CSF IgG Research Articles

Free Kappa light chain in a sample of Egyptian multiple sclerosis patients (a pilot study)

BackgroundMultiple sclerosis is a chronic autoimmune-mediated demyelinating disease of the central nervous system that is usually associated with varying degrees of progressive disability. Free Kappa light chain (FKLC) has attracted growing attention as a significant diagnostic marker of MS. Our aim was to study the diagnostic utility of cerebrospinal fluid free Kappa light chain and related indices in a sample of Egyptian MS patients vs. CSF IgG oligoclonal bands. It was a prospective case–control study of MS patients carried in our hospital during the period from January 2021 till January 2022. Our study carried on 30 patients with multiple sclerosis and other inflammatory neurologic diseases and 20 age and sex matched controls. The study measured FKLC in the CSF and serum sample pairs of patients and control group. Indices calculated using FKLC measured in CSF and serum included; FKLC index, FKLC intrathecal fraction and quotient of FKLC. Indices were used to assess intrathecal synthesis of FKLC considering blood–CSF barrier function. Receiver operating characteristic curve analysis was used to determine diagnostic performance of FKLC and related indices in comparison to CSF–OCB testing.ResultsMeasured FKLC levels as well as its calculated indices have shown statistically significant higher values among MS patients against OIND patients and healthy control group. Both FKLC index and FKLC IF were similarly showing 100% diagnostic sensitivity and 100% diagnostic specificity for MS diagnosis.ConclusionsFKLC biomarkers are proposed to be highly sensitive and easy to detect first-line markers of intrathecal immunoglobulin synthesis with accurate performance and low cost that might prove to be promising diagnostic markers of MS.

Clinical laboratory test utilization of CSF oligoclonal bands and IgG index in a tertiary pediatric hospital

BackgroundCriteria developed for the diagnosis of multiple sclerosis (MS) in adults are also used in the pediatric setting. However, differential diagnosis in pediatric-onset MS (POMS) is distinct from that of adult-onset MS. There is little literature characterizing the utility of oligoclonal bands (OCB) and IgG index in differentiating POMS from other childhood diseases with overlapping clinical presentation which can require immediate treatment. MethodsA retrospective review of all MS panels resulted between March 2022 and May 2023 on patients age ≤ 18 years at one tertiary care pediatric hospital in the northeastern United States was performed with pediatric neurology collaboration to characterize clinical utility (n = 85 cases). ResultsDemyelinating diseases accounted for 31 of 85 total cases (36.5%), 12 of these cases were POMS (14%). Other diagnoses consisted of psychiatric etiologies (17.6%), infectious meningitis/encephalitis (5.9%), and migraine (5.9%). Elevated IgG index was seen in 67% of those with demyelinating diseases, versus only 13% of those with other conditions. Unique OCBs were found in 41% of those with demyelinating diseases, versus only 9% of those with other conditions. Fourteen of 15 patients (93.3%) with psychiatric conditions had normal MS panels. ConclusionsPatients with demyelinating diseases were more likely to have elevated IgG index and unique OCBs versus patients with other conditions. For pediatric hospitals without in-house OCB evaluation, implementation of an in-house IgG index may serve as a rapid screen for differentials that include demyelinating diseases while awaiting OCB results, in the appropriate clinical context. Impact statementIgG index and CSF oligoclonal bands are important tools in the diagnosis of patients with suspected Multiple Sclerosis (MS). In the pediatric population, these markers are used to differentiate pediatric-onset MS (POMS) from other neurologic, psychiatric, and inflammatory diseases that display clinical overlap. The use of these markers in differentiating these conditions has not been thoroughly investigated. We examined the associations between abnormal markers and final diagnoses in pediatric patients undergoing testing for POMS in order to identify trends that may enhance ordering and reporting practices.

Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity

BackgroundGuillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. Materials and methodsWe retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. ResultsIn this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. ConclusionAnti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

Measles to Misfortune: A Case Report on Subacute Sclerosing Panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of children or young adults caused by measles infection. An abnormal immune response to the virus is said to cause brain inflammation, which may last for years. Mortality rate of the disease is around 95%. In this case report, we present the case of a 15-year-old unimmunized boy from rural Assam who presented with progressive sudden jerky movements of his limbs for 2 months, along with difficulty in doing his daily activities and forgetfulness. Although he was initially admitted with a provisional diagnosis of seizure disorder and treated with tab sodium valproate and tab clobazam, his mother, revealed a history of measles infection at 7 years of age. His Electroencephalogram (EEG) reports and CSF IgG measles antibody findings were suggestive of SSPE. He was immediately started on Tab Isoprinosine at adequate doses, but he later succumbed to his illness within 3 months of the onset of symptoms. Immunization of children with the measles vaccine plays a significant role in averting this deadly condition.

Factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorders

ObjectiveTo investigate the factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorder (NMOSD) and provide evidence for disease monitoring and clinical intervention.MethodsEighty-four patients with NMOSD at Xuanwu Hospital Capital Medical University were enrolled in this retrospective study. Before treatment, blood was collected from all patients, and their expanded disability status scores were assessed.ResultsOf the 84 patients assessed, 66 (78.57%) had an expanded disability status scale score < 7, and 18 (21.43%) had scores ≥ 7. The univariate analysis showed that the total bilirubin (TBil), cerebrospinal fluid albumin (CSF ALB), cerebrospinal fluid immunoglobulin G (CSF IgG), QALB, and QIgG levels in the group with scores ≥ 7 were significantly different from those with scores < 7 (P < 0.05). In addition, Spearman’s correlation analysis showed a significant correlation between ALB and expanded disability status scores in patients with NMOSD (P < 0.05), and the multivariate logistic regression analysis showed that TBil was an independent factor influencing the degree of disability in patients with NMOSD (P < 0.05). The receiver operating characteristic curve was constructed using TBil values; the area under the curve of TBil was 0.729 (P < 0.01), and the best cut-off value was 11.015 g/L. Its sensitivity in predicting the severity of disability in NMOSD patients was 51.5% while its specificity was 88.9%.ConclusionTBil is an independent factor that influences the severity of disability in patients with NMOSD. In addition, ALB is closely related to NMOSD severity, and some factors associated with the BBB are significantly increased in severely disabled NMOSD patients.

A dynamic interpretation of κFLC index for the diagnosis of multiple sclerosis: a change of perspective

BackgroundPrevious studies attempted to define the best threshold for κ free light chains (κFLC) index, confirming higher sensitivity (Se) but less specificity (Sp) compared with IgG oligoclonal bands (OCB) for the diagnosis of MS.ObjectiveTo evaluate the diagnostic accuracy of different κFLC index intervals in a miscellaneous cohort of neurological patients, proposing a procedural flowchart for MS diagnosis.MethodsWe analyzed data from 607 patients diagnosed with MS (179), CIS (116), other inflammatory (94) or non-inflammatory neurological diseases (218). Measures of diagnostic accuracy were reported for different potential thresholds of κFLC index, and for IgG OCB and IgG index. Binary logistic regression was to used to calculate the odds of being diagnosed with MS based on each increase of κFLC index.ResultsCSF IgG OCB showed 72.2% Se (CI 95% 68.4–75.7) and 95.2% Sp (CI 95% 93.1–96.7) in discriminating between MS/CIS and controls, with an AUC of 0.84 (CI 95% 0.80–0.87). The highest diagnostic accuracy was reported for κFLC index cut-off of 5.0 (Se = 85.4%, Sp = 90.4%, AUC = 0.88), while a threshold of 11.0 exhibited higher Sp (95.5%, 95% CI 93.1–97.1) than IgG OCB. AUCs for all thresholds between 4.25 and 6.6 were not significantly different from each other, but were significantly higher than the AUC of IgG OCB (p < 0.05). The odds of being diagnosed with MS/CIS increased by 17.1% for each unit increase of κFLC index (OR = 1.17; 95% CI 1.12–1.23; p < 0.001).ConclusionκFLC index performed better than CSF IgG OCB in supporting the diagnosis of MS/CIS, with the advantage of being a cost-effective and quantitative analysis.

Krebs von den Lungen-6 (KL-6) in cerebrospinal fluid from neurosarcoidosis patients.

Krebs von den Lungen-6 (KL-6) is a high molecular weight (MW) glycoprotein mainly secreted by type II pneumocytes because of lung damage or during regeneration. Neurosarcoidosis (NS), where sarcoid granulomas involve the nervous system, occurs in 5-20% of patients with sarcoidosis. No data is currently available on KL-6 in serum or CSF of NS patients. The present study compared KL-6 concentrations in serum and CSF of NS patients versus others with neurodegenerative (ND) or chronic inflammatory demyelinating (DM) diseases. Nine NS patients (mean age 46.2 years, range 16-61 years, M/F 5/4), nine patients with a chronic neurodegenerative disease (mean age 53.1 years, range 37-65 years, M/F 5/4) and nine patients with a chronic demyelinating disease (mean age 46.3 years, range 18-65 years, M/F 5/4) were retrospectively enrolled. Measurable CSF concentrations of KL-6 were detected in 7/9 NS patients but in no ND or DM patients. No significant differences in CSF concentrations of ACE were observed between the three groups (p=0.0819). In NS patients, CSF concentrations of KL-6 were directly correlated with CSF albumin index (r=0.98; p<0.0001), albumin (r=0.979, p=0.0001), IgG (r=0.928, p=0.0009) and total protein concentrations (r=0.945, p=0.0004). KL-6 is a high MW protein, under physiological conditions it is unlikely to cross the blood-brain barrier. We found KL-6 in CSF from NS and not from ND and DM patients. The finding sustains the specificity of changes in KL-6 in this granulomatous disease, suggesting it as a candidate biomarker for recognition of NS.

In Vivo Injection of Anti-LGI1 Antibodies into the Rodent M1 Cortex and Hippocampus Is Ineffective in Inducing Seizures.

Autoimmune encephalitis (AIE) associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is the second most common AIE and is responsible for deleterious neocortical and limbic epileptic seizures. Previous studies demonstrated a pathogenic role of anti-LGI1 antibodies via alterations in the expression and function of Kv1 channels and AMPA receptors. However, the causal link between antibodies and epileptic seizures has never been demonstrated. Here, we attempted to determine the role of human anti-LGI1 autoantibodies in the genesis of seizures by analyzing the impact of their intracerebral injection in rodents. Acute and chronic injections were performed in rats and mice in the hippocampus and primary motor cortex, the two main brain regions affected by the disease. Acute infusion of CSF or serum IgG of anti-LGI1 AIE patients did not lead to the emergence of epileptic activities, as assessed by multisite electrophysiological recordings over a 10 h period after injection. A chronic 14 d injection, coupled with continuous video-EEG monitoring, was not more effective. Overall, these results demonstrate that acute and chronic injections of CSF or purified IgG from LGI1 patients are not able to generate epileptic activity by themselves in the different animal models tested.

Dysregulation of miR-193a serves as a potential contributor to MS pathogenesis via affecting RhoA and Rock1

Multiple sclerosis (MS) is one of the most common neurological diseases that cause chronic inflammation of the central nervous system and demyelination of the myelin sheath. At present, microRNAs (miRNAs) are considered not only a diagnostic and prognostic indicator of diseases but also a new goal in gene therapy. This study aims to find a simple, non-invasive, valuable biomarker for early detection and potential treatment of MS. In the present study, 30 patients with MS were included. The qRT-PCR method was performed to evaluate the expression level of miR-193a, RhoA, and ROCK1. Besides, western blotting was performed to determine the expression level of RhoA and ROCK1 at protein levels. Moreover, we aimed to clarify the possible correlation between miR-193a-5p and its-regulated target genes so that miR-193a-5p mimic was transfected into MS-derived cultured PBMSs, and the expression level of RhoA and ROCK1 were then evaluated by qRT-PCR and Western blotting. In the final step, the correlation between miR-193a-5p and clinicopathological features of patients was investigated. Results showed that miR-193a was decreased while RhoA and ROCK1 were up-regulated in PBMCs obtained from patients with MS compared to the control group. It was also revealed that miR-193a transfection reduced RhoA and ROCK1 expression at mRNA and protein levels. The results from the Chi-square analysis showed that down-regulation of miR-193a was associated with increased CRP level, CSF IgG positivity, and MSSS (Multiple Sclerosis Severity Score), suggesting miR-193a is a potential diagnostic and prognostic indicator. We implied that miR-193a could modulate RhoA and ROCK 1 expression in MS patients, in which its down-regulation leads to increased expression of RhoA and ROCK1 and poor prognosis of patients with MS. Therefore, miR-193a and its associated targets could serve potential prognostic, diagnostic, and therapeutic efficacy in MS patients.

Vitamin D deficiency in relation with the systemic and central inflammation during multiple sclerosis.

During the last decade, vitamin D (VitD) has become a topic of interest in immune regulation, especially in multiple sclerosis (MS) disease. Amongst the wide range of effects reported for this vitamin on the immune system, a regulatory role on cytokines production has been described. Our aim is to analyze the status of VitD and its correlation with the circulating inflammation and the intrathecal humoral response during MS. We analyzed samples of 318 individuals: 108 MS patients and 210 controls. Determination of 25-(OH) VitD3 level in serum was made using electrochemiluminescence method. Circulating inflammatory cytokines (IL-6, IL-8, IL-10, TNF-a, IL12p70 and IL-1b) were investigated using Cytometer Bead Array Technology. The central humoral response was characterized using CSF isofocusing test and IgG Index calculation. As expected, mean value of VitD was significantly lower in MS group (26 nmol/L) than in control group (34.75 nmol/L) (p=0.002), with a severe deficiency in 67% of MS patients. Mean value of VitD was significantly lower in MS female patients. Regarding cytokines, mean value of TNFa was significantly higher in MS patients with oligoclonal bands of IgG in the CSF. IL6 was positively correlated with IgG level in serum of MS patients. Our results support the association of VitD deficiency with MS, especially in female patients of our region. However, the vitamin level seems to not correlate with inflammatory cytokines nor with disability. Interestingly, TNFa and IL6 levels were correlated with the intrathecal synthesis of IgG and the circulating IgG level, respectively.

P014 IgLON5 Disease – A Review of 2 Cases and Sleep Manifestations

Abstract Background IgLON5 disease is a novel autoimmune tauopathy with diverse sleep and neurologic manifestations. Sleep disorder is a common initial presentation and may precede disease progression. Neurological symptoms frequently overlap with extrapyramidal syndromes, motor neuron disease and dementia. Diagnosis is confirmed by anti-IgLON5 IgG in CSF and/or serum. Strong HLA-DRB1*1001 and HLA-DQB1*0501 association supports autoimmune mechanism. Video-PSG is recommended to identify treatable sleep-disordered breathing and parasomnia, present in up to 90% of cases. Treatment is empirical immunomodulation plus supportive cares. Mortality is high due to sudden cardiorespiratory arrest Methods Case reports. Progress to date Case 1 - 70-year-old male with recurrent respiratory arrests of apparent mixed aetiology and progressive dysphagia over 6 months. Preliminary investigations were unremarkable. Tracheostomy was inserted and immunoglobulin empirically commenced. IgLON5 antibodies were identified on CSF. HLA-DRB1*1001 and HLA-DQB1*0501 were positive. Pulse methylprednisolone and rituximab were administered. Intermittent respiratory failure subsided but bulbar symptoms progress. PSG showed NREM and REM parasomnia plus ataxic breathing. Case 2 - 58-year-old man presenting with altered level of consciousness. Examination findings included unsteady gait, strabismus, myoclonus, and truncal instability. IgLON5 IgG was identified on CSF. Sleep study showed ataxic breathing. Patient was treated with IVIG plus rituximab and CPAP. History is suspicious for evolving parasomnia. Intended outcome and impact IgLON5 disease is a newly recognized disorder with sleep manifestations. The ataxic breathing has not been well described. IgLON5 disease teases a novel association between autoimmunity and neurodegeneration.

Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients.

Background and objectivesCerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the ‘glymphatic system’. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients.MethodsWe conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity.ResultsThe median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5).DiscussionIn our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.

Cut-off evaluation of intrathecal oligoclonal bands of IgM in relapsing-remitting multiple sclerosis; a retrospective study

BackgroundMultiple sclerosis (MS) is the most common demyelinating disease and characterized by immunological changes. Oligoclonal bands of IgG in CSF not seen in corresponding serum have been used for many years as part of the diagnostic criteria. However, considerably less is known about the role of IgM, despite several studies showing marked changes to IgM metabolism in MS. Bands of oligoclonal IgM (o-IgM) are more difficult to determine than oligoclonal IgG, thus limiting their study, and there is no agreement as to whether o-IgM in CSF should be part of the clinical work-up of MS. Nevertheless, there is a possibility that such bands might provide a prognostic marker if a cut-off could be established. Materials and methodsIn this pilot study, paired samples of CSF and serum from 37 patients with relapsing-remitting MS (RRMS) and 57 controls with no subsequent signs of neurological disease were analysed for total IgM, and bands of o-IgM were visualised by isoelectric focusing and western blot. Patient records were used to compare mean changes in Expanded Disability Status Scale (EDSS) over a maximum of 17 years. ResultsNone of the controls displayed extra o-IgM in CSF compared to corresponding serum, whereas additional o-IgM band(s) were seen in CSF in most patient samples (70%). After five years of disease, there was a significant difference in the EDSS between patients with no extra o-IgM compared to patients with at least one extra o-IgM band. This difference increased over time. If a cut-off of two or more extra bands of o-IgM in CSF was applied, this difference was not found. ConclusionThese exploratory data suggest that o-IgM support the prognostic potential for RRMS, and though tentative, the occurrence of any bands of o-IgM restricted to CSF seems to result in poorer prognosis. Despite the small size of the groups, the data infer that the absence of CSF-restricted o-IgM is good news for the patient. The results need to be reproduced in a more comprehensive study.

Higher Levels of IgG3 Antibodies in Serum, But Not in CSF, Distinguish Multiple Sclerosis From Other Neurological Disorders.

Increased intrathecal IgG and oligoclonal bands (OCB) are seminal features of multiple sclerosis (MS). Although no such differences in MS blood total IgG antibodies have been reported, serum OCB are a common and persistent finding in MS and have a systemic source. Recent studies showed that IgG3+ B cells and higher levels of serum IgG3 are linked to the development of MS. Additionally, intrathecal IgG synthesis in MS is associated with IgG3 heavy chain gene single nucleotide polymorphisms, and there is a strong relationship between susceptibility to MS and an IgG3 restriction fragment length polymorphism. These studies support the role of IgG3 in disease pathogenesis. Using multiple immunoassays, we investigated levels of total IgG, IgG1, and IgG3 in sera and CSF of 102 MS patients (19 paired CSF and sera), 76 patients with other neurological disorders (9 paired CSF and sera), and 13 healthy controls. We show that higher levels of total IgG and IgG3 antibodies were detected in MS serum, but not in CSF, which distinguishes MS from other inflammatory and non-inflammatory neurological disorders, with Receiver Operating Characteristic (ROC) Curves 0.79 for both IgG3 & total IgG. Our data support the notion that IgG3 antibodies may be a potential candidate for MS blood biomarker development.

Case Report on Subacute Sclerosing Panencephalitis

Introduction: Subacute sclerosing panencephalitis (SSPE), frequently referred as Dawson disease, is a kind of sclerosing panencephalitis, and is an uncommon long-term, continuous cerebral inflammatory condition triggered by a gradual infection with particular faulty types of hyper mutated measles virus.&#x0D; Main Symptoms and/or Important Clinical Findings: Patient came with the complaint of gait abnormalities, sudden fall while walking, loss of speech, staring look, abnormal smile and loss of bladder control, hemiplegia and contracture of all four limbs, seizures, Grade III Malnutrition.&#x0D; The Main Diagnoses, Therapeutic Interventions, and Outcomes: Patient undergone investigation i.e. Blood Test: Hb- 9.8 gm%, TLC- 14,700/mm, Platelet- 2.24 lacs /cu.mm, Total Protein- 8.4 g/dl, HCT- 29.8, Serum Bilirubin- 1.0mg/dl, ALP- 99IU/L, Serum Urea-32mg/dl,SerumCreatinine-0.5mg/dl,SerumSodium-153meq/L,SerumPotassium-.2mmol/L. .CSF igg Measles test was done EEG which revealed burst of periodic complexes with well-preserved back ground activity. Doctor manages with Tab. Valparin 200mg BD, Tab. Frisium 5mg BD, Tab. Baclofen10mgBD,Tab. Samion D3 OD, Syp Q-Carni 5ml BD, Tab. Augment375mg BD.&#x0D; Outcome: After treatment, the child showed some improvement. The patient was admitted to Pediatric Ward No- 22, AVBRH with known case of Subacute sclerosing panencephalitis (SSPE) and he had complaint of swelling over right jaw with caries tooth since4month.

High Dose Steroids as First-Line Treatment Increased the Risk of In-Hospital Infections in Patients With Anti-NMDAR Encephalitis

ObjectiveTo address the effects of high dose steroids on in-hospital infection and neurologic outcome in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients.MethodsWe retrospectively reviewed the clinical data of anti-NMDAR encephalitis patients in West China Hospital, the Third Hospital of Mianyang and Mianyang Central Hospital between October 2011 and August 2020. The development of infections, inflammatory factors, neurologic outcome at discharge and risk factors for in-hospital infection were assessed in patients with and without high dose steroid therapy before and after immunotherapy. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression models were established to assess risk factors for in-hospital infection.ResultsA total of 278 patients with anti-NMDAR encephalitis were included in the study. Thirty-four patients received high dose methylprednisolone (IVMP) therapy only, 84 patients received intravenous immunoglobulin (IVIG) therapy, and 160 patients received IVIG and IVMP therapy. Compared with the IVIG group, IVIG + IVMP group had a higher infection rate (64.38% vs 39.29%, P < 0.001), a higher incidence of noninfectious complications (76.25% vs 61.90%, P = 0.018) and a higher modified Rankin Scale (mRS) score at discharge from the hospital (3 vs 2, P < 0.001). Inflammatory indicators, including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), were higher (9.93 vs 5.65, 6.94 vs 3.47 and 1.47 vs 0.70, respectively, P < 0.001) in the IVIG + IVMP group than in the IVIG group. Moreover, lymphocyte-to-monocyte ratio (LMR) was lower (2.20 vs 2.54, P = 0.047) in the IVIG + IVMP group. The LASSO model showed that mRS score on admission, seizure, body temperature, uric acid (URIC), cerebrospinal fluid immunoglobulin G (CSF IgG), NLR and LMR were risk factors for in-hospital infection. The prediction model exhibited an area under the curve (AUC) of 0.885.ConclusionsHigh dose steroids therapy was significantly associated with higher in-hospital infectious complication rates and a poor short-term prognosis in relatively severe anti-NMDAR encephalitis patients. The established prediction model might be helpful to reduce the risk of in-hospital infection.

Seasonal variability of serum 25-hydroxyvitamin D on multiple sclerosis onset

Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS). However, its effect on the age of disease onset remains unclear. This study examines the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and age of first symptom onset among recently diagnosed MS patients. Serum 25(OH)D was measured from forty MS patients sampled near disease onset. After correcting seasonal variability, the association between 25(OH)D levels, along with other clinical measures such as IgG index, and age at MS onset was examined using multivariable linear regression. Serum 25(OH)D was not correlated with age at onset (P > 0.5). We observed bias among previously reported associations between 25(OH)D and MS disease measures resulting from non-random distribution of sampling by season. After correcting for seasonal 25(OH)D and other clinical measures, only CSF IgG index remained significantly associated with age at disease onset (β = − 5.35, P = 0.028). In summary, we observed no association between age at onset and serum 25(OH)D levels but observed a negative correlation with CSF IgG index, although this will require further investigation.

Clinical and Neuroimaging Changes of Subacute Sclerosing Panencephalitis – Experience 30 Cases in Tertiary Care Center in Bangladesh

Background: Subacute sclersing panencephalitis (SSPE) is a very rare progressive, fatal neurodegenerative disease of the control nervous system of childhood and early adolescence. It is a slow virus disease caused by persistent defective measles virus infection of the brain&#x0D; Objective: To see the clinical andneuro-imaging findings in children with Subacute sclerosing panencephalitis.&#x0D; Methods: This retrospective study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, a tertiary care premier Postgraduate Medical Institution in Bangladesh. Thirty (30) Subacute sclerosing panencephalitis (SSPE) children were evaluated at paediatric neurology ward during the period January 2010 to December 2017. Diagnosis was based on typical clinical characteristic features, the presence of periodic discharges on EEG, demonstration of raised antibody titer against measles in the plasma and cerebrospinal fluid Detected by ELISA in all patients.&#x0D; Results: Total number of studied children were 30. Mean age was 10.2±3.1 year and Male female ratio was 5:1. Most of the patient arrived from poor socio-economic (83.33%) background of rural area (66.67%) of Bangladesh. Among them 46.67% had history of measles infection during early childhood. Progressive deterioration of school performance (50%), gait disturbance (70%), myoclonus (83%) dysarthria (43%) and Ocular manifestations like optic atrophy &amp; papilledema (83.33%) were the main presenting feature of our studied children. All of the patients (100%) showed positive measles specific antibody IgG in CSF and On electroencephalographic findings showed periodic burst suppression in 90.90% cases. Most of the children (56.6%) were in stage II category and other 3.3%, 33.3%,6.6%, were stage I, stage III, stage IV category respectively. Neuroimaging study showed abnormalities in 45.83% cases included periventricular white matter hyper intense signal changes, cortical atrophy and ischaemic change.&#x0D; Conclusion: In our study most of the SSPE patient were in stage II.About half of the patient had history of measles infection during early childhood. Neuroimaging abnormalities found in about half of the cases and majority cases were in stage II. Common neuroimaging abnormalities were periventricular white matter hyper intense signal changes and cortical atrophy.

Author Response: Teaching Video NeuroImages: Pathologic Yawning: A Sign of Brainstem Involvement in Acute Disseminated Encephalomyelitis?

We thank Drs. Fujimori and Nakashima for their comment on our article.1 Their previously published report is certainly an interesting case as well.2 We agree that anti-myelin oligodendrocyte glycoprotein antibody testing is appropriate to include in cases of suspected acute disseminated encephalomyelitis (ADEM). We ordered a broad inflammatory and infectious workup for our patient on both serum and CSF, with the latter being repeated 5 days after initial presentation. Oligoclonal bands were noted in the CSF on 1 of 2 tests. The CSF IgG index was elevated (0.80 initially and 0.68 on follow-up; reference range 0.34–0.66). Anti-AQP4 antibodies were negative. Infectious workup showed negative serology for Epstein-Barr virus and cytomegalovirus. Viral PCR (including enterovirus) was negative, as was CSF mycobacterial culture. Mycoplasma pneumoniae IgM was positive in serum. Bartonella henselae serum IgG was also positive (1:640), but this was not believed to be clinically relevant. We ordered anti-MOG antibodies at the time of initial presentation, but unfortunately these were canceled by the laboratory because of a registration error; we have not reordered the test because the patient has completely recovered and the lesions seen on brain MRI have resolved. At this point, M. pneumoniae infection is the most likely trigger for the ADEM.

Borrelia Invasion of Brain Pyramidal Neurons and Biofilm Borrelia Plaques in Neuroborreliosis Dementia with Alzheimer’s Phenotype

Dementia in Lyme borreliosis complex has been reported, mainly in post-mortem studies without available antemortem evidence of active borrelia infection. Blanc in 2014 studied living patients with Lyme neuroborreliosis dementia and several dementia phenotype illnesses including an Alzheimer’s Phenotype. Herein we report an additional case study of a longitudinal evolution of European neuroborreliosis over eight years from tick bite to mild cognitive disease, to advanced dementia to death with a brain Alzheimer’s disease phenotype and concurrent borrelia deposits in brain Alzheimer’s disease sites at autopsy. Intrathecal borrelia specific antibodies were detected by commercial diagnostic laboratories (antemortem). Molecular autopsy tissue imaging was completed with borrelia specific DNA probes and an immunomicroscopic detection histopathology method. Results: Autopsy showed intact spirochetes, fragmented spirochetes, deposits of borrelia-specific proteins inside plaque lesions and inside of neurons, and borrelia DNA deposits in plaque and neuronal sites. Pure Alzheimer’s disease (without Lewy bodies) was a routine neuropathological finding. CSF evidence for a brain compartment immune response is established here. Intrathecal antibodies to infection presented as oligoclonal total CSF IgG bands (n=twelve increase to n=13 bands) and separate borrelia IgG western blot band analysis in cerebrospinal fluids (seven diagnostic borrelia CSF antibody bands). Blood western blot disclosed triple borrelia species infection; burgdorferi European type (eighteen bands), garinii (twelve bands) and afzelii (eighteen bands). Total borrelia IgG antibodies in blood during life were two hundred-fold higher than normal range. Western blot of cerebrospinal fluid prior to death disclosed 7 protein bands which were not represented in simultaneous blood western blot studies, further validating the intrathecal fingerprint of a separate brain compartment immune response to neuroborreliosis infection. Conclusion: Borrelia protein antigenic stimulation of intrathecal borrelia antibodies was caused by resident deposits of spirochetal protein deposits in plaques, in diseased neurons, and in neuropil brain sites, and in intact brain spirochetes. Deposits of borrelia proteins inside neurons and brain phagocytes and in neuropil sites (invasosomes) confirm remnants of chronic brain infection.