Modeling of inflicted head injury by shaking trauma in children: what can we learn?: Part I: A systematic review of animal models

Abstract

Inflicted blunt force trauma and/or repetitive acceleration-deceleration trauma in infants can cause brain injury. Yet, the exact pathophysiologic mechanism with its associated thresholds remains unclear. In this systematic review an overview of animal models for shaking trauma and their findings on tissue damage will be provided. A systematic review was performed in MEDLINE and Scopus for articles on the simulation of inflicted head injury in animals. After collection, the studies were independently screened by two researchers for title, abstract, and finally full text and on methodological quality. A total of 12 articles were included after full-text screening. Three articles were based on a single study population of 13 lambs, by one research group. The other 9 articles were separate studies in piglets, all by a single second research group. The lamb articles give some information on tissue damage after inflicted head injury. The piglet studies only provide information on consequences of a single plane rotational movement. Generally, with increasing age and weight, there was a decrease of axonal injury and death. Future studies should focus on every single step in the process of a free movement in all directions, resembling human infant shaking. In part II of this systematic review biomechanical models will be evaluated.

Full text

REVIEW
Modeling of inflicted head injury by shaking trauma in children: what
can we learn?
Part I: A systematic review of animal models
Marloes E. M. Vester
1,2
&Rob A. C. Bilo
2
&Arjo J. Loeve
3
&Rick R. van Rijn
1,2
&Jan Peter van Zandwijk
4
Accepted: 1 January 2019
#The Author(s) 2019
Abstract
Inflicted blunt force trauma and/or repetitive acceleration-deceleration trauma in infants can cause brain injury. Yet, the exact
pathophysiologic mechanism with its associated thresholds remains unclear. In this systematic review an overview of animal models
for shaking trauma and their findings on tissue damage will be provided. A systematic review was performed in MEDLINE and
Scopus for articles on the simulation of inflicted head injury in animals. After collection, the studies were independently screened by
two researchers for title, abstract, and finally full text and on methodological quality. A total of 12 articles were included after full-
text screening. Three articles were based on a single study population of 13 lambs, by one research group. The other 9 articles were
separate studies in piglets, all by a single second research group. The lamb articles give some information on tissue damage after
inflicted head injury. The piglet studies only provide information on consequences of a single plane rotational movement. Generally,
with increasing age and weight, there was a decrease of axonal injury and death. Future studies should focus on every single step in
the process of a free movement in all directions, resembling human infant shaking. In part II of this systematic review biomechanical
models will be evaluated.
Keywords Closed head injuries .Child abuse .Forensic pathology .Animal models
Introduction
Head injury in young children (under the age of 5 years) can be
caused by several mechanisms, such as compression/crushing,
blunt force, repetitive acceleration-deceleration, and penetra-
tion. These mechanisms may lead to injuries to the skin and/
or skull and/or intracranial contents. The circumstances under
which these mechanisms arise can be accidental (e.g. traffic
accidents or falls from height) or inflicted (e.g. child abuse).
The most prevalent causes of inflicted head injury in children
are blunt force (IHI-BFT: inflicted head injury by blunt force
trauma) and repetitive acceleration-deceleration/shaking (IHI-
ST: inflicted head injury by shaking trauma) [1]. In the Western
world the incidence of inflicted head injury is estimated to be
20–40 per 100.000 children under the age of 1 year and de-
creases with increasing age [2–8]. In literature, inflicted head
injury in children has been referred to by many different terms
(Table 1). Most of these terms are suggestive and imply a trau-
ma mechanism or a certain intention. Therefore these terms
should be avoided in a forensic context.
Blunt force has never been the subject of much debate as a
causative mechanism in inflicted head injury. Shaking still seems
to be the subject of an ongoing debate, especially in courts,
despite reliable medical and biomechanical scientific evidence
Marloes E. M. Vester and Rob A. C. Bilo contributed equally to this work.
*Marloes E. M. Vester
m.e.vester@amc.uva.nl
1
Academic Medical Center Amsterdam, Department of Radiology
and Nuclear Medicine, Amsterdam UMC, University of Amsterdam,
Room G1-231, Meibergdreef 9,
1105AZ Amsterdam, The Netherlands
2
Specialist Services and Expertise Division, Netherlands Forensic
Institute, Laan van Ypenburg 6, 2497 GB The
Hague, The Netherlands
3
Department of BioMechanical Engineering, Delft University of
Technology, Mekelweg 2, 2628 CD Delft, The Netherlands
4
Division of Digital and Biometric Traces, Netherlands Forensic
Institute, Laan van Ypenburg 6, 2497 GB The
Hague, The Netherlands
Forensic Science, Medicine and Pathology
https://doi.org/10.1007/s12024-019-0082-3

that violent shaking can cause severe head injuries. This ongoing
debate is caused by the fact that ‘shaking’as cause of inflicted
head injury (IHI) is a conclusion that is mainly based on exclu-
sion of other causes (medical conditions, birth trauma, and acci-
dental trauma after birth), combined with the absence of findings
consistent with blunt force trauma (e.g. bruising of the scalp or a
skull fracture) and confessions of perpetrators. Because the use of
human infants as experimental research population is impossible
due to ethical standards, research is restricted to juvenile animals,
mechanical surrogates, and mathematical models.
The aim of part I of this systematic review is to discuss
juvenile animal studies used to cause intracranial and retinal
injuries after repetitively induced head motions without a direct
impact mechanism. Part II will elaborate on the physical and
mathematical models concerning shaking in young children.
In shaking the acceleration-deceleration forces are
mostly oriented within the sagittal plane (forward-back-
ward), but movements in the transverse (‘no’- shaking of
one’s head; around the body axis, also commonly re-
ferred to as axial or horizontal) and coronal (sideways;
ear to shoulder) plane will also occur. Since sagittal
movements are considered to be the main component in
shaking, most of the injury is also believed to be the
result of this motion [9]. In shaking, forces applied onto
the torso (grasping and shaking) are transferred by the
neck to the skull, followed by stresses and strains on the
soft tissues in the skull (Fig. 1). When stress and strain
exceed certain thresholds, material failure of the tissue
(injury) will occur, such as retinal hemorrhages, rupture
of bridging veins leading to subdural hemorrhages
(SDH), and post-traumatic encephalopathy (i.e. diffuse
axonal injury; DAI). These physiological transference of
forces will be discussed in more detail in Part II of this
systematic review. Conclusive data on the exact patho-
physiology and threshold values needed to cause these
injuries in cases where IHI-ST is suspected has not been
reported in the literature. The purpose of this review is to
identify animal models specific for shaking trauma and
their findings concerning tissue damage.
Methods
Database search
MEDLINE (Pubmed) and Scopus® were systematically
searched up to January 1st, 2017. Five search queries were
built, using both free terms and indexed terms for mechanical
models, mathematical models, and animal models that mimic
IHI-ST (Appendix). Articles in Dutch, English, French, and
German were included.
Article selection
Identified articles were de-duplicated in Endnote and
subsequently divided into the three (physical, mathemat-
ical, and animal) study models. Two researchers (RR and
MV) each assessed all articles in the animal subgroup on
title, abstract, and lastly on full text, based on relevance
for the understanding or explanation of (aspects of) IHI-
ST pathophysiology. In case of disagreement, a third re-
searcher (RB) was consulted. Manual reference
snowballing of the included articles was performed by
RR and MV. The main authors of the included articles
were contacted for additional, possibly unpublished stud-
ies and information.
All prospective animal studies on the biomechanics of IHI-
ST were included. Exclusion criteria were direct (blunt force)
trauma to the head, non-objective studies (observational stud-
ies of animal behavior), or adult animals (because of incom-
parable development of the nervous system, matured muscle
strength and weight). Full-texts were assessed on the method-
ological quality using a standardized form adapted from the
Critical Appraisal Skills Program (CASP) (available upon
Table 1 Inflicted head injury by
shaking trauma in children:
synonyms in the medical
literature
Synonym Interpretation / perception
Shaken baby syndrome Trauma mechanism: shaking
Shaken impact syndrome Trauma mechanism: shaking and impact
Whiplash shaken infant syndrome Trauma mechanism: shaking
Schűtteltrauma Trauma mechanism: shaking
Syndrome du bébé secoué Trauma mechanism: shaking
Skakvald Trauma mechanism: shaking
Abusive head trauma Intention: abusive
Non-accidental head injury More or less neutral
Inflicted traumatic brain injury More or less neutral
Inflicted head injury More or less neutral
Forensic Sci Med Pathol

request) [10]. In case of doubt on the methodological quality
or study design, the main authors were contacted for addition-
al information.
Data extraction
Data extraction was performed by authors MV and RB using a
predefined data-extraction form (available upon request).
Baseline features such as study design and animal characteris-
tics (e.g. age, gender) were recorded. Furthermore, trauma
mechanism, measurement of inflicted forces and accelerations,
cerebral macroscopy and microscopy, ophthalmological results,
and the main interpretations and conclusions were extracted.
Results
Search results & quality assessment
The initial search resulted in a total of 4675 articles, of which
1977 eligible articles remained after deduplication (Fig. 2).
1954 articles were excluded based on title or abstract, leaving
23 articles for full-text assessment. Thirteen articles about IHI-
ST were excluded based on no IHI-ST, absence of
neuropathophysiological results, or inadequate methodologi-
cal reporting [11–18]. Therefore, ten articles remained after
full-text assessment, and two additional articles were identi-
fied by snowballing. The remaining 12 articles, three in lambs
and nine in piglets, were published by two research groups.
The two main researchers of these groups (JW Finnie and S
Margulies) were contacted for additional information. The
three articles on lambs originated from a single study, whereas
the nine piglet studies were all individual studies. All studies
were small, prospective studies of low quality as assessed by
CASP.
Studies in lambs
The Finnie-group published three articles on a single study
design [9,19,20]. Table 2provides extensive study details.
The overall design included nine ‘injured’and four control
lambs, 5-to-10-days-old. The ‘free shaking’mechanism ap-
plied by humans on the lambs in this study design, closely
resembled shaking in human babies, according to the authors.
Manual shaking of lambs caused extra-axial hemorrhages in
both ‘younger lambs’(5–6 kg) and ‘older lambs’(8.5–12 kg)
(Table 2). ‘Injured’animals had significantly more β-APP
positive neuronal perikaryons, equal in both age groups.
Fig. 1 The 7-step description of inflicted head injury by shaking in children
Forensic Sci Med Pathol

Nevertheless, total injury scores and cranio-cervical junction
related injury (region of maximal impact loading), hypoxic
edema without ischemia, and C-fos immunoreactivity were
higher in the ‘younger lambs’compared to the ‘older lambs’
in the publications of 2012 and 2013 (Table 2)[19,20]. None
of the spinal cords showed parenchymal hemorrhages or
hypoxic-ischemic damage. The first published article in
2010 did not report on the three ‘younger lambs’, which all
died before the designated survival time of 6 h post-injury,
with signs of Axonal injury (AI), neuronal reaction, and albu-
min extravasation [20].
‘Injured’lambs, more commonly the younger ones,
showed damage of the retina with increased GFAP, multifocal
damage of the inner nuclear layer neurons, mild segmental
splitting, and increased β-APP expression [19,20].
Additionally, there was albumin extravasation in the uvea.
Minor retinal hemorrhages were, amongst others, seen in both
of the ‘older lambs’with a SDH [9].
Overall, the ‘injured’lambs showed injuries of the brain,
spinal cord, and eyes, while the control animals did not show
any relevant abnormalities. Injury was more common and
more extensive in the lower weight, younger lambs, which
all died prematurely.
Studies in piglets
The Margulies-group published nine articles, all of individual
studies with 3-to-5-day-old piglets, apart from the 4-week-old
piglets of Ibrahim et al. [21–29]. See Tables 3,4,and5for
more extensive details of the respective articles. Naim et al.
injected half of their tested piglets with folic acid, which is
beyond the scope of this review and data pertaining tothat part
of the study will hence not be included in this review [25]. In
all pig studies, the animals were secured to a bite plate or
padded snout clamp and moved in a single plane (Fig. 3).
All but Coats et al. [27,29] and Eucker et al. [28], rotated
Fig. 2 Prisma flowchart for the
conducted literature search and
article selection process of animal
inflicted head injury by shaking.
Numbers in the flowchart
following the ‘+‘sign are articles
identified through snowballing
Forensic Sci Med Pathol

solely in the transverse (also referred to as axial) plane
(Table 5)[21–26]. Head movements were applied as single,
consecutive/double-single, or continuously repeated rotations.
Macroscopy and microscopy (HE-staining, β-APP, NF68,
NF200, and/or avidin-biotinperoxidase (ABC) histochemis-
try) was performed in all studies, although not on all brains.
Furthermore, cervical spinal cords were examined by some,
butreportedonbynone.
No unintended mortality or morbidity was described in five
of the nine piglet articles (Tables 3,4,and5)[21,22,26–29].
Friess et al. did not find mortality either but excluded 3 piglets
from their ‘moderate acceleration’group (62.9 krad/s
2
)(2pal-
ate fractures and 1 with inability to feed), see Table 3[23]. A
significantly higher mortality (43%) was reported by Friess
et al. for the double rotation, 1-day apart group (average
55.2 and 54.3 krad/s
2
for respectively the first and second
rotation) (1 apnea, 1 poor neurological outcome, and 1 un-
known), compared to animals in which a single rotation was
applied (average 58.5 krad/s
2
)(1withpoorneurologicalout-
come, p< 0.05) (Table 3)[24]. Three additional animals were
sacrificed because of palate fractures (2 from the ‘single rota-
tion’group, 1 from the ‘1-week apart’group). In the study of
Naim et al. 7 injured piglets died: 2 of hard palate fractures, 1
apnoea/cervical spine hematoma, and 3 large SDHs [25].
Duration of unconsciousness was reported in four articles.
Raghupathi et al. did not find overt or extensive loss of con-
sciousness in their injured piglets [21]. Their double rotation,
1-day apart group (average 55.2 krad/s
2
and 54.3 krad/s
2
for
respectively the first and second rotation) (Table 3) had sig-
nificantly longer unconsciousness durations than controls on
day 0 (10.1 ± 3.4 SD vs. 2.8 ± 0.7 SD min) in the study of
Friess et al. [24]. On day 7, the 1-week apart group (average
57.3 and 56.1 krad/s
2
for respectively the first and second
rotation) also had significant longer unconsciousness dura-
tions than controls (5.1 ± 0.7 SD vs. 2.8 ± 0.7 SD min). In
the study of Naim et al. (Table 3) unconsciousness durations
were significantly longer in the injured group (6.27 ± 0.1 SD
min) compared to the control group (3.58 ± 0.1 SD min; p=
0.01) [25]. Furthermore, all piglets with a moderate-
acceleration (average 61.0 krad/s
2
) injury of Ibrahim et al.
were apneic post-injury, compared to 50% of the low-
accelerated animals (average 31.6 krad/s
2
) and 0% of controls
(p< 0.05) (Table 4)[26].
Ocular examinations were reported on by Coats et al.
[27,29]. In the 51 injured piglets (average 30.6 krad/s
2
)stud-
ied by Coats et al. in 2010 [27] ocular hemorrhages were
found in 73% of these 51 piglets, of which 51% were bilateral
and primarily located near the vitreous base. In cases with
bilateral SDHs 26 (68%) had ocular hemorrhages, compared
to one in a unilateral SDH case. All but two animals with
ocular hemorrhages had brain injury. In their study from
2017Coats et al. [29] found no ocular injuries at all, possibly
explained by a five-times lower rotational velocity compared
to other studies e.g. Coats et al. 2010 [27](Table5).
Friess et al. [24] and Naim et al. [25]didnotreportany
axial or extra-axial hemorrhages, which were reported in all
other studies (Table 6). In general, hemorrhages are more fre-
quent and more severe with increasing force, duration, or rep-
etition. Coronal rotations had less frequent, and less severe
hemorrhages and axonal injury (AI) at microscopy in Coats
Table 2 The single study design used for the three articles by Finnie et al. 2010, 2012, and 2013 [1–3]
Journal Journal of Clinical Neuroscience
Objective To develop a satisfactory biomechanical model for the pathogenesis of non-accidental head injury
Animals 7 lambs + 3 controls (2010 article) [1]
- Age matched 7- to-10-day-old, 8.7 kg (5–12)
9 lambs + 4 controls (2012 and 2013 articles) [2,3]
- Age matched 7- to-10-day-old, 8.7 kg (5–12)group1(n=6):‘older’, 10.3 kg [8.5–12 kg]
- Age matched 7- to-10-day-old, 8.7 kg (5–12)group2(n=3):‘younger’,5.5kg[5–6kg]
- Age matched 7- to-10-day-old, 8.7 kg (5–12)controls (n= 4): 7- to-10-day-old, [5–10.5 kg]
Trauma mechanism Anesthesia and ventilation.
Manually grasped under axilla, vigorously shaken, head back and forth with considerable lateral/rotational
movement for 10 × 30 s in 30 min. No head impact.
Histopathology fixation 6 h full anesthesia before death by formalin perfusion fixation. Brains remained 2 h (‘overnight’in 2012
and 2013 articles) in situ and 7 days ex-situ immersed in formalin.
Outcome measures Macroscopy and microscopy of brains and rostral cervical spinal cord; 5 mm slices of brain and spinal cord:
-β-APP immunohistochemistry and HE-staining (2010 and 2012 articles)
- HE-staining, c-fos-staining, and EMA staining. (2013 article)
Ocular examinations (2010 and 2012 articles)
Head and shaking kinematics Published by Sandoz et al. 2012 and Anderson et al. 2014 [4,5]: shaking by human subjects was applied
with a frequency of about 2 Hz, thus ±40 cycles/episode. Resulting accelerations were between 40 and 80 g,
with an average peak acceleration of 62 g.
β-APP immunohistochemistry: (upregulation indicates differentiation of neurons after injury), C-fos and EMA (epithelial membrane antigen): indication
of neuronal activity. HE-stain hematoxylin and eosin stain
Forensic Sci Med Pathol

Table 3 Study design of piglet articles with shaking solely in a transverse plane (often referred to as axial in the articles) [6–10]
Article Objective Animals Trauma mechanism Fixation Outcome measures Input dynamics
Raghupathi 2002 [6]
Journal of Neurotrauma
Traumatic Axonal Injury
after Closed Head Injury
in the Neonatal Pig
To better understand the
mechanical environment
associated with closed
pediatric head injury, by
animal models including
salient features.
7 piglets + 1 control;
3-to-5-day-old; average
weight: 2.0 kg (1.5–3.0, 3
unknown). Average brain
weight: 35 g (33–38).
Anesthesia and ventilation.
Rapid, inertial,
non-impact, transverse
head rotation 110° over
10–12 ms, centered in
the cervical spine, with
HYGE pneumatic
actuator. Heads secured
to padded snout clamp.
6–8 h anesthesia and
ventilation before death.
Heparin perfusion, in situ
fixation with 10%
formalin, followed by
ex-situ fixation
overnight.
Macroscopy and
microscopy of brain,
cerebrum, and brain
stem with Nissl staining,
NF68 and NF200
immunohistochemistry;
ABC-histochemistry.
Angular velocity of
272 rad/s. Average
PAV of 250 ± 10 rad/s.
Raghupathi 2004 [7]
Journal of Neurotrauma
Traumatic axonal injury is
exacerbated following
repetitive closed head
injury in the neonatal pig
To evaluate the effect of
reducing the loading
conditions on the extent
of regional traumatic
axonal injury, and to
develop a model of
repeated mild brain
trauma.
11 piglets + 3 controls;
3-to-5-day-old. Group 1
(n= 5): single rotation
(15 ms), ± weight 2.0 kg
(1.8–2.4), ± brain weight
36 g. Group 2 (n=6):
double rotation (15 ms,
10–15 m apart), ± weight
2.1kg(1.7–2.5),
and ± brain weight: 35 g.
Anesthesia and ventilation.
Rapid, non-impact,
transverse rotations of
the head centered in the
cervical spine, with
HYGE pneumatic
actuator. Heads secured
to padded snout clamp.
6 h Anesthesia and
ventilation before death.
Heparin perfusion, in situ
fixation with 10%
formalin, followed by
ex-situ fixation
overnight.
Macroscopy and
microscopy of brain,
cerebrum, and brain
stem with NF200
immunohistochemistry,
and
ABC-histochemistry.
PAV averaging 172 rad/s
for single and 138 rad/s
for double loads.
Friess 2007 [8]
Experimental Neurology
Neurobehavioral Functional
Deficits Following Closed
Head Injury in the
Neonatal Pig
To develop reliable
quantitative functional
neurobehavioral
assessments for brain
injury in piglets.
18 piglets + 9 controls;
3-to-5-day-old. Group 1
(n= 10): 1 moderate
acceleration (188 rad/s).
Group 2 (n= 5): controls
moderate group. Group 3
(n= 8): 2 consecutive
transverse, mild
accelerated (142 rad/s)
head rotations,
3.1 ± 0.5 min apart.
Group 4 (n= 4): controls
mild group.
Anesthesia and ventilation.
Single, rapid,
non-impact, transverse
head rotation with the
HYGE pneumatic
actuator, 1–3 min after
end of isoflurane. Heads
securedtopaddedbite
plate.
After 12 days
re-anesthetized, death by
pentobarbital, heparin
andtheninsitufixed
with 10% formalin. Ex
situ fixed overnight.
Macroscopy and
microscopy of brain,
cerebrum, brain stem,
and high cervical spinal
cord with HE staining,
β-APP staining, and
NF68
immunohistochemistry
and counterstained with
Meyer’s hematoxylin.
Moderate acceleration:
62.90 ± 10.10 krad/s
2
,
velocity: 188 ± 7 rad/s.
Mild acceleration:
34.12 ± 2.80 krad/s
2
,
velocity: 142 ± 2 rad/s.
Friess 2009 [9]
Journal of Neurotrauma
Repeated traumatic brain
injury affects composite
cognitive function in
piglets
To develop a cognitive
composite dysfunction
score to correlate white
matter injury severity in
piglets with
neurobehavioral
assessments.
21 piglets + 7 controls (7
littermate groups, of 5
piglets); 3-to-5-day-old.
Group 1 (n= 7): single.
Group 2 (n= 7): double;
1 day apart. Group 3
(n= 7): double; 7 days
apart. Group 4 (n=7):
controls. Group 5 (n=5):
controls for group 3
Anesthesia and ventilation.
Moderate (190 rad/s)
rapid, non-impact,
transverse angle rotation
of 110° over 10–12 ms
with HYGE pneumatic
actuator. Heads secured
to padded bite plate.
After 12 days
re-anesthetised, death by
pentobarbital/heparin,
then in situ fixed with
10% formalin. Ex situ
fixed overnight. Group 3
and 5 sacrificed after
5 days instead of 12.
Macroscopy and
microscopy of brain,
cerebrum, brain stem,
and high cervical spinal
cord with HE staining,
β-APP staining, and
counterstained with
Meyer’s hematoxylin.
Velocity: Gr 1::
193.7 rad/s, Gr 2:
196.7–195.9 rad/s, Gr
3:: 190.3–187.6 rad/s
Acceleration: Gr 1: 58.51
krad/s
2
.Gr2:
55.17–54.35 krad/s
2
.
Gr 3: 57.32–56.12
krad/s
2
Naim 2010 [10] To test if folic acid
supplementation after
4 groups: 40 female + 10
male piglets,
Anesthesia and ventilation.
Rapid, inertial, 90–110°
After 6 days
re-anesthetized, death by
Behavioral testing on days
1 and 4 following injury.
Angular velocity:
Forensic Sci Med Pathol

Tab l e 3 (continued)
Article Objective Animals Trauma mechanism Fixation Outcome measures Input dynamics
Developmental
Neuroscience
Folic Acid Enhances Early
Functional Recovery in a
Piglet Model of Pediatric
Head Injury
injury would decrease
the severity of TAI in our
well-established piglet
model of moderate
pediatric head injury.
3-to-5-day-old. Group 1
(n= 7): injured + daily
intraperitoneal folic acid
injection (IF) 2.24 kg.
Group2(n= 8): injured +
daily saline injection (IS)
2.01 kg. Group 3 (n=8):
uninjured + daily folic
acid injection (UF)
1.8 kg. Group 4 (n=7):
uninjured + daily saline
injection (US) 1.99 kg.
Group 5: behavior
controls.
transverse rotation,
centeredinthecervical
spine with the HYGE
pneumatic actuator.
Heads secured to padded
bite plate.
pentobarbital, heparin
andtheninsitufixed
with 10% formalin.
Macroscopy and
microscopy of brain,
cerebrum, brain stem,
and high cervical spinal
cord with HE staining,
β-APP staining, and
counterstained with
Meyer’s hematoxylin.
IF group:
193.29 ± 5.31 rad/s,
IS group:
194.25 ± 8.11 rad/s
β-APP immunohistochemistry (β-amyloid precursor protein) HE-stain hematoxylin and eosin stain, NF Neurofilament ABC avidin-biotinperoxidase histochemistry, PAV peak angular velocity
Table 4 Study design of 4-week old piglet article [11]
Article Objective Animals Trauma mechanism Fixation Outcome measures Input dynamics
Ibrahim 2010 [11]
Journal of
Neurotrauma
Physiological and
pathological
responses to head
rotations in toddler
piglets
To characterize the
physiological and
pathological responses
of the immature brain to
inertial forces and their
relationship to
neurological
development.
13 female piglets; brain weight
56.04 g, 4-week-old.
Group 1 (n= 2): controls,
Group 2 (n=4):lowrate
angular acceleration, Group 3
(n= 6): moderate rate angular
acceleration.
Anesthesia and ventilation.
Single non-impact,
transverse rotation,
centered in the cervical
spine. Heads secured to
padded bite plate with
snout straps and pneumatic
actuator.
Euthanized 6 h after
injury. Death by
pentobarbital, in situ
perfusion fixation
with 10% formalin.
Exsitufixedin10%
formalin.
Macroscopy and
microscopy of brain,
cerebrum, brain stem,
and high cervical
spinal cord, with
HE-staining, β-APP
staining, NF68 and
counterstained with
Meyer’s
hematoxylin.
Acceleration: low
(31.6 ± 4.7 krad/s
2
,) or
moderate (61.0 ± 7.5
krad/s
2
,). PAV: low:
129 ± 13 rad/s, moderate
194 ± 15 rad/s.
β-APP β-amyloid precursor protein, HE-stain hematoxylin and eosin stain, NF Neurofilament, PAV peak angular velocity
Forensic Sci Med Pathol

Table 5 Study design of piglet articles with movement in multiple planes [12–14]
Article Objective Animals Trauma mechanism Fixation Outcome measures Input dynamics
Coats 2010 [12]
Investigative Ophtalmology
& Visual Science
Ocular Haemorrhages in
Neonatal Porcine Eyes
from Single, Rapid
Rotational Events
To characterize ocular
hemorrhages from
single, rapid head
rotations in the
neonatal pig.
51 piglets + 5 controls;
3-to-5-day-old. Group 1
(n= 13): sagittal rotation,
Group 2 (n= 7): coronal
rotation, Group 3 (n=31):
transverse rotation, Group 4
(n= 5): controls.
Anesthesia and ventilation.
Single rapid (15 ms),
non-impact head rotation,
centered in the C3-C5
spine, with HYGE
pneumatic actuator. Heads
secured to padded snout
clamp.
6 h anesthesia before death
by heparin infusion and in
situ fixation with 10%
formalin. Ex situ fixed
overnight.
Brainmacroscopy(46/51
animals), microscopy
(31/51): brain, cerebrum,
brainstem: HE-staining and
NF68 or APP. Indirect
ophthalmoscopy, (10
injured +2 controls) and
macroscopy, microscopy
(HE staining)
Angular velocities and
accelerations:
117–266 rad/s and
30.6–101 krad/s
2
.
Eucker 2011 [13]
Experimental Neurology
Physiological and
histopathological
responses following
closed rotational head
injury depend on direction
of head motion
Theeffectofsagittaland
coronal rotation on
regional cerebral blood
flow changes,
unconsciousness times,
and apnea incidences,
as well as early
pathological outcomes.
36 piglets; 3-to-5-day-old.
Group 1 (n= 9) HOR-HIGH:
> 90° horizontal (transverse)
rotation, Group 2 (n=7)
COR: > 90° coronal rotation,
Group 3a (n= 6) SAG: > 60°
sagittal rotation, Group 3b
(n= 6) HOR-LOW: 90°
horizontal (transverse)
rotation, Group 4 (n=4):
controls.
Anesthesia and ventilation. A
single rapid (12–20 ms),
non-impact head rotation,
centered at the
mid-cervical spine with a
bite plate.
Euthanized 6 h after injury.
Death by pentobarbital,
perfusion fixation/in situ.
Fixation with 10%
formalin. Ex situ fixed in
10% formalin for over
24 h.
Macroscopy and microscopy
of brain, cerebrum, brain
stem, and high cervical
spinal cord, with
HE-staining, β-APP
staining and counterstained
with Meyer’s hematoxylin.
Group 1: PAV of
198 ± 12 rad/s. Group 2:
PAV 208 ± 11 rad/s. Group
3a: PAV 166 ± 3 rad/s.
Group 3b: PAV
168 ± 3 rad/s. Group 4:
(controls) 0 rad/s.
Coats 2017 [14]
JournalofNeurotrauma
Cyclic Head Rotations
Produce Modest Brain
Injury in Infant Piglets
To systematically
investigate the
post-injury
pathological time
course after cyclic
low-velocity head
rotations and compare
them with single head
rotations.
50 piglets + 4 controls;
3-to-5-day-old. Group A
(n= 5): sagittal, episodic.
Group B (n= 6 sagitt al, 2
transverse): continuous 30 s.
Group C (n= 4): t ransverse,
continuous 10 s. Group D
(n= 8): transverse,
continuous 30 s. Group E
(n= 9): transverse, double
continuous 30 s. Group F
(n= 5): transverse,
continuous 30 s. Group G
(n= 5): sagittal,
single-noncyclic. Group H
(n= 6): sagittal,
single-noncyclic. Controls:
(n=2)6 h+(n=2)24h
post-injury.
Anesthesia and ventilation.
Non-impact, 30° sagittal
or 50° transverse rotations
of the head, centered in the
cervical spine, with
HYGE pneumatic
actuator. Heads secured to
bite plate; hyperflexion/
extension of the neck was
avoided.
Sacrificed 6 h (Group A, B,
G, and Controls), 24 h
(Group C, D, E, H and
Controls) or 6 days
(Group F) after last injury.
Macroscopy and microscopy
of brain, cerebrum, and
brain stem; HE-staining,
β-APP staining with
Mayer Hematoxylin
counterstaining. Eyes:
Indirect fundus
examination, macroscopy,
and HE-staining.
Single axis angular rate
transducer; 2–3Hz.
Sagittal: peak-to-peak
average angular velocity
(unclear how this was
determined)
22.71 ± 3.49 rad/s and
average peak angular
acceleration of
606.21 ± 160.30 rad/s2.
Transverse: peak-to-peak
angular velocity
28.92 ± 2.85 rad/s and peak
angular acceleration
780.08 ± 118.03 rad/s2.
β-APP β-amyloid precursor protein, HE-stain hematoxylin and eosin stain, NF Neurofilament, PAV peak angular velocity
Forensic Sci Med Pathol

et al. and Eucker et al. compared to sagittal or transverse
rotations (Table 6)[27,28]. Eucker found a significantly
higher subarachnoid hemorrhage (SAH) score for high veloc-
ity, transverse (in the article referred to as horizontally) rotated
piglets and sagittal rotated piglets comparedto controls. Extra-
axial hemorrhages were mainly located frontally in the
Raghupathi articles [21,22].
The time between two injuries and the time between injury
and measurement might be of influence on the extent of mea-
sured AI, according to Friess et al. and Coats et al. [24,29].
Single rotated piglets surviving 12 days (average 58.5 krad/s
2
)
had significantly less β-APP staining (sign of AI: 2 h to 4–
6 weeks) compared to single rotated piglets surviving 5 days
(p< 0.03), thus less white matter injury was detected over time
[24]. Episodic and continuous cyclic head rotations for 30 s
had no differences in the amount of AI after 6 h [29]. There
was a significant increase in AI with increasing post-injury
time (24 h vs. 6 h) for 30 s continuous rotated animals (p=
0.035).
No AI was found in the controls. AI was found in all stud-
ies to some extent in injured groups, although not always
significantly different from the control groups. Raghupathi
et al. found no neuronal loss, nor a relation between the ve-
locity and density of AI located in multiple white matter tracts
[21]. In 2004 they reported that two consecutive rotations
caused AI in the peripheral subcortical and central deep white
matter regions, especially more foci with multiple injured
axons (p= 0.05) compared to a single rotation [22]. After a
single rotation, AI was found in the peripheral subcortical and
central deep white matter regions in the frontal lobes. After
two consecutive rotations, AI was also present in the white
matter of the parietal and temporal lobes, corpus callosum,
hippocampus, and basal ganglia. Friess et al. found AI in the
olfactory tract, germinal matrix, internal capsule, and some
posteriorly in the moderately rotated piglets (average 62.9
krad/s
2
), compared to no AI in the mildly rotated group (av-
erage 34.1 krad/s
2
)(Tables3and 6)[23]. In 2009 they report-
ed that the majority of AI was located in the frontal lobes in
injured animals with a significantly greater white matter β-
APP injury volume in all three injury groups compared to
uninjured animals [24]. Naim et al. found white matterinjuries
mostly in the deep white matter of the frontal lobes and some
in parietal and temporal lobes or brainstem [25]. Eucker et al.
found a significantly greater early ischemia score in the sagit-
tal rotations than in controls [28]. High velocity transverse
rotations resulted in significantly more AI than coronal or
low-velocity horizontal rotations (Table 5). Both sagittal and
transverse rotations produced the greatest degrees of tissue
pathology, whereas coronal rotations did not result in any
significant pathology. AI was more extensive in the anterior
regions of the brain compared to other brain regions for every
injury group, after multiple regression analysis. Coats et al.
found injury in 88.5% of the cyclic rotated animals surviving
24hand6days[29]. After 24 h there were significantly more
animals with AI after continuous rotations for 10 s than 30 s
(p= 0.014). There was more hypoxic-ischemic injury and
extra-axial hemorrhages in 30 s continuous rotated piglets
than in piglets with a single head rotation, but this was only
noticeable after 24 h.
Ibrahim et al. compared the result of 4-week-old piglets to
the previously published results by Eucker et al. in 5-day-old
piglets [26,30]. They found no significant differences in SAH
scores and brain volume of AI between those two groups.
However, when comparing these 4-week-old animals to 5-
day-old piglets, based on the mass scaled acceleration princi-
ple of Ommaya and Hirsch, 1971 [31], there was a significant
difference for both SAH scores (p< 0.02) and brain volume of
AI (p< 0.004). In comparison to lower rotational acceleration
(average 31.6 krad/s
2
), larger rotational accelerations (average
61.0 krad/s
2
) caused more severe SAH, more areas of ische-
mia, and larger volumes of AI.
Discussion
Ommaya was the first to describe brain injury after a whiplash
trauma in primates with SDH in 15 out of 19 monkeys with a
concussion [14,32,33]. IHI-ST is, as stated before, still an
Fig. 3 Rotational planes in animal studies of IHI-ST
Forensic Sci Med Pathol

Table 6 Outcomes in piglet studies [6–14]
Article Group Intervention No piglet angular velocity
rad/s (± SD)
angular acceleration
krad/s2 (± SD)
SDH (SAH) PH Ischemia AI (β-APP, NF68,
or NF200)
Raghupathi 2002 [6]: 7 piglets + 1 control; 3-to-5-day-old, 6–8 h till death
a
1 single rapid transverse rotation 7 250 (± 10) 116.70 (± 21.18)
b
+(+) + 4.5–8.7 axons/ mm
2
2 control 1 0 0 - (−)––
Raghupathi 2004 [7]: 11 piglets + 3 controls; 3-to-5-day-old, 6 h till death
a
1 single transverse rotation 5 172 (± 17) 50.84 (± 5.56)
c
60% (−)–80%
2 double transverse rotation, 10–15 ms apart 6 136 (± 8) and
140 (± 6)
34.38 (± 8.88) and
35.98 (± 7.03)
c
100% (−)–83.3%
3 controls 3 0 0 - (−)––
Friess 2007 [8]: 18 piglets + 9 controls; 3-to-5-day-old, 12 days till death
1 single moderate transverse acceleration
188 rad/s
10 (3 excl) 188 (± 7) 62.90 (± 10.1) - (100%) 10% 50%
2 controls moderate group 5 - (−)––
3 2 consecutive rapid transverse acceleration
142 rad/s, ± 3.1 min apart (mild)
8 142 (± 2) 34.12 (± 28.0) - (−)––
4 controls mild group 4 0 0 - (−)––
Friess 2009 [9]: 21 piglets + 7 controls; 3-to-5-day-old, 5 days or 12 days till death
1 single transverse injury, 12 d survival 7 (3 excl) 193.7 58.51 1 severe, 1 moderate 0.07% (2 brain stem)
2 double transverse injury 1 d apart, 12 d
survival
7 (3 excl) 196.7 and 195.9 55.17 and 54.35 2 severe 0.36% (3 brain stem)
3 double transverse 7 d apart, 5 d survival 7 (1 excl) 190.3 and 187.6 57.32 and 56.14 0.37% (1 brain stem)
4 controls, 12 d survival 7 0 0 1 moderate –
5 single transverse injury controls, 5 d survival 5 192 (± 1) 52.55 (± 1.74) 0.25% total brain
(p< 0.03 vs group 1)
Naim 2010 [10]: 40 piglets + 10 controls; 3-to-5-day-old, 6 days till death
d
2 single transverse injury + daily intraperitoneal
saline injection (IS)
8 194.25 (± 8.11) 0.18% (p< 0.02)
4 uninjured + daily saline injection (US) 7 0 0.003% (p= 0.003)
5 controls 10 0
Ibrahim 2010 [11]: 10 piglets + 2–3 controls; 4-week-old, 6 h till death
a
1 controls 2–3? 0 0
2 single transverse injury, low rate 4 128.5 (± 12.6) 31.6 (± 4.7)
3 single transverse injury, moderate rate 6 194.0 (± 14.8) 61.0 (± 7.5) P<0.05more than
controls or low group
P< 0.05 more vs low
group or controls
P<0.05morethan
control or low group
Coats 2010 [12]: 51 piglets + 5 controls; 3-to-5-day-old, 6 h till death
1 single sagittal injury 13 185 (± 17) 30.6–101 100% bilateral 57% x 71% diffuse, 14% focal
2 single coronal injury 7 208 (± 11) 30.6–101 0% bilateral, 71%
unilateral
0% 0% diffuse, 20% focal
Forensic Sci Med Pathol

Tab l e 6 (continued)
Article Group Intervention No piglet angular velocity
rad/s (± SD)
angular acceleration
krad/s2 (± SD)
SDH (SAH) PH Ischemia AI (β-APP, NF68,
or NF200)
3 single transverse injury 31 207 (± 31) 30.6–101 96% bilateral 58% 53% diffuse, 32% focal
4 controls 5 0 0 –– –
1–3 overall results 83% bilateral, 11%
unilateral
48%
Eucker 2011 [13]: 29 piglets + 4 controls; 3-to-5-day-old, 6 h till death
a
1 single horizontal (transverse) high velocity 9 198 (± 12) (100%
e
) 56% 100%
e
2 single coronal injury 7 208 (± 11) 29% 0% 14%
3a single sagittal injury 6 166 (± 3) (100%
e
) 83%
e
100%
e
3b single horizontal (transverse) low velocity 7 168 (± 3) (83%
e
) 33% 100%
e
4 controls 4 0 (0%) 0% 25%
Coats 2017 [14]: 50 piglets + 4 controls; 3-to-5-day-old, 6 h, 24 h or 6 days till death
f,g
A sagittal episodic 6 h survival 5 22.96 (± 2.61) 606.21 (± 160.3) 20% (SDH + SAH) 0%
B sagittal 30 s continuous 6 h survival 6 22.51 (± 4.33) 606.21 (± 160.3) 33% (SDH + SAH) 17%
B transverse 30 s continuous 6 h survival 2 28.52 (± 4.05) 780.08 (± 118.03) 0% (SDH + SAH) 0%
C transverse 10 s continuous 24 h survival 4 30.86 (± 0.77) 780.08 (± 118.03) 50% (SDH + SAH) 100%
D transverse 30 s continuous 24 h survival 8 28.54 (± 2.67) 780.08 (± 118.03) 50% (SDH + SAH) 25%
E transverse double continuous 24 h survival 9 28.75 (± 3.02) 780.08 (± 118.03) 67% (SDH + SAH) 56%
F transverse 30 s continuous 6 d survival 5 28.41 (± 3.87) 780.08 (± 118.03) 40% (SDH + SAH) 80%
G sagittal noncyclic 6 h survival 5 32.19 (± 7.04) 2857.40 (± 1682.91) 0% (SDH + SAH) 0%
H sagittal noncyclic 24 h survival 6 42.86 (± 6.45) 866.33 (± 213.92) 0% (SDH + SAH) 33%
Sham controls 6 h and 24 h survival 2 / 2 0 0% (SDH + SAH) 0%
SDH subdural hematoma, SAH subarachnoid hemorrhage, PH parenchyma hemorrhage, AI axonal injury
a
peak angular velocities instead of angular velocities,
b
deceleration instead of acceleration,
c
maximal deceleration instead of acceleration,
d
Because of intervention piglets injected with folic acid are not
representable for IIHI in human infants, and thus excluded from this table,
e
significant,
f
peak-to-peak angular velocities,
g
angular acceleration in rad/s
2
instead of krad/s
2
. NB: not all brains were
macroscopically and/or microscopically examined
Forensic Sci Med Pathol

important and current topic of debate. It might be expected
that this would be reason for extensive studies in animals in
the past by many different research groups. However, in this
systematic review, only two research groups had usable arti-
cles. Older articles from 1998, 2002, and 2004 in rodents were
excluded for their inconclusive reporting of methodology and
results [12,13,16,17]. Though Ommaya was the first to
describe these kinds of injuries, the used trauma mechanism
is incomparable to that of IHI-ST, why these studies were also
excluded. The included piglet and lamb articles are difficult to
compare because of differences in species, age, trauma mech-
anisms, and small study groups without source data available.
With increasing moral and ethical standards, animals are less
and less used as study objects and replaced by mathematical
and physical models as described in Part II of this review.
These two combined systematic reviews are the novel for
IHI-ST.
Lambs
IHI-ST, as described earlier, is most closely resembled by the
study with shaken lambs. Like in human babies, the lambs
were held by adults around the ribcage leaving the head free
for acceleration-deceleration rotation in any direction for a
significant amount of time (30 s) without a direct impact trau-
ma. Accelerations generated in lambs by shaking have been
reported by Sandoz et al. and Anderson et al. [11,15].
Although the articles state that the lambs were shaken for
20 s, additional information by the main author confirmed that
the shaking was actually for 30 s as in the three Finnie articles.
Anderson added that three adults manually shook the animals,
mainly in the sagittal plane. Shaking speed and perimeter dif-
fered per person and weight of the animals. Forces were mea-
sured with a triaxial piezoresistive accelerometer (8 g,
2000 Hz, model 7268C, Endevco©) and a motion tracking
sensor (9.1 g, 60 Hz, Fastrak-Polhemus©) on the head and
one motion tracking sensor under the axilla. Animals were
shaken with approximately 2 Hz, thus around 40 cycles per
shaking episode [11]. Accelerations (in absolute value, not
otherwiseexplained)werebetween0and5gin94.43%of
cases, with a maximum of 26.64 g [15]. Acceleration of im-
pulses >30 g had peak measurements of 58-79 g and average
peak accelerations of 35.9–41.6 g for the younger animals,
and 39-80 g and 34.1–44.9 g, respectively, for the older lambs.
The lambs were compared to 9-month-old human infants
by the authors, based on their body weight. The pathophysi-
ology of trauma due to shaking was deemed comparable to
human infants since both have weak neck muscles, though
this effect might have been exaggerated by the anesthesia in
the lambs. Both human infants and lambs have a relatively
large head/brain compared to the body, along with a wide
subarachnoid space, allowing a relatively large brain move-
ment within the skull [34]. Both have brains that are not yet
fully myelinated, with a higher brain water content, and there-
by an increased vulnerability to shearing injury [9,35]. This
may explain the more extensive injuries in the younger lambs
compared to the older lambs (Table 2). The lamb brain is more
elliptically shaped and is in line with the myelum and cervical
spinal cord compared to an almost 90-degree angle between
the rounder human brain and the spinal cord. The effect of the
difference in shape and orientation of the brain is not known.
A drawback of these publications on lambs is the fact that,
according to the main author, all three articles were based on
the same nine injured and four control lambs. Results there-
fore should be reproduced by other and larger studies.
Piglets
In all piglet studies, except Coats et al. [29], only single ac-
celerations were applied to the study animals. This reduces its
value for translation to human shaken babies as it is believed
by many that the repeated sudden deceleration, in combination
with the acceleration, causes the intracranial injury [34].
When shaking a human baby, the head will rotate mostly in
a sagittal plane, but may sustain rotations in the transverse and
coronal planes, along with possible chin-chest collisions, de-
pending on body weight and individual shakers [11].
Inconsistency in the use of terminology for rotation directions
hinders interpretation and translation to humans. Different ro-
tation planes have been studied by Coats et al., Eucker et al.,
and Coats et al. [27–29]. However, none of these studies com-
bined the different rotation planes, while simultaneously oc-
curring rotations in different directions might amplify the
forces and deformations exerted on the anatomical structures
in the head and hence worsen the resulting injuries.
Furthermore, chin-chest collisions were avoided within these
studies. More importantly, the single plane movement (only
transverse in 6 out of 9 piglet studies) thus does not represent
the main repeated back-and-forth motions and internal trans-
lation of forces in IHI-ST. Therefore, there are insufficient data
to estimate whether and to what extent the results of these
studies could be translated to IHI-ST.
Though executed and published by a single research group,
specific reports on physics are inconsistent. Angular velocities
are reported by Friess et al. [23,24], Naim et al. [25] and Coats
et al. [27] compared to peak angular velocities by Raghupathi
et al. [21,22], Ibrahim et al. [26] and Coats et al. [29], and
even peak-to-peak angular velocities by Coats et al. [29].
Where most articles report on angular accelerations,
Raghupathi et al. report on decelerations in 2002 and maxi-
mum decelerations in 2004. Furthermore, most reported an-
gular accelerations were in krad/s
2
ranges, such as Coats et al.
[27], who reported 30.60–101 krad/s
2
for angular velocities of
177–266 rad/s. These high angular velocities do, depending
on the angle over which the head was moved (which is, un-
fortunately, not in all articles reported), resemble shaking with
Forensic Sci Med Pathol

frequencies of 20 to 161 Hz, assuming angular ranges of mo-
tion of 110 to 30 degrees.
Shaking in human infants is often not a onetime occurring
incident in time, but an event reoccurring over longer periods
of time. Friess et al. and Raghupathi et al. postulated that
repeating of the trauma within 24 h might increase the sensi-
tivity to injury by latent readjustment or injury accumulation
[22,24]. Besides the aforementioned influences of anesthesia,
buprenorphine and isoflurane anesthetics used in the piglet
studies might have some neuroprotective features and could
affect the results by reducing the injury [36,37]. Mortality was
reported in none of the articles. Friess et al. excluded some
piglets because e.g. palate fractures or an inability to being fed
due to the injury procedure. Because of exclusion those piglets
were not counted as a mortality [23,24].
Like humans, pigs have a gyrencephalic brain, with similar
grey-white differentiation and physiological responses, and
are therefore commonly used as a model for human infants.
A 3-to-5-day-old piglet brain can be roughly compared to a 2-
to-4-weeks-old human baby based on activity, myelination,
and growth. Ibrahim et al. state that a 4-week-old piglet brain
is comparable to a 2- to-4-year-old human brain based on
development and myelination. Like the lamb brain, the piglet
brain is more elliptically shaped and angled in line with the
myelum and cervical spinal cord, compared to an almost 90-
degree angle between the rounder human brain and the
myelum. The single plane rotational movement in the piglet
studies and the unalike anatomy make the results of these
studies difficult to translate to the human infant.
The piglet’s eye has more in common with the human eye
than most other animals’eyes, for example, the retina vascu-
larization and the vitreous base, although there are also differ-
ences such as the absence of a fovea or macula [38,39]. The
acceleration-deceleration trauma in IHI-STis thought by some
to cause the vitreous body to pull on the retina and conse-
quently induce vascular injury. Yet, due to all the differences,
it is hard to estimate whether the results of Coats et al. [27]
could be used for human injury assessment.
Conclusion
Injury sustained by lambs in shaking studies gives some in-
formation on the relationship between the applied shaking
accelerations, the animal, and the clinical outcome. Older,
heavier lambs had less AI and deaths. For piglets, it was found
that rotation direction influenced the neurological symptoms
and neuropathological findings. Tissue strain might be of in-
fluence on these injuries, yet the anatomical differences and
the inconsistent choice of (mostly noncyclic) rotation direc-
tions in the various studies make an adequate comparison very
difficult. With regard to the ocular results in piglets, no direct
translation to human infants can be made due to differences in
anatomy and a lack of evidence of the relevance of these
differences. The study in 4-week-old piglets might provide
some information about single rotational impacts in toddlers,
but lacks confirmation by other studies. Future studies should
therefore focus on understanding each individual step in the
IHI-ST process and its respective accelerations, forces, tissue
deformations and injury thresholds. Ideally, experimental con-
ditions should allow a free movement of the head in all direc-
tions, without any external impacts, in simulations compara-
ble to inflicted head injury due to shaking in human infants.
Key points
1. Despite the importance for understanding IHI-ST, ade-
quate large randomized animal studies are lacking in the
literature.
2. Animal articles, closely representative of IHI-ST as pre-
sumed to occur in human infants, are only available from
a single study in lambs.
3. Studies in piglets provide some information on IHI-ST,
mostly about a fast transverse acceleration, but are other-
wise difficult to translate to human infants because of the
(non-cyclic) rotational movement restrictions.
4. Future research should focus on larger, more consistent
animal studies, validating the applicability of juvenile an-
imal experiments as a model of human IHI-ST.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval and informed consent Not applicable to this system-
atic review.
Appendix 1 Search Queries
Q1. ((finite[All Fields] AND (“elements”[MeSH Terms] OR
“elements”[All Fields] OR “element”[All Fields]) AND
shaken[All Fields]) OR (((biomechanical[All Fields]
AND shaken[All Fields]) OR ((“models,
animal”[MeSH Terms] OR (“models”[All Fields]
AND “animal”[All Fields]) OR “animal models”[All
Fields] OR (“animal”[All Fields] AND “model”[All
Fields]) OR “animal model”[All Fields]) AND (“shaken
baby syndrome”[MeSH Terms] OR (“shaken”[All
Fields] AND “baby”[All Fields] AND “syndrome”[All
Fields]) OR “shaken baby syndrome”[All Fields] OR
(“shaken”[All Fields] AND “baby”[All Fields]) OR
“shaken baby”[All Fields]))) OR (non[All Fields]
AND accidental[All Fields] AND (“craniocerebral
trauma”[MeSH Terms] OR (“craniocerebral”[All
Forensic Sci Med Pathol

Fields] AND “trauma”[All Fields]) OR “craniocerebral
trauma”[All Fields] OR (“head”[All Fields] AND
“injury”[All Fields]) OR “head injury”[All Fields])
AND model[All Fields]))) OR ((“Simulation”[Journal]
OR “simulation”[All Fields]) AND shaken[All Fields])
Q2. (((((((biomechanical) OR animal model) OR finite ele-
ment) OR simulation) OR mannequin) OR dummy))
AND (((shaken baby) OR abusive head trauma) OR
non accidental head)
Q3. (((Biomechanical Phenomena/methods [Mesh]) OR
(((((((biomechanical model) OR biomechanical evalua-
tion) OR biomechanical study) OR biomechanical) OR
biomechanical analysis) OR “Models,
Neurological”[Mesh]) OR “Models,
Theoretical”[Mesh]))) AND ((((((((((((Hematomas,
Subdural) OR Subdural Hematomas) OR Subdural
Hematoma) OR Hemorrhage, Subdural) OR
Hemorrhages, Subdural) OR Subdural Hemorrhage)
OR Subdural Hematoma, Traumatic) OR Subdural
Hemorrhages) OR Hematoma, Traumatic Subdural)
OR Hematomas, Traumatic Subdural) OR Traumatic
Subdural Hematoma) OR Traumatic Subdural
Hematomas)
Q4. (((biomechanic* OR dynamic* OR kinematic* OR mo-
tion OR force OR impact) AND (phenomena OR meth-
od OR model OR evaluation OR study OR analysis))
OR (“finite element”OR “FEM”)OR((animalORneu-
rological OR theoretical) AND model) OR simulat* OR
doll OR mannequin OR dummy OR anthropomorphic)
AND ((shake* AND (infant OR baby OR impact))
AND (“subdural Hematoma”OR “subdural
Hemorrhage”OR ((craniocerebral OR head OR retinal)
AND (injury OR trauma OR bleeding))) AND ((“non
accidental”OR “nonaccidental”OR “non-accidental”)
OR inflict* OR violen* OR abus* OR shaking))
Pubmed was searched using queries Q1 to Q4 and com-
bining their results. Scopus was searched using query Q4.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
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Creative Commons license, and indicate if changes were made.
Publisher’snote Springer Nature remains neutral with regard to jurisdictional
claims in published maps and institutional affiliations.
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