Multiple Sclerosis Journal - October 2017 - 1497

MM Voortman, T Stojakovic et al.
on the levels of KFLC and only a few studies have
also studied LFLC in MS.6-8,12,13
In addition to supporting the diagnostic potential of
FLC in MS we therefore investigated whether quantitative analysis of FLC could add prognostic information. In this respect, we analysed both KFLC and
LFLC and calculated the KFLC/LFLC ratio. As the
presence of CSF OCB modifies the prognosis of
patients with CIS, we wanted to exclude this confounding factor and determine whether quantitative
assessment of FLC could add additional information
on disease prognosis against the background of OCB
positivity. Besides using clinical findings as a marker
of disease progression, we also attempted to substantiate associations of FLC with magnetic resonance
imaging (MRI) markers of disease progression.
Patients, materials and methods
This study was approved by the ethics committee of
the Medical University of Graz, Austria. All participants gave written informed consent.
Patients and controls
This study included patients (n = 61) who were seen at
the MS outpatient clinic of the Department of
Neurology/Medical University of Graz and fulfilled
the following criteria: (1) a diagnosis of CIS suggestive of MS or relapsing-remitting multiple sclerosis
(RRMS) according to available criteria;1,14 (2) availability of CSF and serum samples from a diagnostic
lumbar puncture and parallel blood sampling; (3)
presence of OCB in CSF and not in serum; (4) no
MS-specific treatment prior to sampling, except for
corticosteroids; (5) MRI examination close to sampling; and (6) clinical follow-up.

parallel blood sampling, (3) all routine-diagnostic
variables measured in CSF and serum within normal
range,15 and (4) no immunomodulatory or immunosuppressive treatment prior to sampling.
Clinical assessment and follow-up
Demographic and clinical data recorded included age,
gender, age at disease onset, time between the diagnosis of CIS and conversion to CDMS (upon second
relapse), and degree of disability as determined by the
Expanded Disability Status Scale (EDSS).16
Subsequent to sampling and diagnosis, patients were
followed by experienced neurologists during scheduled follow-up visits.
Relapses were recorded over time according to previous definition, that is, at least one neurological symptom (re)appears or an old symptom attributed to MS
worsens for at least 24 hours succeeding a stable or
improving neurological state during at least 30 days.17
Upon confirmation of a relapse during neurological
examination, patients were usually treated with steroid pulses of either 3- or 5-day 1000 mg/day methylprednisolone. Thus, at baseline, 14 patients received
corticosteroids within 30 days prior to CSF sampling
and none were on long-term disease-modifying treatments (DMTs). At the time of the last available follow-up (time since lumbar puncture median, 4.8 years;
interquartile range (IQR), 1.5-6.5 years), 37 patients
received DMTs, including interferon beta (n = 19),
glatiramer acetate (n = 10), natalizumab (n = 7) and
fingolimod (n = 1).

Patients were considered to be in an active state of
disease at the initial examination, that is, baseline, if
lumbar puncture was performed within 14 days of a
clinical attack. Patients with primary or secondary
progressive MS were not considered.

CSF and serum sampling and analyses
At lumbar puncture, a total volume of 6-10 mL of
CSF and 8 mL of peripheral blood were obtained from
each patient. After routine diagnostic work-up, excess
volumes of CSF/serum pairs were stored immediately
at −80°C until further analyses. All samples were handled and stored according to international consensus
guidelines18 and sample analyses were performed by
trained analysts blinded to clinical information.

Controls (n = 60) consisted of individuals who were
seen at the outpatient clinic of the Department of
Neurology/Medical University of Graz and met the
following profile: (1) diagnosis of a neurological disease of non-inflammatory aetiology (cranial/peripheral palsy - non-inflammatory neurological disease
controls; headache or sensory disturbances - symptomatic controls),15 (2) availability of CSF and serum
samples from a diagnostic lumbar puncture and

Routine diagnostic work-up of CSF and serum were
performed as follows: CSF white cell count was determined using the Fuchs Rosenthal Counting Chamber.
Levels of albumin and IgG, IgA and IgM were determined by nephelometry using the Beckman Coulter
Image 800 analyser (Beckman Coulter Inc., Brea, CA,
USA). The CSF/serum quotient of albumin (Q alb)
was calculated in order to assess the blood CSF barrier
function.19 Intrathecal IgG synthesis was assessed

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Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017

Contents
Multiple Sclerosis Journal - October 2017 - Cover1
Multiple Sclerosis Journal - October 2017 - Cover2
Multiple Sclerosis Journal - October 2017 - Contents
Multiple Sclerosis Journal - October 2017 - ii
Multiple Sclerosis Journal - October 2017 - iii
Multiple Sclerosis Journal - October 2017 - 1436
Multiple Sclerosis Journal - October 2017 - 1437
Multiple Sclerosis Journal - October 2017 - 1438
Multiple Sclerosis Journal - October 2017 - 1439
Multiple Sclerosis Journal - October 2017 - 1440
Multiple Sclerosis Journal - October 2017 - 1441
Multiple Sclerosis Journal - October 2017 - 1442
Multiple Sclerosis Journal - October 2017 - 1443
Multiple Sclerosis Journal - October 2017 - 1444
Multiple Sclerosis Journal - October 2017 - 1445
Multiple Sclerosis Journal - October 2017 - 1446
Multiple Sclerosis Journal - October 2017 - 1447
Multiple Sclerosis Journal - October 2017 - 1448
Multiple Sclerosis Journal - October 2017 - 1449
Multiple Sclerosis Journal - October 2017 - 1450
Multiple Sclerosis Journal - October 2017 - 1451
Multiple Sclerosis Journal - October 2017 - 1452
Multiple Sclerosis Journal - October 2017 - 1453
Multiple Sclerosis Journal - October 2017 - 1454
Multiple Sclerosis Journal - October 2017 - 1455
Multiple Sclerosis Journal - October 2017 - 1456
Multiple Sclerosis Journal - October 2017 - 1457
Multiple Sclerosis Journal - October 2017 - 1458
Multiple Sclerosis Journal - October 2017 - 1459
Multiple Sclerosis Journal - October 2017 - 1460
Multiple Sclerosis Journal - October 2017 - 1461
Multiple Sclerosis Journal - October 2017 - 1462
Multiple Sclerosis Journal - October 2017 - 1463
Multiple Sclerosis Journal - October 2017 - 1464
Multiple Sclerosis Journal - October 2017 - 1465
Multiple Sclerosis Journal - October 2017 - 1466
Multiple Sclerosis Journal - October 2017 - 1467
Multiple Sclerosis Journal - October 2017 - 1468
Multiple Sclerosis Journal - October 2017 - 1469
Multiple Sclerosis Journal - October 2017 - 1470
Multiple Sclerosis Journal - October 2017 - 1471
Multiple Sclerosis Journal - October 2017 - 1472
Multiple Sclerosis Journal - October 2017 - 1473
Multiple Sclerosis Journal - October 2017 - 1474
Multiple Sclerosis Journal - October 2017 - 1475
Multiple Sclerosis Journal - October 2017 - 1476
Multiple Sclerosis Journal - October 2017 - 1477
Multiple Sclerosis Journal - October 2017 - 1478
Multiple Sclerosis Journal - October 2017 - 1479
Multiple Sclerosis Journal - October 2017 - 1480
Multiple Sclerosis Journal - October 2017 - 1481
Multiple Sclerosis Journal - October 2017 - 1482
Multiple Sclerosis Journal - October 2017 - 1483
Multiple Sclerosis Journal - October 2017 - 1484
Multiple Sclerosis Journal - October 2017 - 1485
Multiple Sclerosis Journal - October 2017 - 1486
Multiple Sclerosis Journal - October 2017 - 1487
Multiple Sclerosis Journal - October 2017 - 1488
Multiple Sclerosis Journal - October 2017 - 1489
Multiple Sclerosis Journal - October 2017 - 1490
Multiple Sclerosis Journal - October 2017 - 1491
Multiple Sclerosis Journal - October 2017 - 1492
Multiple Sclerosis Journal - October 2017 - 1493
Multiple Sclerosis Journal - October 2017 - 1494
Multiple Sclerosis Journal - October 2017 - 1495
Multiple Sclerosis Journal - October 2017 - 1496
Multiple Sclerosis Journal - October 2017 - 1497
Multiple Sclerosis Journal - October 2017 - 1498
Multiple Sclerosis Journal - October 2017 - 1499
Multiple Sclerosis Journal - October 2017 - 1500
Multiple Sclerosis Journal - October 2017 - 1501
Multiple Sclerosis Journal - October 2017 - 1502
Multiple Sclerosis Journal - October 2017 - 1503
Multiple Sclerosis Journal - October 2017 - 1504
Multiple Sclerosis Journal - October 2017 - 1505
Multiple Sclerosis Journal - October 2017 - 1506
Multiple Sclerosis Journal - October 2017 - 1507
Multiple Sclerosis Journal - October 2017 - 1508
Multiple Sclerosis Journal - October 2017 - 1509
Multiple Sclerosis Journal - October 2017 - 1510
Multiple Sclerosis Journal - October 2017 - 1511
Multiple Sclerosis Journal - October 2017 - 1512
Multiple Sclerosis Journal - October 2017 - 1513
Multiple Sclerosis Journal - October 2017 - 1514
Multiple Sclerosis Journal - October 2017 - 1515
Multiple Sclerosis Journal - October 2017 - 1516
Multiple Sclerosis Journal - October 2017 - 1517
Multiple Sclerosis Journal - October 2017 - 1518
Multiple Sclerosis Journal - October 2017 - 1519
Multiple Sclerosis Journal - October 2017 - 1520
Multiple Sclerosis Journal - October 2017 - 1521
Multiple Sclerosis Journal - October 2017 - 1522
Multiple Sclerosis Journal - October 2017 - 1523
Multiple Sclerosis Journal - October 2017 - 1524
Multiple Sclerosis Journal - October 2017 - 1525
Multiple Sclerosis Journal - October 2017 - 1526
Multiple Sclerosis Journal - October 2017 - 1527
Multiple Sclerosis Journal - October 2017 - 1528
Multiple Sclerosis Journal - October 2017 - 1529
Multiple Sclerosis Journal - October 2017 - 1530
Multiple Sclerosis Journal - October 2017 - 1531
Multiple Sclerosis Journal - October 2017 - 1532
Multiple Sclerosis Journal - October 2017 - 1533
Multiple Sclerosis Journal - October 2017 - 1534
Multiple Sclerosis Journal - October 2017 - 1535
Multiple Sclerosis Journal - October 2017 - 1536
Multiple Sclerosis Journal - October 2017 - 1537
Multiple Sclerosis Journal - October 2017 - 1538
Multiple Sclerosis Journal - October 2017 - 1539
Multiple Sclerosis Journal - October 2017 - 1540
Multiple Sclerosis Journal - October 2017 - 1541
Multiple Sclerosis Journal - October 2017 - 1542
Multiple Sclerosis Journal - October 2017 - 1543
Multiple Sclerosis Journal - October 2017 - 1544
Multiple Sclerosis Journal - October 2017 - 1545
Multiple Sclerosis Journal - October 2017 - 1546
Multiple Sclerosis Journal - October 2017 - 1547
Multiple Sclerosis Journal - October 2017 - 1548
Multiple Sclerosis Journal - October 2017 - 1549
Multiple Sclerosis Journal - October 2017 - 1550
Multiple Sclerosis Journal - October 2017 - 1551
Multiple Sclerosis Journal - October 2017 - 1552
Multiple Sclerosis Journal - October 2017 - 1553
Multiple Sclerosis Journal - October 2017 - 1554
Multiple Sclerosis Journal - October 2017 - 1555
Multiple Sclerosis Journal - October 2017 - 1556
Multiple Sclerosis Journal - October 2017 - 1557
Multiple Sclerosis Journal - October 2017 - 1558
Multiple Sclerosis Journal - October 2017 - 1559
Multiple Sclerosis Journal - October 2017 - 1560
Multiple Sclerosis Journal - October 2017 - 1561
Multiple Sclerosis Journal - October 2017 - 1562
Multiple Sclerosis Journal - October 2017 - 1563
Multiple Sclerosis Journal - October 2017 - 1564
Multiple Sclerosis Journal - October 2017 - 1565
Multiple Sclerosis Journal - October 2017 - 1566
Multiple Sclerosis Journal - October 2017 - Cover3
Multiple Sclerosis Journal - October 2017 - Cover4
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