293

Journal of Neonatal-Perinatal Medicine 7 (2014) 293–299
DOI 10.3233/NPM-1473313
IOS Press

Case Report

Are we considering neonatal stroke early
enough in our differential diagnosis?
M. Paddocka,∗ , A. Demetrioub and R. Nichollc
a Academic Unit of Radiology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom
b Department of Paediatrics, Imperial College Healthcare, London, United Kingdom
c Neonatal Unit, Northwick Park Hospital, Harrow, Middlesex, United Kingdom

Received 16 June 2014
Revised 30 July 2014
Accepted 9 September 2014

Abstract.
BACKGROUND: Neonatal stroke is an important cause of neurodisability in childhood and in later life. Delay in diagnosis is
often inevitable due to the non-specific presentation, the lack of clinical signs, and not considering stroke early enough in the
differential diagnosis.
CASE: We report the case of a baby who initially presented with apparent newborn “jitteriness” and abnormal movements.
On the background of an unremarkable birth history and negative initial investigations, the baby subsequently developed focal
seizures. The diagnosis was suspected to be neonatal stroke which was later confirmed on magnetic resonance imaging.
CONCLUSION: General Movements assessment is an established useful tool used in the assessment of such babies and proves
helpful in evaluating whether movements are normal or pathological, in addition to prognosticating outcome. Cranial ultrasound
is a commonly employed first-line investigation, however, initial normal intracranial appearances do not exclude stroke. Magnetic
resonance imaging is the gold standard but may not be immediately available to all practitioners.
Keywords: Jittery, jitteriness, abnormal movement, seizure, neonatal stroke

1. Introduction
Stroke in the neonatal period can present with a wide
range of varying, non-specific clinical manifestations
such as lethargy, hypotonia, and apnea [1]. Given that
these may be the presenting symptoms of a wide range
of neonatal conditions, broad first line investigations
are required to exclude other pathologies. Once these
∗ Corresponding author: Dr. Michael Paddock, Academic Unit of
Radiology, University of Sheffield, Floor C, Royal Hallamshire
Hospital, Glossop Road, Sheffield, S10 2JF, United Kingdom. Tel.: +44 1142711643; Fax: +44 1142711714; E-mail:
michael.paddock@doctors.org.uk.

have been excluded, or symptomatology indicates a
neurological focus (abnormal movements; seizures;
hemiparesis), stroke should feature more prominently
in the differential diagnosis. Recognition and characterization of neonatal movements as normal, such as
newborn “jitteriness”, or pathological, such as focal
seizures, is key in determining the level of clinical
concern and the timely initiation of investigations and
treatment. This case report highlights the importance
of assessing movements in those patients whose movements are suspected to be pathological and discusses
the importance of initiating appropriate investigations
promptly.

1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved

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M. Paddock et al. / Early diagnosis of neonatal stroke

2. Case history
A term female infant was reviewed on the postnatal ward on day 2 of life. The mother, who was in a
non-consanguineous relationship, booked for antenatal care late in her pregnancy and was a gravida 2 para
0+1 (miscarriage at 10 weeks). She had an uncomplicated pregnancy with normal booking blood tests and
antenatal ultrasound scans. There were no risk factors
for sepsis and the baby was born in good condition by
spontaneous vaginal delivery with APGAR scores of
9 and 10, at 1 and 5 minutes respectively. Vitamin K
was administered via intramuscular injection.
The midwife caring for the baby had requested a
medical review for witnessed right arm “jittery” movements which eased after a few minutes. This was also
observed by the mother but reported by the father, as
the mother spoke no English. Upon review, the baby
handled well, with no features of dysmorphism and
a normal neurological examination. A capillary blood
gas revealed a normal blood glucose level and baseline
blood tests including urea, electrolytes and bone profile
were normal, excluding hypoglycemia and electrolyte
imbalance as a potential cause. A cranial ultrasound
scan was performed and was reported as normal by the

operator. The baby was kept on the postnatal ward with
the mother.
The night shift midwife requested a further review
of the baby as she was “not happy” with the movements
that the baby was making and felt it was “not normal jitteriness”. The father showed the reviewing doctor some
episodes which he had recorded on his mobile telephone illustrating multiple rhythmic episodes of the
right hand of 1-2 Hz, lasting for 30 seconds. A repeat
blood glucose level was normal. The pediatric registrar
was called to review, where upon multiple episodes of
right hand and leg jerking were witnessed, each lasting
1–5 minutes. It was not possible to control the jerking
movements by holding the limb. The episodes culminated in apparent opisthotonus and central cyanosis.
The baby was immediately admitted to the neonatal
unit.
Intravenous (IV) access was established: repeat
blood glucose level and blood gas values were normal. Blood cultures were taken, IV antibiotics were
started and the baby was kept nil per oram. Initial
blood tests revealed a neutrophilic leucocytosis with
a left shift, a C-reactive protein (CRP) at 6 mg/L, with
normal urea, electrolytes, ammonia and clotting profile
(neonatal reference ranges). Metabolic investigations

Fig. 1. Continuous amplitude-integrated electroencephalography (aEEG) tracing of the neonate on day 2 of life. Top trace (a): the initial trace
demonstrates seizure activity as soon as monitoring is commenced. The labelled line (1) shows resolution of seizure activity with immediate
effect after administration of a loading dose of phenobarbitone. Bottom trace (b): an expanded view of the brain activity at the labelled line (2)
in the top trace post administration of phenobarbitone: normal brain activity is observed.

M. Paddock et al. / Early diagnosis of neonatal stroke

were also sent for plasma amino acids, in addition to
urinary organic acids and reducing substances. A lumbar puncture was performed: clear and colorless fluid
was obtained. No organism was seen on gram staining of cerebrospinal fluid (CSF) with normal glucose,
protein and lactate levels. CSF was sent for herpes
simplex virus (HSV) polymerase chain reaction analysis and IV acyclovir was commenced. Continuous
amplitude-integrated electroencephalography (aEEG)
was commenced revealing seizure activity: a loading
dose of phenobarbitone was administered with immediate effect (Fig. 1).
Repeat cranial ultrasound was performed with
reported normal appearances. After further clinical
and electrical seizures overnight, she was commenced
on maintenance phenobarbitone. Feeds were introduced after a 24 hour seizure-free period with normal
serial neurological examinations and stable observations. Repeat CRP and full blood count were normal.
Cranial ultrasound performed on day 4 revealed extensive left middle cerebral artery wedge shaped increased
echogenicity (Fig. 2). The IV antibiotics were discon-

295

tinued on day 5 after the blood and CSF cultures were
reported negative after 48 hours of incubation, suggesting that the cause of the seizures was unlikely to be
related to infection. The IV acyclovir was discontinued
after a negative HSV result. Repeat cranial ultrasound
on day 5 demonstrated worsening left middle cerebral
artery wedge shaped increased echogenicity (Fig. 3).
A formal electroencephalogram was performed on
day 7 revealing occasional spikes over the left parietal region of uncertain clinical significance. MRI
performed on day 7 revealed loss of grey-white matter differentiation in the left frontoparietal area with
effacement of the sulci and underlying white matter,
in keeping with an acute left middle cerebral artery
territory infarction (Fig. 4): this was confirmed on the
apparent diffusion coefficient (ADC) imaging (Fig. 5).
No space-occupying lesion was shown within the right
hemisphere and posterior fossa structures appeared
normal.
She was discharged home clinically well on full
enteral feed by breast. A plan for outpatient echocardiography and consultant follow up 3 weeks post

Fig. 2. Coronal (a) and left parasagittal (b) cranial ultrasound appearances of the neonate on day 4 of life. Extensive left middle cerebral artery
wedge shaped increased echogenicity, best appreciated on the coronal view at the level of the choroid plexuses.

Fig. 3. Coronal cranial ultrasound appearances of the neonate on day 5 of life. Worsening left middle cerebral artery wedge shaped increased
echogenicity is demonstrated on this coronal view at the level of the choroid plexuses.

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M. Paddock et al. / Early diagnosis of neonatal stroke

3. Discussion

Fig. 4. A T2 weighted axial magnetic resonance image of the
neonate on day 7 of life. There is high T2 signal with loss of
grey-white matter differentiation in the left frontoparietal area with
effacement of the sulci and underlying white matter, in keeping with
an acute left middle cerebral artery territory infarction.

When assessing babies with a range of symptomologies, neonatal stroke is an important differential
diagnosis to consider, particularly when commoner
causes have been excluded. Neonatal stroke is defined
as the disruption of blood flow to the brain within the
first 28 days of life. There is overlap with perinatal
stroke which is defined as occurring from week 28
of gestation to within the first 7 days of life [1, 2].
Neonatal stroke is reported to occur in approximately
1 in 4000 live births, with a likely higher incidence
apportioned to ‘clinically silent’ strokes: cerebrovascular events that do not manifest with any clinically
identifiable pathology [2]. Given the varied, sometimes
non-specific, or ‘silent’ presentation, diagnosis is often
difficult and subsequently delayed [3].
Neonatal strokes can be classified by: type (ischemic
[80%] or hemorrhagic); the blood vessel affected
(artery or vein); the timing of the injury (perinatal or
neonatal, which can be difficult to ascertain given the
overlapping definitions above); the timing of clinically
apparent symptoms. Many infants are born following an uncomplicated pregnancy and delivery with
no identifiable perinatal risk factors. Risk factors and
potential causes can be categorized from mother to
baby (Table 1).
Stroke accounts for approximately 10% of seizure
presentations in the neonatal period, presenting with
focal or multifocal (due to incomplete myelination
of pathways) seizures [3]. If seizures are suspected,
Table 1
Risk factors for neonatal stroke (1, 2)

Fig. 5. An apparent diffusion coefficient (ADC) map from diffusion
weighted imaging of the 7 day old neonate. Restricted diffusion is
demonstrated in the left frontoparietal area (low signal on the ADC
map image) in keeping with an acute left middle cerebral artery
territory infarction.

discharge was established with further joint medical/physiotherapy clinic after 4 months. The results of
the metabolic investigations and thrombophilia screen
that were pending during her admission were negative,
excluding these differentials as a cause for the insult.

Location

Condition

Maternal

Autoimmune conditions
Coagulation disorders
Prenatal cocaine exposure
Congenital heart disease
Trauma, diabetes (prolonged second
stage of labor, shoulder dystocia)
Thrombosis
Abruption
Chorioamnionitis
Polycythemia
Factor V Leiden mutation
Factor VIII deficiency
Lipoprotein (a) deficiency
Disseminated intravascular coagulation
Central nervous system infection
Systemic infection
Dehydration
Extracorporeal membranous oxygenation (ECMO)

Placental

Blood

Baby

M. Paddock et al. / Early diagnosis of neonatal stroke

continuous amplitude-integrated electroencephalography (aEEG) should be employed as an initial measure.
It has been shown that the onset of clinical or electrical seizures beyond 12 hours of birth, and clinically
observed focal seizures, are predictive of stroke [4].
In our patient, a relatively common presentation of
“jitteriness” was the initial concern of the practitioners and parents observing the baby. Further episodes
were witnessed when it became clear that seizures, a
focal neurological symptom, were developing. In contrast to the more common jitteriness which will usually
cease by holding the limb, it was not possible to control our patient’s jerking movements. It is possible that
the general movements of the baby were abnormal
prior to the witnessed initial clinical seizures; however, it is not a formal assessment that is routinely
performed. A greater understanding of the differentiation and characterization of normal and abnormal
movements may have prompted earlier recognition of
such movements, allowing for initial investigations to
be undertaken prior to the onset of focal seizures in our
patient (Table 2).
The neonatal examination finding of jitteriness is
common, with a quoted prevalence of up to 44% in a
study of 936 newborns [5]. Jitteriness can be thought
of as recurrent tremor [6], defined in the literature as
an involuntary, rhythmical, oscillatory movement of
equal amplitude around a fixed axis. Two types have
been described: fine, with a high frequency (greater
than 6 Hz) and low amplitude (lower than 3 cm);
coarse, with a low frequency and higher amplitude
[7]. Jitteriness or tremor can be benign or pathological. Benign jitteriness usually consists of fine tremor
and is usually characterized by movements settling
on soothing and suckling of the examiners finger [8].
These infants will usually appear well on examination
and often will not have any perinatal complications.
Multiple causes for neonatal “jitteriness” are well
described. A non-exhaustive list includes: metabolic
disturbances (glucose or electrolyte abnormalities);
hormonal dysregulation (e.g. thyroid abnormalities);
hypoxic ischemic encephalopathy; sepsis; drug withdrawal [9–11]. Suggested investigations for the
presentation of jitteriness, as well as other symptoms,
are again displayed in Table 2.
A more detailed description and exploration of
infant movements has occurred since the publication of
the General Movements (GM) assessment by Prechtl
[12]. It has since been shown to become an attainable skill after only a few days of standardized training

297

Table 2
Suggested investigations for a range of potential neurological
presentations. Investigations should always be considered in the
context of the antenatal and perinatal history, and patient
examination findings
Presentation

Suggested investigations

Simple jitteriness that
settles on soothing or
suckling
Persistent jitteriness,
coarse jerking, significant
perinatal risk factors

Blood glucose measurement if
persistent

Apnea

Excessive lethargy

Seizures

Blood glucose measurement
Electrolyte measurement including
ionized calcium
Thyroid function tests
Urine toxicology/drugs of abuse
screen
Partial/full septic screen
Cranial ultrasound
Magnetic resonance imaging
Consider obstructive cause
Blood glucose and electrolyte
measurements (Na, Ca, pH)
Partial/full septic screen
Hemoglobin level
Consider seizure as cause, see
investigations below
Consider cardiovascular/respiratory
investigations
Urine toxicology/drugs of abuse
screen
Blood glucose and electrolyte
measurements
Partial/full septic screen
Consider imaging if negative
Blood glucose and electrolyte
measurement
Electroencephalography
Septic screen including lumbar
puncture and TORCH screen
Urine toxicology
Cranial ultrasound
Magnetic resonance imaging
Consider metabolic and genetics
screen

[13], to correlate highly with the neurological outcome
at all ages, and to have a sensitivity and specificity
consistently superior to those of a traditional neurological examination [14]. Following this, there has been
compelling evidence in the literature documenting its
efficacy in predicting neurodevelopmental outcomes:
a systematic review confirmed its effectiveness as a
prognostic tool in predicting which infants will go on
to develop subsequent neurodevelopmental disability
[15].
General movements normally involve the entire
body: they are complex, occur frequently, and for
enough time to be observed. They manifest as variable

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M. Paddock et al. / Early diagnosis of neonatal stroke

sequences of arm, leg, neck, and trunk movements,
and wax and wane in intensity, force and speed, having a gradual beginning and end. Additionally, they are
described as having rotations along the axis of the limbs
with slight changes in the direction of movements
creating the impression of complexity and variability
[16]. It is useful for practitioners to have knowledge of
normal neonatal movements, and by way of the GM
assessment, it can be a useful tool in the evaluation of
those infants about whose movements clinical concern
has been raised.
We know that children who develop hemiplegia in
infancy and childhood often have a period between
birth and a year of age where there are no clinically
apparent signs of the hemiplegia, reflecting evolving
neuroplasticity after an early insult, such as neonatal
stoke. It has been reiterated in the literature that the GM
assessment is an accurate tool in predicting hemiplegia
[17, 18].
The role of cranial ultrasound in confirming or refuting a range of possible diagnostic possibilities cannot
be understated. However, performance and interpretation is limited by operator skill and knowledge. Initial
(within the first 24 to 48 hours) normal intracranial
appearances may be misleading: whilst the diagnosis
of stroke cannot be fully excluded, subtle, non-specific
appearances may evolve over serial scans, such as in
the case of our patient. A high proportion of ultrasound scans reveal abnormalities strongly suggestive
of infarction by around day 3 [19], and as such, serial
scanning is advocated in those patients with suspected
stroke. A caveat with this imaging modality is that
occasionally, a small number of serial scans may be
persistently normal, even with later diagnosed small
middle cerebral or posterior cerebral artery territory
infarcts on MRI [19].
Definitive MRI is required to confirm the diagnosis,
preferably at an early stage in the diagnostic pathway to
refine subsequent investigations and treatment. Precise
description of the insult is mandatory in order to allow
correlation with later potential cognitive and motor
dysfunction or disability. Early MRI findings (location,
depth and tract involvement) significantly contribute
to predicting motor outcomes in those neonates with
middle cerebral artery territory infarctions [20]. Additionally, quantified diffusion weighted MRI of the
descending corticospinal tracts is also highly predictive
of future motor outcome [21]. Computed tomography
with angiography may be used but is not considered the
best diagnostic option given the exposure to ionizing

radiation and the limitations in prognostication and
delineation of anatomical structures.
MRI obtained earlier in our patient would have
allowed us to consider that whilst sepsis could not
be fully excluded at the time of initial presentation, it
would be an unlikely cause of the stroke; particularly in
the context of an unremarkable perinatal history, serial
negative inflammatory markers and negative blood culture results at 24 and 48 hours. This would have allowed
us to discontinue antibiotic and antiviral treatment at
an earlier stage and further investigate other potential
causes of the stroke. Second day seizures in the “well”
baby in the absence of signs of infection, asphyxia,
trauma and congenital anomalies, strongly raise the
suspicion of stroke; exclusion of such pathology by
obtaining an immediate MRI would have allowed us
to optimize patient care.
It is worth remembering that MRI is only one part
of the diagnostic pathway and should be used to help
frame further decision making within the clinical context of the patient. Given that the GM assessment
allows practitioners to differentiate between normal
and abnormal movements, robust protocols and escalation to more experienced members of the pediatric
team must be in place, not only to enhance trainee
skill and knowledge, but to avoid unnecessary admissions for a full diagnostic work up in well babies. GM
assessment also provides invaluable further information when MR is not immediately or readily available,
which may be the case at some centers. Even when
MRI is readily available, the assessment of general
movements should be an important non-invasive and
non-intrusive complementary assessment [22].

4. Conclusion
Neonatal stroke, whilst uncommon, is an important
differential diagnosis to consider in neonates with witnessed abnormal movements on the background of an
unremarkable medical history and normal initial investigations. In the case history above, we have illustrated
that the description of “jitteriness” may be subjective,
and should trigger consideration of a wider differential
diagnosis, of which neonatal stroke is included. GM
assessment is an important skill that can be acquired
to inform practitioners practice and decision making
regarding diagnostic, investigation and treatment pathways. Initial ultrasound imaging may be misleading
given that appearances can evolve, advocating the need

M. Paddock et al. / Early diagnosis of neonatal stroke

for serial scanning until definitive MRI can be performed, as in the case of our patient. Early MRI scans
are an important part of the prognostication process but
may not be readily accessible or available to all practitioners: GM assessment is a proven useful tool to
provide further information about potential long term
neurodisability. Given the long term sequelae that can
result from stroke, an early diagnosis is essential to
identify the cause and to potentially initiate treatment
and prevent recurrence.

[7]

[8]

[9]
[10]
[11]

[12]

Acknowledgments
[13]

We would like to thank Dr Dan J. A. Connolly for
his help in preparing the figure legends.

[14]

Financial disclosure statement

[15]

The authors report no conflicts of interest.
The authors are wholly responsible for the content
of the manuscript.
The authors have obtained signed informed consent
from the parents of the patient and they will be provided
with a copy of the manuscript prior to publication.

[16]

[17]

[18]

References
[1]
[2]
[3]

[4]

[5]

[6]

Chabrier S, Buchmüller A. Editorial comment–specificities
of the neonatal stroke. Stroke 2003;34(12):2892-3.
Sehgal A. Perinatal stroke: A case-based review. Eur J Pediatr
2012;171(2):225-34.
Govaert P, Smith L, Dudink J. Diagnostic management of
neonatal stroke. Semin Fetal Neonatal Med 2009;14(5):
323-8.
Rafay MF, Cortez MA, de Veber GA, Tan-Dy C, Al-Futaisi
A, Yoon W, Fallah S, Moore AM. Predictive value of clinical and EEG features in the diagnosis of stroke and hypoxic
ischemic encephalopathy in neonates with seizures. Stroke
2009;40(7):2402-7.
Parker S, Zuckerman B, Bauchner H, Frank D, Vinci R, Cabral
H. Jitteriness in full-term neonates: Prevalence and correlates.
Pediatrics 1990;85(1):17-23.
Armentrout DC, Caple J. The jittery newborn. J Pediatr Health
Care 2001;15(3):147-9.

[19]

[20]

[21]

[22]

299

Rosman NP, Donnelly JH, Braun MA. The jittery newborn and infant: A review. J Dev Behav Pediatr 1984;5(5):
263-73.
Linder N, Moser AM, Asli I, Gale R, Livoff A, Tamir I.
Suckling stimulation test for neonatal tremor. Arch Dis Child
1989;64(1 Spec No):44-6.
Rosman NP, Donnelly JH, Braun MA. The jittery newborn
and infant: A review. J Dev Behav Pediatr 1984;5(5):263-73.
Armentrout DC, Caple J. The jittery newborn. J Pediatr Health
Care 2001;15(3):147-9.
Parker S, Zuckerman B, Bauchner H, Frank D, Vinci R, Cabral
H. Jitteriness in full-term neonates: Prevalence and correlates.
Pediatrics 1990;85(1):17-23.
Prechtl HF. State of the art of a new functional assessment
of the young nervous system. An early predictor of cerebral
palsy. Early Hum Dev 1997;50(1):1-11.
Valentin T, Uhl K, Einspieler C. The effectiveness of training
in Prechtl’s method on the qualitative assessment of general
movements. Early Hum Dev 2005;81(7)623-7.
Cioni G, Prechtl HF, Ferrari F, Paolicelli PB, Einspieler C,
Roversi MF. Which better predicts later outcome in full-term
infants: Quality of general movements or neurological examination. 1997;50(1):71-85.
Burger M, Louw QA. The predictive validity of general
movements - a systematic review. Eur J Paediatr Neurol
2009;13(5):408-20.
Einspieler C, Prechtl HF. Prechtl’s assessment of general
movements: A diagnostic tool for the functional assessment
of the young nervous system. Ment Retard Dev Disabil Res
Rev 2005;11(1):61-7.
Guzzetta A, Mercuri E, Rapisardi G, et al. General movements
detect early signs of hemiplegia in term infants with neonatal
cerebral infarction. Neuropediatrics 2003;34(2):61-6.
Einspieler C, Prechtl HF, Ferrari F, Cioni G, Bos AF. The
qualitative assessment of general movements in the preterm,
term and young infants – review of the methodology. Early
Hum Dev 1997;50(1):47-60.
Cowan F, Mercuri E, Groenendaal F, et al. Does cranial ultrasound imaging identify arterial cerebral infarction
in term neonates? Arch Dis Child Fetal Neonatal Ed
2005;90(3):F252-6.
Husson B, Hertz-Pannier L, Renaud C, et al. Motor outcomes
after neonatal arterial ischemic stroke related to early MRI
data in a prospective study. Pediatrics 2010;126(4):912-8.
Kirton A, Shroff M, Visvanathan T, deVeber G. Quantified corticospinal tract diffusion restriction predicts neonatal
stroke outcome. Stroke 2007;38(3):974-80.
Spittle AJ, Boyd RN, Inder TE, Doyle LW. Predicting motor
development in very preterm infants at 12 months’ corrected
age: The role of qualitative magnetic resonance imaging
and general movements assessments. Pediatrics 2009;123(2):
512-7.

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