Cerebrospinal Fluid Antibody Titers Research Articles

Contribution of cerebrospinal fluid antibody titers and sex to acute cerebral blood flow in patients with anti-NMDAR autoimmune encephalitis.

The objective of this study was to elucidate the contribution of cerebrospinal fluid (CSF) antibody titers (AT) and sex to acute cerebral blood flow (CBF) in patients diagnosed with anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE). Forty-five patients diagnosed with NMDAR AE were recruited from December 2016 to January 2023. The acute CBF in patients with NMDAR AE at the early stage of the disease was analyzed using arterial spin labeling. The groups were compared based on CSF AT and sex. The connectivity of the CBF in the region of interest was also compared between groups. The patients with different CSF AT exhibited varied brain regions with CBF abnormalities compared to the healthy subjects (p = 0.001, cluster-level FWE corrected). High antibody titers (HAT) in CSF contributed to more brain regions with CBF alterations in female patients than in female patients with low antibody titers (LAT) in CSF (p = 0.001, cluster-level FWE corrected). Female patients with HAT in CSF displayed more decreased CBF in the left post cingulum gyrus, left precuneus, left calcarine, and left middle cingulum gyrus than the male patients with the same AT in CSF (p = 0.001, cluster-level FWE corrected). All patients with NMDAR AE showed increased CBF in the left putamen (Putamen_L) and left amygdala (Amygdala_L) and decreased CBF in the right precuneus (Precuneus_R), which suggests that these are diagnostic CBF markers for NMDAR AE. CSF AT and sex contributed to CBF abnormalities in the patients diagnosed with NMDAR AE. Altered CBF might potentially serve as the diagnostic marker for NMDAR AE.

Analysis of the relation between cerebrospinal fluid antibody titers and clinical characteristics in pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis

ObjectiveThis retrospective study aimed to investigate the relationship between cerebrospinal fluid (CSF) antibody titers of N-methyl-d-aspartate receptor (NMDAR), and clinical characteristics in pediatric patients with anti-NMDAR encephalitis. MethodsThe clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by antibody titers in CSF and disease severity, were retrospectively studied. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and prognosis of patients were recorded, and each observed indicator was statistically analyzed. ResultsA total of 103 pediatric anti-NMDAR encephalitis patients were enrolled in the study, including 41 males (39.8%) and 62 females (60.2%) with a mean age of 8.0 ± 4.0 years. The proportion of patients with cognitive dysfunction and the positive pathogen was higher in the high-titer group than in the low-titer group (p = 0.023, p = 0.042). Consciousness disturbance that occurred as an initial symptom or during the course in the severe group was higher than in the non-severe group (p = 0.002, p < 0.001). More patients in the high-titer group received plasma exchange (PE) than in the low-titer group (p = 0.022). The cure rate of patients was higher with PE (65.2%) than with Corticosteroids and (or) intravenous immunoglobulin (58.1%). ConclusionsPatients with symptoms of disturbance of consciousness may be severer. The severity in pediatric anti-NMDAR encephalitis patients was not correlated with anti-NMDAR antibody titers. Patients with high CSF antibody titers had a better prognosis after early PE therapy.

A hospital-based retrospective study: early recognition of neuronal surface antibodies by clinical manifestations and CSF inflammation indicators in patients with unexplained epilepsy

Background There is a lack of actual and comprehensive data on the detection rate of neuronal surface antibodies in patients with unexplained epilepsy in China. Thus, we attempted to analyze the differences in clinical manifestations, cerebrospinal fluid (CSF) characteristics, seizure types and other aspects of antibody-positive and negative patients, to identify suspected antibody-positive epilepsy patients. Methods In total, 137 inpatients with unexplained epilepsy were consecutively included, and neuronal surface antibodies (NSAbs) were detected by serological and/or CSF evaluations. The clinical features and seizure characteristics were analyzed between the NSAb-positive and negative patients. In addition, patients were divided into four groups based on CSF and blood antibody titers. CSF cell count and protein content were analyzed in relation to antibody titers. Results There were 45 (32.8%) patients tested positive for antibodies. Multivariate analyses revealed that age, mental status changes or memory deterioration, CSF protein, CSF cell count, treatment, days of hospitalization, outcome, duration of symptoms before hospitalization, status epilepticus, and number of antiepileptic drugs were significantly associated with the NSAb-positive group and changes in inflammatory indicators in routine CSF analysis were associated with antibody titers. Conclusions A relatively high proportion of patients with unexplained epilepsy have positive NSAbs. Patients with the above clinical characteristics need to be highly suspected of NSAbs positivity and should be tested for antibodies in time to assist treatment. The decrease of CSF cell count and protein content has suggestive value for the decrease of antibody titer, which should be evaluated in the follow-up.

The relevance of NMDA receptor antibody-specific index for diagnosis and prognosis in patients with anti-NMDA receptor encephalitis

The clinical implications of the presence of anti-N-methyl-D-aspartate receptor (NMDAR)-specific intrathecal immunoglobulin G synthesis and whether it determines the diagnosis of anti-NMDAR encephalitis have not been thoroughly investigated yet. Thus, the aim of this study was to investigate whether the detection of intrathecal anti-NMDAR-specific IgG synthesis contributes to the diagnostic confirmation of anti-NMDAR encephalitis, to disease severity, and to prognosis in patients with positive serum anti-NMDAR-IgG. In this study, patients with detectable anti-NMDAR IgG in serum and/or cerebrospinal fluid (CSF) were included and separated into two groups that either met the 2016 criteria by Graus et al. of definite anti-NMDAR encephalitis (n = 27) or did not (n = 15). In a total, of 80 paired CSF/serum samples, antibody titers were titrated manually and end-point titer levels were carefully determined in a blinded manner to the subgroup attribution. The disease course was assessed via the modified Rankin Scale (mRS) and prognosis was estimated by the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. With respect to whether the diagnostic Graus criteria for definite anti-NMDAR encephalitis were fulfilled, a significantly unequal distribution of intrathecal anti-NMDAR antibody-specific synthesis could be shown with a high negative predictive value in case of a negative anti-NMDAR antibody-specific index (NMDAR AI, p = .008. OR = 23.9, sensitivity = 1.0, specificity = 0.4, negative predictive value = 1). A weak correlation was found between the CSF antibody titer and mRS value at the time of sample collection (rs = .37, p = .008, 95% CI [.09, .59]). During the disease course a higher delta-mRS value formed of the mRS at initial presentation minus that at the last recorded presentation correlated with a higher NMDAR AI at first lumbar puncture (rs = − .56, p = .017, 95% CI [− .83, − .11]). No association with the prognostic NEOS score was found. In conclusion, a negative antibody-specific index for anti-NMDAR IgG antibodies has a highly negative predictive value for the diagnosis of anti-NMDAR encephalitis. Yet, a positive NMDAR AI alone does not allow the diagnosis of anti-NMDAR encephalitis.

Autoantibodies detection in anti-N-methyl-D-aspartate receptor encephalitis.

Autoimmune encephalitis (AE) covers a group of neurological diseases caused by autoantibodies. AE is severe but treatable. It has attracted more and more attention currently. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common AE characterized by specific autoantibody mainly against NMDAR subunit 1. Cell-based assays (CBA) on human embryonic kidney 293 (HEK293) cells and immunohistochemistry (IHC) on rat brain tissue have been widely used to detect antibody in patients with AE. However, few studies focused on the overview of these assays detecting autoantibodies in AE. Here we reviewed the detection assays in AE and compared the sensitivity and specificity of CBA and IHC. It's found that IHC got a higher positive rate than CBA in both serum and cerebrospinal fluid (CSF) when screening potential AE, while CBA was more specific. Besides, more positive samples were found in CSF than in serum by either IHC or CBA. Hence, both serum and CSF should be sent to detect antibodies by two assays to avoid misdiagnosis. CSF antibody titers were believed more clinically relevant. When positive results were shown in IHC but negative in CBA, other kinds of antibodies associated AE instead of anti-NMDAR encephalitis should be taken into account. Further studies should pay attention to serum testing for diagnosis or assessment of the disease, as CSF testing is invasive and not always available.

Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation.

Although the diagnosis is mainly dependent on the detection of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in cerebrospinal fluid (CSF) and/or serum, there was no direct correlations between anti-NMDAR antibody titers in CSF and disease severity and prognosis in anti-NMDAR encephalitis patients. Here, we aimed to extensively identify CSF biomarkers related to the occurrence, development, and prognosis of anti-NMDAR encephalitis using a high-throughput proteomic approach. A CSF cytokine antibody array containing 80 cytokines and inflammatory mediators related to immune and inflammatory responses was applied to identify biomarker candidates in individual CSF samples from a well-characterized cohort comprising patients with anti-NMDAR encephalitis (n = 6) and controls (n = 6). Validation and specific detection were performed in an extended cohort consisting of anti-NMDAR encephalitis patients (n = 13), controls (n = 13), and viral encephalitis (n = 13) by enzyme-linked immunosorbent assay (ELISA). Additionally, the levels of some inflammatory proteins in three groups in cohort 2 reported in previous literatures that may be involved in the development of anti-NMDAR encephalitis were also tested by ELISA. Correlations between candidate biomarkers and clinical characteristics of anti-NMDAR encephalitis patients were analyzed. Three differentially expressed cytokines and inflammatory mediators were screened from the 80-cytokine array in cohort 1. Functional enrichment analysis results suggested that these differentially expressed proteins were related to autophagy, immune/inflammatory responses, cell death, and other processes. In cohort 2, the elevations of cellular inhibitor of apoptosis protein-1 (cIAP-1), macrophage colony-stimulating factor (MCSF), CXC chemokine ligand 13 (CXCL13), and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in anti-NMDAR encephalitis were validated by ELISA. Linear regression revealed that the levels of CSF CXCL13 and cIAP-1 were positively correlated with the highest modified Rankin scale (mRS) score in the acute phase (p < 0.05). The level of cIAP-1 was positively correlated with the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score (p < 0.05). These biomarkers show promising functions to evaluate severity or prognosis of anti-NMDAR encephalitis. The biological processes of immune/inflammatory responses, altered levels of autophagy, and the tumornecrosis factor (TNF) signal pathway may be involved in the pathophysiology of anti-NMDAR encephalitis to some extent.

Clinical Relevance of Cerebrospinal Fluid Antibody Titers in Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis. To date, there has been no study on the relationship between antibody (Ab) titers and clinical phenotype. This study aims to clarify the relationship between cerebrospinal fluid Ab titers and clinical manifestations of anti-NMDAR encephalitis at onset. Seventy-six consecutive patients with a definite diagnosis were enrolled. The relationship between Ab titers and different onset symptoms including psychiatric symptoms, seizures, and memory deficits were analyzed. We further investigated the correlation between Ab titers and clinical severity as assessed by the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE), respectively. The Ab titers had a median value of 1:10 (range 1:1–1:100). There was no significant difference in titers among various clinical factors including gender and combination of tumor and other diseases (each p > 0.05). Patients presenting with psychiatric symptoms at onset had higher titers than those with seizures (p = 0.008) and memory deficits (p = 0.003). The mRS scores revealed a significant but weak correlation with Ab titers (r = 0.243, p = 0.034), while CASE scores did not correlate with the titers (p = 0.125). Our findings indicated that the Ab titers were associated with the type of onset symptoms, with a higher level of patients with psychiatric symptoms. Regarding the clinical severity, the titers showed a weak correlation with the mRS, but no correlation with the CASE.

Longitudinal measurement of cerebrospinal fluid neurofilament light in anti-N-methyl-D-aspartate receptor encephalitis.

Background and purposeBiomarkers reflecting the course of patients suffering from anti‐N‐methyl‐D‐aspartate receptor encephalitis (anti‐NMDARE) are urgently needed. Neurofilament light chains (NfL) have been studied as potential markers for neuroaxonal injury mainly in neuroinflammatory diseases, but so far there have been only in a few small reports on anti‐NMDARE. We aimed to compare the longitudinal course of cerebrospinal fluid (CSF)‐NfL levels and anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) antibodies with clinical parameters in six patients with anti‐NMDARE.MethodsLongitudinal measurement of CSF‐NfL levels and CSF anti‐NMDAR antibodies in six patients suffering from anti‐NMDARE was performed.ResultsThe major finding of this study is that most of our patients showed highly elevated NfL, with peak levels considerably delayed to clinical nadir. High NfL levels were associated with hippocampal atrophy but not with tumors detected. Furthermore, we did not find a clear relationship between NfL levels, CSF antibody titer, and CSF inflammatory markers.ConclusionsCSF‐NfL levels do not predict short‐term outcome but rather are associated with intensive care unit stay and extreme delta brushes. However, high CSF‐NFL levels were associated with long‐term outcome. Our data suggest early aggressive immunotherapy to avoid primary and secondary neuroaxonal damage.

Influencing electroclinical features and prognostic factors in patients with anti-NMDAR encephalitis: a cohort follow-up study in Chinese patients

The clinical manifestations of patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis in East China and factors associated with prognosis were analyzed. A retrospective study of 106 patients (58 females; 48 males) with anti-NMDAR encephalitis in East China was carried out from June 2015 to February 2019. Clinical features and factors influencing outcomes were reviewed. Behavioral changes were observed in 74.5% (79/106) of patients, and comprised the initial symptoms in 61.3% (65/106). Seizures were observed in 67% (71/106) of patients, and served as initial symptoms in 31.1% (33/106). A total of 54.9% (39/71) of seizures were focal seizures. More clinical symptoms were observed in female patients than in male patients (P = 0.000). Similarly, background activity (BA) with high cerebrospinal fluid (CSF) antibody titers at the peak stage was more severe in female patients than in male patients (P = 0.000). The Binary logistic regression and receiver operating characteristic (ROC) curve analyses revealed the factors associated with poor outcomes included consciousness disturbance (OR 4.907, 95% CI 1.653–14.562, P = 0.004; area: 65.4%, sensitivity: 44.2%, specificity: 86.5%, P = 0.014), EEG BA (OR 3.743, 95% CI 1.766–7.932, P = 0.001; area: 76.6%, sensitivity: 73%, specificity: 75%, P = 0.000), number of symptoms (OR 2.911, 95% CI 1.811–4.679, P = 0.000; area: 77.1%, sensitivity: 59.5%, specificity: 78.6%, P = 0.000) and CSF antibody titer (OR 31.778, 95% CI 8.891–113.57, P = 0.000; area: 83.9%, sensitivity: 89.2%, specificity: 78.6%, P = 0.000). EEG BA and number of symptoms were associated with CSF antibody titers. Consciousness disturbances, EEG BA, number of symptoms and CSF antibody titers served as predictors of poor outcomes.

Subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive brain disorder caused by mutant measles virus. SSPE affects younger age groups. SSPE incidence is proportional to that of measles. High-income countries have seen substantial decline in SSPE incidence following universal vaccination against measles. SSPE virus differs from wild measles virus. Measles virus genome recovered from the autopsied brain tissues demonstrates clustered mutations in virus genome particularly in the M gene. These mutations destroy the structure and functioning of the encoded proteins. Complete infectious virus particle has rarely been recovered from the brain. Human neurons lack required receptor for entry of measles virus inside the neurons. Recent in vitro studies suggest that mutations in F protein confer hyperfusogenic properties to measles virus facilitating transneuronal viral spread. The inflammatory response in the brain leads to extensive tissue damage. Clinically, SSPE is characterized by florid panencephalitis. Clinically, SSPE is characterized by cognitive decline, periodic myoclonus, gait abnormalities, vision loss, and ultimately to a vegetative state. Chorioretinitis is a common ocular abnormality. Electroencephalography (EEG) shows characteristic periodic discharges. Neuroimaging demonstrates periventricular white matter signal abnormalities. In advanced stages, there is marked cerebral atrophy. Definitive diagnosis requires demonstration of elevated measles antibody titers in cerebrospinal fluid (CSF). Many drugs have been used to stabilize the course of the disease but without evidence from randomized clinical trials. Six percent of patients may experience prolonged spontaneous remission. Fusion inhibitor peptide may, in the future, be exploited to treat SSPE. A universal vaccination against measles is the only proven way to tackle this menace currently.

Analysis of Relation Between Electroclinical Features and Cerebrospinal Fluid Antibody Titers in Patients With anti-NMDAR Encephalitis.

This study aimed to determine the relation between electroclinical features and cerebrospinal fluid (CSF) antibody titers in patients with anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Clinical symptoms and electroencephalography (EEG) at different stages were analyzed in 51 hospitalized patients with anti-NMDAR encephalitis. Behavioral changes were the initial symptoms in 90.9% (20/22) of female patients with high (1:10 or 1:32) CSF antibody titers. A greater number of clinical symptoms were observed in the patients with high CSF antibody titers than in those with low (1:1 or 1:3.2) CSF antibody titers (mean 3.11 ± 1.06 vs 1.62 ± 0.65, P = .000). The number of clinical symptoms was greater in the female patients than in the male patients (mean 3.52 ± 0.98 vs 2.69 ± 1.09, P = .000). At the peak stage, worse background activity (BA) in EEG recordings was observed in patients with high CSF antibody titers than in those with low CSF antibody titers (Mann-Whitney U test, P = .001). The peak-stage BA in EEG was worse in female patients than in male patients (Mann-Whitney U test, P = .000). Modified Rankin scale scores were higher in patients with high CSF antibody titers than in those with low CSF antibody titers (mean 2.62 ± 1.42 vs 0.75 ± 0.97, P = .000). Brush patterns and constant chewing were observed primarily in female patients with high CSF antibody titers. Epileptic discharges were located predominately in the frontal regions and were noted to vary. The electroclinical features of patients with anti-NMDAR encephalitis were associated with gender and CSF antibody titers.

Allergy in patients with anti-N-methyl-d-aspartate receptor encephalitis

Background and objectiveAllergy is a potential outcome of dysregulated immune system. Previous studies have shown the association of allergy and autoimmune diseases, however, there is few study to investigate the relationship between allergy and anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Thus, we investigate the rate of allergy in patients with anti-NMDAR encephalitis and analyze the risk factors. MethodThe rate of allergy was investigated in patients with anti-NMDAR encephalitis and was compared with patients with virus encephalitis. The clinical cutaneous characters were described in details. All patients with anti-NMDAR encephalitis were divided into allergic and nonallergic group. Clinical factors were compared in the two groups, and logistic regression model was also used to analyze possible risk factors of allergy. ResultsPatients with anti-NMDAR encephalitis had a higher rate of allergy than those with viral encephalitis (22.1% vs 9.2%, odds ratio (OR)=3.23, confidence interval (CI)=1.40–7.42, P=0.006). In patients with anti-NMDAR encephalitis, allergic patients exhibited longer days in hospital (30days vs 22days, P=0.005) and higher occurrence of decreased consciousness (81.5% vs 58.9%, P=0.031), higher rate of complications (77.8% vs 57.9%, P=0.046) and abnormal electroencephalography (EEG) (100% vs 78.6%, P=0.021) than patients without allergy. Cerebrospinal fluid (CSF) antibody titers of allergic patients during the disease course were also higher than nonallergic patients (P=0.004). However, further logistic regression analysis did not reveal independent predictors of allergy. ConclusionsPatients with anti-NMDAR encephalitis show higher allergic rate than those with virus encephalitis. Patients with allergy show higher CSF antibody titers and greater illness severity. However, the final outcome of anti-NMDAR encephalitis was not influenced.

THREE TESLA MAGNETIC RESONANCE IMAGING FINDINGS IN 12 CASES OF CANINE CENTRAL EUROPEAN TICK-BORNE MENINGOENCEPHALOMYELITIS.

Central European tick-borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick-borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick-borne encephalomyelitis, history of a stay in endemic areas for tick-borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick-borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow-up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2-weighted sequences compared to white matter, iso- to hypointense in T1-weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick-borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics.

Epstein-Barr virus persistence and reactivation in neuromyelitis optica

ObjectiveEpstein-Barr virus (EBV) infection has been thought to be a key environmental factor in the development of multiple sclerosis (MS). The aim of this study is to investigate the association...

Familial clusters of HTLV-1-associated myelopathy/tropical spastic paraparesis.

ObjectiveHTLV-1 proviral loads (PVLs) and some genetic factors are reported to be associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, there are very few reports on HAM/TSP having family history. We aimed to define the clinical features and laboratory indications associated with HAM/TSP having family history.MethodsRecords of 784 HAM/TSP patients who were hospitalized in Kagoshima University Hospital and related hospitals from 1987 to 2012 were reviewed. Using an unmatched case-control design, 40 patients of HAM/TSP having family history (f-HAM/TSP) were compared with 124 patients suffering from sporadic HAM/TSP, who were admitted in series over the last 10 years for associated clinical features.ResultsOf the 784 patients, 40 (5.1%) were f-HAM/TSP cases. Compared with sporadic cases, the age of onset was earlier (41.3 vs. 51.6 years, p<0.001), motor disability grades were lower (4.0 vs. 4.9, p = 0.043) despite longer duration of illness (14.3 vs. 10.2 years, p = 0.026), time elapsed between onset and wheelchair use in daily life was longer (18.3 vs. 10.0 years, p = 0.025), cases with rapid disease progression were fewer (10.0% vs. 28.2%, p = 0.019), and protein levels in cerebrospinal fluid (CSF) were significantly lower in f-HAM/TSP cases (29.9 vs. 42.5 mg, p<0.001). There was no difference in HTLV-1 PVLs, anti-HTLV-1 antibody titers in serum and CSF, or cell number and neopterin levels in CSF. Furthermore, HTLV-1 PVLs were lower in cases with rapid disease progression than in those with slow progression in both f-HAM/TSP and sporadic cases.ConclusionsWe demonstrated that HAM/TSP aggregates in the family, with a younger age of onset and a slow rate of progression in f-HAM/TSP cases compared with sporadic cases. These data also suggested that factors other than HTLV-1 PVLs contribute to the disease course of HAM/TSP.

Optic neuritis and rapidly progressive necrotizing retinitis as the initial signs of subacute sclerosing panencephalitis: a case report with clinical and histopathologic findings

We report a case of subacute sclerosing panencephalitis (SSPE) presenting first with optic neuritis and rapidly progressive necrotizing retinitis at the posterior pole. We reviewed the clinical, laboratory, photographic, angiographic, and histopathologic records of a patient with SSPE. A 15-year-old girl was referred after rapid loss of vision due to optic neuritis and macular necrosis in the right eye. She had a history of cardiac valve surgery, but had no systemic symptoms and extensive work-up was unrewarding. Contralateral involvement with rapidly progressive optic neuritis and macular necrotizing retinitis prompted retinochoroidal biopsy of the right eye, which revealed necrosis of inner retinal layers and perivascular lymphoplasmocytic infiltration with intact choroid and outer retina without any findings of inclusion bodies, microorganisms, or atypical cells. The diagnosis was based on histopathologic findings consistent with SSPE, and detection of elevated measles antibody titers in cerebrospinal fluid and serum. It was further confirmed by development of typical electroencephalography pattern at 6 months and neurological symptoms at 4-year follow-up. Clinicians need to be aware that optic neuritis and necrotizing retinitis at the posterior pole may be the presenting features of SSPE.

Four-Year Course of Serum and Cerebrospinal Fluid Antibody Titers in a Patient with Anti-NMDAR Encephalitis

The natural long-term course of antibody titers in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis remains uncertain. We measured anti-NMDAR antibodies in a patient with anti-NMDAR encephalitis who had a severe disease course for 5 years. The antibody titers in the first serum and cerebrospinal fluid (CSF) samples were 1:1600 and 1:320, respectively. During gradual recovery, the serum and CSF titers initially decreased, but remained unchanged during the last 2 years. Four years after the onset of disease, the serum and CSF antibody titers were 1:200 and 1:80, respectively. Anti-NMDAR antibodies can persist for prolonged periods in patients with a poor clinical course.

Accurate Antemortem Diagnosis of Equine Protozoal Myeloencephalitis (EPM) Based on Detecting Intrathecal Antibodies againstSarcocystis neuronaUsing the SnSAG2 and SnSAG4/3ELISAs

Recent work demonstrated the value of antigen-specific antibody indices (AI and C-value) to detect intrathecal antibody production against Sarcocystis neurona for antemortem diagnosis of equine protozoal myeloencephalitis (EPM). The study was conducted to assess whether the antigen-specific antibody indices can be reduced to a simple serum : cerebrospinal fluid (CSF) titer ratio to achieve accurate EPM diagnosis. Paired serum and CSF samples from 128 horses diagnosed by postmortem examination. The sample set included 44 EPM cases, 35 cervical-vertebral malformation (CVM) cases, 39 neurologic cases other than EPM or CVM, and 10 non-neurologic cases. Antibodies against S. neurona were measured in serum and CSF pairs using the SnSAG2 and SnSAG4/3 (SnSAG2, 4/3) ELISAs, and the ratio of each respective serum titer to CSF titer was determined. Likelihood ratios and diagnostic sensitivity and specificity were calculated based on serum titers, CSF titers, and serum : CSF titer ratios. Excellent diagnostic sensitivity and specificity was obtained from the SnSAG2, 4/3 serum : CSF titer ratio. Sensitivity and specificity of 93.2 and 81.1%, respectively, were achieved using a ratio cutoff of ≤100, whereas sensitivity and specificity were 86.4 and 95.9%, respectively, if a more rigorous cutoff of ≤50 was used. Antibody titers in CSF also provided good diagnostic accuracy. Serum antibody titers alone yielded much lower sensitivity and specificity. The study confirms the value of detecting intrathecal antibody production for antemortem diagnosis of EPM, and they further show that the antigen-specific antibody indices can be reduced in practice to a simple serum : CSF titer ratio.

Anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma: clinical presentation, diagnosis, treatment, and surgical management

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly recognized autoimmune disorder with prominent neuropsychiatric symptoms, usually part of a paraneoplastic syndrome. We present two cases of patients with anti-NMDA receptor encephalitis related to ovarian teratoma. Our two patients developed neuropsychiatric symptoms and later evolved into a state of impaired consciousness. The physical examinations and investigations, including routine laboratory testing, a basic metabolic panel, MRI of the brain, and the cerebrospinal fluid (CSF) analysis were non-specific. CT scan and MRI of the pelvis revealed a calcified tumor that was suspected to be an ovarian teratoma in both patients. Each patient underwent salpingo-oophorectomy, and histopathological diagnosis of the patient of case 1 was mature cystic teratoma and that of case 2 was immature teratoma. Finally, the result of the anti-NMDA receptor antibody assay demonstrated high antibody titers in CSF, leading to definite diagnosis of anti-NMDA receptor encephalitis triggered by ovarian teratoma in both cases. Given that anti-NMDA receptor encephalitis often results in severe symptoms regardless of the tumor size of the ovarian teratoma, accurate diagnosis of the teratoma followed by prompt surgical resection of the tumor is crucial for the treatment of anti-NMDA receptor encephalitis. The clinical presentation, diagnosis, treatment, surgical management, and prognosis, as well as a review of this disorder, were discussed in this case conference.

Importance of Diazepam Administration During Electroencephalography in the Differential Diagnosis of Cortical Visual Loss

A 14-year-old boy presented with acute visual loss due to cortical blindness. Two weeks after the visual symptoms, the patient developed behavioral abnormalities. Brain magnetic resonance imaging (MRI) revealed hyperintense lesions at parieto-occipital lobes on T2-weighted and fluid attenuated inversion recovery images. Sleep and awake electroencephalography (EEG) were normal, but diazepam administration revealed bilateral periodic synchronous complexes occurring every 20 to 30 seconds. Elevated measles antibody titers in cerebrospinal fluid confirmed the diagnosis of subacute sclerosing panencephalitis. We conclude that visual loss due to cortical blindness is an important finding of subacute sclerosing panencephalitis. Diazepam administration during EEG should be a part of investigation in cases with unexplained cortical blindness.