\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Axonal Sensory-Motor Polyneuropathy in Ankylosing Spondylitis: A Case
Report}



\author[1]{Amirreza Khalaji}%
\author[1]{Susan Kolahi}%
\author[1]{Leyla Ghadakchi}%
\author[1]{Mehdi Jafarpour}%
\affil[1]{Tabriz University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 21, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


Title: Axonal Sensory-Motor Polyneuropathy in Ankylosing Spondylitis: A
Case Report

Introduction

Ankylosing spondylitis (AS) is an inflammatory disorder with many
unidentified reasons. The primary involvement in AS cases is an axial
skeleton, defined by joint deformity, stiffness, enthesitis with pain,
and sacroiliac arthritis (1). Systemic inflammation leads to stiffness
and pain in the entheses, spine, and sacroiliac joint resulting in
spinal curvature loss and movement restriction. Advanced disease is
possible to lead to spine and sacroiliac joint fusion, causing a
''bamboo spine'' condition. Enthesopathy, including plantar fasciitis
and Achilles tendonitis, may happen early stage of the disease and
result in structural damage. Peripheral joints, primarily in the lower
limbs such as the hip, and knee, can also be affected (2).

Neuropathic pain can be experienced in AS cases, endorsed by
abnormalities in the brain's gray matter and neural correlates. The AS
clinical picture includes neuropathic pain, mood deficits, and motor
impairment. Hence, back pain in subjects with AS may be related to
neuropathic pain (3). Also, in AS cases, no precise data showed Axonal
Sensory-Motor Polyneuropathy in these patients. Although, some research
found a correlation between AS and peripheral neuropathy (3-5). Thus,
this case report revealed an AS subject with polyneuropathy, a rare
disease manifestation.

Case Presentation

A 45-year-old male with no prior medical history was diagnosed with AS
about ten years ago following bilateral Achilles tendonitis, rupture of
the left Achilles tendon, inflammatory low back pain, positive HLA B27,
and increased inflammatory markers. Sacroiliac X-ray showed bilateral
Sacroiliitis (Figure 1), then he was managed with Sulfasalazine and
NSAID at anti-inflammatory. About one year ago, the case felt tingling
and numbness, firstly in the upper limbs and then in the lower limbs.
Upon consultation with a rheumatologist, he underwent tests such as
EMG-NCV, vitamin B12, and folate levels. EMG-NCV result showed
axonal-type sensory-motor polyneuropathy and laboratory tests
demonstrated a normal range of vitamin B12 and folate levels. Laboratory
tests showed in Table 1.

Considering the inconsistency between the patient's neuropathy and AS,
additional examinations were performed, including CT scans of the lungs,
abdomen, and pelvis and tumor marker tests to investigate the
possibility of malignancy. The tumor markers range is shown in Table 1.
All requested tests demonstrated normal results, and the criteria for
demyelinating neuropathy were absent in the EMG-NCV; this neuropathy
subtype was not considered a potential etiology. Eventually, based on
the findings, no justification for the patient's neuropathy was
identified, and the absence of any secondary cause was proposed as the
etiology; hence, AS considers an etiology of Axonal Sensory-Motor
Polyneuropathy, a rare presentation for this disease.

Discussion

0.1--0.5\% of people are affected by AS, and it is defined by
radiographic sacroiliitis, inflammatory back pain, excess spinal bone
formation, and positive HLA-B27 in most cases (6, 7). AS
spondyloarthropathy features are associated with human leukocyte antigen
(HLA)-B27 (8, 9). Positive HLA-B27 AS patients are susceptible to
younger AS cases, have a higher uveitis frequency, better response to
management with tumor necrosis factor-alpha (TNF-\selectlanguage{greek}α\selectlanguage{english}) inhibitors, and have
a lower IBD or psoriasis prevalence (10).

\emph{Pain} ~is the AS main symptom known as one inflammatory pain (IP)
(11). Although, AS subjects' pain always does not relate to the
inflammatory indexes, including erythrocyte sedimentation rate (ESR) and
C-reactive protein (CRP) (12).

Chronic inflammatory arthritis patients like AS with peripheral
neuropathy is an infrequent condition. Peripheral nerve involvement is
one extra-articular rare striking AS involvement, and maybe it has no
association with the clinical variables (13). Furthermore, in
asymptomatic AS patients, the involvement of the peripheral nervous
system can be the central nervous system (4).

A case-report study showed a case with swelling in his knees and ankles,
chronic pain, and neck and low back pain. The patient additionally had
tingling and numbness in his hands and feet. On examination, he has
impaired sensation, muscle wasting, weakness, absent ankle jerks, and
equivocal plantar response. EMG suggests chronic demyelinating
polyneuropathy with secondary axonal involvement. Additionally, the
patient has a positive HLA-B27 and microcytic hypochromic anemia (13).
Their study involved patient who, like ours, had developed neuropathy,
but the type of neuropathy differed.

In addition, another study investigated the relationship between
peripheral neuropathy and AS by evaluating the peripheral nervous system
of 32 AS patients without symptoms of neuropathy. The study found that
18.8\% of the AS patients had sensory or sensorimotor peripheral nerve
involvement, and 21.9\% had focal nerve involvement. The study also
found correlations between tibial nerve motor conduction velocity and
Schober and chest expansion tests and negative correlations between
sural nerve sensory action potential amplitude and age and disease
duration. The study suggests that asymptomatic AS patients can have
peripheral nervous system involvement, and further studies are needed to
confirm the results and evaluate the clinical significance (4). The
results of their study were in line with ours, but their cases did not
have any symptoms of neuropathy, while ours did.

In summary, our case report presented a case of AS under medication with
a rare peripheral neuropathy presentation. Our case report differs from
previous studies and case reports.

References

1. Zong HX, Xu SQ, Tong H, Wang XR, Pan MJ, Teng YZ. Effect of
anti-tumor necrosis factor \selectlanguage{greek}α \selectlanguage{english}treatment on radiographic progression in
patient with ankylosing spondylitis: A systematic review and
meta-analysis. Modern rheumatology. 2019;29(3):503-9.

2. Ebrahimiadib N, Berijani S, Ghahari M, Pahlaviani FG. Ankylosing
Spondylitis. Journal of ophthalmic \& vision research. 2021;16(3):462-9.

3. Wu Q, Inman RD, Davis KD. Neuropathic pain in ankylosing spondylitis:
a psychophysics and brain imaging study. Arthritis and rheumatism.
2013;65(6):1494-503.

4. G\selectlanguage{ngerman}ündüz OH, Kiralp MZ, Ozçakar L, Cakar E, Yildirim P, Akyuz G. Nerve
conduction studies in patients with ankylosing spondylitis. Journal of
the National Medical Association. 2010;102(3):243-6.

5. Erdal A, Gündüz OH, Duruöz T. AB0759\selectlanguage{english} Peripheral Nervous System
Involvement and Neuropathic Pain in Ankylosing Spondylitis. Annals of
the Rheumatic Diseases. 2015;74(Suppl 2):1152-3.

6. Wang R, Ward MM. Epidemiology of axial spondyloarthritis: an update.
Current opinion in rheumatology. 2018;30(2):137-43.

7. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic
criteria for ankylosing spondylitis. A proposal for modification of the
New York criteria. Arthritis and rheumatism. 1984;27(4):361-8.

8. Howe HS, Zhao L, Song YW, Springer L, Edmonds J, Gu J, et al.
Seronegative spondyloarthropathy--studies from the Asia Pacific region.
Annals of the Academy of Medicine, Singapore. 2007;36(2):135-41.

9. Akassou A, Bakri Y. Does HLA-B27 Status Influence Ankylosing
Spondylitis Phenotype? Clinical medicine insights Arthritis and
musculoskeletal disorders. 2018;11:1179544117751627.

10. Akkoc N, Yarkan H, Kenar G, Khan MA. Ankylosing Spondylitis:
HLA-B*27-Positive Versus HLA-B*27-Negative Disease. Current rheumatology
reports. 2017;19(5):26.

11. Lindstrom U, Bremander A, Haglund E, Bergman S, Petersson IF,
Jacobsson LT. Back pain and health status in patients with clinically
diagnosed ankylosing spondylitis, psoriatic arthritis and other
spondyloarthritis: a cross-sectional population-based study. BMC
musculoskeletal disorders. 2016;17:106.

12. Bidad K, Gracey E, Hemington KS, Mapplebeck JCS, Davis KD, Inman RD.
Pain in ankylosing spondylitis: a neuro-immune collaboration. Nature
reviews Rheumatology. 2017;13(7):410-20.

13. Biswas S, HAM NA, Biswas PK, Rashid MHU, Sarkar PK, Chowdhury MK, et
al. Ankylosing Spondylitis with Peripheral Neuropathy-A Rare Case
Report. Journal of Medicine. 2016;17(1):36.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1. X-ray of the Sacroiliac joint shows bilateral sacroiliitis

Table 1. Laboratory parameters of the patient\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Laboratory parameters & Patient's values & Normal range\tabularnewline
\midrule
\endhead
Leukocyte count, per \selectlanguage{greek}µ\selectlanguage{english}L & 6.1\selectlanguage{ngerman}×10\textsuperscript{3} &
4-10\selectlanguage{ngerman}×103\tabularnewline
Hemoglobin, g/dL & 14.4 & 12.3-15.3\tabularnewline
MCV & 93 & 80-100\tabularnewline
Platelet count, per \selectlanguage{greek}µ\selectlanguage{english}L & 300000 & 150000-450000\tabularnewline
ESR, mm/h & 7 & 0-30\tabularnewline
CRP, mg/L & 1 & \textless{} 6\tabularnewline
Creatinine, mg/dL & 1 & 0.7-1.3\tabularnewline
Na, mmol/L & 138 & 136-145\tabularnewline
K, mmol/L & 4.5 & 3.5-5.2\tabularnewline
Vitamin D, ng/mL & 40 & 50-70\tabularnewline
Vitamin B12, pg/mL & 290 & 187-883\tabularnewline
Folic acid, ng/ml & 15 & 3-17\tabularnewline
Ferritin, ng/ml & 28 & 21-274\tabularnewline
TSH, mIU/L & 3.7 & 0.5-5.0\tabularnewline
CA-125, U/mL & 6 & \textless{}21\tabularnewline
CA19-9, IU/mL & 8 & \textless{}40\tabularnewline
CEA, ng/mL & 102 & \textless{}602\tabularnewline
AFp, IU/mL & 2 & \textless{}505\tabularnewline
\bottomrule
\end{longtable}

Na: Sodium, K: Potassium, TSH: Thyroid stimulating hormone, CA: Cancer
antigen, CEA: Carcinoembryonic antigen, AFp: Alpha-fetoprotein

\selectlanguage{english}
\FloatBarrier
\end{document}

