ABSTRACT
OBJECTIVES: Oligoclonal bands (OCB) analysis is the reference standard for detecting an intrathecal IgG synthesis. Alongside OCB, free light chains kappa (FLCκ) are considered an additional sensitive biomarker for determining patterns 2 or 3, indicating intrathecal Ig synthesis. However, kFLC IF is not suitable for detecting a monoclonal pattern 5. The primary aim of this study was to evaluate the impact of incorporating FLCκ analysis into routine cerebrospinal fluid (CSF) diagnostics instead of OCB testing on the rate of missed monoclonal IgG detection. METHODS: A two-center retrospective biomarker study was conducted. OCB were identified using isoelectric focusing in polyacrylamide gels followed by silver staining or in agarose gels followed by immunofixation. FLCκ were quantified using nephelometry and FLCκ assay (Siemens). RESULTS: Out of a combined total of 17,755 OCB analyses conducted between 2011 and 2021, a subset of 269 cases (1.5â¯%) exhibited pattern 5. 98 samples (36â¯%), which included 18 samples with intrathecal inflammation as determined by additional OCB pattern 2 were included in the FLCκ analysis. Of those, 16 (89â¯%) had intrathecal FLCκ synthesis. CONCLUSIONS: While FLCκ offers a promising avenue for detecting an intrathecal inflammation, the pattern 5, though rare, remains a valuable additional finding of OCB analysis. A combined approach of FLCκ and OCB analysis is recommended for a comprehensive assessment of the humoral intrathecal immune response.
ABSTRACT
Background: The intrathecal humoral response is the characteristic diagnostic finding in the cerebrospinal fluid (CSF) analysis of patients with multiple sclerosis (MS). Although the average age of MS patients increases, little is known about the sensitivity of diagnostic markers in elderly MS patients. Methods: In this retrospective two-center study, intrathecal free light chains kappa fraction (FLCk IF) and oligoclonal bands (OCB) were studied in a large cohort of patients with early and late onset relapsing (RMS) and progressive (PMS) MS. Furthermore, the humoral immune profile in CSF was analyzed, including the polyspecific intrathecal immune response measured as the MRZ reaction. Results: While the frequency of CSF-specific OCB did not differ between early and late onset RMS and PMS, the sensitivity of positive FLCk IF and absolute FLCk IF values were lower in PMS. The positivity of the MRZ reaction was equally frequent in early and late onset RMS and PMS. PMS patients had higher local IgA concentrations than RMS patients (p = 0.0123). Conclusions: OCB are slightly superior to FLCk IF in progressive MS in terms of sensitivity for detecting intrathecal immunoglobulin synthesis. The MRZ reaction, as the most specific parameter for MS, is also applicable in patients with late onset and progressive MS.
ABSTRACT
BACKGROUND: This observational study was done to develop a score based on clinical predictors that enables a guided decision for the necessity of cerebrospinal fluid (CSF) analysis after first unprovoked epileptic seizures and to validate this score in a retrospective patient cohort. METHODS: Clinical predictors were identified by two panels of epilepsy experts and selected according to content validity ratios. Based on these predictors a score was created and applied to a cohort of patients with first epileptic seizures. RESULTS: The "IDEAL score" consists of 9 items (fever, prolonged disturbance of consciousness, headache, imaging results, cognitive dysfunction, status epilepticus, malignancy, autoimmune encephalitis symptoms) that are collected at two different time points (< 3 h [A-score]; > 3 h [B-score] after hospital admittance). A CSF analysis is recommended, if at least one clinical finding is present, either one of the items evaluated during the acute phase (A-score) or later in the diagnostic process (B-score). In 41 patients (13%) CSF analysis provided essential clues to the cause of the seizure. The combined IDEAL score reached a sensitivity of 98%, a specificity of 53%, a positive predictive value of 24% and a negative predictive value of 99% in this patient cohort. CONCLUSIONS: A CSF analysis after first epileptic seizures provided decisive etiological findings in only 13% of all investigated patients. The IDEAL score offers clinicians a simple and easy-to-implement algorithm to assess the necessity of a CSF analysis, and to prevent unnecessary diagnostic procedures.
Subject(s)
Encephalitis , Epilepsy , Status Epilepticus , Epilepsy/diagnosis , Humans , Retrospective Studies , Seizures/diagnosisABSTRACT
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare, acquired demyelination syndrome that causes cognitive impairment and focal neurological deficits and may be fatal. The potentially reversible disease mainly affects children, often after vaccination or viral infection, but may be seen rarely in adults. OBSERVATIONS: A 50-year-old woman presented with loss of visual acuity of the left eye. Magnetic resonance imaging (MRI) revealed an intra- and suprasellar mass, which was removed successfully. On postoperative day 1, MRI showed gross total resection of the lesion and no surgery-related complications. On postoperative day 2, the patient presented with a progressive left-sided hemiparesis, hemineglect, and decline of cognitive performance. MRI showed white matter edema in both hemispheres. Cerebrospinal fluid analysis revealed mixed pleocytosis (355/µL) without further evidence of infection. In synopsis of the findings, ADEM was diagnosed and treated with intravenous immunoglobulins. Shortly thereafter, the patient recovered, and no sensorimotor deficits were detected in the follow-up examination. LESSONS: Pituitary gland pathologies are commonly treated by transsphenoidal surgery, with only minor risks for complications. A case of ADEM after craniopharyngioma resection has not been published before and should be considered in case of progressive neurological deterioration with multiple white matter lesions.
