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\begin{document}

\title{Meniscal Disruption Associated with Septic Arthritis in 3 Neonatal Foals}



\author[1]{Jessica Johnson}%
\author[1]{Endrigo Pompermayer}%
\author[1]{Masa-aki Oikawa}%
\author[2]{Tatiana Vinardell}%
\author[3]{Mohamed Ali}%
\author[4]{Sarah Puchalski}%
\author[5]{Florent David}%
\affil[1]{Equine Veterinary Medical Center}%
\affil[2]{Equine Care Group}%
\affil[3]{Affiliation not available}%
\affil[4]{Puchalski Equine Inc. }%
\affil[5]{EquiTom Equine Clinic}%


\vspace{-1em}



  
  \date{June 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{Objective:} To report clinical characteristics, surgical
management, and medium-term outcomes of 3 Arabian neonatal foals with
meniscal disruption associated with septic arthritis of the lateral
femorotibial joint. \textbf{Methods:} Three neonatal Arabian foals with
septic arthritis of the lateral femorotibial joint (LFTJ), were
diagnosed with lateral meniscal (LM) tears, based on persistent lameness
despite improving synovial parameters, ultrasound (US) findings
(protrusion of meniscal tissue beyond the level of the condyles, with
hypoechoic regions), contrast Computed Tomography findings, and
confirmed on arthroscopy. Treatment included arthroscopic debridement
and lavage of the joint with debridement of the meniscal tear.
Postoperative care included systemic and intra-articular antimicrobials,
based on culture and sensitivity results. Two of the foals received
intra-articular injections of autologous mesenchymal stem cells.
\textbf{Results:} Grade III meniscal tears were observed in the LFTJ of
the affected joints of all foals, involving the meniscal body (n=3) and
caudal horn (n=1). Purulent material within the torn tissue, was
debrided with a synovial resector. Foal 1 was lame-free as a yearling.
Foal 2 was lame at walk at 7.5 months and euthanatized due to poor
prognosis. Foal 3 showed mild lameness at trot in a straight line at 6
months. Disruption of the LM continued to be visible on US in both foals
at these time-points. \textbf{Conclusion:} Meniscal disruption and
infection should be considered a differential in neonatal foals with
persistent femorotibial septic arthritis. In such cases, the LM could be
the primary nidus of infection.%
\end{abstract}%



\sloppy


\textbf{TITLE PAGE}

\textbf{Title:} Meniscal Disruption Associated with Septic Arthritis in
3 Neonatal Foals

\textbf{Running title:} Meniscal Disruption in 3 Neonatal Foals.

\textbf{Authors:}

Jessica P. Johnson\textsuperscript{1}*, BAgrSc, MVB, MRCVS, Dipl. ECVS,
DVMS

Endrigo Pompermayer\textsuperscript{1}, DVM, MSc

Masa-aki Oikawa\textsuperscript{1}, DVM, PhD, Dipl. JCVP

Tatiana Vinardell\textsuperscript{2}, DVM, IPSAV, MSc, PhD

Mohammed Ali\textsuperscript{3}, DVM, MSc, PhD

Sarah Puchalski\textsuperscript{4}, DVM, Dipl. ACVR

Florent David\textsuperscript{5}, DVM, MSc, Dipl. ACVS \& ECVS, Dipl.
ACVSMR \& ECVSMR, ECVDI Assoc.

\textbf{Authors' Addresses:}

\textsuperscript{1}Equine Veterinary Medical Center, Doha, Qatar.

\textsuperscript{2}Equine Care Group, Lummen Belgium.

\textsuperscript{3}Ontario, Canada.

\textsuperscript{4}Puchalski Equine, British Colombia, Canada.

\textsuperscript{5}EquiTom -- Namur, Belgium.

\textbf{*Corresponding author:}

Dr. Jessica P. Johnson

jjohnson@qf.org.qa

\textbf{Conflicts} of Interest: None.

\textbf{Presentation of Findings:} 30th ECVS Annual Scientific Meeting;
Friday July 9th, 10:15 - 10:30.





\textbf{Abstract}

\textbf{Objective:} To report clinical characteristics, surgical
management, and medium-term outcomes of 3 Arabian neonatal foals with
meniscal disruption associated with septic arthritis of the lateral
femorotibial joint.

\textbf{Methods:} Three neonatal Arabian foals with septic arthritis of
the lateral femorotibial joint (LFTJ), were diagnosed with lateral
meniscal (LM) tears, based on persistent lameness despite improving
synovial parameters, ultrasound (US) findings (protrusion of meniscal
tissue beyond the level of the condyles, with hypoechoic regions),
contrast Computed Tomography findings, and confirmed on arthroscopy.
Treatment included arthroscopic debridement and lavage of the joint with
debridement of the meniscal tear. Postoperative care included systemic
and intra-articular antimicrobials, based on culture and sensitivity
results. Two of the foals received intra-articular injections of
autologous mesenchymal stem cells.

\textbf{Results:} Grade III meniscal tears were observed in the LFTJ of
the affected joints of all foals, involving the meniscal body (n=3) and
caudal horn (n=1). Purulent material within the torn tissue, was
debrided with a synovial resector. Foal 1 was lame-free as a yearling.
Foal 2 was lame at walk at 7.5 months and euthanatized due to poor
prognosis. Foal 3 showed mild lameness at trot in a straight line at 6
months. Disruption of the LM continued to be visible on US in both foals
at these time-points.

\textbf{Conclusion:} Meniscal disruption and infection should be
considered a differential in neonatal foals with persistent femorotibial
septic arthritis. In such cases, the LM could be the primary nidus of
infection.

\textbf{Keywords}

Horse, Foal, Meniscus, Septic arthritis.



\textbf{INTRODUCTION}

In the adult horse, traumatic meniscal injuries result in lameness, and
are amongst the commonly reported soft tissue injuries of the
femorotibial joints (De Busscher \emph{et al.} , 2006; Nemery \emph{et
al.} , 2016; Ribitsch \emph{et al.} , 2018). There are relatively few
documented cases of soft tissue injuries of the stifle in foals,
including cases of popliteal tendonitis (Gabriel and Marta, 2020), an
avulsion of the combined origin of the long digital extensor tendon and
fibularis tertius from the extensor fossa (Blikslager and Bristol,
1994), a complete tear of the vastus medialis muscle with patellar
luxation (Ogden \emph{et al.} , 2019), and a complex stifle injury
involving the medial meniscus and cranial cruciate ligaments
(Santschi\emph{et al.} , 2020). These lesions were believed to be
traumatic in origin with no septic processes reported.

The stifle is a commonly-reported site for sepsis in foals
(Wright\emph{et al.} , 2017; O'Brien \emph{et al.} , 2021). Compared to
other stifle compartments, sepsis of the lateral femorotibial joint
(LFTJ) is relatively rare (Reeves, Trotter and Kainer, 1991; Vacek, Ford
and Honnas, 1992; Hennessy \emph{et al.} , 2012). It has been estimated
that up to 1\% of all foals, and 13\% of those in neonatal intensive
care, are affected by septic arthritis and osteomyelitis (McIlwraith,
1983; Martens, Auer and Carter, 1986; Richardson DW and Stewart S, no
date). Neonates are susceptible to septic arthritis due to their
immature immune systems (Richardson DW and Stewart S, no date). Partial
or complete failure of passive transfer of immunity is a common risk
factor for hematogenous spread leading to septic arthritis (Richardson
DW and Stewart S, no date). Rapid growth of bones and joints is
associated with an increased vascular supply, which is believed to
facilitate infectious foci becoming established in the physes and
surrounding structures (Firth, 1983; Richardson DW and Stewart S, no
date). Septic arthritis is commonly divided into 3 broad categories
(Richardson DW and Stewart S, no date). S-type infections, of the
synovial fluid and membrane, are usually seen in very young neonates
(Richardson DW and Stewart S, no date). E-type infections affect the
epiphyseal bone adjacent to the articular cartilage, and typically
present in older foals(Richardson DW and Stewart S, no date). Finally,
P-types are mainly seen in older foals, involving the physes of long
bones, and may extend to the joint capsule (Richardson DW and Stewart S,
no date). One limitation of this classification system is the lack of
inclusion of soft tissue structure involvement, aside from the joint
capsule and synovial membrane.

To the authors' knowledge, there have been no reports of meniscal
involvement in cases of septic arthritis of the stifle of the foal.
Furthermore, although septic arthritis associated with osteochondral
lesions in the femoral condyle of the stifle joint has been reported, to
date histopathological findings of such lesions is missing
(Haggett\emph{et al.} , 2012).

The objective of this short case series was to report the clinical
characteristics, surgical management, histopathological findings and
medium-term outcomes of 3 Arabian neonatal foals with meniscal
disruption associated with septic arthritis of the LFTJ.

\textbf{Case History}

Three neonatal foals presented with lameness of variable duration: Foal
1, a 7-day old filly, 36 hours' duration; Foal 2, a 7-day old filly, 96
hours' duration; and Foal 3, a 17-day old colt, 6 hours' duration. All
foals had received systemic antimicrobials and nonsteroidal
anti-inflammatories (NSAIDs) prior to referral.

\textbf{Clinical Findings}

Foal 1: Physical examination revealed pyrexia (39.6\selectlanguage{ngerman}°C). Static
examination revealed marked effusion of both tibiotarsal and LFTJs,
including the subextensorius recess (SER). The foal showed a
non-weight-bearing left hindlimb (LH) lameness (American Association of
Equine Practitioners (AAEP) grade 5/5).

Foal 2: Physical examination revealed pyrexia (39.7°C). Static
examination revealed marked joint effusion of the radio- and
inter-carpal, tibiotarsal, and femoropatellar joints, bilaterally, as
well as both LFTJs. The foal was lame on all four limbs at walk, with
the LH being the lamest limb (AAEP grade 4/5).

Foal 3: Physical examination revealed pyrexia (39.9°C). Static
examination revealed heat, swelling and pain on palpation over the
lateral right (R) stifle and tibia, with moderate effusion of the SER. A
right hindlimb (RH) lameness was seen at a walk (AAEP grade 4/5).

\emph{Radiography}

Screening radiographs of all effused joints were taken on admission.
Findings were unremarkable (Figures 1 b \& c).

\emph{Ultrasonography (US) of LFTJ on admission}

Foal 1: Marked effusion of the left (L) LFTJ and SER was seen with
hyperechoic synovial fluid and fibrin formation (Figures 2 a \& b). The
LM was abnormal in shape, protruding beyond the level of the
tibial/femoral condyles, with a horizontal hypoechoic line running
through it (Figures 2 a \& b).

Foal 2: Moderate effusion of the L LFTJ and SER was seen, with fibrin
formation in the caudal pouch and surrounding the LM (Figure 1 a). The
synovium and joint capsule were thickened. The LM was abnormal in shape,
protruding beyond the level of the tibial/femoral condyles, with a
hypoechoic region within it (Figure 1 a).

Foal 3: Marked effusion of the R LFTJ and SER was seen, with fibrin
accumulation at the distal aspect of the SER. The LM was largely
protruding beyond the level of the tibial/femoral condyles, with a
heterogenous appearance and a hypoechoic line running through it.

\emph{Computed Tomography}

Foal 2: Plain computed tomography (CT) of the L stifle revealed marked
effusion of the LFTJ with irregularity of the subchondral bone of the
lateral femoral condyle (LFC) and the lateral tibial condyle (Figure 1
d). Contrast arthrogram revealed disruption of the LM caudally, with
lateral displacement (Figure 1 e). Disruption of the meniscofemoral
ligament was present at its attachment to the caudal horn of the LM
(Figure 1 f). The cranial lateral meniscotibial ligament (MTL) was also
irregular in appearance.

Foal 3: Marked effusion was present within all three compartments of the
R stifle. The proximal, lateral articular margin of the tibia was mildly
irregular. The LM was diffusely abnormal with several tears in multiple
orientations within the lateral and caudal aspects (Figure 3 b). A
large, pyramidal shaped tear of the axial aspect of the caudal horn of
the LM was present (Figure 3 c). The caudal lateral MTL was not clearly
identified and a central region of hypoattenuation was present in the
cranial lateral MTL (Figure 3 d).

\emph{Laboratory findings}

On presentation, Foal 1 had a neutrophilic (13.3 x10\^{}9/L)
leukocytosis (18.2 x10\^{}9/L). Foal 2 had a marked neutrophilic (15.74
x10\^{}9/L) leukocytosis (18.34 x10\^{}9/L), with hyperlactatemia (4.21
mmol/L), hypoproteinemia (46 g/L) and hypoalbuminemia (24.3 g/L).
Hematology in Foal 3 was unremarkable, with a mild hypoproteinemia (58
g/L) and hypoalbuminemia (23.5 g/L). IgG levels \textless{} 400 g/dL,
indicating failure of passive transfer, were found in Foals 1 \& 2.

Synovial fluid analysis at admission of the LFTJ of Foal 1 revealed a
WCC of 133 x10\^{}9/L; 93\% polymorphonuclear cells (PMNs) and total
protein (TP) 37 g/L. Synoviocentesis for foal 2 was unsuccessful, with
only gelatinous-like fibrin obtained. For Foal 3, LFTJ synovial fluid
WCC was 103 x10\^{}9 cells/L, 97.1\% PMNs, and TP 33 g/L.

LFTJ synovial fluid culture results were negative for bacterial growth
in Foal 1. In Foal 2, \emph{Micrococcus luteus} was cultured from the
fibrinous tissue obtained; in Foal 3, \emph{Staphylococcus
schleiferi}was cultured; both had a broad antimicrobial sensitivity
pattern.

\textbf{Treatment}

High-volume arthroscopic lavage and debridement of the affected LFTJs
(including SERs) was performed. A cranial approach was taken and a
synovial resector was introduced between the lateral patellar and
lateral collateral ligaments to clear the visual field. Examination of
the menisci revealed grade III tears in all cases (Figures 2 d \& 3 f).
In Foal 1, tearing of the cranial MTL was also apparent. In all cases,
the meniscus appeared prolapsed and displaced craniolaterally (Figure 2
c; Figures 3 e \& f). Fibrinous deposits were present adjacent to the
tears, with purulent material apparent within the torn fibers (Figure 3
e). The unhealthy tissue and torn fibers were removed using a synovial
resector. In all 3 Foals, the caudal aspect of the LFTJs were also
arthroscopically examined, and in Foal 2, evidence of meniscal tearing
could also be seen in the caudal horn. Where multiple joint involvement
was present, other joints were treated similarly, with high volume
arthroscopic lavage and debridement.

Postoperative treatment included a combination of broad-spectrum
antimicrobials (parenteral and IA), based on culture and sensitivity
results, where available; analgesia (NSAIDs and opioids, as indicated),
and gastroprotectants. Hyperimmune plasma was administered to Foals 1 \&
2. Response to treatment was monitored based on comfort levels, US
findings, and synovial fluid analysis.

Foal 2 and 3 required a second arthroscopic lavage and debridement of
the L LFTJ 14 days, and 3 days respectively, after the initial surgery
to remove further fibrin accumulations around the LM. In both cases,
progression of the tearing and meniscal protrusion/displacement could be
seen.

In Foals 2 \& 3, following resolution of the septic arthritis and
recovery, US and radiographic-guided bone marrow aspirates were taken
from the sternebrae under general anesthesia, for production of
autologous bone marrow-derived mesenchymal stem cells (BMSCs) (Figure 5
a). Briefly, the sternum was aseptically prepared, and the
intersternebral spaces identified using US. A stab incision with a No.
11 scalpel was performed through the skin and a Jamshidi biopsy needle
(11 gauge, 10 cm) introduced into the sternebra, using digital x-ray to
guide depth of needle introduction (Figure 5 a). A 60 ml syringe,
preloaded with 1000 IU of heparin was used to aspirate the bone marrow.
BMSCs were isolated aseptically and expanded in high glucose Dulbecco's
modified eagle's medium (DMEM) supplemented with 10\% v/v fetal bovine
serum and 100 U/mL penicillin --100 mg/mL streptomycin (all Gibco,
Biosciences, USA) at 20\% pO2(Smith \emph{et al.} , 2013). Following
colony formation, BMSCs were obtained with accutase (Gibco, Biosciences,
USA), counted (Countess\selectlanguage{english} II FL Automated Cell Counter, Thermo Fisher,
USA), seeded at density of 5000 cells/cm\textsuperscript{2} and expanded
until Passage 3. A final cell suspension of 2-4 million cells per ml was
obtained and suspended in saline for final injection in the patient.

Foal 2 received 3 US-guided IA injections of 10 million autologous
BMSCs, in the L LFTJ, at 44 d, 65 d, and 97 d post-operatively (Figure 5
b). Foal 3 received 3 US-guided IA injections of autologous BMSCs, in
the R LFTJ, at 19 d, 51 d and 86 d post-operatively.

\textbf{Outcome}

\emph{Foal 1}

Foal 1 was discharged 23 days after admission. She was reported to be
without lameness as a yearling and lost to follow-up thereafter.

\emph{Foal 2}

At 6 months post discharge, Foal 2 was lame at a walk on the LH (AAEP
4/5). There was palpable thickening and fibrosis over the LM (Figure 4
c). Left gluteal muscle atrophy was apparent with resentment of passive
global flexion of the limb. US revealed synovial effusion within the
LFTJ and SER (Figure 4 b). The LM was displaced laterally, with an
irregular outline, and areas of increased echogenicity suggestive of
mineralization (Figure 4 b). Radiographs revealed multiple coalescing
radiolucencies within the lateral femoral condyle (LFC), which appeared
flattened (Figure 4 d). Mineralization was visible in the soft tissues
in the region of the LM. A small radiolucent area was evident on the
lateral tibial plateau, surrounded by sclerosis (Figure 4 e).
Arthroscopic exploration of the L LFTJ and femoropatellar joint (FPJ)
was performed under general anesthesia. The cranial horn of the meniscus
was enlarged and fused with the joint capsule. It was displaced
cranially, rigid and fibrotic on palpation. Three subchondral bone cysts
with deep cloacae could be appreciated within the LFC. The lateral
tibial plateau lesion could not be visualized. After a further 7 weeks,
the filly's comfort levels had not improved any further. Repeat
radiographs revealed significant deterioration. The filly was humanely
euthanatized and submitted for post-mortem investigation.

\emph{Post-mortem macroscopic findings} : Increased viscosity and volume
of articular fluid were found in the left LFTJ. Edematous thickening of
the joint capsule was observed with hypertrophy of synovial villi and
increased yellow-ness of the synovial fluid (Figure 6 a). The LM showed
marked roughness and edematous loosening/malacia and was significantly
thinner than the medial meniscus (Figure 6 b). Examination of the
proximal tibia revealed diffuse gray-white lesions in the cancellous
bony tissue immediately below the articular cartilage, as well as
multiple focal erosions on the caudal articular surface of the lateral
condyle of the proximal tibia adjacent to the meniscus (Figure 6 c).

\emph{Post-mortem histological findings} : Histological evaluation
focused on the articular capsule of the left LFTJ, LM, articular
cartilage of the proximal tibia, and the subchondral bone tissue
beneath. Diffuse villous proliferation of the capsular synovium was
observed. In the superficial layer of the synovium, slight hyperplasia
of the epithelium covering the superficial layer of the synovium was
noted (Figure 6 d). In the sub-synovial stroma, infiltration of
inflammatory cells (neutrophils, lymphocytes, macrophages with
hemosiderin deposition, and plasma cells), interstitial edema, and
capillary angiogenesis were observed (Figure 6 d). In the LM, irregular
arrangement of collagen fibers, multifocal coagulation necrosis, fibrin
deposition in the collagen fiber tissue, infiltration of inflammatory
cells (neutrophils, lymphocytes, and macrophages), and capillary
angiogenesis, were detected (Figure 6 e).

In the lateral condyle of the proximal tibia, surface irregularities of
the superficial layer of the articular cartilage were found, associated
with the multifocal erosions seen grossly on the articular cartilage
surface. In addition, septic cartilage canals, characterized by
neutrophil/macrophage infiltration into the articular cartilage canals,
and the presence of fibrin-like material within the canals were found
(Figure 6 f). Multifocal-to-continuous bone
necrosis/hemorrhage/inflammatory cell infiltration, and fibroblasts as
well as angiogenesis, were present at the periphery of the bone tissue,
immediately below the articular cartilage. These lesions were not
detected within the deeper epiphysis.

\emph{Foal 3}

At 6 months post discharge, Foal 3 showed a mild AAEP 3/5 RH lameness
which was positive to global flexion. There was minimal palpable
effusion of the right stifle, however there was a firm palpable swelling
over the LM (Figure 4 c). Radiographs revealed mild soft tissue
thickening over the R LFTJ. A radiolucent area, surrounded by a rim of
sclerosis, could be seen on the lateral aspect of the tibial plateau,
indicating development of a possible cystic formation (Figure 4 d).
There was mild remodeling of the lateral tibial plateau and femoral
condyle, which was flattened in appearance (Figure 4 e). Mineralization
within the soft tissue in the region of the LM could be appreciated.
Moderate hypoechoic effusion of SER was seen on US. The LM continued to
protrude beyond the level of the condyles. Previously seen clefts were
visible but had reduced in size, evidence of mineralization could be
seen within the body of the meniscus which retained its triangular shape
(Figure 4 b). Remodeling of the LFC could be appreciated, and a zone of
irregular subchondral bone could be seen on the tibial plateau within
the joint space.



\textbf{Discussion}

This case series describes meniscal involvement in 3 foals with septic
arthritis of the LFTJs. To the authors' knowledge, this form of meniscal
involvement has not been reported heretofore. Conventional
classification systems of septic arthritis and osteomyelitis in horses
do not make provision for involvement of IA soft-tissue structures, such
as the menisci (Richardson DW and Stewart S, no date). This highlights
the need for an additional classification subtype, to extend the S-type
infection from involving not only the synovial membrane and fluid, but
also to other soft tissue structures within the joint.

The progression of the pathophysiology in these cases is unclear. Given
that the meniscal lesions were most marked at the site of attachment
with the capsular synovium, it was theorized that extension of purulent
inflammation occurred from the joint \emph{via} the vascular network of
the capsular synovium supplying the meniscus at this location (Arnoczky
and Warren, 1982). Purulent osteomyelitis was found at the junction
between articular cartilage and subchondral bone (Firth and
Goedegebuure, 1988). The presence of septic canals below erosive
articular cartilage lesions, in the absence of any lesions in the
underlying epiphysis, suggests that the inflammation spread from the
joint to the subchondral bone through septic cartilage canals
(Wormstrand \emph{et al.} , 2018). Therefore, the authors believe that,
due partial/complete failure of passive transfer, the original IA septic
focus established within the synovial membrane and fluid, and
subsequently extended to the meniscus, articular cartilage and
subchondral bone, leading to their disruption.

From the current series, it appears that a septic meniscus can act as a
persistent nidus of infection perpetuating septic arthritis, and also
leading to septic osteomyelitis and subchondral bone cyst formation. In
these cases, once infection became established within the menisci,
arthroscopic lavage and debridement of IA fibrin alone was inadequate to
address the sepsis within the meniscus, which did not resolve until the
purulent focus within the meniscus itself was debrided. For this reason,
in cases where foals with septic arthritis of the LFTJ relapse following
arthroscopic debridement and lavage, the authors advocate paying close
attention to the appearance and position of the meniscus using US, and
CT where available, to examine for evidence of displacement or
disruption. Meniscal disruption should also be considered in cases where
synovial parameters resolve post-operatively following arthroscopic
debridement and lavage for LFTJ septic arthritis in foals, however
lameness persists for no apparent reason.

It has been reported that sepsis of the LFTJ usually occurs as an
extension of infection from the FPJ, as the two communicate in 1-17\% of
cases (Reeves, Trotter and Kainer, 1991; Vacek, Ford and Honnas, 1992;
Hennessy \emph{et al.} , 2012). In this case series, only one of the
three foals was presented with additional joints affected in the stifle
(Foal 2), with the other two foals having only LFTJ involvement.
Furthermore, in adults, meniscal tears occur three times more often in
the medial meniscus than the LM (Walmsley, Phillips and Townsend, 2003;
Cohen \emph{et al.} , 2009), which was not the case in this series.

In adults, advanced imaging of the stifle is challenging due to size
limitations, and thus arthroscopy has traditionally been relied on for
the diagnosis of pathology of menisci and meniscal ligaments(McIlwraith
CW, Nixon AJ, Wright IM, no date). US does not always accurately predict
meniscal tears in adults (Cohen \emph{et al.} , 2009). The small size of
the patients in this series allowed for CT to be performed in 2 of the
foals, providing valuable additional information regarding IA soft
tissue involvement in these cases.

In adult horses, only limited portions of the meniscus are visible with
arthroscopy, requiring examination of the cranial and caudal pouches of
the femorotibial joints from separate approaches (McIlwraith CW, Nixon
AJ, Wright IM, no date). Grade 3 tears, which extend beneath the femoral
condyle, are typically inaccessible (Walmsley, Phillips and Townsend,
2003; McIlwraith CW, Nixon AJ, Wright IM, no date). Furthermore,
according to McIlwraith \emph{et al.} , accessibility to the LFTJ can be
difficult due to the IA location of the long digital extensor and
popliteal tendons (McIlwraith CW, Nixon AJ, Wright IM, no date). In the
current series, the authors found the foal LFTJs relatively easy to
maneuver within, most likely because of laxity due to their young age,
which facilitated better access to a greater extent of the tears for
debridement.

Regenerative therapies, including IA platelet rich plasma (PRP) and
interleukin-1 receptor antagonist protein (IRAP) have been proposed as
adjunctive therapies for meniscal injuries (Fowlie JG, Richardson DW,
Ortved KF, no date). A clinical study in adult horses has shown that IA
administration of BMSCs may promote meniscal regrowth and decrease the
subsequent development of osteoarthritis (Ferris \emph{et al.} , 2014).
Similarly, caprine models have demonstrated significant regeneration of
medial meniscal tissue, with implanted cells shown to be incorporated
within newly formed tissue, following IA delivery of adults BMSCs
(Murphy \emph{et al.} , 2003). The use of BMSCs for treatment of similar
injuries in foals has not been previously reported until now.

Prognosis for grade III meniscal tears in adults horses is poor, with
only 6\% of horses returning to previous athletic function (Walmsley,
Phillips and Townsend, 2003). In adults, grade III tears preclude
complete removal of torn tissue (McIlwraith CW, Nixon AJ, Wright IM, no
date). The results of the current series suggest that the short-medium
term prognosis in foals with meniscal disruption associated with septic
arthritis, is also guarded to poor for return to soundness, with only 1
Foal lame-free out of 3 after 1 year. The prognosis in foals may be more
favorable than adults, due to their greater healing potential, low
weight and easier access to the tears by arthroscopy due to their small
size, allowing more complete debridement. It has been hypothesized that
dystrophic mineralization of the meniscus, visible on radiographs and
US, may lower the prognosis for return to athleticism (Fowlie JG,
Richardson DW, Ortved KF, no date). Early signs of mineralization within
the soft tissue lateral to the LFTJ, and within the LM, in Foals 2 and
3, seen at 6 months, may indicate a poorer long-term prognosis for
soundness.



\textbf{Conclusion}

Meniscal disruption and infection should be considered in neonatal foals
with persistent femorotibial septic arthritis. In such cases, the
meniscus could be a nidus of infection. Meniscal disruption in neonatal
foals, associated with LFTJ sepsis, is associated with a guarded to poor
short-medium term prognosis for return to soundness.

\textbf{Acknowledgements}

The authors would like to express their gratitude to the hospital staff
of the Equine Veterinary Medical Center, for their precious help and
care of the patients. We also would like to thank Al Shaqab and Al
Rayyan farms, for their support with this publication.

\textbf{Funding:} Part of the professional care and use of the equipment
necessary to diagnose and treat these horses were subsidized by Qatar
Foundation and EVMC, however no specific grant from funding agencies was
received.

\textbf{Disclosure:} The authors declare no conflict of interest related
to this report.

\textbf{Ethical Statement:} This publication is in compliance with
regulations on the ethical treatment of animals.

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\textbf{FIGURE LEGENDS}

\textbf{Figure 1:} US images of Foal 2 (a) on admission with moderate
effusion (*) and fibrin formation of the L LFTJ. The LM was abnormal in
shape, protruding beyond the level of the tibial/femoral condyles, with
a diffuse hypoechoic region within it (arrowhead). Screening radiographs
of the L stifle of Foal 2 were taken on admission, findings were
unremarkable (b \& c). Plain CT of the L stifle of Foal 2 revealed
marked distension of the LFTJ with irregularity and sclerosis of the
subchondral bone of the LFC and the lateral tibial condyle (d). Contrast
CT-arthrogram revealed disruption of the LM caudally, with lateral
displacement (e). At its attachment to the caudal horn of the LM,
disruption of the meniscofemoral ligament could be seen (Figure 2 f). F
= lateral femoral condyle; POP = popliteus tendon; T = lateral tibial
condyle.

\textbf{Figure 2:} US images of Foal 1 on admission (a) with marked
effusion and fibrin formation within L LFTJ (*). The LM was abnormal in
shape, protruding beyond the level of the tibial/femoral condyles
(covered by epiphyseal cartilage), with a horizontal hypoechoic line
running through it (arrowheads). Figure (b) shows normal R LFTJ for
comparison. Figure (c) shows arthroscopic image of the cranial aspect of
the L LFTJ of Foal 1, the LM can be seen prolapsed and displaced
craniolaterally, with fibrin accumulation (*), meniscal hyperhemia and
synovial proliferation. Figure (d) shows probe revealing Grade III tear
of LM (\#) extending beyond the margin of the lateral femoral condyle. F
= lateral femoral condyle; T = lateral tibial condyle.

\textbf{Figure 3:} CT images of Foal 3, left (normal) stifle (a) for
comparison with right (abnormal) stifle (b). The LM was diffusely
abnormal with multiple tears in multiple orientations, primarily within
the lateral and caudal aspects (Figure 3 b). A large, pyramidal shaped
tear of the axial aspect of the caudal horn of the LM was present,
resulting in marked irregularity of the axial margin of the meniscus
(Figure 3 c). There was a small tear of the distal substance of the
cranial cruciate ligament. The margin of the caudal cruciate ligament
was minimally fibrillated (Figure 3 d). Figure (e) shows an arthroscopic
image of R LFTJ of Foal 3, the LM can be seen prolapsed and displaced
craniolaterally, with fibrin accumulation. Figure (f) shows Grade III
tear (arrow) of LM extending beyond the margin of the lateral femoral
condyle (F -- femoral condyle; T -- tibia).

\textbf{Figure 4:} US images of Foal 3 R LFTJ 3 days after initial
presentation (a) and 6 months after initial presentation (b). US 6
months after initial presentation revealed increased synovial effusion
within the LFTJ (*) (Figure 4 b). The LM position continued to be
displaced laterally and was abnormal in appearance with areas of
increased echogenicity suggestive of forming mineralization (arrows)
(Figure 4 b). There was a marked palpable thickening and fibrosis over
the region of the LM (Figure 4 c). Radiographs of the L stifle 6 months
after initial presentation showed the LFC was flattened in appearance
with remodeling of the lateral tibial condyle (Figure 4 d). A small
radiolucent area (4 x 3 mm) was evident on the lateral tibial plateau,
surrounded by a rim of sclerosis (arrow) (Figure 4 e).

\textbf{Figure 5:} Radiograph showing a Jamshidi needle approaching the
sternebra for bone marrow aspiration performed under general anesthesia.
This is the first step for production of autologous bone marrow-derived
mesenchymal stem cells (BMSCs) (a). Foals 2 \& 3 received 3 US-guided
injections of autologous BMSCs, in the SER of the affected LFTJs post
initial discharge. T = tibia.

\textbf{Figure 6:} Gross post-mortem images of Foal 2 showing left
stifle joint (a). Image showing ventral/tibial surface of the menisci of
L LFTJ (b), with medial meniscus (left side) and LM (right side). The LM
showed marked thinning with loosening of collagen fibers, especially
caudally (b). Figure (c) shows the posterior articular surface of the
lateral condyle of the proximal tibia, revealing the presence of diffuse
gray-white lesions in the subchondral bone, immediately below the
articular cartilage. Figure (d) shows synovitis with diffuse villous
proliferation and infiltration of inflammatory cells in the villous
stroma. Figure (e) shows meniscitis with irregular arrangement of
collagen fibers, infiltration of inflammatory cells and capillary
angiogenesis. Figure (f) shows a septic cartilage canal with
inflammatory cell infiltration and deposition of fibrin-like material
within the cartilage canal of the articular cartilage. Bar=200 \selectlanguage{greek}µ\selectlanguage{english}m.\selectlanguage{english}
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