oligoclonal bands
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2022 ◽  
Vol 8 (1) ◽  
pp. 205521732110521
Author(s):  
Benan Barakat ◽  
Steve Messina ◽  
Shreya Nayak ◽  
Roman Kassa ◽  
Elia Sechi ◽  
...  

Background Elevated intrathecal immunoglobulin G (IgG; oligoclonal bands (OCBs)) or IgG in people with progressive motor impairment due to “critical” demyelinating lesions are of uncertain significance. Objective Compare clinical/radiological features of people with “critical” demyelinating lesion-induced progressive motor impairment with/without elevated intrathecal IgG synthesis. Methods A total of 133 people with progressive motor impairment attributable to “critical” demyelinating lesions (corticospinal tract location, consistent with the progressive motor deficit) were compared regarding clinical and radiological presentation with and without ≥2 unique cerebrospinal fluid (CSF) OCB and/or IgG index ≥0.85. Results Ninety-eight (74%) had CSF-elevated OCB and/or IgG index, higher with increased magnetic resonance imaging-lesion burden. No differences were found with/without CSF abnormalities in sex (46 of 98 female (47%) vs. 22 of 35 (63%), p = 0.11), onset-age (median 49 vs. 50 years, p = 0.5), progression from onset (62 of 98 (63%) vs. 25 of 35 (71%)), progression post-relapse (36 of 98 (37%) vs. 10 of 35 (29%), p = 0.4), and duration between demyelinating disease onset and CSF examination (30 (0–359) vs. 48 (0–323) months p = 0.7). “Critical” lesions were radiologically similar, most commonly cervical spine located (72 of 98 (74%) vs. 19 of 35 (54%), p = 0.18) both with/without CSF abnormalities. Conclusions People with “critical” demyelinating lesion-induced progressive motor impairment typically have elevated intrathecal IgG (OCB and/or IgG) and similar clinical and radiological presentation regardless of CSF findings, therefore representing valid presentations of progressive demyelinating disease.


2021 ◽  
pp. 135245852110641
Author(s):  
Gaetano Bernardi ◽  
Tiziana Biagioli ◽  
Paola Malpassi ◽  
Teresa De Michele ◽  
Domizia Vecchio ◽  
...  

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.


Author(s):  
Dharti Meshram ◽  
Sonali Wavare ◽  
Trupti Uke ◽  
Shabnam Sayyad

Schizophrenia is a severe mental illness with a high death rate and significant societal implications. Curative treatments are not available due to a lack of understanding of its etiopathogenesis. The mild encephalitis hypothesis of schizophrenia, established primarily by Karl Bechter and Norbert Müller, is one of the new research hypotheses. According to this theory, a significant subset of schizophrenia patients suffers from a mild but persistent form of encephalitis caused by a variety of etiology ranging from viral infections to traumas to autoimmune illnesses. This inflammatory method is believed to occur in the start or during the course of the disease. The authors present case of a 65-year-old female got admitted in female psychiatric ward AVBR Hospital Sawangi Meghe, Wardha Maharashtra with chief complaint of forgetfulness, interest in environment decline, unable to communicate, poor performance at work, muttering to self, sleep disturbance, seeing people which are not seen other, fearfulness. all necessary investigation done, in mental status examination founded impairment in memory, disorientation cognitive function impairment, RBC count 3.82, WBC count 5300, Hb% 12, calcium 8.1, urea 26, creatinine 0.6, sodium 142, potassium 4.0. Alkaline phosphate 89. HIV, HBSAG non-reactive, A large number of white blood cells in the CSF An MRI that reveals evidence of brain inflammation. There was a slight increase in antinuclear antibody (1: 40 titer). Blood and CSF were positive for oligoclonal bands. The patient was received symptomatic treatment antianxiety, antipsychotic drug alleviates hallucinations and delusion.  Disturbances of consciousness and orientation, catatonia, speech dysfunction, focal neurological signs, epileptic seizures/EEG abnormalities or autonomic dysfunction are warning signs in psychiatric patients which should always induce cerebrospinal fluid analysis with determination of antineuronal autoantibodies. Currently established immunotherapy strategies are summarised, taking into account international expert advice. Guided by clinical warning signs, our qualitative review enables rapid and reliable diagnosis of definite autoimmune encephalitis. This is of high relevance for the affected individuals, since early and sufficiently intense immunotherapy often leads to a good prognosis despite severe illness.


2021 ◽  
Author(s):  
Jonathan Douglas Santoro ◽  
Rebecca Partridge ◽  
Runi Tanna ◽  
Dania Pagarkar ◽  
Mellad Khoshnood ◽  
...  

Abstract Background Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determine if abnormalities are indicative of responses to therapeutic intervention. Methods A retrospective, multi-center, case-control, study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living and/or a new movement disorder) and no other explanation for symptoms. Results Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p= 0.02, 95%CI: 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n=19, 26%), neuroimaging (n=16, 22%) and CSF (n=9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within two years of symptom onset were more likely to have neurodiagnostic abnormalities (p= 0.01, 95%CI: 1.64-37.06). In individuals with neurodiagnostic abnormalities immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR: 4.11, 95%CI: 1.88-9.02). In those with normal neurodiagnostic studies (n=43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. Conclusions This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology.


Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2230
Author(s):  
Ranjani Ganapathy Subramanian ◽  
Dana Horakova ◽  
Manuela Vaneckova ◽  
Balazs Lorincz ◽  
Jan Krasensky ◽  
...  

Background: There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment. Aim: We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures. Methods: Together, 411 patients were screened for eligibility and 93 subjects with ≥2 CSF examinations ≤6 months before and ≥12 months after natalizumab initiation were recruited. The effect of natalizumab on CSF as well as clinical and paraclinical measures was analyzed using adjusted mixed models. Results: Natalizumab induced a decrease in CSF leukocytes (p < 1 × 10−15), CSF protein (p = 0.00007), the albumin quotient (p = 0.007), the IgG quotient (p = 6 × 10−15), the IgM quotient (p = 0.0002), the IgG index (p = 0.0004), the IgM index (p = 0.003) and the number of CSF-restricted oligoclonal bands (OCBs) (p = 0.0005). CSF-restricted OCBs positivity dropped from 94.6% to 86% but 26 patients (28%) had an increased number of OCBs at the follow-up. The baseline to follow-up EDSS and T2-LV were stable; a decrease in the relapse rate was consistent with a decrease in the CSF inflammatory markers and previous knowledge about the effectiveness of natalizumab. The average annualized brain volume loss during the follow-up was −0.50% (IQR = −0.96, −0.16) and was predicted by the baseline IgM index (B = −0.37; p = 0.003). Conclusions: Natalizumab is associated with a reduction of basic CSF inflammatory measures supporting its strong anti-inflammatory properties. The IgM index at the baseline predicted future brain volume loss during the course of natalizumab treatment.


2021 ◽  
pp. 135245852110530
Author(s):  
Susana Otero-Romero ◽  
Pere Carbonell-Mirabent ◽  
Luciana Midaglia ◽  
María Zuluaga ◽  
Ingrid Galán ◽  
...  

Objective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.


2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Simone ◽  
Claudia Palazzo ◽  
Mariangela Mastrapasqua ◽  
Luca Bollo ◽  
Francesco Pompamea ◽  
...  

Introduction: The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS).Objective and Methods: The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab– and in two subgroups MOG-Ab+ with/without encephalopathy.Results: About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17–17.5 vs. 14.7/9–17; p = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; p = 0.013) compared to MOG-Ab–. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab– (p = 0.0006). Higher sNfL levels (p = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8–1,129) and MOG-Ab– (median/range = 11.6/4.3–788) compared to age-matched controls (median/range = 2.98/1–4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17–11.17 vs. 14.16/9.8–17.5; p = 0.004), had higher sNfL levels (median/range:75.24/9.1–1,129 vs. 10.22/6.83–50.53; p = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04–0.69 vs. 0.05/0.04–0.28; p = 0.1) in comparison to those without encephalopathy.Discussion: We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.


2021 ◽  
Vol 57 (2) ◽  
pp. 1-8
Author(s):  
Jolanta Stacherzak-Pawlik ◽  
Paulina Boćko ◽  
Ewa Zagocka

Introduction: Oligoclonal bands are the result of the synthesis of antibodies of limited heterogeneity, that is, directed against one or more specific antigens. Their detection is an important element in the diagnosis of autoimmune diseases. In multiple sclerosis, the diagnostic sensitivity of the determination of oligoclonal bands is high. Aim: The aim of this study is to answer the question whether the detection of oligoclonal bands a more valuable study is than the Tibbling-Link index and reibergram analysis in the context of the diagnosis of multiple sclerosis. Material and methods: Oligoclonal bands were tested in the cerebrospinal fluid and serum from 9 patients suspected of multiple sclerosis using the Sebia HYDRAGEL 3 CSF ISOFOCUSING kit. Results: In 7 out of 9 patients the Tibbling-Link index, reibergram analysis and oligoclonal bands detection clearly indicated intrathecal IgG synthesis. In 2 of 9 patients, detection of oligoclonal bands indicated intrathecal IgG synthesis and the value of Tibbling-Link index and reibergram analysis did not indicated intrathecal IgG production or these tests indicated limit values. Conclusions: The detection of oligoclonal bands in many cases allows for faster diagnosis and introduction of therapy. This test should be an integral part of SM diagnostics.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3056
Author(s):  
Franz Felix Konen ◽  
Philipp Schwenkenbecher ◽  
Konstantin Fritz Jendretzky ◽  
Stefan Gingele ◽  
Kurt-Wolfram Sühs ◽  
...  

Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in particular the kappa isoform of FLC (“KFLC”), has been investigated for more than 40 years. Based on an extensive literature review, we found that an agreement on the correct method for evaluating KFLC concentrations has not yet been reached. KFLC indices with varying cut-off values and blood-CSF-barrier (QAlbumin) related non-linear formulas for KFLC interpretation have been investigated in several studies. All approaches revealed high diagnostic sensitivity and specificity compared with the oligoclonal bands, which are considered the gold standard for the detection of intrathecally synthesized immunoglobulins. Measurement of KFLC is fully automated, rater-independent, and has been shown to be stable against most pre-analytic influencing factors. In conclusion, the determination of KFLC represents a promising diagnostic approach to show intrathecal inflammation in neuroinflammatory diseases. Multicenter studies are needed to show the diagnostic sensitivity and specificity of KFLC in MS by using the latest McDonald criteria and appropriate, as well as standardized, cut-off values for KFLC concentrations, preferably considering non-linear formulas such as Reiber’s diagram.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4738-4738
Author(s):  
Soon Khai Low ◽  
Matthew Ho ◽  
Saad Jamshed

Abstract Introduction: The detection of abnormal protein bands (APB) different from the original monoclonal protein in patients with multiple myeloma (MM) who underwent stem cell transplantation and/or chemotherapy has been reported. These atypical serum immunofixation patterns may be monoclonal (also termed secondary monoclonal gammopathy of undetermined significance) or oligoclonal bands (OB). The prognostic significance of this phenomenon remains controversial. This systematic review and meta-analysis aimed to summarize and analyze the evidence for the association between APB with survival in MM patients. Methods: A systematic search of PubMed, Cochrane, Google Scholar, Medline-Ovid, CINAHL, and ERIC, was conducted using relevant search terms. All studies were screened using predefined selection criteria and critically appraised for quality assessment following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All studies that described the presence of APB, defined as monoclonal spike with heavy or light chain immunoglobulin distinct from the original paraprotein at initial diagnosis of MM, and its associations with survival were included. Studies that reported multivariate adjusted hazard ratios (HR) were further included for meta-analysis. Random-effects model was used to synthesize the pooled HR estimate for the association of APB with survival. Cochran's Q statistics and I2 tests were used to evaluate statistical heterogeneity. Results: A total of 24 out of 181 eligible studies were included for qualitative synthesis. Four studies (including 1115 patients) that reported HR estimates were included in the final meta-analysis. The random-effect summary HR for the progression-free survival among patients with APB was 0.44 (95% CI, 0.31-0.65) with no statistical heterogeneity (I2=0%, p=0.93). The pooled HR for the association with overall survival was 0.31 (95% CI, 0.14-0.66) with moderate statistical heterogeneity (I2=45%; p=0.16) for patients with APB. One study (Silva et al, 2017) only included patients with at least very good partial response while the other three studies reported similar findings of higher occurrence of APB with complete response (Tovar et al, 2013; Jo et al, 2014; Zou et al, 2014). These results are also consistent with the presumed association of APB with complete response as suggested in other studies included in qualitative review. Conclusions: This study indicated a potential prognostic value of APB for favorable outcomes in the context of both overall and progression-free survival in MM patients after treatment. Further research is needed to evaluate the prognostic impact of the sole emergence of APB irrespective of treatment response. Figure 1 Figure 1. Disclosures Jamshed: Takeda: Honoraria.


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