Background and Objective: Plasma homocysteine (Hcy) levels have been investigated among patients with multiple sclerosis (MS). However, the changes in Hcy levels and the association between Hcy levels and inflammatory/immune/cerebrospinal fluid (CSF) parameters in neuromyelitis optica spectrum disorder (NMOSD) patients have not been investigated yet. Methods: Case data were collected from 97 acute-phase NMOSD patients and 39 stable-phase NMOSD patients. Patients in the acute phase were divided into 2 groups based on the EDSS score with cutoff equal to 4. Hcy levels, immunoglobulins (Ig) A, G, and M, complement 3 and 4, CH50, C-reactive protein, erythrocyte sedimentation rate (ESR), and CSF examination including white blood cells and total protein were determined. Results: No significant differences in Hcy levels are observed between acute-phase and stable-phase NMOSD patients. Hcy and ESR levels were significantly higher in acute-phase NMOSD patients with EDSS score ≥4. Besides, EDSS is positively correlated with Hcy level, ESR, 1/aquaporin-4 titer and Hcy level is negatively correlated with IgM in acute-phase NMOSD patients. Conclusion: Elevated plasma Hcy has the potential to affect the pathogenesis or progression of NMOSD.

1.
Wingerchuk
DM
,
Banwell
B
,
Bennett
JL
,
Cabre
P
,
Carroll
W
,
Chitnis
T
, et al;
International Panel for NMO Diagnosis
.
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders
.
Neurology
.
2015
Jul
;
85
(
2
):
177
89
.
[PubMed]
0028-3878
2.
Jarius
S
,
Paul
F
,
Franciotta
D
,
Waters
P
,
Zipp
F
,
Hohlfeld
R
, et al
Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica
.
Nat Clin Pract Neurol
.
2008
Apr
;
4
(
4
):
202
14
.
[PubMed]
1745-834X
3.
Papadopoulos
MC
,
Verkman
AS
.
Aquaporin 4 and neuromyelitis optica
.
Lancet Neurol
.
2012
Jun
;
11
(
6
):
535
44
.
[PubMed]
1474-4422
4.
Jasiak-Zatonska
M
,
Kalinowska-Lyszczarz
A
,
Michalak
S
,
Kozubski
W
.
KalinowskaLyszczarz A, Michalak S, Kozubski W. The immunology of neuromyelitis optica-current knowledge, clinical implications, controversies and future perspectives
.
Int J Mol Sci
.
2016
Mar
;
17
(
3
):
273
.
[PubMed]
1661-6596
5.
Kamath
AF
,
Chauhan
AK
,
Kisucka
J
,
Dole
VS
,
Loscalzo
J
,
Handy
DE
, et al
Elevated levels of homocysteine compromise blood-brain barrier integrity in mice
.
Blood
.
2006
Jan
;
107
(
2
):
591
3
.
[PubMed]
0006-4971
6.
Faraci
FM
,
Lentz
SR
.
Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction
.
Stroke
.
2004
Feb
;
35
(
2
):
345
7
.
[PubMed]
0039-2499
7.
Ho
PI
,
Ortiz
D
,
Rogers
E
,
Shea
TB
.
Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage
.
J Neurosci Res
.
2002
Dec
;
70
(
5
):
694
702
.
[PubMed]
0360-4012
8.
Dawson
H
,
Collins
G
,
Pyle
R
,
Deep-Dixit
V
,
Taub
DD
.
The immunoregulatory effects of homocysteine and its intermediates on T-lymphocyte function
.
Mech Ageing Dev
.
2004
Feb
;
125
(
2
):
107
10
.
[PubMed]
0047-6374
9.
Chang
L
,
Zhang
Z
,
Li
W
,
Dai
J
,
Guan
Y
,
Wang
X
.
Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS-NF-kappaB pathway
.
Biochem Biophys Res Commun
.
2007
Jun
;
357
(
3
):
772
8
.
[PubMed]
0006-291X
10.
Holven
KB
,
Halvorsen
B
,
Schulz
H
,
Aukrust
P
,
Ose
L
,
Nenseter
MS
.
Expression of matrix metalloproteinase-9 in mononuclear cells of hyperhomocysteinaemic subjects
.
Eur J Clin Invest
.
2003
Jul
;
33
(
7
):
555
60
.
[PubMed]
0014-2972
11.
Mansoor
MA
,
Seljeflot
I
,
Arnesen
H
,
Knudsen
A
,
Bates
CJ
,
Mishra
G
, et al
Endothelial cell adhesion molecules in healthy adults during acute hyperhomocysteinemia and mild hypertriglyceridemia
.
Clin Biochem
.
2004
May
;
37
(
5
):
408
14
.
[PubMed]
0009-9120
12.
Holven
KB
,
Aukrust
P
,
Retterstol
K
,
Hagve
TA
,
Mørkrid
L
,
Ose
L
, et al
Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic subjects
.
Scand J Clin Lab Invest
.
2006
;
66
(
1
):
45
54
.
[PubMed]
0036-5513
13.
Besler
HT
,
Comoğlu
S
.
Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis
.
Nutr Neurosci
.
2003
Jun
;
6
(
3
):
189
96
.
[PubMed]
1028-415X
14.
Vrethem
M
,
Mattsson
E
,
Hebelka
H
,
Leerbeck
K
,
Osterberg
A
,
Landtblom
AM
, et al
Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid
.
Mult Scler
.
2003
Jun
;
9
(
3
):
239
45
.
[PubMed]
1352-4585
15.
Ramsaransing
GS
,
Fokkema
MR
,
Teelken
A
,
Arutjunyan
AV
,
Koch
M
,
De Keyser
J
.
Plasma homocysteine levels in multiple sclerosis
.
J Neurol Neurosurg Psychiatry
.
2006
Feb
;
77
(
2
):
189
92
.
[PubMed]
0022-3050
16.
Sahin
S
,
Aksungar
FB
,
Topkaya
AE
,
Yildiz
Z
,
Boru
UT
,
Ayalp
S
, et al
Increased plasma homocysteine levels in multiple sclerosis
.
Mult Scler
.
2007
Aug
;
13
(
7
):
945
6
.
[PubMed]
1352-4585
17.
Triantafyllou
N
,
Evangelopoulos
ME
,
Kimiskidis
VK
,
Kararizou
E
,
Boufidou
F
,
Fountoulakis
KN
, et al
Increased plasma homocysteine levels in patients with multiple sclerosis and depression
.
Ann Gen Psychiatry
.
2008
Sep
;
7
(
1
):
17
.
[PubMed]
1744-859X
18.
Zoccolella
S
,
Tortorella
C
,
Iaffaldano
P
,
Direnzo
V
,
D’Onghia
M
,
Paolicelli
D
, et al
Elevated plasma homocysteine levels in patients with multiple sclerosis are associated with male gender
.
J Neurol
.
2012
Oct
;
259
(
10
):
2105
10
.
[PubMed]
0340-5354
19.
Guzel
I
,
Mungan
S
,
Oztekin
ZN
,
Ak
F
.
Is there an association between the Expanded Disability Status Scale and inflammatory markers in multiple sclerosis?
J Chin Med Assoc
.
2016
Feb
;
79
(
2
):
54
7
.
[PubMed]
1726-4901
20.
Oliveira
SR
,
Flauzino
T
,
Sabino
BS
,
Kallaur
AP
,
Alfieri
DF
,
Kaimen-Maciel
DR
, et al
Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis
.
Metab Brain Dis
.
2018
Oct
;
33
(
5
):
1393
9
.
[PubMed]
0885-7490
21.
Teunissen
CE
,
Killestein
J
,
Kragt
JJ
,
Polman
CH
,
Dijkstra
CD
,
Blom
HJ
.
Serum homocysteine levels in relation to clinical progression in multiple sclerosis
.
J Neurol Neurosurg Psychiatry
.
2008
Dec
;
79
(
12
):
1349
53
.
[PubMed]
0022-3050
22.
Kurtzke
JF
.
Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)
.
Neurology
.
1983
Nov
;
33
(
11
):
1444
52
.
[PubMed]
0028-3878
23.
Conradsson
D
,
Ytterberg
C
,
von Koch
L
,
Johansson
S
.
Changes in disability in people with multiple sclerosis: a 10-year prospective study
.
J Neurol
.
2018
Jan
;
265
(
1
):
119
26
.
[PubMed]
0340-5354
24.
Sicras-Mainar
A
,
Ruíz-Beato
E
,
Navarro-Artieda
R
,
Maurino
J
.
Impact on healthcare resource utilization of multiple sclerosis in Spain
.
BMC Health Serv Res
.
2017
Dec
;
17
(
1
):
854
.
[PubMed]
1472-6963
25.
Harding
KE
,
Wardle
M
,
Carruthers
R
,
Robertson
N
,
Zhu
F
,
Kingwell
E
, et al
Socioeconomic status and disability progression in multiple sclerosis: A multinational study
.
Neurology
.
2019
Mar
;
92
(
13
):
e1497
506
.
[PubMed]
0028-3878
26.
Malinow
MR
,
Bostom
AG
,
Krauss
RM
.
Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association
.
Circulation
.
1999
Jan
;
99
(
1
):
178
82
.
[PubMed]
0009-7322
27.
Sacco
RL
,
Adams
R
,
Albers
G
,
Alberts
MJ
,
Benavente
O
,
Furie
K
, et al;
American Heart Association/American Stroke Association Council on Stroke
;
Council on Cardiovascular Radiology and Intervention
;
American Academy of Neurology
.
Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline
.
Circulation
.
2006
Mar
;
113
(
10
):
e409
49
.
[PubMed]
0009-7322
28.
Klimovich
VB
.
IgM and its receptors: structural and functional aspects
.
Biochemistry (Mosc)
.
2011
May
;
76
(
5
):
534
49
.
[PubMed]
0006-2979
29.
Kerekes
G
,
Szekanecz
Z
,
Dér
H
,
Sándor
Z
,
Lakos
G
,
Muszbek
L
, et al
Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity
.
J Rheumatol
.
2008
Mar
;
35
(
3
):
398
406
.
[PubMed]
0315-162X
30.
Cheng
C
,
Jiang
Y
,
Chen
X
,
Dai
Y
,
Kang
Z
,
Lu
Z
, et al
Clinical, radiographic characteristics and immunomodulating changes in neuromyelitis optica with extensive brain lesions
.
BMC Neurol
.
2013
Jul
;
13
(
1
):
72
.
[PubMed]
1471-2377
31.
Doi
H
,
Matsushita
T
,
Isobe
N
,
Matsuoka
T
,
Minohara
M
,
Ochi
H
, et al
Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody
.
Mult Scler
.
2009
Mar
;
15
(
3
):
304
10
.
[PubMed]
1352-4585
32.
Kuroda
H
,
Fujihara
K
,
Takano
R
,
Takai
Y
,
Takahashi
T
,
Misu
T
, et al
Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica
.
J Neuroimmunol
.
2013
Jan
;
254
(
1-2
):
178
82
.
[PubMed]
0165-5728
33.
Wang
H
,
Wang
K
,
Wang
C
,
Qiu
W
,
Lu
Z
,
Hu
X
.
Increased soluble C5b-9 in CSF of neuromyelitis optica
.
Scand J Immunol
.
2014
Feb
;
79
(
2
):
127
30
.
[PubMed]
0300-9475
34.
Nytrova
P
,
Potlukova
E
,
Kemlink
D
,
Woodhall
M
,
Horakova
D
,
Waters
P
, et al
Complement activation in patients with neuromyelitis optica
.
J Neuroimmunol
.
2014
Sep
;
274
(
1-2
):
185
91
.
[PubMed]
0165-5728
35.
Wang
J
,
Li
X
,
Zhang
DQ
,
Yang
CS
,
Qi
Y
,
Li
MS
, et al
Quantitative analysis of aquaporin-4 antibody in longitudinally extensive transverse myelitis
.
J Neuroimmunol
.
2015
Jan
;
278
:
26
9
.
[PubMed]
0165-5728
36.
Jarius
S
,
Wildemann
B
.
Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature
.
Brain Pathol
.
2013
Nov
;
23
(
6
):
661
83
.
[PubMed]
1015-6305
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