patients with presumed encephalitis but negative microbiological investigations, who exhibited dyskinesia, autonomic instability or psychosis were tested for antibodies against the NR1 subunit of the glutamate (type-NMDA) receptor using an indirect immunofluorescence assay. ResultsOf 99 patients admitted with all-cause encephalitis over an 18month period, 9.1% (n=9 patients, 5 female, median age 28years) had confirmed NMDAR encephalitis. All patients were admitted from one mental health hospital, and the incidence may therefore be an underestimate. Common features included reduction in speech (n=9), catatonia (n=9), convulsions (n=7), dyskinesia (n=9), rigidity (n=9) and autonomic dysfunction (n=7). Aside from a modest lymphocytic pleocytosis, routine CSF analysis was usually normal. No female patient had ovarian teratoma detected by abdominal ultrasound. Most patients were treated with high dose corticosteroids, and one patient received intravenous immunoglobulin. The median duration of hospitalization was 75days and no patient died during admission. ConclusionsAnti-NMDA receptor encephalitis is an important differential diagnosis to consider for patients presenting with acute onset psychiatric symptoms, who develop ensuing seizures, movement or autonomic disorder in Vietnam. A stronger evidence base for management and access to second line immunotherapy agents may help to reduce morbidity from this disease.