IgG and kappa free light chain CSF/serum indices: evaluating intrathecal immunoglobulin production in HIV infection in comparison with multiple sclerosis.

OBJECTIVES: To study intrathecal kappa free light chain (KFLC) synthesis in people living with HIV (PLWH) in comparison with multiple sclerosis (MS). METHODS: Cross-sectional analysis including 56 untreated and 150 well treated PLWH, and compared with 58 controls, and 223 MS patients. RESULTS: Elevated serum/cerebrospinal fluid (CSF) IgG and KFLC indices were observed in untreated PLWH. Seventy percent of untreated PLWH had KFLC index above 6.1, a threshold associated with clinically isolated syndrome/MS diagnosis. No association was found between KFCL index and CSF markers of neuronal injury in either PLWH or MS patients. CONCLUSIONS: HIV-related immune system dysfunction is often associated with an elevated KFLC index akin to those observed in MS. HIV infection should be considered as a differential diagnosis for patients presenting with neurological symptoms and increased intrathecal immunoglobulin synthesis.

Diagnostic MALDI-TOF MS can differentiate between high and low toxic Staphylococcus aureus bacteraemia isolates as a predictor of patient outcome.

Staphylococcus aureus bacteraemia (SAB) is a major cause of blood-stream infection (BSI) in both healthcare and community settings. While the underlying comorbidities of a patient significantly contributes to their susceptibility to and outcome following SAB, recent studies show the importance of the level of cytolytic toxin production by the infecting bacterium. In this study we demonstrate that this cytotoxicity can be determined directly from the diagnostic MALDI-TOF mass spectrum generated in a routine diagnostic laboratory. With further development this information could be used to guide the management and improve the outcomes for SAB patients.

The History of Diagnosis and Treatment of MS: a Brief Overview.

PURPOSE OF REVIEW: This overview of the history of diagnosis and treatment of multiple sclerosis serves as an introduction to the rich history of multiple sclerosis, and shows we are on a continuum of incremental advances that date back centuries. RECENT FINDINGS: The current understanding of MS demonstrates a dramatic series of advances and this brief historical overview will provide some context for these discoveries. Although cases we would now recognize as multiple sclerosis can be found in older literature and diaries, the contribution of Jean-Martin Charcot at the Salpêtrière in Paris in 1868 was to frame the clinical and pathological features of a disorder he called la sclérose en plaque disséminées. Soon after, reports came from many countries. Over the next half-century, the diagnosis was a clinical conclusion with no confirmatory tests. Some CSF and evoked potential tests later helped but it remained for the MRI imaging and oligoclonal banding to substantially aid the clinical diagnosis. It is tempting to think that therapy is new in MS, but in previous centuries, hundreds of drugs, procedures, and surgeries were applied to patients with MS, many more than we use today. It remained for the development of the randomized clinical trial to show which therapies were beneficial and safe. Everything changed in 1993 when the first of a long list of new therapies was approved, therapies that were shown to alter the activity and outcome of the disease.

The "central vein sign" in patients with diagnostic "red flags" for multiple sclerosis: A prospective multicenter 3T study.

BACKGROUND: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective. OBJECTIVES: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases. METHODS: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory "red flags" (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed. RESULTS: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%; p < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value. CONCLUSION: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features.

IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis.

Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS and has been associated in previous smaller studies to increased disability and disease activity. Here, we wanted to further address IL-6 as a possible CSF biomarker of MS by investigating its detectability in a large cohort of 534 MS patients and in 103 individuals with other non-inflammatory neurological diseases. In these newly diagnosed patients, we also explored correlations between IL-6 detectability, MS phenotypes, and disease characteristics. We found that IL-6 was more frequently detectable in the CSF of MS patients compared with their control counterparts as significant differences emerged between patients with Clinically isolated syndrome (CIS), Relapsing-remitting (RR), and secondary progressive and primary progressive MS compared to non-inflammatory controls. IL-6 was equally present in the CSF of all MS phenotypes. In RR MS patients, IL-6 detectability was found to signal clinically and/or radiologically defined disease activity, among all other clinical characteristics. Our results add further evidence that CSF proinflammatory cytokines could be useful for the identification of those MS patients who are prone to increased disease activity. In particular, IL-6 could represent an interesting prognostic biomarker of MS, as also demonstrated in other diseases where CSF IL-6 was found to identify patients with worse disease severity.

Multiple Sclerosis Re-Examined: Essential and Emerging Clinical Concepts.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by exacerbations of neurological dysfunction due to inflammatory demyelination. Neurologic symptoms typically present in young adulthood and vary based on the site of inflammation, although weakness, sensory impairment, brainstem dysfunction, and vision loss are common. MS occurs more frequently in women and its development is complex-genetics, hormones, geography, vitamin D, and viral exposure all play roles. Early MS is characterized by relapsing-remitting course and inflammation of the white matter, although as patients age, the disease often transitions to a pathologically distinct secondary progressive phase with gradual disability accrual affecting gait, coordination, and bladder function. A minority of patients (10%) have disease that is progressive at onset. In the past decade, there has been a remarkable expansion in disease-modifying therapy for MS, but treatment of progressive disease remains a challenge. This article reviews foundational concepts in MS and emerging work that has reshaped understanding of the disease, providing new insight for therapeutic advance.