In contrast to relapsing-remitting multiple sclerosis (RRMS), the cerebrospinal fluid (CSF) examination remains a part of the McDonald diagnostic criteria[6]

In contrast to relapsing-remitting multiple sclerosis (RRMS), the cerebrospinal fluid (CSF) examination remains a part of the McDonald diagnostic criteria[6]. (QALB) was elevated in 29.6% of the patients, while intrathecal immunoglobulin G (IgG) oligoclonal Bopindolol malonate bands (OCBs) were detected in 91.1% of the patients. CSF-lactate levels as well as local IgM- and IgA-synthesis were correlated with the yearly disease progression rate, as assessed by EDSS. Conclusion We present the results of the hitherto largest and most detailed CSF biomarker profile in a cohort of 254 patients with PPMS. As reported previously, OCBs are the most sensitive marker for intrathecal IgG synthesis. CSF-lactate concentrations are positively correlated with the progression rate, which might suggest that mitochondrial dysfunction plays a relevant role in PPMS. The negative correlation between intrathecally produced IgM and IgA and disease progression may indicate their hitherto unexplored protective role. Introduction Primary progressive multiple sclerosis (PPMS) is currently considered an entity in multiple sclerosis (MS) disease spectrum, representing about 15% of MS patients[1]. However, PPMS patients differ in many clinical, pathological, and imaging aspects, which explains the necessity of various diagnostic guidelines[2]. Indeed, the diagnostic guidelines for Bopindolol malonate PPMS have been revised over the last few years[3C6]. In contrast to relapsing-remitting multiple sclerosis (RRMS), the cerebrospinal fluid (CSF) examination remains a part of the McDonald diagnostic criteria[6]. At present, many studies addressing the CSF profiles of various MS subtypes have been published. However, these studies had obvious limitations, including a relatively small number of PPMS patients (only one study reported data from more than 100 PPMS patients) as well as limited CSF parameter datasets[7C9]. Therefore, we initiated a multicenter study to systematically collect and analyze detailed CSF profiles containing all parameters commonly assessed in clinical practice in a well-characterized PPMS cohort consisting of more than 250 patients. Methods Data collection CSF Bopindolol malonate data were collected from four university hospitals in Germany (Ulm, Frankfurt, Rostock, and Freiburg). We included PPMS in- and outpatients treated between 2010 and 2015. Each PPMS diagnosis was established according to the 2010 revisions of the McDonald criteria[6] after careful exclusion of relevant differential diagnoses. Lumbar puncture (LP) was performed for diagnostic purposes only with the written consent of all patients. CSF and serum samples were taken on the same day and stored according to consensus protocol for the standardization of CSF collection and biobanking[10]. Records KBTBD6 of all available patients matching these criteria were retrospectively reviewed regarding age at onset, initial neurological complaints, age at first diagnosis, time between clinical onset and diagnosis, expanded disability status scale (EDSS) at the time of LP (EDSSLP), EDSS at the last documented follow-up (EDSSFU), and treatments. Age at clinical onset and initial complaints were obtained from the available medical records and assessed according to the first documented neurological symptoms attributable to the disease. We divided the initial complaints into four main categories: motor, sensory, cerebellar, and other. The other category comprised brain stem syndromes, visual disturbances, cognitive symptoms, complex partial seizures, and bladder dysfunction. The clinical severity of MS was assessed using the EDSS score[11] and determined by a certified EDSS rater. We calculated the yearly progression rate by dividing the EDSSFU over the period between clinical onset and date of the EDSSFU. CSF analysis included basic parameters, such as the total cell count; the CSF-serum quotient for albumin (QALB); quotients Bopindolol malonate of immunoglobulin G, M, and A (IgG, IgM, and IgA); CSF-lactate concentration; oligoclonal bands (OCB) pattern[9]; and measles, rubella and zoster (MRZ) reaction[12]. In cases of repeated LP for the same patient, only the results of the LP used to establish the diagnosis were analyzed. QALB was used as an indicator for the blood-CSF barrier (BCB) function[13], and it was assessed according to the age-related reference range (4+ age/15)[14]. The IgX index was calculated using the following formula: (IgX CSF / IgX Serum: Albumin CSF / Albumin Serum)[15]. IgG-index values > 0.7 [16], IgM-index values > 0.061 [17], and IgA-index values > 0.34 [18] were considered elevated. The concentration of intrathecal IgG, IgM, and IgA -synthesis (IgGloc, IgMloc, and.