Multiple Sclerosis Journal - October 2017 - 1562

Multiple Sclerosis Journal 23(11)
In this case report, Zambon and coworkers describe a
young man with progressive, severe, and global cognitive decline associated with neuropsychiatric dysfunction who was eventually diagnosed as a peculiar,
aggressive form of primary progressive multiple sclerosis (PPMS), after 4 years from the initial clinical
manifestation.
Cognitive and behavioral symptoms are common in
MS, even from the early stages of the disease,1 but
they are considered to be rarely the inaugural and predominant manifestation of the disease, thus jeopardizing early and accurate diagnosis. Such a presentation
constitutes a diagnostic dilemma, particularly in differentiating MS from primary neurodegenerative
dementias or vascular and metabolic diseases. Indeed,
although the recent revision of MS diagnostic criteria2
has significantly improved their sensitivity, in several
cases, the "no better explanation" requirement is difficult to fulfill and the acquisition of MS diagnosis
may be delayed.
So far, cognitive and psychiatric disorders as inaugural features of MS remain poorly understood.
However, the increasing number of patients described
in the literature share a number of peculiar characteristics2-7 that should be taken into consideration in
case of primary cognitive/neuropsychiatric dysfunction and white matter lesions of unclear origin, in
order to prompt appropriate diagnostic workup. A
vast proportion of the study patients presenting with
cognitive dysfunction also exhibit a wide variety of
psychiatric disorders, sometimes justifying a first
psychiatric referral and/or diagnosis; cognitive and
psychiatric disorders are disproportionately represented in comparison with other major, classical neurological symptoms and signs; the disease course at
presentation has been dichotomized as "subacute fulminant" or "chronic progressive,"3 although a progressive onset has been reported more frequently; in
a sizeable proportion of cases, besides more typical
cognitive deficits described in MS patients, involving information processing speed, executive functioning, and memory,1 the neuropsychological
evaluation can document cognitive symptoms of the
cortical type. These are represented more commonly
by language and praxic disorders, which would substantiate the evidence for a peculiar disease phenotype, identified as a "cortical variant" of MS.7 Indeed,
during the past decades, it has become clear that,
besides white matter, also gray matter damage of the
brain is of major importance in patients with MS.
Thanks to improved magnetic resonance imaging
(MRI) techniques, the in vivo detection of gray matter pathology became possible, enabling a better
1562

understanding of the manifestation of various clinical
symptoms, in particular cognitive and neuropsychiatric disorders.8 In patients with pure cognitive and neuropsychiatric presentation, MRI findings are notable
for the documentation of both discrete and confluent,
diffuse white matter abnormalities. More remarkable,
severe brain atrophy at presentation is another common characteristic of these cases. In line with the
hypothesis of prominent gray matter involvement, a
study using a quantitative neuroimaging5 approach
showed a higher reduction in gray matter fraction as
compared with white matter fraction and reported a
high number of cortical lesions in the double inversion recovery (DIR) sequences. Moreover, selective
atrophy of midbrain tegmentum with relative sparing
of pons,5 prominent cortical, and hippocampal
involvement6 have been described in a few cases.
Failure to recognize the above-mentioned characteristics may delay diagnosis and may expose patients to
potentially dangerous and invasive investigation.
Because the neuropsychiatric and cognitive features
of these cases are a major cause of disability and
handicap, their early recognition may be particularly
relevant in view of emerging treatments for MS.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or
publication of this article.
Funding
The author(s) received no financial support for the
research, authorship, and/or publication of this article.

References
1.

Amato MP, Zipoli V and Portaccio E. Multiple
sclerosis-related cognitive changes: A review of
cross-sectional and longitudinal studies. J Neurol Sci
2006; 245: 41-46.

2.

Polman CH, Reingold SC, Banwell B, et al.
Diagnostic criteria for multiple sclerosis: 2010
revisions to the McDonald criteria. Ann Neurol 2011;
69: 292-302.

3.

Staff NP, Lucchinetti CF and Keegan BM.
Multiple sclerosis with predominant, severe
cognitive impairment. Arch Neurol 2009; 66(9):
1139-1143.

4.

Assouad R, Louapre C, Tourbah A, et al. Clinical and
MRI characterization of MS patients with a pure and
severe cognitive onset. Clin Neurol Neurosurg 2014;
126: 55-63.

journals.sagepub.com/home/msj


https://journals.sagepub.com/home/msj

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
https://www.nxtbookmedia.com